Redirecting Immunity to Fight Cancer with VerImmune's Dr. Joshua Wang
Episode show notes and transcript
About The Guest
Dr. Joshua Wang is a bio-entrepreneur with experience in founding, securing early stage financing and operating early stage biotech companies. His technical background in virology, vaccines and immunology informs his mindful but competitive approach to evolve scientific discoveries into medicines to serve critical unmet needs. Joshua’s experience spans the globe having lived and worked in Singapore, the UK and the USA.
📄 Summary
In this episode, Josh shares his journey from having an interest in infectious diseases to leading a biotech startup that spans across the US and Singapore. VerImmune specializes in developing Virus-Inspired Particle (VIP) technology for targeting cancers. Josh discusses his academic background, including his PhD work at Johns Hopkins, and how serendipitous events led him from vaccine research to entrepreneurship. He explains the mechanics and advantages of VerImmune's VIP technology, its application in cancer treatment, and its potential for other therapeutic areas. The episode also covers challenges in biotech entrepreneurship, the importance of manufacturing and scalability, and the strategic decisions behind relocating some operations to Singapore. Dr. Wang offers valuable advice for aspiring biotech founders, emphasizing the significance of discernment, persistence, and leveraging global opportunities.
🥡 Key Takeaways
Biotech Startup Challenges: Building a biotech startup involves navigating complex regulatory requirements, particularly in manufacturing (CMC). Consistency, reproducibility, and scalability are critical for gaining regulatory approval.
Innovation Through Differentiation: VerImmune’s technology leverages Virus-Inspired Particles (VIPs) for cancer therapy, repurposing the body's existing immune memory. This unique approach provides a differentiated edge in a competitive field.
Strategic Partnerships and Global Expansion: Collaborations with institutes like A*STAR and strategic presence in both the US and Singapore enable VerImmune to leverage diverse ecosystems for R&D and manufacturing.
Adaptive Growth Strategy: VerImmune strategically focused on platform development in Asia while advancing its lead program in the US, demonstrating adaptability in global operations.
Long-term Vision and Cultural Alignment: Emphasizing manufacturing scalability and maintaining core cultural values across geographically distributed teams are crucial for sustainable growth.
💬 Quotes
"The process is the product. CMC people will tell you that. Because at the end of the day, it's about saving patients, but we are fundamentally a business making products, and you have to have a good, solid manufacturing strategy."
"Fortune favors the bold. We didn't know what we didn't know, and so we went around asking people for advice."
"A no today does not mean a no tomorrow. You never know what will happen if you just take the first step. Of course, discern, discern, discern."
"Building the right culture is really critical in starting a company. We find the right people who understand the core values we've built, even without the infrastructure of a big company."
⏱️ Timestamp
00:26 Josh's Background and Early Career
05:13 Founding his first Startup
06:27 Challenges in the Vaccine Business
07:46 VerImmune and their VIP Technology
21:24 Collaborations and Global Expansion
29:48 Advice for Aspiring Bioentrepreneurs
32:38 Conclusion and Final Thoughts
🎙️ Transcript
Episode Preview
Dr. Joshua Wang: One of the important things that you will learn as you get into biotech and you try to bring a drug to the clinic is that when you start meeting the regulators, you really need to show that what you're making is consistent, reproducible, and you know exactly how to control that manufacturing. You know exactly what it is when you make it ten times out of ten times. The bar is obviously a lot at phase one, but it gets harder and harder. And this is why CMC is such a beast. At the end of the day, it's really tough. It's something I learned a lot in my first startup because of the government grants and it's something we made a very big principle and ethos in our company.
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.
Introduction
Dillon Chew: Today joining us is Dr. Joshua Wang, who is a bioentrepreneur with experience in founding, securing early stage financing and operating early stage biotech startups. Josh is currently the CEO and founder of VerImmune, a biotech company focused on developing novel virus inspired particle technology platform that can be used as a delivery system to target cancers.
So welcome, and thank you for joining us, Josh.
Dr. Joshua Wang: Nice to be here. Thanks Dillon.
Dillon Chew: So maybe to start, you know, can you give us a bit of a background about yourself?
Dr. Joshua Wang: Yeah, sure. So basically, if I were to describe myself four key things. So I'm actually born and raised Singaporean. I lived here all my life until I had to go to college. The second thing was I am a vaccine scientist by training. I did my PhD around developing platforms to prevent or treat different diseases. So that's my technical experience. I'm currently the founder and CEO of VerImmune. It's been an honor, a pleasure to lead this company for the past five years. And finally, I'm very proud to be a father of a bumbling cute three year old. And I think that's a real honor and a blessing. Yeah, that's basically me, I would say.
Dillon Chew: Yeah, that's nice to hear. So, you know, you shared you have quite a diverse experience, right?
So you've lived in Singapore. You've also worked in the US. You did your PhD in the US, right? And then up there also at the same time, you've also worked in equity research. You founded two startups along the way. So could you kind of walk us through your journey? How did you get there, from Singapore and what really inspired your transition from academic research into entrepreneurship?
Dr. Joshua Wang: It was actually serendipitous. My main interest when I was growing up was in today, I will, I will basically coin it as drug development. But back then I didn't know, I was not able to distill it to these two key words. I was just very interested in treatments and medicine and how to like help people, you know, get better health outcomes essentially. And so, for the longest time, I thought I was more interested in the practice of medicine and I wanted to be a physician. But I quickly realized that wasn't what I was truly interested in. I was really more interested in infectious diseases.
So I was actually much more interested in the bugs and the viruses and the parasites than actually the, I mean, I'm interested in the disease and the treatment outcomes and everything. But I found myself more interested in those aspects, and so after my undergraduate degree at Imperial, where I was doing biology, I opted to actually do a PhD in vaccines, because I was really interested in the vaccine world. I was really interested in how you could use your immune response to prevent diseases so I got lucky, I applied for a program in Johns Hopkins, and then so I went there in 2010 to do my PhD.
I was very lucky because this was a very translational program. The program was called the pathobiology program. I joined a lab called the department of viral oncology. My mentor's lab, Richard Roden, his lab was focused on developing viral platforms to prevent certain infectious viruses. It just so happened that these viruses cause cancer and so if you think about it if you have in your mind right now a triangle, I had a chance to work on not only just virology, I was exposed to immunology and then on the other hand, cancer. And so that was what I was doing in the first two years of my PhD, vaccines against infectious disease, infectious viruses.
And then around, I think 2012, 13, the immunotherapy wave hit and I was pulled into cancer vaccines and whatnot. But I digress. The main point is that was my fundamental basic training. My lab was very translational. My mentor had a lot of collaborations with big pharma companies. I got to see firsthand how these things were actually being moved beyond just science. I quickly realized that was what I wanted to do. That was how I started moving into this career.
How it happened into entrepreneurship was a totally different transition. It was towards the end of my PhD and I was clearly not interested in academia. I did not want to just work on science that resulted in papers that would say, this might have therapeutic implications or whatever, right? You see that a lot in papers. It's just that, I wanted more.
So it actually started in this class towards the end of my PhD, there was a particular class on how to translate your ideas into an actual business plan. I went there with a few classmates who were also going to graduate. It was a class around taking projects from the engineering school and making it into a whole business plan. At the end of the course, you're supposed to do that.
Now, I was not interested in the project I was given at all. I was in fact quite frustrated with the project. This was the first class. I basically stood up and walked to the front and I told the director, Look, I'm a vaccine scientist to be. It's a really awesome vaccine that I've worked on in my mentor's lab. This is what I'm truly more interested in. I want to write a business plan around this. I don't want to work on this engineering project. And I thought the director would say no, but he actually was very encouraging. He said, Oh, this is great. Do it!
From that academic exercise of thinking about how to put a high level pitch on a next generation of vaccines that was developed in my mentor's lab. Me and a couple of my classmates realized that this could be something more. And that was the beginnings of our first startup company. It was kind of serendipitous. I just wanted to do this. And one thing led to another, basically.
Dillon Chew: Yeah, I think it's great that you followed what you really wanted to do. Instead of just following a standard academic track where you publish papers and then look for the next experiments to do and then repeat that so I think that's really inspiring. So from that entrepreneurship class, you spun out a company?
Dr. Joshua Wang: Yeah. So that was my first startup. It was based of a next generation universal vaccine against this virus called HPV, Human Papilloma Virus. This is a virus well known to cause cervical cancer, head and neck cancer. So we basically developed a pan preventative vaccine against all kinds of cancers that were caused by this virus.
One beautiful thing about this program was that the science was obviously strong. My mentor at the time had secured a huge grant from the National Institutes of Health in the US. That's the equivalent of A*STAR in the US. The value of that, of paying for manufacturing, doing toxicology studies, filing and what we call an investigational new drug, which is the FDA filings you need to do before starting a trial was all covered. So it was like a true train to phase one. We saw an opportunity. It was something that clearly worked against the current standard of care. And so we went all in this year.
Dillon Chew: So I think that's really interesting because back then when you were still doing your PhD, you guys just wanted to start a company and I think we all know, starting a biotech company versus starting a tech company is very different. What were some of the biggest challenges you faced, deciding to become a founder back then, you probably hadn't had your PhD yet. You were still studying, right? And then you didn't have business experience. What were some of the challenges you faced back then?
Dr. Joshua Wang: Yeah, I think the biggest challenge we faced back then was basically, and to be honest, this is what everyone faces even today is you know, convincing people that you had what it takes to do it. The vaccine business is not an easy business. There are only so few companies in the world that can do vaccine from end to end. We had great aspirations on what we wanted to do but people were not encouraging. I would not say they were discouraging. I think they were just concerned that we did not know what we were getting ourselves into. I don't think they were a hundred percent wrong either. Fortune favors the bold and this was something we thought was transformative.
And so we believe that we could do this and I think one of the things we had the guts to say, we didn't know what we didn't know. And so we went around asking people for advice. We were lucky also that Johns Hopkins is based in Baltimore, Maryland, and the Maryland region, it's not as famous as Boston or San Francisco, right? But, there are companies like MedImmune, which is now AstraZeneca. You probably heard of the Genentech Mafia in San Francisco. There's a MedImmune Mafia in Maryland. There's a lot of experienced people that have been there, done that. And so we were very lucky to have those people to be advisors to help us along the way. Raising money, getting people to understand what we're doing. It's all the standard things you would face as an early stage.
Dillon Chew: Thanks for sharing. I think a lot of our listeners would also face similar challenges. So, you know, I just wanted to go back and touch on it. You've mentioned that you have a background in vaccines, but I also understand that your current startup, VerImmune, is focusing on cancer. How did that shift towards cancer and what really drives your passion towards innovating in cancer therapeutics?
Dr. Joshua Wang: Yeah. So maybe I'll answer this question in a different way. So the story around VerImmune, it's really focused on two things.
The first is solving a huge problem, which is still a problem today. And it's the problem of delivery. Based on my experiences in viral platforms, we came out with a global technology called virus inspired particles, which is basically inspired from the geometry of viruses to use that as a delivery system to target different diseases.
The second thing is, I also spent some time in a venture fund in Boston, Flagship, and it was an eye opening experience. I actually learned the difference between me too, and truly wide-space and orthogonal and it really changed my perception on what is truly differentiated. And that's something critical when you are starting a company, because you have so much challenges ahead of you. You really have to be sure that what you're doing is truly differentiated. So using our novel VIP, when we wanted to serve a certain therapeutic area it had to be truly differentiated.
So we picked cancer as our first problem because it's still a problem. People are dying from cancer every day. What is the connection between vaccines and cancer? This is another serendipitous story.
I was stuck in a snowstorm in Buffalo, New York with a bunch of tech bros. Back then they knew I was a vaccine scientist and they were saying, Josh, you should start working on cancer vaccines. You should use this cancer vaccine technology to help people. And I'm like, well, first and foremost it's not that straightforward.
I was explaining to these tech bros. It's hard to create an immune response against cancer. It's one of the biggest issues because cancer patients are not doing well. It's hard to create that immunity. And that's why people are doing cell therapy because it's another way of putting back that immunity in them, right?
And so one of the tech bros was like, I just vaccinated my kid three weeks ago with the measles vaccine and he's protected for life. So what's going on there? I was like, that's different, this is a vaccine you're given as a child. It's lifelong. It's protective. You have it all the way when you're older. And that was kind of an ah ha moment. It was like, what is in your body that's lifelong, that's protective? And it became like, Oh, what if you could repurpose that to target cancer? And that's really the differentiation of our lead program at VerImmune, which we call AIR or Anti-Tumor Immune Redirection.
It's really the concept that all of us when we were young, were infected by some virus or got a childhood vaccine. So we developed this lifelong immunity. As you get older, if you get cancer, could you trick the body to see the cancer as Chicken pox, or the flu, and reignite your immunity to kill the tumor?
When I was conceiving this thought process, there was a lot of interest in personalized medicine. You know, all that screening of your body to find the right biomarkers to give the appropriate treatment. We saw this approach of immune redirection for cancer patients as personalization based on a patient's immune history. You could check a patient's vaccine records or do a blood test, see what sort of past immunity he has, or she has and give the appropriate treatment. It could be fundamentally personalization, but off the shelf at the same time.
Great idea, great concept. How are we going to do it? Right. And that is where we married the concept of using these VIPs as the delivery system. We realized our VIPs could target tumors, and so we found a way to link certain viral proteins on the tumor, on the VIP. And then this VIP with the linked viral proteins would go to the tumors, paint the tumors and make tumors look like a virally infected cell and reignite your immunity to kill the cancer.
Our lead program, VERI-101, is focused on cytomegalovirus responses or CMV. We picked CMV because everyone's actually infected with this virus. It's a ubiquitous infection that everyone has. Somehow, the body has evolved to actually keep your immunity against CMV. Even if we went to our golden years, we still have strong CMV memory immunity. The key is memory. So the whole concept of what we're doing with our LEAD program is, the body already remembers CMV. The body knows what CMV infection looks like. If it happens, it's cleared. So we are using our VIPs to trick the body to suddenly see cancer as a CMV infection and the body remembers and goes, Oh, you shouldn't be here. It's a bait and switch.
Dillon Chew: That's really interesting. Thanks so much for sharing in detail about how this particular technology works. So, how is this different versus some of the vaccines that are currently popular like mRNA vaccines, which came out during COVID, how is this a lot more advantageous than some of these other delivery systems?
Dr. Joshua Wang: Yeah, so I'll try to be succinct. Fundamentally those mRNA vaccines are cancer vaccines. And so the first problem as I've explained to the tech bros many years ago is you need these mRNA. Every technology has its place in the circle of life, as I like to call it.
Our differentiation between what we're doing and an MRNA cancer vaccine is the mRNA cancer vaccine has to create a specific anti cancer response and one of the key problems in cancer immunotherapy is it's hard to create that response.
The second thing is our VIP technology for immune redirection. It's a virus drug conjugate. So you've heard of antibody drug conjugates? This is a virus drug conjugate, a VDC. The mechanism is very similar in the sense that the VDC will target tumors. You will release these viral proteins that decorate the tumor. There's no need for expression of the protein. It's already there, repurposing immunity that you already have so you don't have to create it. So we're targeting the tumor as opposed to trying to create an immune response, which then has to target it.
Dillon Chew: So in that case, using a virus drug conjugate, so is the virus themselves immunogenic? Can it actually trigger an unwanted immune response when you put it into the body?
Dr. Joshua Wang: That's actually why we call these VIPs and not VLPs, virus-like particles. So taking a step back, each VIP particle is based off 60 copies of a re-engineered papillomavirus protein. It was inspired from the sequences of papillomaviruses because a single protein can somehow self-assemble into a larger quaternary particle structure. Serendipitously, as we developed the VIP monomer protein, we found it to self-assemble into these different structures that papillomaviruses would not normally form.
Papillomaviruses fundamentally form 60 nanometer structures. After re-engineering the protein, unexpectedly itself assembled into this current 30 nanometer structure, which was not obvious, not intended. And my IP lawyer would be proud of me, one skilled in the art would not be motivated to do this anyway.
Long story short, the structure is so different and we found it to be less immunogenic. So there was opportunities for re-dosing. It does produce some antibodies but we found them to be non neutralizing. These antibodies don't block the binding of our particle to tumors. It's still able to release the CMV peptides to decorate the tumor and achieve that pharmacological effect.
Dillon Chew: And maybe on that, when you're talking about the delivery part, how would some of these be modified to actually target different cancer cells? Does it mainly target cancer cells or could you re-modify this to target other receptors of interest?
Dr. Joshua Wang: Yeah, that's another very good question. And this is why the VIP was actually inspired from Papillomaviruses. Our scientific advisors, one of them was John Schiller from the NIH, found that the natural virology of these papillomavirus particles tended to infect broken tissue. It's just part of their viral life cycle, they like to go to broken tissue and infect the basement membrane of an epithelium.
That was a basic science observation. Now, when you think about the tumor microenvironment it's a very disrupted place.The entire epithelium is disrupted. There's no differentiation actually. The cancer is just one big lump. I mean, there's heterogeneity in certain receptors, but fundamentally it's just this one lump mass. I'm simplifying things here.
And there's this particular sulfated proteoglycan that is actually only supposed to be in the basement membrane. It's now everywhere, all over the tumor because of this non differentiation. And so what actually was just a basic science observation of how papillomaviruses targeted broken tissue at the basement membrane, was subsequently realized in the context of the tumor microenvironment, this same overexpression of this receptor was there only for cancers, but not normal tissue. So we realize that these proteins could be actually used to discriminate normal versus cancer and that was fundamentally why we looked into using these VIPs.
Dillon Chew: That's really innovative. You mentioned that because everybody gets infected with CMV throughout their life but then, are there actually any specific childhood vaccines or infections that could be beneficial for AIR apart from CMVs, is this just specific to people who have CMVs or if you were to give them other types of vaccination, right? Let's say, those from the childhood, like measles, right? Could this actually be repurposed in that sense?
Dr. Joshua Wang: Yeah, actually we looked at many kinds of past immune responses. I would say in the end CMV was the best immune response to make our lead product, because CMV undergoes this natural phenomenon called memory inflation. So, as you get older, your amount of CMV memory T cells goes up. Stuff like measles and the flu vaccine over time the immunity does wane. So it actually goes lower, you could give a boost. No question about it. But, CMV immunity at that point seemed to be the better choice.
We considered which was the best immunity. Who has it? Are there models available to demonstrate proof of concept? Cause you can imagine this whole idea of repurposing. Yeah, it sounds cool. Right. But many investors were intrigued when we first tried to do this, but nobody was really willing to pony up the funding to support this. And so we got really lucky securing a National Science Foundation grant in the US that allowed us to demonstrate proof of concept.
Yeah. So in a nutshell, these other immune responses is a possibility. We actually filed patents all around the place to make sure we protect it. But I would say that, you know the VIP itself is unique in many ways that it actually executes AIR well. So once I came up with this idea, I finally thought of something cool. I started going to conferences and noticed a couple of folks actually doing this. But very lucky that, you know, we all have a common goal of providing patients this unique mechanism as a different treatment opportunity, and so they became our scientific advisors and we are working together now.
Dillon Chew: That sounds really interesting. So maybe just to touch on because you've mentioned mainly about targeting cancers, I also wanted to understand, could the VIP approach coupled with the AIR actually have potential applications beyond oncology? So let's say, for treating autoimmune diseases or infections?
Dr. Joshua Wang: Yes I will speak in high level terms for the VIP. Fundamentally the VIP is a highly amendable viral particle. You can attach payloads on the outside or as we've discovered quite recently you can put stuff inside.
And that gives us a huge opportunity in developing different kinds of therapeutic products from this single platform to target many therapeutic areas. Autoimmunity is an interest of ours, but we have decided to still first focus and prioritize our cancer program.
The AIR approach definitely is also, you know, if you can redirect something one way, you obviously can do it the other way. But we think there are other more exciting ways to deal with these diseases so stay tuned.
Dillon Chew: So we've talked a lot about your technology, but in terms of the whole product development, I would also like to touch a little bit about the next step after you've developed your product, how do we actually start to scale it up and get it out into the potential patients. So I think one aspect that you shared about your VIP technology is that the manufacturing part is a lot easier .
Can you actually share a little bit about, you know, how is this a lot more advantageous as compared to the current treatments like gene therapy where, the supply chain is a big issue?
Dr. Joshua Wang: I think the future, just my personal opinion, today, the real issue is delivery. Payloads and drugs are not getting any smaller. So I don't think antibodies, it's not gonna be able to deliver huge cargoes or whatnot, right? It's limited. And so viral vectors viral particles is to me the next wave. They've been around for a while, but it hasn't hit that kind of renaissance. I really believe viral particles is the next one. And we're seeing this already, actually, right? Besides AAVs and obviously lipid nanoparticles, LNPs you're seeing a lot of these new startups that are coming out in Boston from the big guys, Dr. David Liu, Jennifer Doudna, Feng Zhang, making these new viral particles. But one of the things we noticed is that all of them require two or three proteins to self-assemble.
And a key differentiation with VerImmune's VIP is it's a single protein. When you have to make a particle of two or three proteins, there's a lot of questions around homogeneity, consistency, reproducibility. Maybe when you're doing it in a lab, it's not a big deal, right?
One of the important things that you will learn as you get into biotech and you're trying to bring a drug to the clinic is that when you start meeting the regulators, you really need to show that what you're making is consistent, reproducible, and you know exactly how to control that manufacturing. You know exactly what it is when you make it 10 times out of 10 times, the bar is obviously a phase one, but it gets harder and harder. And this is why CMC is such a beast. At the end of the day, it's really tough. It's something I learned a lot in my first startup because of the government grants and it's something we made a very big principle and ethos in our company.
There's actually a saying that goes, the process is the product. CMC people will tell you that. Because at the end of the day, it's about saving patients, but we are fundamentally a business making products, and you have to have a good, solid manufacturing strategy, because it will cost you.
Dillon Chew: Yeah, that definitely rings a bell because when we talked to other startups before, we learned that a lot die out in terms of funding when they start going towards the manufacturing side of things, and they realize that their product cannot be scaled up as economical and that results in their funding running out and all that. So I think that really hits the target.
So I think talking about manufacturing, we've learned in the news recently that VerImmune is collaborating with ASTAR. Specifically, it's the Bioprocessing Institute? And at the same time, you guys are also collaborating with some of the local partners like NSG Labs, Amgen, on top of having that strong partnership with JLabs at Washington DC. So how do you guys actually start thinking about collaborating externally, even though you are a startup. How did that partnership actually start to come about?
Dr. Joshua Wang: Very good questions. I'll try to tackle them piecewise. Yeah. But just one more point, because I'm really passionate about CMC. Yeah. You asked me what's the differentiation, right? It's really the single protein that can be made. So going on to your next question, why did VerImmune decide to collaborate with BTI and why CMC?
So first of all, BTI is one of the few rare institutes in the world where they really care about bioprocess even at a discovery level, and it's very rare and we felt that that was actually very important in terms of further developing the VIP platform.
One of the things as we thought about the growth of VerImmune was to be a global company. While we could definitely do some R&D in the US and keep doing R&D in the US also for platform development, we started to ask the question, well, where else can we do this where we have the right people, the right ecosystem of folks where they have a specific interest, it aligns with us. And where can we do this fundamentally and really BTI was one of those institutes where they really cared about CMC. We cared about CMC. We didn't want to get distracted into doing target biology. Don't get me wrong. That's important, but we wanted to solve certain manufacturing questions here.
And those are fundamentally very important engineering science questions that doesn't really excite a lot of people, unfortunately, because those are more of an art than a science sometimes. But these are key important know how intellectual property questions that will fundamentally make your platform stronger.
Platform development is hard. And so we decided to focus on the manufacturing and scalability of the platform as one of the key pillars of the company because the company is as good as its platform. At some point you need to have an asset and that's one going to the clinic next year. But we never forgot that we're going to grow beyond that. That was the prime decision to work with BTI.
The other decision, which is more of a long term strategic view is again, like I said, we are looking at things globally. We wanted to have a presence in Asia. I'm Singaporean, born and raised here. I have a strong belief in our work ethic and people and our intelligence. So I really wanted to bring this back home and build this and using this as a launchpad to punch our way in Asia basically.
Dillon Chew: That sounds really good. You were speaking about coming back to Singapore? You are based in DC right now, but you've actually recently moved some of your operations back into Singapore? So you're kind of split between both sides, right? So we just wanted to understand, what were some of the advantages of splitting both teams and, were there any constraints you had to navigate by splitting a team across two different countries?
Dr. Joshua Wang: Since it's the end of the year, let's start with the positives, right? I think the focus on platforms in Singapore and Asia per say, was better for our team in the US because the 101 program on AIR was already something that proof of concept was developed. We had a process to make it. We met the FDA for a pre-IND meeting to basically get blessings on your manufacturing and tox plan before you actually file for the IND for clinical trials.
It was a much later stage at some point as a company you actually have to show that your assets coming out from your platform can actually show value in the clinic, right? At the end of the day, you want to help people. So we needed to focus on that. And so, the US team was set up for that already. And that was what they were tasked to do.
The platform part of it, you can be pulled in so many directions, the fact that we found the right collaborator Dr. Wei Zhang, her team was really a blessing because they're excited about the same things we are. And with their institutional R&D knowledge and our understanding of the VIP know-how, they were able to lead the way in pushing some of this platform development. So positively it allowed us to focus on what needed to be done here from a platform and asset perspective.
I would say the challenge obviously is time zones. It's much easier now with zoom and all that, but obviously that's a constraint. The second was we intend to really build our team in Singapore eventually. And the other constraint I would say is we had made this decision actually in 2023. That was when we won the golden ticket. I had three phases to this plan and I'm happy to share this because I've been telling everybody who's willing to be listening to me. Was that we really want to do platform development in Asia. Phase one was finding the right groups to work with us because we don't have the capital to set up a lab. So it's like BTI and a couple of others.
Phase two was infrastructure. We needed a space where we felt like there was a right ecosystem to interact and learn from other founders who were doing this. And with the Amgen golden ticket this was a great opportunity for us because there were other companies, startup companies like ChoonPeng you know, the CEO of Immunoscape, who has stuff in Singapore and the US and Jeff Lu from Engine BioSciences. They are branching from Singapore out, we were trying to understand how to come back and do both. And so there's nothing more helpful than learning from another fellow founder. That was phase two. We were lucky enough to secure the Amgen golden ticket to help us move along the plan.
Phase three was basically fundamentally boots on the ground, but then the economic crisis happened. So it really slowed down our plans in terms of hiring. You know, my personal view is when you bring on somebody to join a startup, it's a longterm thing, right? You're investing in this person so we didn't want to have a situation where we brought on someone and then suddenly things go kaput. It took longer than expected, but we're in the right place right now to do that.
So that was one constraint. It was money. But all is good now. We obviously still need to raise more money, but now we're in a good place. The other was making sure that the same cultural values we had in the US would be respected as we set up things. We're a small team and when we do not have the infrastructure or HR, like a big company, it's very important that we find the right people that understands the core values that we built. We didn't really have time to talk about this, but you know, building the right culture is really critical in starting a company.
Dillon Chew: So you've mentioned your Phase 1, Phase 2 and Phase 3, and I know just now you've also shared with me a little bit about, you guys were able to raise a bit of money recently. What are your next key milestones, your phase four, potentially, or even phase five in the next year when we go to 2025?
Dr. Joshua Wang: Yeah. Going back to the platform versus asset story, our 101 program is clearly something truly differentiated. And, we plan to get into the clinic by the end of next year. We are currently doing our GLP talks. GLP manufacturing will start soon. And we plan to start our phase one trials in Australia. So the train has left the station and that's really one something that we are looking forward to making it happen, you know, demonstrate that clinical safety and eventually proof of concept in the next two years.
On the other side we have been fortunate to have investors who understand the intricacies of both, and they understand and actually see the value and like Singapore as well as understand that it's a global world. You can do things everywhere, not just one place. And that will be another key thing as we move into 2025. The main point is we want to really develop the program further with BTI, mature it and start looking at some potential candidates to make this into another program.
Dillon Chew: Potential candidates in terms of partners?
Dr. Joshua Wang: No, sorry. So we've been working a lot on the CMC, and we've been looking a lot on certain payloads. And we've been working on trying to improve the efficiency and make sure that it's actually working and all that stuff. At some point you actually have to start doing biology again. You have to find that unmet need, that differentiated area. And I think at some point you have to really grow the company. That's a very big endeavor. It will require a lot of resources also. And so we're taking it slowly, but that's just a natural evolution of how we see we're growing a company with a novel VIP technology that can be used for different areas.
The 101 program will validate the safety and eventual efficacy of a virus drug conjugate using a VIP system. And we hope that with Singapore, we can demonstrate the ability of these. I'm still thinking of a cool acronym, but, you know, virus inspired nucleic acid therapeutics, basically. It's a mouthful, right? I gotta get back the acronym Singaporean in me to think of a nicer lingo, yeah.
Dillon Chew: Well, with Phase 1 trials, I really do hope that we can see some good positive results next year, or maybe the year beyond.
Right. So maybe just to wrap off, coming from yourself, as a serial bioentrepreneur, you've done so much work in the biotech sector. We just wanted to end by asking you if you do have any advice you would actually give to our listeners who are scientists or researchers that are looking to start their own biotech companies?
Dr. Joshua Wang: Yeah. So Dillon, thank you so much.
I hesitate to call myself a serial entrepreneur. I've only done this twice. It's an honor to be on this podcast. The first advice I would give to people who want to start their own companies or be founders is take all advice with a pinch of salt, practice what I call discernment. Because even the most well meaning advice sometimes might not be truly applicable for your situation.
A lot of times there's a saying, I forgot who said this, being a founder is like choosing between bad and terrible. Sometimes, you only have bad choices. And what I've learned, as a founder is there have been times where I got advice that was really, well intentioned, well meaning, really wanted the best for it, but it's just totally not applicable.
I guess we're running out of time, but a quick example is, oh, you need to like quit your job and go all in. There's a time and place for that. You need to really make sure that you're all in at some point because this is not an easy task, certain blanket advice needs to be taken with discernment and understanding context. And it's a thing I guess, you know, you could not just apply in your startup life, but basically in life in general.
The other thing I would just leave with everyone is there are no forever goodbyes in biotech. A no today does not mean a no tomorrow. When we applied to JLabs the first time with this idea of immune redirection, they basically said, no, you have no data. And I was like, okay…? But we were creating it. What was really great about JLabs is they came back with feedback. Like what kind of science would make sense to support, your concept of immune redirection. We actually already knew that, so we were doing it. When we had the data, they accepted us and we were very happy to be part of this ecosystem beyond NSG Biolabs in Singapore getting to know other JLab founders.
So the last piece of advice is to talk to many founders if you're interested in starting up, talk to them. Talking to tech bros led to the whole AIR concept and going to this class and talking to the director that led us to start our first company so you never know what will happen, if you just take the first step of course discern, discern, discern, discern.
Dillon Chew: It's a little going outside of your bubble? People outside like tech bros might have ideas or inspiration that could give you some good ideas.
Dr. Joshua Wang: Yeah, and you can't do it alone and one of the most free things on earth besides the sun's energy was people's opinions. You get that, you know, you ask for one you get three. So you need to discern but it's helpful. It helps you in the long run. So maybe it's because I'm a scientist. I'm very data driven. I like many data points. But yeah, that's really how I see things. It's just my opinion.
I really like what Nucleate is doing and I really hope we can get more founders and people who want to be founders excited.
Dillon Chew: Thanks so much for the shout out. So, I just would like to end off by saying thanks for joining us for this podcast session and I hope you enjoyed it. And I hope that our listeners would also learn a lot from all the sharing that you gave.
Dr. Joshua Wang: Yeah, sure. Thank you!
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.
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