Building the local microbiome community with AMILI's A/Prof. Jeremy Lim

Episode show notes and transcript

Sep 27, 2023

About The Guest

A/Prof. Jeremy Lim is the Director of the Leadership Institute for Global Health Transformation at the NUS Saw Swee Hock School of Public Health and the CEO and co-founder of Asian Microbiome Library (AMiLi). AMiLi is Southeast Asia’s first and only precision gut microbiome company. AMiLi houses Southeast Asia’s first and only gut microbiome transplant bank and is building up the world’s largest multi-ethnic Asia gut microbiome database.

📄 Summary

A/Prof. Jeremy Lim is the Director of the Leadership Institute for Global Health Transformation at the NUS Saw Swee Hock School of Public Health and the CEO and co-founder of Asian Microbiome Library (AMILI). In this episode, he discusses his transition from surgical practice to public health, policy, and entrepreneurship. He explains the important work of cataloging the Asian microbiome and describes the work AMILI has undertaken in building the world's largest multiethnic Asian microbiome database. He highlights the potential of personalized gut health treatments and the role of partnerships in advancing research and development. A/Prof. Lim also shares his insights on Singapore's healthcare system and the challenges and opportunities in the biotech ecosystem.

🥡 Key Takeaways

A/Prof. Lim emphasizes the need for Asia, particularly multi-ethnic Asia, to manage its own microbiome data and studies.
The alternative to implementing Healthier SG, a major system change in Singapore's healthcare, is even more challenging.
Changing behaviors is crucial for promoting health, and the healthcare financing system should incentivize health promotion rather than sick care.
The microbiome is a promising field for personalized gut health treatments, and the gut-brain axis offers potential in various conditions.
Partnerships between startups and public institutions are essential for advancing research and development in the biotech ecosystem.

💬 Quotes

"If we in Asia...did not put our hand up and start to manage our own destiny, collect the data, run these studies, we would have to accept the handed down wisdom from countries that are geographically very distant from us."
"The alternative to Healthier SG...is by far the greater risk...The intended changes are monumental...but the alternative of not doing Healthier SG is even worse."
"Changing behaviors is not at all trivial...it's a heck of a lot more work and resource to help change behaviors than it is to prescribe and dispense medicine."
"The microbiome is primarily driven by diet, lifestyle, and the environment...keeping people healthy is really around the social determinants."
"The microbiome's intimate relationship to the immune system holds promise in inflammatory bowel disease and a whole host of other immune-mediated conditions."

⏱️ Timestamp

00:39 - Introduction
02:30 - Experience in public health and civil service
12:41 - Transition into entrepreneurship
16:53 - Co-founding AMILI
23:26 - Building the world’s largest multi-ethnic Asian gut microbiome database
31:59 - Partnerships and IP
42:54 - Growing the local microbiome community
49:34 - Biology, behavior, bureaucracy, budget

🎙️ Transcript

Episode Preview

A/Prof. Jeremy Lim: It was very clear to me then that if we in Asia, particularly multi-ethnic Asia, did not put our hand up and start to manage our own destiny, collect the data, run these studies, we would have to accept the handed down wisdom from countries that are geographically very distant from us, with very different lifestyle, very different diet.

And particularly in the microbiome world, it was just that we saw the need and no one else was doing it and we thought that for the good of the ecosystem, this was something we should put our shoulder against it and really try our best.

Introduction

Joson Ng: Hi, thanks for joining us on Nucleate Singapore Pulse, Singapore's premier podcast on the biotech ecosystem. I'm your host, Joson Ng, an MD-PhD candidate at Duke-NUS Medical School.

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.

So joining us today is Prof Lim, who is the director of the Leadership Institute for Global Health Transformation at the NUS Saw Swee Hock School of Public Health, as well as the CEO and co-founder of AMILI, or Asian Microbiome Library. Thank you for taking the time for this interview. We're so glad to have you here. Do you mind giving a quick introduction of yourself to our audience?

A/Prof. Jeremy Lim: Certainly. And John, thank you for the invitation to come and share some perspectives. And maybe for the listeners, a very quick background. My name is Jeremy. I'm a medical doctor by training, surgery first and later public health slash preventative medicine. And over the last 25 odd years, I've been gradually transitioned out of clinical practice surgery, and then later into the world of healthcare management as well as policy.

And finally, into what I guess would be best described as a really portfolio life, where I have one foot in the startup world and another foot in academia, in policy work, and a fairly mixed bag of different things that I do, but really, they are bound together by healthcare as a central theme, and the ability to make an impact and really help to contribute to moving the ecosystem forward.

Joson Ng: So the public knows you best through your involvement in public health and in civil service. Could I ask, what was your experience like in civil service?

A/Prof. Jeremy Lim: Oh, the Singapore Civil Service is very different from most other countries. We have incredibly competent civil servants who are well paid and they are efficient. However, that is both good and bad in the sense that, Singapore has been described as the unlikely nation, and because of the perceived success over the last 50 years, it is inherent in every successful organization that the risk taking, the entrepreneurial appetite lessens over time, because there is more to lose.

It is also why startups are, and particularly in the consumer tech space, are primarily founded by younger folks because the opportunity cost is much lower. And in the Singapore civil service, I would say that if I look across the last 25 years, we have become technically more and more competent, but probably less and less tolerant of mavericks and outliers and these big bold bets, because it's just the nature of large and successful organizations.

Joson Ng: Speaking of taking risks, we do have a lot of big endeavors right now in terms of public health and public policy, one of which is Healthier SG. Were there any huge endeavors like this back then when you were in civil service in the scale similar to Healthier SG? And are there any, like, changes in how these endeavors are perceived from then and now?

A/Prof. Jeremy Lim: Well, John, we should have started Healthier SG 15 years ago, right? But better late than never. And if you parse through Minister Ong's comments very carefully, it's clear that we are going into Healthier SG not just because it's the right thing to do, but because as we look at the ageing, epidemiology, the worsening healthcare spending cost curve, and so on, we don't actually have a lot of choice, right?

It is pretty clear that if we don't keep the population as healthy as we can, and really throw serious money, serious political will behind it, and we stick to the current sick care model. Singapore is going to find it, not just from a healthcare servicing point of view, but from an economic prosperity point of view, it is going to be very, very challenging.

So back in my time, when I was still in the public sector, the biggest thing was not ageing though it should have been, but the biggest thing was really this push towards biomedical excellence, the start of the entire Biopolis vision, as well as medical tourism. This sort of population health movement, it is certainly bold, but I can say that it's been primarily driven by the Health Minister's vision and his ability to persuade first his cabinet colleagues and secondly, the rest of the public sector that the alternative to Healthier SG, meaning not doing Healthier SG and business as usual, is by far the greater risk. And therefore, as challenging as Healthier SG looks like in terms of the whole system transformation, the alternative of tugging along the current model, makes it an even more challenging proposition.

Joson Ng: Right now, when you look at endeavors like Healthier SG, do you find yourself looking at it more from the lens of a former civil servant or a policymaker, or do you find yourself thinking more about it as an entrepreneur, given your venture into startups?

A/Prof. Jeremy Lim: It's probably a little bit of both, and I certainly look also through the lens of a taxpayer.

All right. Because nobody likes to pay tax, but we do pay taxes because the country does need revenue and income to keep all the public services going. And I guess from the lens of an entrepreneur, any major system shifts creates challenges as well as opportunities. And the optimist will see the opportunity and ask what can he or she do to seize these opportunities. From a policymaker's lens, it will be much more around fiscal implications, whether it can be executed well, what are some of the slippery slope consideration and really so on.

So it's a bit like the analogy of seven blind men feeling different parts of the Healthier SG. As what I have said publicly it's the biggest system change since Singapore's independence. So let's have no illusions about it. The the intended changes are monumental, the operational challenges and obstacles, they will be formidable.

But as what we alluded to earlier, the alternative of not doing Healthier SG is even worse. Hopefully through these multiple lenses, I can then come up with reasonably balanced views and that will serve the stakeholders in the ecosystem, whether in the entrepreneurial world, whether in the policy world, more really usefully than just a unipolar lens.

Joson Ng: Absolutely. I think both in the public health, public sector, as well as the private sector, a lot of people are looking at Healthier SG in terms of the opportunities that could arise from it.

A/Prof. Jeremy Lim: So, I mean, if you look at the opportunities, keeping people healthy is a very different proposition from treating sick people. Keeping people healthy is really around the social determinants, right, of the food we eat and really so on, and it's about behavior. Because here in Singapore, we have the privilege that we don't have a lot of trauma, violent crimes. So a lot of it is individual and really community behavior. And if we take a step back, the five things that drive individual as well as community health, it's really diet, activity, sleep, stress, and high risk behavior such as binge drinking, smoking, and really so on. And if you look at all of these five, they're about the choices that individuals make, and whether community support them in making the right choices. And the classic public health metaphor for this is that of someone pushing a cylinder up a slope, the individual will have to push, but the gradient of this slope is determined by society, determined by government, by the sorts of policies, and the challenge in Healthier SG at its core is how do we make it easy or easier to do the healthier thing?

Joson Ng: This really dovetails quite nicely with the idea of sick care versus health care that you also mentioned a while ago. And I know like one of your research interests is also health care financing as a public health expert. Could you tell us what sick care versus health care mean and how your different modes of healthcare financing actually promote very different kinds of health outcomes?

A/Prof. Jeremy Lim: I'll go back to one of my favorite quotes from the Undercover Economist, and the book opens with this statement, "People respond to incentives, the rest is commentary."

And what this really at it's most primal level represents is that we do what we are paid to do. And thankfully in the healthcare system, most people are reasonably bright once they know the rules and how to optimize for themselves, for the health systems, they will do so.

And in today's model, we are predominantly a sick care model. And the more you work, and the more one works with his or her hands, the higher one seems to be paid. Therefore, proceduralists will earn more than the non proceduralists. And those who love to do the long consults and spend one, one and a half hours talking to patients will be paid marginally more, on a per patient basis, than the doctor who spends five, six minutes and quickly sends the patient off.

And if we go back to the earlier point, that in healthcare, as defined by health promotion, because it's about behavior, changing behaviors is not at all trivial. One really needs to spend a lot of time, a lot of effort in helping individuals to understand what the right behaviors are, and to support them in making the right choices.

The really traditional public health model, which we have long since debunked is this so called KAP framework: K for knowledge, A for attitude, and P for practice. And the very simplistic notion was that if we educated people, give them the knowledge, the knowledge would change their attitudes and the attitudes would then drive practice.

And it's a bit like in the world of economics, it's the behavioral economics versus the so called rational man. Right. And it's a heck of a lot more work and resource to help change behaviors than it is to prescribe and dispense medicine or to put people into MRIs and really so on.

And if we look at funding model today, which is a fee for service model, the incentives are largely skewed towards providing for sick people, providing the diagnostics, the interventions and so on, rather than keeping people healthy. But certainly I go back to the point that I made that people respond to incentives. And if we change the financing system, such that health promotion, good health outcomes are incentivized rather than procedural work, then the behaviors change because at its core, if we incentivize the right things, we get the right behaviors.

Transition into entrepreneurship

Joson Ng: Speaking of really starting impact quite early, you brought it up during your introduction as the reason why you transitioned from surgical practice to public health into policy and to management.

What were then your considerations for transitioning into entrepreneurship?

A/Prof. Jeremy Lim: I transitioned from clinical practice into public health really because there's no shortage of doctors wanting to do surgery. But at least at that point in time, there weren't many doctors who were interested in public health in basically general management.

So as I looked at it, I thought it would be more useful taking the road less traveled. And I was fully confident that there'll be far more competent surgeons who would take my place in the world of surgery. And on this transition into entrepreneurship, really it was more by accident and it's really to support my now co-founders who have impressed upon me how important the microbiome was in human health as well as disease.

And secondly, and more importantly, just how local and regionally driven the microbiome is in terms of the microbiome being predominantly influenced by diet, lifestyle, and the environment. And it was very clear to me then that if we in Asia, particularly multi-ethnic Asia, did not put our hand up and start to manage our own destiny, collect the data, run these studies, we would have to accept the handed down wisdom from countries that are geographically very distant from us with very different lifestyles, very different diet.

And particularly in the microbiome world, it was just that we saw the need and no one else was doing it. And we thought that for the good of the ecosystem, this was something that really we should put our shoulder against it and really try our best.

Joson Ng: I actually want to focus later on as well how big of an endeavor this is in terms of building the world's largest multi-ethnic Asian gut microbiome database. But I wanted to sort of still link up your experience in entrepreneurship to your previous career as a surgeon. Do you think that for people going to medicine, which is traditionally understood to be a calling, it's kind of a high wall to climb over to get into entrepreneurship where we don't really think of it as a calling, right?

A/Prof. Jeremy Lim: I wouldn't really bifurcate this into practice of medicine versus entrepreneurship. And the guiding principle is really impact, or we can use the word value, right? And I guess that all of us enter into medicine, wanting to help people and make the world a better place. And if that's the overarching objective, then the next order of questions are, where would John, where would Jeremy be most useful, create value to have an impact.

And if it is in seeing patients, then that's well and good. That's very noble, very, very legitimate. If it is in government, then that's perfectly fine. If it's in entrepreneurship, creating new products and services that help move the world forward and help make the world healthier, then really, that's the right place.

And there's no... Technically or absolutely right answer, right? There is a time and season for everybody, and the right thing for maybe John to do in 2023 might be the wrong thing for John in 2033, right? And so what I would advise the young students is learn, be the best you can be. And always listen to that little voice inside, help give volume to that voice, talk to your seniors and talk to your mentors and don't be afraid to move out of the comfort zone.

Most of us, at least particularly John, those in your generation will live to be a hundred at least, which essentially means two, three, maybe even four careers. So it's really not such a big deal to step out of clinical medicine fractionally full time for a period you can always return later.

Co-founding AMILI

Joson Ng: Thank you for offering that.

I think we are seeing a lot more doctors really going into entrepreneurship even at the early stages of the career. I think hearing that from you is super helpful as well. Towards your venture, specifically AMILI, or Asian Microbiome Library, you shared with us about how you kind of stumbled into it by accident.

You had two co-founders with you who were very trained in the study of the microbiome as well. And I think we can all agree that the fascination with the microbiome is a more recent phenomenon. What's the importance of timing in the context of starting a venture, especially in a not as well explored area like precision gut microbiome.

A/Prof. Jeremy Lim: We call ourselves AMILI, which is a compression of three words, Asian Microbiome Library. And we deliberately use the term Asia as a geography rather than Asian as an ethnicity. Because to my earlier point that the microbiome is primarily driven by diet, lifestyle, the environment. So the person who moves from, say, Boston to Singapore, after a couple of months of immersing in the Singapore milieu, the microbiome of the individual will look more and more like a Singapore microbiome rather than a Boston one.

And hence, we are very particular that we are focusing on multi-ethnic Asia, people who live in this part of the world with basically diets and lifestyles that could be categorized as Chinese, Indian, Malay, and so on and so forth. And this really takes us to the question of timing, and timing is tied to luck.

And frankly, luck is massively underrated in the startup world, particularly in the healthcare startup world, because if you're too early, you run out of money before you get to the promised land. And if you are too late, by the time you get to the promised land, there are 15 other guys there with you and the market's very, very crowded.

So maybe if I look at AMILI specifically, when we founded it, the microbiome was very nascent here in Asia, and particularly Southeast Asia. And in fact, I would say without any false modesty that because there's a bunch of middle aged academics who are setting up AMILI, people looked at it a bit more serious.

Right. Because many of us come with some background and some experience in doing things. And therefore people look and say, okay, we have no idea what this microbiome is or why these guys are doing it, but because they're doing it, let's just listen. Right. And I'm really very heartened that when we started in 2019, frankly, more than a few of friends thought that we were in a midlife crisis and we have nothing better to do.

But at least today, if you look at where we are in 2023, every medical school has its own microbiome program, right? And the microbiome has become very, very topical. So the efforts we have put in the last four years to really build up the database and to establish what's, I don't want to use the word normal, but what the variability of phenotypically healthy people living in multi-ethnic Asia as represented by Singapore, Malaysia, and the region look like, that's been invaluable.

We've been very fortunate also that when we started, we were able to keep our costs very, very low, and therefore we were able to live long enough to see the microbiome really take off globally as well as in this part of the world. And so we still have enough money. We have been very fortunate that we did our Series A in June last year, in June of 2022, raising 10.5 million that basically gives us a fairly good runway. And as long as we keep our costs very, very disciplined, we can ride this wave and follow the trajectory of the incredibly good microbiome science that is emerging primarily for now in North America, Europe, but increasingly right here in Asia also.

Joson Ng: When you were pitching the idea of AMILI to the investors, definitely it was very novel at that time. How did you go around that novelty and then how did you make it understood and what kind of impact did it have in terms of the investors understanding AMILI's risk profile as a startup?

A/Prof. Jeremy Lim: Well, first thing is that nobody listens to what Jeremy says, but it was very helpful that Bill Gates had spoken quite extensively about the microbiome. And so when folks like Bill Gates say the microbiome is the future of nutrition and so on, that actually gives us a very good tailwind to basically harness. And so when we first started in 2019, when we went around talking to, and we passed the hat around friends, family, and investors, we had nothing but our personal reputations from having done things before, my co-founders having led the first microbiome transplants in the region back in 2014, and a couple of very, very impactful quotes and speeches by luminaries such as Bill Gates and others to essentially say, " I like that the microbiome is going to be such an important part of human health."

And of course I think it did help that I only started paying myself a salary in April this year. So for the, probably the first three and a half years, I do think that investors and VCs like to see that everyone is suffering together and you know, put capital in at risk. The founder, the management team is also putting in a lot of sweat equity. I guess it's this constellation of different factors that essentially helped us to raise a sum of money to be able to take AMILI forward into now where we are in 2023.

Joson Ng: I like that term sweat equity.

It feels like it's really part of the process to suffer a bit before things get stabilized with a startup.

A/Prof. Jeremy Lim: So John, I think startups are all about struggling and about suffering, but in a sense, it is necessary because if you want to do anything that is pioneering, right? And as a former boss used to tell me, all the easy things have been taken.

So if you want to make a difference, you've got to, you know, settle on doing the hard things, right? And when you do hard things, struggling at some degree of suffering, it's just par for the course.

Building the world’s largest multi-ethnic Asian gut microbiome database

Joson Ng: Speaking of doing the difficult things, you mentioned a while ago that AMILI has already established the first gut microbiome transplant back in Southeast Asia, and you're on the way to building the world's largest multi-ethnic Asia gut microbiome database, and Asia in the sense of geography.

Could you explain what this entails to our audience, what's the significance of this, and what kind of advancements in gut health research and treatments this could lead to?

A/Prof. Jeremy Lim: Okay, let me start with the transplant bank, and it certainly helped that my co-founders had done microbiome transplant before, out of the National University Hospital, Singapore.

So, that was incredibly helpful. It was also very helpful that a journalist from the Straits Times was very into gut health and so kindly featured AMILI a couple of times, helping to raise the awareness. And of course, I am eternally grateful to Wunderman Thompson, which is a creative agency under the WPP Group, the world's largest creative company when it supported us on a pro bono basis to launch our microbiome donor program.

And I still remember this vividly. And I must thank COVID for this also, because I guess during COVID business was slow for many, many companies, particularly in early 2020. And so when the Wunderman Thompson team said we'd like to support a microbiome transplant because it's just so novel, and they were able to get the bus companies, the train companies to basically provide advertising space and so on.

So we explained what a microbiome transplant was, how it involves taking a stool, processing the microbiome out of the healthy stool, and then putting it into recipients with specific health conditions.

And essentially in a nutshell, it's a poop transplant, right? They came back a couple of weeks later and said that we'll design a campaign called #poopsaveslives. And I went, Oh my God, but it was a very valuable lesson that all of us are good in some things and we are blindingly ignorant in other areas and we should respect expertise.

And so as I listened to the ideas, I said, wow, it sounds absolutely ridiculous, but you guys are experts in creative communications and running campaigns. I know my own areas in gut health, public health, healthcare financing, and so on. So if you guys think this is the way to go, sure. And of course, they totally proved me wrong.

A very successful campaign mobilized hundreds of donors who came forward to basically say, I want to help you in your mission to save lives and to advance gut health. And on the back of that, A lot of publicity, a lot of awareness, we're able to build out the transplant bank. And today we serve a number of countries across the region.

So I think Singaporeans can be very proud that our group is indeed saving lives, not just in Singapore, but across the region. And really secondly, even for those who are not found to be suitable donors, our experience is that only 2 out of 100 people who step forward thinking that they'll be suitable as healthy donors eventually are eligible.

But everybody very, very happily says we would donate a microbiome sample to the database, we'll answer questionnaires, we'll put in blood samples and all, and this has helped us very, very much to build up not just the transplant bank, but also the database with bio samples, with the metadata around diet, lifestyle, medical histories, and really so on.

And with this incredible resource, we can then work together with many partners to analyze the data, to see the associations between weight and microbiome profiles, whether you have diabetes and really so on and so forth. So that's been a very powerful resource. And because these are largely healthy people, they then form a very, very useful reference database when we do work with our hospital colleagues to look at the microbiome in people with Crohn's disease, ulcerative colitis, and ask how do they differ from a healthy population.

And most microbiome science starts with the initial observation that is translated into associations between the health state and specific microbiome profiles, specific metabolites or the small molecules that the microbes produce. And typically this then goes into animal models, more and more advances before finally going into clinical studies, much like you'll find for pharmaceuticals, medical devices, and maybe so on.

Joson Ng: You mentioned that only 2 out of 100 people eventually turn out to be suitable donors. Maybe just to dive into the science of it a little bit, could you maybe explain why is it that that's the case?

A/Prof. Jeremy Lim: Well, firstly, Many of us only think that we're healthy, and then when we're screened for diabetes, high blood pressure, hyperlipidemia, and really so on, we then find that whoops, we're not as healthy as we thought we were.

So that's the first thing. Secondly, it's... really harder to be a microbiome donor than it is to donate your kidney because we not only have to screen the blood, we screen the stool and all to make sure that there's no disease known to mankind and importantly that individuals don't inadvertently carry multidrug resistant microbe in their microbiome because this really would be, would be harmless to the individual who is healthy, has a functioning immune system, but if we unknowingly transplant into someone who's very frail, immunocompromised, the consequences can be devastating.

Therefore, microbiome banks are very stringent in the eligibility. And we do find that even after we do the first filter of people who don't have any disease risk as measured by their clinical phenotype, by their blood chemistry and so on, a good number still host a multidrug resistant organism.

Joson Ng: You've mentioned cases where AMILI has been working towards finding potential treatment towards Crohn's disease, IBS even. Are there success stories that you usually share in terms of what the database has shown light upon so far?

A/Prof. Jeremy Lim: What I can speak about publicly is that we are part of a major liver disease study together with the National Cancer Centre and a couple of other centres and this is a cohort study of individuals at high risk for liver cancer, so hepatitis B, C, liver cirrhosis, and so on. And we track these individuals over time with baseline microbiome, MRIs, and we then see which individuals in the cohort would go on to develop liver cancer, who would have liver disease progression. And thankfully, even at this early stage in this cohort, We've been able to see that there are very meaningful differences in the microbiome profiles of those who develop liver cancer versus those who don't.

And in the metabolites, colleagues who are involved in this study from other institutions have been analyzing the metabolites and quite unsurprisingly, there are metabolites that are significantly different between those who have stable disease and those who progress into liver cancer. And the question now is, can we take this insight and develop a predictive tool so that we know that individuals who have high risk for liver disease, for liver cancer, who is most likely to progress?

We then adjust the screening frequency with ultrasounds, AFPs, and really so on, as well as once we understand the mechanism of action, are there particular metabolites as well that were predisposed?

And the mechanistic pathway when it's more clarified, will then give the opportunity to start to design potential therapeutics, right, to then reduce the risk of developing liver cancer by say 90% down to 30%. That's certainly something very very meaningful.

Partnerships and IP

Joson Ng: Absolutely. And I think that's really exciting research as well. But that also segues quite well to what I wanted to ask you next, because AMILI is collaborating with a lot of different partners. And you just now mentioned that you're working together with NCCS, the National Cancer Center of Singapore for this research.

And I know personally that you are also a huge proponent of public private partnerships in Singapore. How easy or difficult is it for companies like AMILI to engage in these sort of partnerships, especially in the context of designing or proposing therapeutic interventions in healthcare?

A/Prof. Jeremy Lim: I would say that it has become easier in the, my past role in the public sector in SingHealth was running research as well as education. And if I look at that period, almost 15 years ago, and now it's become a lot easier to effect meaningful public private partnerships, but it's still very difficult.

And I think it's probably at really three levels. One is that as with any meaningful partnership, it takes time for people to get to know each other, for the relationships to become trusted, to become mature. And on this point, because AMILI's founders and our team have been in the ecosystem for a while, we do come in with this modicum of trust and goodwill to help to accelerate that entire partnership and really relationship building. So on the people front, that's been easier for us.

The second piece really comes around funding and a lot of public sector funding is really tied to industry alignment, having skin in the game. And therefore, if the public sector puts in X dollars, the expectation will be that the private or the industry partner will put in Y, which then becomes challenging for really modestly funded startups, such as AMILI, because to a multinational putting in a million or 2 million dollars, it's really no big deal, right? But for young biotech startups here in Singapore, it can be very, very onerous. And it's literally in many cases, it is betting the company because once you have, once you have committed this money, you don't have money to do anything else. So the stakes may be fairly small or manageable for a multinational, but for a young startup, this notion of industry alignment and the industry partner putting in serious money, at least from the perspective of the startup, that is very challenging.

And I do hope that we start to calibrate so that we match the requirements with not just the philosophy. It's certainly very important that the industry partner is serious about the public sector partnership. But at the same time, we have to calibrate the investment so that it is manageable for all parties.

Then the third challenge typically runs around the legal and intellectual property. And here, I guess AMILI has been a bit more fortunate in the sense that we are very happy to share, because having 30 percent of a really big pie is better than having 70 percent of a very small pie, right? And in the microbiome world, particularly, I think that the signs are all there, that the trajectory of the science is very, very positive.

The opportunities, whether in healthcare or in consumer health or in food. They are incredible and it cuts across multiple diseases. The gut brain axis offers potential in Parkinson's, autism, dementia, and really so on. The microbiome's intimate relationship to the immune system holds promise in inflammatory bowel disease, and a whole host of other immune mediated or really immune relevant conditions.

And therefore, AMILI's approach has really been, we're very happy to share. What's important is that we help to grow the entire sector and we move quickly. So we don't want to get bogged down in months and months of arguing over, is this IP yours? Is that IP yours? And our philosophy has been, let's go be jointly successful, then like mature adults in a trusted relationship, we can then figure out, okay, you brought this, I brought that, you should get X, and I should get Y.

We have a very sensible discussion around it. And then we agree, we move on because there will always be the next project that we will work together. So we are very happy to partner. At the same time, we want to partner with folks who we can see ourselves partnering for a very long time. So our first project may be in disease X, but we can see diseases Y, Z, A, B, C, D.

Joson Ng: I want to talk about two of the points that you talked about a while ago, which was first on financing, and it really does seem like a tightrope walk for young startups in terms of managing their finances, making sure they validate that their product works, but at the same time having enough to keep operations.

And I also wanted to tie in the news that in June in 2022, AMILI announced its partnership with CordLife in terms of synchronizing or synergizing the specializations for both companies in terms of processing the gut microbiome and storing it, cryopreservation by CordLife, and the idea of a tightrope walk of finances, what are your thoughts in terms of partnership versus developing those capabilities in house?

A/Prof. Jeremy Lim: I would say that it's really driven by the company's philosophy, as well as the practical realities around the macro environment. And for us in AMILI, at least, we were very clear that we're good in certain things, we're appallingly bad in other things.

And we did not want to stray into areas where we have very limited competency. And if I can use this term, we have no right to win. And it makes sense for us to then partner. So really, philosophically, the founders are really aligned towards partnering, right? Secondly, the macro environment in terms of funding for startups, probably in the last year and a half has become very, very challenging.

So it also makes sense that if you can partner, you can borrow, then really, why build? Like, building is expensive, it takes time, it has limited expertise in building, you have to factor in mistakes and expensive rework, just share. With the quiet confidence that if we were successful, the pie will grow so big that it makes everything worthwhile for everybody.

Joson Ng: That leads to the second point that I wanted to ask about in terms of you mentioned patents and IP and how do you manage that? And in the other context... So AMILI has also worked with public institutions like SIT or Singapore Institute of Technology, and the partnership involves a lot of research work as well as human capital development.

What's AMILI's approach to talent development, and how does that work around the ideas of privacy, of trade secrets, IP, and patents?

A/Prof. Jeremy Lim: John, very good question. A very good set of questions. Let me take them one at a time. First, I would put on record, SIT has been a wonderful partner, and we're delighted and very honoured to be working with SIT, not just in the R&D, but in taking students as interns and on various projects.

Our own approach has really been that as one of the pioneers in the microbiome space, we have a duty and a responsibility to build the community. And we do this so much better when we partner, particularly with institutions that have students that are young people who are flowing through. So whether they end up with us, or end up anywhere else if they have been, I guess, immersed in how wonderful and how impactful the microbiome is, whether they go to a peer company, and I use the word peer rather than competitor because the ecosystem is, is at the stage where as long as it grows, everybody wins. Right. So, so we encourage students to come and join us, to intern with us, six, 12 months, and, and in the context of an institutional partnership, such as with SIT, just becomes more organized and more efficient.

And secondly, on your question around privacy and trade secrets, we're not starry eyed or naive about this, right? Certainly the risk of really having your intellectual property exposed and stolen, it is there. We have to be very clear, what are the things that we can share freely? What are the things we share with our trusted partners?

And what are the things that we will never share? Because that's really core. So, it's going to sound really frivolous, but I look at, say, KFC. 11 secret herbs and spices. I guess he will be very happy to partner with PepsiCo and so on to launch that joint propositions and promotions bundle products in, in really meal plans and all of this, but will KFC ever tell PepsiCo or any other partner that our 11 secret herbs and spices are this, this and this?

I think the answer is no. And the same way AMILI has our own secret sauce or secret blends and that's what makes us special. The other thing where we do share like some of the proprietary methods for how we process the microbiome and how we bank is really because as we look at it and say, wow. In the startup world, in the world of science, ideas are, ironically, relatively cheap, right?

The tenacity to really knock your head until you get it right, that is much rarer. And we look and say, wow, okay, folks can learn this from us. Can they do it as well as us in this particular context? The answer is probably no. And does it help our partners? Does it help the ecosystem if we share some of this knowledge?

And I go back to the earlier point that as long as the pie grows, everybody wins.

Growing the local microbiome community

Joson Ng: I really like the idea of building the pie, building the ecosystem. I think creating an environment that can be competitive but also supportive is really great. But how do you envision the idea of personalized gut health treatments or precision gut health as a broad environment or as a field in the future?

And where will Amelie place within that ecosystem?

A/Prof. Jeremy Lim: Okay, let me just say that it's been, it's a bit of a pity that the term precision medicine has become so tightly coupled to genomics. Because this notion of precision and personalization really is a much broader concept.

In the world of public health, we talk about the social determinant. What does the environment, what does the milieu look like in which the choice architectures are laid out? Why do you choose the fried chicken versus the broccoli salad and all? All these are as important, if not more important, than the healthcare system, than an individual's genomics. And previously, they weren't actually easy to study.

But today, as we see from the consumer tech companies, Right? That nudging behaviors at scale has become a lot more doable. If we look at, let's just take a common example, Netflix, right? Everyone's screen looks a little bit different. The recommendations are also somewhat different based on your viewing history and all.

And so what this then means is that beyond genomics, you are able to add skills, start to personalize the nudges, the recommendations. And I think that in the microbiome, because it's so intimately tied to brain health, immune function, digestion, metabolism, that precision medicine, as well as precision health will really flourish in the milieu of the gut microbiome. And I say this for two other reasons.

Number one, the gut microbiome is computationally much more complex than the human genome. Two to three million genes versus the human genome, 23,000 or so genes. And secondly, the gut microbiome is modifiable through fecal transplants, through supplements, through changes in diet and, and therefore the ability to impact human health through microbiome study, diagnostics, as well as modification becomes so much greater.

And so I am personally very bullish about personalized gut health treatments in the relatively near future.

Joson Ng: It sounds super exciting and I can't wait to see how we move towards that in the future. Specifically towards AMILI, the company is rapidly expanding throughout Southeast Asia. You have partnerships with Malaysia and other regional markets as well, like India and Hong Kong.

What's the impetus for expanding within the region as opposed to big markets that a lot of other startups aim for, like the US, Europe, or China?

A/Prof. Jeremy Lim: John, there are a few reasons. The first reason that is intensely personal is that I am a child of the region. So I care emotionally much more about the region.

And there are enough people in the US and Europe to care about themselves. So given why we set up AMILI in the first place, it makes sense that we at least initially focus on Singapore and our immediate neighborhood. Because from a research, from an application point of view, this part of the world is pretty underserved.

And as alluded to earlier, it's important in the microbiome space where so much is driven by local factors. I mean, we are rice-eating people living in the tropics, right? We're not wheat-eating people living in temperate countries. So our microbiomes are different. Our microbiome tests and our microbiome interventions can logically also be different.

So our own commercial strategy is really partnership, and we can talk about that later. But we have to be successful in our own neighborhood before we earn the right to go into markets like the U.S., Europe, China. I mean, very, very reasonably, if we popped up in the U.S. and say, you should work with us, any potential partner would look and say, yes.

You're so modestly successful in your own, in your own region. Why exactly should we take you seriously? So we have to earn the right to enter into the high fence markets like Europe, China, and so on.

Joson Ng: Speaking of doing well locally, how do you compare Singapore's ecosystem in terms of its capability of nurturing companies like AMILI as compared to the ecosystems of our Southeast Asian neighbors?

A/Prof. Jeremy Lim: I think Singapore startups are very blessed relative to our neighbors and we may bitch about it and complain, but in the grand scheme of things, we're actually a heck of a lot better placed than our neighbors.

And so we have much to be grateful for, Singapore is clearly the most expensive place in this part of the world to do science. But at the same time, there is good infrastructure, and someone has to pay for that, right? There are probably far more grants in Singapore than in a combination of our neighbors combined. So it is part of the deal. And I think that particularly for companies like us having regulatory authorities that are nimble, forward looking, help a lot. Having a jurisdiction that is trusted in terms of data security and so on, also very, very helpful. And lastly, it's really about talent. Can we get the best talent in this part of the world out of Singapore or is it from any other country? And at least in the microbiome space, Singapore is the natural starting point, but certainly we do see that this is, and I wouldn't call it a hub and spoke, but it'll be a network of nodes.

Cause I shy away from the term hub and spoke because it wrongly connotes that the hub is more sophisticated than the spoke. I prefer a network of nodes because we're all good in different areas. And particularly like AMILI, they're very passionate about the food space. Singapore is not an agricultural country in the traditional sense.

So we look at the Philippines, we look at Vietnam, we look at Thailand, food and microbiome. Clearly many countries are much more advanced than maybe Singapore or can accelerate much more because they have natural markets, they have natural research material to move very quickly in this space. So a network of nodes makes perfect sense for us.

Biology, behavior, bureaucracy, budget

Joson Ng: Zooming out a little bit, I wanted to look more into Singapore as a whole and the ecosystem here. And you wrote in an article to Today Online about the four B's of Singapore healthcare being biology, behavior, bureaucracy and budget. I think that was a very nice and helpful framework for looking at the ecosystem.

A/Prof. Jeremy Lim: John, maybe if I can say firstly that the four B's came out of the context of really pandemic preparedness and this reality you can make the world's best vaccine but individuals if they don't roll their sleeves up you're not gonna get the outcome that you seek for.

Joson Ng: Starting with the first B in terms of biology.

And of course, you've talked about it at length during the interview, but biotech companies, startups are inherently extremely risky. And Singapore is not new to this. We have had a 20 year ish runway and there are successful companies, but then there are also companies that are quite established that have stopped operations as well.

So I wanted to get your thoughts on what are the developments in the biotech industry in Singapore?

A/Prof. Jeremy Lim: Yeah, I would say it is mixed. We clearly have the privilege of having some of the largest budgets in this part of the world. Has it been commensurate with the progress that we've seen so far? The answer is probably no.

But remember that science and industry development is non linear, right? I do think that the Singapore biotech scene will continue to surprise us in a positive way. And I do hope that for us in Singapore, we take the punches as just part of the cycle and the ups and downs of an, as what you say, an inherently high risk industry.

Joson Ng: We're all waiting in bated breath for the newer developments that will happen in the years to come. The next B that you mentioned was behavior. And I think, especially with a company like AMILI that looks at the gut microbiome and you give recommendations as to how your customers can modify their microbiome through their diet.

What do you foresee as sort of the challenge for the consumers then adopting that corrective or optimal behavior after being provided that information?

A/Prof. Jeremy Lim: John, I go back to my comment that people respond to incentives. Right. And the challenge with a lot of behaviors is that not just the providers are not incentivized to try to change behaviors, but the consumers or patients likewise.

Right. In Singapore, with Healthier SG, we have spoken a lot about social prescribing. I have not seen any doctor prescribe walks in the Botanic Gardens three times a week, and therefore the company is required to provide a 90 minute lunch instead of the 30 minute lunch. So today, the behavior side of the house, the so called social prescribing, whether it's diet, it's activity, it's lifestyle, stress, sleep, massage, and all of these, are largely a self pay or an out of pocket.

So, this necessarily means that the private companies will have to go where the customers are. And in this case, it's not just the customers who want it, but the customers who can pay for it. And I think that quite regrettably, as a public health professional, that this will be something that will initially be much more available and accessible to those who have more resources.

It will trickle down to everyone else and at some point the government will then see fit to, to reimburse diet, food interventions and really so on.

Joson Ng: The third B that you mentioned was in terms of bureaucracy and especially given your experience as a policymaker. What are the policies that are currently in place that are helping a lot of the local companies thrive? And what do you think are policies that Singapore should learn to adopt from other ecosystems that can actually help mature our own local ecosystem?

A/Prof. Jeremy Lim: I think we've been quite good in the medtech and the digital health space with all the sandboxes and the pilots. And I think that these are useful for proof of concept, but really startups don't need grants. They need customers.

And I would love to see the day when the healthcare providers here think my first choice is to work with a local company. The government supports with a sandbox and to make the regulatory milieu a favorable and safe one. And the mindset of the large healthcare providers is not, I want to look to North America and Europe for technology or for a solution. My first choice is to buy local. And only if local doesn't meet what I'm looking for, then I look outside.

But today I would certainly say that it's more commonly the converse. The local companies need to need to demonstrate that they are as good if not better than the foreign company.

Joson Ng: And then lastly, in terms of budget, especially with your interest in healthcare financing, there's a heavy skewing towards the public sector in terms of funding, especially when you mentioned a while ago about the work with NCCS.

It's really serendipitous or rather fortunate that there are these public private partnerships to help allay the financial concerns with the validation studies and all that. So do you think there's room to create infrastructure for biotech and health tech companies to flourish similar to what is present in the U.S. with the Medicare system.

A/Prof. Jeremy Lim: John, I don't think there is a need for a major overhaul. I do think that our healthcare financing system fits what Singapore needs. And let's be realistic that the primary role of the healthcare financing system is to ensure that there is adequate and appropriate delivery of healthcare services.

So the biotech, the healthtech companies are really the icing or the add-on. So the tail cannot wag the dog. Right. It has to be the other way around. What I would say would be two things. One, is that the mindset needs to be more partial towards innovation, more partial towards buying local, and secondly a bit of seed money to essentially financially de-risk, to give the local company a decent shot. And I'm not saying to open the door wide and keep everyone else. Something that folk probably don't remember, but during the global financial crisis of 2008, the Finance Ministry created schemes where buying local would be incentivized with basic financial support. And then there was an effort to keep the local ecosystems going.

And I do think COVID has amply demonstrated that Singapore, like all other countries, we need to grow our own fair share of companies, of enterprises, because when push comes to shove, there's no one to depend on except ourselves.

Joson Ng: And last question, within the idea of an ecosystem, how do you foresee Singapore's life science ecosystem evolving over the next two to three years, especially given the recent very challenging macroeconomic climate?

A/Prof. Jeremy Lim: I still remain quietly optimistic. I do think that the overall trajectory is going to be a positive one.

That said, as what Warren Buffett says, that when the tide goes south, you see who is wearing clothes or swimming costumes. And I do see that there will be a flight towards quality. And so the more successful companies, they will see funding and they'll probably be oversubscribed in their fundraising rounds and so on. Whereas those that are less able to demonstrate, and I'm not saying that they are not as good, it may be just a function you didn't raise enough in your last round, you just ran into cash flow issues and really so on, and I do hope that we play as Singapore, Inc. or a Team ASEAN, and if we see that there is consolidation, that's not a bad thing.

Because all of us, to my earlier point, we're all good in some things and not so good in other things. And if I take AMILI very, very specifically, right, and if we stumble, and if another player comes in and says, you guys have the multi-ethnic Asia data, you got all the samples, we have great technology, we should pull together. That's certainly something that would be worth really looking at. Because at really steady state, still, efficiency matter a lot. Right.

And so maybe not in the next two to three years, but at steady state, I do see that the life sciences world will increasingly become a consolidated one where there'll be a couple of giant assets that will anchor the systems, a larger number of startups and small biotech, healthtech companies, and that will probably be what our desired steady state ecosystem ought to look like.

But certainly having thousands of different startups in a small place like Singapore, probably not the way to go for us.

Joson Ng: I think we're definitely still in our nascency, but we'll wait with bated breath again to see what kind of steady state outcome and which main players we'll see emerge out of this.

To round off the whole interview, you had a lot of experience as a surgeon, as a public health expert, as a policymaker in the public sector. Now you're in academia as well as stepping into your role as an entrepreneur as well. What advice would you offer based on all your experiences, especially with pioneering a company like AMILI which is really novel and really ahead of its time as well.

What advice would you impart to aspiring biotech entrepreneurs, researchers, junior doctors as well?

A/Prof. Jeremy Lim: Well, I don't want to influence the upcoming presidential elections, but something that Mr. Tharman said previously about the T fit manager really resonates with me.

And what he describes as the T fit manager is that one has to be very deep in a given vertical. It could be microbiology, it could be cell biology, it could be whatever, but develop that set of vertical skills and hence the key and that vertical skills around managing human resource, finance and really so on. So, I would urge. the aspiring startup entrepreneurs, the researchers, be damn good in your personal spike, but also from there venture out to be broad.

And finally, recognize that it is a team game. If you think you can run alone, you are sadly mistaken and really find a friend, find the co-founders, find a team that will enable you to be successful.

And maybe the very last point that I'll make is that nobody does a startup to be rich. People embark on startups because they see that there are ways to make the world better. And the mission really drives the motivation. And that's what will keep you going through the trust and there will be many, many trusts in this building. If it's about the money, forget about it, many, many more easier ways to earn money than doing a startup. But if it's about making an impact, changing the way things are done, then a startup is an eminently good place to be.

Joson Ng: All right. Thank you so much, Prof. Lim.

A/Prof. Jeremy Lim: All right. Thanks, John. All right. Take care then.

Joson Ng: 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 me an email in the episode description.

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A guest post by

John Joson Ng

MD-PhD Candidate at Duke-NUS Medical School | Director of Programmes and Education (Podcast) at Nucleate Singapore @nucleatesingapore

Nucleate Singapore