Innovating new cancer-selective biologics with PairX Bio’s Dr. David M. Epstein
Episode show notes and transcript
About The Guest
Dr. David M. Epstein is the President and co-founder of PairX Bio, a company specializing in the next generation of cancer biologics. David was first trained in chemistry as an undergraduate before attaining his Ph.D under Dr. Robert Abeles, commonly known as the father of modern enzymology. After working in a plethora of biotech companies and big pharma institutes, he eventually began his entrepreneurial journey leading up to the founding of PairX Bio. David’s passion in science and immense curiosity in how nature works is evident in all that he has done and is currently undertaking, which is devising a host of targeted therapies for cancer treatment.
📄 Summary
In this episode, David shares his experience and journey from working in various biotech companies and big pharma institutions to eventually building his own companies. One of these is PairX Bio, a company specializing in the next generation of cancer biologics. David stresses the importance of how being able to follow the science and being transparent and open with the discussions on data collected from research projects plays a key role in the success of a company. He also touches on the success of targeted cancer therapies, some of which has led to an increase in lifespan, as well as the limitations in terms of the range of diseases that can be treated with this therapy. He also highlights the future of therapeutics in general, discussing the push in biotherapeutics and immunotherapeutics and expanding the horizon where these new innovative treatments can be effective. Lastly, he touches on the importance of how to handle IP matters and protecting one’s IP.
🥡 Key Takeaways
The understanding of the transcriptome of tumors and cancers allows the possibilities of targeted therapies, allowing the patient to reduce the need for harsher therapies.
For companies to flourish, it is vital to be transparent and open with discussing data generated by experiments and research projects.
The current trend of therapeutics is skewed towards biotherapeutics and immunotherapeutics, which allows more focus on oncology therapy and targeted therapy.
It is common practice for many academic institutions to hold the original patent application of startups that journeyed through their pipeline.
💬 Quotes
"So following the science and then really not being afraid to have a transparent conversation with the people involved in the project to make sure that we have a clear understanding of what the data is telling us and the directions that, you know, it will likely lead us into."
“What we did at PairX is we just simply asked a question about the transcriptome instead of the genome. So remember the first three principles of targeted therapies were really based on genomic descriptions of the disease, but it's a paradox.”
“What we do is we focus on the transcriptome and we showed two things. We showed that many transcripts are alternatively spliced specifically in cancer and that those transcripts can be characterized as new druggable targets”
“I think that if you look at the positive reasons to work in Singapore, there are many. I think the funding for basic research is substantial, the talent pool in basic research is substantial. I think the transparency and the way that scientific results are communicated in Singapore is a plus.”
⏱️ Timestamp
01:01 - Introduction
05:14 - Origins of PairX Bio and Key Characteristics for a Successful Startup
13:11 - Key differences in the Process of IP patenting
18:20 - Singapore VS USA Biotech Ecosystems
20:51 - Future of Singapore’s Biotech Ecosystem
🎙️ Transcript
Episode Preview
Dr. David Epstein: Follow the science, I think, is a really good and important aspect to make for success. Both in academia as well as in the biotech spheres. Following the science and then really not being afraid to have a transparent conversation with the people involved in the project to make sure that we have a clear understanding of what the data is telling us and the directions that, you know, it will likely lead us into.
Aakash Kumar: Hi, thanks for joining us on Nucleate Singapore Pulse, Singapore’s premier podcast on the biotech ecosystem. I am your host, Aakash Naresh Kumar, the Lab Community Manager at Life Science Incubator. Whether you’re a student thinking about creating your own startup or an industry professional looking for diverse perspectives, this is the podcast for you.
The show notes and transcripts for the episode can be found on nucleatesingapore.substack.com.
Aakash Kumar: Today, we are very glad to have with us Dr. David Epstein. David is the co-founder and president of PairX Bio, a company that specializes in the next generation of cancer selective biologics. Thank you so much again for joining us today, David.
Dr. David Epstein: Thank you and nice to meet you and, nice to say hello to everyone.
Aakash Kumar: All right. So before we start, could you give our audience a brief introduction about yourself?
Dr. David Epstein: Sure. I am a chemist by undergraduate training and a biochemist and biophysicist for graduate training. I've spent the bulk of my working career in a variety of biotech and larger pharma institutions. And, I've basically focused on aspects of drug discovery and early clinical development, and I believe that's why we're having this conversation today.
Aakash Kumar: I see, like you mentioned, you have a wide variety of background across academia and industry. Could you share what initially sparked your interest in science and how that led you to a career focusing on cancer research and drug development?
Dr. David Epstein: I would have to say I get this question frequently from my kids and from others, and I would say that I knew pretty early in my life that I liked science and that I was interested in understanding nature and so I was always a science geek.
That didn't really predict that I would be in drug discovery and development. I think that after getting an undergraduate degree in chemistry and demonstrating an interest in I think the emerging biotech area in the U.S., at the time, it really took me into a graduate program where I met a couple of my scientific heroes.
I was really excited to be able to do a Ph. D. thesis with a man by the name of Dr. Robert Abeles at Brandeis University in the Boston area and he was a fantastic chemist and really the father of modern enzymology.
And that's really what I was interested in. I was interested in chemistry at the time, and I was interested in how enzymes catalyzed chemical reactions. And that led to a longer interest in just how basic research was done and I was learning at the time that my background would fit nicely, both into academia as well into industry.
And so I elected to do a postdoc with another person who is a hero of mine in science. And his name is Steven Benkovic. And so when I was working with Steve, I was able to combine interest in biophysics and structural biology, and I got to do a really, really fun postdoctoral study at the Scripps Research Institute in La Jolla, California.
And I would say my journey in basic research really was catalyzed by those two individuals, Robert Abeles and Steve Benkovic, and really just think the understanding at the time that there were great ways to contribute to society by developing drugs to benefit patients in a variety of unmet needs in areas of, I think critical importance in healthcare and that ultimately led me into really a focus on oncology. But also some work in other areas of therapeutics that maybe I'll touch on later in the interview.
Aakash Kumar: It's really good. People say it's lucky you get to work with your hero. So that must've been very nice.
I, as well, when I was young, I knew from a young age, I want to do science. So that's really nice to hear that. It's also quite interesting, you mentioned that you started out from doing chemistry and then you slowly shifted into something more towards biology or towards therapeutics and things like that.
So, in that sense, what would you say are some of the key characteristics, to differentiate between chemistry work or, let's say, doing biology related stuff? Is there any difference? How so?
Dr. David Epstein: Well, the biology that I focused on was really sort of biological chemistry or these days, often called bioorganic chemistry.
It was really just using chemical principles to understand how life happens. So in that sense , they're kind of the same. I just, for me, I wasn't as interested in material science or chemical synthesis. And so my interest in biology was kind of at the nexus of where chemistry meets biology.
And that's really what led me into all the stuff that I'm doing today.
Aakash Kumar: I see. So it all basically comes together. And then PairX Bio was born.
Dr. David Epstein: Not that simple, but okay.
Origins of PairX Bio and Key Characteristics for a Successful Startup
Aakash Kumar: Fair enough. But, since you mentioned that how all the influences led you to PairX Bio, what would you say right now are the key characteristics for the importance for the success of a startup?
Dr. David Epstein: Well, so I've had the opportunity to be involved in four different kinds of startups over my career, coming from work that I had carried out directly.
Yeah, so, I would say that, in retrospect, there's a couple things. I mean, one, you have to be committed and committed to your vision, to trust in your sort of own intuition.
And I would say that , that commitment and the trust in my own intuition really has led me to want to continue to do these kinds of startups. And the reason I think is really, just driven by the passion and my interest in science. But also over the years, I guess it's just a belief that I can find my way forward, with enough fortitude and attention to the work at hand.
Follow the science, I think, is a really good and important aspect to what will make for success. Both in academia as well as in the biotech spheres. Following the science and then really not being afraid to have a transparent conversation with the people involved in the project to make sure that we have a clear understanding of what the data is telling us and the directions that, you know, it will likely lead us into.
And I think if you trust yourself, you're honest with the data and you're transparent with interpretations of the data, with everybody involved in the project, you increase your chances of moving into an area that is meaningful and that could eventually be funded as a startup or, could be a major project in an academic lab.
I think the principles are the same. You know you have to be honest and you have to be transparent about what the data is saying.
Aakash Kumar: Hmm. I think that is really important to be transparent to really, like you said, you know, focus on the science, having that strong vision and that does definitely help. So now that you mentioned the focus in the science, could you give us an overview of what PairX Bio is focused on and the inspiration behind its founding?
Dr. David Epstein: Sure. So I would say my previous years of work were focused on the development of molecular targeted therapies. So in some ways, it's the first generation of genomic medicines in oncology. What that really meant was that if we knew a mutation that was driving tumor growth, and it was in a druggable target.
We felt that we could develop drugs that would be specifically capable of targeting the mutant isoform and leaving alone the vast pool of wild type isoform that would exist, that does exist in, in our bodies. So targeted therapies focusing on genetic alterations was really the, I think the cornerstone of the work that I did at OSI and the cornerstone of the work that we do and is being done at Black Diamond Therapeutics. That said, I think, after many years of genomic sequencing and the sort of successes that we've seen in targeted therapies, it's become fairly clear that the number of novel targets that are amenable to that approach is diminishing and, in fact, is probably nonexistent. And what you actually see in the field is a kind of iteration towards best in class, which is good for patients. It makes better, safer drugs. But the disease and the indications that you can target with that approach are also limited. So we've made great advancements in the treatment of cancer in a variety of solid tumors, as well as liquid tumors over the last 10 to 15 years.
We've certainly increased lifespan. We've made what was essentially, a dire diagnosis livable, anywhere from, I would say, 1 to 5 years before having to revert into chemotherapy and some of the harsher treatments that are associated with oncology. So, what has happened in addition to the successes is the recognition of the limitations. So smaller patient populations, defined tumor types, and essentially a limited number of validated oncogenic targets. So those are the three things that I think are really sort of what we are facing today in targeted therapy and oncology therapy.
And so you see a push into biotherapeutics and immunotherapeutics. And other areas where we potentially can expand the treatment population with these innovative medicines. What we did at PairX is we just simply asked a question about the transcriptome instead of the genome. So remember the first three principles of targeted therapies were really based on genomic descriptions of the disease, but it's a paradox .
What we do is we focus on the transcriptome and we showed two things. We showed that many transcripts are alternatively spliced specifically in cancer and that those transcripts can be characterized as new druggable targets. So we did that. But the important point is we showed that the prevalence of these transcripts and these changes in splicing are essentially shared within patients within a given tumor type and are shared across tumors.
So, for example, the very well known oncogene KRAS has two critical splice variants, and those variants are shared in pretty much all KRAS positive tumors. So would that principle be the same for other as yet undetermined oncogenic targets?
And we've shown that it does. And that's really what we've essentially done. We've converted biotherapeutics into targeted therapeutics with specific patient populations in mind, and with the ability to develop drugs to broader groups of patients. That's what PairX is all about.
Aakash Kumar: I see. So there's really many rounds of trying to figure out what is the issues, trying to solve that. And as we all know, This kind of work does take a lot of time and support as well.
So, trying to pivot a bit towards the more business side of things. For this support, PairX Bio has received all this support from different investors, such as Esco Ventures to Avende sora or to Versant. So what is your process for managing these investor relations at these different stages of PairX Bio's growth?
Dr. David Epstein: I mean, I think the main thing again, it kind of comes back to transparency and making sure that we're satisfying, you know, whatever the needs are for given investor groups in terms of, access to information. So I have regular meetings with each of the board members and investors in the company, just to provide them an update on progress and direction that we're taking .
Maybe the broader question is how do we identify these investors? And really it's essentially as much networking as well as understanding what certain investors will look for in an early, mid or late stage investment.
Aakash Kumar: I see, yeah, It's really all about transparency, letting them know what you guys are going to be doing, what's the investment going to be used for.
So, moving on, the PairX Bio, as we understand, was spun out from Duke-NUS Tech Transfer Office. How different is it, the process of spinning out from academia versus directly approaching investors and incubators, like you mentioned, all these networking sessions?
Dr. David Epstein: Well, I mean, I think that in some ways, they're kind of the same.
I think that the reality is each comes with their own requirements based on what the institution, wants out of a commercialization effort and then, of course, what an investor wants in the acquisition of IP in order to build a company. And so they're clearly fundamentally different entities with different responsibilities to their core supporters.
But at the end of the day you have to find the common ground. The common ground is essentially having a positive impact on patient care, through the development of technologies that come from one entity and a licensed into the other. As long as everybody recognizes that's the goal. Then I think all of this can happen fairly smoothly and efficiently. And certainly that's been my experience as long as you are able to sort of get everybody to see the mutual benefit and things can move along quite well.
Aakash Kumar: It's really all about teamwork in this sense.
Dr. David Epstein: Yeah, exactly.
Key differences in the Process of IP patenting
Aakash Kumar: So in terms of all these different kinds of people of different backgrounds that you speak to, what are some of the key differences in the process of IP patenting?
Dr. David Epstein: I would say that maybe a company is willing to take a little bit more risk and patent earlier, whereas, in an academic setting money is tight and, has to be managed more carefully per say. And the patents have to match the goals of the institution. So I would say from that perspective, what gets patented. And when is somewhat different between the two institutions. You know, ultimately a patent is a patent.
It's just a, you know, what is the strategy and how are you trying to maximize the benefit to whichever institution you're talking about.
Aakash Kumar: That's true. So thinking of from an academic point of view, since PairX Bio did spin out from Duke-NUS, does PairX Bio own the majority of the patent or is it licensed from CTED?
Dr. David Epstein: No, it's essentially an example of where institutions want to own their own IP. So, Duke-NUS, like many other academic institutions hold the original patent application and sort of prosecuted on behalf of their licensees. So we licensed the initial patents from Duke-NUS. And then we returned commercial benefit to the institutions upon success with the company.
I would say the important point here is if we stopped at the Duke-NUS patents, we wouldn't really have a company and so we're continuing to innovate on our own and file our own IP. And that built, essentially on the foundation of what we license from Duke-NUS. But it's not owned by Duke-NUS. It's owned by the company.
Aakash Kumar: I see. Yeah, having an IP system is very important. Do you have a centralized group of people in your team who help with this IP?
Dr. David Epstein: Yeah, we do. We hire experts.
Aakash Kumar: With all this IP and stuff, what would you say are the most significant milestones that you're working towards in the next year or two for PairX Bio, both in terms of scientific discoveries and also clinical development?
Dr. David Epstein: So we've got two programs that are moving forward in antibody discovery.
And the goal is to bring those, in the next two years, into the clinic for both those two programs. So that's our major objective for the upcoming two years, along with commensurate financing to support the growth of the company now and into the future.
Aakash Kumar: Sounds like a very exciting time for you guys.
Dr. David Epstein: It's busy.
Aakash Kumar: Busy is good, busy is good. You mentioned this antibody if I had to call it antibody therapies, what potential impacts do you think these therapies could have on patients, particularly those with difficult to treat cancers?
Dr. David Epstein: Again, it kind of comes back to that longer answer on how we evolve PairX.
And so we believe we have essentially a method for identifying patients that carry the variants that we're targeting. We target those variants with selective antibodies. Then, we treat patients with those antibody therapeutics that are identified as variant positive patients. So I would say you go full circle, you identified variants in patients, develop drugs to those variants and now treat patients with a similar profile of variant expression in the clinic.
So, the nice thing is those patients would not have had any benefit through other targeted therapies. So the approach that we're taking adds to the, I would say the armamentarium of therapeutic choices that clinicians will have to provide to the patients that come into their clinics.
Aakash Kumar: I think it's really inspiring to see companies like yourself working on these real world problems that we face and it definitely will help whoever who hears these stories to push on and also, make them inspired to do something good for society, I guess.
Dr. David Epstein: We hope so.
Aakash Kumar: So now we just pivot slowly more towards the ecosystem of Singapore. You've now brought yourself and your expertise to Singapore. You're also closely involved with Duke-NUS. So what actually motivated your decision to work in Singapore?
Dr. David Epstein: I came initially to Singapore in 2013 .
And it was an interesting opportunity to help build another stage of the biotech ecosystem, that's constantly evolving in this country. So I would say I'd spent a bulk of my career associated with Asia or working in Asia. Through OSI, through Astellas, through teaching opportunities that I had before graduate school.
And, this seemed like a natural approach and an interesting challenge to sort of affect positive change in the Singapore biotech ecosystem. And that's really what has kept me interested in working here.
Aakash Kumar: It's really nice to hear as well, we have another fellow supporter of the Singapore local biosystem.
So you mentioned that you were mostly in Asia. Would you say that within Asia itself, each of the different countries biotech system, is it different from each other from the way they work?
Dr. David Epstein: It has to be, but I don't think I could explain , what those differences are. Fundamentally, people bring not just their scientific intuition and what the focus is, but there are needs associated with each society that are different.
As an example, there are just specific needs in Singapore that may not be matched anywhere else in Southeast Asia or in the U.S. But, the needs for therapeutic intervention, the needs to help patients, that remains the same, obviously.
Aakash Kumar: Hmm. It's all about we're all one human race, right?
Singapore VS USA Biotech Ecosystems
Aakash Kumar: You mentioned the U.S., so I would also like to ask, like, between Singapore's biotech ecosystem and the U.S. How does it compare, and do you think there's something that needs to be worked on, or something you would like to see more of in Singapore's biotech ecosystem?
Dr. David Epstein: I think that if you look at the positive reasons to work in Singapore, there are many. I think the funding for basic research is substantial, the talent pool in basic research is substantial. I think the transparency and the way that scientific results are communicated in Singapore is a plus.
I think, as you can tell from other parts of this conversation, to me, that's an essential piece for success in health care and innovation in general. That said, there are certainly differences between the U.S. And Singapore. I don't think it really helps to sort of focus on those differences. I think what's really important is to understand, there are gaps in experience and there are gaps in understanding how to move these startups and biotech initiatives forward in Singapore.
There are gaps everywhere, but that's a specific gap to Singapore. And the more that we do it in Singapore, the more experience that we have, the more companies that start and churn out experienced researchers, the better off Singapore will be. And I think what we're actually seeing is that growth in the ecosystem, the maturing of the ecosystem it's happening at a, I would say, a reasonable pace.
It's not perfect but, I think we've been able to succeed with PairX in Singapore and I think others can do the same.
Aakash Kumar: It is very nice to hear the success of PairX by itself. And I could not agree with you more. We are seeing that it's maturing in Singapore slowly, but surely.
Speaking of your success, we also would like to also take this time to congratulate you and your company on receiving the Amgen Golden Ticket and the GLX Navigator Award. Congratulations.
Dr. David Epstein: Thank you.
Aakash Kumar: How have these awards and resources impacted the company's growth and the ability to accelerate your R&D efforts?
Dr. David Epstein: Well, it's a little early to say we just received them a couple of months ago, but it does, I think, gives us access to these two great companies. It gives us access to other companies that are looking to build in Singapore. So, I think from that perspective, the networking and the essentially the basic awareness of what's going on both at the company level and at the Singapore level was fantastic for us.
Future of Singapore’s Biotech Ecosystem
Aakash Kumar: That's really nice to hear. So, with all this that you have mentioned earlier, what do you envision the Singapore biotech ecosystem would look like in the next five to 10 years?
Dr. David Epstein: Well, let me get out my crystal ball. Oh, I don't have one. I would say that, I think we expect continued growth.
I think the number of biotechs that we're seeing develop out of Singapore IP continues to expand. Without putting a number on it, I would just say that, I would expect to see more and more experienced people here to help with new companies that are spawning at that time.
Aakash Kumar: I couldn't have said it better, it's really about finding the right people to help each other out.
So, in terms of developing therapies, the idea can be groundbreaking and trying to develop this novel therapies can be a monumental effort. So on a day to day basis, what would you say is that one thing that motivates and inspires you to push on with your work?
Dr. David Epstein: You know, I think that if you don't believe that you're helping, you have the ability to help patients in the future. It's hard to imagine wanting to do this because it is a long haul. You know, it's years in the making. And you just have to believe that what you're doing is going to provide benefit to patients.
It really ultimately comes down to improving patient care.
Aakash Kumar: What you say does feel like there's like a personal touch to it. So learning from all these multiple cancer research programs and founding biotech companies that you have done, in that case, what would you say are some of the key lessons that you've learned about translating this scientific research into impactful therapies?
Dr. David Epstein: So not surprisingly, I'm going to go back to transparency and honesty and following the science and being confident in one's capabilities. So, I think that if one follows all of that, then at the end of the day, if you're a good listener and you're stubbornly optimistic, you have a chance of succeeding here.
Aakash Kumar: I see. Very important qualities, I must say. So in your whole illustrious career, this is just a fun question to ask. Is there anything that you would have done differently? And if so, why?
Dr. David Epstein: You know, I'm not a person that has a lot of regrets, I don't. So in, in many ways, I think you have to learn from past mistakes and you have to learn from the sort of people that you sort of view as heroes and kind of goes into your personal make-up.
But that said you know, having an open mind, being humble and having humility, learning from other people, being confident. At the end of the day, I don't think it does anybody any good to say what I could have done differently, because we could have done everything differently and everything better.
But I just am not a person that lives with a lot of regrets, particularly from a career perspective.
Aakash Kumar: Not living with regrets. That is a wonderful lesson for any aspiring scientist. I think in science, if we'll have too many regrets, we'll be frustrated.
Dr. David Epstein: My graduate advisor used to tell me that you know, your experiments, 90 percent of the time they fail, so you might as well get used to failure.
10 percent of the time, the experiments may work. But you spend 90 percent of that 10 percent trying to confirm that initial observation. So at the end of the day, 99 percent of your time is essentially fraught with failure and frustration. And I used to think that was the most humorous piece of advice, but I think it's probably turned out to be true.
It's the nature of, what we do and it's really important to embrace it and just, keep your head down and focus on the data and see where it takes you.
Aakash Kumar: I have to agree with you 100 percent on that. Yeah. I had the same issue when I first started research and someone told me you will fail most of the time.
So if you're going to be frustrated, you will, you will suffer.
Dr. David Epstein: Science is a difficult taskmaster.
Aakash Kumar: It really is. It really is. But I think we have come to the end of our podcast . Thank you so much for taking your time out to, let us interview you for his podcast . What you said and everything and what we've discussed will definitely help our listeners and inspire people to, you know, following your footsteps and help the Singapore local biosystem.
Dr. David Epstein: That's great. Thank you. I hope so.
Aakash Kumar: Stay tuned for monthly podcasts with key stakeholders of the biotech ecosystem including founders, investors, and policy makers.
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