Imagine living a long and healthy life. Imagine not getting sick at all at 80 years old, or who knows, maybe 100 years old. The possibilities are endless thanks to today’s advancements in science and technology, and today, Victor Bustos joins us as the COO and co-founder of Refoxy Pharma.
Refoxy is a biotech startup whose goal is not to extend the human lifespan but primarily to extend health. Basically, Refoxy aims to keep people healthy for as long as possible, which is both noble and challenging in itself, right?
Initially, Victor was working in academia, but then he was motivated by the fact that life seemed too short coupled with him having read studies on how it was possible to change how long and how healthy people could live.
Thus, Refoxy Pharma was born. Pivoting from the academe to creating a startup, however, was no easy feat, so Victor had some amazing insights and lessons to share with us about his journey from PhD student to startup founder. You won’t want to miss what he has to say.
Maiko Schaffrath 00:00
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You are listening to Impact Hustlers, and I am your host, Maiko Schaffrath. I have made it my mission to inspire the next generation of entrepreneurs to solve some of the world's biggest social and environmental problems.
And for this reason, I am speaking to some of the best entrepreneurs out there who are solving problems such as food waste, climate change, poverty, and homelessness.
My goal is that Impact Hustlers will inspire you, either by starting an impact business yourself, by joining the team of one, or by taking a small step, whatever that may be, towards being part of the solution to the world's biggest problems.
In today's episode, I speak to Victor Bustos, the co-founder and COO of Refoxy Pharma, a company dedicated to developing medication that extends the human lifespan and especially maximizes the healthy lifespan of people. Victor has a background in academia.
He's actually done a PhD and has been a postdoctoral researcher at Max Planck Institute for Biology of Ageing in Germany, and he made the transition from academia into co-founding a company, and I'm really excited to speak about that and the state of the art of the signs around aging and how we can prevent it. So, thanks so much, Victor, for joining me.
Victor Bustos 02:53
Well, thank you very much, Maiko, for the kind introduction and for inviting me. I'm very happy to be here.
Maiko Schaffrath 02:59
Appreciate it. So, the first question I'd like to ask is to understand a bit more about you and your personal journey. It seems, really, like you've discovered this topic of allowing healthy aging to happen and extending the human lifespan as your life's work.
Again, you've come from an academic background in that space, you've done a PhD, you've done postdoctoral research, and now, you have started a company in that space. So, tell us, what motivates you to do that? And what is your personal journey to get here?
Victor Bustos 03:41
Yeah, thank you for that question. I mean, before I start, I think it is important to correct a little bit of the statement that you made, because even though longevity or the idea of extending a lifespan is a very attractive and intriguing one, and there's many people trying to work on it, our goal really is to extend health.
We know that as people get older, they become more susceptible to disease, and the idea is just to extend the healthy years that people get. But, let me start by telling you a bit about my motivations.
Very briefly, I'm actually originally from Colombia, and I started biology back there, and already doing my Bachelor's studies, I was fascinated with genetics and a little bit troubled by mortality and how finite it is.
It's sort of annoying, because I was always very eager to learn and experience new things, and I always thought and I always felt that life was a little bit too short, or at least it felt that way, at that time.
And so, while I was doing my Bachelor studies, I actually read a number of publications, a number of papers that identified that by intervening in different model organisms, in modifying their genetics, you could actually, in turn, modify how long and how healthy they would live, and this was really a revelation for me, because it basically implies that this aging process can be modulated through genetic factors which, in turn, also means that genetic or the aging process can also be seen as a disease.
If there are specific proteins, specific genes that can be, let's say, targeted with medicines or with different drugs, maybe there is a way for us to not necessarily just age and become more fragile and more susceptible to disease but potentially, there could be a way for us to age in a more graceful manner, if you may, and become basically less susceptible to those diseases that come with age.
Maiko Schaffrath 06:03
Got it. I want to zoom in on that, because on the on the first point that you mentioned, there is this school of thought, and there [are] a few people basically setting themselves the mission to cure the disease of death, so to say that, basically, the ultimate goal is that we eliminate death, and we basically live forever.
That's the goal of it. Did I understand you correctly that that's not really a goal, or do you think that's a goal that we should aspire to? What's the ultimate goal here?
Victor Bustos 06:36
Yeah, that is a great question, and I don't know if there's any right answer there, because just to frame things a little bit, what we consider death today is not the same thing as we consider death 50 years ago or 100 years ago. A heart attack used to kill you instantly, and there was nothing nobody could do.
Nowadays, thanks to advancements in medicine, you could actually recover from a heart attack and live plenty of years after that. And so, the concept of death is really complex.
Again, I'm not an expert in this area, but I do know that we need to continue aspiring to have healthier lives, because the economic and the societal burden of having older individuals that are more and more fragile and susceptible to disease is just too high. In addition, you need to think that we have been treating disease as they appear for many, many years, but that mentality is slowly changing.
We're starting to become more aware that perhaps the best approach would be to try to prevent those diseases in the first place. So, I think it's a little bit of the combination of these two things that we're trying to move forward.
Maiko Schaffrath 07:57
Got it. Amazing. And then, yeah, just zooming in as well on your personal motivation. Is there any kind of moment in your life or any circumstance that got you to say, "Hey, this is what I want to work on. This is what I want to do for at least the next couple of years of my life"?
Victor Bustos 08:16
I mean, it was very clear. Again, since the first time, I can tell you exactly the paper. This was a paper by the lab of David Sinclair that basically highlighted how specific mutations in a gene called Sir2 was able to extend the lifespan of yeast.
Again, this was really impressive for me. It just made things so much clearer. It facilitated that decision for me that this is indeed what I needed to do with the rest of my life. And at least until now, that has been the case. It might change in the future, who knows, but until now, I'm very eager and very motivated to continue working in this space.
Maiko Schaffrath 08:55
Got it. Alright. We haven't actually covered much on specifically Refoxy yet, so let's give people a bit of an overview of what does Refoxy do and the drugs that you're developing, how do they work?
Victor Bustos 09:11
Yeah, so very briefly, Refoxy is an early stage biotech startup that I co-founded along with Apollo Health Ventures, and we are exclusively focused on trying to develop new medicines that can regulate or, in a way, turn on a specific protein.
This protein, which is called FOXO, is very, very interesting, because we know from multiple studies in animal models, in animal model organisms, that by modulating or by regulating these proteins, you can intervene in different diseases, you can prevent different diseases, you can even treat In different diseases.
But what is even more fascinating is that thanks to genetic studies, in long-living human populations, we know that there are specific genetic variants from these genes that are associated with that long life in humans. I mentioned just the correlation at this stage.
However, there seems to be mounting evidence from multiple sources that highlight these proteins as a very interesting target. One of the challenges, however, is that this protein is, in a way, regulating multiple other downstream genes. And so, it is very challenging to try to develop medicines for it.
However, we are in a fortunate situation that we found a scientific co-founder that has expertise on trying to drug this target, and we're trying to basically perform these early, what we call, killer experiments to determine whether the hypotheses that we have generated can be correct. And if they are, then we will have more arguments to continue developing these novel medicines.
Maiko Schaffrath 11:22
Got it. And at what stage are you at? Are you conducting mainly the research at the moment or are you already at the stage that you're starting to produce some medicines?
Victor Bustos 11:32
No, no, no, we are very, very early stage. We have started research and development a bit more than a year ago. And just to put things in context, on average, from idea for a novel medicine to the generation and actually, the marketing of that medicine, on average, you could be looking at 12 years, and the reason for this is because not only [do] you have to do early research experiments with different animal models, but you also have to go into clinical trials and determine the safety and efficacy of these medicines in a specific disease context.
Maiko Schaffrath 12:11
Got it. That means you now have a situation where you actually co-founded the company with Apollo, and I'd love to understand a bit more about that arrangement. I assume there's actually just a quite a small subset of investors that are willing to invest in those type of timelines, especially with startups that are just starting out, that don't have all the resources that Big Pharma has to develop new medicines.
So, tell us a bit about that challenge and how you tackled it.
Victor Bustos 12:42
Absolutely, and it's actually a very, very important point. I'm in the fortunate situation of working with Apollo, that it's a little bit of an unconventional venture capital firm for two reasons.
The first one, they are exclusively focused on developing therapeutics for the treatment of aging and aging-associated disorders, and the second reason is because they not only invest in biotech companies, they also create them.
And so, originally, when I finished my academic career, I started working with Apollo as an entrepreneurial resident with the idea of creating biotech companies. And out of that initial work, we started Refoxy Pharma in 2020 precisely because Apollo has this focus on company creation, and they understand the risk of a biotech and life science investment.
The ideas that you generate or we create small biotech projects, ideas, companies, and we test hypotheses as fast and as cheaply as possible with the idea that if something is actually worthy of more investment, then the science and the result are going to inform that. But in general, just like you said, this is not the case for many investors or more traditional investors.
It is possible that you can have perhaps angel investors in the biotech space that could have tolerance and appetite for that kind of early stage deals that will allow you to test early hypotheses. However, in general, this is actually a challenging spot to finance, particularly in Europe, the transition from academic research directly into biotech. And so, because of that, I believe that or we believe that Apollo is doing a great job trying to bridge that gap.
Maiko Schaffrath 14:40
Got it. And you said validate hypotheses, that's what you did as fast as possible. Again, it sounds to me as somebody that's not in that space, but that's started to learn a bit about the space that validating anything fast is a big challenge, like if you truly want to validate a science and medication as you said, it's these 12-year timelines.
So, what does it actually mean, in practical terms, to validate hypotheses? And how much work did you do to then decide, "Okay, we're actually going to launch this. This is something that we can do"?
Victor Bustos 15:16
Yeah, that is a great question, and there is no real easy answer. But briefly, we know that there [are] plenty of scientists and researchers around the world that are conducting very, very interesting basic research, and we know that that basic research can have the potential to be translated into potentially a new biomarker or a new medicine.
And so, the approach that we took or we take to the beginning is to reach out to researchers, professors, postdocs, and discuss with them their science, their current findings, whether they have thought about a translational project.
We do this either directly reaching out by email or by going to conferences and speaking with them. Once we have identified an area of research or technology that could be potentially interesting but just needs a little push to be actually tested, we define whether a company can be founded.
We speak with a potentially scientific co-founder; we speak with their institutions to understand under what kind of rules of collaboration could take place. And based on that, we set up a timeline, anywhere between one to two or three years, because, again, we're trying to test this fast, but biotech and science is not tech.
It's not like writing software, and you're done. This actually takes time. You are depending on the cell models, the animal models, the chemistry. And so, we are aware of that risk, and that is a little bit of the reason why we try to do many companies in parallel, because that is going to mitigate a little bit the risk of being able to test those hypotheses fast and early enough.
Maiko Schaffrath 17:13
Got it. So, it is still a portfolio approach then for Apollo. We're talking about Apollo now, but for them, it's a portfolio approach to say, "Okay, we're going to make a lot of small bets here in the space and hope that at least a few of them work out and actually develop the best solution."
Victor Bustos 17:32
Correct. That is the approach. But just to be clear, this is a much more active investment than just making the bets. This is an active engagement with entrepreneurs are the people that could be hired to push those new startups forward.
Maiko Schaffrath 17:49
Got it. And then, what I'd like to understand is really the advantage and disadvantage of the position you're in. Obviously, you're backed by a great investor that has knowledge in the space. You have certain advantages of being a small team, fast moving, etc. Y
ou don't have to deal with the red tape and maybe also, lack of priority sometimes in Big Pharma companies where certain things are not necessarily highest on the priority list, because there [are] maybe more lucrative things to do or other priorities and focus areas, so there's a ton of advantages.
Obviously, there's a ton of disadvantages. That's why I assume that there [are] biotech startups, like in Germany, the one that developed one of the COVID vaccines partnering with Big Pharma to actually bring it out.
So, that's BioNTech. I'm just wondering, how do you see that role? Do you think it's overall an advantage to be a small startup in that space to be able to develop something or do you feel at some point, you may need this kind of partnership with existing incumbents to actually bring this to market?
Victor Bustos 19:12
To be honest, I think that both the small biotech and the Big Pharma are necessary players in the field, because, like you mentioned, being a small startup has a lot of advantages. You can move fast, you can, like we do, test hypotheses.
And if they fail, well, they fail and then you move to the next one, but you're very much focused and committed to a particular area or a particular disease or a particular approach.
This is actually very, very useful, because once you have validated your hypothesis, once you have generated enough scientific data that backs up your claims, you can go to Big Pharma or other investors that have more experience in things that you know you don't have the skills. I'll give you an example, manufacturing.
I have no real experience with anything related with full-scale manufacturing of particular medicines. It would be naive of me to think that I could figure that out by myself. And so, going to people like Big Pharma that has that kind of experience actually makes things easier for everybody.
It accelerates the generation of that potential medicine, it allows you to tap into the knowledge base of that particular company, it allows patients to potentially have access in a much faster and ready manner to that potential medicine.
So, I think it is a really important balance between those two approaches. Whether in the end, Refoxy or any of the companies [are] actually just partnering with pharma or [have] been acquired, it's a different story, but I think you need all of those players to be in the field.
Maiko Schaffrath 20:54
Got it, super interesting. Let's move a bit into lessons learned on your journey. We spoke to this previously, is one of the things that you managed so far is you made the transition from academia into entrepreneurship. There's a huge debate around loads of research taking place at the best universities and Institutes like the Max Planck Institute and then getting stuck there and not getting commercialized into actual solutions.
There's also, I told you, my girlfriend is actually a PhD student right now, a PhD researcher and a doctor, and I just see the world of academia and entrepreneurship as so vastly different in many, many ways that I'm just amazed by anyone that makes that transition even in terms of maybe your own mindset.
Maybe you already had it, maybe you always had this entrepreneurial drive in you, but I'm just wondering, how did that go for you, that transition from academia to entrepreneurship, both in terms of mindset, but also really practical things of actually launching the company?
Victor Bustos 22:10
Yeah, I think it's, like you said, not easy. I want to believe that I have always had that sort of entrepreneurial mindset, but the reality is that I was always very curious about this idea of building something from the ground up.
Just to be a little more specific, already during my, probably second year of the PhD, I realized that even though I love academia and I really enjoy doing science, I felt I could be a better fit for roles outside academia and more translational.
Not only that, I also felt that I would be more motivated doing something that had had much more immediate impact. And so, based on that, is that I made the decision early on that I wanted to transition into potentially a company creation role or potentially joining a startup that already existed and just try to push that forward.
I think the point that you bring up is very important that, indeed, there [are] a lot of academics and basic research out there and that you may feel they get stuck.
I cannot speak for many institutes, of course, but the impression that I do get is that we, as a society, could be much better if we had more scientists in different roles outside academia, and I'm thinking about roles like configuration roles, entrepreneurship roles, but also politics and the like.
I think we need more of this critical thinking approach towards reality to make informed decisions for us and for our society in our immediate but also long-term future.
Maiko Schaffrath 24:06
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That's a really good argument to make that, yeah, there is a need for more scientists to be in charge. Now, you're in Germany right now. You actually have an epidemiologist of the health minister.
I'm not asking you to make any comments there, but yeah, I guess it's interesting, especially with the pandemic that we've been through to see, okay, when can experts actually then come in and take some of these roles that before maybe were done by generalists that weren't experts in the field?
But yeah, I don't want to talk much about that. I'd be really keen from a practical point of view as well, for anybody that's not in academia to understand, how does this work?
So, you've done a PhD, you've done a postdoctoral research position at the Max Planck Institute for Biology of Ageing, and you probably discovered a bunch of things there. And then, you decided to start a company.
How does it work in practical terms? Who actually owns the IP? How do you actually go about this? How does it generally work? [Are] there any kind of general rules that need to be applied?
Victor Bustos 25:54
I mean, there are general rules, but in the end, this is a case-by-case scenario. There are different options.
If, for example, somebody was doing research and, during their PhD or postdoc, discovered something that could be patented or could be translated, then this person could theoretically start a company, ask the institution or the professor, whoever owns the IP, to license that technology into the company, and then coordinate from the other side with investors to get enough money to get started. I think that is a valid, but also very challenging approach.
Like you mentioned, the transition from academia to entrepreneurship is not easy, but I do believe that this entrepreneurial mindset is actually very much present among researchers. What is a scientist if not an entrepreneur?
You're trying to come up with ways to test ideas, and then based on the information you get, you are trying to come up with new questions to ask.
And so, in the end, I believe that the approach is very similar. However, the practical terms in terms of long-term thinking, like how are you going to justify doing research in this area but not that one, how are you going to justify asking for this amount of money, not that one, those are the details that are important, that are hard to wrap your head around once you're transitioning.
I think it is, again, important to not sell yourself short as a scientist, because I do believe that there is a lot that one can bring as a scientist into any endeavor. And so, just having this open mind of being able to learn anything and try to learn anything, that's going to give you a lot of ground.
Maiko Schaffrath 27:55
Got it. And that's interesting that you brought that up as well. In my mind, the worlds of science and entrepreneurship are so different, but so many of the basic tools and ways of working and thinking should be overlapping quite a lot.
And if you look at things like lean startup and experiment-driven approach and all these things, and applying the scientific method to entrepreneurship rather than just randomly, sometimes, in the public media, you get the impression that entrepreneurship is only about geniuses coming up with genius ideas, and then they just execute the best way possible, and then they become billionaires.
But in reality, most entrepreneurs are probably running experiments constantly until they find something that works. So, do you think it's actually closer to each other than it sometimes seems to be the case? Or how's the difference in mindsets there between those two things?
Victor Bustos 28:53
Yeah, I think they are absolutely closer to each other than people might be at least consciously aware of. But in reality, both scientists and entrepreneurs are constantly testing and asking questions and trying to figure ways out to make things work.
And if they don't work, you ask why didn't they work, and if you figure it out, then you can try a different way. But in the end, it's just a matter of asking the right questions and trying to find the right tools to answer those questions.
Maiko Schaffrath 29:25
Got it. And then, on that journey of making the transition, what was the biggest learning for you or anything unexpected on that journey that came up that you can share with us?
Victor Bustos 29:40
Well, I mean, even though I tried to educate myself and read a little bit about entrepreneurship and venture capital and try to understand a little bit the world of business, I think I was very naive at the beginning on how exactly companies are created and how they're created and why they're created, because, again, a scientist or at least I always had this very romantic idea like, oh, if the science works, we follow the science, and that's it.
But in reality, you really need to make an effort to not only make the science work, but have a compelling story as to why this makes sense to do it today and to make an investment today, because you need to be able to align incentives for yourself, for the researchers, for the investors, and so on.
And so, I think at the beginning, I was really naive about this, thinking that if the science was good enough, everything else would fall in place, but that is not the case. There is plenty of fantastic science and technology that even though they have a lot of potential, since nobody has been able to actually leverage that, it's really, really challenging to see how they could be implemented in the real world.
Maiko Schaffrath 30:58
I guess that refers to, largely as well, just the ability of building a business with a compelling business model. It's all great if the science is amazing, but if you don't have a business around that, you'll unlikely be able to scale it up, right?
Victor Bustos 31:11
Maiko Schaffrath 31:11
Is that a challenge that you had to learn about more? How did you tackle that?
Victor Bustos 31:17
That is one of the things that I have been learning about. I'll give you an example. Everybody knows that's familiar with the pharma models of selling medicines to patients that need them, and they would pay for those medicines either themselves or their insurances, but the question becomes a little bit more complicated when you're talking about different modalities, like for example, gene therapies.
These are interventions that took many years and many millions of dollars to develop, but that have the potential to cure genetic diseases in one single dose. And so, the question that companies are actually trying to answer at this stage is, how do you price that one single intervention?
And so, one of the approaches that they have been taking is the fee for success model where you only get charged if the intervention is successful, which makes sense. The other one is that you could try to not only charge what the generation that medicine is, but for example, try to mitigate the cost of long-term treatment with other less effective interventions.
And so, for example, if you were having a genetic disorder, and normally, you would have to take around $50,000 worth of medicine for the next 20 years, then maybe this curative genetic treatment could charge you a fraction of that cumulative spending to make it worth it for the biotech company to continue producing that and to make it worth it for the kind of system, the machinery that is in place.
Maiko Schaffrath 33:06
Got it. Let me just have a think. I had three questions I wanted to ask. I need to prioritize a message to the editor just to edit that out. Alright, so one question I was keen to cover as well on that journey that you've been on is, really, what do you think is like one of the riskiest assumptions for you at Refoxy at the moment that you're making?
Is there something that really stands out? Again, don't feel the urge to uncover the secrets, but is there a theme or basic assumptions that you're trying to prove that you've uncovered through that journey?
Victor Bustos 34:01
I mean, I think the riskiest assumption that we're making would probably be that the models that we're using could actually recapitulate what we will see in humans. I think that can be said by or for many, if not most biotech companies.
We work in an imperfect world, because we don't have necessarily the best models for every disease. And so, we work with the information we have and the models we have to generate data that could support a particular hypothesis.
But even if that is the case in the cellular models or in the animal models, that does not guarantee that that's going to be the case in humans. That is the reason one why we have clinical trials, to test and to evaluate whether things are actually effective in humans.
And two, that is the reason why many medicines that have been developed throughout many, many years end up failing in those trials, and in the end, you never do anything with those.
Maiko Schaffrath 35:18
Got it. And then, how do you mitigate that risk as an entrepreneur? We spoke about Apollo perspective, and they have a portfolio approach, but now, you're in one of their bets. You're inside Refoxy, so all your chips are basically on the Refoxy table, isn't it?
So, how do you mitigate that risk that all these pharma companies and pharma startups have to take off really betting on something? Any advice on that? I know it's a tricky question very generically, but yeah, would love to hear some thoughts on that, yeah.
Victor Bustos 36:01
It's a great question and actually something that I think about constantly. I think there are two different approaches that are very popular. The first one is to try to have different assets within your company.
The fact that I'm trying to generate these regulators of FOXO doesn't mean I'm going to settle with having just one. I would like to have a number of them, so I can mitigate that risk.
But in addition to that, you also can think about the possibility of testing your approach, your intervention, your new medicine in different disease models, because, again, you cannot guarantee that if it works in one model, it's going to be translatable.
But if you start to see that this is actually a regular constant that you can recapitulate in cell models, including human cells, and also in animal models, then maybe you start building up enough evidence to say, "Hey, this has the potential to be highly translatable."
Maiko Schaffrath 37:12
I guess, to some degree, that's the company I mentioned before, BioNTech, which is based in Germany, and they developed one of the vaccines against COVID. That's what they actually did. They had actually, I think, the focus mainly on cancer initially, to use mRNA against cancer, then COVID came up. They shifted their focus to that for the moment.
So, I guess you need to have that flexibility in your head as well like, "What could this apply to? And how can I also pivot if one of the avenues doesn't work or not as quickly as we thought?"
Victor Bustos 37:45
Correct. That is absolutely correct.
Maiko Schaffrath 37:49
One last question for you before we run out of time is, if you think forward 10 years from now, how does the world look like if Refoxy succeeds? What's the vision that you're trying to work?
Victor Bustos 38:01
Well, if Refoxy succeeds in 10 years, we will likely be already testing our medicines in different human diseases associated with aging. And in that scenario, I want to believe that we're going to have the capacity to not only at least treat those disorders, but potentially start thinking about expanding its use to prevent them, which is in the end the goal that we're trying to achieve.
Maiko Schaffrath 38:32
Thank you so much, Victor. I really appreciate your time and your insights. I think we could do many podcast episodes together on this. We only barely scratched the surface, but thanks so much for joining today and really appreciate and all the best for your journey.
Victor Bustos 38:47
Thank you very much, Maiko. It was a pleasure talking with you and happy to take your word on it. I'm happy to do more podcasts talking about this fascinating subject.
Maiko Schaffrath 38:56
Yeah, absolutely. Let's do it. We can already set a calendar reminder maybe for 12 years' time, and then we'll do one around the public release of the drugs that you've developed. There's something in me that loves this long-term thinking that you're forced to adopt.
If you could release the drug next year, you would, but there's something about this, like even the question I asked, "What does the world look like in 10 years?," I'm like, "Okay, maybe we should ask him about 100 years and not 10." But in your case, but yeah, thanks so much for joining, and I really enjoyed it.
Victor Bustos 39:36
My pleasure. I also enjoyed it. And just a quick clarification, just because the average time is 12 years, that doesn't mean that that's what we're aiming for. We have a much higher bar that we're trying to achieve in a much shorter time.