About The Guest

Dr. Boon Chong Goh is the co-founder and CTO of ArrowBiome, a Singapore-based biotech startup developing precision microbiome solutions through its lysin engineering platform.

Spun out from the Singapore-MIT Alliance for Research and Technology and NTU Lee Kong Chian School of Medicine, ArrowBiome develops proprietary and patented platform technologies that enable highly selective bacterial targeting and killing. With “arrow-like” precision, the company is advancing microbiome solutions across applications including body odour, acne, other bacteria-associated skin conditions, gut health, and antimicrobial resistance.

In this episode, Boon Chong shares how his journey from physics, protein structure, and molecular simulations led him into antimicrobial resistance research and eventually entrepreneurship. He discusses why lysins are powerful tools for precision microbiome control, how ArrowBiome moved from academic research to commercialization, and why the company strategically entered skincare and personal care before tackling more complex antimicrobial challenges. He also reflects on startup fundraising, Singapore’s biotech ecosystem, scaling production, global expansion, and the personal shift from scientist to entrepreneur.

🥡 Key Takeaways

🧬 Precision bacterial targeting is reshaping microbiome care: ArrowBiome uses proprietary lysin-based platforms to selectively target bacteria involved in body odour, acne, gut health, and antimicrobial resistance.

🧫 Lysin technology offers speed, selectivity, and resistance resilience: Unlike many conventional antimicrobial approaches, lysins can act quickly while having low likelihood of bacteria developing resistance.

🧴 Cosmeceuticals can be a strategic entry point for entrepreneurship: Starting with skincare and personal care allows ArrowBiome to generate clinical proof, regulatory experience, and commercial traction before moving into more complex antimicrobial applications.

⚙️ Commercialisation requires more than scientific proof: Founders must navigate manufacturing, cost reduction, regulatory registration, formulation, partnerships, and sales.

🇸🇬 Singapore provides a strong launchpad for biotech startups: ArrowBiome’s journey highlights the role of SMART, NTU LKCMedicine, NHIC, Enterprise Singapore, and Singapore’s global reputation in supporting deep tech commercialisation.

🧑‍🔬 Scientists must evolve into strategic decision-makers: Entrepreneurship requires moving beyond technical feasibility to consider brand, market fit, opportunity cost, IP, scalability, and long-term business value.

💬 Quotes

“If you feel very passionate about certain technology, especially if it’s a technology that you invented, then absolutely go for it.”

“No one else will advocate for your technology. No one else will push the technology to its very limit other than you.”

“Lysin is perfect because it has three good features: it’s extremely fast, it’s very selective, and it’s very difficult for bacteria to develop resistance against lysins.”

“As scientists, selling is the one thing that we really underappreciate — how hard and how important it is to sell.”

“You have a fancy title like Founder and CEO, but in actual fact, you are the C Everything Officer.”

“Something that I had really taken for granted is this Singapore brand. It does equal to quality and stability and it has a lot of good connotations that’s attached to it.”

“If you want to do deep tech companies, it has to be global from day one.”

⏱️ Timestamp

00:00 Introduction to Dr. Boon Chong Goh

00:54 Journey From Physics to Antimicrobial Research

01:36 Why Lysins Became the Focus

04:24 Why Lysin Technology Matters for AMR

05:25 Funding Early Antimicrobial Projects

07:19 From Research Scientist to Entrepreneur

09:19 From CEO to CTO

14:10 Building ArrowBiome in Singapore

15:48 Why Singapore for Deep Tech and Cosmeceuticals

17:28 ArcherZyme and SmartArrow

19:19 Why Start with Cosmeceuticals

21:15 Regulatory Pathways and Clinical Testing

22:01 Measuring Success in Acne and Body Odor

23:23 Microbiome Differences Across Populations

24:51 Scaling Fermentation

25:37 B2B Partnerships and Global Clients

26:33 Formulation Partnerships with CHAKS

27:49 Singapore Startup Ecosystem and Partnerships

29:01 Winning Gold at In-Cosmetics Asia

31:06 Belgium Subsidiary and Global Expansion

32:20 What Next for ArrowBiome

33:20 M&A Strategy and Exit Planning

34:22 Advice for Researcher-Entrepreneurs

36:31 From Scientist to Strategic Founder

🎙️ Transcript

Boon Chong:  If you feel very passionate about certain technology, especially if it’s a technology that you invented, then absolutely go for it, because no one else will advocate for your technology. No one else will push the technology to its very limit rather than you, so you’re the best person to do it. Go ahead and do it.

Shamieraah:  Hi, thanks for joining us on Nucleate Singapore Pulse, Singapore’s premier podcast on the biotech ecosystem. I’m your host, Shamieraah Jamal, a computational biologist. Whether you’re a student thinking about creating your own startup or an industry professional looking for diverse perspectives, this is the podcast for you. The show notes and transcripts for the episode can be found on nucleatesingapore.substack.com.

Today, we are joined by Dr. Boon Chong Goh. Boon Chong is the co-founder and CTO of ArrowBiome, a Singapore based startup specializing in precision microbiome solutions with their flagship lysin engineering platform. Thanks for coming on today, Boon Chong.

You started your PhD in physics, and you worked a lot on biophysical simulations. So how did you go from doing that to anti-microbial research?

Boon Chong: It has to stem from my interest in protein structure.

Since my undergrad days, I’ve been working on protein folding. And during my PhD I was doing molecular simulations on proteins and how they interact with bacterial membranes, how they interact with viruses, receptors. So, after I completed my PhD at the University of Illinois of Urbana-Champaign, I came back to Singapore. There was quite a new entity called the Anti-Microbial Resistance (AMR) group under the Singapore-MIT Alliance for Research and Technology (SMART). I wanted to apply what I know, what I learned, and tried to apply it in more drug discovery.

Shamieraah: So from that, how did lysins become the focus of your work?

Boon Chong: There was a moment in my postdoc, two years into my postdoctoral research. I asked myself the question. Do you want to be a postdoc forever, or you want to create something that belongs to you and something that you can be proud of and you can make a career out of? So this is when I went into some soul searching. Right now, in the age of AI it’s called Deep Research, but back then we didn’t have those tools. I literally closed myself in a room for two weekends straight and tried to brainstorm all the possible topics and possible technologies that I can develop.

Then I came up with this lysin technology that has a lot of lure to it. But I want to describe the process of me coming to the lysin technology. As a physicist and mathematician, I love Venn diagrams, if you remember from high school. So I drew three circles. One is the computational techniques that I have. The other circle is on the experimental techniques that I have. When I came back to Singapore, I learned about structural biology, crystallography, and drug discovery. So those are the pieces that I want to combine. And the third circle is the area of interest - what problem I want to solve.

So when I looked around, anti-microbial resistance was one of the toughest problems to tackle. Not only is it technologically challenging, but economically it’s also very difficult. Because not so much VCs are actually investing into antibiotics. During the 2017-2018 days, there was a period where you read on the news: a lot of pharmas are exiting the antibiotic programs, and some biotech companies actually struggled and filed for bankruptcy even though they managed to get a FDA approval for the antibiotics. So, it was a really tough time to work on this. But, I don’t run away from the problem. I wanted to tackle this in my own way.

So this is when the three intersections come in, I can use protein and tackle anti-microbial resistance. And lysin is perfect because lysin has three good features: one, it’s extremely fast and within half an hour you can see the bacteria being destroyed and popped like a balloon, literally; and second, it’s very selective - you only target certain species, certain bacterial genus; and third, which makes it particularly suitable for anti microbial resistance, is that it’s very difficult for the bacteria to develop resistance against lysins. And I know that this is a technology that has a lot of potential, antimicrobial resistance is one, but there’re so many features that we can leverage.

Then we go back to the second point on it being very selective. That makes it very suitable for microbiome, microbiome modulation, microbiome editing. This is where we can introduce precision microbiome control and management into a whole heap of different applications. And for us at ArrowBiome, we chose to start with personal care and skincare.

Shamieraah: There’s a lot of courage in tackling antimicrobial resistance when, as you said, a lot of big companies were running away from the problem. Was there a certain point in your research, was there a specific experiment or project where you actually realized how pivotal lysins are to anti-microbial research?

Boon Chong: It’s one of the very few technologies that has the feature of resistance-proof, it’s very difficult to force the bacteria to develop resistance against lysin. And if you look at other technologies like the antibiotics and even phage therapies, the resistance is quite a common thing.

Shamieraah: But was there some simulation that you did, that you observed this effect?

Boon Chong: This is where we leveraged on the previous people who looked into lysins. I am not the first person or the father of lysins. So we looked at the father of lysins, the pioneering research that he did. Back then, in his lab he did a bunch of experiments, with serial passaging to really force the bacteria to develop resistance. After a month or two, he still couldn’t see any resistance developed.

Shamieraah: So I want to go to your time at the Singapore-MIT Alliance for Research and Technology, or SMART, as they call it. What difficulties did you face to raise grants or fundings for your anti-microbial projects at this time?

Boon Chong: At the beginning, it’s definitely not easy because when you were hired as a postdoc, you had a certain project that’s attached to it. And if I go to my supervisor and say that, I want to work on something that is entirely different, that has no funding right now. Obviously it’s gonna be difficult. I think back in SMART, I was quite fortunate to be on the SMART Scholars program.

So, as part of the fellowship or scholarship, we were given a small research grant. I can’t remember how much is it, but it’s a small amount, but we had complete discretion of what to do with it. I think that is a very privileged position. So that’s when I used that small little grant to do the first set of experiments.

Looking back, I would say that I was quite lucky. I chose a couple of lysins to try to express and produce it, and one of them ended up really good. With good preliminary results, then we went to the grant committees and showed them the results.

We did a quick test. It expresses pretty well and it does kill the bacteria as intended. And now we want to apply all the protein engineering techniques that we have into this. So that’s when I got my first grant and I still remember it was a SMART Ignition Grant from the Innovation Centre.

It was a small 50k. A lot of people, they’ll say, “Oh, what can we do with 50k?” But I really got creative in terms of managing the budget, half of it goes to hiring a diploma holder as a lab tech. And the other half is the consumables to run the experiments. We did some really good work and ended up in the publication in Frontiers in Microbiology.

Shamieraah: That’s quite remarkable to achieve that with a small grant. For our listeners who don’t understand the scale like what you said, you have to spend half of that just hiring someone to do the work . That grant money gets used up quite quickly. So it is quite amazing that you managed to get the findings that you did at the time. So you spent eight years at SMART as a research scientist , what made you switch from that to an entrepreneurship journey?

Boon Chong: It is definitely the potential of lysins. To be honest, when I started developing the technology, I wanted to be a professor - to be a faculty member so that I can write a research proposal around this technology and get a position. That was the very original plan. But as I went through the innovation boot camps run by SMART Innovation Center, I realised that what I have in hand has a lot more potential than just that.

And when I looked into it, being a professor is great when they publish a bunch of papers, then you may get cited a lot, you may not get cited at all, but what’s the real impact of it? And to me I want to maximize the potential of the technology; it is like your own child. You give birth to the child and want to make sure that he or she achieves the maximum potential. To me, commercializing it under a startup is the way to go. And I think about two, three years into the development of the technology, that’s when I decided that, yes it has the legs to form a startup and we just had to find the right team member, making sure that the data is solid and there’s enough commercial traction. And that’s when we started the company.

Shamieraah: Yeah, so that is quite a big change from being a scientist. As a scientist, I think most of us, we do our work, we get the results, and we are just chasing the science, we’re chasing the questions. And to go from that to seeing something that had commercialization potential is a very big change in perspective.

So at first, you were CEO and then you took on the position of being CTO, which I’m sure you are well placed to manage the product development. But for many of us in science, it’s a kind of a culture shock to transition to entrepreneurship and think in terms of selling the product . So how was the experience of being a CEO and then wearing a different hat of a CTO, and how did you choose someone to lead the company that you founded?

Boon Chong: That’s several questions into one, but I will address them one by one. In terms of selling a product, I think as scientists, that is the one thing that we really underappreciated, like how hard and how important it is to sell. Being a naive scientist before starting the journey, I always thought that you just create a killer product, killer technology, then the technology and the product will speak for itself and people will recognize it, then people would wanna buy it. It couldn’t be further from the truth. And it’s true, we do have really solid technology, really good active ingredients that we’re trying to sell to the multinationals, to the regional players. But only when you’re trying to sell, that’s when you know what they actually are looking for and what they want to see more.

I think the first trade show that we went to, it was in Bangkok for In-Cosmetics Asia 2024. Back then we thought we had a product, we can make the proteins, so that’s a product. We went to sell. That’s when we learned that people are genuinely interested, but they want to see more. The two key things is: has it been clinically proven as a new biotech ingredient, and has it been registered in the regulatory point of view in cosmetic ingredients, that is, INCI, the International Nomenclature for Cosmetic Ingredients. Get it registered before they can even sell it. I wouldn’t say that we knew that during the trade show, but it definitely further reinforced the importance. That’s when we shift our focus to get those two done as soon as we can. We’ll get to the In-Cosmetics Asia last November later.

But I want to go back to the earlier questions on the experience of wearing the different hats. I think at the very beginning, the journey will feel a little bit lonely at times. You have a fancy title like the Founder and CEO, but in actual fact, you are the C Everything Officer. You do HR, you process payroll, you pay bills, you look for the cheapest vendors to buy your consumables. So it’s a lot of work. But that is needed when the company is very small. And I was fortunate to be joined by my very first employee who was my intern previously. She was really helpful to make sure not everything’s on me. Forever grateful for that - she took the risk to join this early and to spearhead the company from almost from day one.

But as the company grew, back then there were 2- 3 people. We knew exactly what we needed to do. Then that’s what we did. And then we grew the team after we secured the seed investment from Cocoon Capital. That was in June 2024. That allows us to accelerate everything. We have slightly bigger team to run the clinicals that we have been wanting to run.

At some point the company grows to a point where you cannot be everything anymore. I was a CEO, CTO, COO, HR, finance, everything. And we did a transition in August and that does coincide with the fundraising needs, and the rapid needs to manufacture, to file more new IPs. That’s a lot. If you ask me, do I want to hold onto my CEO hat or I take on a new hat - not really new because I’ve been wearing it - the CTO hat, what will put the company in the best position? I have very little ego to begin with. I want to do what’s best for the company, which is also my child, my baby in a way. I want the company to be in the best position to grow. So with me focusing on the CTO role, doing what I do best, is the natural choice.

Then the question is, who will take on the CEO role? And I think a lot of companies when scientist, entrepreneur, when they started, they are the C Everything Officer. When they want to transition to a more technical role, the CEO role was not easy to fill in. For ArrowBiome, we are quite fortunate that we have now Dr. Bert Grobben, who started as a business advisor for ArrowBiome. Then he stepped up his role to executive commercial director. Then he picked up the role of CEO last August. He has a wonderful background. It’s almost like you couldn’t find a more suitable person. He’s commercially savvy. He spent 14 years in P&G, knowing how corporate works, how open innovation works, and also spent the last 10 years being a serial entrepreneur. I would consider myself really lucky that the company has such a capable person who is willing to spend the entire full time in the company.

Shamieraah: I think you’re really lucky to find someone who is equally passionate and able to nurture your child, as you call it. So I wanna move on to what ArrowBiome has accomplished. First of all, what were the challenges and the supportive factors when you started ArrowBiome in Singapore?

Boon Chong: Challenges-wise, when we started, I didn’t know what to do, like the mechanics of it. This is when the business advisor, Bert, was really helpful because he was previously assigned as a mentor back in the innovation bootcamp. He knows exactly what to do, what’s the best steps, the order of doing things. Because you shouldn’t register too early, shouldn’t register too late, that you sign agreements under academic institution, that is irreversible. So that was really helpful.

In terms of supportive factors, I definitely have to thank my co-founder Professor Maurice Van Steensel who is really supportive. During the beginning, he was our commercial person because he’s a dermatologist by training, so he’s well connected. So he was pulling strings and trying to promote and market our product as well. The first sales that we generated is thanks to his connection. That was really helpful.

And there is another government institution that helped. I think one particular one that I have to shout out is NHIC, National Health Innovation Center. The two officers that were assigned to us were really helpful. Technically, NHIC’s mandate is as an academic institution. When I was still a researcher, having NHIC grants, they were very helpful. But once we transitioned to entrepreneurship, they were still there and ready to help. So they even managed to link us up with several investors, let us meet, and continue to ask, “Oh, how else can we help?” So we are really grateful.

Shamieraah: It sounds like there’s been a very helpful local innovation ecosystem that really supported the founding of your company. So is that one of the factors that make Singapore an attractive choice to enter the cosmeceutical market? And are there any other factors you would like to highlight?

Boon Chong: I think what makes Singapore special in a broader context is that a lot of the spinoff companies that got spun off from the universities, they do already come with very strong technologies. And that makes it investible to the local VCs.

And also I didn’t manage to say it, but other than the NHIC, we also got supported by Enterprise Singapore. They have a Startup SG Deep Tech POC grant that we got. The Singapore government actually put money into it, so that actually convinced our first seed VCs to invest in us. So that was really helpful.

In terms of cosmeceutical or not, another factor that makes Singapore special is that if you wanna do deep tech companies, it has to be global from day one. You’re not restricted to just the Singapore market or the Southeast Asia market - needs to be global from the get-go.

Singapore is a really good place to start, right? Something that I had really taken for granted is this Singapore brand. When we were at Bangkok, we were in Amsterdam, and going to Paris in April, when you say that you are from Singapore, people give you a different look like, “Oh, Singapore, yes. Oh, it’s good.” Yeah, like it does equal to quality and stability and it has a lot of good connotations that’s attached to it. So I think we count it to give the Singapore government a pat on the back and say yeah, thanks for making the Singapore brand so strong.

Shamieraah: I didn’t know that Singapore had such a good name recognition. So I wanna move on to your product line as well . So could you share with us more about the story behind ArcherZyme and SmartArrow, which are the two active ingredients of your company and how they work?

Boon Chong: I’ll try to keep it brief, but ArcherZyme and SmartArrow are derived from two platform technologies that we have. One, the first platform that we have is Archer, that’s the protein engineering platform. The second platform is the Forge, which is a combination between protein and particles. That’s where SmartArrow was generated from.

In terms of the story behind ArcherZyme and SmartArrow, it is definitely an interesting story, because when we first started, we had the lysin technology, and then we want to tackle acne, right? And when we look at acne biofilm, it’s a big problem.

If you just use lysin alone, it’s not probably optimal. And that’s when we got creative and took the recognition domain of the lysins and fused it with a particle such that the binding domain will physically catch and latch on the biofilm. And because that is a nucleation point in the polymeric particles, it comes off the biofilm mechanically.

So note that you don’t need to put any chemicals inside the particles, it’s just the empty particles. By mechanically removing the biofilm, it’s the gentlest possible way to manage your acne. Our clinical studies did show a 40% reduction in the mild inflamed acne. That was really good.

And then for ArcherZyme, it is more straightforward in some sense. You design the lysins. They have two domains, then you create a library around it. Then you screen for the best activity. Then that’s where we identify one that works very well, in terms of preferentially targeting Staph hominis over the other bacteria. And for our clinical studies, you can see that within less than two hours, you see the armpit odor actually reduces by 60%. So that’s really good.

Shamieraah: And also, why did you start targeting cosmeceuticals like body odor production and acne reduction instead of other anti-microbial concerns like MRSA ?

Boon Chong: I want to link back to the earlier comments that I have about not running away from the problems, running towards it. No, it’s not as linear as that. It is definitely a big problem that you can’t just dive straight in or morph into a sun, right? You have to be strategic around it. If we are like other lysins-based companies that, from day one, they declare “ We want to tackle anti microbial resistance. Please give us the money.” We could do that, but we want to be practical and strategic in a sense - a low hanging fruit and cosmeceutical is one. The regulatory barrier is lower, faster path to revenue, and even the clinical doesn’t take that long. You don’t have to go through the phase 1, 2, 3 and get FDA approval. You can get the proof of concept, proof of principle, proof of value of your technology as soon as possible. And once you are revenue generating, you are in a much better position compared to just a pure startup that relies on fundraising to survive. So we want to get to that stage as soon as possible.

We also realized it’s not as low of a hanging fruit as we thought. We have different challenges, for one, it’s that the production costs need to be a lot lower. For pharmaceuticals, I can charge a lot. Don’t necessarily have to squeeze your cost of production to minimal. But for the case of cosmeceuticals, you are competing with the other ingredients. They are really cheap, if you can’t bring your cost to a point where it’s parity or a little bit of premium, at least in the same ballpark, no one’s ever gonna buy and there goes the dream of being self-sufficient and revenue generating, et cetera. So we were now pushing ourselves really hard to find the best possible systems to produce the highest quality, to necessary purity at the lowest possible cost.

Shamieraah: So that makes a lot of sense as a strategy. You wanna target something that generates revenue quickly and then pivot to something more substantial. And I wanted to touch on something you mentioned earlier, which is on the regulatory pathways and compliance requirements, which you mentioned is slightly different from drug discovery. So maybe could you explain what were these pathways and requirements that you had to go through for ArrowBiome?

Boon Chong: Yeah, that would be the INCI registration. Yeah, the International Nomenclature for Cosmetic Ingredients and also showing there are in vivo studies that’s being done on consumer testing. Those are the two main ones that we have to go through to be able to do B2B sales and we will continue to support our clients as they register their products containing our ingredients in their respective regions.

Shamieraah: And when you were doing these clinical trials, what were the endpoint measures that are required to prove compliance, like for acne treatment and body odors? So what does the successful endpoint look like?

Boon Chong: Good thing for acne and body odors - they’re either very visible or you can literally smell them. So success looks like it’s not too difficult in a sense. Yeah. So for body odor we have a professional sniffer panel, their job is to smell armpits and then they’ll put their ratings and that’s where we see the dramatic reduction.

For the case of acne, you can take pictures and you can count the different acnes at their different stages. Some are still mostly comedones, The black heads or white heads. Some are more inflamed - that’s when you have pus in it. Then we will just count them accordingly, and once SmartArrow is applied on it, you’ll see the reduction in the inflamed acne.

In the process of really scaling up the production, keeping the cost low, and knowing the full cycle of things from production to sales to regulatory registration, when the time is right, when we go into anti microbial resistance, again, we are in a much better position. Because we have the manufacturing mostly figured out, we can get the cost low. So in terms of starting point, we will start at a much better starting point and we don’t have to keep relying on fundraising to make it work.

Shamieraah: So you already have these pipelines established as to how you can push a product and test it and go through all the compliance measures that you need.

I want to pivot a little bit and talk a bit about how your product targets microbes and is there difference in the microbiome between different populations, for example, in Singapore or Asian populations versus Western populations?

Boon Chong: Yeah, very fair, good question. For the case of body odor and acne, there are main culprits. There’s a Unilever study that looks at all the different people with body odor problems and they swab and they do the microbiome sequencing, and they identify that Staphylococcus hominis is the main culprit. There will be other bacteria that contribute to the unique smell of the armpit, but Staph hominis is the foundation, the common culprit, so that’s where we target.

So for the case of acne, acne almost knows no borders, and it’s always linked to Cutibacterium acnes, so that’s the same globally.

Shamieraah: So would your strategy be the same in product development if you are moving to a different market?

Boon Chong: For the case of acne, we don’t change our strategy because acne is the same everywhere. But for body odor, it does open up an opportunity to tailor the solution such that it’s more suitable for Caucasian skin or more for Asian skin, East Asia, South Asia, Middle East. We target the most abundant bacteria, but the second most abundant might be different. So if you target that also, then you can create a more customized solution.

Shamieraah: Previously, you mentioned the importance of scalability in growing ArrowBiome. So how were you able to accomplish this in your pipeline?

Boon Chong: The way we produce proteins by precision fermentation and the economy of scale is playing a huge part. The cost of production of a single litre in a shake flask, is vastly different when it comes to cost efficiency as compared to a 10,000 liters biofermenter. So we leverage the scale of synthetic biology fermentation to really lower the cost tremendously.

Other than the volumes of the fermenters, the strain optimization and the yield optimization is also super important. If you can double the protein yield within the same volume, then effectively the production cost is halved.

Shamieraah: So I see that’s where you would leverage the actual biology of the production strains and that’s very important. So as a B2B company, ArrowBiome produces proteins for other cosmetic product developers as well. So how do you approach these partnerships and what is the scope of clients? Is it just local people or are you expanding to regional and global as well?

Boon Chong: From day one, we are global, so our clients and partnerships are all around the world. In terms of B2B sales, we sell our two flagship products, ArcherZyme and SmartArrow, to everyone.

But for certain multinational companies they’ll look at our offerings and say, “Oh, your technology is actually very interesting, but we are more interested in these other applications. Can you develop something for us?” And we will look at the opportunity, assess whether it’s technically possible. Then if it’s good, we’ll say yes. We would love to work with you to co-develop this custom solution, custom technology, for you. And with that typically they will have to co-fund it. And we’ll then work out the IP arrangement from there on.

Shamieraah: And ArrowBiome has also partnered with CHAKS Cosmetic Design, and you won their Most Esteemed Partner award. From what was mentioned, CHAKS Cosmetic has integrated ArrowBiome’s formulation and created new cosmetic prototypes. So could you elaborate more on what that means , and what they could be used for?

Boon Chong: We do work very closely with CHAKS, who’s our formulation partner, because what ArrowBiome is, is an active ingredient developer. What we do best is that we produce the protein, we can freeze-dry them into powder form and then we sell them, And a lot of clients, when they look at the white powder, they can’t quite envision how to formulate it into a final product, and that’s when CHAKS really come in.

So they, when it comes to developing a commercial formulation with the right sensorial, feel, and texture, CHAKS is the best person for it. And during this partnership, we do work very closely because there will be some ingredients in the formulation that may not be as compatible as the other ingredients.

Obviously we can’t quite test the thousands and thousands of possible cosmetic ingredients for compatibility, and that’s when we work with CHAKS and then they’ll help us to narrow down to a few key ingredients. And that’s where we crosscheck for compatibility and work together closely to develop a formulation that our clients are familiar with.

Shamieraah: Another partner ArrowBiome has worked with is Sequential for skin microbiome testing. How has the Singapore biotech ecosystem encouraged these kinds of partnerships between startups and how do startups benefit from this?

Boon Chong: Yes, I think the Singapore biotech ecosystem is a close-knitted community. The country is not big to begin with, and if you narrow it down to just the biotech, deep tech community it’s even smaller, right? Especially if you reside around the Biopolis area, everyone is just a stone throw away. You can have coffee with them and discuss about potential new ingredients at one test, and they can share the new offerings, that new service that they offer. It is no longer just a pure sales conversation, but it’s more like a conversation between a friend to a friend, scientist to scientist, to explore what was possible, right?

So other than Sequential, we also work with Revivo Biosystems on their skin tissue testing, Sequential is good when it comes to skin microbiome testing, and you can feel that when you have coffee with them, they will always give that extra touch and extra tender loving care when they do the experiments.

Shamieraah: It’s nice to feel like you are part of a community and you can lean on people that you know for support.

Shamieraah: Previously, you also mentioned that your company won a gold award in In-Cosmetics Asia in November of last year . First of all, congratulations to you.

Boon Chong: Thank you.

Shamieraah: And what plans do you have for ArrowBiome after this?

Boon Chong: We are very very proud that we were awarded with the Gold award as the best active ingredients in In-Cosmetics Asia, so that’s out of 120 ingredients. Most of them are from much bigger multinational companies, and we emerged on top. We out-innovated the big boys, so we couldn’t be more proud than that, and it’s a prestigious award that’s widely recognized in the industry ‘cause it was judged by 14 independent panelists.

They all shared that the way ArcherZyme manages the microbiome and to reduce the body odor, is a truly different way. We are glad that the panelists are aligned and think alike. We are glad that the panelists actually support our vision when it comes to precise microbiome management, right? And after this, we hope to repeat the feat at In-Cosmetics Global in April. It will be in Paris this year. We have another breakthrough ingredient that’s been clinically proven, it’s SmartArrow. That’s a really special first of its kind mechanism-of-action to mechanically remove the acne biofilm. I think we stand a very good chance.

Shamieraah: Yeah, we’ll hope for the best. It is a big accomplishment that you not only outcompeted big companies, but you got a boost of credibility from industry scientists who have looked at your work and found it to be very worthy. And also you brought the Singapore name to a regional stage and hopefully to the global one as well. So we’re all rooting for you.

Boon Chong: Yeah, thank you. I would say that after we got the gold award, the commercial traction has been increased dramatically. Now we have a luxury problem, right? We can’t produce fast enough, right? Right now, any new client that wants our ingredient, we have to wait until July, which is a few long months. I would say this luxury problem is still a problem, mainly my problem, I have to really accelerate the manufacturing as fast as I can do, so that’s what is keeping me up at night.

Shamieraah: It’s a good problem to have and it definitely shows that you are moving in the right direction. For example, you’ve also expanded globally with a subsidiary in Belgium. So could you elaborate a bit more about that? Why Belgium and what does that mean for the future of the company?

Boon Chong: Yeah. When you look at the personal care cosmetic scene - a lot of the big companies - they all reside in Europe. So it’s really important for us to have our presence and footprint in Europe. When you want to do business with them, face-to-face interaction is important and there’s only so many trips we can fly from Singapore, right? So ultimately, one of the first to-do is to have a local sales person on the ground to run sales for us.

But when we were looking to set up a subsidiary in Europe, we considered five different countries. Belgium emerged on top. One is the physical location: it’s really close to France, Germany and the Netherlands. And second is the R&D: so in terms of microbiome research, there’re a lot of KOLs (Key Opinion Leaders) in Belgium that we hope to be part of their ecosystem. And they do have really good grants to do product development, to generate new IP assets - that is something that we want to leverage on as well.

Shamieraah: And so, as the company is now growing from early stage to a bigger company, you’re gaining more visibility. So what are the challenges going forward? Is it more operational, logistical, regulatory, technical or something else? What gets the bigger priority?

Boon Chong: It’s definitely all of the above but it’s important to stay focused. I think when it comes to 2026, it’s important for us to complete the sales cycle, to push the sales of SmartArrow and ArcherZyme.

I always describe those two active ingredients as the twin engines of the company. It takes a lot of effort to get those engines going and we want to make sure they’re fully operational and getting registered in their regional regulatory agencies.

Once we have the twin engines going, then we will look into expanding to adjacent applications, generating the next generation of SmartArrow and ArcherZyme into a slightly broader set of applications. We have to be strategic and conscious of which applications that we are going into that’s technically possible so that the whole portfolio of products are coherent.

Shamieraah: So as the company grows, what is going to impact the future M&A strategy? And how does the biotech ecosystem in Singapore contribute to decisions regarding what exit strategy might be the best?

Boon Chong: From the get-go we are very clear that ArrowBiome is the M&A play, so when you look at M&A is to create the portfolio that makes it very attractive for people to acquire you. So one is to be able to show that your product can sell. Second, is that you show that your platform can make more products that can sell. We have the potential to sell more.

And show that you have the complete team, that can cover all the way from technology development, from clinical studies, from commercialization, from product to production and regulatory, and then you present that as a complete portfolio.

Shamieraah: That makes a lot of sense. And as we wrap up the podcast, I wanna switch to what is some aspirational advice that you would give to researchers who are looking to become entrepreneurs? How can they start to build their skills for it?

Boon Chong: I think the very first thing is that they have to be financially secured to a certain extent, right? They need to make sure that they have the emergency cash, making sure that the basic insurance is covered, then only you go into entrepreneurship. There will be times that you have to dip into your savings, and if you have no savings then you’re looking into loan and debt - that’s when you get into trouble. So #1 advice is to make sure the financial part is settled. You don’t have to be rich, you just have to be secured.

If you have families, you have to make sure that the family part is supportive, number one. And second, that their livelihood will not be compromised by doing the entrepreneurship. But once you have that settled, I would say if you feel very passionate about a certain technology, especially if it’s a technology that you invented, then absolutely go for it, ‘cause no one else will advocate for your technology. No one else will push the technology to its very limit other than you, so you are the best person to do it. Go ahead and do it.

And I would like to quote Steve Jobs, things will make sense once you connect it backwards. So if you look at my journey, starting as a young little undergrad doing protein folding, then do molecular dynamics simulations to see how protein interacts with bacteria and viruses, then going into postdoc to do crystallography, structural biology and drug discovery, learning how to do high throughput screening. If I look back 15 years ago, I wouldn’t have even imagined that I’ll be sitting with you doing a podcast. I think it’s to take on entrepreneurship with a fate knowing that things will make sense. Once you do it, you look backwards. Everything will make sense.

Shamieraah: So in a way, every step has built on each other, all the previous steps. And its connected the dots.

Boon Chong: Yes. They may seem disconnected in the beginning, but when you look back, yeah. Everything happened for a reason and they do add up and they do connect.

Shamieraah: That’s very sound advice. I like that you mentioned to be stable and in a good place, but also believe fully in your idea and have faith in the process.

So on a personal level, how have you evolved with the business? If your past scientist self could see you today, what would be the biggest change?

Boon Chong: I think definitely more strategic when it comes to thinking. When I was a scientist, if there’s a project that comes by and collaborators and say, “Oh, use your lysin in this particular bacteria to try on this particular system, solving this particular problem,” potentially then I’ll almost always say yes, because that would mean getting another paper, getting another publication. Being a researcher in an academic institution, your performance is mainly measured by how many publications you have. So I would say yes to almost anything. You’re interested in my technology to collaborate, I would say yes.

Fast forward to today. I’ll have to consider a lot more factors. It’s not just whether it’s technically feasible, it’s not just whether I can do it or not. It’s more than that. When you consider, how does that impact your brand, your reputation, and also any distraction or any divergence, it is a resource, right? You put this amount of resources to explore this opportunity. Now, what’s the opportunity cost? What’s the potential ROI that you can get out of that? And the product, the IP that’s generated, does it belong to a premium product or if you are making a commodity that is very difficult to sell at a premium anyway.

So there’re a lot of factors that will be taken into consideration when making a decision. It’s no longer just a technical decision. It’s a business decision.

Shamieraah: So knowing the purpose of why you make the decision or why you take that direction.

Boon Chong: Yes.

Shamieraah: Thank you for the comprehensive look from your journey as a scientist to becoming an entrepreneur and what operating ArrowBiome has been like, I’m sure our listeners really benefit with all the perspectives you’ve shared today. So once again, I wanna thank you for coming on, Boon Chong, it’s been a pleasure.

Boon Chong: No, thanks for having me. Pleasure is mine.

Shamieraah:   Stay tuned for monthly podcasts with key stakeholders of the biotech ecosystem, including founders, investors, and policymakers. If you have suggestions for the podcast or who you’d like to hear from, feel free to send us an email in the episode description. Subscribe to our newsletter, The Nucleate Artery on Substack to stay engaged with Singapore’s biotech ecosystem. Join the Biotech Kopitiam Telegram channel, powered by Nucleate Singapore, where we are building an open community to enable conversations in the life science ecosystem of Singapore.

📚 Further readings

[1] ArrowBiome

[2] Dr. Boon Chong Goh

If you enjoyed reading this post, comment and give us a like! Or let us know your thoughts here.

🍽️ Digestibles

High potential SG research, hot off the press

BIOENGINEERING: Engineering Friendly Gut Bacteria to Fight Brain Complications of Liver Disease

@Senuri De Silva

TL;DR:

• Hepatic encephalopathy occurs when liver failure causes ammonia to build up in the blood and brain, leading to serious neurological symptoms.

• NUS researchers engineered beneficial Lactobacillus bacteria to reduce ammonia levels and rebalance key metabolites involved in the disease.

• In mouse models, the engineered strains lowered ammonia in the blood and brain, restored metabolic balance, and improved cognitive and anxiety-like behaviours.

Hepatic encephalopathy (HE) is a serious neurological condition that can develop in people with liver failure. When the liver can no longer properly remove toxins from the blood, ammonia levels rise sharply in the body. This excess ammonia can cross the blood–brain barrier and disrupt normal brain function, leading to symptoms such as confusion, memory problems, anxiety, poor coordination, and in severe cases, coma.

The condition is closely linked to the gut–liver–brain axis; the constant communication network between gut microbes, the liver, and the brain. In HE, this balance breaks down, causing harmful changes in metabolism and brain chemistry. Current treatments mainly focus on lowering ammonia levels, but they often have limited effectiveness and can disrupt healthy gut bacteria.

To tackle this problem, scientists at NUS Synthetic Biology for Clinical and Technological Innovation and Yong Loo Lin School of Medicine engineered two strains of the beneficial gut bacteria, Lactobacillus plantarum, to specifically correct the metabolic imbalances seen in HE. One strain was designed to absorb excess ammonia while producing helpful branched-chain amino acids (BCAAs), while the second strain reduced the production of ammonia by enhancing the breakdown of glutamine, a key metabolite that acts as a source of ammonia in the disease.

When tested in mouse models of hyperammonemia and HE, the engineered bacteria dramatically lowered ammonia levels in both the blood and brain, restored metabolic balance, and improved anxiety-like and cognitive behaviours. Remarkably, the treatment performed better than rifaximin, a commonly used HE drug, while also preserving the diversity of healthy gut microbes.

This work highlights how engineered “friendly bacteria” could become a new type of living medicine; one capable of precisely reshaping metabolism across the gut, liver, and brain to treat complex diseases.

Explore how biotech is reshaping treatments in this field:

• Key HE biotech players that shape the market with strategic partnerships and innovative therapies.

• Irish biotech Aerska raises $39m Series A to deliver RNA meds to the brain.

• Ipsen scuttles liver disease candidates from $952M Albireo acquisition.

CANCER: Muscle-Derived Extracellular Vesicles Emerge as a New Anti-Cancer Strategy

@Senuri De Silva

TL;DR:

• Sarcopenia, the age-related loss of muscle mass and strength, is linked to higher cancer risk and poorer survival, but the biological connection has remained unclear.

• Researchers found that healthy skeletal muscle releases extracellular vesicles (EVs) that help suppress tumour growth, while aging muscle produces fewer protective EVs with altered cargo.

• In mice, exercise was shown to partially restore EV production pathways that decline with age.

As we age, our muscles naturally become weaker and smaller; a condition known as sarcopenia. This gradual loss of muscle mass and strength often begins around the age of 40 and accelerates later in life, leading to frailty, reduced mobility, and a higher risk of falls. But beyond affecting movement and independence, sarcopenia has also been linked to something more serious: poorer survival outcomes in many cancers, including lung, colorectal, gastric, pancreatic, and oesophageal cancers.

Scientists have long known that exercise can help protect against cancer, but exactly how aging muscles influence tumour growth has remained a mystery. Researchers have recently begun focusing on tiny particles released by muscle cells called extracellular vesicles (EVs). These microscopic “packages” carry signals between cells and tissues throughout the body. Importantly, the types of EVs released by muscle appear to change with age, raising the possibility that healthy muscle may actively help suppress cancer.

Researchers at Duke-NUS Medical School explored this idea by studying muscle-derived EVs in both fruit fly and mouse cancer models. They discovered that healthy skeletal muscle acts almost like an anti-tumour organ, releasing EVs that help slow down tumor growth. However, in aging and sarcopenic muscle, EV production drops and their contents change, causing this protective effect to weaken.

The team identified a small molecule called miR-7a-5p as one of the key anti-cancer signals carried by EVs from healthy muscle. This molecule helps suppress tumour growth by blocking cancer-promoting pathways inside tumour cells. As muscles age, levels of miR-7a-5p decline, reducing this natural defence. Interestingly, the researchers also found that voluntary exercises (think mice running on wheels and treadmills) could reactivate a signalling pathway involved in EV production, partially restoring the muscle’s protective communication system.

Together, the study reveals an unexpected connection between muscle health, aging, and cancer, suggesting that maintaining healthy muscle may influence far more than strength and mobility; it may also help shape the body’s natural defences against tumour development.

Editor’s note: Let this be your friendly reminder to get some exercise done today! Leg day for cancer prevention and anti-aging, anyone?

Learn more about biotech advances in sarcopenia and EV-based cancer therapy:

• Marine oligo fucoidan has been developed as a clinically supported non-protein solution for muscle strength in Sarcopenia.

• GLD Partners flexes muscle-wasting ambitions, launching Altagenics with an assist from Heligenics to develop first-in-class medicines for muscle-wasting conditions.

• EVIR Therapeutics develops engineered dendritic cells harness tumour EVs to boost cancer immunotherapy.

• INOVIQ advances exosome-based cancer therapy with promising preclinical results.

🗞️ Industry Spotlight

News from the Singapore life sciences industry

• Singapore and China renew commitment in enhancing regulatory collaboration on health products.

• US-based 10x Genomics establishes their first dedicated R&D lab in Singapore.

• UltraGreen.ai secures regulatory approval for Verdye in Singapore to strengthen fluorescence-guided surgery.

• Taiwan’s Formosa Pharma and Singapore Eye Research Institute partner to advance novel ophthalmic formulations for corneal diseases.

• Huwel Lifesciences & AVIO Smart Market Stack Ltd onboard Singapore-based partner to accelerate Southeast Asia expansion.

• Singapore’s Esco Lifesciences Group announces acquisition of US-based Allwin Medical

• Singapore and Japan deepen collaboration to enhance access to health products.

• Mindray embarks into strategic partnerships to drive med-tech innovations in Singapore.

• India partners with Biocell Innovations to develop advanced CAR-T therapy for multiple myeloma.

• NUS Medicine partners with MitoQ New Zealand to deepen mitochondria targeted research for healthy ageing.

• International Vaccine Institute signs MOU with Hilleman Laboratories to advance vaccine R&D and manufacturing for safe, effective, and affordable vaccines.

🎧 Nucleate Singapore Pulse

Singapore’s premier podcast on the local biotech ecosystem.

Listen now

📆 Events happening this month

Conference/Seminars

• HealthTechX Asia
  (6-7 May, TBA, in person, early bird registration)

• SCRI Clinical Trials Symposium
  (30-31 July, in person, early bird registration until 31 May)

• CHI INNOVATE 2026
  (3-4 July, TBA, in person)

Networking

• Sat Health & Bio Brews Singapore

  (Every Sat, 9:00 AM - 10:30 PM, in person)

Seminars/Panel discussion

• Decoding biomedtech investment strategies
  (21 May, 2:30 PM - 5:30 PM, in person)

• Where East Meets West: Scaling Global Innovation Through Southeast Asia
  (21 May, 5:30 PM - 8:30 PM, in person)

• Validate Your Pitch (Panel & Pitch with VCs)
  (21 May, 6:00 PM - 9:00 PM, in person)

Workshop

• RNA Medicines: From Code to Impact
  (19 May, 9:00 AM - 5:00 PM, in person)

• Investing in the Future of Health Workshop: Precision, Tech, and Impact
  (26 May, 9:40 AM - 4:00 PM, in person)

If you enjoyed reading this post, comment and give us a like! Or let us know your thoughts here.

🍽️ Digestibles

High potential SG research, hot off the press

DIABETES: A Smart Hydrogel Tackles Diabetic Wound Healing

@Senuri De Silva

TL;DR

• Diabetic wounds heal poorly due to ongoing inflammation, high oxidative stress, and infection.

• NUS researchers developed a smart hydrogel that reduces stress, fights bacteria, and releases healing signals to support recovery.

• The approach was tested in cell studies and diabetic rat models, where it improved healing outcomes.

Wound healing in people with diabetes is a major and often overlooked challenge. These wounds often remain open for long periods and can lead to serious complications, including infections and even amputation. The reason is not just one problem, but a combination of issues of persistent inflammation, high oxidative stress, and bacterial infection that trap the wound in a state where healing cannot properly begin. In countries like Singapore, where diabetes is highly prevalent, this continues to be a significant clinical burden.

Researchers at the Department of Biomedical Engineering, NUS have developed a next-generation “smart” hydrogel dressing designed to tackle all three of these problems at once. This hydrogel is made from natural, sugar-based materials that form a flexible network through multiple types of molecular interactions, helping it stay intact while responding to the needs of the wound. Made from a biodegradable material, it detects harmful conditions and signs of oxidative stress, releasing interleukin-4 (IL-4) to help shift the immune system from inflammation to repair. At the same time, the hydrogel helps neutralize harmful reactive oxygen species that damage tissue and delay recovery.

Importantly, the material itself also has antibacterial properties, helping prevent infection without the need for additional antibiotics. The team observed that the hydrogel reduced harmful stress levels in cells and successfully reprogrammed immune cells toward a healing state. In diabetic rats, it significantly accelerated wound closure, improved collagen formation, and promoted the growth of new blood vessels, all of which are essential for proper tissue repair. It also reduced inflammatory signals while enhancing anti-inflammatory responses, and showed strong antibacterial effects in infected wounds, demonstrating its ability to address multiple challenges simultaneously.

Together, this work highlights a shift toward smarter, more responsive biomaterials that do more than just cover wounds; they actively guide the healing process. This hydrogel offers a promising direction for developing more effective treatments for chronic diabetic wounds, where conventional approaches often fall short.

Read more about global innovations in diabetic wound care:

• Ace Therapeutics unveils advanced animal models to unlock breakthroughs in diabetic wound healing.

• BiomX’s bacteria-killing virus reduces diabetic bone ulcers in midstage test.

• Leading biotech advancements in wound care.

GENETIC DISEASE: A New Genetic Link to Accelerated Aging and Neurological Decline

@Senuri De Silva

TL;DR

• Progeroid syndromes are rare genetic conditions where children show signs of accelerated aging, but the biological causes behind these disorders are not well understood.

• Researchers identified a new subtype, progeroid neuropathy, linked to a mutation in the IVNS1ABP gene.

• This mutation disrupts cell division and accelerates cellular aging, resulting in impaired nerve development and neurological symptoms.

Aging-related neurological disorders can affect both the brain and nerves, leading to symptoms such as muscle weakness, poor coordination, memory loss, and even dementia. Among these conditions are rare genetic diseases known as progeroid syndromes, where individuals, often children, show signs of accelerated aging. According to the Progeria Research Foundation, about 32% of registered cases globally are from Asia. Currently, there are no effective treatments, and the condition is associated with a very high mortality rate. Despite their severity, the underlying biological mechanisms driving these disorders remain poorly understood.

Scientists at Duke-NUS Medical School and A*STAR Skin Research Labs have now identified a previously unrecognized subtype of this condition, which they call “progeroid neuropathy.” Patients show unusual skin pigmentation patterns along with progressive movement difficulties, intellectual disability, and structural changes in the brain. While these clinical features are severe, what causes them at the molecular level has remained unclear.

To investigate this, the researchers analyzed patients’ DNA and identified a mutation in a gene called IVNS1ABP. They then studied patient-derived cells, including skin cells and stem cell–derived nerve cells. These cells showed clear signs of premature aging; they grew more slowly, had trouble dividing properly, and often failed during cell division. Digging deeper, the team found that the mutation disrupts the cell’s internal “skeleton” (made of actin), which is essential for proper cell division. When this system fails, cells stop dividing and age prematurely. In developing nerve cells, this leads to fewer neurons, weaker connections, and impaired brain function, helping explain the neurological symptoms seen in patients.

This study provides an important step toward understanding how certain genetic mutations can drive accelerated aging in the nervous system, and offers new clues that could guide earlier diagnosis and future treatment strategies for progeria patients.

Learn how biotech is bringing new hope to this rare condition:

• The Progeria Research Foundation and Forge Biologics announce manufacturing partnership to advance gene therapy for children with progeria.

• Sentynl Therapeutics to license experimental progeria drug.

• Ground breaking new RNA therapy reverses symptoms of progeria.

🗞️ Industry Spotlight

News from the Singapore life sciences industry

Editor’s note: It’s been a happening month in the biomedical field!

• Nestlé and NTU partner to advance research on healthy longevity and women’s health.

• Future Health Technologies (FHT2) programme launches to advance healthier aging.

• Lonza launches Media Development Lab in Singapore for cell culture media optimization.

• NTU boosts innovation with the launch of UOB Innovation Hub.

• A*STAR EDDC launches innovative research collaboration with Daiichi Sankyo to advance next-generation NK cell engagers.

• Nelipak announces opening of APAC Technical Development Center to develop healthcare packaging solutions.

• Genedant Capital and Singhealth partner to accelerate formation of high-quality healthcare startups for novel technologies.

• NTU and UMC Utrecht collaborate to tackle global health challenges.

• MGI Tech and NUS announce collaboration on DCS Lab to accelerate multi-omics innovation in pharmaceutical sciences.

• Thermo Fisher Scientific collaborates with PRECISE-SG100K Singapore to advance population-scale proteomics.

• Expecto Health Science partners with Neuratrial to pioneer AI-driven CRO operating model.

• Meiji Pharma Asia commences operations in Singapore, focusing on infectious diseases, hematologic cancers, and lifestyle-related diseases.

• NUHS launched the National University Centre for Genomic Medicine (NUGEM) to advance precision medicine.

• NUH launches Innovation Hub to accelerate smart solutions and transform healthcare delivery.

• Sonova partners with EDB to open Innovation Center for affordable hearing solutions in Singapore.

🎧 Nucleate Singapore Pulse

Singapore’s premier podcast on the local biotech ecosystem.

Listen now

📆 Events happening this month

Conferences

• 17th World Ageing Festival 2026
  (14-15 April, 8:00 AM - 6:00 PM, in person)

• HealthTechX Asia
  (6-7 May, TBA, in person, early bird registration)

• SCRI Clinical Trials Symposium
  (30-31 July, in person, early bird registration until 31 May)

• CHI INNOVATE 2026
  (3-4 July, TBA, in person)

Networking

• Sat Health & Bio Brews Singapore

  (Every Sat, 9:00 AM - 10:30 PM, in person)

• Science first: a focus on end-to-end drug discovery | J&J
  (24 April, in person)

Seminars/Panel discussion

• CHI Masterclass: How can virtual care transform healthcare delivery at scale?
  (15 April, 2:00 PM - 4:00 PM, in person)

• Integrated mRNA & circRNA-tLNP Platform Empowering In Vivo CAR-T Therapies | ProBio
  (16 April, 2:00 PM - 3:30 PM, online)

• From QMS Struggles To EQMS Success: Transforming Quality For Start-Ups
  (16 April, 11:30 AM - 1:30 PM, in person)

• From Research To Venture: Building And Protecting An Investable IP Strategy
  (23 April, 11:00 AM, in person)

• Guide to starting your business in Singapore with Confidence
  (23 April, 5:00 PM - 6:30 PM, in person)

• The Future of Fundraising
  (27 April, 2:00 PM - 5:00 PM, in person)

• Climate Change and Healthcare Risks: Building Resilient Hospitals and Healthcare Facilities in Singapore
  (28 April, 4:00 PM - 5:00 PM, in person)

Workshop

• Market Validation and Analysis: Turning Ideas into Successful Startups or Businesses with Digital Tools
  (23 April, 9:00 AM - 6:00 PM, in person)

Opportunity

• Amgen x NSG Biolabs Golden Ticket Programme 2026
  (Apply by 1 May)

About The Guest

Mr. Kit Yong is the co-founder of Forte Biotech, a Singapore-based agritech startup developing rapid, point-of-care molecular diagnostics for aquaculture.

Forte Biotech was founded in 2021. The concept behind RAPID was inspired by the founders’ experiences working with farmers in Vietnam, as well as insights from their own family businesses. Having witnessed firsthand the challenges faced by farmers, their families, and their livelihoods, the team remains committed to developing solutions that can make a meaningful and lasting impact.

In this episode, Kit shares how Forte Biotech was founded to address a critical but overlooked problem in shrimp farming: catastrophic losses due to undetected disease outbreaks. He explains how the company built a portable isothermal amplification platform and proprietary DNA extraction chemistry capable of handling challenging shrimp samples, enabling farmers to conduct reliable, onsite pathogen detection without complex laboratory infrastructure.

🥡 Key Takeaways

Key Takeaways

🔬 Diagnostics are the gateway to treatment: Without accurate and timely detection, even the best therapeutics and vaccines cannot be applied effectively.

🦐 Aquaculture faces major disease risks: Early detection of pathogens is critical to preventing catastrophic losses in shrimp farming and improving farm sustainability.

⚙️ Technology must be designed for real-world users: Successful field diagnostics need to be simple, robust, and usable outside traditional laboratory environments.

🌏 Local partnerships are essential for scaling: Expanding across Southeast Asia requires trusted local connections who understand regulatory and cultural landscapes.

🧑‍🔬 Field insights matter as much as lab research: Scientists must engage directly with end users to understand real problems and design practical solutions.

💬 Communication is a key scientific skill: Translating complex science into language that farmers, investors, and partners understand is essential for real-world impact.

💬 Quotes

“Farmers are hardworking, smart people — at the heart of it, they are business people trying to use biology to make money. In that sense, they are already running biotech companies.”

“Diagnostics is really the gateway to treatment. You can develop vaccines and therapeutics, but if you don’t know when or how to apply them, there is no point.”

“In applied science, especially in agriculture, scientists need to go out into the field. It’s hot, it’s sweaty, it’s uncomfortable — but that’s where the real problems are.”

“In the startup world there is no clear guide. You take what you learn, internalize it, test it, refine it, and repeat the cycle again and again.”

“One of the biggest milestones for any startup is simply reaching profitability. Funding is tough — and in agritech or aquaculture, it’s even tougher.”

“Before starting a company, it’s often better to build broad experience first. When the right problem appears, it becomes much easier to build something meaningful.”

”Biotech is a lot of work and the pay can be terrible at the beginning — so you need to be very sure that the problem you’re tackling is worth it.”

⏱️ Timestamp

00:00 Meet Kit Yong

02:33 No Manual for Startups

04:09 Why Forte Bio Started

06:53 Net Zero and Farm Impact

09:35 Rapid DNA Extraction Breakthrough

11:57 Sample Degradation and False Negatives

14:44 Major Shrimp Diseases Explained

18:26 Bridging Farmers and Scientists

20:18 Portable Hardware and Isothermal Tech

21:19 Balancing Cost Accuracy

21:55 Rapid Hardware Overview

22:52 On Farm Reliability Lessons

24:53 Scaling Across Southeast Asia Markets

25:46 Regulation And Local Partners

31:09 Building An Agile Team

33:40 Diagnostics And Food Security

35:57 Milestones Profitability Goals

36:47 Science Communication For Impact

🎙️ Transcript

Aakash Naresh Kumar: Today we are very glad to have with us Mr. Kit Yong. Kit is the co-founder of Forte Bio, a company that specializes in the testing of diseases in shrimp farms. Thank you so much again for joining us today, Kit.

Kit Yong: Yes, thank you for having me, Aakash.

Aakash Naresh Kumar: So Kit, you have had a very interesting journey starting from back at school, from your family business.

Your path is actually quite fascinating if begin by working in your family business to an online e-commerce, even a hospitality business in Vietnam. After that, you began your own grocery store brand during COVID. So could you share what was the motivation behind exploring so many different types of ventures?

Kit Yong: A lack of discipline and a inability to study, I think. For me, I’ve always enjoyed, I’ve enjoyed science. I like the idea that, you know, you have a hypothesis, you test your hypothesis, you see the results and then you refine it further. But I feel that this is, can be used in many ways, right? Not just whether it’s in science or you design an experiment. You can also use it for business to see what works in business. It’s a very good philosophy for life.

I realized from the very start that I’m not a very good student. I can study, but I find it very hard to memorize things. I find it very hard to work like in undergrad mods. You’ve got to memorize what are the codons, my God! I really cannot do all those, especially in the day and age when you can just Google. So I realized very early on that I probably won’t have discipline or the ability to go far. Pursuing a scientific career. So I started to look out elsewhere for other things that I could possibly do and make money.

So I’m very fortunate that my family runs a business, so I have the chance to actually work with them throughout my studies. And that also gave me opportunities to start up ventures, like the hospitality business in Vietnam, which was done with a good friend of mine. All of these are good experiences that I’ve learned how to work with people, how to further refine the own way that I think the whole scientific method thingy and, sort of, build up my experience.

And all of these are skills that I still use on a day-to-day basis. If you’re asking me about motivation, it’s more or less a motivation to survive because I’m frankly speaking quite terrible at studies.

Aakash Naresh Kumar: I think I can agree with you that I certainly do not miss studying as much as well.

How would you say, how did your experience running your family’s wholesale business or pioneering e-commerce transitions, how did it prepare you to finally found and enter the startup world and eventually founding Forte Biotech?

Kit Yong: I think a lot of times as Singaporean, we are very used to instruction manual, right?

A lot of times, let’s say you buy the furniture from IKEA, first thing you do, you look at a panel, right? And then figure out which screw is what, which screw goes where. But unfortunately I’ve never really had that discipline to do so, and I think in startup world, there’s no manual you gotta go and figure out which crew goes where, which part goes where.

I think one thing, when I got my own house and we were getting furniture, we got a lot from TaoBao. And then some of the instruction sheets just thought were not packed. So you to figure out which part goes into the way. And I feel that’s a lot of what happened when I was working in my family’s business.

Plus there is no user guide, right? There are SOPs, but some of the new things like how do you run a business? How do you do online business, if no one’s family done the online business before. What are the best strategies? Of course, all of this you need to learn and you need to go online, see what people do, study and refine and find out a method that works eventually.

So I think this whole experience of taking what we learned, internalizing it, refining it, executing it, and reiterating the whole process was very helpful. And that’s something I should do today, whether it’s with customers, how do I sell to a customer? What do a customer want? Or how do I refine my technical skills a bit more?

How do I refine my own product more? I think these are very important considerations, whether it’s from the technical, scientific side, on the commercial, the business side. This is still the same cycle pretty much.

Aakash Naresh Kumar: I think that’s a good way , if you could share about the origin story of Forte Biotech.

What inspired you and your co-founder to start a test kit for Farmers Company and what problem or unmet need were you trying to tackle?

Kit Yong: We weren’t trying to start a biotech company, to be honest. I think our main aim and motivation was to be a known shark.

Now, why do I say that? It’s because I think farmers are hardworking, smart people and at the heart of it, they are business people trying to use biology to make money. So basically they are biotechs company, if you look at it that way. Just that instead of shiny new bioreactor, they’re doing protein synthesis in a living animal.

So your bioreactor can also spoil and your living animal bioreactor will also spoil, right? And a lot of the reason why it’s spoils is because of diseases. Let’s say you have a fish, you feed protein to the fish, the fish turns it into edible protein. You sell it to a human. That’s the whole idea behind it.

But the fish could fall sick and die. The shrimp could fall sick and die. And if they fall sick and die, you don’t get any money back. So all the money that you spend on fish feed or prawn feed, for example, you throw it in, it doesn’t get converted into money that you can take back if it falls sick. So we realized that there was a lot of problems with financing these farmers because the risk is big.

My own parents, we sell a much more predictable product, so it’s easy to get financing from the bank and they use the financing quite wisely to then build up a business. Farmers don’t have the opportunity to do that, and we want to step in to be able to do that. So that was the original disease. Can I lend money to a farmer and understand what’s the risk that he faces?

Now, most of the risks and most of the losses are because of diseases. They fall sick, they die, and it’s terrible for everyone, not just the farmer, but also the distributor that sells the feed to the farmer, and the factory that sells the feed to the distributor is terrible. So you wanna find a way to find out the risk of what’s going on in the farm.

And at that time, COVID just started and then we saw the pictures of people queuing up in China and everywhere around the world queueing up for PCR tests. It takes two, three weeks for the results to come back because the labs are so overwhelmed and then you fall sick, you think you’re sick. PCR results comes back negative. All these horror stories. And we thought, “Why can’t we do the test ourselves?” And this is a problem that’s happening every day in the animal, in the livestock industry, whether it is chickens, pigs, cows, sheep, fishes, prawns. We have the same pandemics going on all the time. So I realized that it was a good thing to do.

And also the ideas evolve from there to point of care test kit.

Aakash Naresh Kumar: I guess probably will be a good time to also bring up, based on all the different challenges you’re trying to tackle, that you were the winner of the Net Zero Challenge 2023. So congratulations on that.

Kit Yong: Thank you.

Aakash Naresh Kumar: Comparing that with the outcomes that you mentioned and the types of problems you’re trying to solve, what are some of the sustainability outcomes going through this whole journey of this Net Zero Challenge that stood out to you?

Kit Yong: I think the first thing, of course, when we talk about emissions from farming. There are two. The first is the emissions that’s needed to get the feed on site and feeding it through the fish or the shrimp in our case. The second is basically the energy that you need to invest into it. Because you need to run aerators and all that. I think that’s definitely a big problem. Imagine you raise the shrimp to nearly ready for harvest. Spend 90 days of effort and all that, and suddenly you lose everything overnight because of white spot virus, it kills everything overnight. I think that’s terrible. It’s not fun. You’ve wasted all these resources you’ve put in, whether it’s financial or a toll on the environment. You throw all these sick things out without disinfection. It pollutes the environment further, so that’s one thing. The second damage, which I think is the bigger damage , more so than the emissions, is antibiotic abuse.

Antibiotics are being taken as prophylactics in farming. That is ridiculous to me. And I am terrified because I do know that farmers, some of them, they grow some of the shrimp for their own consumption, and the rest is for the market. I think it’s terrible, but I understand it from their point of view.

Why do they do this? Because they’re terrified of what diseases can do to them, and there’s no good way of detecting and managing these diseases early. So I do understand from both the business point of view as well as the scientific point of view, what works and what doesn’t work. So maybe it works for them from the business point of view.

Because antibiotics are cheap. And their objective is just to feed themselves. Today, it’s very hard to plan long term and if you’re going to go hungry tomorrow. So yeah, just do it and it’ll be someone else’s problem. But what we are seeing is they’re getting the seeds of that they’ve planted are now sprouting.

We are getting antibiotic resistant vibrio outbreaks in shrimp farms. They have diseases which they add super in front of it now because it’s a totally more infectious, more virulent strain like it used to be. Caught just EMS, early mortality syndrome. Now they got EMS as well as super EMS. So we are seeing all these challenges and I think to me, if our company can prevent one more super disease from appearing, I will be very, very satisfied.

Aakash Naresh Kumar: It is a scary thing with all the antibiotics, not just in bugs, but now I should mention from the feed as well, even among animals. But I think it’ll be a good time to transition a bit to talk more about Forte Biotech’s technology, described as the rapid system that employs a propriety chemistry to extract PCR grade DNA.

So what was the inspiration behind this propriety chemistry?

Kit Yong: Currently, when you want to do a PCR, you normally need to use column based methods or magnetic beads methods, right? The chemistry behind, it’s actually very simple, but the problem is how do we apply this? Concept into the field in an effective manner.

Recently I was at the University of Arizona to take a short course on shrimp pathology, and then it’s all PhD level students. Most of the participants are much more educated than me. We split into five groups to do a PCR test on shrimp. Of these five groups of very well educated people, much more than the general lab population in aquaculture, only two groups managed to get the answers correct for the samples. I’m glad to say my group is one of them. So it’s actually difficult because shrimp are very, very challenging samples to work with. You’ve got a high enzyme activity inside a lot of DNAs, RNAs. You’ve got a lot of lipids inside. You’ve got a lot of proteins inside because it’s basically mix of the liver and the pancreas.

I was very lucky to work with Dr. Chung-Pei of DXD hub, previously of NUS, during the NUS GRIP program. And with his experience, we came out with a product that is able to use the Boom’s method and other similar methods to then do the extraction. We wanted to make it something that was so easy to even a drunk farmer can do.

So we have to limit a lot of things so that we are able to actually use it onsite without centrifuge. And at the same time, make it suitable for ENT transportation. Because I think no insulation will be able to pack something that is needed to be stored at minus 18 all the way to the remote village in Vietnam.

No insulation’s gonna do that. So you need to make something that is able for, I would say even the most drunk farmer and the most remote villagers of Southeast Asia to use. So I think that was the inspiration behind what we did.

Aakash Naresh Kumar: It’s really good to know, though. It’s also interesting to understand that prawn samples, as you mentioned, with all this high protein content enzyme, it’s difficult to extract DNA. So could we dive a bit deeper as to how do you isolate this clean PCR grade DNA from this very hard to get samples?

Kit Yong: Yeah, it’s really quite easy, you just use sugar spice and everything nice. And then we add chemical X into it. The way that we do it is basically we look through a lot of the protocol.

And then it came a two year process of then optimizing what’s necessary. We have a very good team that did all this experimental work working through countless amounts of shrimp, whether that is the one that we grow or the ones that we buy from Sheng Siong, which credit to Sheng Siong actually has the freshest prawns.

So if you are a seafood fan, buy from Sheng Siong or Prime, they tend to have the best seafood in Singapore among supermarkets. We know this because if you test only fresh shrimp, you can detect diseases. We detect diseases, we know that a shrimp is really, really fresh. And that’s one of the challenges because a lot of farms, they will sample and send it to the lab. But because of the transport process, the shrimp is not well preserved. It’s not so fresh anymore. The diseases actually get digested. The pathogens get digested away by the enzymes in the liver or in the shrimp. So you get a false negative. It’s not a false negative because the PCR, that is a false negative because the sample is already degraded.

So that’s all the challenges that we had to go through. For our extraction chemistry, that’s basically, sort of rethinking of how can we use the various methods that literature already have to combat this along with the restraints that we have. That’s how we came up with our methods.

Aakash Naresh Kumar: So in a way, if I could repackage that it’s more of like you are trying, if there is any pathogens inside a particular group of samples, you want to find it before it gets degraded by the liver.

Kit Yong: Yes, pretty much. So basically, our license buffer has to do quite a lot of things at the same time. And one unintended ability of our lysis buffer is that we can actually store samples for quite some time in ambient temperature for further processing, whether it’s by column base or other methods. That was a very surprising finding that you have because even samples which I’ve taken from the furthest of places I live in my luggage, I forget about, one month later I take out is still working, we still can get DNA from it.

So I think that’s something that is quite surprising and something that we realized on hindsight that other people have already commercialized. So I think that’s something that we can also go down, but our main focus is still on point of care because that’s where we feel it has the biggest benefits business wise.

Aakash Naresh Kumar: It’s quite distinct. Learning is like a, something that you were not planning on finance. Somehow you found it by chance.

Kit Yong: Yeah, but I mean, we also have to be lucky if Isaac sat under a durian tree, we wouldn’t know much about gravity.

Aakash Naresh Kumar: Very well put, I think of all these diseases, what are some of the major diseases and pathogens that affect these shrimp farms?

Kit Yong: We have a lot of, so maybe we just start through the different types of living things. Viruses are a big problem, so shrimp, they do not have adaptive immunity. They only have innate immunity. So basically their immune response is to swell up, malise and die, if I were to put it that way. So they’re very prone to infections, right?

So for viral diseases, they’re basically defenseless. Because they have no way to stop viral replication inside there other than apopthosis. So that’s one issue that they have. So white spot virus is a very bad problem that they have in Southeast Asia. There are also other diseases such as Taura, for example, that was the first big disease back in the 1980s coming out from Ecuador.

Pretty much they’ve been able to bring resistance to it. By sort of taking out the receptors that make them vulnerable to the Taura virus. They’ve also other diseases in China, like DIV decapod iridescent virus, IMNV, RNA virus that basically rots half the prawn. So you have some prawns, the front half is working, the back part is rotten.

It is very interesting and I think there’s a bit of a disconnect between the lab and the farm. Because the farmer basically tell you, oh, we seem to have two IMNV types. One is the smelly type and one’s the non-smelly type. I say, what do you mean by that? Oh, smelly type is when they get infected, they smell very bad. Non-smelly is when they get infected. They just look infected, but they’re not smelly. So what does it mean for the farmer and what does it mean for the lab? Because he said in the smelly type, basically everything died overnight. Non-smelly type still worth a hundred, a few two, three days, so it’s about bridging these differences.

I feel that’s very important. So that’s one side of the virus. For bacteria, they tend to have better defenses. But now we have bacteria that have plasmid that produce toxin, so vibrio is a very commonly seen bacteria, normally quite well managed, but they have managed to take on plasmids from bacterias that infect butterflies of all things, caterpillars. And those have proven to be very toxic for shrimp for some strange reason. So God knows how the plasmids got in there, right? But you have a lot of antibiotics being used. It’s no surprise that there’ll be horizontal transmission or all this plasmids. People just transfer to each other. Bacteria just transferred to each other and all that. I’m not surprised that this infectious started. So we have one that decimated the Thai industry, AHPND. And recently we have another one that’s starting from China now. Very bad in Vietnam, the translucent post larva disease. All of these are basically plasmids that are in vibrio, so it’s very interesting to me.

Sorry, I’m nerding out here. And finally, another big problem that we have is what we call EHP Enterocytozoon hepatopenaei. It’s actually a fungi, a microsporidian that causes the shrimp to slow down in growth. It doesn’t kill the shrimp, so it’s a very big problem because your shrimp are not dying, so you cannot tell that it’s a disease.

The only way that you know is you keep feeding and they’re not growing bigger on the business side, you lose a lot of money. Because by the time you realize you have probably invested a lot of money into the feed and you realize it’s not growing and they also as a gateway for other opportunistic bacteria to come in.

So yeah, it’s a lot of diseases. And I’m sorry, I realized I. It just went on a lot. This is what happens when you get a biologist to come and do a podcast. We just start rambling about all the science that we like.

Aakash Naresh Kumar: Actually yes , we do dove into the science. So you actually at home, but there’s one interesting fact that you mentioned that I would like to just a little bit deeper in.

Would you say that the current sort of crosstalk between farmers and scientists. Do you think there’s a gap over there that needs to be bridge in terms of communication between the two?

Kit Yong: I think sometimes we all speak different languages, and I don’t mean the fact that in Southeast Asia we still speak Malay, Thai and all that.

Yes, that’s one challenge. But the bigger challenge is what does it mean? Like in the case of the virus, smelly IMNV versus normal IMNV, how do you define smelly in a scientific sense. How do you compare, oh, this one is a nine of 10 in terms of smell. This one is seven out of 10 or okay, three out of 10 means it’s the non smelly.

So some of these observations need to then be, or the business side on the field side needs to then be translated in a way that the scientists can understand. And similarly, the findings that the scientists know should also then be translated into something that the farmers can understand.

I think that’s the big difference that we have now. In this case, I was very lucky in Arizona, I met Dr. Arun Dhar, he runs the lab over there, and when I tell him about this scenario, he said, oh, okay. It’s very interesting because smelly means that it’s rotting faster. If it’s rotting faster means the cells are dying faster, and if the cells are dying faster, means there is a higher virulence. So if there’s a higher virulence, there should be a higher mortality. I went to check and yes, the smell one is actually about the higher mortality. So it does take a mix of experience and scientists who actually bought it to go into the field work.

I feel like maybe in Singapore sometimes, we are very non-field work. We like to be in the lab. Sometimes scientists, especially in this applied field, do need to go out to field. Do need to work on a fuel more, even if it’s hot, sweaty, uncomfortable.

Aakash Naresh Kumar: My next question was gonna be talking about some of the other key features of your platform, which revolves around portability.

Going on a field is definitely a very important part of any scientific work, but you’ve developed proper hardware like the rapid heater, reader, rapid plus, a rapid mix with various specs, what are some of the different parts that make up this hardware? Could you just briefly talk about what they do?

Kit Yong: A huge reason why PCR machines are very expensive is because we need to control the heating and cooling very accurately. I think that’s something that’s expensive. And you also, for the case of PCRs, you need to have very powerful lasers or rather precise lasers that can shoot good receptors, right?

We try and reduce the cost of all this hardware, so by doing so, we make two decisions. The first was to use isotherm amplification because it makes the thing a lot simpler, with one temperature, you just heat it up to, in our case, 65 degrees, 67 degrees. It just runs steady. You don’t need to worry.

The heater is cheap, right? You don’t need to precise temperature control. Save a lot money. The second thing is basically the information they need. Because basically, isothermal is very famous for non-specific amplification. It’s hard to control, but we have taken steps to design such that we spend a bit more.

So instead of Cyber base, we go a bit deeper into molecular beacon and stuff like that. Yes, it’s a bit more costly, but for us it’s important because the savings that we have from every other part can pay a little bit for this bigger part. So that’s how we balance the cost with the accuracy.

And in terms of this, the different parts of the hardware basically for Rapid. As far as Rapid Max, this are qualitative systems. I give you a yes no result at the end of the day, using my reader, which can also send the data back via email at the moment. But we are also trying to add WhatsApp, Telegram as well as our own AD Plus, and then on Rapid Plus is a development together with DXD Hub from A-STAR what we do is a semi- quantitative lab. So we are able to tell when where’s amplification, we’ve devised a sort real time ability to measure fluorescence at a very low budget. So if I’m not wrong, we are compared to equivalent machines from China, we actually can undercut them by up to 10 times because our engineering is cheap and our company boss is stupid.

He doesn’t want to raise the price. So I think that’s also a big problem.

Aakash Naresh Kumar: So in terms of on -farm operations, do you have to bridge any gaps when it comes to letting the farmers know how this whole system will work? How do you ensure that when the runs are happening is reliable?

What are some of the key engineering constraint that you have to solve? And do you have to communicate all these to the farmers on the ground?

Kit Yong: Oh, yes. Actually, it’s very interesting you mentioned this ‘cause we had a mini crisis couple of months back. Because for some reason, whenever we take our machines to Thailand, they do not work for whatever reason.

And I realize you’re so simple, so silly. Thailand, the power plugs can take either too round or too straight. Straight ones tend to sit more tightly as compared to the round ones. So we were equipping them with the round ones instead of the straight ones. The wire came loose, probably doesn’t work. Stuff like that.

So it is really the details. I think we learned a few lessons along the way, right where, as much as I was telling you earlier about we need to cut the cost, but we also need to invest in good enough quality. So, especially in these sort areas, I think robustness is very important. So we try and build things that are simple and robust. Your screen is busted. Okay, nevermind. I send you a new screen. You just put it in, or it’s not working. Never mind you just send a thing back to me. I send you a new one. I think we we need to make it cheap enough and easy enough to use so that we are able to effectively service these customers.

Because the customers, aside from Thailand, no one else ever asked for operational manual for some reason. So it is so simple, you just put it on YouTube video and you understand, right? Most of them is all okay. We need to really dumb down the operation and make it really as simple as possible for people to use it effectively. Because if people don’t use it effectively, the first person they blame is, oh, this device is not accurate, right? It’s never, oh, I didn’t know how to use it. So I think that’s a very important part.

Aakash Naresh Kumar: I think that’s probably a good time for me to also ask. You launched Forte Biotech in 2021 and it’s now expanded to at least five Southeast Asian markets.

So how have the different farming cultures or regulatory landscapes shaped your approach to your expansion to these countries?

Kit Yong: Oh, a lot, a lot. I think it’s quite interesting because the whole shrimp farming industry is very big, but we are small at the same time. So it is one of those industries where everyone knows each other, all the companies know each other. We were exhibiting in Thailand where we meet our distributor in Philippines, and our distributor in Philippines helped get us a customer in Vietnam. Who then gets another customer for us in Thailand. So it’s a very interconnected industry. Everyone seems to know each other. Everyone has tea on each other and all that. I mean, this is not Aquaculture podcast, so I can spill a tea. I’m just kidding. But it’s a very small industry. I think when it comes to regulatory landscape, we have to track carefully because unfortunately we operate in a very awkward space.

We are not a hundred percent biotech. We are not a hundred percent healthcare. We’re not a hundred percent anymore health. We occupy something in between all of this. Sometimes it’s hard for regulators to decide where we land, so we do have to be quite careful. Most of the time we find the easiest way, anything more detailed will probably get me into jail or trouble.

I’m just kidding. Nothing will get me in jail, I hope. But. We’ll have to find the most efficient way to get into a market, and if the most efficient way is also too difficult, then we have to put our focus elsewhere or need to find other ways to do so. I would say that recently I was at a APEC convention and there was actually a whole session about regulation on farming products.

In that discussion, it happened to be about CRISPR, gene editing and all that. Which level of gene editing would you need to get approval for, or which are just go ahead and do it I think it’s something that industry and regulation need to catch up to the sites because our science is evolving so quickly, right?

CRISPR is opening up so many possibilities. Not just that, we also have AI, we are just speaking ahead for this about how AI can also help us about, experimental design and the things that can do. So I think it’s very important that regulators need to update their mindset fast enough, and I’m glad that quite a few of them know that and they’re working on that.

So that’s good, I think I’m optimistic.

Aakash Naresh Kumar: Absolutely right about the fact that landscape’s changed really quickly, especially with AI now coming in. When you do enter a new market, for example, would you say that it’s important to have a local connection, someone that can push you in the right direction for regulation and all that?

Kit Yong: Yes. That is essential. Absolutely. It’s essential, I think you need someone. We are lucky we’re from Singapore. Singapore has a set brand name already, that we are reliable and trustworthy in most of the cases, so that helps as a diagnostic company, but the other part of it is the connection.

So no one’s going to talk to a random Singaporean knocking at your door. You need a connection and all that. We as a people tend to be a bit weaker. Because we are very business first, right? Normally in the rest of the world it’s friends first business later. So I think that’s something that I was quite lucky with.

Because we make good friends, we show them the video , our product, they feel like, hey, these guys are reliable. We can work with them. And then they push you into different markets, they help you with quite a fair bit of stuff. So I think that’s important. But we do need to make friends.

Yeah. It’s very hard to be just a company like that.

Aakash Naresh Kumar: Connections are very important. And the Forte Biotech also has a partnership with NUS GRIP. Speaking of connections, how would you describe your collaboration with them?

Kit Yong: I think NUS has been a very good supporter from starting being our first funder, giving us a good space to use at NUS Agritech Center and giving us the exposure.

No one’s going to believe a random guy on the street that says, hey, I can make a PCR for chip. I can make a molecular diagnostic system for chip. But having a brand name that actually helps to bring a bit of credibility and it helps us with the getting our foot into the door. But beyond that, of course we have to rely on ourselves to make sure that it’s a good product so that we can keep ourselves, our walk through the door eventually.

So yeah, I’m very grateful for the initial partnership and we make quite a lot of friends there. We get to ask people for help sometimes, or bounce ideas with people, which I think is the most important. At NUS Agritech Center, we gotta talk a lot with NUS GRIP seniors. The whole team has been super generous.

And super happy to share their information and experience. That helps us, even if we are not working on strawberries, for example. But it helps us a lot in understanding the market and thinking about ideas. That whole Kampung spirit, they have there, is very helpful.

Aakash Naresh Kumar: See, that’s also interesting to know, this is all data you mentioned with your current partnerships. What would you say are some of the other factors that you look for when exploring a potential new partnership?

Kit Yong: I feel it’s a lot of factors you look for in a wife or husband, whatever, the partner, first of all, there must be the same direction.

There must be a common goal, then must be compatibility. Maybe you just want some benefits from each other, but friends with benefit will never really last for very long. You need to really hunker down and say, okay, are we working in the same direction? Is this something that can be long term? Because I think for bio, as you mentioned earlier, it’s a very small industry, like everyone knows each other. If you play bunk, people know that you are not nice, and that harms the future chances for anyone involved in this. So I think we are very lucky, we have picked up good production partners along the way. We’ve picked up good research partners along the way, but we’ve also picked up partners who are not so good.

I think a lot of it comes down to experience and basically fights. If the guy is trustworthy, if they’ve done good work and they’re putting in a good research or production agreement. Then to qualify things like QC, things like your standards that you need to meet and all that, at least it’s clear on both sides and a good prenup must be there. It’s pretty much like getting married, I say.

Aakash Naresh Kumar: That’s a really interesting analogy to use. With a partnership, you have to make sure that the goals are aligned. It’s something that is mutually beneficial, but looking within as well. Can you share how you build and empower your multinational team across different markets you are in and also how do you keep them agile, like innovation, focus in this rapidly evolving tech space.

Kit Yong: I think we’re just very lucky to have gotten a very good team, for example, in Vietnam, my manager over there actually came from all the way back when I was doing the Airbnbs in Vietnam. So you’ve known each other for eight years, even before I started this business. I’m just very lucky to have the fit to meet good people.

I am very lucky to have had good bosses in the past, like in NUS. I strongly believe as a leader we need to empower our team to have ownership of their decisions to take ownerships of their little things. And we have to take responsibility, those decisions to not work out. So I think that’s very important to know that they can go and explore, go and learn, go and iterate, and if things screw up, we all take responsibility for it because we are building something.

I think that’s the way it is. And opening a very open chain of communications right between them. I think there are times when I need to also do better as a leader when it comes to this, but I’m just thankful that we’ve got a team that is very motivated and quite easy to manage, to be honest. We have had interns who basically with us through their school and intern out, convert to full time right afterwards.

We build a certain sort of spirit and experimental spirit, I think that is what we want to encourage. So instead of all tabletop exercises, I just gonna try. If you say you want to run an experiment, can I test oysters or can I test muscles for disease? Just go to market by a few muscles.

Do spike experiments. If our extraction works, how much would that cost? Maybe four, five hours of your time? Maybe, I don’t know, 20, $30 for the muscles, $50 for the reagents and all that. So I think that also, if they’re confident, they can then decide what they want to do and think and react fast, right?

So it’s just like an octopus with a decentralized nervous system. I just had one of those, raw octopus in Korea where they would chop it up for you and then you just have it, and then you see every arm still move for their own. I don’t want my company to be chopped out like that, but I like to think that our company functions like octopus in that sense.

It’s decentralized, but our octopus is too smart, can do a lot of things.

Aakash Naresh Kumar: It’s very interesting that team spirit, that family spirit, everyone is supporting each other. But it’s good to also transit more to the future outlook of Forte. How do you envision Rapid or even similar diagnostics impacting global food security in the future?

Are there any other livestock or disease areas that you see as something that you can target in the future?

Kit Yong: I think diagnostics is the gateway to treatment. We’re spending tons of money on making therapeutics. You’re spending tons of money making treatments, vaccines, but if you don’t know when to apply it, how to apply it, and how effective it is.

That was the point. So I feel we are being hampered by the lack of suitable onsite diagnostics for care testing. We see more diseases happening, as I mentioned earlier, a EMS, not fun. The fact that we are bringing nature and humans a lot closer together. So not take transmissions, not fun either, right? So we do see that there will be more diseases, outbreak and all that, right? They will trend out food security, but at the same time, on the optimistic side, we also do feel that, there is a lot of AI and a lot of new tools that are not available to farmers to take out the pain of the brain work screening through all the papers.

Doing all the testing, but instead a sort of brain to then suggest that, Hey, look, you could have problem A, B, C. Let’s solve it. A, you do this just to make sure it’s not a B. You do this just to make sure it’s not B, C. You do this to confirm the C, and then they can take the right decisions and the right treatment for our next plans, we are definitely looking at fish, we are looking on the ground. But I don’t want to say too much for the fear of jinxing it. So we’ll be moving through more animals because after it’s a platform, right? So that’s what we are looking at.

Aakash Naresh Kumar: And obviously we wish you all the best in that! Speaking about being the gateway to developing therapeutics in the future, would you say that the companies that do diagnostics, they have to really work well? The companies will be developing those therapies that comes out from the findings of your diagnostics.

Kit Yong: Yeah, I think that’s the goal. It needs to be a team, right? In agriculture, we need to have good animal health, we need to have good nutrition, we need to have good husbandry.

Only then you can have success. Everyone just wants, oh, I want to do this. I want to go on my own. It never works.

Aakash Naresh Kumar: That’s true. But looking ahead, what would you say are some of the key milestones or goals Forte Biotech in the next few years?

Kit Yong: The first is to reach profitability.

Funding for biotech is tough. Funding for agritech is even worse, and funding for aquaculture is the worst because of whatever happened with fraud and e- phishery. So I think that’s definitely the near term goal. We need to be able to feed ourselves, and moving forward we want to expand to these other animals, and we would hope that we have a role to play in preventing the next animal pandemic.

Whether it’s things like African swine fever, avian flu, or even strep in tilapia and all that. These are all big problems we face now. If we can play a part to soften the blow of these problems, that’d be fantastic.

Aakash Naresh Kumar: I think speaking about, solving these problems, one key factor is also having to explain scientific theories or scientific information to members of companies who may not have that subject background.

How would you say you can bridge the gap to explain in a way like, this is what we need from a business point of view and from a science point of view.

Kit Yong: I feel that with the little experience I have so far, it helps to be a good listener. Because being able to listen and actively listen. You understand what people like, what people feel, and when you’re able to get in touch with other people’s feelings.

Then you are much better able to explain. We as scientists sometimes we’re grounded in facts. It’s all about facts, facts, facts, facts, facts. We fixate onto the fact that we are telling facts, which should be the truth. But at the end of the day, if people are going to think that vaccines cause autism, and no matter how you throw the facts at them, they’re just not gonna listen.

But instead, if you say, okay, why? Why do you feel this is the case? What is the truth behind this? You can start to understand what’s the fear. We can start to understand what’s the thought process, and then we can use that to build our own arguments against this, right? For what we think is the truth, and what is proven to be the truth sometimes. I do think that’s a very important thing, which sometimes we as scientists neglect.

Aakash Naresh Kumar: So would you say that in the future there has to be more focus on scientific communication, not just between scientists, but scientists and business individuals, or even maybe the hospitals.

Kit Yong: I think it’s about making it easy to understand. It’s hard for me to go to farmer to explain difference between a digital PCR, qPCR as well as a point of care task, right on using isothermal amplification. But if I tell, okay, that one is Ferrari, this one is Mercedes, mine is a Toyota. She understands straight away, right?

I think it’s not about simplifying things, but rather understanding who the partner in this, who you’re talking to, and building a solution that works. So that they understand, they can appreciate. Because it’s like playing catch, right? If I throw a ball to you, I must throw to within no matter what, to somewhere that is near you.

Because even if you’re the best catcher in the world and I throw the ball like 40 meters away, you’re not gonna catch that. So we need to learn how to throw better, but we need to learn how to catch better so we can throw better. I think that’s what we are doing.

Aakash Naresh Kumar: Well put. I think having to be able to communicate this kind of scientific communication is really a hallmark of a good scientist and something that we all definitely do. It is important in our work. But moving on to a more personal level, what keeps you motivated in this quest to make testing accessible and accurate?

And also if you could offer any piece of advice to aspiring biotech founders tackling real world problems, what would it be?

Kit Yong: I think on a personal level, what keeps you motivated is to make money. I think it’s difficult to not make much money. I wanna make more money. I think that’s a big problem that we have in biotech for the amount of work that we do the pay is terrible. So yes, I want to pay myself more, I want to pay my team more.

So I think that’s a motivation, right? Of course, if we can help our customers do better, that’s nice. But that’s a corporate thing for me to say. That’s not a personal thing for me to say. If I could offer one piece of advice to aspiring founders, it would be don’t, because I think this climate is terrible.

Don’t do it at this time. I think there are quite a lot of problems that we like to make up ourselves. We don’t know if it’s a real problem that people care about, we don’t know if it’s the best way for us to treat things, but I would say that it would be good to take a job or a position where you get to be exposed to a multitude of things.

Build your experience from there. And I think when the climate or when the need arises, it’s much easier to build startup. I think it’s a lot easier to build now in 2025 as compared to 2021 because of Chat GPT and other large language models. I think they do help a lot with scientific work, scientific research and stuff. I think that’s good. But then that also puts the owners on you to really identify a good problem that cannot really be solved that easily. I do feel that agriculture is one of those which are basic human needs, right? So as long as you go for basic human needs, I do think that would be quite safe.

Aakash Naresh Kumar: We are all super excited for what Forte Biotech has upcoming in the future. Thank you so much for your time today.

Kit Yong: I really appreciate it and thank you very much for the time.

Aakash Naresh Kumar: Thank you.

Kit Yong: Thank you.

📚 Further readings

[1] ForteBio

[2] Kit Yong

[3] Catch & Culture Review: Is the shrimp disease AHPND spread by an airborne pathogen?

[4] NUS Enterprise | Forte Bio

[5] WEForum | Want your shrimp healthy and antibiotic free?

[6] Vietcetera | Net Zero Challenge

About The Guest

Dr. Edison Liu is a medical doctor turned cancer geneticist, whose work focuses on cancer genomics, breast cancer biology, and translational medicine. He has held senior leadership roles in biomedical research institutions in the United States and Asia, as the founding executive director of the Genome Institute of Singapore (GIS), and later the president and CEO of the Jackson Laboratory, one of the world’s leading genetics research institutions. Along the way, he helped shape Singapore’s biomedical landscape, led genomics research through crises like SARS, and expanded global position medicine efforts across Asia and North America.

📄 Summary

In Part 2, Dr. Edison Liu covers covers accountability and KPIs for Singapore’s biomedical initiative and how the 2003 SARS crisis validated translational research and GIS’s role, leading to recognition, embedding in MOH pandemic planning, and expanded work on H1N1/H5N1, Chikungunya, and Dengue. He shares that Singapore engineered healthcare as a discovery engine that supports economic welfare through pandemic control, precision medicine, and healthy aging, contrasting Singapore’s efficient population-based system with the US. He describes Singapore’s planned hospital/research cluster model versus evolving academic medical centers in the US, then explains leaving GIS after 11 years after developing successors. He recounts leading Jackson Laboratory’s transformation from 2012, scaling revenues and endowment and expanding campuses internationally, and emphasizes leadership traits (risk-taking, humility, learning), self-sufficiency in training, PhD reform, and Singapore’s bilingual role bridging a “two-systems” world while noting small size can enable global excellence.

🥡 Key Takeaways

💰 Biomedical Initiative’s Dual Economic Role: Dr. Liu noted that the Singaporean biomedical initiative is vital to the economy as a standard driver (attracting companies) and as a discovery engine to find solutions for the country’s health problems.

🧑‍⚕️ Singapore’s Health System Efficiency vs. US Spending: In a striking comparison, Dr. Liu highlighted that the US spends 18% of its GDP on health with poor metrics, while Singapore spends around 8-10% and achieves top health statistics, signifying high economic value and efficiency.

⏳ The 10-Year Leadership Cycle: He explained that his decision to transition out of major leadership roles, such as at GIS and JAX, was consistently based on seeing “patterns repeat itself” after about 10 or 11 years, signaling a personal need for new challenges.

👨‍🎓 Success in Succession, Nurturing Local GIS Talent: Dr. Liu proudly confirmed his success in succession planning by developing local talent, noting that three of the four leaders who succeeded him at GIS had previously worked under him directly.

🎓 The Call for PhD System Reform: He strongly critiqued the US PhD education system as “archaic” for its two years of upfront coursework, lack of a clear endpoint, and failure to integrate advanced tools like AI into learning and assessment.

💬 Quotes

“The piece that I always find is the most important is how can we teach self-reliance, self-sufficiency and self-motivation. In other words, I don’t have to spoonfeed you.”

“What Singapore learned in 2003, was that the pandemic control, which is a health-based problem, was essential for the welfare, the economic welfare of the country.”

“I am just astonished at how Singapore has actually engineered their healthcare system in the most dramatic way to be a discovery engine.”

“If you follow those three principles, you’ll do okay. Arrogance kills. Laziness kills.”

“So, the fact that Singapore is bilingual, it’s one of the few countries that are truly bilingual, okay? It’s brilliant... So long as US and China are jostling with each other, Singapore will be preeminent in its position to broker the two worlds.”

“Opened my eyes to the fact that size doesn’t matter. In fact, the smaller the size you are, the more likely to solve huge problems.”

⏱️ Timestamp

02:40 KPI and doubts

05:25 Health as Economic Engine

09:50 Knowing When to Step Down

13:10 Why join JAX

14:01 Scaling JAX Globally

18:15 Leadership Traits for Scientists

21:10 Rethinking the PhD in today’s era

26:10 Singapore and Asia’s Biotech Future

🎙️ Transcript

Welcome back to Nucleate Singapore Pulse.

This is Part 2 of our conversation with Dr. Edison Liu, founding executive director of the Genome Institute of Singapore and former president and CEO of the Jackson Laboratory.

In the first episode, we explored how Dr. Liu moved from clinical medicine into science, and how he built the Genome Institute of Singapore into a globally recognised centre for genomics research.

In this second part, we talk about the bigger picture, how scientific ecosystems are built, how Singapore positioned itself in the global biotech landscape, and what today’s scientists need to understand about leadership, value creation, and the future of research.

Joson Ng: That’s an amazing story. I also can’t help but feel that with all this, building up of GIS, that the government will also have to be accountable for taxpayer money. For example, they would have to set several KPI and they feel like there’s a need to validate the existence of pushing Singapore towards the biomedical front. And you also brought up the SARS crisis back in 2003, and you mentioned how Dr. Lisa also ran ahead with, looking at the virus itself. Do you feel like that crisis validated the need for people to really look more into translational research?

Edison Liu: Absolutely. In fact, I came in 2001, prior to 2003, I used to get routinely asked, very politely, what’s your KPI and how we ever gonna get our return of investment? Exactly those two questions. Very often by ex civil servants, because the civil servants are too polite. The government wanted this and they’re not gonna question it. But the ex civil servants were very clear, what are you doing? And the thing that quite frankly, I found not very helpful, was the statement that I heard on a couple occasions, that Singaporeans aren’t very creative and that we should stick to things that we can copy. Literally, people said that and I found that personally offensive because I didn’t think the people of Singapore had that phenotype. It just doesn’t make any sense to me. It just used to be a hub of commerce and everything. So that’s not correct.

So when SARS happened, it was a big struggle, but we persisted. We contributed significantly so that, quite gratefully I got awarded the president’s medal. GIS was acknowledged as the key agency to help solve the SARS crisis. We became embedded in MOH’s pandemic planning process, for H1N1 and H5N1, and then of course Lisa started to do the Chikungunya and Dengue type of stuff, when she took over some more and we did a bunch of Dengue things. But after 2003, nobody asked that question, at least they didn’t ask it to me.

To be honest with you, it was then asked, and I think it was the right question to ask. But I think what has happened over the years, especially in today’s A*STAR and today’s the biomedical initiative, what you see here in this incubator is a deep understanding of how the biomedical aspects is important for the economy of this country for two reasons.

Number one, the usual. Can I get a company and get invested, can I bring multinationals here, et cetera, et cetera. It’s a standard economic driver. But equally important, you need to, I am just astonished at how Singapore has actually engineered their healthcare system in the most dramatic way to be a discovery engine. And that discovery engine enhances the product development, but very importantly is going to be the basis of solutions for health problems at this country.

What Singapore learned in 2003, was that the pandemic control, which is a health-based problem, was essential for the welfare, the economic welfare of the country. Absolutely essential. And you hear now in the RIE 2030, the framework of precision medicine and healthy aging, right? It makes total sense, my friend. We have an aging society here. How do you actually keep people growing older, healthy becomes an essential part of the economic equation, and can we actually extend the productivity of people of my age, is going to be essential. As essential as the time that people were saying should women be in the workforce? People actually originally asked that question, and now it’s crazy for you to say, women should not be in the workforce. That’s half of humanity that could be productive in society. So that’s what I’m trying to say is that the basis of health is embedded in the economic welfare of a country. And all you need to do is take a look at the US where we spend 18% of our GDP on health and have one of the worst health statistics of the G 20. One of the worst. Whereas Singapore has, what, 8% of the GDP. Some people argue maybe up to 10%. But that’s nearly half of what the US spends, and you now have a number one, or number two, or number three in health metrics. That’s economic value.

Joson Ng: I think Singapore really does well in terms of learning from past experiences, adapting and engineering, even better solutions. And in terms of healthcare and biomedical research, Singapore took its way to find where it wanted to be, what kind of innovator it wanted to be. And so far things that we’ve come up, for example, like HealthierSG, things that take care of healthy aging.

But one of those models is actually the tight partnership or very close knit partnership between hospitals and research institutions, where we have Singhealth being paired together with Duke-NUS, the NUHS system to NUS. How do you think, that kind of model or system in Singapore compares with what we have in the US or in Europe?

Edison Liu: The US has always had the concept of academic medical center, but it wasn’t done by planning, it was done by just evolution. And it wasn’t structured to fundamentally deliver care like it’s done here. The thing that amazed me was the whole time I was here, this was discussed, we talked about how it was really necessary to have a discovery based medical system that is continuously learning rather than simply being a mechanic to deliver, fixing problems.

Joson Ng: Like just fighting crises.

Edison Liu: It’s just fighting crises, personal crises, important crises, but fighting crises to be framed in the planning process for the whole of health for our country. What they did to structure the three clusters, used to be two. And by the way, the two clusters were structured in the past so that the health system had competitors. Which was very smart. But the problem is that this is one of the reasons why he had a problem during the SARS was there was a thought that infectious diseases was a disease of third world. And we are now approaching first world. So let’s not worry so much about infectious diseases. It’s chronic diseases, cancer, heart disease, and what have you.

Well, they were caught completely flatfooted when SARS came about. Let me put it this way. Singapore has learned enormously well and put that in within the system. China didn’t do very well as well. So I wouldn’t say a lot of institutions didn’t think about epidemics like this as the challenge. Everybody had a flu season, everybody had a few infections and so forth. But to have it affecting the entire country the way it did was not planned for in most cases.

But I think what we have now, is that the three clusters are done not only to deliver care, but also to discover better ways to deliver care. That was a very distinct difference from the previous model. Now these clusters are charged to discover new ways to improve health. That’s brilliant. That’s beautiful. Yeah. And it covers the population. Whereas in US, you have Medicaid, for people who can’t afford it, and the healthcare systems are really fundamentally for who can afford it. It’s very haphazard and it’s not efficient, whereas it’s as efficient as it possibly can be in the Singaporean system. But the beauty of it is that they’ve now embedded, it’s not perfect, but they’ve embedded the discovery process and the learning process within the healthcare environment and machinery itself.

Joson Ng: At what point during your journey or your time here in Singapore did you decide, okay, now I’ve learned all that I can, I think I’ve set up a good foundation for this institution to continue and grow stronger even without me. And now it’s time for me to move on to my next role?

Edison Liu: Well it was 11 years after I was here. Actually, I did that when I was in Jax because I left at my 10th year of presidency. And somehow, it’s not that I get tired of things, I could continue in either leadership jobs, for me that 10 year mark is when I was seeing patterns repeat itself.

And that’s when I decided that. Especially when I was in GIS, I realized that I had one big job left, in terms of the 10 year timeline or 15 year timeline, and that staying in Singapore would’ve been very pleasant. But I don’t think it would really add that much compared to my first 10 years here or 11 years here.

Furthermore, I always knew from the day I arrived that one of my job was to make sure I had good successors. That was a very important point for me. That’s why I was developing local talent. And I was so pleased when Huck Hui succeeded me I actually had suggested that and after him was Patrick Tan, then JJ Liu, and now Wan Yue.

Of those four leaders that succeeded me, only Wan Yue did not work under me directly. And I have to admit, I’m very proud of that. That they carried on because they believed in the concept of GIS not as some ephemeral institution, but the culture of what we had, they wanted to stay on, to build on that culture.

And that was great. The fact that I was able to identify at least the three individuals that Astar decided had leadership potential at this level, not to speak of Lisa Ng. I’m very proud of that.

Joson Ng: The fact that they took it seriously and led GIS to grow from strength to strength.

Edison Liu: Well, it’s the fact that whatever I did at the GIS provided an environment where leadership rose. And that’s really important. Leadership is very important as Lee Kwan Yew will tell you.

Joson Ng: Of course. Eventually, JAX or the Jackson Laboratory recruited you in 2012. They weren’t just looking for a world class geneticist, they were also looking for a leader, a CEO to navigate what they wanted to be a major transformation.

What was the specific mandate that they gave you and how did your experience building GIS, and leading the NCI back in the US provide you the blueprint for expanding then JAX as a non-profit organization’s global footprint?

Edison Liu: Let me just say that my experience at the GIS and at Singapore was transformative because it gave me the concept. I was completely untethered while I was here. Philip Yeo and Singapore used me for every possible angle that I was even useful in.

So, the breadth of my experience here was just remarkable. I would never have accomplished that in a US context.

The thing about it is that, it’s a matter of being in a position where you can actually touch other leaders in the world, exchange ideas with the very best and that gives you a unique perspective. What had happened was that I was looking and then I was asked to do things like run an entire academic hospital system or being chair of medicine or being dean of a school.

And I found those unbelievably boring, in the US context, and for a lot of reasons. When the Jackson Labs called me through a headhunter, I actually thought they called the wrong guy because they are very well known of being a mammalian genetics institute that are focused on the mouse.

I’m not a mouse geneticist. Several things really intrigued me. First, they wanted transformation, just like Singapore wanted transformation. I love that context. Second of all, I looked at their books and they were unbelievably well endowed, not by philanthropy, by just simply their fantastic operations.

And I looked at the books of Singapore and said they’re willing to fund the GIS really well to make it successful. So, there was intention, there was unified idea of where JAX should go and they were solid in their finances. Furthermore, it was a structure unlike any university structure, where I was the one who was gonna call the shots.

I like that and I decided to take the job. I also knew during my negotiations that there was a possibility of $300 million to be given by the state of Connecticut to build an entire human genetics institute in Connecticut from Maine. And what happened was that in their negotiations, they said, we have our primary candidate who’s likely to come is a person who’s done all this stuff in human genetics.

So, it made Connecticut even more interested. It was really a synergistic framework. When I arrived, I was the one who signed the deal with the state of Connecticut. The first week I was here, I was the signatory for that deal. The piece about this was they wanted somebody to transform. I love transformative challenges. They wanted somebody to expand their really hardcore genetics into genomics, which I’m capable of doing. They wanted somebody who could actually lead their moneymaking operations internationally, which I could do also.

But, there are two things. Whatever job I take, I always ask the question, what can I learn from this position? The two things I could learn from this position, which I didn’t know very well, is the depth of mouse genetics. It’s just really quite remarkable, at the Jackson Labs. We’re talking about 90 year history of mouse genetics. The foundation of mouse genetics was done at the Jackson Labs. The second was business. This was one of the most efficient businesses I’ve ever seen. It’s mainly because the Chief Operating Officer, Chuck Hewitt, is just absolutely fabulous human being. We became close friends. Under my watch, working with Chuck, we increased the revenues by threefold in 10 years. 300%.

We increased our endowment by fivefold. We doubled our headcount, but think about it. Doubled the headcount, but three times the revenues. That means we’re became much more efficient. We then moved from Maine to California to Connecticut. Three different campuses in the US, expanded to a second campus in Maine. There were a total of four campuses under my watch. Then, we moved to China and Japan.

Joson Ng: International.

Edison Liu: It was international. Our margins were fabulous. At the same time, our NIH grant getting capabilities, we increased the faculty by twofold but our grant getting capacity was 2.5 times national average, for the same number of people.

The idea that I could learn business because I’m not a primary businessman and I could also learn mouse genetics that enhance my own science was actually a great attraction. So, that’s the major reason for the change.

Joson Ng: You mentioned a while ago that you managed to grow Jackson’s revenue significantly during your tenure, and it’s been shown as well. Throughout your transitions across many of those transitions, you were able to sort of move past what you initially thought of yourself as just a medical doctor, as just someone who knows a little bit about genetics and then into human genetics, setting up the GIS and then what did you know about mouse genetics and also, helping lead, Jackson eventually growing their books.

How do you think clinician scientists or even just scientists in general, can move beyond just grant writing to talk about the language of value proposition to stakeholders, to managing teams, leadership, overall.

Edison Liu: I think that there are several characteristics that you must embrace. Number one, you can’t be fearful of taking chances. Number two, you have to be humble. People who push their weight around too much, it just doesn’t work. You have to put your intellect and weight behind it. In other words, you have to seek truth and you have to learn.

If you follow those three principles, you’ll do okay. Arrogance kills. Laziness kills. Right?

Joson Ng: Yes, absolutely.

Edison Liu: And being fearful, you’ll never take the next step. . It’s very, very simple, but it’s very difficult to execute.

Joson Ng: I see. Now we kind of round up the whole interview by asking some sort of rounding out questions.

If there was one system level skill that you would say is the most missing in any kind of scientist or clinician training system, what would that be? And how do we teach researchers or clinicians, budding or otherwise to think about the whole ecosystem in general rather than just focusing on where they are?

Edison Liu: I will say unequivocally the thing that is missing is to train people to be self-sufficient. Because I hear this a lot. I say, there’s not enough training on gender equity or there’s not enough training on genetics and genomics. Well, how much are you gonna stuff into a human being. It’s very short, a one year period in preclinical in Duke.

Joson Ng: Yeah.

Edison Liu: You know? People are very skeptical about what you can learn in one full year. You can’t. The piece that I always find is the most important is how can we teach self-reliance, self-sufficiency and self-motivation. In other words, I don’t have to spoonfeed you. You don’t know much about this, go look it up yourself. Come back to me when you have questions. Don’t ask me to give you an answer. And that has been, I think the piece that I find most disturbing to me about the progressive generations of both physicians and scientists. Feed me, feed me, rather than, hey, leave me alone so I can do what I think is important.

Joson Ng: Right.

Edison Liu: You get my drift.

Joson Ng: You did mention a while ago that, one of the people you would definitely reject outright is someone who says, no, I don’t know this. I can’t do it. I don’t want to do it.

Edison Liu: That’s right. In this day and age, people like that in the discipline that we’re in will never survive.

Joson Ng: I see. The other thing that I wanted to ask was what critical insight do you have about the scientific ecosystem, that it was never taught in a PhD? In terms of where do scientists belong in this very dynamic, very rapidly changing sort of way that we look at the biotech ecosystem?

Edison Liu: I think you really hit the nail on its head. I think that more and more of us, and I’m one of them, is saying that the PhD education process is archaic. In the US, you stuff two years of coursework before you go into the laboratory. When you go into the laboratory, there’s really no true end point.

Sometimes, in European system they’re better. They say you need three papers. Doesn’t matter what quantum they are, you need three papers that had to be bound into a theme.

Joson Ng: Mm-hmm.

Edison Liu: In the US you have this problem which I found kind of despicable, where you’re working there and your mentor says you’re not ready. Well, what’s ready? Then, it becomes the sixth year and seventh year PhD student. Then, they have to graduate you because the university says you can’t keep them beyond eight years.

Is that right? I’m not sure that’s right.. I really am not.

This is why the Duke NUS training program, I remember when it first got started and Bob Kamai, who’s a good friend of mine, was the person who started it. It was so revolutionary because it wasn’t about book reading.

It was about, I expect you to read. And then let’s work on synthesizing afterwards. In the past, when I was in medical school, you could read, but the person would give a lecture. Everybody copies down the notes, and you shared the notes. And that was the exam. What’s the purpose nowadays? You could just record the lecture and then and do that. So that’s why it was really revolutionary in that it framed the new communications at that time.

I don’t think the PhD programs across the world has even taken advantage of the fact that AI is just unbelievable. Is there another way for us to acquire knowledge and test whether you acquired that knowledge using advanced tools? And then use the time with the professors in a manner like you and I are talking.

Joson Ng: Mm-hmm.

Edison Liu: I have a problem. How do you wanna solve it? And I challenge you and it’s all about challenging and do the experiments.

Joson Ng: Something a bit more Socratic as well.

Edison Liu: Little more Socratic, but also what’s happening in bio is everything is computational now. Your need to learn so many different skill sets makes it very difficult to frame it like the old ways.

This is the other aspect I do not believe in two years of coursework and the rest of your time in research. What I believe in is, yeah, you probably need a year of just preparatory stuff, including, how do you code? How do you use databases? How do you use AI in what you do?

Some fundamentals about what you might need to teach because you’ll be in a biochemistry department and what’s expected of you to teach. The rest of the time we should have two, three week modules tucked away in the four years that you’re in a laboratory. That gives you the modules for sequencing, the modules for single cell interpretation, the models for animal surgery and so forth.

You get my drift, right?

Joson Ng: Yeah.

Edison Liu: The technologies become essential in what you fundamentally do. The exercise in summarizing scientific information, I think is really, really important these days.

Joson Ng: They say extra packets of like what skills people would like to be able to tackle. A question that they would like to answer.

Edison Liu: That’s right. That’s exactly right. Now, there are a lot of people who don’t believe that this is the right thing. I do think it is the right thing. Now, different disciplines have different requirements and I totally respect that.

In biology, what I learned in Mike Bishop’s lab is I cannot be just a physician worried about breast cancer. I have to be able to read drosophila data. I have to be able to read yeast data, yeast genetics. I don’t have to be an expert in that, but I gotta understand it, alright?

Joson Ng: Mm-hmm.

Edison Liu: That was the biggest transition for me, that I wasn’t gonna be locked into humans and disease. Because biology is the rest of the world. It is the rest of all the species that we have. So, that’s really changed my worldview in terms of the educational system.

Joson Ng: Alright. Thank you again so much Dr Edison, for that very insightful sharing. We hope everyone listening to this has also found that extremely insightful. With that, we last want to ask you about rounding out your perspective on Asia and Singapore in general. How do you envision eventually Singapore’s role in the global biotech and research landscape?

Because, a lot of things will always shift. As we know from the US, their current leadership in science and biotech has also shifted a little bit. Where do you see Singapore headed in terms of like, where’s that hub going?

Edison Liu: Yeah that’s an excellent question. First of all, Asia has parity with the West and will probably exceed the west in innovation, in the bio space in the next 10 years.

Now, does it totally dominate? I don’t think so, because there’s a lot of good people in the west. But, this craziness in the United States right now, it can’t last. It just can’t. It’s just ridiculous. And when people come to their senses, there’ll be a little more interaction, but there’s always going to be an element of suspicion.

More importantly, we have embarked on a two systems world now, on a technology basis. It’s the west and there’s China. It really is, in all aspects of technology. So, the fact that Singapore is bilingual, it’s one of the few countries that are truly bilingual, okay? It’s brilliant, but often maligned initiative of Lee Kuan Yew, makes Singapore indispensable in the world order.

So long as US and China are jostling with each other, Singapore will be preeminent in its position to broker the two worlds. It takes a little finesse to be able to do that. It’s really metastatic.

Joson Ng: It takes a lot of finesse.

Edison Liu: Takes a lot of finesse, but boy, you can’t be but impressed with the longevity of this vision, and the success of Singapore. And I am so proud to have been part of this during a critical phase of its development.

Now, the only thing that you do worry about is little critical mass issue. Let me give you an example. Singapore, small country, we succeeded. Jackson Labs dinky little place in Maine. We’re world known. I can tell you that it started when I was at NCI.

Because I was asked to help out Northern Ireland in developing their cancer program. By a good friend of mine, who unfortunately had passed away, Patrick Johnston. He said to me, Ed, he was in the US at the time, but I’m going to Northern Ireland and I’m gonna really want to change their cancer, how they deliver cancer care. I want your help.

Because I was the director of the division of Clinical Sciences at the NCI. I said, well, Patty, you know, I can’t help you until the troubles are over. He said, give me a few months and we’ll be over. And sure enough, the Good Friday accord was announced, call me up. We went and started a program called the NCI All Island Cancer Consortium that still stands to this day.

And what it was the NCI was going to help the Republic of Ireland and Northern Ireland to develop an all Ireland cancer consortium around clinical trials, around disease registry and around telemedicine. At the days where telemedicine was crazy. We had to get our own machines and everything of the sort. That literally changed the face of cancer research in Northern Ireland from complete back woods to one of the best cancer programs in the UK.

During my visits there and working to get that developed. I was struck. I was struck by how a country of one point, a jurisdiction of 1.2 million, 1.4 million at that time, captured the concerns of the world. I received a honorary degree from Queens University of Belfast in Northern Ireland for some of the work that I did for them.

George Mitchell, who was the US Senator, was the chancellor of the Queens University. When I received my honorary degree, the person who also received it was Desmond Tutu, who was Nobel Peace Prize winner of South Africa. The whole commencement party, the lectures and what have you was about reconciliation, that a country of 1.2, 1.4 million people actually showed the way for reconciliation of a process that was ongoing for a hundred years. Opened my eyes to the fact that size doesn’t matter. In fact, the smaller the size you are, the more likely to solve huge problems. This is one of the reasons why I had no fears of coming to Singapore. Small Singapore as it is. To try to achieve global excellence in a discipline that they didn’t invent, that they had no role at that time that we had no role in Singapore.

This is a reason why I had no fear of going into downstate down east Maine, in a town of 10,000. To build one of the strongest, mammalian genetics programs in the world.

Joson Ng: World class.

Edison Liu: World class. Small is beautiful, as long as you know how to manage it, and you know where the puck is going to be.

Joson Ng: With that, thank you again so much Dr. Edison. This has been a very insightful talk, and we hope everyone has found this insightful as well.

Edison Liu: My pleasure.

Joson Ng: Dr. Liu’s career reminds us that science doesn’t happen in isolation.

The discoveries that shape medicine often come from people who are willing to build institutions, connect disciplines, and think far beyond the boundaries of a single laboratory.

📚 Further readings

[1] Why Singapore? | Science | AAAS

[2] Edison Liu Leaves Singapore to Head Jackson Lab | Science | AAAS

[3] Edison T. Liu, M.D.

[4] Genetic Variability Affects How Tumors Respond to Immunotherapy | The Scientist

[5] Edison Liu | Nature Biotechnology

[6] Watch: Like A Boss: One-on-one with Edison Liu, president and CEO of The Jackson Laboratory

About The Guest

Dr. Edison Liu is a medical doctor turned cancer geneticist, whose work focuses on cancer genomics, breast cancer biology, and translational medicine. He has held senior leadership roles in biomedical research institutions in the United States and Asia, as the founding executive director of the Genome Institute of Singapore (GIS), and later the president and CEO of the Jackson Laboratory, one of the world’s leading genetics research institutions. Along the way, he helped shape Singapore’s biomedical landscape, led genomics research through crises like SARS, and expanded global position medicine efforts across Asia and North America.

📄 Summary

In the first part of this episode, Dr. Edison Liu shares his journey from being motivated from childhood by medicine, then pivoting into basic science late in training after frustration with empiric cancer care and inspiration from oncogene discoveries, leading to work at UCSF with Nobel laureate J. Michael Bishop. He explains how clinical experience shaped his research questions, how he balanced lab discovery with focused clinical work and molecular trials, and how leading a 1,200-person NCI division taught institutional-scale leadership. Recruited to Singapore by Philip Yeo and others, Liu chose functional and transcriptional genomics over sequencing alone, built GIS’s collaborative culture, recruited fearless, high-performing, non-“jerk” talent, and empowered young leaders during events like SARS, helping establish preeminence within a decade.

🥡 Key Takeaways

Key Takeaways

🔬 The Evolution of Medicine: Dr. Liu's career pivot from physician to scientist was motivated by his discontent with the "empiricism of medicine" and a vision to transition to a highly molecular basis for understanding human cancers.

⚙️ Scaling and Leadership: He learned that moving into institutional leadership, such as running the NCI clinical science division, presents a "scaling problem" where one's skill set must adapt to managing smarter people and larger structures.

🌏 Building Ecosystems (The Singapore Gamble): His decision to join the Genome Institute of Singapore (GIS) was an opportunistic risk, drawn by the strong top-down government vision, free reign to establish the institute's direction, and the belief that the endeavor "cannot not work."

🧑‍🔬 Recruiting for Fearlessness and Skill: His core recruitment criteria for junior talent are fearlessness (willingness to try new things), superlative track record in a few things (flexibility), and being personable and non-selfish (not a "jerk").

💬 The Importance of Culture: The complete freedom to establish a culture of collaboration, openness, and "fearless exploration" was instrumental to GIS's preeminence and is the most remembered aspect by former staff.

💬 Quotes

“More importantly, we have embarked on a two systems world now, on a technology basis. It's the west and there's China. It really is, in all aspects of technology. So, the fact that Singapore is bilingual, it's brilliant, so long as US and China are jostling with each other, Singapore will be preeminent in its position to broker the two worlds.”

“The pivotal moment was really my discontent of the empiricism of medicine and then my jump, it's serendipity. It's not like I planned it. I just said, well, let me try it. And when it became the most compelling thing in my life, I decided to go ahead and do it.”

“I think the major advantage I had was I knew deeply the basis of the disease and also the impact of the disease... Very importantly, I saw the clinical conundrums, the clinical contradictions, why would something that should work not work? Those are the type of things that always raise the question so that I can be a better scientist, actually.”

“I always adhere to Wayne Gretzky's statement that, I don't go to where the puck is, I go to where the puck will be. And throughout my entire life, I realized, only in retrospect, that that's what drove me.”

“Whenever somebody says, I've never been trained in something and I don't wanna do it, you're never gonna be hired by me.”

“Jerks don't win. And I don't wanna work with jerks. So I actually look for people who are not meek but who are personable, who actually like to work with each other and not selfish.”

“So it's not what title you are or even your history, it's can you produce? And I'm watching carefully if you can.”

⏱️ Timestamp

02:18 Childhood Doctor Dream

06:00 Deep Dive into Molecular Biology

09:40 The value of being a Clinician Scientist

15:00 Juggling Clinic Lab And Trials

19:50 Recruited to Singapore

23:00 Leading GIS and Recruiting the right talent

29:40 Culture of GIS

🎙️ Transcript

Joson Ng: What does it take to build a world class scientific institution from nothing? Today’s guest has done it twice. Dr. Edison Liu is a medical doctor turned cancer geneticist, who went on to become the founding executive director of the Genome Institute of Singapore or GIS, and later the president and CEO of the Jackson Laboratory, one of the world’s leading genetics research institutions.

Along the way, he helped shape Singapore’s biomedical landscape, led genomics research through crises like SARS, and expanded global position medicine efforts across Asia and North America. In this episode, we are not just talking about science or biotech. We’re talking about decisions, leadership, and what it means and what it takes to build ecosystems, not just the laboratories.

My name’s Joson, and this is Nucleate Singapore Pulse. Today I’m honored to be joined by Dr. Edison Liu.

Dr. Edison, your career spans four identities as a physician, a scientist, a nation builder in Singapore, and then a CEO who transformed one of the world’s leading genomics institutions. Today, I want to explore not just what you did, but how you decided when to pivot at each stage.

Could you start with a brief introduction in your own words, focusing not on title, but on what has motivated your career choices?

Edison Liu: Well, first of all, I just wanna say I’m absolutely delighted to be here and having been partied to Singapore’s journey in this bio space, I’m just really impressed with people like you, coming out of the education system that we have, who are so bright, so motivated, and yet so open to discovery and to new experiences that I hadn’t seen when I first arrived in early 2000s here. Congratulations, kudos to you, and I certainly hope to continue to contribute to Singapore’s success.

You asked a very important question is that, what actually motivated me and did it start late in the game or early in the game? I can tell you that I wanted to be a physician. Not a physician scientist, but a physician ever since I was five years old. Both my parents were physicians. We immigrated from Hong Kong to the US when I was five years old, and they set up office in San Francisco, Chinatown. Throughout my life, I actually would visit them in their office, watch them interact with their patients.

And I always felt a real sense of wonderment of how an individual, by just being a helper for somebody else, had gained not only the respect of that individual, but of the community itself. Now, don’t get me wrong, the respect issue wasn’t the major driving force, but the idea that I could be a force by using my intellect to help other people through a scientific enterprise was really a wonderful framework.

So that vision never left throughout my whole life. While that has driven me, the conversion into science came very late in the game. I went my undergraduate degree. I was a major in chemistry and psychology. I got my MD degree. I even did research during my MD, I took a year off to do research, but I was never serious about research. It was always about preparing me to be the best doctor possible. And I went into oncology, what I considered one of the best oncology programs in the country at that time, which is at Stanford University. Even then I was planning on being a practitioner of the art. It was there that I began to question whether or not the art of the science was enough to push the envelope of treating cancer.

Everything was so empiric. What I mean by that is all by trial and error. Of course, there were some principles, but there wasn’t any really fundamental universal principle about cancer at that time, except, let’s just try this in a clinical trials framework. It was at that time that several things were happening in my life. I come near the end of my fellowship, I completed all my medical training, including internship, residency, fellowship before I even considered going into the laboratory.

It was at that time I said, I’m ready to see patients and take care of patients, but I’m not sure I’m gratified by that alone. There was something that I needed to do, an itch I needed to scratch, which was really to learn more. It was just at that time that, Weinberg and Ben Shilo came out with this paper where the fundamental science of oncogenes, which was all about animal viruses, became relevant for human disease, for human cancers, and all of a sudden that was a light bulb. I heard all this really interesting basic science, and I thought, again, it was not relevant to me because I wanted to be a doctor, for the very first time that had relevance. And so I said, look, I’m young enough. I’m not married at this time. I don’t have family. I might as well just give it a try. And I applied to a number of laboratories, including two future Nobel Laureates. One of the Nobel laureates took me on is J Michael Bishop, who won with Harold Varmus, the Nobel Prize for the discovery of oncogenes.

And that was my research. So for three and a half years at UCSF, I went deep into basic science. It was my first time on a conceptual level dealing with that. And it opened my mind because prior to that, everything about science was practically about treating a disease, taking care of a patient. It’s very important, don’t get me wrong, but the end point was always, you have heart failure, how do I treat it? You have breast cancer, how do I treat that? It was never about how did breast cancer get started? Why did the heart fail?

So, when I went into the laboratory, all of a sudden it was a whole new world of molecular biology. It was, in the 1982 to 1987, molecular biology, the ability to clone genes, ability to transfer genes into cells was a phenomenal new experience, and it completely opened my mind. It was like a veil was lifted. The veil that was, all of a sudden everything that had to do with biology, whether it’s viruses, or drosophila, which is flies, or worms, C. elegans, or mouse biology, was all of a sudden relevant, when before I didn’t think it was relevant. That really then just propelled me to say, I want to do an academic career. I never sat down and said, oh, gee wiz, that was a revelation. It was just so exciting that I was going to do that. That was the pivotal point in my life, to go into the sciences.

At that time, we didn’t have the terminology of clinician scientists. I was just a clinician doing science and in American history at least, and certainly in European history, they were all physicians doing science. You didn’t call them clinician scientists because they were doing science, but their science was to attack a disease, right? This type of science I was involved with was really to understand the disease. And not simply to attack it. On the other hand, this was a portal to how I could actually be precise in my addressing of diseases that were categorized by pathologists in general.

So I became a professor and the rest is history. The pivotal moment was really my discontent of the empiricism of medicine and then my jump, it’s serendipity. It’s not like I planned it. I just said, well, let me try it. And when it became the most compelling thing in my life, I decided to go ahead and do it . I wanted to do it in conjunction with being a doctor. That was very different. I have some friends who decided I’m not gonna be a doctor. It’s just too boring. I’m just gonna go in a lab and discover. There were several of my friends who were MD PhDs and decided they wouldn’t even go into residency. But for me, I knew what I wanted to do was apply the science to solving, to understanding and solving human cancers. That was really my deep, deep goal going forth.

Joson Ng: You mentioned a while ago that you had some peers who decided to, focus on entirely to science while you yourself chose to make a balance between the clinical side and the bench side.

How was your decision seen at that time, by people who are your peers who also perhaps already finished residency or when you made that decision?

Edison Liu: Fully accepted. And in fact, some of them are envious. Don’t get me wrong. I have friends who have MD PhD, went through everything and then finally became much more clinically oriented. Not practicing, but much more clinical oriented. Then, I don’t have a PhD, my two mentors who won the Nobel Prize, none of them had PhDs, they were MDs. It doesn’t mean that clinician scientist does not mean you have to get a PhD. Joson, I’m sorry about that.

Joson Ng: No worries at all.

Edison Liu: But in truth, nowadays, I think you’re better off getting one.

And why do I say that? It’s because, unlike in the past, the technologies are so powerful but so broad. The methodologies are much more complicated than ever before. So having the formal exercise of working through an entire project is really what you need to understand the fundamental of science itself. Science is orderly. Science is about methodologies and applying to some end points. And the best science is a continuum of discoveries, not sporadic discoveries. So the training and a PhD actually gives you the experience of that longitudinal continuum of discovery.

Joson Ng: I see. How did your experience as a clinician at that time, shape how you thought about hypotheses that you had in the lab as opposed to some of your other colleagues who perhaps didn’t have that more clinical perspective?

Edison Liu: I think the major advantage I had was I knew deeply the basis of the disease and also the impact of the disease. My colleagues only knew it in the context of an abstract endpoint. You have breast cancer. Well, what does that mean? Because I treated breast cancers, many of them. I knew how they felt. I knew how they looked. I knew the consequences if they’re not under control. I saw how things shrank. I saw how things didn’t work. Very importantly, I saw the clinical conundrums, the clinical contradictions, why would something that should work not work? Those are the type of things that always raise the question so that I can be a better scientist, actually.

Joson Ng: Oh, that’s back in the era of trial and error part of medicine?

Edison Liu: To move medicine from a trial and error into a highly molecular basis was my fortune to be in that transition. Let’s face it, all the greats in medicine had a pathway, had a protocol, had an approach to addressing. They were meticulous and how they address it, but very few of them really were in the molecular framework. They may have been biochemical in nature, but they really weren’t molecular. So it was my generation that allowed us to actually, touch the gene, to sequence it and to know exactly what it was. Powerful stuff that you don’t really understand because I lived it before cell phones ever existed. But you really begin to appreciate how the transitions in medicine have been really absolutely fabulous. And I’ve been remarkably grateful that I’ve been party to many waves of discovery and seeing not only how they affected my own science, but the entire practice of medicine.

Joson Ng: It was then in your career that you transitioned to University of North Carolina Chapel Hill, where you took up a professorship and you were able to juggle both clinical work and work at the bench side. And you were both seeing patients running a lab, how do you actually manage those dual roles in practice? Because everyone has a different set of experiences, and as you mentioned, your peers, some of them chose one path over the other while you decided to go ahead, to juggle both of these.

Edison Liu: Well, actually a lot of us did juggle both, and in fact, you’ll find some of the best investigators even to this day have the clinical responsibilities. Granted, their clinical responsibilities are less intense than those who are focused on the clinical material. Now, you have to understand a clinician scientist isn’t just somebody working in a laboratory. In fact, some of the best clinician scientists I know spend most of their time doing clinical work, but it’s very structured clinical discovery work to improve, let’s say, therapy, diagnostics, screening, what have you. And, it’s highly methodologic, it’s rigorous, and in fact, there’s a skillset to that that is unique to the clinical scholar, a skillset that is really very important. The best clinical trialists are the ones who understand molecular biology, but they don’t have to do it in a laboratory.

So in many ways, the whole enterprise of translational medicine starts from the basic concepts and ends in actually the clinical applications. And the clinical application is never a haphazard trial of a single agent by one single doctor on a single patient. But it’s an organized experiment on a clinical trials arena, which has very strict methodology going forward.

Joson Ng: I see. And your experience just sort of managing both that kind of mindset with running clinical trials, for example, and also doing the molecular side of things, continuing on your work, that was very instrumental for you?

Edison Liu: It was very instrumental, but let’s be honest, I could not be a hardcore clinical trialist and be a hardcore molecular biologist and be a clinician for my patients simultaneously. You just didn’t have enough hours in a day. But I maintain both interest and experience in different aspects, but focusing on the discovery, the laboratory discovery piece. I saw patients, it became progressively limited to breast cancer and rather than general oncology. And then I did some clinical trials, but all the clinical trials that I did were not therapeutic clinical trials, but molecular trials. So I was the person who doing the molecular science for the therapeutic trials that my colleagues ran on a national basis. So I was the chairman of the science group for the national cancer clinical trials called LGB. My responsibility was to organize, to vet, and to manage all the molecular testing, the molecular questions that were applied, or asked in the solid tumor clinical trials for this entire national group. So whatever I did was really tailored to a fundamental portfolio around breast cancer, breast cancer molecular biology, and breast cancer therapeutics.

Joson Ng: Eventually you then also took up the position as scientific director of the division of clinical Sciences at the National Cancer Institute, the NCI, as part of the National Institutes of Health, NIH. Eventually you’re also running basically a 1,200 person clinical science division and running an institution at that scale was probably an extremely different experience compared to your experience back at UNC. How is that?

Edison Liu: So true! This is actually one thing you’ll find, whether you’re a PhD or a medical student or what have you. Whenever you get a different chump in your responsibilities, it’s a scaling problem that is the real issue. What you’re used to doing as a student is no longer applicable when you’re running a laboratory. Now, don’t get me wrong, the fundamentals are still the same, but scale is different, right?

Joson Ng: Right.

Edison Liu: You understand what I’m trying to say? Are you married?

Joson Ng: Not yet.

Edison Liu: Okay. Not yet. The first thing is you live by yourself and you can be as dirty as you want. Then you have a significant other, alright? And then you have to make compromises. Then you have kids. The scale from having a couple to having two or three kids is immense. For somebody who’s been through this process, and it’s the same thing when you run a laboratory, there’s a certain element of scaling that you have to do from the time you were a postdoc. But when you run an institution, especially an institution where people under you are smarter than you are, then it takes a different skill set altogether, and it was fantastic experience. It was tough, don’t get me wrong. It was really difficult, but I wouldn’t have exchanged it for anything.

Joson Ng: What made you decide to do that transition to the NCI?

Edison Liu: This is actually one thing that I’d like to underscore for your listeners. Nothing in my life was planned except being a doctor. Zero. Okay? Everything was about getting an opportunity, weighing whether that opportunity was, first of all, interesting, second of all, impactful and doing it, taking the risk. And the third aspect of that, and this is very important and Jessie and I just had a conversation about this, is that whenever I took a new job, I didn’t worry about the next job. I concentrated on doing my very best at the job that I was doing. While I was doing that, while I was maturing in that new plateau, I began to learn more about myself and also learn more about what makes me tick so that the next job, I had a much better idea of what I wanted to do in my next job.

So, what happened was I was doing very, very well in the university. I ran the breast cancer program. I ran one of the most unusual translational programs in the country that was, started. I was a professor of epidemiology, medicine, genetics and chemistry. I had a endowed chair. But the opportunity to run something that big with people who were that good, in a structure that’s completely different than what I had, was something I had to try, on a national scale. And let me just tell you, at that time, I was the only Asian American in a group of 21 scientific directors. So there was a little bit of that with me as well. So five years into that, I really learned a lot and made mistakes. The key is to learn from your mistakes and that actually prepared me for coming to Singapore. Now, do you know how I got to Singapore?

Joson Ng: As I understand you were headhunted by Mr. Philip Yeo. But of course everyone wants to know how the story of how it actually happened.

Edison Liu: So Philip Yeo comes to the US in early 2000 with his EDB team and wants to meet with a whole bunch of people in the United States. And so he met with me, which was scientific director of NCI and my director, my direct boss. I still remember sitting there listening to Philip talking about what Singapore wants to do. I was very impressed, but I was also very skeptical. You live in the US you’re used to this scale, and how could little Singapore, who really at that time didn’t have any presence in bio, could actually make it. But I was intrigued, intrigued enough that when he asked whether or not I could go onto the board of the Singapore Genome Project, I said yeah, I’d love to help you do that. It was at the same time that John Wong was the dean of the school here, and the chief executive at NUHS before, has become one of dear friends of mine, asked me to help him through my NCI position to help conceptualize the Southeast Asian Clinical Trials Group.

So I actually flew out with a contingent from the NCI and had a conversation with the group in Hong Kong, which is where the meeting took place and John was there. And John was telling me that they really are very serious about building the biomedical initiative for the economy. One of the challenges was they couldn’t really find people at the appropriate senior level like me. And I said, well, give me a try. And then he immediately called the bright people, including Philip. And next thing I knew, I had a 24 hour trip to Singapore where I met a key group of people.

And, when I arrived back in Singapore, I had a job offer. After some discussions, I decided it was the right time. You talked about how did a professor go into the government and it was at a scale. The issue here was I was going to give up a trajectory in the US that was pretty darn good to go to Singapore, where nobody knew what it was going to do and to do genomics, which was not my area of expertise. I knew genetics and I also knew the elements of genomics, but I was not a classical genomicist at that time. But there was something about the intention here. When there was cohesion in the vision of where Singapore needs to be from top down. I’ll just give you an example. I was taking a cab during that visit and somebody said why are you here? And I said, well, because I’m looking at this, oh, you mean the cab driver knew about the biomedical initiative? The cab driver. So I said, you can’t beat this. The framework of that was that the intentions were there, the substrate was there, the people were very smart. Furthermore, they gave me fundamental free reign to recruit the right people and also to style the genomics the way I wanted to. You have to understand, at that time everybody was just trying to sequence the human genome. That was 2000. In 2001 they published human genome and people were saying, just sequence the Asian genome.

I knew for a fact that was only a one time stamp collection exercise. What we really needed was to move genomics into functionality, that went beyond just the ATCG of your genome into what those things actually did. So I was already working in the fringe field that was transcriptional genomics, of which, Craig Venter actually invented. And, I said, well, this is a unique opportunity here. I basically set up Genome Institute fundamentally to address the functional genome. And the rest was history. Because we chose a topic, that there were no true incumbents, everybody was all more or less in the same starting point. We became preeminent in the field, within seven years we were preeminent. By the 10th year we were putting things out that were just really quite remarkable.

Joson Ng: How did your various experiences, all the way from your clinical experience to your leading a lab at UNC as well as your directorship at the NIH, shape how you strategized, which people to recruit, what domains to focus on, as you mentioned, transcriptional genomics in building up GIS?

Edison Liu: I always adhere to Wayne Gretzky’s statement that, I don’t go to where the puck is, I go to where the puck will be. And throughout my entire life, I realized, only in retrospect, that that’s what drove me. I talked to you guys earlier about PCR, the fact that we were doing PCR on three water baths and people just don’t understand this stuff. But I did it, and I was among the first people to use PCR on clinical samples. Because that’s where the puck was going to be. The problem with that is who’s gonna let you experiment like that?

The NIH system tends to be very conservative, The NIH, NCI, when I went there, I was the one who managed a hundred million dollars budget. I gave money away, so I could help direct where it should go. And I found out that I was pretty good at it. So when I came to Singapore, they actually gave me the option to approach a problem where I think the puck will be. And it was a gamble. Everything’s a gamble. But the framework of this is, I knew there was a vision and I was certain that it had to work. Simply because it cannot not work. It’s a matter of both time and how does it land? It’s a little bit like if you know internal combustion, all you have to do is recognize that you need to harness that to make machines, And the next thing is, why not make propulsion? That is the natural process. Once you have this kind of technology, it’s a matter of how do you get there. So, consequently, it was the same principle. So in that framework I said, when you say functional genomics and in transcriptomics, did I have a game plan exactly how to get there? No. I just knew that was the direction and I wanted to recruit people who had the same vision and who will want to experiment with me. And I was very fortunate to recruit the right people. During that period of time, you could ask, well, how did I know who to recruit? Do you know in baseball, how they measure how good of a batter you are?

Joson Ng: Is it some kind of standardized machine that you used?

Edison Liu: No, no. It’s a measure of how many hits you have. You’re batting 300. That’s 0.300. That means that, of all the times you are at bat, you hit 30%. That’s considered excellent in Major League baseball.

Joson Ng: 30%?

Edison Liu: 30%. It’s considered absolutely excellent. I can tell you that recruiting people, there’s never a perfection ever. If you recruit only people with Nobel prizes, you’ve got a problem on your hand for different reasons. They’re brilliant, but is it that exactly what you want? We couldn’t do that. But I always understood when young talent had a thirst, a young talent that has an intellect, and we recruited a lot of young people, and I fostered them. But in this framework, I also wanted a place where if they didn’t work out, I didn’t had to keep them. I hate to say this, but that is really the necessary framework. Throughout the period that I was there, I kept most of the people, but I always said, if you don’t work out, you really need to find jobs elsewhere. And over those 10 years, the people who stayed became the best, became the absolute best. So that’s how it works out.

To this day, what do I look for in individuals? For the senior ones, you have a track record and you can do a lot of things and there’s a different criteria, but for the junior ones pertinent to you, Joson is number one, how fearless are you? Are you saying when I say, you should try this, and I say, wow, that sounds interesting, tell me a little bit about it, rather than say, I’ve never been trained in it. Whenever somebody says, I’ve never been trained in something and I don’t wanna do it, you’re never gonna be hired by me.

The second issue here is do you have a track record of doing something really well, and then you do something else really well? I don’t want somebody who does five things on an average, but I want to have somebody who’s done two things and they’re superlative. I always find people who can do that are unbelievably flexible. They can catch on very fast, and then excel what they have. I have quite frankly never been wrong in that capacity.

The third thing is jerks don’t win. And I don’t wanna work with jerks. So I actually look for people who are not meek but who are personable, who actually like to work with each other and not selfish.

Those are the three characteristics. I have to admit, when I look back at the successes and the failures, I haven’t been far off for most of them, And it’s kind of did me very well.

Joson Ng: I see. You mentioned a while ago some of the things that helped draw you to Singapore and I would assume also made your work at GIS lot more exciting, a lot more easy as well. You mentioned things like a very strong government vision for what it could be, a lot of support that was given to you and flexibility for how you would want to strategize and recruit the people. What were the other things that you felt were instrumental for you being able to lead GIS in the way that you wanted it?

Edison Liu: Very, very good. The complete freedom to establish the culture. When I first started out, I literally was able to define the rewards and even the titles. And I structured the internal division of delivery of funds in my own way to encourage collaboration and not contention. I always have sought to do that, including when I went into the Jackson Labs and what have you. And if you talk to people who’ve been through the GIS including many senior people they’ll tell you that they always come to this thing, it’s the culture of the GIS that I remember. And you ask them, what’s the culture? It’s I’d say interesting. It’s a culture of collaboration. It’s a culture of openness and it’s a culture of fearless exploration, but within the boundaries that you have to deliver.

Joson Ng: I can’t help but notice that some of these qualities that you mentioned are, and I don’t mean to put this in racial terms, but sometimes these are more associated with more western very individualistic values while, I think most likely at that time in Singapore that we didn’t necessarily start off with that culture? And probably starting that culture then in GIS probably met with some friction here and there, what was some of the friction that you encountered in getting people to think like that? To think like a scientist as well, being a bit more collaborative, but also brave and trying out new things.

Edison Liu: Well, actually, I didn’t have really problems with, with the Singaporeans, doing that. I do think, however, a lot of the young scholars were always looking over their backs about, am I doing enough? They were more concerned about, what people might say what they’re doing than actually what they were doing at that time. This has changed dramatically. Certainly even at the end of my 10 years, everything changes over time. But if you talk about east and west, all you have to do is take a look at China. They’re pretty fearless. They really are very bold, very experimental, and they’re kicking ass. So I’m not sure it’s an east, west thing, but I do think that there is something to conformity that is more common in Asia. But think about it, you can’t have a bunch of renegades succeeding. It just doesn’t work, right? So everything is a balance between exploration and fearlessness and actually communal effort. That’s where I really found a balance. In the US you’re herding cats most of the time, and leadership tends to need to herd cats. In Singapore, I didn’t have to herd anybody. It was a matter of really letting them loose. And when you do, they just did remarkably well.

Joson Ng: Right. But at the time that you recruited all these talents to Singapore, what was your pitch to them when you were still setting up GIS?

Edison Liu: I was asked in one of the sessions, must have been really difficult to recruit to Singapore. I said, not really. I didn’t have that much of a problem. And you know what it was, it was hey, we heard of Ed Liu and he’s a pretty good guy, and he’s not stupid and he’s in Singapore. There must be something to it. And by the way, I wanna do something different. By the way, remember I said I want fearless people and I tended to attract people overseas who were saying, I don’t care if this is in Singapore, this sounds really exciting.

Joson Ng: Like attracts like.

Edison Liu: Like attracts like, and sure enough, some of the people I’ve recruited are now just doing extraordinarily well wherever they are in the world, And I’m extremely proud of that. I’ll tell you the other thing that might be a little different, certainly different from early China, where everything’s very hierarchical, definitely in Japan, is, I took on a very different concept, which hierarchy was not based on your title, it was really based on can you produce.

What happened, just a classic example was the guy that I appointed ultimately to run my entire computational biology program was the youngest computational biology faculty member that I ever recruited. It’s just because he knew what he was doing and he had the right attitude and he knew how to manage people. Now he’s a big shot in McGill. But he was literally 33 when I gave him that opportunity.

Prof. Lisa Ng, who’s now the Executive Director (ED) of A*IDL, she was a first year postdoc at GIS. SARS hit. Looked around. There was nobody who knew virology except Lisa Ng. She was the only person who knew what a coronavirus was. So immediately I appointed her, the point person to run how to create the diagnostic for SARS. She did extraordinarily well as a first year postdoc. And that experience, I’m told, gave her the competence to take on more and more responsibilities. And then now she’s the ED for A*IDL, doing an exceptional job.

So it’s not what title you are or even your history, it’s can you produce? And I’m watching carefully if you can.

Joson Ng: So she just took an idea and ran with it, and...

Edison Liu: I said, that’s your goal. And she would report to me, bang, bang, bang, bang, bang. And it was beautiful. The guy, the two people that I had run my whole sequencing enterprise. I had originally people from a French company who actually ran that. They knew how to run sequencing and what have you. They were so boring. But Yijun Ruan and Wei Chia Lin came from a company in California and they had no academic credentials whatsoever. But when I looked at what they were doing this precisely what I wanted, which was on transcriptional genomics of looking at transcripts. And in talking to them, they were renegade-like. They had an idea, they wanted to do things, they wanted to do it in Asia and et cetera. Brought them in. Yijun and Chia Lin became the most famous people ‘cause they developed the paired-end technology. They did the first series of cDNA libraries that were really way cool. We used their technologies to do transcription factor mapping. They published the first paper in 2009 that became an industry. And I recruited them to the US afterwards. A university would never have recruited them, but we did.

Joson Ng: Dr. Liu’s story shows that building scientific institutions isn’t just about infrastructure or funding, it’s about culture, talent, and the courage to bet on where science is going next.

In the second part of this conversation, we zoom out from building institutions to building entire ecosystems.

We talk about how Singapore’s biomedical strategy evolved after SARS, how Dr. Liu later transformed the Jackson Laboratory into a global genetics powerhouse, and what today’s scientists need to learn if they want to lead beyond the laboratory.

Stay tuned for Part 2 of this conversation with Dr. Edison Liu.

📚 Further readings

[1] Why Singapore? | Science | AAAS

[2] Edison Liu Leaves Singapore to Head Jackson Lab | Science | AAAS

[3] Edison T. Liu, M.D.

[4] Genetic Variability Affects How Tumors Respond to Immunotherapy | The Scientist

[5] Edison Liu | Nature Biotechnology

[6] Watch: Like A Boss: One-on-one with Edison Liu, president and CEO of The Jackson Laboratory

If you enjoyed reading this post, comment and give us a like! Or let us know your thoughts here.

Meet the Start-ups is back! Scan the QR code or click here to register and secure your spot now.

🍽️ Digestibles

High potential SG research, hot off the press

CANCER: New Clues to Treating Lymphoedema

@Senuri De Silva

TL;DR:

• Lymphoedema, often caused by cancer treatment that damages lymph nodes, leads to long-term swelling and currently has no cure.

• NUS researchers found that poor lymph drainage causes cholesterol to build up in skin tissue, worsening the condition.

• In mice, removing this excess cholesterol reduced swelling and helped restore lymphatic function.

Lymphoedema is a condition where fluid builds up in parts of the body; most commonly the arms or legs because the lymphatic system cannot drain fluid properly. This often happens after cancer treatments such as surgery or radiotherapy, which can damage or remove lymph nodes. Based on recent statistics from National Institutes of Health (NIH), worldwide, around 250 million people live with lymphoedema. According to Singapore Cancer Society, in Singapore, about 30% of breast cancer patients develop lymphoedema after treatment. Despite its widespread impact, there is currently no cure, and the biological causes behind the disease are still not fully understood.

Scientists from the Department of Microbiology and Immunology at NUS Medicine have uncovered an important piece of the puzzle. The lymphatic system normally helps remove excess cholesterol from tissues and return it to the bloodstream. The researchers found that when lymphatic drainage is impaired in people with lymphoedema, cholesterol begins to build up in the skin and around lymphatic vessels. Over time, this cholesterol buildup changes the surrounding tissue. Fat cells in the skin become enlarged and dysfunctional, eventually leading to cell damage, scarring, and tissue thickening, which worsen swelling and stiffness in the affected areas.

Encouragingly, the team also found that improving lymphatic drainage surgically could reduce cholesterol accumulation and improve tissue aberrations observed in lymphoedema. In mouse models of lymphoedema, a cholesterol-removing compound called cyclodextrin reduced swelling and helped repair damaged lymphatic vessels. By restoring lymphatic function and clearing excess cholesterol, the treatment improved the overall condition.

This study suggests that cholesterol buildup may be a key driver of lymphoedema, opening the door to new treatment approaches that target cholesterol in affected tissues; an exciting step toward better therapies for a disease that currently has no cure.

For more in lymphoedema biotech:

• ImpediMed accelerates growth strategy on strong results and expanding market reach on lymphoedema.

• Nanotechnology advances the lymphedema treatment

• UQ technology aids early detection of lymphoedema in cancer patients

NEUROREGENERATION: Fixing the Cell’s Power Plants Can Improve ALS Symptoms

@Senuri De Silva

TL;DR:

• In ALS, nerve cells that control movement struggle to produce energy because their mitochondria; the cell’s “power plants” do not function properly.

• Researchers at IMCB, A*STAR found that a protein called BLOC1S1 disrupts mitochondrial function in ALS motor neurons.

• Reducing BLOC1S1 with a new molecule restored energy production and improved survival and movement in ALS mouse models.

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease that gradually destroys the nerve cells responsible for controlling muscle movement. As the disease progresses, patients lose the ability to move, speak, and eventually breathe. Despite decades of research, the biological processes that trigger ALS and drive its progression are still not fully understood.

Scientists at Institute of Molecular and Cell Biology, A*STAR have long suspected that mitochondria, the tiny energy generators inside our cells, play a key role in ALS. In motor neurons affected by the disease, mitochondria often fail to produce energy efficiently. In this study, researchers found that mitochondrial dysfunction in ALS is linked to excessive acetylation of mitochondrial proteins. This modification disrupts the normal activity of metabolic enzymes inside mitochondria, impairing cellular respiration and reducing the ability of motor neurons to generate the energy they need to function.

The team identified a protein called BLOC1S1 (also known as GCN5L1) as an important regulator of this process. They found that BLOC1S1 levels are unusually high in ALS motor neurons, driving the harmful changes in mitochondrial proteins. When the researchers reduced BLOC1S1 in motor neurons derived from patient stem cells, many of the disease-related problems improved, suggesting that this protein plays a central role in ALS pathology.

Building on this insight, the scientists developed a new experimental molecule designed to reduce BLOC1S1 levels by triggering the breakdown of its DNA. When tested in an ALS mouse model, the treatment extended survival and improved motor performance.

Together, these findings reveal an unexpected link between mitochondrial protein regulation and ALS progression. By targeting BLOC1S1 and restoring healthier energy metabolism in motor neurons, this work highlights a promising new direction for developing therapies against this currently incurable disease.

Learn more about ALS biotech:

• Leading biotechs working on the challenge towards cure for ALS

• China-based biotech Shionogi buys Tanabe’s ALS business in a $2.5 billion deal, plus potential future royalties

• UK-based biotech NRG Therapeutics takes aim at ALS by drugging mitochondria

• New approaches to ALS receive support as Axoltis Pharma secures €18 million

• Neurizon Therapeutics entering ‘a promising new horizon’ as ALS program advances

CANCER: Reversing Pancreatic Cancer Aggression by Restoring Cell Differentiation

@Devika Menon

TL;DR:

• Pancreatic cancers driven by KRAS mutations pushes tumour cells into a more aggressive, poorly differentiated state.

• Scientists at Duke-NUS Medical School discovered a molecular switch that suppresses normal cell identity in these tumours.

• Restoring this differentiation pathway made cancer cells more sensitive to chemotherapy, pointing to a potential new treatment strategy.

Pancreatic cancer is one of the deadliest cancers, ranking as the fourth most common cause of cancer death in Singapore. It is known that 85-95% of Pancreatic Ductal Adenocarcinoma (PDAC) cases have a mutation in the oncogene KRAS, which regulates cell growth. When mutated, KRAS continuously activates signalling pathways that fuel tumour growth and prevent cells from maturing into their normal specialised forms.

Scientists at Duke-NUS Medical School have uncovered an important mechanism behind this process. They focused on GATA6, a transcription factor that normally helps pancreatic cells maintain their differentiated, epithelial identity and restrains tumour progression. Loss of GATA6 is frequently associated with more aggressive forms of PDAC.

Through a genome-wide CRISPR screen, the researchers identified JUNB as a key transcriptional repressor that suppresses GATA6 expression. The study found that oncogenic KRAS signalling activates a pathway which reduces the expression of GATA6, shaping tumour cell identity by preventing differentiation and promoting an aggressive PDAC phenotype.

Encouragingly, restoring GATA6 expression made pancreatic cancer cells more responsive to chemotherapy. In preclinical models, combining KRAS/ERK inhibitors with chemotherapy produced stronger anti-tumour effects than either treatment alone.

Together, these findings reveal a KRAS–ERK–JUNB signalling axis that drives pancreatic cancer aggressiveness. Targeting this pathway could offer a new strategy to restore tumour cell differentiation and improve treatment responses in KRAS-driven cancers.

Read more about:

• KRAS-inhibitor combinations for pancreatic cancer identified by Singapore-based KYAN Technologies

🗞️ Industry Spotlight

News from the Singapore life sciences industry

• NTU collaborates with longevity biotech firm Aria Bioscience to translate the technology into consumer healthcare products

• NTU and US-based Activate launch S$12 million fellowship to accelerate science entrepreneurship and develop deep-tech start-ups

• Cytek Biosciences expands Singapore facility with US$3 million investment

• Terumo introduces cell & gene therapy ecosystem blueprint for APAC region

• Singapore’s ImmunoScape announces MoU for clinical trial with US-based cancer centre

• Cirrus Therapeutics expands global footprint to Singapore with ocular immunology business

🎧 Nucleate Singapore Pulse

Singapore’s premier podcast on the local biotech ecosystem.

Listen now

📆 Events happening this month

Conference/seminars

• Exploring Japan’s dynamic healthcare innovation ecosystem
  (18 Mar, 10:00 AM, online)

• Opportunities and Innovation Pathways in Dermatology
  (23 Mar, 01:00 PM - 04:00 PM, in person)

• LaunchPad Carnival
  (22 Mar, 02:o0 PM - 08:00 AM, in person)

• From Experimental Proof of Concept to Technology Demonstrators
  (26 Mar, 10:30 AM - 11:30 AM, in person)

• GITEX AI ASIA
  (9-10 Apr, TBA, in person)

• HealthTechX Asia
  (6-7 May, TBA, in person, early bird registration)

Networking

• Sat Health & Bio Brews Singapore

  (Every Sat, 9:00 AM - 10:30 PM, in person)

• GROWTHLAB & *SCAPE (Somerset Partners Appreciation Session)

  (20 Mar, 3:30 PM - 5:00 PM, in person)

Workshop

• MVP Masterclass
  (19 Mar, 9:00 AM - 3:00 PM, in person)

• Connecting Singapore Startup Founders to Indonesia Market Opportunities
  (26 Mar, 9:00 AM - 12:30 PM, in person)

Opportunity

• GIA Manila Acceleration Programme
  (20 Mar, 06:00 PM, apply online)

• Morning Pitch Asia - Regenerative & Aesthetic Medicine
  (26 Mar, 6:00 AM - 7:00 AM)

• Activate Global Fellows - Singapore Fellowship
  (Deadline 31 Mar, 59: PM, apply online)

• 𝐎𝐩𝐞𝐧 𝐂𝐚𝐥𝐥 𝐟𝐨𝐫 𝐒𝐮𝐛𝐦𝐢𝐬𝐬𝐢𝐨𝐧𝐬: 𝐒𝐡𝐚𝐫𝐞 𝐘𝐨𝐮𝐫 𝐖𝐨𝐫𝐤 𝐨𝐧 𝐂𝐇𝐈𝐋𝐃!
  (Deadline 31 Mar, apply online)

• RETVRN Alpha Program by SOSV
  (Deadline 31 Mar, 59: PM, apply online)

If you enjoyed reading this post, comment and give us a like! Or let us know your thoughts here.

🍽️ Digestibles

High potential SG research, hot off the press

INFECTIOUS DISEASES: Turning Down the Immune Alarm: How E. faecalis Persists

@Senuri De Silva

TL;DR:

• Enterococcus faecalis suppresses immune cells by releasing lactic acid, which makes the local environment more acidic.

• Scientists found that this acidity shuts down macrophage immune signaling, preventing effective bacterial clearance.

• Lactic-acid–mediated immune suppression allows E. faecalis to persist and even support other bacteria during mixed infections.

Enterococcus faecalis is a bacterium that normally lives harmlessly in the human gut, but it can become a serious opportunistic pathogen, especially in hospital settings or in people with weakened immune systems. It is a common cause of wound and catheter-associated infections, often occurring alongside other bacteria. Treating these infections is increasingly difficult due to antibiotic resistance, biofilm formation, and the bacterium’s ability to survive inside host cells.

Scientists at SMART, CREATE and SCELSE, NTU uncovered how E. faecalis weakens the immune system to persist in the body. They found that the bacterium produces lactic acid using an enzyme called lactate dehydrogenase (LDH), which lowers the acidity of the surrounding environment. This acidic environment directly interferes with immune cells known as macrophages, which are normally responsible for detecting and eliminating bacteria.

Macrophages detect this change through surface receptors, which then activate signals that suppress key immune pathways. As a result, macrophages fail to activate important inflammatory responses needed to clear infection. In mouse wound infection models, lactic-acid–producing E. faecalis survived longer and even helped other bacteria, such as E. coli, thrive during mixed infections. When researchers tested lactic-acid–deficient bacteria in the mice, these immune-suppressing effects disappeared, confirming lactic acid’s key role in modulating host immune responses.

By uncovering how E. faecalis suppresses immunity using lactic acid, this work highlights potential molecular targets that could be exploited to restore immune function and improve treatment of chronic infections.

Learn more about antibiotic resistance biotech:

• GSK ushers in new UTI antibiotic with FDA nod for first-in-class Blujepa

• Lixa and GARDP to collaborate on tackling antimicrobial resistance

• Danish BioTech scale-up SNIPR Biome raises €35 million to target antimicrobial resistance in diseases like cancer

CANCER: RNA-Based Targeting of Tumor Immunosuppression

@Devika Menon

Tumors evade immune surveillance not only by escaping recognition by cytotoxic T cells, but also by actively recruiting regulatory T cells (Tregs) that suppress anti-tumor immune responses. In this study, NUS scientists presented a targeted RNA-based strategy designed to disrupt this mechanism. Their approach focuses on CD137, a surface receptor that is highly enriched on intratumoral Tregs and is associated with poor clinical prognosis.

They engineered aptamer-shRNA chimeras for targeted silencing of genes that drive immunosuppression. An aptamer is a short RNA molecule that binds a specific target while short hairpin RNAs (shRNAs) are RNAs that can silence specific genes. They fused a CD137-specific aptamer - that binds to intratumoral Tregs - to a shRNA that silences genes responsible for Treg suppression.

As a result of the study, they discovered that the CD137 aptamer can effectively bind to Tregs and deliver shRNAs to target cells so that genes sustaining the suppression of Tregs may be silenced. This results in weaker shielding of the tumor from the immune system. Additionally, the authors found that the aptamer itself may co-stimulate effector T cells, activating further immune responses.

These findings highlight the potential of RNA-based strategies to overcome tumour immunosuppression while activating immune responses, offering a possible path to enhance the effectiveness of current immunotherapies.

For more on RNA-based immunotherapies:

• Eli Lilly buys Orna in $2.4B deal to enter in-vivo CAR-T arena

CANCER: The Molecular Bodyguard Protecting EGFR in Lung Cancer

@Senuri De Silva

TL;DR:

• Many lung cancers are driven by mutant EGFR proteins that are initially sensitive to targeted drugs but later become resistant.

• Researchers found that cancer cells release ATP, which activates the P2Y2 receptor to stabilize mutant EGFR and protect it from degradation.

• Disrupting this ATP–P2Y2 protective system in mouse models reduced EGFR stability, and key components of this pathway were also elevated in lung cancer patients, pointing to potential relevance in humans

Lung cancer is the leading cause of cancer-related deaths worldwide, with about 85% of cases classified as non–small cell lung cancer (NSCLC). In many patients particularly in Southeast Asia, NSCLC is driven by mutations in the EGFR gene, which normally regulates controlled cell growth. These mutations are found in up to 40–60% of lung adenocarcinoma cases, a major subtype of NSCLC. While targeted treatments known as EGFR inhibitors are initially effective and have significantly improved patient outcomes, cancer cells often develop additional mutations over time, allowing them to escape therapy. This acquired drug resistance remains one of the biggest challenges in treating EGFR-driven lung cancer.

Beyond genetic changes, researchers have long observed that mutant EGFR proteins are unusually stable, allowing cancer cells to continue growing even when treatments attempt to shut them down. Until recently, the reason for this enhanced stability was poorly understood. Scientists at IMCB, A*STAR addressed this gap by uncovering a mechanism through which cancer cells actively protect mutant EGFR from being destroyed.

Their work revealed that EGFR-mutant cancer cells release high levels of ATP, a molecule best known for its role as cellular energy. This extracellular ATP activates a surface receptor called P2Y2, which in turn helps stabilize mutant EGFR. The researchers showed that P2Y2 cooperates with other helper proteins to form a protective complex around mutant EGFR inside the cell, preventing its degradation. When this protective system was disrupted in mouse models, mutant EGFR became less stable and easier to eliminate. Importantly, elevated levels of these helper proteins were also observed in lung cancer patients, indicating that this mechanism operates in real tumors.

This study points to new therapeutic opportunities beyond traditional EGFR inhibitors by revealing how cancer cells actively stabilize mutant EGFR. Targeting this stabilizing machinery alone or alongside existing drugs could weaken tumor defenses, restore treatment sensitivity, and improve the durability of targeted therapies in EGFR-mutant lung cancer.

Learn more about EGFR and lung cancer biotech:

• J&J and Google’s venture arms line up to back EGFR protein degradation biotech EpiBiologics‘ $107M series B.

• ImmunityBio’s drug Anktiva succeeded in restoring immune cells for lung cancer.

• Kelun-Biotech touts front-line lung cancer win for ADC partnered with Merck & Co.

🗞️ Industry Spotlight

News from the Singapore life sciences industry

• First fibrotic disease drug of Singapore by Duke-NUS and SingHealth advances into Phase II clinical evaluation.

• Singapore’s Industry-Academic Partnerships Augment Oligonucleotide Therapeutics Innovations by NTU Oligo Foundry.

• HistoIndex teams up with Houston Research Institute to expand advanced MASH diagnostic services.

• Engine Biosciences, a Singapore- and Silicon Valley-based biotech company, has raised $13.6 million in its latest funding round, according to its recent filings.

• Singapore Paincare expands operations and client base with TS Medical acquisition

• $45b state surge triggers global VC influx to Singapore’s Biopolis.

• HSA clears cancer-detecting AI for routine hospital use

🎧 Nucleate Singapore Pulse

Singapore’s premier podcast on the local biotech ecosystem.

Listen now

📆 Events happening this month

Conference/Seminars

• From Bench to Business: Building MedTech Ventures That Matter
  (24 Feb, 4:00 PM - 7:00 PM, in person)

• ANDlightenment: The Joy of Seeing and Leveraging Polarities
  (25 Feb, 1:00 PM - 3:00 PM, in person)

• JDI Reality Check: Scaling Healthcare Systems to Asia
  (26 Feb, 9:00 AM - 10:30 AM, in person)

• Festival of Innovation 2026
  (3-4 Mar, 9:00 AM - 5:00 PM, in person)

• HealthTechX Asia
  (6-7 May, TBA, in person, early bird registration)

Panel discussion

• Activate Global Fellows: SG Panel
  (25 Feb, 4:00 PM - 6:00 PM, in person)

• 𝗨𝗻𝗯𝗼𝘅𝗶𝗻𝗴 𝗗𝗮𝘆: 𝗛𝗲𝗮𝗹𝘁𝗵𝗰𝗮𝗿𝗲 𝗜𝗻𝗻𝗼𝘃𝗮𝘁𝗶𝗼𝗻 𝗦𝗵𝗼𝘄𝗰𝗮𝘀𝗲
  (25 Feb, 3:00 PM - 5:00 PM, in person)

Networking events

• Sat Health & Bio Brews Singapore

  (Every Sat, 9:00 AM - 10:30 PM, in person)

• GROWTHLAB & *SCAPE (Somerset Partners Appreciation Session)

  (20 Mar, 3:30 PM - 5:00 PM, in person)

• MedTech Actuator World Connect

  (26 Feb, 4:00 PM - 6:00 PM, in person)

If you enjoyed reading this post, comment and give us a like! Or let us know your thoughts here.

🍽️ Digestibles

High potential SG research, hot off the press

Finding the Real Drivers of Gastric Cancer

@Senuri De Silva

TL;DR

• Gastric cancer stem cells drive cancer progression and are difficult to identify due to unreliable markers and a lack of functionally validated models.

• Researchers at IMCB identified and validated AQP5 as a highly specific cancer stem cell marker, presenting a potential new target to combat gastric cancer spread and recurrence

Not all cancer cells are equal. Among them is a small but powerful group called cancer stem cells; cells that can keep a tumor growing, help it spread, and cause the cancer to return even after treatment. Because of this, understanding and eliminating these cells is seen as a key strategy for long-lasting cancer therapy. Cancer stem cells have been identified and studied in several cancers, including blood and colon cancer. Surprisingly, they have been much harder to pin down in gastric (stomach) cancer, even though the stomach normally contains many stem cells. One major reason is that scientists have struggled to reliably identify these cells. Many proposed markers are shared across different cell types, lack strong functional proof, or are studied in models that don’t fully reflect how human tumors behave.

To overcome these challenges, scientists at Institute of Molecular and Cell Biology (IMCB) developed a new approach to isolate a specific group of gastric cancer stem cells marked by a protein called Aquaporin-5 (AQP5). AQP5 is a highly specific gastric cancer stem cell surface marker arising from the lower end of the stomach. They successfully identified AQP5-positive cells in both mouse and human stomach tumors, including metastatic samples. When they examined these cells more closely, they found that AQP5-positive cells were rich in gene programs linked to stem cell activity.

Importantly, the study did not rely on marker expression alone. The authors rigorously validated function, confirming true cancer stem cell behavior. AQP5-positive human tumor cells were able to form long-lasting organoid cultures and regenerate invasive tumors when transplanted into mice. In contrast, AQP5-negative cells failed to do so. Even more strikingly, removing AQP5-positive cells reduced tumor formation and caused existing tumors to shrink, showing that these cells are true drivers of the disease. Further experiments revealed that AQP5 fuels tumor growth and invasion by activating well-known cancer pathways across realistic organoid and animal models.

Together, these findings place AQP5 at the center of gastric cancer’s ability to adapt, resist treatment, and come back. In short, this work identifies AQP5 as a functional marker and vulnerability of gastric cancer stem cells, offering a clearer path toward therapies that target the root of tumor recurrence rather than just the bulk of the cancer.

Learn more about stem cells biotech:

• Orca Bio announces $250M in aggregate financing in preparation for potential commercialization.

• Century Therapeutics secures oversubscribed $135 million private placement financing to support lead program, CNTY-813, a potentially curative therapy for type 1 diabetes.

Starving Tumors to Train Immunity: A New Strategy for Cancer Vaccines

@Senuri De Silva

TL;DR

• Cancer vaccines often fail because tumors create an immunosuppressive environment that blocks immune cells and weakens immunotherapy.

• Researchers at NUS medicine targeted abnormal tumor metabolism-specifically glycolysis by incorporating anti-glycolytic molecules into a cancer vaccine strategy.

• In melanoma mouse models, this approach eliminated tumors, triggered immune-mediated tumor cell death, and prevented cancer recurrence.

Cancer vaccines are a promising form of targeted therapy, designed to train the immune system to recognize and attack cancer cells while causing fewer side effects than many conventional treatments. This is especially important in immunotherapy, where powerful immune activation can sometimes lead to serious autoimmune complications.

However, tumors are highly adaptive. Many cancers actively protect themselves by releasing immunosuppressive molecules that block immune cells such as T cells and B cells from entering the tumor. As a result, the tumor microenvironment becomes hostile to immune attack, making it difficult for cancer vaccines to trigger effective tumor cell killing. This is one of the key reasons why current cancer vaccines often show limited success.

Researchers at the NUS School of Medicine identified abnormal tumor metabolism, specifically excessive glycolysis, the process by which cells break down sugar for energy, as a major driver of this immune suppression. Tumors rely heavily on glycolysis to fuel growth and create an environment that weakens immune responses. To counter this, the team developed a cancer vaccine strategy that includes anti-glycolytic molecules to disrupt tumor metabolism. Importantly, the vaccine is delivered using tumor cell–derived microparticles, which enable highly specific targeting, deep tumor penetration, and efficient delivery of the therapeutic payload directly into the tumor microenvironment.

In mouse models of melanoma, this approach completely eliminated tumors and prevented recurrence. Importantly, the treatment triggered immunogenic tumor cell death, allowing immune cells to “learn” the tumor’s identity and form long-lasting immune memory. This work highlights a powerful new direction for cancer vaccines-one that combines immune training with metabolic targeting to achieve durable anti-tumor immunity.

Learn more about cancer vaccines,

• Korea’s Dx&Vx signs $220 M agreement for mRNA cancer vaccine development with US biotech firm.

• TransCode rewrites future, securing $25M lifeline and phase 3 cancer vaccine.

FAT10 protein reprograms metabolism in cancer cells

@Devika Menon

TL;DR

• FAT10 protein is upregulated under inflammatory conditions and promotes tumorigenicity in cancers

• This study found that it shifts the priorities of the cell away from growth towards survival, allowing cancer cells to persist under metabolic stress

The ubiquitin-like protein FAT10, primarily expressed in immune cells, has been known to support immune function. While its levels are usually low, it is upregulated under inflammatory conditions and promotes tumorigenicity in inflammation-driven cancers. Aside from its immune functions, FAT10 has been known to interact with proteins related to metabolism and cell cycle processes. Hence, in order to better understand the pathways regulated by FAT10 in cancer cells, scientists at NUS Yong Loo Lin School of Medicine and Duke-NUS Medical School conducted a multi-omics analysis by integrating quantitative proteomics, interactomics and metabolomics using a colon cancer cell model.

They discovered that FAT10 simultaneously upregulated metabolism-related proteins (associated with energy uptake, production and storage such as glycolysis, lipid biosynthesis) and downregulated energy-consuming processes such as transcription, translation and cell cycle progression. While it stabilizes glycolysis-related proteins, it destabilises RNA processing and transcription related proteins. In doing so, the upregulation of FAT10 shifts the focus of the cell away from replication and growth to survival. Under inflamed, nutrient-poor conditions, cancer cells upregulated FAT10 so as to reprogram metabolic pathways and favor energy uptake and storage in order to improve cell survival. Together, these findings identified FAT10 as an immunometabolic switch that cancer cells use to rewire metabolism, prioritize survival over growth, and persist even under inflamed, nutrient-poor tumor microenvironments, revealing it as a potential target against cancer survival.

Learn more about:

• Unique nature of the FAT10 protein

• Structure of FAT10 protein provides insight into potential cancer drug

🗞️ Industry Spotlight

News from the Singapore life sciences industry

• Singapore’s Zeya Health secures $575,000 Pre-seed funding from Antler and strategic angel investors.

• Singapore-based Zuellig Pharma expands partnership with Lundbeck for commercialisation of neuro-psychiatric health solutions in Asia.

• Singapore approves Intelligent Scopes Corp (ISC)’s AI software tool CystoSmart for bladder cancer detection.

• Esco Aster provides CMC manufacturing support for shine on biomedical’s HLA G targeted exosome program.

• Respiree secures HSA approval for ai driven acute deterioration detection software

• ChemLex establishes global headquarters and self driving laboratory in Singapore with USD 45 million funding

🎧 Nucleate Singapore Pulse

Singapore’s premier podcast on the local biotech ecosystem.

Listen now

📆 Events happening this month

Conference/Seminars

• IBM AI Innovation Day 2026
  (23 Jan, 9:00 AM - 12:00 PM, in person)

• From Lab to Clinic: Next-Gen Diagnostics for Precision Care
  (23 Jan, 10:00 AM - 02:00 PM, in person)

• Tea & Jam: Design & Build for Healthcare

  (23 Jan, 03:00 PM - 05:30 PM, in person)

• Sustainability Analysis for Future Foods – Life Cycle Assessment and Beyond
  (23 Jan, 2:00 PM - 05:30 PM, in person)

• The Future of Cognitive Health in the Age of AI
  (30 Jan, 06:00 PM - 09:00 PM, in person)

• Precision Fermentation in Singapore - An Ecosystem Perspective through the lens of Engineering Biology
  (03 Feb, 11:00 AM - 12:00 PM, in person)

• Beyond Borders Series: Scotland–Singapore Synthetic Biology Exchange
  (12 Feb, 9:30 AM - 10:30 AM, online)

• HealthTechX Asia
  (6-7 May, TBA, in person, early bird registration)

Competitions

• Morning Pitch Asia - Healthtech for Aging Society (AGEtech)
  (16 Jan, 10:00 AM - 11:00 AM, in person)

Networking

• Sat Health & Bio Brews Singapore

  (Every Sat, 9:00 AM - 10:30 PM, in person)

About The Guest

Dr. Lewis Hong is the Vice President of Paratus Sciences, a biotech company uncovering novel therapeutics by studying the extreme biology of bats. With a background spanning genomics research, pigmentation genetics at Stanford, and leadership roles in translational sciences at MSD, Lewis brings deep scientific and industry expertise to this pioneering field.In this episode, Lewis shares how Paratus was founded to explore bats as a unique model for human health. He explains how the company built a large-scale bat genomics and bioinformatics platform which combines global sample collection, industrial sequencing, and a powerful knowledge graph, to identify high-impact therapeutic targets.

Lewis highlights Paratus’ two lead focus areas:

• Immunology & inflammation, featuring their ASC inflammasome inhibitor program now entering IND-enabling studies;

• Cardiometabolism, inspired by bats’ remarkable metabolic resilience and cardiac performance.

He also discusses the challenges of scaling bat genomics, the role of academic partnerships, building an R&D team in Singapore, and the broader trajectory of Singapore’s biotech ecosystem. Lewis closes with practical advice for scientists entering biotech, emphasizing resilience, long-term thinking, and the importance of strong mentors and collaborators.

🥡 Key Takeaways

• 🦇 Bat biology reveals unique mechanisms of disease resistance, offering powerful inspiration for human therapeutics.

• 🧬 Paratus has built an industrial-scale bat genomics platform that rapidly uncovers high-value drug targets.

• Insights from bat immunity led to a first-in-class ASC inflammasome inhibitor now entering IND-enabling studies.

• ❤️‍🔥 Bats’ extreme metabolic and cardiac adaptations are guiding new approaches in cardiometabolic drug discovery.

• 🤝 High-impact collaborations with leading academic groups accelerate validation and translation of bat-derived insights.

• 📈 Singapore’s biotech ecosystem is rising, but continued growth depends on experienced talent and stronger private investment.

💬 Quotes

• Bats are remarkable because they can carry a wide range of viruses, but they don’t get sick from them.

• It was not long ago that a large group of scientists would work for a few years to sequence and analyze the genome of a new species of mammal and then get that published. We have essentially done this 150 times over the same time period, but with a very small team.

• This approach is a lot quicker than traditional approaches for target identification, and it can iterate much faster and help us to rapidly prioritize the most promising targets to pursue.

• So, you know, is government support important to keep growing the sector and are they doing all the right things? Yes, absolutely… the trend may be realizing that the government cannot do it all, and we may need slightly different approaches to attract private capital, to cultivate a stronger entrepreneurial culture, to build deeper global partnerships.

• In biotech, it is often the person who is the most disciplined, that is the more persistent, the more resilient, that will be more successful in the long run.

⏱️ Timestamp

• 01:07 Introduction

• 01:28 Early Career Journey

• 06:20 Transition to Industry

• 10:35 Bat Biology & Drug Discovery

• 16:28 Scaling Bat Genomics

• 20:58 Pursuing ASC2 as a Therapeutic Target

• 23:43 Future Directions & Partnerships

• 34:52 Advice for Aspiring Biotech Professionals

• 39:16 Closing Remarks

🎙️ Transcript

Episode Preview

Dr Lewis Hong:  There are actually more than 1400 species of bats, which comprises about 20% of all mammals, and they are the only mammals that have evolved powered flight. And so along with their ability to fly, bats have acquired extreme physiological fitness. They are very long-lived, and they have acquired different mechanisms to resist disease. At Paratus Sciences, we created the operational and scientific machinery to access very large numbers of bat samples from all around the world.

Aakash Naresh Kumar:  Hi, thanks for joining us on Nucleate Singapore Pulse, Singapore’s premier podcast on the biotech ecosystem. I’m your host, Aakash Naresh Kumar, the lab community manager at the Life Science Incubator. Whether you’re a student thinking about creating your own startup or an industry professional looking for diverse perspectives, this is the podcast for you. The show notes and transcripts for the episode can be found on nucleate. singapore.substack.com.

Today we are very glad to have with us Dr. Lewis Hong. Lewis is the Vice President of Paratus Sciences, a company that specializes in understanding bat biology to unlock therapeutics. Thank you so much again for joining us today, Lewis.

Dr Lewis Hong: It’s great to be here, Aakash. Thank you for having me.

Aakash Naresh Kumar: So to begin, could you start by sharing a bit about your background? What sparked your fascination with genomics and eventually into therapeutics?

Dr Lewis Hong: I’m Singaporean, born and raised here in Singapore. Growing up I’ve always been fascinated with science and biology, and I spent most of my time in secondary school and junior college thinking that I wanted to be a medical doctor, which I think was quite a conventional path for somebody who was interested in the life sciences.

But ultimately I decided it was going to be more intellectually stimulating to study the life sciences rather than practice the science of medicine. As a kid, and definitely even today, I was very fascinated by the natural world and trying to understand everything about it, and so I felt that deciding to go to medical school and train as a doctor at the age of 20, would just put me down a very focused and specialized path to learn about human physiology and how to treat patients and all of that, which of course, many years later is what I’m doing now, applying my skills as a scientist to develop drugs that help patients.

But at that time, my heart told me that I would really just enjoy learning biology and going after basic research questions that would interest me. So after serving National Service in Singapore, I found myself at the University of Wisconsin-Madison. There was a very big change, you know, culturally, it was trading the jungles of Pulau Tekong for the harsh winters of the American Midwest.

But it was there that I found myself in a really excellent academic environment, absent from distractions. And in my first year I started working many hours as an undergrad in a research lab and I loved it. You know, I love being in a lab interacting with fellow scientists working at the bench. And at that time I was working in a lab that was using Arabidopsis as a model organism.

So that’s a plant. And we were identifying the genes and pathways that control flowering plants. I enjoy myself thoroughly. I would spend weekends and summer breaks working in the lab and fell in love with the research. And of course at that time I knew I would want to go to grad school to do a PhD and I ended up in the genetics department at Stanford University.

I knew that my love was for basic science and basic research at the time, and so I ended up in a lab that was very interested for a long time to study the genetics of pigmentation in mice and later in humans. But what really caught my interest and what I ended up doing was a really exciting new project at the lab to study the molecular basis of pigment patterning.

And so this is about understanding how the cheetah got its spots and how the zebra got its stripes. For me, that just felt like such a cool research project to work on as a grad student. And the reason we were able to study this question was that next generation sequencing methods were just coming out.

And we were beta-testing some of the first generation instruments in our department, and we were able to imagine how we can collect samples from animals like zebras and cheetahs and do RNA sequencing on their skin to understand what were the differences in expression patterns between, for example, the black spotted region of a cheetah and the yellow region of the skin.

And this, so this is where I also picked up bioinformatics because this was a time where library preparation kits for NGS were not available. There were no software tools that we have nowadays to do rapid bioinformatic analysis. So everything had to be done by yourself. And I developed a method to do digital gene expression profiling on the skin of these non-model organisms.

And so this was a really exciting project where I had to figure out where we would get the samples, how we would develop a protocol to measure gene expression in these animals, and then develop a bioinformatic method to analyze the gene expression profile. It was very fun trying to figure all that out, and we ended up identifying a small peptide that was over-expressed in the black spotted region of cheetah.

That small peptide is known to interact with melanocytes in the hair follicle in cheetah skin to produce that black pigment. And when this peptide was over-expressed in a mouse that would normally produce yellow hair, those hairs turned black. So we found this factor that is responsible for maintaining black spots in cheetahs.

Looking back, it was all this very fun research that I did as an undergrad and PhD student that showed me the power of applying genetics and genomics to study nature-inspired biology, which, of course, now many years later is what I’ve circled back to do at Paratus Sciences.

Aakash Naresh Kumar: But that’s a really good outline of your early career journey, which I’m sure our listeners can relate to.

It was a long journey and the different things that you did definitely would’ve shaped your future career aspects as well. Like for example, in your PhD after that, you did spend some time at A*STAR IMCB as a research fellow, and after that you moved on to working at MSD for eight years on translational sciences before you finally joined Paratus.

Could you share how each of these experiences influenced your decision to eventually move on to the entrepreneur spaces and the sort of insights you’ve gained from this progression?

Dr Lewis Hong: Yes, I’m happy to talk about that. So I decided after doing a post-doc that academia was really not where I wanted to stay.

I did not see myself becoming a professor, but I wanted to stay in a research focused role because I enjoyed generating and analyzing data, thinking about scientific problems and how to solve them. I also wanted to work in an area where I could see more direct application of helping people with the work that I do.

So the obvious thing for me was to move to industry and an opportunity came up to join the MSD site in Singapore. They were looking for a genomics expert at that time to join the biomarkers team, and it felt like a good fit for me. Eventually, I was promoted to lead the team and took on broader responsibilities supporting multiple platforms for biomarker discovery, biomarker development, as well as target discovery for different therapeutic areas within MSD.

And to get back to your question, there were two general areas that were really impactful for me during my time in Big Pharma. One was learning about drug discovery and drug development. And the second area is developing what I would call a strong corporate quotient or corporate intelligence.

First of all, working in a Big Pharma company, you really get to learn from many, really impressive colleagues that are experts in their respective domains.My colleagues came from different functions across the entire value chain of drug discovery. From discovery research to preclinical, to toxicology, to clinical research, and outside of R&D, in medical affairs, commercialization, et cetera. So there was a tremendous learning opportunity for me at the time to really just learn from the best in the business.

Second thing that I mentioned was developing the intelligence to succeed and to be impactful in a corporate setting, which for me, at the individual level was about what enables a person to think and act and be in alignment with organizational purpose, organizational strategy, and then to adapt to the needs of the business in an evolving environment.

It’s about developing strategic thinking skills to understand how to connect my role as an individual to the larger vision and the goal of the company. It’s about making decisions with a sense of purpose. Being accountable to stakeholders about what you’re supposed to deliver is about systems thinking, seeing interconnections and interdependencies across teams and functions, and how to navigate corporate dynamics and exert influence at the right level to impact decision making.

The nice thing about being in a big company is, you have many role models and very high standards of professional competency from people that you can just learn from every single day. So I think these experiences, and developing these skills, was an important part of my early experience in industry and prepared me quite well for the challenges that I took on later.

Aakash Naresh Kumar: I think you hit the nail right on the head with regards to having colleagues that you can learn from. There’s so much you can learn that you cannot really learn from school, like you said. Learning, not just about the science that you mentioned, but there’s a lot of things that a company- a biotech company that is rooted in life science of biotech- there’s not just the science, it’s not just the research; you gotta think about IP regulation, licensing, and also the business aspect of things as well. So moving on to Paratus, it was established to unravel the mysteries of bat biology for the betterment of human health. Based on all that you have mentioned, all the different things that you’ve learned over working with many different people, in layman terms, how would you describe-- how do bats inform drug discovery at Paratus?

Dr Lewis Hong: Paratus Sciences is a biotech startup that was founded about four years ago with Series A funding. Our co-founders are Rick Young, who is a professor at the MIT Whitehead Institute, Paul Matsudaira, who was a professor here at NUS and Thomas Zwaka, who is from the Mount Sinai School of Medicine, and together they came up with the idea that bat biology can be a platform to identify and develop novel therapeutics for human health.

So the question that you may have is why bats? Bats are incredibly successful. They have evolved for over 65 million years on this planet. There are actually more than 1400 species of bats, which comprises about 20% of all mammals, and they are the only mammals that have evolved the power of flight. And so along with their ability to fly, bats have acquired extreme physiological fitness.

They are very long-lived and they have acquired different mechanisms to resist disease. At Paratus Sciences, we created the operational and scientific machinery to access very large numbers of bat samples from all around the world. And over the last few years, we have built a very large and robust genomics dataset from those samples.

All that data that we generated was used to build a proprietary platform that was developed with the tools and methods necessary to understand the extreme and unique attributes of bat biology, and then to apply those scientific insights to identify and develop new therapies for human diseases of high unmet.

Aakash Naresh Kumar: That’s really cool. I think just from the last two minutes, I learned more about bats than I ever did before, but since you mentioned about how Paratus is using bat biology to understand possible therapeutic targets, we do understand that the way that Paratus functions is, the platform that you guys have built, fully integrates bat genomics and informatics to mine these therapeutic targets through high throughput screening and in vitro or in vivo functional assays and disease models. Could you walk us through how these different pillars interlock in the day-to-day R&D work and the sort of unique insights or advantages that this integration delivers to accelerate your discovery?

Dr Lewis Hong: At the moment, we are focused on two therapeutic areas.

One is immunology and inflammation, and the second is cardiometabolism. Both of these areas are informed by unique aspects of bat biology. From the immunology perspective, we know that bats are exceptional viral reservoir hosts. Bats are remarkable because they can carry a wide range of viruses, including SARS, like coronaviruses, Ebola virus and Rabies virus, but they don’t get sick from them.

Studies have shown that bats can achieve this by finely tuning the immune systems so that they can defend against infection without triggering excessive inflammation. We have been leveraging this unique biology to develop anti-inflammatory therapies that can mimic this disease-resistant state in bats.

And our lead program in inflammation targets a protein called ASC, which is a central node of the inflammasome pathway. This target was inspired by research from Professor Linfa Wang’s lab at Duke-NUS Medical School. We in-licensed this technology and, since then, we’ve made rapid progress and have recently advanced this program into IND-enabling studies.

On the cardiometabolic side, we leverage the ability of bats to handle a very wide range of diets. You may know that most bats, about 70% of bats, are insectivores, so they feed on insects primarily. Most of the other insects feed exclusively or primarily on a diet of fruits or nectar. Nectar is essentially made up of about 70% simple sugar by weight, which is like seven times more concentrated than Coke, but bats can avoid developing obesity, fatty liver, or diabetes so clearly there are some fascinating mechanisms that have evolved in bats, which make them a compelling model to discover protective metabolic mechanisms. We’ve used our discovery platform to launch a very early-stage metabolic program that’s already showing very strong and exciting in vivo efficacy.

Finally, bats are the only mammals that are capable of flying and their cardiac physiology is really quite extraordinary. The heart rate of bats can go up from about a hundred to two hundred beats per minute when they’re resting, to over a thousand beats per minute when they’re flying. Despite such extreme physiological stress on the heart, bats can maintain very robust cardiac function and resistance to mitochondrial dysfunction, and this suggests that they must have evolved mechanisms to support myocardial energetics and protect against contractile dysfunction.

We have been collaborating with Professor Derek Hausenloy and Chrishan Ramachandra at the National Heart Center in Singapore, to study these adaptations and use batsas a model for discovering novel therapeutic targets for cardio protection.

Aakash Naresh Kumar: What are some of the biggest challenges that Paratus has faced and how do you manage to overcome them when you are first trying to understand about bat genomics?

Dr Lewis Hong: So a major challenge that the company needed to solve for initially was to access high quality tissue samples and try to get this from all around the world. To solve this problem, we established the BBF or the Bat Biology Foundation, which works directly with local researchers. It supports field expeditions and to ensure that we get high quality sample collection. The BBF also helped with building trust with our academic partners as we share data back with them to support their own research. The second challenge was to scale the actual genomics data generation. Over the last few years, Paratus has sequenced and analyzed close to 150 new bat species, which is about 10% of all known bats. These bats have been sequenced and analyzed at both DNA and RNA level.

This is really an undertaking that goes far beyond what any academic consortium or genomics company has attempted. It was not long ago that a large group of scientists would work for a few years to sequence and analyze the genome of a new species of mammal, and then get that published. We have essentially done this 150 times over the same time period, but with a very small team.

And we were able to address this challenge thanks to a very specialized team that’s built an industrial level of highly efficient sequencing and computational infrastructure.

Aakash Naresh Kumar: I see. How much are you able to share in terms of how this infrastructure will actually help to map out the bat biology?

Dr Lewis Hong: Yes.

One of the things we have seen in our platform is just how much faster and more precise we can be in identifying new drug targets compared to traditional approaches. As I mentioned just now, we’ve generated an enormous amount of genomic and biological data from bats, and we built something called a knowledge graph, which is like a giant map that connects everything we know about genes and proteins, phenotypes, diseases and drugs, both in bats in humans. And this map that we created has tens of millions of connections. By analyzing this map, we can spot patterns and hidden relationships that point us to new therapeutic approaches and ways to treat disease. And what we have realized so far are two things. One, this approach is a lot quicker than traditional approaches for target identification, and it can iterate much faster and help us to rapidly prioritize the most promising targets to pursue.

And the second is that it captures really interesting relationships that we will not have uncovered if we had just used a conventional approach to target identification.

Aakash Naresh Kumar: That’s really interesting. Another question about this infrastructure is, you mentioned that one of the challenges is trying to acquire quality bat samples.

Well, you do collect all these bat samples from all over the world. Do you have to factor in the genetic variation and how do you try to overcome that when trying to figure out a common therapeutic target?

Dr Lewis Hong: Well, yes, it can be challenging because the genome sequences of different bat species can be quite different from one another. Just like a mouse genome could look quite different from a human genome. However, there are very high levels of conservation in terms of gene sequence, protein sequence, and the structure of the bat genome. So we have been able to leverage computational tools that have already been developed by others in the field to assemble and annotate the genomes of bats.

Of course, we had to spend time to figure out what the best methods are. We had to optimize those workflows, and then we had to industrialize it so we can automate it and do it in a very efficient manner. The other thing we have learned also is that bat proteins are very well-conserved and largely perform similar functions as their human counterparts, which means that that can be a very good translatable model for human disease.

I’ll be happy to talk more about some specific examples.

Aakash Naresh Kumar: That was gonna be my next question actually, in regards to some specific targets that you have identified, or even maybe going a bit into deeper detail about what are some of the things that you have shortlisted in your pipelines. For example, cardiometabolism, and also for the immunology and inflammation side.

Dr Lewis Hong: Sure, I can expand on an example that I mentioned earlier, which is our ASC program. The original insight for this project came from Linfa’s lab in Duke-NUS, who has been studying the ASC2 protein. The scientist that was leading this project, Matae Ahn, has now started his own lab in NTU. We licensed the IP from Duke-NUS a few years ago and built upon it to uncover deeper mechanistic insights that ultimately led us to target ASC. ASC is a key component of the inflammasome complex. It’s a highly conserved and essential part of the mammalian innate immune system that acts like an alarm system that detects dangerous signals, such as infections, and then triggers inflammation. Sometimes when you have excessive inflammasome activity, it can lead to chronic inflammation, and we know that that results in a number of human diseases.

There are actually more than 10 types of inflammasomes that each respond to different types of danger signals. But ASC, which is our target, is the common adapter protein among these inflammasomes, and it helps to assemble and activate all of them. So we have taken this novel approach of targeting ASC, which is inspired by what bats are doing.

Our hypothesis is that by inhibiting ASC, we can broadly suppress multiple types of inflammasomes all at once. And we believe this has the potential to improve on current anti-inflammatory drugs. We have identified a human disease where we think this mechanism will have real impact, and we’ve also developed an excellent drug candidate that is highly potent.

It reduces inflammation in several disease models, and we’ve invested significant effort to demonstrate that this molecule that we’ve developed can be manufactured reliably and with the quality that’s needed for clinical development. I’m excited to share that, we have now decided to take this molecule that we’ve developed into IND-enabling studies, which will bring us one step closer to testing in patients.

Taking a step back on a personal level, it has been very exciting for me to see how academic work that was just published in a scientific journal two years ago has now been translated into a promising drug candidate and hopefully a new treatment for patients in the future.

Aakash Naresh Kumar: Yeah, really sounds exciting and we are all rooting for you guys.

Happy to see what comes out of all the hard work that you guys are doing. So you’ve shared a lot about the immunology and inflammation side of things. Would you foresee that Paratus might branch out to other areas of therapeutics, besides just immunology, inflammation and cardiometabolism?

Dr Lewis Hong: We are a small company, so we have to be as focused as possible with limited resources and to advance our projects as far as we can.

Ultimately, we would really like to be able to develop breakthrough therapies that can impact patients in the short term. It does limit us on the number of projects we can take on and the number of disease areas that we will work in, and that’s why one of our goals is to partner with Big Pharma companies to fully leverage the potential of our platform and to be able to take it into other areas like oncology, like aging, areas where we believe bat biology is also unique.

Aakash Naresh Kumar: I am glad you brought up collaboration also because I was hoping to pivot a little bit more to that. Actually, you have mentioned that Paratus has partnerships with the National Heart Center or even working with NUS as well, so how do you actually go about identifying the right academic or clinical partners for advancing discoveries?

Like what makes a partnership high impact for you?

Dr Lewis Hong: I think that first of all, you want to work with academic partners who are doing world-class, cutting-edge research. As a company, you are asking yourself if accessing a new technology or gaining novel scientific insights through a collaboration can provide you with a competitive edge.

But great partnerships go both ways, right? The academic team also needs to see you or see us as the right industry partner to help translate their discoveries into something meaningful for patients. My experience is that when both sides are aligned and see that value in each other, that’s when you can achieve that strong engagement that is necessary for successful partnerships to happen.

Here in Singapore, we’ve been very fortunate to work with outstanding scientists like Dr Linfa Wang at Duke-NUS and Dr. Derek Hausenloy at the National Heart Center of Singapore. Both of them are global leaders in the fields, and their research happens to intersect very nicely with our bat biology-focused discovery platform, which I think has resulted in really synergistic science.

Aakash Naresh Kumar: Speaking about that as well, you, as the site head - you’ve built the Singapore team from scratch when you’re establishing the presence here. So what have been some of the key steps in recruitment, scaling operations that you have carried out, and how has being in Singapore specifically shaped the type of science or partnerships you’ve mentioned that you’ve been able to pursue that you might not elsewhere?

Dr Lewis Hong: Having had some experience in building and leading teams in previous roles, I knew that hiring the right people from the start was going to be absolutely critical. And in a startup environment, you need to be very deliberate, not just about who you hire, but why you hire them. And we focused early on in identifying the key roles that would have the most strategic impact and also thought carefully about how those roles might evolve as the company grew.

And these days, a lot of R&D work can be outsourced quite effectively, both for speed and for cost. So the internal team was purposely built to be very lean, to be highly skilled, and to be extremely adaptable. And I think being in Singapore has been a real advantage because I’ve been part of the biotech ecosystem here for quite a while now, and that network that I have has been incredibly valuable in helping me to recruit top talent, to build these meaningful collaborations, that I mentioned earlier, that we might not have had access to elsewhere.

Aakash Naresh Kumar: Looking at the road ahead, as you now move on to the next phase of growth, what are some of the key preclinical readouts, first-in-class IND filings or even these new partnerships that you feel our audience should look out for from Paratus Sciences?

Dr Lewis Hong: So there are two key areas as we enter this next phase of growth. First of all, we are advancing programs that have emerged directly from our bat biology platform, such as the ASC Inflammasome Inhibitor Program that I just mentioned, and we have another program that’s a promising early stage metabolic program.

Our goal is to move these drug candidates into the clinic as quickly as possible, and that will serve as important proof-of-concept for the therapeutic potential of our platform.

Second thing is we’re very excited by the compelling targets that have already emerged from our platform, but we’re a small company and we cannot pursue all of them, and that’s why we are actively looking to establish collaborations with pharma partners who are interested in accessing our proprietary discovery engine.

Whether it’s uncovering totally new targets or revealing new biology around known targets, we believe that our platform is very well positioned to contribute to that effort.

Aakash Naresh Kumar: It does sound really, really exciting. Will there be any plans to branch out to other parts of the region perhaps, or maybe even further away like the US?

Is there any plan for that in the future?

Dr Lewis Hong: Yes, I realized that I forgot to mention this earlier. I should clarify that at the moment, Paratus Sciences is headquartered in New York City in the US and we also have a growing team in Boston. And of course we also have the R&D site here in Singapore.

This is our footprint at the moment. We don’t have intentions to establish a third site right now. But we have plans to scale and grow at both locations in the US and Singapore as our company evolves.

Aakash Naresh Kumar: So in your experience, what are some of the trends you foresee in the bioinformatics-driven genetic therapeutics industry in Singapore?

Dr Lewis Hong: For a company like Paratus, the time and investment that’s required to build a high quality data set and a proprietary discovery platform is really quite substantial. And we’ve been fortunate to have investors who understand the long game and back us to build something that is truly differentiated - something we believe can seed many novel drug discovery programs. If we zoom out to look at the broader landscape in Singapore, I think that many of the key ingredients are already in place to translate strong science into successful biotech ventures. We have world class clinician-scientists and our hospitals are driving cutting-edge medical innovation.

Many of them are working in close collaboration with academic researchers, universities, and local research institutes. And all of this has led to a wealth of disease-relevant, really valuable datasets and resulted in many scientific discoveries. It is clear that the Singapore government has put in substantial investment in the life sciences sector over the past 20 years or so, but it wasn’t just about creating jobs or funding great research, right?

I think it was always about building a biotech sector that can deliver that long-lasting economic impact. So how do we turn this solid foundation that we already have here in Singapore into a globally competitive biotech ecosystem? I think talent will be a key driver. Our biotech ecosystem is still very nascent, right?

The talent pool here, you know, especially people with deep biopharma experience is quite small. I remember when my classmates in JC were applying to university, the Life Sciences program, majors in NUS and NTU was just starting their first year. So that’s telling you that in Singapore, you’re not gonna find many people above the age of 45 or 50 that have more than you know, 10-15 years of biopharma experience. In biotech, experience matters. It’s an industry where failure rates are very high. Progress will often depend on people or leaders who have been through this full cycle of failures and pivots and successes. And just as research institutions in Singapore, like A*STAR and NTU and NUS have attracted seasoned academics from all around the world to build a base for local talent, we will probably see a similar shift in biotech where we’re bringing in experienced operators to anchor companies, build companies and to mentor the next generation, and I think we’re already seeing some of that. I think another key area is the funding that is necessary to launch and grow biotech companies, and the government here has historically played a very proactive role in building essentially every sector of our economy.

And the life sciences is one of the most heavily government-supported R&D sectors in Singapore. In terms of investment dollars, you can say that the government has basically built almost the entire ecosystem up to now. You have agencies like EDBI, ClavystBio, who have also played a huge role in capitalizing innovation in attracting external partners such as life science-focused venture capital firms, corporate VCs, corporate incubators, and providing them with not only a lot of support, but encouragement to build companies here in Singapore and we have certainly been the beneficiary of this type of support. So, you know, is government support important to keep growing the sector and are they doing all the right things? Yes, absolutely. But is the government support alone sufficient to transform Singapore into a global biotech hub? That’s probably the subject of a whole separate podcast, and I’m sure you can find more qualified people to discuss this.

To go back and try to answer your question, I think the trend may be realizing that the government cannot do it all, and we may need slightly different approaches to attract private capital, to cultivate a stronger entrepreneurial culture, to build deeper global partnerships, especially with emerging biotech hubs like China, so that we can get to that next level.

Aakash Naresh Kumar: I think we can all agree with you on that. I think my next question will be nicely linking up to the first thing we talked about. You mentioned about how, in biotech, it’s important to have people with experience, people with the expertise to handle this very tricky industry. So just as a last question to you, what advice would you give to scientists or researchers who are looking to enter biotech or trying to build a startup?

And what are some of the qualities or mindsets that have helped you thrive in biotech leadership?

Dr Lewis Hong: Let me answer that first question first, which is about advice. First of all, a career in biotech is an incredibly purposeful and rewarding journey. The intellectual stimulation that you get from working at the cutting-edge of science combined with this deep sense of purpose, comes from developing something that could one day save or improve human lives.

I honestly cannot think of anything that is more fulfilling than that. I think most people who are in biotech or considering a career in biotech understand this quite instinctively. But that said, it’s a difficult journey with many ups and downs, right? Biotech is filled with uncertainty, long timelines, and many setbacks.

And so I think you need a high tolerance for pain, tolerance for ambiguity, for failure, and for hard work. I once heard someone say before that, in biology, unlike in other fields like art or math or physics, there are no geniuses, right? So unlike some disciplines where individual brilliance can result in fast breakthroughs, in biotech, it’s often the person that is the most disciplined, that is the more persistent, the more resilient, that will be more successful in the long run. So my advice to anyone that’s considering a biotech career is to take a long-term view, be prepared to put in the work. Know that success doesn’t happen overnight, but that over time, if you stay focused, stay humble, and keep learning and keep working hard, you will eventually accomplish this body of work that you will feel is meaningful and is something you can be proud of. And I think finally, you want to surround yourself with people that share that passion and that perseverance, because the journey is too long for you to walk that alone.

I think you had a second question there, which is about qualities and mindsets. I think a key quality is having a growth mindset.

I look for this whenever I’m hiring. For me, with the growth mindset, the approach I take is that I tell myself, “I am an expert in almost nothing, but I will learn quickly and I’ll work very hard”, and as long as I know what I want to accomplish at the end of the project and I have a general idea of what needs to be done to get us there, then I’ll tell myself, and I’ll tell the team, “Let’s figure this out.”

Another approach I take is to assume that there’s always somebody around me that I can learn from.

Aakash Naresh Kumar: I think that’s really sound advice and I think our listeners have really learned a lot, not just about Paratus as well, about the very interesting and cool work that you guys are doing, but this is really some valuable advice–surrounding yourself with people with the same mindset and journeying on together. I always say that, there’s a very famous saying that, you know, it takes a village to raise a child, but I also believe it takes a village to raise a whole new company, basically.

Dr Lewis Hong: It does, you know, it’s a lot about teamwork and collaboration.

Know that you’re not doing this alone. You know, within the company there are also these really important functions, finance, legal, HR, et cetera, and they all need to collaborate and work well together to enable a successful outcome. Outside of your immediate sphere of work, you’ve got to have that support system around you, whether it’s your family or your friends who you can talk to and grumble about certain things when things don’t go well, and be that pillar of support for you while you are on this journey.

Aakash Naresh Kumar: That is really true. You do need someone to grumble to once in a while. Thank you so much for joining us on this podcast. We really learned a lot from you and you shared some really valuable insights. Thank you for taking time out of your very busy schedule and yeah, thank you.

Dr Lewis Hong: Thank you, Aakash. Thank you for having me.

Aakash Naresh Kumar:  Stay tuned for monthly podcasts with key stakeholders of the biotech ecosystem, including founders, investors, and policy makers. If you have suggestions for the podcast or who you’d like to hear from, feel free to send us an email in the episode description. Subscribe to our newsletter, the Nucleate Artery on Substack, and stay engaged with Singapore’s biotech ecosystem.

Join the Singapore Life Science community Slack channel, powered by Nucleate Singapore, where we are building an open community to enable conversations in the life science ecosystem of Singapore.

📚 Further readings

1. Lewis Hong | LinkedIn

2. Paratus Sciences | Harnessing Bat Biology for Better Human Health

3. How Animals Are Inspiring Potentially Life-Saving Human Medicines

4. Duke-NUS and Paratus collaborate on a human anti-inflammatory drug based on insights from bat immunology

5. Bats Reveal Superior Adaptation To Endure Heart Stress: National Heart Centre Singapore Partners Paratus Sciences Singapore To Accelerate Heart Failure Care - SingHealth Duke-NUS Academic Medical Centre

6. Bat Biology Foundation | Bat Bio

If you enjoyed reading this post, comment and give us a like! Or let us know your thoughts here.

Interested in how you can protect, strengthen, and leverage your IP for growth? Join Nucleate Singapore and Baker McKenzie (Wong & Leow) for an informal session designed for early-stage biotech founders navigating the complex world of intellectual property. Click here or scan the QR code in the poster below to sign up now!

And now, let’s get into the rest of the article! Enjoy!

🍽️ Digestibles

High potential SG research, hot off the press

INFECTIOUS DISEASES: Fighting Superbugs with a Smart PIE

@Senuri De Silva

TL;DR

• Multidrug-resistant bacteria no longer respond to many common antibiotics, including last-resort drugs, creating a major global health challenge.

• NTU scientists designed a biodegradable molecule called P8 that enters bacterial cells and triggers abnormal phase separation of nucleic acids, disrupting essential processes like transcription and translation.

• In mouse models of muscle, lung, and systemic infections, P8 showed strong, broad-spectrum activity and effectively killed drug-resistant bacteria in muscle, blood infection, and lung infections.

Antibiotic resistance is one of medicine’s biggest ticking time bombs. It’s the reason once-reliable drugs no longer work: bacteria adapt, evolve, and eventually outsmart our best treatments. Some have even learned to resist the strongest “last-resort” antibiotics like carbapenem and colistin, leaving doctors with few options. The fight against these superbugs has become a race between biology and biotechnology.

At NTU’s School of Chemistry, scientists took inspiration from the way bacteria organize their internal world through a process called liquid–liquid phase separation (LLPS), where molecules cluster into tiny droplets without needing membranes. Normally, this helps bacteria function, but the researchers wondered: what if we could use this same principle against them?

They developed a new biodegradable compound called P8, part of a family of designer polymers known as poly(imidazolium ester)s (PIEs). By tweaking the chemical links in these molecules, they found the perfect balance; one that breaks down at just the right rate while powerfully killing bacteria. Unlike typical antibiotics, P8 works inside the bacterial cell, triggering phase separation of essential molecules like nucleic acids. This jams up the bacteria’s internal machinery, halting gene transcription and protein production until the cell simply can’t survive.

In mouse models of serious infections including those of the lung, muscle, and blood; P8 wiped out bacteria that had resisted even the strongest antibiotics. It was also safe, selective, and biodegradable, giving it a clear edge over conventional drugs.

P8 introduces a novel way to stop bacteria by systemically disrupting their internal organization rather than relying on traditional antibiotic tactics which are more targeted. Its ability to act inside cells, combined with strong performance in multiple infection models, positions it as a promising next step in the fight against hard-to-treat bacterial infections.

Discover how biotechnology is reshaping the fight against antibiotic resistance:

• Singapore’s Peptobiotics is using synthetic biology to produce novel livestock antibiotics that do not cause resistance

• NTU and SMART scientists develop safer and more sustainable antimicrobials to prevent infection of cow udders

• Smartbax - a Munich-based BioTech company raises €1.2M to create next-generation antibiotics

• Phagos, a French tech-bio company, has built a unique AI model on AWS designed to tackle antibiotic resistance

INFECTIOUS DISEASES: How Old TB Lesions Create a Hidden Niche for Dangerous Secondary Infections

@Senuri De Silva

TL;DR

• People who previously had TB are unusually prone to secondary infections like Mycobacterium abscessus, but the biological reason for this has been unclear.

• Using mouse and zebrafish models, researchers examined how lung tissue changes after TB infection, focusing on the granulomas left behind.

• They discovered that residual TB granulomas with their calcium-rich, necrotic cores create a microenvironment where M. abscessus can survive and grow, even in hosts with otherwise intact immune systems.

Singapore has largely eliminated widespread tuberculosis (TB), but people who previously recovered from TB remain surprisingly vulnerable to secondary infections—especially from Mycobacterium abscessus, a difficult-to-treat non-tuberculous mycobacterium (NTM). The biological reason behind this long-lasting susceptibility has been unclear, creating a major gap in our understanding of TB-related disease burden.

Researchers at A*STAR’s ID Labs have now uncovered a compelling mechanistic explanation. During TB infection, the lung forms granulomas—specialized immune structures designed to contain the bacteria. These granulomas develop a calcium-rich, necrotic core, which persists long after the primary infection is treated. The team discovered that this residual, nutrient-rich microenvironment behaves like a biological “safe house”, allowing opportunistic pathogens such as M. abscessus to enter, survive, and replicate.

Using mouse and zebrafish models that mimic human TB granulomas, the researchers demonstrated that M. abscessus can thrive inside these leftover structures even when the host’s immune system is fully functional. This overturns the assumption that secondary infections arise solely from weakened immunity—instead revealing that the physical and metabolic features of old TB lesions themselves create vulnerability.

In essence, the study shows that unresolved TB granulomas are a previously unrecognized reservoir that seeds secondary bacterial infections. Beyond providing a clear mechanistic explanation, this work establishes a valuable preclinical model for probing pathogen–host interactions and for developing next-generation therapeutics targeted at post-TB lung disease.

Read more on global efforts against TB infections:

• MIT scientists reveal targets for new tuberculosis vaccines.

• UK-based PBD Biotech broadens patent for tuberculosis diagnostic

• Bill & Melinda Gates Foundation and Wellcome Trust funnel $550M into ex-GSK tuberculosis shot

AGEING: Uncovering a Novel Pathway Behind Age-Related Muscle Loss

@Chi Dam

TL;DR

• With the Singaporean and global population ageing rapidly, aged-related muscle loss is an urgent public health issue.

• Scientists from Duke-NUS have found exciting clues on why our muscles weaken as we age – including a protein called DEAF1 as a key driver.

• Using aging mouse models that mimic aged-related muscle loss, the team found a novel pathway to be a promising druggable target to improve muscle loss in aging populations.

As we age, our muscles naturally shrink and weaken, a condition known as age-related muscle loss, or sarcopenia. This impacts a person’s ability to carry out everyday tasks, reducing mobility and independence. It also increases risk of falls, fractures and overall frailty. Over time, it can severely impact quality of life, especially in older adults.

At the cellular level, muscle health depends on a delicate balance between protein production, repair, and clearance. One of the key systems involved is mTORC1, which normally supports muscle growth and regeneration. With ageing or disease, however, this system can become overactive, paradoxically damaging muscle instead of maintaining it.

A team of scientists at the Duke-NUS Cancer & Stem Cell Biology programme found that DEAF1 is the key regulator of this mTORC1 system, and it needs to be at a balanced level for optimal cell quality control. With age, DEAF1 levels are increased in skeletal muscles. This can then cause the mTORC1 system to produce excess protein, clear damaged proteins poorly, and gradually weaken muscles.

In aged mouse models, lowering DEAF1 expression reversed excess protein production and slowed muscle deterioration, pointing to the DEAF1-mTORC1 axis as a previously unrecognised driver of age-related muscle loss. By restoring balance in this pathway, targeting DEAF1 could offer a new therapeutic strategy to preserve muscle health as we age.

Learn more about biggest global commercial pull for muscle loss:

• Weight-loss drugs such as GLP-1 agonists (Ozempic, Wegovy, Mounjaro) are slimming waistlines and accidentally sparking a new market for sarcopenia.Veru, Eli Lilly, Regeneron, are among leaders in muscle-preserving drug development. (Editor’s note: when a blockbuster solution creates its own sequel problem… and the same companies get to sell the fix…)

CANCER: EVs Deliver Safe and Effective Combination Therapy for Pancreatic Metastasis

@Devika Menon

TL;DR

• Pancreatic cancer is challenging to treat as it is often resistant to therapy and driven by the “difficult-to-target” KRAS oncogene.

• Scientists from NUS School of Medicine used Extracellular Vesicles (EVs) to deliver a combination therapy that targets the driver mutation (KRAS) while activating immune response.

• Synergestic effect of the therapy was observed, resulting in better survival outcomes compared to either treatment alone.

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest forms of cancer, due to difficulty of early diagnosis, aggressive spread and limited treatment options. Over 90% of PDAC cases are driven by mutant KRAS, a key oncogene that fuels aggressive growth and resistance to therapy. PDAC tumors also create an immunosuppressive microenvironment, making immunotherapies largely ineffective. To make matters worse, KRAS is challenging to directly target, leaving very few safe and effective therapies for pancreatic metastasis.

Hence, scientists from NUS YLL School of Medicine investigated whether a form of combination therapy that targets KRAS directly while activating innate immunity (the body’s first line of defense) might be effective.

The treatment involved a combination of KRAS-targeted antisense oligonucleotides (ASOs - short, synthetic pieces of DNA that bind to specific RNA transcripts) which suppresses KRAS at the RNA level, along with RIG-I agonists, a viral RNA mimic, that activates the innate immune response. Since Extracellular Vesicles (EVs) are known to be stable and efficient for nucleic acid delivery, the scientists utilized EVs to deliver the treatment to PDAC models.

As a result, they observed a synergistic effect of the combined therapy on suppression of KRAS signalling and immunogenic cancer cell death. In patient derived organoids, the combined therapy was found to be more effective than either therapy alone; and in mouse models of peritoneal metastasis, it significantly improved survival. The scientists also report that the therapy was found to be safe and well-tolerated, establishing such an EV-mediated combination therapy as a potential highly safe and effective treatment modality for metastatic PDAC.

Learn more about:

• A pre-clinical study from University of Pennsylvania School of Medicine on a combination therapy for pancreatic cancer with potential for future clinical trials

🗞️ Industry Spotlight

News from the Singapore life sciences industry

• UK and Singapore launch new regulatory innovation corridor to fast track health technologies

• Rhinocare Korea accelerates global expansion with Singapore joint venture on drug-free respiratory care

• Singapore unveils S$37 billion RIE2030 Plan to advance research and innovation

• AI-for-science startup ChemLex raises USD 45M, launching self-driving lab for drug discovery in Singapore

• NUS Medicine and Cyclotek to strengthen radiopharma capability in Singapore and across ASEAN region

• Johnson & Johnson announces breakthrough in Lung Cancer treatment with combination therapy

• Singapore’s Prestige Biopharma to commercialise cancer drug Tuznue® in Latin America

• Australian healthtech firm Heidi unveils its Southeast Asia hub in Singapore to drive healthcare AI innovation

• Apriori Bio and A*STAR ink strategic partnership to advance next generation influenza vaccines

🎧 Nucleate Singapore Pulse

Singapore’s premier podcast on the local biotech ecosystem.

Listen now

📆 Events happening this month

Conference/seminars

• IP in Biotech

  (13 Jan, 5:30 PM - 7:00 PM, in person)

• InnoVision 2026

  (26-27 Jan, 9:00 AM - 06:00 PM, in person)

• Financial Literacy for Entrepreneurs and Small Businesses: Mastering Accounting and Cash Flow with Digital Tools

  (26 Jan, 9:00 AM - 6:00 PM, in person)

• HealthTechX Asia 2026

  (06-07 May, TBA, in person, early bird tickets)

Networking events

• Sat Health & Bio Brews Singapore

  (Every Sat, 9:00 AM - 10:30 PM, in person)

If you enjoyed reading this post, comment and give us a like! Or let us know your thoughts here.

🍽️ Digestibles

High potential SG research, hot off the press

DRUG DELIVERY: Tiny Molecular Machines Promise Smarter, Longer-Lasting Drug Delivery

@Senuri De Silva

TL;DR

• Most medicines release too quickly, causing side effects or reduced effectiveness.

• Scientists at NUS Department of Pharmacy and Pharmaceutical Sciences have designed a tiny molecular system called a pseudorotaxane, where a ring slides off an axle to control how fast a drug is released.

• By adjusting the molecular design, they could extend drug release from hours to days; the induced slower release of the drug led to steadier, longer-lasting drug action.

Delivering the right drug at the right time is one of biotechnology’s biggest challenges. In many chronic diseases like diabetes, hypertension, and heart disease, patients need a steady amount of medicine in their bloodstream. If too much is released at once, it can cause side effects; if too little, the drug won’t work. That’s why scientists are working on smarter drug-delivery systems that can release medication slowly and predictably over time.

Nature already does this beautifully. Inside our cells, molecular machines like ribosomes precisely control when and how molecules are made. Inspired by this natural precision, scientists are now creating artificial molecular machines that can control how and when drugs are released inside the body— a major leap toward personalized, programmable medicine.

Scientists at NUS Department of Pharmacy and Pharmaceutical Sciences designed a tiny molecular system called a pseudorotaxane. Pseudorotaxane contains a “ring” threaded onto an “axle.” By controlling how fast the ring slides off the axle — a process called dethreading — they were able to change how quickly a drug is released. In turn, they were able to extend the duration of drug release from a few hours to several days

As a proof of concept, they attached an anti-cancer drug called camptothecin, which normally dissolves poorly and breaks down quickly in the body. In this new setup, the drug was held inside a tiny ring-and-axle structure, where the speed of the ring slipping off controlled how quickly the medicine was released. When the ring moved slowly, the drug was released gradually and kept working longer in lung cell tests. Using advanced imaging and computer modeling, the team also visualized how tiny structural changes affected the speed and stability of drug release.

This work shows that drug delivery can be programmed at the molecular level, opening the door to next-generation treatments where dosage and timing are as precisely controlled as in nature’s own machinery.

Learn more about drug delivery biotech,

• AmacaThera signs an exclusive global licensing agreement with Pacira Biosciences for up to US$230 million, validating its tunable drug delivery platform.

INFECTIOUS DISEASES: What’s in a Bite? The Hidden Molecule That Makes Chikungunya Worse or Better

@Senuri De Silva

TL;DR

• The 2025 global chikungunya outbreak has intensified due to expanding Aedes mosquito habitats driven by climate change, making traditional control measures like vaccines and insecticides less effective.

• Researchers at A*STAR Infectious Diseases Labs identified sialokinin, a mosquito saliva molecule that interacts with human immune cells, reducing inflammation and affecting how the chikungunya virus spreads and persists.

Chikungunya virus (CHIKV) is spread by Aedes mosquitoes and has become a growing health concern because it can cause long-lasting joint pain. As global temperatures rise and weather patterns change, these mosquitoes are now able to survive in new regions, increasing the spread of mosquito-borne diseases. In 2025, several large outbreaks have been reported worldwide. For example, more than 240,000 infections and 90 deaths were recorded across 16 countries.

Although vaccines, insecticides, and antiviral treatments exist, their effectiveness is decreasing as the virus and mosquitoes develop resistance. This highlights the need for new ways to stop transmission and reduce disease impact. One promising strategy focuses on mosquito saliva. When a mosquito bites, it injects both its saliva and the virus into the person’s skin. The saliva contains many active molecules that help the virus spread by affecting blood flow and the immune response.

Researchers at A*STAR Infectious Diseases Labs identified one such molecule, sialokinin, which interacts with human immune cells. It appears to suppress certain immune reactions, helping the virus spread more easily early in infection. In experiments with mice, they show that treatment with sialokinin led to less joint swelling and lower virus levels, showing that it can reduce inflammation. However, in human patients with severe chikungunya disease, higher levels of antibodies against sialokinin were found; these antibodies were linked with greater inflammation and higher viral loads.

This suggests that sialokinin may play a complex, “double-edged” role: it can reduce inflammation, but in people who are bitten by mosquitoes often, their immune system may block its effects, worsening disease. Overall, this study shows that targeting mosquito saliva molecules like sialokinin could become a new way to reduce the severity of mosquito-borne diseases in the future, especially as global warming allows mosquitoes to spread further.

Learn more about mosquito-borne viruses news and biotech

• China releases millions of modified mosquitoes to reduce Chikungunya outbreak

• Bharat Biotech gets sec nod to begin Phase III trial of inactivated Chikungunya vaccine

🥡 Event Takeaways

Exclusive insights from biotech events in SG

Why Singapore’s biotech future depends on you getting comfortable with failure

ICYMI at Nucleate Singapore’s 2^nd anniversary biomixer: a guppy’s reflections from a panel discussion with whales

@Jiaqi Liang

At a recent panel featuring Lim Jui (CEO of SGInnovate), Edison Liu (former president & CEO of The Jackson Laboratory), and Evelyn Pang (GM of Moderna Singapore), they got real about where we’ve been, where we are, and what it’ll take to stay in the game.

The startup nation paradox

Thirty years ago, Singapore had nothing to lose. No infrastructure. No credibility. Just the audacity and vision to turn a trading and manufacturing-based economy into a biotech powerhouse.

The crazy part? It worked.

Edison Liu dropped this phrase about Singapore’s strategy: attract world-class “whales” who create an environment where local talent (the guppies) can thrive.

And here’s the thing: whales don’t come just for money. They come for freedom, mission, and the chance to do work that matters. We built a culture where trying new things and taking risks was expected. The most interesting career opportunities went to those who dared to say yes to the unknown.

Now? We’re more careful. More calculated. A series of failed experiments sends us scrambling to pick low-hanging fruit to serve up a deliverable before the project deadline hits.

Don’t get me wrong – there’s real value in protecting what we’ve built and maintaining our strengths. But how do we recapture that startup energy and keep the momentum going for the next decade?

The infrastructure we need to build

At Moderna Singapore, teams openly share failures and see them as invaluable learning experiences. As their GM, Evelyn Pang, put it:

Building this kind of culture takes time – and a whole village. We need more industry-academia exchange programs that let researchers experience how different sectors approach risk and problem-solving. We need grants like the NRF Fellowship that fund potential and exploration, not just proven feasibility. And we need more lab PIs who reward bold thinking and rigorous reasoning, not just successful outcomes.

The career advice every over-planner & worrier needs to hear

On an individual level, there are already things you can do today.

Have broad interests. Like, literature-and-arts broad. Breakthroughs come from connecting unexpected dots. The whales just gave you permission to procrastinate and read that novel instead of yet another research paper. On that note – highly recommend Neither Civil Nor Servant, a biography of Philip Yeo, the visionary who helped build Singapore’s biomedical landscape. Or (re)start those Duolingo Vietnamese lessons so you can one day help connect us better to our ASEAN neighbours.

Know your “why”, not just your “what”. Didn’t get into the course of your dreams? Go in with an open mind! Most curriculums are so interdisciplinary and flexible nowadays that you’ll surely find something you enjoy, perhaps even more than the original course you wanted. Did you want to study medicine because you want to help people stay healthy? There are many other ways to help people in the healthcare industry, e.g. pharmacists, drug research, even regulatory roles to help get new drugs to patients faster.

Don’t over-plan your life. Don’t over-plan your life. Repeating this for the kiasu Singaporeans. No one is going to hold you to the detailed 10 year plan you laid out during your job interview. Say yes to that new role no one wants because there’s no JD or clear progression. For Edison Liu and Evelyn Pang, their biggest career accelerators and defining moments were “accidents” or “risky moves”. One unsuitable role won’t end your career, and what you learn there could be exactly what you need three jobs later. Focus on doing today’s work exceptionally well and let opportunities emerge.

Get comfortable with failure. Or just stop seeing everything that doesn’t go according to plan as a failure. It’s an invaluable learning experience. Biotech is hard, and you’d do better with an oversized dose of resilience than with a pea-sized drop of perfectionism.

Where we go from here

Singapore’s biotech ecosystem wasn’t built by playing it safe. It was built by people willing to do hard things that might not work.

The whales came and created the environment. The infrastructure is here. The regulatory credibility exists. And the regional opportunity is real.

It’s now on us to recapture that same boldness from thirty years ago and adapt it for what comes next. The most interesting chapter might be the one we’re about to write!

🗞️ Industry Spotlight

News from the Singapore life sciences industry

• NTU and Activate to launch S$12 M fellowship to accelerate science entrepreneurship and develop deep-tech startups

• Nanyang Biologics plans NASDAQ listing through a $1.5 B biz combination.

• Hyphens Pharma and Medac expands subcutaneous autoinjector pen into Thailand and Cambodia markets

• Raffles Medical Group partners with Gene Solutions to expand access to global cancer clinical trials

🎧 Nucleate Singapore Pulse

Singapore’s premier podcast on the local biotech ecosystem.

Listen now

📆 Events happening this month

Conference/Seminars

• Science first: Harnessing data analytics in pharma
  (20 Nov, 3:30 PM - 6:30 PM, in person)

• Feeding Tomorrow: Cultivated Meat & Energy Efficient Nutrition Session
  (15 Nov, 4:00 PM - 5:00 PM, in person)

• BioClina 2025 - International Conference on Biological & Clinical Studies
  (21 - 22 Nov, 9:00 AM - 5:00 PM, in person)

• The 5th World Biological Science and Technology Conference 2025 Singapore
  (9 Dec, 8:00 AM - 10:00 PM, in person)

Networking events

• Sat Health & Bio Brews Singapore

  (Every Sat, 9:00 AM - 10:30 PM, in person)

• 2025 MEDTECH Connect

  (20 Nov, 10:00 AM - 12:00 PM, in person)

Competitions

• Voice for BT - International
  (Deadline: 27 Nov)

Like what you’re reading, or have some feedback for us? Share your thoughts here!

Want to be featured in The Nucleate Artery? Know of an exciting technology or topic that keeps you up at night? Write to us at singapore@nucleate.org

If you enjoyed reading this post, comment and give us a like! Or let us know your thoughts here.

Nucleate Singapore is celebrating its second anniversary, this time round we’re bringing back the biomixer in a bigger fashion!

The Nucleate Singapore Anniversary Biomixer will feature a themed panel discussion “From Legacy to Future Frontiers: Building Upon Singapore’s Science and Biotech History for the Next Wave of Innovation.” Not only is this topic pivotal for the foundation of Singapore’s rapidly developing biotech scene, it is also at the heart of our mission to empower academic trainees to connect with the local biotech ecosystem.

Spaces are limited and all registrations will be curated. Sign up now to secure your spot.

And now, let’s get into the rest of the article! Enjoy!

🍽️ Digestibles

High potential SG research, hot off the press

EYE DISEASE: Cracking the Retinal Barrier: How Junction Genes ZO-1 and ZO-2 Safeguard Vision'

@Senuri De Silva

TL;DR

• Retinal diseases often involve dysfunction of the retinal pigment epithelium (RPE) and breakdown of the outer blood–retinal barrier (oBRB), but whether barrier loss is a cause or consequence has remained unclear.

• This study created single and double knockout mouse models for the tight junction genes ZO-1 and ZO-2, key components of the oBRB.

• The double knockout caused loss of RPE integrity, retinal thinning, and poor wound repair, confirming a critical role for ZO-1/2 in barrier maintenance and retinal health.

Retinal diseases are one of the main causes of permanent blindness. They generally fall into two groups. In degenerative diseases such as age-related macular degeneration, the light-sensing cells of the eye slowly die off, leading to vision loss. In proliferative diseases like diabetic retinopathy, fragile new blood vessels and scar tissue grow where they shouldn’t, also damaging sight.

At the center of many of these conditions is a delicate layer of cells called the retinal pigment epithelium (RPE). This layer acts like a caretaker for the retina, providing nutrients and keeping harmful substances out through what’s called the outer blood–retinal barrier (oBRB). The integrity of this barrier depends on special proteins, including ZO-1 and ZO-2, which help hold the RPE cells tightly together. Scientists have long suspected that the breakdown of this barrier contributes to blindness. But a key question remains: is the barrier’s breakdown the cause of retinal disease, or simply a consequence of the disease as it progresses?

Researchers at IMCB, A*STAR addressed this question using genetically engineered mouse models lacking ZO-1, ZO-2, or both together. Strikingly, the double knockout mice developed severe retinal abnormalities, including loss of RPE integrity, retinal thinning, and abnormal proliferation. These cells also showed aberrant activation of the YAP pathway, a regulator of uncontrolled growth. Over time, this resulted in progressive structural and functional deterioration of the retina. In response to injury, the knockout RPE displayed persistent hyper-proliferation, impaired wound repair, and sustained YAP activation, confirming that ZO-1/2 are essential for both barrier maintenance and proper regenerative responses.

These findings position ZO-1 and ZO-2 not only as fundamental barrier proteins but also as potential therapeutic targets in blinding diseases. Targeting this pathway could lead to treatments that stabilize or restore the blood–retinal barrier, slow disease progression, and enhance repair after injury. Furthermore, the engineered mouse models provide a valuable preclinical platform for testing small molecules, biologics, or gene therapies aimed at protecting vision in patients with otherwise untreatable retinal disorders.

Learn more about retina diseases:

• French biotech SeaBeLife raises €2M to treat liver and eye diseases

• Hong Kong biotech start-up Alephoson eyes international trial for eye-drug delivery

• NASDAQ listed biotech Ocugen (OCGN) is focused on modifier gene therapies for inherited retinal diseases, with key catalysts expected by 2026.

INFECTIOUS DISEASES: Why Dengue Vaccines Work Better in People Previously Infected?

@Senuri De Silva

TL;DR

• Dengue vaccines work better in people who have had a prior infection (seropositive) compared to those who are dengue-naive (seronegative).

• Gene expression analysis showed that prior natural dengue infection had reprogrammed innate immune responses, whereas TAK-003 vaccination alone did not induce this reprogramming.

Dengue is tricky to vaccinate against. People who have already had dengue (seropositive) respond much better to vaccines than those who have never been infected (seronegative). Among available vaccines, TAK-003 can be given to anyone, regardless of infection history, while Dengvaxia is only recommended for those previously infected; in people without prior exposure, it can actually increase the risk of severe disease. Interestingly, after the first shot of a two-dose vaccine (TAK-003), seronegative individuals do produce antibodies and become “seropositive” before their second dose. But even after two doses their protection still doesn’t reach the level of people who had prior natural dengue infection. Why does it appear that natural infection is a ‘more effective’ protection from disease than vaccination?

Scientists at Duke-NUS dug into this puzzle by comparing gene activity in the blood of people with and without prior dengue exposure before and after TAK-003 vaccination. TAK-003 itself is a weakened dengue-2 virus engineered to include components from dengue-1, -3, and -4. In dengue-naive people, the first dose mainly triggered a strong dengue-2 response, while responses to the other strains remained weaker. Even with a booster, these responses didn’t catch up to those in previously infected individuals.

Using RNA sequencing, the researchers found the explanation: natural dengue infection had already reprogrammed the innate immune system of seropositive people. This reprogramming gave them a head start, allowing broader and stronger responses to the vaccine. In contrast, vaccination alone did not create this same “immune memory reset” in those who were seronegative at baseline. This means that natural dengue infection, but not the current live-attenuated vaccine, rewires the innate immune system in ways that shape stronger, more balanced protection. That said, dengue vaccination remains important for people living in high-risk regions, and individuals should always consult medical professionals for advice before vaccination. These findings new possibilities for biotechnology: future vaccines may need to deliberately mimic this reprogramming to achieve broader efficacy, especially for dengue-naive individuals. Beyond dengue, the findings raise urgent questions about how innate immune “training” might affect responses to secondary infections and even other viral vaccines.

Learn more about dengue vaccines:

• T-cell based dengue vaccine PRAHR wins best innovation award at GBU-Biothon

• Trial of new dengue vaccine begins recruitment for child participants in Singapore

• Taking multiple vaccines? Not to worry - co-administration of dengue and HPV vaccines found compatible

🗞️ Industry Spotlight

News from the Singapore life sciences industry

• Mirxes secures regulatory approval in China for a microRNA blood test for gastric cancer

• Cirrus Therapeutics raises $11 million to tackle eye diseases using gene therapy

• IHH Healthcare launches incubator programme for early-stage healthcare startups

• Campus Create promotes collaborations between Japanese medtech startups and Singapore-based VCs

• Siemens Healthineers and NUH partner to develop non-invasive liver disease diagnostics

• Johnson & Johnson MedTech and SGH partner to optimize robotic surgery workflows

• Pioneering bioscience endeavours celebrated at the 2025 President’s Science and Technology Awards

• NUS Medicine receives S$2 million grant to combat antimicrobial resistance

• Singapore researchers develop novel Nanovaccine to halt tumour growth

🎧 Nucleate Singapore Pulse

Listen now

📆 Events happening this month

Conferences

• Singapore Week of Innovation and Technology (SWITCH)

  (29-31 Oct, 10:00 AM - 05:40 PM, in person)

• TechInnovation 2025
  (29-31 Oct, 09:00 AM - 06:00 PM, in person)

Networking events

• Sat Health & Bio Brews Singapore

  (Every Sat, 9:00 AM - 10:30 PM, in person)

• National GRIP Info Sharing & Networking Dinner

  (22 Oct, 6:00 PM - 8:30 PM, in person)

• FusionX:Singapore 2025

  (30 Oct, 12:30 PM - 7:00 PM, in person)

Competitions

• Cursor Hackathon Singapore
  (18-19 Oct, 9:00 AM onwards, in person)

• QAI Ventures Global Hackathon
  (24-26 Oct, 9:00 AM onwards, in person)

Like what you’re reading, or have some feedback for us? Share your thoughts here!

Want to be featured in The Nucleate Artery? Know of an exciting technology or topic that keeps you up at night? Write to us at singapore@nucleate.org

If you enjoyed reading this post, comment and give us a like! Or let us know your thoughts here.

Nucleate Singapore is celebrating its second anniversary, this time round we’re bringing back the biomixer in a bigger fashion!

The Nucleate Singapore Anniversary Biomixer will feature a themed panel discussion "From Legacy to Future Frontiers: Building Upon Singapore's Science and Biotech History for the Next Wave of Innovation." This topic is pivotal for the foundation of Singapore’s rapidly developing biotech scene and is at the heart of our mission to empower academic trainees and connect the local biotech ecosystem. This panel features: Lim Jui (CEO of SGInnovate), Edison Liu (Former CEO & President of Jackson Laboratory, Founding Executive Director of GIS), and Evelyn Pang (General Manager of Moderna Singapore).

Following the panel, there will be a networking session with light refreshments, offering a great opportunity to reconnect, exchange ideas, and look towards the future of biotech within the Singapore biotech community.

🗓️Date: 24 October 2025, Friday

🕗Time: 6pm - 8.30pm

📍Venue: To be sent to confirmed participants

Spaces are limited and all registrations will be curated. Sign up now to secure your spot.

And now, let’s get into the rest of the article! Enjoy!

🍽️ Digestibles

High potential SG research, hot off the press

EYE DISEASE: Cracking the Genetic Code of Irreversible blindness

@Senuri De Silva

TL;DR

• GIS researchers identified rare gene variants (UBOX5) that double the risk of primary angle-closure glaucoma, a major cause of irreversible blindness

• These gene variants disrupt the UBOX5–BIP protein pathway, leading to faulty protein regulation impairing protein control in eye cells

Primary angle-closure glaucoma (PACG) is one of the leading causes of irreversible blindness worldwide, affecting more than 20 million people. Despite its prevalence, the genetic factors that drive this disease are still not fully understood, making it difficult to predict risk or design targeted treatments.

To uncover the genetic drivers of PACG, researchers at the Genome Institute of Singapore sequenced the parts of the human genome that directly code for proteins, known as the exome. They compared the DNA of more than 4,600 PACG patients and 5,400 healthy controls, focusing on rare genetic variants that alter protein function. This analysis revealed that changes in a gene called UBOX5 were strongly linked to a higher risk of PACG, with loss-of-function variants appearing more often in patients than in controls.

To investigate why, the team carried out laboratory experiments in mice, showing that UBOX5 interacts with a key protein called BIP, tagging it for degradation. The researchers then tested dozens of UBOX5 variants and confirmed that the UBOX5-BIP was significantly enriched in PACG patients.

Carrying damaging UBOX5 variants more than doubles the risk of developing PACG. The study also identified a potential disease mechanism: disruption of the UBOX5–BIP pathway, which may disturb protein quality control in eye cells.

Importantly, this is the first strong genetic evidence linking UBOX5 to PACG, offering a new biological pathway to explore for risk prediction, early detection, and therapeutic targeting. These findings bring fresh hope for tackling one of the world’s leading causes of blindness.

Read about biotech innovations target irreversible blindness,

• Singapore biotech Intra-ImmuSG’s cancer drug PRL3-zumab shows promise as treatment for blindness; trial to start soon.

• PulseSight launches with gene therapy platform targeting age-related blindness

INFLAMMATORY DISEASE: Telomerase's unexpected role in driving inflammation

@Senuri De Silva

TL;DR

• Researchers at IMCB found that telomerase (TERT), beyond its role in protecting DNA, drives inflammation.

• Disrupting TERT in the cases of colon inflammation reversed the disease, pointing to a new and more precise treatment strategy for inflammatory disorders.

Inflammatory bowel diseases are usually studied through the lens of immune dysregulation, with attention on T cells, macrophages, and cytokines that sustain chronic inflammation. Unexpectedly, telomerase; a protein usually studied in aging and cancer, has now been implicated in regulating these inflammatory responses through DNA damage signals. What isn’t clear is whether telomerase itself, beyond its role in protecting DNA, can directly regulate inflammation.

Researchers at the Institute of Molecular and Cell Biology used mouse models of colitis, a condition that mimics human inflammatory bowel disease, to test how telomerase activity affects immune-driven inflammation. They discovered a specific group of immune cells, which they call T-MACs, that become activated during inflammation in the colon. In these cells, the telomerase protein (TERT) boosted inflammatory responses by activating the cGAS–STING pathway, a system that normally detects harmful DNA inside cells. Importantly, this effect did not depend on telomerase’s usual job of maintaining DNA ends, meaning TERT was playing a separate, unexpected role. They also confirmed that similar inflammatory T-MAC cells are present in people with Crohn’s disease. Blocking this pathway with a STING inhibitor in mice reversed colitis, suggesting a new way to treat these conditions.

Unlike traditional telomerase inhibitors that harm stem cells and failed in cancer trials, targeting this specific non-canonical function of telomerase could offer safer, more precise treatments for chronic inflammatory diseases. In other words, a protein long associated only with aging and cancer may now represent a new hope for tackling hard-to-treat inflammatory disorders.

Learn more about biotech on inflammatory diseases:

• Cancer biotech firm Hummingbird Bioscience to target inflammatory diseases with precision drugs.

• Odyssey Therapeutics heralds $213M series D to strengthen clinical portfolio.

• Abivax scores major win with ulcerative colitis trials

🗞️ Industry Spotlight

News from the Singapore life sciences industry

• Neuvocor named one of Forbes Asia’s “100 to Watch”

• NSG BioSuites launches at Geneo, providing private lab suites for biotech teams

• Singzyme wins the 2025 Amgen x NSG BioLabs Golden Ticket

• Singapore's A*STAR BTI spinoff AuctuCel launches AI platform to slash cell medicine production costs by 80%

• Enterprise Singapore to advance global health care innovation in partnership with Northwell Health

• Strides Singapore partners with Kenox for development of nasal spray products

• Nanyang Biologics partners with NVIDIA, HPE & Equinix to build AI-powered drug discovery platform

• Sanofi and AstraZeneca’s Beyfortus Receives HSA Approval to Prevent RSV in Infants

🎧 Nucleate Singapore Pulse

Listen now

📆 Events happening this month

Conferences

• OPEN SOURCE: Reinventing Healthcare
  (17 Sep, 10:00 AM - 8:30 PM, in person)

• CHI FLYING Summit 2025
  (19-20 Sep, 8:30 AM - 5:30 PM, in person)

• Singapore Health & Biomedical Congress
  (09-10 Oct, 8:45 AM - 6:00 PM, in person, Registration deadline: 17 Sep)

• TechInnovation 2025
  (29-31 Oct, TBA, in person)

Networking events

• Sat Health & Bio Brews Singapore

  (Every Sat, 9:00 AM - 10:30 PM, in person)

• NUS Enterprise i³ Building Launch

  (16 Sep, 8:40 AM - 05:30 PM, in person)

Seminars/Panel discussion

• Navigating IP in the Creative Economyle
  (15 Sep, 2:00 PM - 04:00 PM, in person)

• The Longevity Blueprint: Decoding Aging in Place with Biology, Technology, and Community Care
  (19 Sep, 2:00 PM - 04:00 PM, in person)

• From Setbacks To Breakthroughs: The Development Of Smart Healthcare Regulation

  (22 Sep, 6:00 AM - 8:45 AM, hybrid)

• co11ab Lunch & Learn with Evovian and Twist Bioscience

  (23 Sep, 11:30 AM - 1:30 PM, in person)

• Drug Discovery and Development in Singapore: Opportunities and Challenges
  (10 Oct, 9:00 AM - 10:30 AM, in person, Registration deadline: 17 Sep)

• First Cheques: Backing Futuremakers to Solve the Impossible
  (14 Oct, 3:30 PM - 05:30 PM, in person)

Competitions

• CHISEL Healthcare InnoMatch 2025 Finals
  (26 Sep, 8:00 PM - 01:30 PM, in person)

• Falling Walls Lab Singapore 2025
  (24 Sep, 2:00 PM - 05:00 PM, in person)

Like what you’re reading, or have some feedback for us? Share your thoughts here!

Want to be featured in The Nucleate Artery? Know of an exciting technology or topic that keeps you up at night? Write to us at singapore@nucleate.org

If you enjoyed reading this post, comment and give us a like! Or let us know your thoughts here.

Are you a student or scientist passionate about venture creation, talent development, and building collaborative relationships? Join the Nucleate Singapore leadership team and be part of a dynamic team driving innovation in the life sciences sector! Check out our open positions for the coming term and apply here. We can’t wait to hear from you!

And now, let’s get into the rest of the article! Enjoy!

🍽️ Digestibles

High potential SG research, hot off the press

What has been brewing in our young and vibrant biotech landscape?

For this issue, we’re taking a step back to highlight some of the most exciting and high-impact research we’ve covered over the past half year.

P.S. We added in some updates on what was reported - things move quickly in this space 💦

AGING

• A step closer to cleaning the Alzheimer’s brain: NTU scientists discovered that stopping fat buildup in brain immune cells restores their power to clear harmful plaques, slowing the disease in mice.

  • Singapore-based biotech startup NeuroVanda is leveraging translational models that have been developed over decades in the labs of our scientific founders and are guided by the deep expertise to further establish pathophysiologically relevant models.

• Turning a cancer weapon into an eye-saver: Scientists at IMCB, A*STAR found that blocking the protein PRL3, already targeted in cancer trials, could safely treat blinding diseases like age-related macular degeneration (AMD) and diabetic Retinopathy (DR) without invasive surgery.

  • A*STAR spin-off Intra-ImmunSG is advancing PRL3-zumab, targeting PRL3, with proven clinical trial success across Singapore, China, and the USA.

• Could unlocking hair regrowth be simpler than we thought? Duke-NUS scientists discovered that the protein MCL-1 shields hair follicle stem cells from stress, enabling regrowth. Loss of MCL-1 causes hair loss in mice, but activating ERBB signaling or blocking death signals can reverse it.

  • US-based Turn Biotechnologies is developing mRNA cocktails to restore cell function, including reversing wrinkles and hair loss.

  • Check out this list of startups on a mission to prolong human life.

• A potential target for Arthritis therapy: IMCB scientists discover that blocking the movement of two proteins within the cell, can reduce cartilage damage and alleviate arthritis symptoms in mice.

  • York University scientists identify a specific mutation in TRAF protein that could reduce inflammation, pointing to a possible target for arthritis treatment.

CANCER

• Supercharging the body’s tumor killers: IMCB, A*STAR scientists discovered liver cancer patients with more active natural killer cells have lower recurrence, and identified proteins like spondin-2 that boost their attack, paving the way for better prediction and prevention.

  • A*STAR-based startup ImmunosQ aims to empower clinicians and biotech with a digital platform that transforms complex spatial omics data into actionable therapeutic insights.

• Revolutionizing brain cancer diagnosis: NUS researchers harnessed advanced imaging techniques and AI to map tumor metabolism, enabling rapid, non-invasive detection and classification of brain tumors with 99.6% accuracy.

  • Scientists at Duke University are using deep-learning based methods to predict recurrence in brain metastasis patients following surgery.

• Could boosting tumor immunity from the gut be the key to better survival? In a collaboration with China, scientists at NUS engineered gut bacteria to release LIGHT, a cytokine that promotes immune cell clusters called tertiary lymphoid structures inside tumors, slowing tumor growth in mice.

  • Based in Cambridge, UK, Microbiotica is developing precision microbiome medicines using defined live microbial consortia that are being tested in combination with Keytruda to enhance immunotherapy responses in cancer.

BIOINSPIRED ENGINEERING

• Could this be a breakthrough for obesity treatment? NUS scientists engineered bacteria to deliver appetite-regulating hormones directly to the brain via the nasal cavity, bypassing the blood-brain barrier and successfully controlling obesity in mice.

  • Singapore’s AMILI is SEA’s first precision gut microbiome company, hosting the region’s only gut microbiome transplant bank and capturing uniquely Asian insights and their impact on health.

• A heartbeat that heals and disappears: NUS researchers developed an injectable, self-powered, bioresorbable cardiac pacemaker; no wires, batteries, or surgery needed - offering a safer, less invasive way to manage temporary heart rhythms.

  • The innovative technology is now under translation and commercialization under NuSera Biosystems!

🗞️ Industry Spotlight

News from the Singapore life sciences industry

• Respiree Closes US$11.6M Series A Financing Round Led by We Venture Capital and Clavystbio

• Cornerstone Robotics signs MoU with NHG Health and NTU Singapore.

• Singapore unveils Venture Capital Programme with S$150 M to boost growth of deep tech startups

• WuXi Biologics Singapore CRDMO hub to build world's largest modular biologics Drug Product (DP) facility

• Singapore launches MAGNET initiative to combat muscle loss among the aging with S$10M in grant

• Body Vision Medical Receives Pre-Market Approval for LungVision® in Singapore, Advancing AI-Powered Imaging for Early Lung Cancer Diagnosis

• Singapore-based health tech startup Naluri raises $5 M for SEA expansion

• ImmunoScape raises $9.2M from EDBI with new shares

• Health Sciences Authority Signs Memorandum of Understanding With Hong Kong Department Of Health To Enhance Healthcare Regulatory Cooperation

• ABC Impact marks entry in PH health sector with AC Health deal

• Hyphens Pharma Launches Winlevi® in Singapore and Malaysia, Ushering in a New Era of Acne Treatment in Southeast Asia

• 10x Genomics and A*STAR GIS Join Forces to Advance Precision Medicine Through AI-Powered Spatial Biology

• Shanton Pharma’s SAP-001 Receives FDA Fast Track Designation for Refractory Gout Treatment

• WuXi Biologics Begins Construction of One of the World’s Largest Modular Biologics Drug Product Facilities in Singapore

• 65LAB awards US$1.5M to Duke-NUS platform to advance antifibrotic drugs for lung and kidney disease

📆 Events happening this month

Conferences

• Healthcare AI Symposium (HAI) 2025
  (22 Aug, 8:30 AM - 5:00 PM, in person)

• IP Week @ SG 2025
  (26-27 Aug, 8:30 AM - 5:30 PM, in person)

• Singapore Heath & Biomedical Congress
  (09-10 Oct, 8:45 AM - 6:00 PM, in person, Registration deadline: 17 Sep)

Networking events

• Sat Health & Bio Brews Singapore

  (Every Sat, 9:00 AM - 10:30 PM, in person)

• Angel Investors Social Gathering

  (27 Aug, 6:00 PM - 8:00 PM, in person)

Seminars/Panel discussion

• Advancing Menstrual Health: Scientific Innovations and MenSCs for Cell & Gene Therapy

  (27 Aug, 5:30 PM - 8:30 PM, in person)

• Fireside Chat: Deep-Tech & the Future of Ageing
  (19 Aug, 4:00 PM - 5:30 PM, in person)

• 2025 CoRE Conversation with Dr Yasuhiro Fujiwara
  (20 Aug, 4:00 PM - 5:00 PM, online)

• Inside the Engine: How Cedars-Sinai powers healthcare innovation in US and Beyond
  (21 Aug, 2:30 PM onwards, in person)

• Business Forward: Scaling Smarter with Market Insights, Strategy & Innovation
  (21 Aug, 9:00 AM - 1:30 PM, in person)

• Adapting to Change: Reinventing Roles and Reskilling for the AI Economy
  (21 Aug, 3:00 PM - 5:00 PM, in person)

• ShowcACE with DBS: Optimising Startup Cash Flow and Working Capital
  (25 Aug, 2:00 PM - 5:00 PM, in person)

• Built for Success: The Startup Stack for Global Ambition
  (27 Aug, 6:00 PM onwards, in person)

• Navigating Kobe’s Biomedical Ecosystem and Japan’s Medical Device Regulatory Landscape, featuring experts from the KOBE Biomedical Innovation Cluster (KBIC).
  (28 Aug, 9:00 AM - 11:00 AM, online)

• IP in Industry
  (28 Aug, 2:30 PM - 4:30 PM, in person)

• Biotech IP Strategies: IP Protection and Commercialization
  (28 Aug, 5:00 PM - 8:00 PM, in person)

• Drug Discovery and Development in Singapore: Opportunities and Challenges
  (10 Oct, 9:00 AM - 10:30 AM, in person, Registration deadline: 17 Sep)

Workshop

• Healthcare AI Masterclass
  (25 Aug, 8:30 AM - 5:25 PM, in person)

• A*SPIRE Co-Founder Matching Programme
  (27-28 Aug, in person)

Competitions

• Healthcare Innovation Pitch Challenge 2025
  (22 Aug, in person)

• Falling Walls Lab Singapore 2025 Applications
  (22 Aug, 2:00PM 0 5:00 PM in person)

• The 13th Chaoyang International Talent Entrepreneurship Conference Global Competition
  (24-25 Sep, online, deadline: 31 Aug)

If you enjoyed reading this post, comment and give us a like! Or let us know your thoughts here.

🍽️ Digestibles

High potential SG research, hot off the press

INFECTIOUS DISEASES: Smart Macrophages and Glowing Molecules: A New Way to Treat

@Senuri De Silva

TL;DR:

• Sepsis is hard to treat due to rising antibiotic resistance and immune system failure after infection.

• Researchers developed a glowing molecule (TPA2PyPh) that loads into macrophages’ fat droplets and kills bacteria hiding inside cells by damaging their DNA.

• In mice with drug-resistant sepsis, this strategy greatly reduced bacterial levels and improved survival, showing promise as a new treatment when antibiotics fail.

Sepsis is a life-threatening condition caused by the body’s overwhelming immune response to infection, affecting over 30 million people each year. Treating sepsis has become increasingly difficult due to rising antibiotic resistance, and a weakened immune system post-infection makes matters worse. Bacterial sepsis triggers a massive immune response, causing widespread inflammation and potential organ damage throughout the body. Even when patients survive the initial inflammatory phase, many quickly enter an immunosuppressed state, where their weakened immune systems can no longer clear infections on their own, making antibiotics the primary treatment option. However, the growing rise of antibiotic-resistant bacteria severely limits their effectiveness, leaving patients vulnerable and sepsis harder to treat. To address this, scientists are exploring ways to restore immune function in sepsis patients without relying solely on antibiotics. One promising approach is adoptive cell transfer (ACT), where immune cells like T cells or macrophages are engineered and given to patients to boost immunity.

Among these, macrophages are especially promising because of their strong ability to swallow and kill bacteria, as well as their role in activating both the innate and adaptive immune responses. However, many bacteria have evolved clever ways to hide and survive inside macrophages, avoiding destruction and causing recurring infections. This is where lipid droplets (LDs) come into play. These fat storage structures inside cells can also serve as delivery hubs for therapeutic agents. Some fluorescent molecules, like BODIPY or Oil Red O, have already been used to track these droplets.

Building on this idea, researchers at NUS Department of Chemical and Biomolecular Engineering developed a special glowing molecule called TPA2PyPh, cleverly designed to target both lipid droplets and bacterial DNA. Its structure includes both a positively-charged hydrophilic end that can bind tightly to and disrupt negatively charged bacterial DNA, as well as hydrophobic units that allow it to easily cross cell membranes and accumulate in lipid-rich environments such as fat droplets. When loaded into macrophages, TPA2PyPh sits quietly until the cells encounter bacteria. The molecule is then transferred from the lipid droplets to the bacteria through the cells’ natural lipid uptake pathways, disrupting both the bacterial membrane and DNA, effectively killing the infection from within.

What makes TPA2PyPh even more powerful is its fluorescent property. When exposed to light, it emits strong glowing signals, making it highly useful for real-time tracking and treatment monitoring. This enables researchers and clinicians to visualize the molecule’s movement and confirm it reaches infected sites, offering both therapeutic and diagnostic value in fighting drug-resistant infections.

In tests on mice with multidrug-resistant sepsis, this treatment significantly reduced bacterial levels and greatly improved survival rates. This strategy offers a powerful new way by improving ACT to treat severe bacterial infections and sepsis especially in cases where antibiotics are no longer effective.

Learn about biotech advances in Sepsis,

• MedTech Inflammatix collects FDA clearance for ER sepsis diagnostic test

• ABIONYX Pharma is awarded €8.7 million from the French government to fight against Sepsis

• Sepsis fatalities reduced as Microbio, ARM Hub combine AI with pathogen detection biotech

• Cytovale gains momentum with $100M for its sepsis screening test

CANCER: Repurposing a psychiatric drug to treat liver cancer

@Chua Damien

TL;DR:

• Ketanserin, a psychiatric drug that blocks the serotonin receptor 5-HT₂A, boosted anti-tumour immune cells in liver cancer, resulting in similar therapeutic efficacies as leading immunotherapies

• Combinatorial therapy of ketanserin with the leading immunotherapy demonstrated even higher therapeutic effectiveness against liver cancer.

A new study by A*STAR IMCB positions the serotonin receptor 5-HT₂A as an unexpected but highly actionable switch for rousing immune attack in hepatocellular carcinoma (HCC), the most common form of liver cancer. Using a high-throughput chemical screen, the team pinpointed 5-HT₂A signalling as a brake on anti-tumour immunity and showed that blocking this receptor slowed tumour growth and boosted T-cell infiltration in mouse and patient-derived models of HCC.

In an inducible HCC mouse model, daily ketanserin (5-HT₂A-specific inhibitor) monotherapy prolonged survival as much as the frontline atezolizumab + bevacizumab strategy (anti-PD-L1 + anti-VEGFA). This enhanced survival vanished in genetically modified mouse models lacking adaptive immunity, confirming that adaptive immunity—rather than direct tumour toxicity—drives this therapeutic effect. Treated mice showed higher intratumoural CD8⁺ T-cell infiltration and elevated IFN-γ, a cytokine linked to better clinical outcomes in HCC patients. Importantly, adding ketanserin to the PD-L1 + VEGFA antibody combination therapy preserved—and in some mice improved—the spontaneous tumour regressions seen with the antibody pair alone, pointing to straightforward synergistic effects.

Because a wide range of 5-HT₂A antagonists—including several antipsychotics and next-generation psychedelic modulators—are already in clinical use, the work charts a swift translational path: drug-repurposing could plug an urgent gap for the 70 % of HCC patients who fail first-line checkpoint therapy or targeted kinase inhibitors.

From a commercial vantage, the timing looks ideal. Global liver-cancer drug sales stand at roughly US $3.7 billion and are forecast to top US $9.8 billion by 2030, expanding at nearly 18 % CAGR as clinicians pivot toward immunotherapies and combination regimens. HCC itself is projected to be a US $3 billion niche by the end of the decade, yet durable treatment responses remain rare with current treatments. Off-patent 5-HT₂A blockers such as ketanserin or risperidone offer low-cost, low-risk entry points for rapid Phase II trials, while patent-protected serotonergic agents (e.g., selective 5-HT₂A inverse agonists in psychiatric pipelines) could be licensed or co-developed for oncology. Safety data from thousands of neuro-psychiatric patients further de-risks development, trimming time-to-market compared with first-in-class biologics.

CANCER: Engineered Bacteria for Colorectal Cancer Immunotherapy

Devika Menon

TL;DR:

• Clusters of immune cells formed inside tumors, also known as tertiary lymphoid structures (TLSs) are associated with better survival outcomes

• Bacteria in the gut and certain type of immune cells (ILC3s) have been closely linked to improved growth of TLSs

• Scientists engineered bacteria to release a cytokine called LIGHT that can promote TLS formation and maturation, thereby inhibiting tumor growth in mice

Although Colorectal Cancer (CRC) is responsible for approximately 10% of deaths globally and is the second leading cause of cancer related deaths, it remains hard to treat. While immunotherapy has not been found to be particularly effective, tertiary lymphoid structures (TLSs) - which are clusters of certain types of immune cells that can form in tumors- and especially, mature TLSs (mTLSs) have been linked to better survival rates in patients. Factors that could promote the formation of these clusters include several types of harmless bacteria present in the gut and a specific group of immune cells in the gut - ILC3s. These immune cells can regulate adaptive immunity and could be interacting with other immune cells as well as the microbiome, together playing a significant role in maturation of TLSs. However, these cells are reduced in CRC, hindering the formation and growth of TLSs.

NUS scientists hypothesized a close relationship between gut microbiota, ILC3s and TLSs, and engineered a bacteria (VNP20009 - a strain of Salmonella typhimurium) that can grow inside tumors. The bacteria, upon colonizing the tumor, releases a cytokine known as LIGHT (a signalling molecule that is a regulator of T-cell activation) - which can promote TLS formation and maturation. Upon treatment of mice models of CRC with the engineered strain of the bacteria, ILC3 levels in tumors increased. They also observed an increase in the number and size of TLSs, as well as the level of TLS maturity after treatment. Tumor growth was inhibited and tumors reduced in both size and number following treatment, resulting in mice having better survival post-treatment compared to the control mice that were treated with only bacteria or only LIGHT, indicating that the bacteria and LIGHT have a synergistic effect in promoting TLS maturation.

Tests revealed that ILC3 cells activate cancer-killing immune cells through the LIGHT-HVEM signal (a signalling pathway in T-cell activation), improving immune response to tumors. The method was found to be safe as the bacteria largely remained in the target tumors and did not cause any harmful damage to other organs. This bacterial-based immunotherapy could pave the way for a treatment of CRC that is specific and more effective.

Read more about how:

• Other designer bacteria are being used for cancer immunotherapy

• Gut bacteria can improve cancer immunotherapy outcomes

CANCER: Balancing Act: How Calpain Enzymes Shape Inflammation and Tumor Growth in Liver Cancer

Senuri De Silva

TL;DR:

• In liver cancer, tumor-promoting inflammation driven by the cytokine IL-1α contributes to disease progression. While calpain 1 is known to activate IL-1α, the role of its close relative, calpain 2, remains unclear.

• NUS researchers found that calpain 2 keeps calpain 1 and consequently IL-1α in check, inhibiting tumour progression.

The tumor microenvironment (TME) plays a key role in shaping how the immune system responds to cancer. It contains a mix of cancer cells, immune cells, fibroblasts, and other supporting cells. Some of these immune cells; like tumor-associated macrophages (TAMs), regulatory T cells (Tregs), and myeloid-derived suppressor cells (MDSCs) can actually suppress the body’s anti-tumor response, helping the tumor grow. In advanced cancers, these cells release signals that promote blood vessel growth, dampen immune attack, and are often linked to poor survival.

The TME is also rich in cytokines, chemical messengers that either help or hinder cancer. For instance, IL-17 encourages tumor growth by attracting MDSCs, while IL-37 can slow tumor growth by reducing blood supply to the tumor. Another important cytokine, IL-1α, is known as an “alarm” signal that sparks inflammation. It exists in an inactive form (pro-IL-1α) and is activated when cut by an enzyme called calpain 1. Once active, IL-1α can worsen cancer by attracting MDSCs into the tumor.

In liver cancer models, researchers at the NUS Life Science Institute previously found that calpain 1 activates IL-1α, a molecule that promotes tumor growth. Now, they've discovered that calpain 2, a closely related enzyme, also plays an important role. When calpain 2 was removed from liver cancer cells in mice, tumors grew even faster. This was due to a rise in calpain 1 levels, which led to increased production of pro-inflammatory IL-1α.

Further experiments showed that losing calpain 2 increased levels of proteins called FoxO3 and FoxP2, which in turn boosted calpain 1 expression. This suggests that calpain 2 normally keeps calpain 1 in check, and both enzymes work together to regulate IL-1α secretion.

This newly uncovered balance between calpain 1, calpain 2, and IL-1α highlights a potential weak spot in tumors, one that could be targeted to reverse immune suppression and slow cancer growth.

Learn about recent biotech in liver cancer,

• HepaRegeniX secures $23 million to push liver drug into Phase II

• GSK makes $2bn bet on liver drug from US biotech

BIOSENSORS: Flexible, Reusable Biosensor Precisely Maps Arteries for Safer Surgeries

Chua Damien

TL;DR:

• NUS researchers invented a flexible and reusable hydrogel biosensor to non-invasively and precisely locate critical blood vessels during surgeries, outperforming traditional methods.

• This new method utilises infrared photoplethysmography (PPG) signals to map and detect damaged blood vessels.

Perforating arteries (PAs) are small but vital blood vessels connecting deeper arteries to the skin's surface, playing a key supporting role in facilitating successful surgeries like tissue transplantation, minimally invasive procedures, and targeted embolization therapy. Precise identification of PAs is crucial—especially in free-flap surgeries, where tissue harvested to repair wounds depends entirely on these vessels for survival. Current mapping methods range from handheld Doppler ultrasound to CT angiography, but each has trade-offs: expensive equipment, radiation or contrast dye exposure, and operator-dependent accuracy. To counter these, NUS researchers have developed a flexible hydrogel-based biosensor patch that noninvasively pinpoints these vessels by reading infrared photoplethysmography (PPG) signals from the skin’s surface. The thin sensor array rapidly detects the subtle pulsations of blood flow and highlights viable arteries within minutes, consistently matching gold-standard CT imaging results and eliminating the false positives that often plague Doppler probes (demonstrated in the paper, use cases 1-5).

Although traditional PPG systems struggle with skin adhesion and flexibility, the team designed an innovative hydrogel layer that conforms tightly to the skin, dramatically improving signal quality. Importantly, this hydrogel is detachable and replaceable. A brief electrical stimulus quickly weakens the gel’s attachment to the device, allowing easy removal and replacement after each patient. By combining precise PA detection, ease-of-use, portability, reduced cost, and safety (no cross-infection risks), this technology addresses critical unmet needs in reconstructive surgery. Moreover, its versatile hydrogel platform could easily adapt to other medical monitoring devices, highlighting broad clinical and commercial potential (demonstrated in the paper, use cases 6-10).

This reusable hydrogel-based biosensor technology offers substantial translational potential within the rapidly growing medical device market, particularly for surgeries requiring precise blood vessel identification. By addressing key limitations of current methods—high cost, complexity, radiation exposure, and infection risks—this flexible, wireless, and easy-to-use solution significantly lowers barriers to clinical adoption. Its adaptable design ensures wide applicability beyond flap surgeries, extending to minimally invasive procedures and vascular treatments. As global demand rises for cost-effective, patient-safe, and reusable medical technologies, the hydrogel-based biosensor is strategically positioned for rapid translation into clinical practice. This presents compelling opportunities for partnerships, licensing, and commercialization within healthcare innovation markets.

🗞️ Industry Spotlight

News from the Singapore life sciences industry

• Chugai and Gero link on antibody drugs for age-related conditions.

• Singapore-Korea partnership to apply AI in hair follicle regeneration research.

• Switzerland’s RDP Pharma and Singapore’s A*STAR EDDC Join Forces to Develop Precision Autoimmune Therapies

• WuXi XDC accelerates global expansion of bioconjugates manufacturing by revitalising Singapore site.

• Gero’s ProtoBind‑Diff redefines drug discovery by designing molecules from sequence alone

• Medtech player Alcon expands its manufacturing facility in Singapore.

• Singapore contributes $1M to Gavi for better access to vaccines.

• Danone invests in Singapore Digital Lab to expand global innovation capabilities

• IHH Healthcare launches a $5M grant to boost clinical research, innovation

🎧 Nucleate Singapore Pulse

Listen now

📆 Events happening this month

Conferences

• Singapore Cell and Gene Therapy (SCGT) Pan Asia Summit 2025

  (16-18 Jul, 8:00 AM - 6:50 PM, in person)

• Frontiers in Cancer Science 2025

  (5-7 Nov, TBA, abstract submission deadline 28 Jul, in person)

Networking events

• Sat Health & Bio Brews Singapore

  (Every Sat, 9:00 AM - 10:30 AM, in person)

• BLOCK71 Founders and Funders: Meet Ventures Edition

  (24 Jul, 06:00 PM - 08:00 PM, in person)

Seminars/Panel discussion

• Building a Board that Drives Impact

  (16 Jul, 02:30 AM - 05:30 PM, in person)

• AngelCentral Masterclass Series: Implications of Deal Terms using Real World Case Studies

  (16 Jul, 02:30 AM - 05:30 PM, in person)

• Founders Fundamentals

  (23 Jul, 01:00 PM - 05:00 PM, in person)

• Growth Hacking and Digital Marketing for Start-ups

  (24 Jul, 11:30 AM - 01:30 PM, in person)

Workshops

• Developing Roadmap for Startup Success

  (17 Jul Sat, 09:00 AM - 06:00 PM, in person)

About The Guest

Dr. Goh Wei Jiang is the Co-founder and CEO of CraftHealth, a pioneering Singapore-based startup revolutionizing personalized medicine through 3D printing. With a background in pharmacy and a PhD-MBA from NUS, Dr. Goh brings both scientific expertise and commercial insight to the forefront of MedTech innovation. Drawing on his clinical experience and translational research, he co-founded CraftHealth to solve a real-world challenge: simplifying polypharmacy and improving drug compliance through customizable, on-demand medications.

📄 Summary

In this episode, Dr. Goh Wei Jiang shares his journey from hospital pharmacist to a Healthtech founder. Motivated by the challenge of polypharmacy and the pill burden faced by patients, Dr. Goh and his co-founder developed a 3D printing platform that enables personalized medicine—combining multiple drugs into a single, tailored pill with customized release profiles.

He walks us through the early ideation phase, shaped by his experiences in Stanford Biodesign, GRIP, Lean Launchpad, and other innovation ecosystems, and how they tested their first 3D printed pill using a small grant. Dr. Goh explains how CraftHealth's proprietary platform integrates hardware, software, and material science to create a modular, scalable approach to medication production.

Dr. Goh also explores real-world applications: from improving precision dosing in pediatric or renal patients to enabling compounding pharmacies and supplement companies to rapidly prototype and personalize products. He discusses regulatory challenges, automation, hospital partnerships, and long-term visions for decentralised drug manufacturing. Finally, he shares his reflections on entrepreneurship, emphasising the importance of customer validation and building what people are willing to pay for.

🥡 Key Takeaways

• 💊 Solving Polypharmacy with Technology
  CraftHealth’s 3D printing platform transforms multiple medications into a single customizable pill, helping reduce pill burden and improve compliance.

• 🛠️ 4-Part Printing Ecosystem
  The platform includes 3D printers (using no heat/UV), software with no-code interface, customizable drug-release paste materials, and a growing formulation database.

• 📈 From Prototyping to Commercialization
  Already deployed in Australia, Europe, and the U.S., CraftHealth is proving the value of low-volume, on-demand manufacturing in both pharmaceutical and supplement sectors.

• 🏥 Hospitals as Micro-Factories
  Dr. Goh envisions decentralised drug production with printers in hospitals or clinics, starting with niche clinical use cases and expanding over time.

• 📍 Growth Strategy
  Due to the low prevalence of compounding pharmacies, CraftHealth is focusing on partnerships with hospitals, R&D institutions, and universities across the region.

💬 Quotes

• “You see patients going home with bags. Full of medications, very colorful pills, 3, 4, 5 times a day before the food. And we wonder at the point in time whether there is a easier solution. Because all of this adds to a lot of pill burden to the patients.”

• “We both publish and want to do something that can translate into a real world setting and we revisited that problem. It turns out that perhaps the solution was right under our nose in the form of my co-founder's' thesis.”

• “We wanted to look at the pharma angle and we realized that we're not there to replace the traditional pharmaceutical manufacturing.”

• “We are back in the hospitals working to local hospitals. So that's where we started. And that's where eventually we want to have the greatest impact. So like what you mentioned, I think the key thing is eventually we have what you call decentralized production of medicines.”

⏱️ Timestamp

• 01:15 – Dr. Goh’s Background & Identifying the Problem of Polypharmacy

• 08:50 – CraftHealth’s 3D Printing Platform (Hardware, Software, Materials, Data)

• 13:15 – Use Cases

• 15:15 – Addressing Challenges, Regulatory & Commercial Fit

• 24:00 – Expansion and growth strategies

• 34:00 – Vision for Decentralized Drug Manufacturing and Closing

🎙️ Transcript

Episode Preview

Dr. Goh Wei Jiang: I think the one thing that always resonate with us is that it doesn't matter who is right? You have a lot of opinions. You have a lot of advisors. The one person that will always be right will be whoever who pays for the product. So if you have someone who's able to pay for the product, it means that you're onto something. And I think that is the way that we have to be very prudent on, especially in today's climate, everyone's very prudent about their spending. If you can identify a group that's willing to pay for your product, you are onto something. And that's probably the path that you should consider.

Dillon Chew: Hello, and thank you for joining us on Nucleate Singapore Pulse, Singapore's premier podcast on the biotech ecosystem. I'm your host, Dillon, and whether you're a student thinking about creating your own startup or an industry professional looking for diverse perspectives, this is the podcast for you.

The show notes and transcripts for the episode can be found on nucleatesingapore.substack.com.

Dillon Chew: Joining us today is Dr. Goh Wei Jiang, who is a pharmacist, turned entrepreneur, and currently serves as the CEO and co-founder of CraftHealth. CraftHealth is a Singapore based startup, which aims at transforming personalized medicine through 3D printing. So welcome and thank you for joining us Wei Jiang.

Dr. Goh Wei Jiang: Yep. Thank you, Dillon, thank you very much for inviting me to this podcast.

Dillon Chew: Great. So could we start by sharing a little bit first about your background and what led you eventually towards starting CraftHealth.

Dr. Goh Wei Jiang: Sure. So the story of how we all started the CraftHealth journey was really between myself and my co-founder, Dr. Lim Seng Han. So we are both pharmacists, so we both practiced as pharmacists at SGH for a couple of years, and that was where we first saw the problem. And the problem was polypharmacy, too many pills.

So you might recall when you go to the hospital or clinic, you see patients going home with bags. Full of medications, very colorful pills, 3, 4, 5 times a day before the food. And we wonder at the point in time whether there is a easier solution. Because all of this adds to a lot of pill burden to the patients, they may or may not remember, definitely it's not easy, and as a result, the compliance to the medication is not really high. So a drug is only as effective as if you take it correctly. So we thought that that was the major problem, and it'll only compound over time as populations, not just Singapore, but populations across the world age.

So fast forward, both myself and my co-founder, we went back to school to do our PhDs. So it just so happened that his PhD was on 3D printing for personalized medicines. So he's the subject matter expert, he's been doing 3D printing for more than 10 years already. So in our final year, we decided let's do something more translational. We both publish and want to do something that can translate into a real world setting and we revisited that problem. It turns out that perhaps the solution was right under our nose in the form of my co-founder's' thesis. So we managed to get a small grant, check the technology, see if it works. It did, and when we graduated, we joined NUS GRIP. We were in the first batch, and that was how it all started.

Dillon Chew: So I think just now you also mentioned a little bit that you went back to school actually after working as a pharmacist for a while. And you did a PhD, MBA, so what actually motivated this transition after working for a while?

Dr. Goh Wei Jiang: Yeah, I think it really goes back to sort of personalities that most founders are. So in a way, you need a challenge. You always look out to do new things. And, you know, being in a work environment, you start to learn about the intricacies of dispensing, of being a pharmacist. And over time you realize that, hey, it's time to move on, it's time to learn new things. And from the earliest part of my undergraduate days, I've always been interested in research R&D. So I decided that hey, let's do a PhD, so talk to some people, talk to some seniors, realize that that could be something that is very interesting to do.

Turns out that NUS at that point in time, they offered a dual program, an NUS PhD, MBA program. So why not? And that way you can get the best of both worlds. R&D you have research and really the development part and subsequently learn about how to commercialize it and the idea for this program is that you incubate the next generation of entrepreneurial scientists. I hope it turned out that way. So that's how we look at things from that perspective.

Dillon Chew: Well, did you actually know that you wanted to do a startup when you were actually working or was it even way before?

Dr. Goh Wei Jiang: Not really. So when I was undergrad just like any other undergrad, I think it was a bit unclear of what you want to do and that's why you just follow the typical career path. You study, you get good grades, you try to get good grades and you get your first job.

But when you do get into the first job, and that's when you see more of the real world setting, then it struck you as what could be more meaningful to you what can do better, right? So that's how we, look at it.

Dillon Chew: So I also noticed that in your CV, you've actually been through several innovation ecosystems like Entrepreneurship First, the Stanford Biodesign, Lean Launchpad, as well as GRIP. So how do actually all these experiences converge to shape your vision for CraftHealth?

Dr. Goh Wei Jiang: So I think at the point in time it was where the startup scene was still very nascent, but it's definitely growing. So I thought that it was a wonderful opportunity that you can go through all these different programs and just to learn how to do it. I think a key thing would be the frameworks of how you should approach a problem and how you should launch a startup. I think the key learnings would be to fail fast, fail early, right? Test the problem, talk to a lot of people, get real world feedback. These are all things that doesn't change and this would be more of a timeless principles that we still can apply. Because it's what that doesn't change that you can actually work on.

So looking at all of these programs, I think, you know, we learned a lot. Personally I did. And some of it, like for example, Stanford Biodesign is more specialized in the form for MedTech. So what could be applicable in a MedTech setting, may not be a hundred percent used, let's say for e-commerce. So in a way, I managed to get a lot of exposure to different business models. And that really had me thinking at the start of how to formulate the approach.

At that point in time, we did not have the idea for CraftHealth yet. So it is still looking at different possible solutions, possible angles, perspectives to do something.

Dillon Chew: So then when was that pivotal moment where you knew the idea could actually become a startup because you've actually been through so many programs and then what led you, or what was that inspiration that led you like, Hey, let's move this thesis out from the lab and then into a startup where we can actually start to commercialize this.

Dr. Goh Wei Jiang: So I think, in a way it also goes back to our experience as pharmacists. You know, we saw the problem. So the problem is real, the problem is there, it is real. The question that we had at that point in time was whether or not the technology was able to do what we wanted it to do. So, the best way to get forward is to just test it.

We managed to obtain a small grant and we tested out the tech. So when we had that first 3D printed pill out. And we were looking at it and you realize that actually it's not that difficult. Of course there are intricacies. There are nuances to it. But the core technology, no, it's not that difficult. And if it can be applied directly to, let's say, the patients, that would be wonderful. So that's where we decided, hey, it's time to move out. You know, maybe you can publish papers on it, but it will not necessarily move the needle immediately. And at that point in time you also did a search of what are the competitors. There weren't many. The field for 3D printing of medicines six years ago was very empty. And we saw the opportunity to be a first mover. So that's where we decided. Hey, you know, let's try, push this out as fast, as far as you can.

Dillon Chew: Sure thing. Now that we've kind of started talking a little bit about CraftHealth, I think it will also be great if you could share with us a little bit more about your company. So my understanding is that your aim is to use 3D printing to personalize medications. So you have 3D printed pills. So can you just walk us through a little bit as to what are some of the key platforms and technologies that your company has to actually enable some of these innovations.

Dr. Goh Wei Jiang: Yeah, certainly. CraftHealth, we started six years ago. So at that point in time, it was just two PhD students with one laptop. We shared a laptop. That was when we started off with just a presentation of what we plan to do. We managed to raise some funds and six years later, happy to share that we now have the commercial CraftHealth 3D printing platform, and it really consists of four components.

The first is the hardware, the 3D printer. The unique selling point is that we use the technique of semi solid paste extrusion. There's no heat, there's no UV curing. So the entire process is done at room temperature and pressure, which I think very important if we are dealing with medicines. We have print biologics, actually we were able to print probiotics. So that's the element where no heat or no UV curing or no harsh elements come to play.

The second component will be the printing software itself. And the key thing that we want to highlight is that there is no coding required. All the coding is all done back end. So for example, the operator asked I want a particular shape. Typically, oral dosage forms are all rounded, otherwise it's difficult to swallow. So I want this particular shape, particular size or dose, and we put it into a program for them to select. So all the operator does is they select the right program, select the right cartridge and print. So that's relatively straightforward for them.

The third component is the materials. How do we have a 3D printable paste that fulfill two things. One is 3D printable. It's not too thick, it's not too stiff. You can't push it out, you can't extrude it. It's not too wet that can't hold it shape. So it has to be just nice. You have to have some visco-elastic properties, so the more pressure you add to it, the better the flow. So once you release it. It becomes stiffer. So it holds the shape better. So that's the first.

The second is that we are able to adjust the release profiles of the active through the use of the non-active ingredient. So for example, we can have a particular base that you can have for an immediate release profile. So within 30 minutes of consuming this pill, its released in the body. You can have another formulation for sustained release. So it releases the active slowly over four to six hours. So if one more for delayed release, we have one more for chewables, et cetera. And how we did this particular piece on the materials is that we have standardized the different release profiles into pre-mixes.

So to the operator, you don't have to worry about what are the different non-active ingredients that I need to mix and match. We take care of that for you. You obtain the base premix, you add in the active, you add water, it becomes a paste. Voila you can print. So that's how it is.

But the fourth component is where it gets interesting, is that we are actually collecting the hardware, software, and the material data points into a database. So, I think the key thing is that most people thinks that 3D printing is just pushing something out, right? It's not actually the case for us, because when we give paste materials, you want it to be very precise. So instead of just pushing, there are instances where you have to do a suck back. So the paste actually goes backwards and the extrusion process there and that, so there's no overdose for a very small tablet.

And all of this hardware, software, and the material data points, it goes in our database so that the more we understand the interplay of the different materials, the hardware and the software, the faster we can formulate new formulations. So if tomorrow, pharma company A or supplement company B says, Hey, CraftHealth, can you formulate this particular product? I do need to know what it is. I just need to know the properties. Input into a database. You can have the formulation out quickly without testing in the lab immediately. All the different empirical testing, cut through that. So that is the 3D printing platform that we have.

Dillon Chew: That sounds really interesting. So I'm also a little bit curious because you mentioned about the problem about poly medicines at the start of this interview. So, I'm just wondering how do these all come together to achieve this objective of poly medicines, or even precision dosing where you're able to customize the dosage .

Dr. Goh Wei Jiang: Yeah. I think the key thing for poly pharmacy is where you have multiple different medicines that you take in a day. Now, from our perspective, we are able to reformulate the entire pill in a sense that we only take the active ingredients.

We take the active ingredients and then we mix it with our premixes. So you can have one layer, for example for aspirin, another layer for stomach protectant, and that's where it can be a bit different. For example, aspirin and a stomach protectant. Usually you take it before and after food. So, one layer that's released now, one layer that's released two hours later. So that's a before after food combination. So in this way, we are able to string the burden of huge number of pills into just a few.

Now, the other spectrum that what you had mentioned, is that we are able to dose very precise dosing in terms of titrations. So for example, if one layer is one milligram and you need three milligram, you can just print three layers. In this case, problems like for example, you have to split the pill, crush the pill. These are all very inaccurate measures, very troublesome measures. Or even the instances that like in Singapore, although we are a first world country, a distributor may not have that incentive to bring in certain medicines, or certain strengths. So maybe it's only available in 25 mg, but you need a 10 mg for let's say a kid, or certain dosing for renal or for impairment, you need 10 mg. How do you get 10 mg? So we can print it on directly for you. So that's how we can do a lot of precise titrations just for the individual.

Dillon Chew: Appreciate the sharing. After you mentioned all these, it also gets me thinking about some of the potential challenges that you might face. So the first thing that comes to my mind is, for example, when you do a combination of multiple actives, there might be challenges with regards to toxicity, and maybe some of these actives are not stable.

So how do you actually manage all these things because I believe you might be working with certain pharmaceutical companies to launch it because what you would have is actually a platform for printing? Or correct me if I'm wrong?

Dr. Goh Wei Jiang: Yeah, excellent question. So how we approach this issue is from different angles.

So the first is always from the workflow side. Anything that is contraindicated for prescribing, the doctor should not prescribe it. So if two medicines or two drugs should not be taken together, the doctors shouldn't be prescribing it. So it wouldn't end up us to put both together. Even if that's the case, we have to reflect back to the doctor that, "hey , these two are probably incompatible".

Now what happens particularly is that there's a lot of mild interactions. And that's why we have the instruction to space this out two hours. You know, so that it doesn't react. So what we do is that we can actually print it into different compartments. So one compartment is drug A, one compartment is drug B and to prevent mixing, you can actually have a blank spacer.

But in actual fact, when we test it out, because they're all dry, it doesn't really mix. It's just that they're taking two tablets. If needed. We can also change the release profile. So one is released now, one is released later. So there's the temporal kind of separation. So in the stomach and the intestines, it's about two hours apart when they're released. So that's how we can resolve that.

Now, the question about toxicities and whether it's safe, I think safety is a key thing of what we look at. So again, different perspective. The first is that how do we ensure that the entire supply chain is safe, there's two parts to it. There's the active ingredients and there is the non-active ingredients, our base formula. So naturally we have to source all of it from GMP sources or WHO sources. So the manufacturer is very important, and that's the sourcing part. Now what we do is that we also run tests for the content uniformity before, during, and after print. So in a way, we make sure that there is no changes. Especially because we do not use any heat or UV. We do not expect there to be changes, but we run HPLCs, we run FTIR techniques to make sure there's no change. So basically we should have the same profile.

And the last part of it, of course, is to look at things like, for example, heavy metals. Things like microbial count, Pseudomonas, E. coli, et cetera. So we send this out for testing, third party testing. And earlier on I mentioned know all the different tests we do, we typically follow USP, so anything that's done according to United States Pharmacopia, it doesn't matter if you're doing it in the US in Singapore, wherever. You follow the same guidelines and the same prescribed technique. So the results you all collect in the dossier, and that's how we ensure the safety part of it.

Dillon Chew: Speaking about this, because when you mentioned that one of your goals is actually personalization and then thinking back that traditional pharmaceutical models, big companies or big pharmas, they're actually built for mass production. So what do you think are some of these technical or logistical and even commercial challenges to actually make this feasible at scale?

Dr. Goh Wei Jiang: So this is actually a very good question. So at the start, we wanted to look at the pharma angle and we realized that we're not there to replace the traditional pharmaceutical manufacturing. Case in point, know a tablet press, you know, you can churn turn out anything from a thousand to 10 of thousands of tablets a minute. So 3D printing, because you're doing it pill by pill, it's much slower. So for us, it takes us about 10 seconds to do a hundred mg tablet, for example. So there's key difference in terms of the speed.

Now where we differ is where you have a lot of changes to the SKU, for example, you wanna change the dose, you wanna change the combination. So that's where 3D printing comes in if you're looking at a low volume behind mixed approach. And that's where we realize that it's actually very complimentary to the pharmaceutical model.

And where would the product market fit be the greatest? You know, we look across the spectrum and realize that compounding pharmacy, that's where it'll be an excellent product market fit. So compounding pharmacy is where you approach the pharmacist or the chemist to compound or to prepare. Preparation that is customized or personalized for the individual. It could be reasons like, you know, you're allergic to something. It could be reasons that you can't swallow tablets, you want to do a chewable. It could be reasons like simply because that particular dose or the drug, it's not available commercially. And it is actually done quite at mass, but manually.

And that's where we realized that hey, actually our platform could be a very opportune automation platform for this compounding pharmacy. So the workflow doesn't change. The regulatory route is still via compounding, they still take the active and mix it into a base, but this time it's our base. And the difference is that instead of a human operator doing all the manual workflow, you plug it into our 3D printer, print, and you can do other tasks. So that's how we help them to reduce the manpower constraints and to improve their productivity while maintaining the consistency of the product through automation.

Dillon Chew: So, apart from these compounding pharmacies then, do you actually envision, or where else do you actually envision your platform fitting into the broader healthcare ecosystem? So let's say, do you think that this might go into hospitals or it might even end up in my home, for example?

Dr. Goh Wei Jiang: Yeah. So I think for the compounding pharmacy part, it is to where I would say it's the path of least resistance. That's where product market fit is there, regulatory, is there, everything makes sense. I think eventually, we would definitely want to work with the clinics, the hospitals and the overall vision is that each hospital, clinic itself have one or two printers.

And that's where you do not need to print for a lot of patients. So a drug manufacturing plant you are manufacturing for the whole of Asia Pac. So you're doing tons of tons of pills, but if you are just a hospital clinic, maybe you are doing with four or 500 patients, a day, so that volume shrinks. It becomes more focused because a cardio clinic only deals with cardio patients. So you can churn out that permutations for that group. So that's where we are looking at, we are working with the local public hospitals SGH, Tan Tock Seng. So that's where we take a more measured approach. You know, we obtain grants, we work with clinicians, we work with pharmacies, innovators, and the idea is to push this forward.

So it's more of the adoption and how we can move into the different phases of adoptions. So we're looking at the early adopters, you know, the clinicians, the pharmacy innovators, and we identify different niche areas that 3D printing could have the most impact, and that's how we move into that space. And in part it's also training. Training, exposure, so they learn what we can do, what we can't do, and what the hospital system is able to support. So I think it takes time, but you'll get there.

Dillon Chew: And I guess how close are we to actually seeing that as a reality today?

Dr. Goh Wei Jiang: I think for Singapore probably, it'll be faster to the hospitals because we do not have a lot of compounding pharmacies in Singapore. So the hospital part, probably you will see the next five 10 years. We are already in the hospitals running studies with them, so it's a matter of time when studies are published, we can share more.

Most of that validation work and go to market is actually done overseas. So we've just sold to to compounding pharmacies in Australia, they're live now. We have sold to Europe in the UK. So this year we actually did quite a bit of commercialization. Most of our sales is actually overseas. We sell to compounding pharmacists because they do face a problem. Manpower restrictions or manpower constraints. The workforce is aging. And in order to do all these manual preparations, it takes time and effort and that's where you can come in quite nicely, basically it's a onetime CapEx instead of a long term OpEx.

Dillon Chew: Definitely. Thanks so much for sharing. Yeah, because I actually work in the consumer goods space, it gets me thinking as there could be quite a bit of interesting possibilities for like supplements, nutraceuticals for instance?

So where do you actually see your technology intersecting with consumer health or rather something that's closer to the everyday consumer where personalization would be more scalable and definitely the regulatory aspects will be way lower?

Dr. Goh Wei Jiang: Yeah, so if you're looking at supplements, nutraceuticals, even food, the regulatory oversight is much, much lesser than pharma. And that's exactly what we've been doing. So we do have long term projects for the pharma angle, but in the near term, the one that brings in the cash flow quick in terms of the projects side, typically all the supplements.

So we work with nutra companies, whether they're startups or MNCs. Whether they're local, overseas, we have printed things like tablets. And the most interesting thing is that, it seems like everyone is moving towards chewables these days. So a nice chewable without the act of swallowing, you can have the flavor burst in your mouth with all the taste, form, factor, color, and in a way, that's exactly what we can do. So you can have, for example, Christmas special, Christmas tree Santa Claus, you know, chewables. That is seasonal. So it's exclusive for the time period. You can play around with the flavors, play around the quantities, play around with the scent, so it changes the experience. And that's what we are working with for the different companies.

Another thing that we've been doing for them is really to do quick prototyping. So for a lot of the supplement companies, before they launch a new product, they have a lot of ideas. You know, of what will work in the consumer market and typically know they want to test the ideas that because what they ideate in the office may not be you know what works in the market settings. So eventually you move the focus group setting, they pick the different individuals for the demographic that they're targeting, put them in the focus group, and, and they run through it, you know?

And if we can have it to prototype it with low quantities, at a lower cost with a relatively short period of time to be ideal. And this is exactly what we do. So instead of finding an OEM, you do a minimum 200, 300,000 units, you can do 20 to all the way to 10,000, depends on how you look at it. So you can actually test it through the different focus group and change the SKUs. So once they identify that two or three formulations or preparations that they like to move on, then they can find a way in. So that's where we function as well.

Dillon Chew: So am I right to say that you are also supporting not just at the drugs manufacturing end, but also in terms of rapid prototyping for R&D?

Dr. Goh Wei Jiang: Correct. Correct. So we also do supplements, nutra. We have printed TCM before, Indian ayurvedic medicine. And recently we are doing some food snacks, so sweets candies. So the technology is robust. Wherever you can do for pharma, definitely you can do for supplements because the technology is the same, the specifications, you just have to change it a little. In fact, you know, maybe if you do for pharma, it's too high a spec for food, for example. Yeah. Right. So you can afford to give out some of the specs for speed, for example.

Dillon Chew: So I guess we are one step closer to achieving this 仙丹 kind of approach, right? I mean, like the idea, right, where you have one pill that solves multiple problems. Eventually.

So looking five to 10 years ahead, what does success look like for CraftHealth, not just in terms of technology, but how do you think it will also change the overall patient experience in healthcare delivery?

Dr. Goh Wei Jiang: Yeah, I think the key thing is, we have done a lot, we look at compounding pharmacies, we've done projects with different companies and now I think we've go one full circle. We are back in the hospitals working to local hospitals. So that's where we started. And that's where eventually we want to have the greatest impact. So like what you mentioned, I think the key thing is eventually we have what you call decentralized production of medicines.

So even in Singapore, you can have one printer in each clinic printing for that particular specialty, the kind of medicines they need, it could be cardio, it could be infectious disease, it could be for pediatrics. They take a lot of different dosing by weight.

So, Singapore, we're very blessed. You know, everything is a stones throw away. The infrastructure is fantastic, right? But in other countries, the access in healthcare may not be that easy. So that's where we are looking at if we are able to introduce our printing technology into spaces where it's not so easily accessed.

And you can actually store the different actives that dry powder form before they are actually mixed with the base. Shelf life is much longer. You can store it for much longer and you can print on demand, so there's less wastage. So these are some of the opportunities that're looking at that we can make an impact.

Dillon Chew: So being in Singapore, do you actually see that the Southeast Asia market might be something that you'll be going after? Because you've also shared that actually all of your current customers are Europe or in Australia?

Dr. Goh Wei Jiang: Yes. The way we see it is that we need to tweak the business model according to the markets we're looking at. So the reason why we have quite a bit of sales in fact, you know in Australia and Europe and just last month in the States, is really because these are the countries where compounding pharmacies are very prevalent. So for example, in Australia there's more than 500, if not mistaken, compounding pharmacy. US I think is about 7,000. In Singapore, probably we have about four, five. So there's a big difference in terms of the market.

Now, in South Asia, we don't really have compounding pharmacy, and the GDP of these country typically a bit lower compared to the market countries. So that's where we approach it from the angle of working with the R&D institutes, the hospitals, and the universities. So that's how we could get adoption in Southeast Asia, so I would say a bit longer because you require buy-in from the institutional level. Whereas for places like Europe, Australia, US, we sell directly to the business owner.

And South East Asia as a whole, most people see it as a block when the actual fact is not. So if you're selling to the Thai market versus the Indon market versus the Malaysian market, it's very different. So each of it, you know, we need to have people, local people, local distributors, because sales people who understand the nuances of how to to work there and talk to the different customers there. So that's where it becomes interesting because we are also navigating that space.

Dillon Chew: I was just a bit curious about one thing that you've mentioned is because you mentioned that these countries it's not as well to do as like Singapore or like in Europe and Australia. So can you just speak a little bit about how does this technology that you have, enable the accessibility in terms of cost to these countries?

Dr. Goh Wei Jiang: Yeah. So I think the key thing is what we can do is that we can do at a very small scale, a unit level. So a lot of these countries instead of buying let's say your medicines by month. You purchase it by day, so it's actually cheaper on the absolute level. And that's where we can actually 3D print it on a much lower scale. That's one.

The second is that we are also looking at how we can introduce the access to where it is not so prevalent and the access may not be geographical. It could be a city that you do not have distributors so you become your own defacto manufacturer, so to speak, through the compounding route.

Dillon Chew: And in terms of cost, would there be any advantages because traditionally the understanding is that mass manufacturing, you do have economies of scale, but when you start going to 3D printing, then it's very challenging to reach that level.

Dr. Goh Wei Jiang: So definitely if you are comparing apple to apple, something that is 3D printed versus something that is mass manufactured, the one that is mass manufactured is definitely cheaper. The question is will it be there in the first place? So if there's no access, then you have to find an alternative, and the price then becomes irrelevant because there's no alternative. Number two. How much more expensive? I do not foresee that it'll be a lot more expensive.

We did some bag of hand calculations, it is not something that is going to be out of the world kind of expensive. Because you look at it this way, the non-active ingredients, it's not expensive. And we deal with the active ingredients. They are all generics. So we don't deal with proprietary medicines because that the IP protection is still there. So if you deal with generics, you are able to buy not from the finished product supplier, but from the raw ingredient supplier. So we actually strip out a portion of the cost. So it will be slightly more expensive, but it's not a lot more.

I think the other angle that we can also consider is that, it might be more expensive near term, but if you look at from the supply chain resilience point of view, that's where it makes sense to actually pay an insurance. And what do I mean is that, for example, in the case of COVID, you have cases where countries are locked down, so it becomes in a way, every man for themself. Yeah. So things like, for example, Paracetamol for while it was in short supply. What we do is that our platform, number one, taps a different part of the supply chain. We don't tap the finished product. We tap the active ingredient, so you approach a different part of supply chain.

Number two, you now are able to produce it on the spot for your demographic in the particular niche. So that's where we convert that reliance on manufacturing from, let's say, a plant in Singapore Tuas, to wherever you want for the period of time.

Dillon Chew: I think that really sums up or at least gives a very good clear overview as to how this technology actually is able to really transform what the pharmaceutical industry might be in the future. And I do see this as something that is probably parallel with big pharma at this point in time, but eventually, I think as more and more people start going towards a personalized concept, maybe this will be something that we will all appreciate.

So what is actually something that you wish that more people would appreciate more about this technology?

Dr. Goh Wei Jiang: So I think one of the key thing is that the technology wise not an issue. It's really the logistics backend. And this two need to go hand in hand. For example, if you say that I want to create 1,001 permutations. Technologically no issue, but back end, it means that you have to keep stock of that thousand and one permutations.

You have to purchase amount that makes sense at a certain scale. So typically you buy the raw ingredients. You have maybe 25 kilograms at least, or 20 kilograms. So imagine each material active, you keep stock of that amount. First you need huge storage.

Second, how do you adjust that logistically? And the third, the documentation for that will increase. So it is more of finding that right niche where existing processes that are really doing it, so we don't introduce new friction, new workflow. And that's where we see as, you know, the path of least resistance. And once we get that validated, once they're familiar with it, then you can expand.

Dillon Chew: So I just wanted to close off with asking you a couple of personalized questions. First is that, is there any like adjacent technologies or current trends in manufacturing or in healthcare you are particularly excited about? I think you've mentioned AI earlier on, and maybe how might any of these supplement what you're actually building at Craft Health.

Dr. Goh Wei Jiang: Well, we're quite interested in the space of the digital health, especially those led by AI companies. And the reason for that is. Twofold. One is that, we're looking at how we are the so-called provider of the actual medicines or supplements, but to do so, you need someone to fit in that information about an individual, consumer or patient.

So these companies are very good at picking up, you know what are the possible conditions, what are the possible treatments that will be the most optimal for the particular setting. And the idea is that, now that you have that piece of information, what do you do? So that's where it could be very interesting, where we can work with them to partner so that we have what you call a one-stop service or flow of information from the patient. Different parts of the parameters that you test all the way into the drug or a combination that you print specifically for the individual. So that's one aspect that we're looking at.

The other aspect that we are also looking at is how we can, in a way use AI to help us to do quality checks for our own printing. So instead of the individual, you have operator looking at a screen for one printer, you can have multiple printers all run by an operator. So that's what we are doing now with a dashboard and everything. But what if instead of operator keeping an eye on a dashboard, the AI looks after for you and only tells you when there is a pending problem or troubleshooting that you need resolved. So that's where we are looking at. We have introduced cameras into all our printers. So there's eyes on the ground, so to speak, and it fits into a system for computer vision. The idea is eventually, you know, the operator that runs the printer not be there for a long period of time.

Dillon Chew: Ideally you want it to have it completely autonomous, I would say?

Dr. Goh Wei Jiang: Yes. And that's the dream Yeah.

Dillon Chew: I think that is really interesting because you mentioned that tighter partnership or collaboration with let's say companies that are doing the diagnostics for instance? So you identify the problem, and then after that, somehow you guys can develop an algorithm together to propose what the ideal supplement or ideal drug might be like.

Dr. Goh Wei Jiang: Exactly? Yeah.

Dillon Chew: All right. That, that's really cool. To end off, I just have one last question to ask you. So, our audience is pretty much young scientists, mostly students and a lot of them are aspiring entrepreneurs like yourself. So, if that's one thing that you really want to share, what is that one thing that you want them to take away from your experience?

Dr. Goh Wei Jiang: Yeah. So in our rather short experience as entrepreneurs for six years, I think the one thing that always resonate with us is that it doesn't matter who is right? You have a lot of opinions. You have a lot of advisors. The one person that will always be right will be whoever who pays for the product. So if you have someone who's able to pay for the product, it means that you're onto something. And I think that is the way that we have to be very prudent on, especially in today's climate, everyone's very prudent about their spending. If you can identify a group that's willing to pay for your product, you are onto something. And that's probably the path that you should consider.

Dillon Chew: So thanks so much Wei Jiang for sharing your experiences with CraftHealth and your personal experiences, through school, all the way to your entrepreneurship journey, and I think we really appreciate it.

Outro

Dillon Chew: Stay tuned for monthly podcasts with key stakeholders of the Singapore biotech ecosystem including founders, investors, and policy makers. If you have suggestions for the podcast or who you’d like to hear from, feel free to send us an e-mail in the episode description.

You can also subscribe to our newsletter, the Nucleate Artery on Substack & stay engaged with Singapore’s biotech ecosystem.

Join the Singapore Life Sciences Community Slack channel, powered by Nucleate Singapore, where we are building an open community to enable conversations in the life science ecosystem of Singapore.

📚 Further readings

1. Wei Jiang Goh, PhD, MBA | LinkedIn

2. Craft Health | 3D Printed Personalized Medicines and Supplements |Home

3. Craft Health - NUS Enterprise

4. S'pore's Craft Health the first 3D-printing medicine firm in SEA

5. Interview with Wei Jiang Goh of Craft Health on Personalized Medicine and Nutrition - 3DPrint.com | The Voice of 3D Printing / Additive Manufacturing

If you enjoyed reading this post, comment and give us a like! Or let us know your thoughts here.

Nucleate Singapore’s Ignite Business Development Workshop is back! Whether you’re in a research institute, startup, or biotherapeutics company, come and learn from industry experts on the essential skills and strategies to navigate partnerships, deal-making and sustainable growth. Sign up now by scanning the QR code above or clicking here!

And now, let’s get into the rest of the article! Enjoy!

🍽️ Digestibles

High potential SG research, hot off the press

This month, we cover innovations in pacemaker technology and lung disease treatment, as well as immunotherapies for eye disease, stroke and cancer.

CARDIAC CARE: A Heartbeat That Heals and Disappears

@Senuri De Silva

TL;DR

• Researchers at NUS have developed an injectable, self-powered, and bioresorbable cardiac pacemaker that eliminates the need for wires, batteries, or surgical removal, offering a safer and less invasive solution for temporary heart rhythm management.

Temporary pacemakers are life-saving devices that help keep the heart beating steadily, especially for patients with dangerously slow heart rhythms following surgery or due to underlying cardiovascular conditions. However, traditional pacemakers come with their own problems. They often need open-heart or complicated procedures inside blood vessels to implant and remove, which is risky, especially for children and older adults. There’s also the danger of infections, damage to the heart tissue, and wires or external batteries getting dislodged.

In a groundbreaking advancement, researchers from Department of Biomolecular and Engineering at NUS have developed an injectable, self-powered, bioresorbable cardiac pacemaker that represents a paradigm shift in temporary cardiac support. This wireless device operates without batteries and is controlled optoelectronically using light. Once implanted via a simple injection or minimally invasive catheter, the device delivers effective cardiac pacing and then gradually dissolves in the body after fulfilling its therapeutic function, eliminating the need for surgical removal.

What makes this tiny pacemaker groundbreaking isn’t just its function, but its design. About the size of a grain of rice, it’s made from biodegradable, body-safe materials that allow it to safely power the heart and then naturally break down in the body. The body’s own fluids act like the electrolyte in a battery, helping generate the tiny currents needed to keep the heart beating steadily. A light-sensitive switch lets doctors control the device wirelessly with near-infrared light. All components are enclosed in a biodegradable shell, making it a safe and intelligent solution for short-term heart support.

The system has demonstrated robust performance across multiple preclinical models, including mice, rats, pigs, dogs, and human cardiac tissue models. It can stimulate the heart from a single spot or multiple locations at once, even coordinating between the left and right sides of the heart. Moreover, the team has shown in the human heart that these injectable pacemakers could be paired with other procedures like valve replacements, making heart procedures safer, faster, and more effective for millions of people around the world.

The broader potential of this technology is particularly compelling. Its modular design, biocompatibility, and minimally invasive delivery open new avenues for a wide range of transient bioelectronic therapies; not only in heart conditions but also for nerve and bone healing, wound care, muscle stimulation, and even pain relief. The possibilities are vast: smaller devices, smarter materials that dissolve on demand, safer surgeries, and better ways to fix the device in place, especially in small hearts.

Read more about pacemaker biotech advancements:

• FDA approval of Medtronic's tiny, wireless, minimally invasive pacemaker implant

• Abbott reels in FDA approval for dual-chamber leadless pacemaker

EYE DISEASE: A New Ray of Hope in the Fight Against Blindness

@Senuri De Silva

TL;DR

• Researchers identified PRL3, a protein previously linked to cancer, as being specifically elevated in neovascular eye diseases like AMD and DR.

• The anti-PRL3 antibody, PRL3-zumab, already in Phase II cancer trials, demonstrated superior efficacy and safety in preclinical eye disease models, suggesting strong potential for repurposing as a less invasive, safer treatment for vision loss.

Aging comes with its fair share of challenges; but for millions, one of the most devastating is the slow and irreversible loss of sight. Diseases such as age-related macular degeneration (AMD) and diabetic retinopathy (DR) are among the leading causes of blindness in the elderly. These conditions are driven by a biological process known as neovascularization, where fragile, abnormal blood vessels grow uncontrollably in the eye, leading to leakage of blood and fluid, and gradually destroy vision. Over the past two decades, vascular endothelial growth factor (VEGF) has been identified as a key driver of this pathological process. Anti-VEGF therapies have since become the mainstay of treatment, preserving vision in many patients.

However, several limitations remain. A subset of individuals; particularly those with severe or chronic forms of neovascular AMD show limited or no response to these treatments. Another significant drawback is the method of drug delivery. Current anti-VEGF agents are administered via injection directly into the eye, a procedure that carries the risk of serious ocular complications such as infection, retinal tears, or even permanent damage.

To address these limitations, scientists at the Institute of Molecular and Cell Biology, A*STAR have discovered a potential new avenue for treatment. They identified a protein named Phosphatase of Regenerating Liver 3 (PRL3), previously associated with cancer, as being specifically upregulated in disease-affected eye tissues in models of AMD and DR. Notably, this was observed in both the choroid and retina; two key areas affected in neovascular eye disease.

In mice, when an anti-PRL3 antibody (PRL3-zumab) was administered intravenously in preclinical models, it significantly reduced vascular leakage and abnormal blood vessel growth in the eye. Interestingly, the intravenous route allowed for higher systemic dosing with fewer risks compared to direct injections into the eye. Further supporting its therapeutic potential, PRL3-zumab demonstrated excellent safety in ongoing Phase II clinical trials for cancer, suggesting a strong possibility for repurposing the drug for neovascular eye diseases.

The identification of PRL3 as a therapeutic target introduces a promising alternative to existing anti-VEGF therapies. With the potential to provide comparable or superior efficacy, reduced toxicity, and a less invasive delivery method, PRL3-zumab represents a meaningful step toward safer and more effective management of vision-threatening diseases. While further clinical studies are warranted, this discovery underscores the value of translational science; where insights from one disease area may unlock new solutions in another. For millions at risk of blindness, this innovation could offer a much-needed new line of defense.

Learn more about:

• PRL3-zumab for cancer treatment: having completed a Phase II trial, ASTAR researchers are eyeing fast-track approval for market launch

• Intra-ImmuSG, the A*STAR spin-off advancing the above immunotherapy!

CARDIOVASCULAR DISEASE: Humanized Antibodies as a Potential Stroke Treatment

@Devika Menon

TL;DR

• TRPM4 channels on the cell membrane which are activated during stroke lead to cell death and tissue damage.

• Scientists at the National Neuroscience Institute developed antibodies that target TRPM4, effectively reducing the harmful effects of stroke in animal models.

Face drooping. Arm weakness. Slurred speech.

These physical symptoms appear within minutes, when a stroke is underway.

Inside the cell, chaos ensues quickly. During a stroke, obstruction of blood vessels in the brain leads to ischemia, or interruption of blood flow, resulting in the depletion of oxygen and glucose, which are essential for producing ATP inside cells. In the absence of ATP, membrane channels that pump calcium ions out of the cell no longer function effectively and the ions build up inside the cell.

The TRPM4 (Transient receptor potential melastatin 4) channel- present on the surface of neurons, heart muscle cells, and several other tissues - is activated by these high levels of intracellular calcium ions and leads to an influx of sodium ions into the cell. The excessive amount of sodium ions causes extreme swelling of cells and eventually, cell death. Hence, blocking of these channels has been investigated as a potential form of treatment for stroke patients. However, the existing mouse antibody-based TRPM4 inhibitors have off-target effects, turning scientists towards more specific antibody-based inhibitors which target the human TRPM4 channel.

Scientists at National Neuroscience Institute developed a humanized antibody – grafting the key binding regions of the mouse antibody onto a human antibody framework - that inhibits the channel, reducing the immunogenicity of non-human antibodies. They developed a few humanized antibodies (Ab2-Ab7) with different mutations and selected the top three antibodies (Ab2, Ab4 and Ab6) based on binding affinity. They found that all three variations of the humanized antibodies tested could effectively bind to the channel on human cells and stay stable under heat and acidic conditions. In TRPM4-activated cells, the two most stable antibodies displayed strong inhibition of the channel, almost completely blocking its activity. The inhibitor that was both very stable and most effective at inhibition – named M4H – was chosen for further analysis. In human brain blood vessel cells and mouse models of stroke, it blocked the harmful activity of TRPM4 and cell swelling in damaged brain regions and only under oxygen-limitation. M4H did not display binding to similar channels, tissues in healthy animal brains or under normal oxygen conditions, confirming target specificity and correlated activity with TRPM4 upregulated brain regions.

Stroke is the fourth leading cause of death in Singapore and 80% of these are ischemic strokes. The specificity combined with efficacy of this treatment discussed, places M4H as a potential antibody-based treatment for stroke and other neurological diseases.

Read more about:

• AI-powered triage tool for stroke patients to inform with clinical decision making, developed in Singapore

• Stem-cell based therapy for stroke treatment discovered in Singapore

CANCER: Self-Promoting Immunostimulant Renders Resistant Breast Tumours Susceptible to Immune Killing

@Chua Damien

TL;DR

• Immune checkpoint blockade drugs don’t work against breast tumours that don’t produce enough of the PD-L1 protein due to inhibition by HDACs.

• NUS scientists built a nanomedicine that carries the HDAC inhibitor trichostatin A and photodynamic chlorin e6, wrapped in a PD-L1-binding peptide.

• Each dose boosts PD-L1 levels, creating more docking sites for the next dose, while laser-activated chlorin e6 triggers immunogenic death—rendering resistant tumours susceptible again

Some cancer cells are able to overexpress certain proteins on the cell surface, such as PD-L1, to escape immune destruction. PD-L1 acts as a “don’t-attack” signal in cancer cells by binding to PD-1 receptors on T cells and halting their cancer killing functions. The development of immune checkpoint blockade drugs that target the high levels of PD-L1 disrupted this pathway and allowed immune cells to attack the tumours again, creating new hope for cancer patients. However, some breast cancers subtypes fail to respond to these drugs due to insufficient expression of PD-L1. This happens because enzymes called histone de-acetylases (HDACs) are over-active in these tumours; they epigenetically reduce PD-L1 expression by organising the DNA into tight coils, making the cancer nearly invisible to the immune system and treatment.

A team at the National University of Singapore has built a nanomedicine that tackles this evasion in a single bio-solution that executes three coordinated steps. Each nanoparticle carries trichostatin A (TSA), a well-studied class-I HDAC inhibitor, and chlorin e6, a light-activated photosensitiser widely used in photodynamic therapy; its surface is finished with a small peptide that locks onto any PD-L1 it encounters. Once inside the tumour, TSA loosens DNA coils and boosts PD-L1 expression, providing even more interaction molecules for the next wave of treatment particles to latch on to—a self-reinforcing delivery loop that concentrates the drug precisely where it is needed. A brief laser pulse then activates chlorin e6, releasing bursts of reactive oxygen species that kill cancer cells and creating a tumour micro-environment that is now able to recruit killer immune cells.

Global spending on breast-cancer medicines is projected to reach roughly US $64 billion by 2030, and the broader immunotherapy market could top US $230 billion in the same window. Epigenetic drugs—where TSA already has a clinical pedigree—are forecasted to triple in value over the next decade. Because this nanoparticle uses two agents with established safety records and is built by standard self-assembly, its manufacturing and regulatory hurdles should be modest . The design also dovetails neatly with existing PD-1/PD-L1 antibodies: by intentionally raising PD-L1 levels, this nanomedicine could make those blockbuster biologics work better, echoing recent high-value deals around next-generation checkpoint combinations. Swapping the PD-L1-binding tag for other targeting motifs (HER2, EGFR, αvβ3), the same scaffold could be retuned for pancreatic, ovarian or other immunologically-unresponsive tumours with minimal re-engineering, giving companies a flexible, low-risk entry into multiple fast-growing oncology segments.

LUNG DISEASE: A Natural Fungal Molecule Poised to Improve Lung Scarring Disease

@Chua Damien

TL;DR

• Calcaratarin D, a natural compound from Calcarata fungi, reverses lung scarring in mice by blocking pro-scarring and inflammatory pathways.

Idiopathic pulmonary fibrosis (IPF) is a lethal lung-scarring disease where its progression is fuelled in part by aberrant Wnt signalling; this keeps cells responsible for tissue scarring (known as fibroblasts) locked in a pro-fibrotic state. Currently, only two modestly effective drugs are available for IPF treatment. Fortunately, NUS researchers discovered that a natural product, Calcaratarin D (CalD), isolated from Calcarata fungi, and a natural small-molecule Wnt therapeutic blocker, has broad anti-fibrotic activity to treat IPF.

In an IPF mouse model, CalD treatment cut inflammatory-cell infiltration, collagen deposition and mucus hyper-secretion, improved lung functions, and even reduced mortality compared with untreated controls. Mechanistically, CalD works because it inhibits activation of fibrogenic genes, while simultaneously boosting the lung’s own “brake” signals that stop healthy cells from turning into scar-producing myofibroblasts. At the cellular level, CalD blocks key molecular messengers that would otherwise direct lung cells to undergo more extensive fibrosis. The drug has a reactive chemical “hook” that locks tightly onto protein targets of Wnt signalling that modulate fibrotic activation, giving chemists a clear handle to tweak if they need to fine-tune safety or potency. Earlier research in allergic asthma also found that CalD was able to improve disease and does not harm normal lung tissue, adding confidence that it could one day translate into a safe, effective therapy for people with IPF.

This opportunity is sizeable commercially: analysts project the IPF therapeutics market will climb from roughly US $3–4 billion today to US $6–7.5 billion by 2030. CalD’s first-in-class natural scaffold differentiates it from other pipeline IPF treatments that have stumbled on toxicity issues due to their synthetic design, while CalD’s oral bioavailability and synthesis technology also simplify manufacturing. Since pathological Wnt signalling also drives systemic sclerosis, kidney and cardiac fibrosis, the similar mechanistic concept in CalD could be rapidly re-purposed for multiple indications, extending market runway. Taken together, CalD offers a compelling early-stage asset: a safe, orally active Wnt antagonist that addresses the fibrosis and IPF biotherapeutic pipeline, an area in need of innovative solutions.

🗞️ Industry Spotlight

News from the Singapore life sciences industry

• ClavystBio and A*STAR partner to grow medtech ventures in Singapore.

• US Biotech Elpis Biopharmaceuticals and SGH in collaboration to develop next generation allogeneic CAR technologies.

• Enigma Health, Singapore’s AI spin-off inks MOUs with Roche, ST Engineering to optimize healthcare operations.

• SingHealth Duke-NUS Academic Medical Centre leads S$10m national effort to tackle muscle-loss in ageing Singapore.

• Singapore, Netherlands forge economic ties in medtech, pharma, biotech, and heathtech fields.

• New HealthX Sandbox 2.0 accelerates HealthTech Innovation in Singapore.

• Cytiva’s $1.6B expansion Across Europe, Asia-Pacific, and North America to boost bioprocessing supply.

• DHL opens $14.6m pharma hub in Singapore to meet a critical need for resilient medical supply chains

• Temasek-backed SeaTown invests $115m in Singapore-headquartered healthcare and life sciences firm AddVita.

• Quadria Capital raises $1.4b in oversubscribed Fund III exercise.

• Enigma Health partners with Roche, ST Engineering to boost AI healthcare solutions.

📆 Events happening this month

Workshops

• Nucleate Ignite Business Development Workshop

  (15, 21 & 29 July 2025, 6:00 PM - 8:30 PM, in person)

Conferences

• SuperAI

  (18-19 Jun 2025, 9:00 AM - 5:45 PM, in person)

• Angel Investing: Navigating Opportunities and Risks

  (9-11 Jun 2025, 9:00 AM - 5:30 PM, in person)

Networking events

• Sat Health & Bio Brews Singapore

  (21, 28 Jun 2025, 9:00 AM - 10:30 PM, in person)

• Meet the Drapers Exclusive Networking Event 2025

  (7 Jul 2025, 10:00 AM - 1:30 PM, in person)

• Growth & Grapes – Demo Day and Investor-Partner Networking Night

  (25 Jun 2025, 6:00 PM - 10:00 PM, in person)

Seminars/Panel discussion

• Doubling Down in APAC: Strategies for Pharma Growth

  (28 Jun 2025, 5.00PM - 8.00PM, in person)

• AI for Public Good: Transforming Public Services

  (2 Jul 2025, 4.00PM - 6.00PM, in person)

• FundrACE: Sprint to Series A

  (10 Jul 2025, 2.30PM - 5.00PM, in person)

• Growth hacking and digital marketing for start-ups

  (24 Jul 2025, 11.30AM - 1.30PM, in person)

Episode show notes and transcript

Dr. Abbas Sahili is the CTO of Singzyme, a biotechnology company pioneering next-generation bioconjugation technologies. With a strong background in biochemistry and structural biology, Abbas brings deep scientific expertise and entrepreneurial vision to the field of precision medicine. His transition from academia to biotech leadership is marked by a commitment to developing antibody-drug conjugates (ADCs) that are more efficient, effective, and accessible. Under his leadership, Singzyme has developed a proprietary platform leveraging Peptide Asparaginyl Ligase (PAL) technology, setting a new standard in ADC manufacturing and performance.

📄 Summary

In this episode, Dr. Abbas Sahili walks us through his unique journey from academic research in structural biology to founding Singzyme, a cutting-edge biotech startup. He shares the motivations that led him to pivot from lab-based research to real-world therapeutic development and the founding story of Singzyme.

Dr. Sahili breaks down complex concepts like antibody-drug conjugates and bioconjugation in a way that’s easy to understand. He discusses Singzyme’s PAL technology, a novel enzymatic platform that offers significant advantages over traditional methods, particularly in oncology and diagnostic imaging. He explains how PAL improves efficiency and precision in linking payloads to antibodies, unlocking new possibilities in targeted therapies and radiodiagnostics.

He also sheds light on the operational and strategic challenges faced by a young biotech company and outlines how Singzyme is overcoming them through innovation, industry partnerships, and a strong vision. Looking ahead, Abbas discusses the potential for expanding beyond cancer into other areas like autoimmune and infectious diseases, and the roadmap for product development and partnerships.

🥡 Key Takeaways

• 🔬 From Research to Real Impact
  Dr. Sahili’s academic training in biochemistry and structural biology shaped his scientific approach and inspired his pivot toward translational biotech innovation.

• 🧪 Game-Changing Bioconjugation
  Singzyme’s PAL technology allows for more precise, efficient, and scalable production of ADCs, improving both efficacy and safety of targeted therapies.

• 🧭 Navigating Biotech Growth
  As a company founded in 2021, Singzyme has already hit key milestones in R&D and partnerships. The focus now is on scaling operations and ensuring broad access to novel therapies.

• 🌍 Expanding the Horizon
  Beyond oncology, PAL-based ADCs and diagnostics could have a huge impact in other disease areas. Singzyme’s roadmap includes exploring these unmet medical needs.

💬 Quotes

• “What I found fascinating is that we always think in academia that the business is all about the money, but turns out it's about other people's problem, solving that problem.”

• “Why I wanted to jump is I felt that we had something really interesting, something really valuable that could help a lot of people making their drugs, for example. And I didn't want it to die in some pharma's drawer or forgotten just in a paper because no one picked it up. I really believe in what we are doing and so, at some point you have to take the courage and do it yourself and jump towards it.”

• “Today the main challenge for ADCs is further reducing the toxicity of these ADCs. I'm pretty sure a lot of your auditors actually had or know a patient that suffered from cancer, and the main issue is the toxicity for the patient. Is the patient able to take in the treatment? And very often the patient stop the treatment because it's just too hard for them. And this is something that we can no longer accept in, in the field.”

• “I would say what do you have to lose? You have nothing to lose by trying, you will only learn. There's really nothing to lose in there. Every experience that you have is valuable. And at least you won't regret trying it. Every idea is worth looking into.”

⏱️ Timestamp

• 01:10 – Dr. Sahili’s Background and Academic Journey

• 04:30 – Transition from Research to Entrepreneurship

• 07:00 – Founding Story of Singzyme

• 10:15 – Overview of Antibody-Drug Conjugates (ADCs)

• 13:45 – What Makes PAL Technology Unique

• 17:30 – Challenges in Traditional Bioconjugation Methods

• 21:00 – Application of PAL in Radiodiagnostics

• 24:45 – Singzyme’s Milestones Since 2021

• 28:30 – Partnerships and Industry Collaboration

• 32:15 – Future Expansion Beyond Oncology

• 36:00 – Roadmap for the Next 3–5 Years

• 40:20 – Advice for Young Scientists and Aspiring Founders

🎙️ Transcript

Episode Preview

 Dr. Abbas Sahili: Today the main challenge for ADCs is further reducing the toxicity of these ADCs. I'm pretty sure a lot of your auditors actually had or know a patient that suffered from cancer, and the main issue is the toxicity for the patient. Is the patient able to take in the treatment? And very often the patient stop the treatment because it's just too hard for them. ADCs are really amazing at this. But we can improve it a lot better to bring them to the first line of treatment. And this is what we're trying also to do at Singzyme.

Dillon Chew: Hello, and thank you for joining us on Nucleate Singapore Pulse, Singapore's premier podcast on the biotech ecosystem. I'm your host, Dillon, and whether you're a student thinking about creating your own startup or an industry professional looking for diverse perspectives, this is the podcast for you.

The show notes and transcripts for the episode can be found on nucleatesingapore.substack.com.

Dillon Chew: Hello, and welcome to another episode of the Nucleate Singapore Pulse. Joining us today is Dr. Abbas Sahili, who currently serves as the Chief Technology Officer at Singzyme, which is a startup aimed at revolutionizing the field of therapeutics development and precision medicine through their protein ligation technologies.

Welcome and thank you for joining us, Abbas.

Dr. Abbas Sahili: Thank you for having me.

Dillon Chew: So could you start by sharing a little bit about your background and what led you into the field of biomolecular engineering?

Dr. Abbas Sahili: I was always passionate about biology and how life works. From a very young age. I wanted to be in research in general. And of course in my studies, very early on I was attracted to the field of biochemistry, which is at the crossing of physics, chemistry, and biology. And you have to master all three to understand how the reaction works, how these processes are happening and the different aspects that can affect them.

So from there, it was almost a natural field to go into Enzymology, and that includes of course protein engineering and enzyme engineering in general. And one aspect again of the enzymes or the protein work is understanding how they work and for that we need to access their 3D structures. Because the structure is generally linked to the function of these enzymes, and thus the structural biology aspect of my training, so in biochemistry and structural biology.

Now after my PhD in France, I moved to Singapore, initially working on viral enzymes. Through life, through projects, I got to know about these peptide ligase in the plants that I found really interesting and that could bring me back to the beginning of my studies, which was in Enzymology. So that's how I got hooked onto these enzymes.

Dillon Chew: That's interesting. So, what you did in your postdoc actually linked back up to what you studied in the start?

Dr. Abbas Sahili: Yes, exactly.

Dillon Chew: You mentioned that you studied in France before coming over here. Yeah. And how many years was that ago? About 10. Was it?

Dr. Abbas Sahili: Yeah, 10 years ago. I graduated from my PhD.

Dillon Chew: What was it like transitioning from France over here to Singapore? Were there any differences or challenges along the way?

Dr. Abbas Sahili: The main challenge for me was actually language, although my English is, I would say decent. But when you're thinking in a language and your mother tongue and then you transition to a life and thinking into another language, there's always its challenge.

And I think Singapore is a pretty good place to understand that because everyone comes from somewhere and has a different mother tongue. And so English being the common language here, that is one challenge that I had. But we rather quickly adapt. You try to immerse yourself in a different culture, in different ways and habits, but I was able to actually adapt pretty well and like it.

Dillon Chew: You also mentioned that you did your postdoc over here and you spent quite a bit of time actually in academia before joining Singzyme in about 2021, was it?

Dr. Abbas Sahili: So I joined full time in 2024 last year actually. Previous to that, I was involved in the founding of Singzyme, helping the co-founders, the professors in NTU to set up the company, draft a business plan and actually make it into a business. By doing that, I actually got hooked by the entrepreneurship, and that's how I wanted to transition from academia into the entrepreneurship, into a company and to make what we were discovering in the lab into a product that we can sell or use for therapeutics.

Dillon Chew: Right. So during your postdoctoral phase, was there actually any sort of like moment or inspiration that kind of triggered you to say like, Hey, I wanna start exploring entrepreneurship. Because I think many a times, most people in academia, the goal is always to go for a tenured position. A professor position. So was there any such moments for you?

Dr. Abbas Sahili: So after the publication of the first article where I was a co-author on these enzymes, we were doing a patent disclosure to the university and that engages you into a process where you have to do basically a training of entrepreneurship. It's called the Lean Launchpad program in collaboration with NUS, for example, or the bootcamps that are happening at the CREATE institute. And along these, I met with certain professionals, certain people who are teaching us what is a business plan, what is a business, what's the point of doing that.

And this is where I actually got the virus of it, because I was meeting people who were interesting and interested in my idea. During the course of patenting the family of enzyme to use for protein ligation, I was involved in bootcamps and the Lean Launchpad with NUS. And I met mentors and people in those programs who introduced us to the business field. What I found fascinating is that we always think in academia that the business is all about the money, but turns out it's about other people's problem, solving that problem.

And this is something that even including in my studies, was always at the core of what I like to do, which is solving the problem, solving the puzzle, answering that question. The question may be different, but the process is the same. And this is something that really piqued my interest and thus I wanted to do that for entrepreneurship.

Another reason why I wanted to jump is I felt that we had something really interesting, something really valuable that could help a lot of people making their drugs, for example. And I didn't want it to die in some pharma's drawer or forgotten just in a paper because no one picked it up. I really believe in what we are doing and so, at some point you have to take the courage and do it yourself and jump towards it.

Dillon Chew: I guess the starting point is kind of meeting people who share the same interests, such as the launchpad programs. Right. Because you know this, it is pretty much a self-selecting group, right?

Dr. Abbas Sahili: Yes.

Dillon Chew: And especially at the postdoctoral level where most of the time you are actually in the lab. You actually have to take extra time out to do all these things.

Dr. Abbas Sahili: Absolutely. It was a lot of Saturdays and Sundays work, doing interviews in the night with other side of the world. To understand what is the field like? Is there a need for what we were proposing? Does it solve a solution? And is anyone willing to pay for it? You encounter people with very diverse backgrounds.

Dillon Chew: I think that's really great to hear. So I also wanted to move on and touch a little bit about Singzyme, because that's really where you're at right now and that's really the core of this conversation. So you've just mentioned that you were part of actually the founding team. You've helped to draft the business plans and all that. So I think before we even start talking about Singzyme and technology, I think what's great is if you could share a little bit about the story behind Singzyme? How did you guys come about, you know, what was really behind the company?

Dr. Abbas Sahili: So it's actually a beautiful Singaporean story because in 2014, a group led by Professor James Tam from NTU discovers that some of the medicinal plants, the traditional Chinese medicinal plants used contain cyclic peptides.

But the cyclic peptides were not produced by any known enzyme, and , they found that they were close to a family of peptidases, that were supposed to do protease activity. So cleave a peptide bond, and they had a little bit of knowledge that in some cases, these enzymes were able to perform a ligation reaction. But that was a very rare and almost parasitic reaction. Now they kept digging and they found that one of these enzymes, and that was the first enzyme discovered called butelase-1 was actually responsible to cyclize of the cyclization of these peptides. And that's what led to the discovery of this family of enzymes that today we call PALs or Peptide Asparaginyl Ligases.

Now, why I say it's a Singapore study is because it could have only been discovered in Singapore because that original plant, the blue pea flower, is originating from the Malaysian Peninsula. It's widely known in here, and it was found in NTU garden. So it's actually a beautiful story to say, well, this is something that could not have emerged from another place had it not been for this beautiful flower. And from there we discovered a whole variety of these enzymes, and now we're using some of them in our conjugation process.

Dillon Chew: That's really inspiring. Yeah. So I guess, you know, you've also mentioned just now, that you have your technology, but you really need to understand the problem. So, what exactly is that specific unmet need that Singzyme aims to address?

Dr. Abbas Sahili: So this is where the co-founders of Singzyme, Prof Liu Chuan Fa and Prof Lesc ar from NTU understood very early on is you could sell these enzymes as reagent for people to attach proteins together.

But that generally, is not the most valuable application as a reagent company. But rather, there was a need at that moment of being able to attach a drug to an antibody specifically at a known place in order to create a clean antibody drug conjugate. At that moment, antibody drug conjugates were getting hot, but not as hot as it is today as a field. And so it was answering a problem, where a number of conjugation technologies do exist, but they very often rely on a lot of chemistry. They are producing molecules that are heterogeneous in their nature. Some of them are highly conjugated, some of them are not conjugated.

And the so-called site-specific conjugations that were available were good, but were not good enough in our opinion, including the ones that use enzymes because then the enzymes that are used are very complex to produce, or require a lot of modification to the antibody or the sites of attachments are not optimal.

What we could do with these enzymes, that we discovered with the PAL, no other system could do right. And produce something that would really fit the need for antibody drug conjugates. Now, ADCs in general, are amazing molecules. They're really revolutionizing the cancer treatment, but the way we manufacture them is not always scalable.

Today the main challenge for ADCs is further reducing the toxicity of these ADCs. I'm pretty sure a lot of your auditors actually had or know a patient that suffered from cancer, and the main issue is the toxicity for the patient.

Is the patient able to take in the treatment? And very often the patient stop the treatment because it's just too hard for them. And this is something that we can no longer accept in, in the field. And that's why we're looking for drugs that are of course, very efficient, very powerful against the disease, but at the same time that preserve the quality of life of the patient. ADCs are really amazing at this. But we can improve it a lot better to bring them to the first line of treatment. And this is what we're trying also to do at Singzyme.

Dillon Chew: Sure. And I guess at the core of it is the PAL technology that you've mentioned, right?

Dr. Abbas Sahili: Yes.

Dillon Chew: Can you briefly just explain, you know, I think you've talked about the bio conjugation aspect of it.

Dr. Abbas Sahili: Yeah.

Dillon Chew: But , what's so unique specifically about the PAL technology?

Dr. Abbas Sahili: So the PAL, as the name indicates, Peptide Asparaginyl Ligases. It only requires three amino acid, an asparagine followed by two amino acids that can be a number of combinations. The specificity is well defined in our research. We understood it very well, but it can be a number of residues there. So it has a very small requirement of a sequence compared to other enzymes that require generally much longer sequences. I'm thinking for example, sortase- A. This is one of the first ligases discovered and it requires five amino acids on one side and then another five glycine s on the other side to do the conjugation. So you have 10 amino acids required. In the case of these enzymes, only three are required. And that makes it small enough to add to an antibody or any other protein and be able to perform the conjugation efficiently, without being too common in the protein to have unspecific reactions. So it's really a sweet spot there.

The second aspect of it is very early on, these enzymes are amazingly efficient. One enzyme per hundred or a thousand substrate like protein two conjugate And the conjugation happens within minutes or an hour, or two maximum. So you do not need a lot of enzyme to perform the ligation. You don't need a lot of time, you don't need a co-factor. There's no need for extra energy added or anything like that. It's really adding the protein to ligate. The element to ligate to that protein, and then the enzyme, you leave it for an hour, for example, and at the end the conjugation reaction is, is done. And this is something that is scalable, is easy to use and simplifies the whole manufacturing without the requirement of a lot of chemistry in the process. So this is something really unique in the world to have.

Dillon Chew: Right. You've mentioned a little bit about how it works and it kind of gets me thinking, I think it was just last year or two years ago where, the Nobel Prize in Chemistry was on biorthogonal click chemistry. So, I just wanna understand, because  biorthogonal click chemistry essentially accomplishes bioconjugation. And I think the difference is instead of using amino acids, they're using things like alkynes, certain functionality groups. So, what makes it different in this case, or maybe what makes it superior to some extent?

Dr. Abbas Sahili: So. There are different aspects, mostly on the application part. If you wanted to do a click chemistry on an antibody, for example, or a protein, we need to insert somewhere in that protein, the one pair of the click, what we call click handles. And that is by itself, modification of that protein. So whether we are able to do it genetically, that's not always easy. That reduces the yields.

On the other hand of the reaction on the click reaction, the alkynes, the one that work really well, are generally quite big. There's a lot of cycles in there. I'm not chemist, by training. I'm a biochemist, so of course I always vouch for, for biochemistry, but from a chemical point of view, those are complex molecules. They bring in hydrophobicity. They have a certain cost because these technologies are also protected by IP. So not everyone can can use it. Of course, ours is also protected by IP. But that reaction of conjugation, despite the name click is actually not that easy. You still have to leave it overnight in quite large amounts in order for the reaction to be efficient.

Ours requires a lot less amount of the different elements to attach. And it's done in an hour instead of overnight. So when we compared our conjugation to the click chemistry, to the sortase, to other enzymes out there, we thought it was always easier to use ours compared to all these technologies, it was always cheaper as well. So this is where we are a class apart in this field.

Dillon Chew: But I will say if you were factor in the production of the PAL, for instance, would that really dramatically increase the cost of the reaction?

Dr. Abbas Sahili: Yeah. In the course of the 10 years of work on these enzymes, we engineered them. So we made them extremely efficient, which help reduce the amount of enzyme that we use in the reaction. We also immobilize the enzyme in order to be able to recover it, reuse it, and thus divide the cost by a lot for the usage. So another element to add is the amount of what we call the payload, or one of the elements that we want to attach to the protein is also the requirement for it, is also reduced to have an efficient ligation reaction.

So even if we had a small cost added for the enzyme to be produced. The reduction of the cost in all the other elements is so big that you're winning at the end by using a conjugation technology versus another one in terms of manufacturing, actually the added cost is, is ridiculously small, and the advantage that it brings is so big that it's a winning for sure. It's a no-brainer to use our technology.

Dillon Chew: And I also do have another question. I just wanna understand because there are many different bio conjugation methods. And so, how do these methods actually influence the final product or the therapeutic efficacy? Because I think just now you briefly mentioned about the homogeneity of the final product? So, you know, to what extent of this actually determined by the conjugation process?

Dr. Abbas Sahili: So the final product is affected. For the antibody drug conjugate ,it's affected by the location of the conjugation, the nature of the linkage, the stability in circulation. And that is for a given antibody and a given payload. And this is where there's a lot of research happening today. The payloads are known, and we're looking for new types of payloads, of course, with a different mode of action in order to overcome resistances. But we take the known aspects of an antibody drug conjugate today.

For a lot of these technologies, the conjugation site makes it or breaks the ADCs to give a good molecule. Because if it's too exposed to the environment, we'll have a faster degradation. Or more off target toxicities just due to the fact that the payload is accessible to the environment to interact with .

On the opposite side, if the payload is too hidden or too stably connected to the antibody, then we have on-target toxicities in other tissues that are uptaking that antibody specifically or un specifically through a number of receptors. So it's always a balance. And honestly, ADCs are always like, that is balancing multiple players. At the same time, between all the different toxicities and the efficacy of the ADC in the body. So one has to always think about all the different aspects of that.

Dillon Chew: Great. So I think since you've been talking a little bit about the ADCs, would you be able to share with us a little bit about your product pipeline? I think in particular you've mentioned about the ADCs, but are there anything else that you guys are looking at?

Dr. Abbas Sahili: So, since the platform allows us to have a protein glue, we can attach any type of molecule to any type of proteins. We often talk about ADCs because that's the most difficult application, at least for our conjugation technology, and the most trendy in the current field. But our conjugation technology allows us to do a number of things beyond antibody drug conjugate.

So, one aspect that is really interesting to me is the antibody radio element conjugation. And this is something where our platform's efficiency allow us to do reactions in a few minutes, which is not allowed by other technologies that require a long time. And that translates into a shorter reaction time. So, the product is usable, but at the same time we're protecting the manufacturer.

The operator making the conjugation reaction would require less exposure. We're opening the door for shorter half-life radio elements, for example, for diagnostics. This is something that is quite interesting and we're reducing also the amount of radio element required to produce the radio conjugate because then we could use as much radio element as we want of antibody or nanobody radio conjugate. And in this case, we eliminate or reduce greatly the waste, the radioactive waste. So there is an impact on the whole manufacturing chain there. This is one aspect.

Another type of conjugation that we can do that works pretty well is with RNA or DNA conjugate . And that again works really well. We eliminate the requirement for a lot of RNA to be able to perform the conjugation efficiently while bringing the advantages from the ADC, which is better stability, site specificity, better tumor penetration or tissue penetration of our conjugate to bring in the efficient dose into the final tissue.

Dillon Chew: So this conjugate you're talking about is a antibody with an RNA?

Dr. Abbas Sahili: Yes. So for this we have a proof of concept that we are able to do the conjugation really well, but we are not expert in RNA therapeutic in this case. So we always are looking for partners who are looking into conjugating their RNA to an antibody or to another protein to perform that.

But at least we know that this works really well with our platform. So these are the aspects there. And even beyond that, we're still coming back to the oncology field, I think in the inflammation disease, it's something where conjugates, whether antibody or others can also bring a bunch because of the targeting to a specific tissue. Bring it just to these cells, so that we can actually lower the dose and bring in good amount of effect.

Dillon Chew: So I think I would say that you guys are playing therapeutics, theranostics, to some extent also.

Dr. Abbas Sahili: Yes, absolutely.

Dillon Chew: As well as going even maybe to vaccines where you're looking at like RNA and things like that.

Dr. Abbas Sahili: Yes.

Dillon Chew: Wow.

Dr. Abbas Sahili: Or RNA therapeutic, where there's a number of generally rare disease that require these type of conjugates. And this is thanks to the fact that we are a platform. We do not eliminate any proteins. We've had examples of conjugation published already about that.

Dillon Chew: Right.

You've talked about your platform, but, at Singzyme, do you guys also do any sort of like design of the end product itself?

And because like what you've mentioned, you know, the ADC space is getting more and more competitive right now. So what sort of innovations actually being done in the ADC design space, for instance?

Dr. Abbas Sahili: So in our case, we went back to the board. We looked at disease areas, indications in cancer because we have to reach the clinic with our conjugation.

And we identified indications where product with the current technologies or the technologies that are available there would probably not be successful because of the reasons of too high toxicity, lack of efficiency. So we identified targets that could benefit greatly from our conjugation end product, conjugation ADC. And we identified the right payload for that indication. We combine the antibody with the right payload, with our conjugation, and then we apply it for, for that indication. So we're looking for colorectal cancer, pancreatic cancer, and also prostate cancer where we can actually have an effect on those indications and have a product that can benefit the patient ultimately.

Dillon Chew: Thanks so much for sharing. Yeah. So it seems that you have quite a lot in your pipeline ready to go for the next couple of years?

Dr. Abbas Sahili: Yes. So we have three to four assets that are in the pipeline right now that we would like to focus on. And we're also partnering with universities in Europe for the radio conjugates on a diagnostic tools for example, that also help these universities to do the diagnostics and develop their tools for radio conjugate.

Dillon Chew: Are you comfortable to share these assets, where are they at currently in the entire lifecycle of the drug?

Dr. Abbas Sahili: So, we're currently in preclinical, which means that we have proof of concept in vitro. Of course. And we are now putting them in the animals. We have for some of them early results that it works pretty well. But this is where we touch the core issue of all biotechs, is to get the funding to support all these preclinical studies and the toxicity studies to reach the IND stage. At which we can then pass these assets to a pharma company or have people who are expert in taking a molecule to the patient be able to take charge of that.

Dillon Chew: So I think one thing that you've just mentioned was that at the end of the day you guys would need to have the asset. And what's really critical would be that these assets are protected based on IP, right? So, for example, the enzymes that you've mentioned, like PAL. They can actually be found in nature and I would say hypothetically, there could be other similar enzymes that could also facilitate similar catalytic reactions. And on the asset side, there, there could be an infinite combination of bioconjugation technologies, linkers payloads and all that.

So, could you be able to share what the IP strategy looks like to protect our innovation in this really, really crowded space?

Dr. Abbas Sahili: So for these enzymes of course because they are present in multiple plants. One could think that, okay, I'm just gonna take another enzyme and make it work. It's not that trivial. That's one aspect.

The second aspect is that in our IP protection, we try to protect not only one enzyme with one sequence, but rather a family of enzymes. And as I mentioned earlier, we actually engineered them in order to improve their efficacy. So, an enzyme found in the plant could not be used. You have to recombinantly express it. That's the first thing, which is the first challenge. And the second challenge is actually to bring it to a level of activity that is scalable and usable.

The second avenue is of course to protect not only the enzyme itself, but also the use cases of it. So that's how we try to protect our IP around that.

Now, on the asset side, of course, we don't just take an antibody that is commercially available. For one, we have to engineer that antibody, but also, we do a discovery of antibodies against the targets that we identified as interesting for the indications that we are interested in. We raise an antibody, and that antibody is then proprietary to Singzyme. And that's what is also protected along with the conjugate.

Dillon Chew: Sure. With the rise of AI recently in the whole protein design space, does it really affect how you guys have been operating so far?

Dr. Abbas Sahili: So of course every one of us is using ChatGPT a lot lately and all the different AI tools that are available. You whether embrace it or die type of thing. So in our case, for the research part, of course we use as researchers, but in terms of the discovery, because we have to be a little bit careful, we're looking at antibodies. We don't have yet implemented any AI in our antibody discovery because we take advantage of CROs, Contract Research Organization that are discovering the antibody.

And I think that overall, AI will at some point come to that field where you just design an antibody denovo against that target and that works. But today we would still prefer to go through phage libraries, for example, is something I like, so that we prevent the animals from being hurt, but also mice and rabbit libraries. And then humanize those antibodies. This is currently our strategy.

I think we need more examples of success of drugs from these AI company, pure AI players in order for people to accept that a new payload or a new antibody or a new linker or something like that coming from that pure AI company is something that we can go for safely.

As a young biotech, we are already bringing in innovation, which is our platform. If we bring in too many innovations, there are way too much risk and we have to, to mitigate that risk for sure early on.

Dillon Chew: Yeah. Because if you were to draw parallels, there are many or rather some good success stories, right in the enzyme engineering field, right. Let's say, you know, to catalyze certain reactions or to get rid of plastics and things like that. Yes. So, would you say that antibody is still far away?

Dr. Abbas Sahili: I don't think it's far away. I think that it's coming. I think that a number of examples mm-hmm where successful engineering, has been done. De novo is a lot more difficult. There's a number of ifs there that has to be solved. There's a number of cases where the targets that we're raising antibodies against, we do not have a structure for it, including a structure from AlphaFold is not a guarantee for proper folding.

So raising an antibody, using a structure from an AI model is a little bit dangerous and will have a lot of risk failure.

Dillon Chew: That's really insightful. I guess it's always good to know what the key limitations are despite all the big hype out there right now in the media.

Dr. Abbas Sahili: I think AI is really good for doing a repetitive task very quickly and being able to screen a number of proposition that we feed to the AI. But we have to be in control of the outcome because of the input. And of course, not trust the outcome blindly. It's not gonna be a problem for therapeutic because if it doesn't work, it doesn't work, but rather a loss of time for the people waiting for it.

Dillon Chew: Well, that, that's really, really insightful. I guess because from some of our previous podcasts, I think a lot of I would say investors, they tend to hop on to this kind of trendy topics. In the sense that you have a biotech and the moment you add AI, it gets the investors attention. But I'm glad you guys stay true to your basics and your fundamentals.

Dr. Abbas Sahili: Yeah. At the end, it is the science that speaks. It's the results that speak. You need something that makes sense as a final product rather than just a nice catchy tool name in there.

Dillon Chew: So I also like to move on a little bit and touch about your assets. I guess the next step of your assets is then to know how, then you start moving on to your preclinical and clinical studies. So we've learned that you've also had a partnership with Lonza on using them like a CDMO to be able to scale up your manufacturing processes. So, how has Singzyme actually approached forming this type of strategic partnerships with big players like Lonza, you know, to facilitate your commercialization and scaling up?

Dr. Abbas Sahili: This is where Singapore's ecosystem is quite interesting because it was actually during our mentorship from the early days of the company, looking for key players to talk to.

We were introduced to people in Lonza who were aware of the power of the Singapore ecosystem, who were interested at that moment. A bit of serendipity there where we actually met them and they were like, okay, we're looking into building this toolbox, of theirs in the early discovery for bio-conjugates. And well, your technology could be a right fit. So this is how the collaboration started.

Today, if a drug developer is looking for a conjugation technology and they approach Lonza, ours is a proposition and they can use this conjugation technology.

In this case, Lonza is our preferred CDMO because they have already the technology. They know how it works and they have the expertise to bring bio-conjugate from an idea all the way to the market.

Dillon Chew: And maybe just one thing to ask because you guys are mainly working at the discovery stage. So, that transition between connecting the discovery and the CMCs. Is that something that you guys are actively doing or is that in partnership with some of the big CDMO players?

Dr. Abbas Sahili: We, today, as a small biotech, we have to rely on these big CDMO players. They have the experience, they know where the caveats and the pitfalls for a number of companies. So we rely on those partners to be able to bridge that knowledge gap between what we know, what we are able to do in a lab and what they have to do in order to secure a supply of good products for the clinic later on.

Dillon Chew: Of course going past preclinical or even going to clinical is one challenge. But the other challenge is always the manufacturing of the asset and that always becomes a big killer.

Dr. Abbas Sahili: Yes.

Dillon Chew: So in your case, apart from the PAL platform that really helps to accelerate that, do you see any other potential threats that might actually cause that ADC asset of yours to be harder to produce at the end of the day?

Dr. Abbas Sahili: So this is where very early on with our discussion with Lonza, we took the problem the other way around. We started looking at the manufacturing, what are the issues of manufacturing of ADC. And how we can solve them. We always had in mind not to modify at all or as little as possible the current ADC manufacturing. If we had to modify it, it would be to simplify it rather than to add a complexity there.

This, at the end, allow us to date to move more securely into manufacturing. We can say, well, the road is well defined because we will not take any new way of manufacturing in this case. So we really learned from the giants that were before us of course, but also all the other biotechs that went before us into the clinic and into manufacturing. To be like, that is going to be costly and it's not doable. This is too complex, the CDMO is just not gonna do. This is too dangerous and that will not produce a product in the end that makes sense. So by doing that and then coming to the asset side simplifies the future of the company.

Which is actually a lot of companies do not do that. They try to rush for something that is efficient, and then they start thinking, how can I manufacture that? And then by the time they solve all their CMC issues, they run out of funding in general. We went the other route. A little bit by accident by meeting Lonza, but that proved to be a good thing in the end.

Dillon Chew: I guess that's a really important meet with Lonza, right? That really helped you guys to move forward.

Dr. Abbas Sahili: Yes.

Dillon Chew: Beyond oncology, I think you've mentioned a little bit about the inflammation type of diseases? So, are there any other spaces that you guys are actually planning to play in or any other unmet medical needs that you're thinking of pursuing?

Dr. Abbas Sahili: In terms of possiblities, sky is the limit in this case. So we are open to anything after approving clinically that our conjugation is as safe as we think about it. We know from other examples of other ligases that the risk is actually quite low. But we still have to prove it in the clinic, as I mentioned. At the end, the result has to speak. So we need to reach that that level. But beyond that, large number of applications can be used with these enzymes from manufacturing, vaccines, antimicrobials, or inflammation or metabolic disease. Conjugates is something that of course we would be able to do quite easily.

Dillon Chew: Right. And I guess, you know, being in Singapore, very often we are always thinking about, when you're gonna get clinical approval, you go to FDA first. So is that the strategy that you guys are thinking of right now?

Dr. Abbas Sahili: So FDA is always the go-to thing because it has the highest standards. And this is the one that approves it for everyone. Now, the American market is also the biggest market so having an FDA approval is also a good sign for future in terms of revenue for a company. But that should not limit people to focus only on the FDA approval, but have something where you have to look everywhere. China, Japan, Europe as well, India and Australia.

Dillon Chew: So are there any plans for Singzyme to actually expand your footprint beyond Singapore for now?

Dr. Abbas Sahili: We prefer to do that with partners in the US or in China or in Europe, rather than expand ourselves. Because that would require stretching your resources and complexifies the whole structure of the company. But at the end of the day, money decides. So if you have enough funding and you're able to establish a base in the US and or in China or Japan, you would have to do that.

Dillon Chew: Sure. Thanks so much for sharing the entire journey from discovery all the way until where you guys at and what you really hope to achieve. So, before we close, I also wanna understand a little bit, you've been with Singzyme since they started. Right now you're the CTO, what do you think is the biggest challenge you have faced since the start of Singzyme?

Dr. Abbas Sahili: Transitioning from an academic mindset to an entrepreneurial mindset, where it's no longer about making a nice paper having the right set of data for the publication, but rather having the right set of data to convince other stakeholders that this is valuable and this is the right way to go. The two are often overlapping, but not always. So changing that mindset is always a challenge, but it's an exhilarating one.

Dillon Chew: That's great to hear. I believe that a lot of the listeners here, a lot of them are potential entrepreneurs, or early career scientists or researchers. And a lot of them are actually planning going to biotech. So I guess we'll end off, if there's any one advice you would give for some of these potential listeners who are really interested to go into the biotech entrepreneurial space?

Dr. Abbas Sahili: I would say what do you have to lose? You have nothing to lose by trying, you will only learn. There's really nothing to lose in there. Every experience that you have is valuable. And at least you won't regret trying it. Every idea is worth looking into. If you're able to make it, you'll be happy. If you don't make it, you'll also be happy because you would've learned a lot of things that will be useful to you in your future career, whatever it may be.

Dillon Chew: That's really, really insightful. So, yeah, thanks a lot Abbas for your generous sharing about Singzyme as well as your personal journey and I believe that a lot of our listeners would definitely be inspired after listening to what we've discussed today.

Dr. Abbas Sahili: Thank you very much. It was a pleasure.

Dillon Chew: Thank you.

Outro

Dillon Chew: Stay tuned for monthly podcasts with key stakeholders of the Singapore biotech ecosystem including founders, investors, and policy makers. If you have suggestions for the podcast or who you’d like to hear from, feel free to send us an e-mail in the episode description.

You can also subscribe to our newsletter, the Nucleate Artery on Substack & stay engaged with Singapore’s biotech ecosystem.

Join the Singapore Life Sciences Community Slack channel, powered by Nucleate Singapore, where we are building an open community to enable conversations in the life science ecosystem of Singapore.

📚 Further readings

1. Abbas Sahili | Linkedin

2. Singzyme

3. A Cascade Enzymatic Reaction Scheme for Irreversible Transpeptidative Protein Ligation

4. Lonza and Singzyme Enter Bioconjugates Partnership

5. Bioconjugation Technology Selection during Early-Stage Development - A Strategy to Streamline IND and Manufacturing Timelines » ADC Review

If you enjoyed reading this post, comment and give us a like! Or let us know your thoughts here.

Meet the Startups is back! This time, we’re delighted to have two trailblazers in the therapeutics space share their startup journeys. Whether you’re a student, researcher, or aspiring founder, come hear from Harshyaa and Mathieu, connect with like-minded folks, and unwind over refreshments! Register now!

Are you a student or scientist passionate about venture creation, talent development, and building collaborative relationships? Join the Nucleate Singapore leadership team and be part of a dynamic team driving innovation in the life sciences sector! Check out our open positions for the coming term and apply here. We can’t wait to hear from you!

And now, let’s get into the rest of the article! Enjoy!

🍽️ Digestibles

High potential SG research, hot off the press

This month, we cover innovations in cancer, tissue regeneration, autoimmune and lung disease.

CANCER: A new model that predicts liver cancer recurrence with high accuracy

@Senuri De Silva

TL;DR

• Scientists at IMCB, A*STAR found that increased infiltration of natural killer cells into liver tumours were associated with lower recurrence rates

• They also found that the SPON2 protein (alongside 4 other markers) boosted NK cell activity and anti-tumour immunity

• Using these markers, they developed a predictive model that outperformed existing options, offering a powerful approach for early detection and management of recurrence.

Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer. Even after successful surgical removal of the tumor, up to 70% of patients experience cancer recurrence, which remains a major clinical challenge. Current tools—such as tumor staging systems (TNM, BCLC) and molecular biomarkers—help predict recurrence risk, but their accuracy is limited, especially in early-stage HCC. One reason for this limitation may be that these tools do not capture the spatial complexity and immune interactions within the tumor microenvironment.

To tackle this, researchers at A*STAR IMCB analyzed the spatial proteomic and transcriptomic profiles of tumors from both recurrent and non-recurrent HCC patients. A key finding was that patients whose tumors had high infiltration of natural killer (NK) cells at the invasive edge were less likely to experience recurrence.

Digging deeper using mouse models, the team showed that a protein called Spondin 2 (SPON2), when expressed specifically in NK cells, boosted their migration, interferon production, and overall tumor-killing ability. This protein also enhanced NK cell interactions with T cells, further strengthening anti-tumor immunity. Building on this insight, the researchers incorporated SPON2 with four additional spatially resolved markers—ZFP36L2, ZFP36, VIM and HLA-DRB1—to develop a predictive model called the Tumor Immune MicroEnvironment Spatial (TIMES) score for diagnostic use. The TIMES score achieved 82.2% accuracy and 85.7% specificity in predicting HCC recurrence—outperforming existing clinical tools like the TNM and BCLC staging systems. Moreover, TIMES score was validated in 231 patients across five independent clinical cohorts, showing its reliability in real-world scenarios.

This study not only reveals a powerful SPON2-driven immune mechanism in NK cells but also showcases the TIMES score as a promising leap toward spatially informed, precision diagnostics for HCC recurrence. By capturing the overlooked complexity of the tumor microenvironment, this approach paves the way for smarter surveillance and personalized immunotherapy strategies that could redefine how we manage liver cancer.

Learn about HCC biotech updates:

• Boston Scientific picks up chemotherapy infusion implant maker aimed at inoperable liver tumors.

• Tempest granted fast track designation from the US FDA for Amezalpat to treat patients with HCC.

• MAIA Biotechnology announces clinical supply agreement with Beigene for upcoming phase 2 trials in three cancer indications including HCC, small cell lung cancer and colorectal cancer.

CANCER: Harnessing analytical chemistry and AI for in-situ diagnosis and metabolic profiling of brain cancers

@Chua Damien

TL;DR

• NUS researchers used an advanced imaging technology called Stimulated Raman Scattering to create detailed, label-free maps of tumor metabolism, distinguishing between less and more aggressive brain cancers based on their unique molecular features.

• AI trained with these maps can now detect and classify tumors with an incredible 99.6% accuracy, providing a fast, non-invasive tool for cancer diagnosis and personalized treatment.

  

Cancer cells reprogram their metabolism to support rapid growth, and these metabolic shifts are closely linked to treatment outcomes in many cancers. Yet, detecting these changes in situ—directly within the living tissue—has remained a major challenge, with current diagnosis methods still relying on invasive biopsies. Researchers from NUS have addressed this limitation by developing an advanced imaging approach that combines hyperspectral stimulated Raman scattering (SRS) with biochemical spectral modeling, enabling the creation of detailed, label-free metabolic maps of human brain tumors with unprecedented precision.

Stimulated Raman Scattering (SRS) is an imaging method that uses two synchronized laser beams to amplify the tiny vibrations of specific chemical bonds, producing clear, real-time pictures of molecules like proteins and fats. Because it works without any dyes or labels, SRS lets researchers observe the natural chemistry of cells and tissues as they live and function. By analyzing the intrinsic Raman signatures of lipids, proteins, DNA, and cofactors like FAD/NADH, the team revealed distinct metabolic fingerprints differentiating low-grade slow-growing brain cancers from aggressive glioblastomas. Specifically, they found that high-grade tumors showed elevated protein, DNA, and cholesterol levels alongside a reduced FAD/NADH redox ratio—all of which are hallmarks of a pro-malignant state.

Beyond metabolic insights, the researchers trained a neural-network classifier on 4,547 SRS spectra, achieving an impressive 99.6% accuracy in tumor detection and grading. This rapid, spatially resolved platform not only promises to enhance histopathology by reducing reliance on stains and labels but also opens avenues for metabolome-targeted diagnostics and precision oncology. As biotech firms seek robust, non-invasive tools for early cancer detection and therapy monitoring, this SRS-based approach stands out for its speed, specificity, and compatibility with existing clinical workflows.

Learn more about other Raman scattering-based spin-offs:

• Surfaced-enhanced Raman scattering (SERS) used for COVID-testing breathalyzer

TISSUE REGENERATION: New targets that prevent cellular stress-induced hair loss

@Senuri De Silva

TL;DR

• Duke-NUS scientists found that a protein named MCL-1 protects activated hair follicle stem cells from stress-induced death, allowing proper hair regrowth.

• Loss of MCL-1 leads to hair loss in mice, but this can be reversed by activating the ERBB signalling pathway or by reducing pro-death signals like Bak.

Losing hair over work? So are your hair follicle stem cells. They are not only responsible for growing hair, but also helping to heal wounds and maintain healthy skin. But activating them, like during hair regrowth, comes with a cost: stress. Without proper survival signals, this stress can trigger cell death, eventually leading to hair loss. The BCL-2 family of proteins helps protect these stem cells, but studying them has been difficult— as completely inactivating some of them can be lethal early in development, making it hard to untangle their specific roles

Fortunately, researchers from Duke-NUS have identified MCL-1, a critical survival protein from the BCL-2 family that plays a unique survival role in hair follicle stem cells and is not lethal when inactivated. When they deleted MCL-1 from skin cells in mice, hair still grew at first, but over time, stem cells slowly died as they cycled naturally, eventually leading to hair thinning. This slow decline is likely due to the asynchronous nature of hair growth cycles across follicles. However, when patches of hair were removed, triggering synchronized stem cell activation for regrowth, the absence of MCL-1 caused a much sharper effect: stem cells died rapidly, and hair regrowth failed completely. This revealed that MCL-1 is crucial for protecting hair follicle stem cells when they become active.

Digging deeper, the scientists found that the ERBB signaling pathway plays a key role in safeguarding hair follicle stem cells by regulating the survival protein MCL‑1. ERBB signaling directly increases the levels of MCL‑1 protein, particularly during critical windows of hair follicle regression and apoptosis, when stem cells are especially vulnerable. In parallel, the researchers uncovered that BAK, a well-known pro-death protein, acts as a major driver of apoptosis in hair follicles when MCL‑1 is absent. Strikingly, deleting just one copy of the Bak gene was sufficient to fully rescue hair regeneration and preserve the hair follicle stem cell pool, even in the complete absence of MCL‑1.

In conclusion, MCL-1 is essential for shielding hair follicle stem cells from stress when they become active, enabling proper hair growth and tissue regeneration. MCL-1 activity is also supported by ERBB signalling and antagonised by Bak protein activity, offering insights into multiple potential targets for the development of new regenerative treatments in hair growth and skin healing.

Learn more about cutting edge therapies for hair growth:

• TRI-K’s new biotech ingredients address hair thinning and skin sensitivity

• Copper peptides for hair growth launched by Limitless Biotech

• Mallia Therapeutics and Northway Biotech partner to produce CD83 protein for hair loss treatment.

• Hair loss and disruptive tech: how stem cell treatments can deliver?

AUTOIMMUNE DISEASE: Utilizing a biomimetic nanodrug to reprogramme immune responses in rheumatoid arthritis

@Chua Damien

TL;DR:

• NUS researchers developed a macrophage-mimicking nanodrug to deliver RA-specific antigens and immunomodulators to inflamed joints, reprogramming the immune system to restore tolerance.

• This precision therapy showed strong preclinical efficacy and safety in mouse models, holding promise in the growing autoimmune disease sector.

Rheumatoid arthritis (RA) is a chronic autoimmune disease where the body’s immune system mistakenly attacks its own joint tissues, due to the wrongful recognition of specific proteins—called autoantigens—as threats. This immune misfiring leads to painful inflammation, cartilage damage, and ultimately irreversible joint destruction. Current RA treatments rely heavily on broad immunosuppressive drugs to reduce this inflammation. While effective in symptom control, these drugs suppress the immune system indiscriminately, leaving patients vulnerable to infections and other complications. They also fail to address the underlying autoimmune cause of the disease.

To overcome this, researchers from NUS have developed an immune-engineered nanodrug that shifts the paradigm from blanket immunosuppression to precise, antigen-specific immune tolerance. At the core of this innovative biomimetic platform is a nanodrug cloaked in a PD-L1-enriched macrophage membrane—mimicking the natural properties of macrophages to achieve both targeting and immune regulation. Macrophages are innate immune cells that naturally migrate to sites of inflammation and help modulate immune responses. By coating the nanodrug in a membrane derived from macrophages, the researchers gave it two powerful advantages: the ability to home in on inflamed joints, and the expression of PD-L1, a molecule that helps dampen overactive immune responses by interacting with PD-1 on T cells. This clever design ensures the nanodrug can reach the disease site and actively suppress inflammation in a more controlled way.

Encapsulated within this shell is a therapeutic combination: 1) citrullinated peptide (CitP), an autoantigen commonly targeted in RA, which helps retrain the immune system to stop attacking joint tissues; 2) and a low dose of triptolide (TPL), a potent compound that shifts immune cells toward a regulatory, anti-inflammatory state. Together, this setup promotes “immune tolerance induction”—essentially teaching the immune system to tolerate specific self-antigens rather than broadly shutting it down. In animal models, this targeted strategy not only reduced joint inflammation and damage more effectively than existing treatments, but also did so with fewer side effects, offering a promising step toward smarter, safer autoimmune therapies.

The commercial potential of this biomimetic nanodrug lies in its precise mechanism of restoring immune tolerance —a strategy that could extend beyond RA to other autoimmune diseases like lupus and multiple sclerosis. Its modular, disease-targeted design allows the core components to be adapted for different conditions by simply swapping out the autoantigen payload. This flexibility addresses a pressing need for safer, more effective therapies in the global RA market, which is projected to exceed USD 30 billion by 2030. With strong preclinical efficacy, a favorable biosafety profile, and scalable nanoemulsion manufacturing, the platform is well-positioned for clinical translation and out-licensing. Additionally, its use of macrophage membrane coatings and PD-L1 targeting aligns with emerging trends in both immuno-oncology and autoimmune drug development, making it an attractive candidate for biotech investment and co-development partnerships.

Check out other biopharmas leveraging on similar strategies:

• COUR Pharmaceuticals uses innovative nanoparticles to treat autoimmune conditions like myasthenia gravis and primary biliary cholangitis

• While Zylo Pharma uses amorphous silica particles to encapsulate therapeutic cargo to treat chronic autoimmune issues

LUNG DISEASE: Novel proteins found to drive disease progression by activating macrophages in the lung

@Devika Menon

TL;DR:

• Duke-NUS scientists discover that two transcription co-activators, YAP & TAZ, drive disease progression in pulmonary fibrosis (PF) by activating macrophages in the lung

• This activation works through the CCL2 pathway

• Deletion of these proteins displayed improvement in lung repair and reduced PF progression

  

Pulmonary fibrosis (PF) is a condition characterized by scarring of lung tissue that cannot be repaired and results in difficulty breathing. Approximately 3 million people worldwide suffer from Idiopathic Pulmonary Fibrosis (IPF – where the cause of PF is unknown) with the disease progressing unpredictably and often quickly. This disease progression is led by macrophages – which is the most common immune cell type found in the lung.

Scientists from Duke-NUS Medical School discovered that two proteins - YAP and TAZ, which are transcription co-activators - play a key role in disease progression. YAP/TAZ were found to be activated in the macrophages of patients with PF as well as in mouse models of lung injury. The scientists found that upon deletion of YAP/TAZ in myeloid cells (immune cells that originate in the bone marrow), the macrophage population as well as pro-inflammatory and pro-fibrotic cytokine expression - all markers of PF progression - were reduced in mice. Upon deletion of these proteins in macrophages themselves, better regeneration and repair of lung tissue was observed, resulting in a direct improvement of the disease. On the other hand, a constitutively active YAP mutation worsened PF considerably, resulting in severe fibrosis, epithelial damage and more collagen deposits. These results highlight the direct role that YAP/TAZ play in PF progression.

Furthermore, it was found that in myeloid cells that had YAP/TAZ deleted, there was a marked decrease of protein CCL2 (C-C Motif Chemokine Ligand 2), suggesting that YAP/TAZ works through the CCL2 pathway to recruit macrophages. Hence, when CCL2 was blocked, YAP/TAZ mutants did not display worsening of fibrosis.

The identification of YAP/TAZ in PF progression and the pathways involved, could allow for development of therapies targeting these proteins to slow down PF progression and even repair scarred lung tissue.

More IPF news in other parts of the world:

• Repurposing an FDA-approved cancer drug to treat IPF with positive results in mice

• Eli Lily enters the IPF field, offering $99M to Mediar Therapeutics for global rights to their immunotherapy asset

🗞️ Industry Spotlight

News from the Singapore life sciences industry

• Singapore's Nuevocor raises $45 M to develop mechanobiology-centered therapy for cardiomyopathy.

• Gates Foundation to establish in Singapore to strengthen regional partnerships in global health and development.

• Turion Labs launches in Singapore to power Southeast Asia’s biotech breakthroughs.

• Sequential Skin and AMILI secure a $1.8 M grant to uncover gut-skin microbiome connections.

• HistoIndex secures S$9 Million investment to drive the next phase of expansion in digital pathology in Singapore.

• Heinz College announces collaboration with the National University of Singapore and FriendsLearn to promote research & development activities on digital therapeutics

• T Cell Diagnostics (TCD) license IP from Duke-NUS Medical school to develop point-of-care T-cell analysis

• ACM Biolabs receives $2.87 million for pre-clinical proof-of-concept of its mRNA-delivery technology

• GenScript Biotech and NSG Bio announce strategic partnership to grow biotech innovation and accelerate the path to commercialization

📆 Events happening this month

Fireside chat/Panel discussion

• Meet with SoftBank | JLABS Singapore
  (20 May, 3:30 PM - 6:30 PM, in person)

• The Global Ripple Effect on Biotech and Medtech in Asia
  (20 May, 5:00 PM - 8:00 PM, in person)

• MedTech Prototype to Production: Navigating Manufacturing, Regulatory, and Resource Challenges | co11ab Novena
  (28 May, 2:30 PM - 5:00 PM, in person)

• Intersection Between AI and Longevity Medicine
  (28 May, 3:00 PM - 5:30 PM, in person)

Networking events

• Health & Bio Brews Singapore
  (17, 24, 31 May, 9:00 AM - 10:30 AM, in person)

• Meet the Startups! | Nucleate Singapore & NTU LKC
  (2 June, 5:00 PM - 7:00 PM, in person)

Conferences

• HealthTechX Asia
  (21-22 May, in person)

• AI in Health x ATxSummit 2025
  (27 May, 8:30 PM - 12:10 PM, in person)

Opportunity

• 2025 Amgen Golden Ticket Programme | SGInnovate, Amgen & NSG Bio
  (Deadline 6 June)

• Falling Walls Lab Singapore | SGInnovate & Falling Walls Lab
  (Deadline 31 July)