Biotech 2050 Podcast
Autoimmune Innovations: Insights from Marshall Fordyce, Founder & CEO, Vera Therapeutics on Biotech
Synopsis:
In this engaging episode, host, Rahul Chaturvedi welcomes Marshall Fordyce, Founder and CEO of Vera Therapeutics, to discuss his transformative journey from physician to biotech entrepreneur. Marshall shares the story behind Vera Therapeutics' strategic pivot to focus on IG nephropathy and their development of atacicept, a promising B-cell modulator. He provides valuable insights into the biotech industry's landscape, emphasizing the importance of scientific rigor, adaptability, and maintaining a lean, effective operating model. Marshall's enthusiasm for advancing autoimmune disease treatments and his advice for aspiring entrepreneurs make this a must-listen episode.
Biography:
Dr. Fordyce brings more than 15 years’ experience leading teams in drug discovery, development, clinical translation, and commercialization of new treatments. Before founding Vera, Fordyce was the founder and CEO of gene-editing company Trucode Gene Repair, Inc., having previously served as an entrepreneur in residence at Kleiner Perkins Caufield and Byers. Earlier in his career, Fordyce served as Senior Director of clinical research at Gilead Sciences, Inc., where he contributed to seven new drug approvals and served as project lead for Gilead’s TAF/GENVOYA development program. With subspecialty training in infectious disease from Columbia University Vagelos College of Physicians and Surgeons, Fordyce was previously Chief Resident at NYU Bellevue and spent two years as a translational research fellow at Rockefeller University. Fordyce currently serves on the Board of Directors of the Albert and Mary Lasker Foundation. He received his BA from Harvard University and his MD from Harvard Medical School.
- Duration:
- 32m
- Broadcast on:
- 01 Aug 2024
- Audio Format:
- mp3
[MUSIC PLAYING] Hello, and welcome to the BioTech 2050 podcast. BioTech 2050 is a think tank, rungling the disruptions changing the biotech industry over the next several decades. Check out our website at BioTech2050.com or on your favorite podcast-listening platform. I'm Rahul Chutta-Baidi, co-founder of this podcast, and today's host. I'm also the founder and CEO of Chlora. Chlora is a platform that enables BioTech's to augment their teams while accessing the best talent. You can check us out at Chlora.com. I'm excited to welcome a repeat guest onto the podcast, Marshall Fordyce, CEO of Vera Therapeutics. Marshall had joined us for episode number 88 of the podcast quite some time ago. So great to have you back on, Marshall. Thanks so much for the opportunity, Rahul. Marshall, before we jump into all that's changed in the exciting world of Vera Therapeutics, let's start off again with your own entrepreneurial journey and what led initially to the founding of Vera Therapeutics. Thanks so much Rahul for the opportunity to share some of the story. As Vera is now a public company and we've been a public company for about three years. We are developing the new therapeutic in the immunology space of B-cell modulator called the Tacky Sept. And our lead program is in hygiene and neuropathy, which is an automated disease with a kid needy that affects young people. And we've just been sharing this year some phase two data suggesting that we have a disease modifying profile. This is an incredibly exciting time for Vera. The team is based here in San Francisco and we're still under 100 employees full time. So we're turning the corner into phase three. We expect phase three enrollment in the third quarter and read out next year and commercialization in 2026. It's incredible to be at this stage as a company and I began Rahul as a physician trained in intero medicine and infectious disease on the east coast. And it was really my clinical work and research work and HIV that got me interested in drug development. I moved out to California to work for Gilead Sciences, which as a physician and HIV, I thought, that's the company California that made one pill once a day for HIV. And as we know, without new therapeutics, HIV would still be a death sentence. It leads to AIDS and early death. And so that really made an impression on me as a physician and as a young person more to make an impact. As you think about me and my entrepreneurial journey, it really began with clinical experience and then seeing how a new therapy can transform outcomes for patients. I was at Gilead at a great time. So I got great training in a drug development organization at a really timely moment. Gilead was only 4,000 employees when I joined in 2010. And when I left, we're close to 12,000 employees. And I got the great opportunity under my mentor, Andrew Chang, to lead project teams for drugs that made it through clinical development into commercialization. So having some sense of how clinical trials are designed and how product development happens between IND and NDA, in the case of a small molecule, and how that translates into a label that empowers a sales force to drive revenue for a new product. And I really captured those learnings at Gilead. And my transition to being an entrepreneur happened in 2016. I can't believe it has now been eight years. And I was introduced to Beth Seidenberg at Kleiner Perkins. And really, one of the things I hope I shared with you last time, Rahul, is how important it is to have an excellent founding investor. And I really have had that with Beth in McConor Perkins group. Of course, she's moved on now and raised a new fund at Westlight. But having that kind of relationship as a founder, CEO, has continued to pay dividends in terms of someone who brings much more than an investment, but also know how network perspective on company building has been incredibly important to me over that time. So happy to touch back on that. But that's how I began, was really coming through clinical work into drug development and then saying, you know what, I want to choose the science. I want to build the team. I want to raise the money. I want to set the culture. And I began as an end of one. And now we're just under 100 people and heading to the market to sell a product in two years. It's been an incredible journey so far. - Great, Marshall, thank you. If I can ask you to reflect a bit, I think it's been about seven years since you founded Vera Therapeutics now. What's an example of something that comes to mind in terms of something that you didn't know or appreciate at the time you founded Vera, which has become abundantly clear and is core to how you operate it or your perspective now? - Hard to look back and say, yeah, I wish I knew that back then. You did ask me earlier, Rahul, about the first technology we worked on. And I think that's an important lesson that's worth sharing here. I founded the company in 2016. And between 2017 and 2019 for the first two years, we worked on a free clinical gene editing platform that we licensed from an academic center. And when I think about that, those early days, making sure that we set up our structure correctly. So I think many of your listeners might be involved in that kind of early relationship where there's a for-profit venture that takes in academic work. And I think applying industry level rigor to science and reproducibility and robustness of data is really a major step that needs to happen. And that's something that we did in the early days where we were called true code G repair. And I'm very proud of the team. We brought in a CSO who was an experienced industry scientist who built essentially a very intellectually forward leaning lab team. And we asked tough questions. And we found that eventually the technology was not ready for commercialization. We took those findings and published that work. When I look back, that was one of the key lessons was making sure that there's really industry level rigor applied to the science as you, that ideas that are either ready or not ready for commercialization or further development. - Yeah, Marshall, thanks for bringing that up. I think there's lots of important lessons to unpack in terms of making that switch from the fundamental gene editing technology to now very much being focused on kidney disease. What was the initial reaction of your board when you decided to make that switch? And then also any helpful tips in terms of the framework that you use or the mental model you use in terms of making that decision at that point in time. Obviously, it's been a really successful decision and I'd love to now talk about what you've done since the last time we talked. But I think important to unpack this a little bit more. - It's hard to not get a little bit high-minded about this raw rule and say, one of the early corporate values that we set was to understand reality. It's very easy as an early stage entrepreneur to have aspirational ideas, but you have to back that up with the science. And that transition, I think, is a subtle one. You got to reach for the stars, but you need the science to back it up. And understanding the reality, not only of the science that I like to say, we're lucky in biotech because science drives everything, whether it's preclinical or clinical trial data, you can actually use the tools of science, whether it's a randomized controlled trial or the reproducibility of preclinical data as a tool to say what's likely and what's not likely to work. So I would say that moment was relatively easy once we had the data to say, you know what, this is not ready for commercialization at this stage. So being science-driven, we all talk about it, but when it means that you're gonna actually pivot your company from the core asset that you raised your initial funding in and pivot away from that, it's a big deal. And you have to, number one, give up on the big drain. Number two, be driven by the data. Number three, essentially restructure and pivot your company. And that's something I'm really proud of and that's based on the relationship that I and my team had with our board and our core investors. To put it into scale, Rob, I started a company with a million dollar convertible note without an idea or an asset. This first idea, we capitalized the company to about 35 million, which allowed us to do this initial effort. But once we had that data, we weren't out of money. We had money, but we recognized the need to pivot away from the initial idea. That is, I think a core business concept. I like to call it getting to Plan B, which is Randy Commissar's book. Randy Commissar's a partner at Cloner Perkins. One of the best business books I read prior to becoming a founder, it goes to the theme that most businesses don't end up succeeding based on Plan A. It's usually Plan B, C, D, or E. And that was our story. And I think that's the story of really most businesses. So number one, you've got to be able to see reality. Number two, we're lucky in biotech to be supported by the rigor of science. The science doesn't support it, you shouldn't go forward. Then there is an emotional component over getting over your dream. And if you can do all of those things and maintain the relationships that you have with the board and the investors, then yeah, you might end up having the opportunity that we had and have a chance to take the core asset, which I would say is always the people. If you have good people who know how to find their way to good science and know how to match that to solve an important medical problem, then no, you shouldn't give up on the company. You should just give up on the initial asset. And that's what happened with us. 2019, we spent probably a year and a half looking at new assets. They were both pre-clinical and clinical stage assets. We looked at platforms. And essentially, the way we got to a tackycept was asking a clinical question. And I hate to say it, but it was a classic Silicon Valley moment where it was the CSO and I in the office. Everyone had gone home. We're like at the whiteboard thinking about our future, thinking about what we thought was an interesting opportunity. And it started with my clinical question, which was what have we done lately for patients with autoimmune disease? What's a shown that we still only have steroids to offer some patients with autoimmune disease? We can do much better than that, given everything we know about immunology at this stage. So we started with a clinical question, and then we quickly got to what mechanism we would be interested in. And we started with lupus. We knew that in systemic lupus, patients had access to a product called Benlister or bilimamab, which was an anti-baff agent. And it was tracking to about a billion in revenue, annuality and the hands of its sponsor. And the CSO turned to me and said, "Gosh, if that's what anti-baff is, then anti-baff plus April should do better." And so we started with literally a first principles view of what mechanism could move the needle. And anti-baff was clinically validated and commercially validated. And that's an insight that we had early on between Lauren Franff, our CBO, and Alan Ebenz, our CSO at the time and myself. And we got interested in the mechanism first, and we literally did a PubMed search looking for molecules that targeted bath in April. We found ourselves a tackycept. It had a history in clinical development that we understood well from a clinical safety and clinical efficacy perspective. And we got very comfortable with the fact that we believed the mechanism would work, that it would be safe at the right dose in the right clinical context. And what we solved for that molecule that hadn't been solved before was, what is the disease area? What is the clinical trial designed to demonstrate safety and efficacy? And we got lucky with respect to the status of the molecule at the time. Merck KGA, the prior sponsor based in Darkstar, Germany, was looking to re-prioritize its pipeline. This was pre-COVID. You and I have talked about COVID before, but I was able to visit the company pre-COVID and meet every project team member and make sure I understood that the molecules history and the enthusiasm for the molecule, and essentially that company was looking to re-prioritize. It was not an issue with the target or the molecule itself. And what we offered was a focused effort to position an attack except into IgNIVopathy and demonstrate safety and efficacy and the potential for disease modification. We've now set that standard. Just this past January, we shared year and a half data where in IgAN, as I mentioned, IgAN is a terrible disease. It affects 35-year-olds on average. And they're all looking at dialysis within the lifetime. About half of them end up on dialysis before the age of 50, which is how old I am now. And that means that if you can stop that process, you've really changed outcomes for patients. You've given a real tool to physicians and you have a really good pharmac economic to payers to say, why wouldn't you support the value proposition of a drug that prevents patients from getting to end-stage kidney disease in the next 10 years plus? And we're now in that position. Our Phase 2 data support that. We ran a rigorous Phase 2 global randomized control trial. We're the only ones to show year and a half data. And we're now almost fully enrolled in our Phase 3 primary cohort for IgAN. So it's been an incredible transition for us. And we now think we're in a moment where we can choose standard of care, which as a physician, that's what I wanted to do here is to improve standard of care and give a new tool to physicians. If you're an HR or hiring manager in biotech, you know all too well that the pool of experts seeking full-time employment is shrinking. Filling key full-time positions can be a long, drawn out ordeal. It can slow the pace of execution and growth. Throw away the old hiring playbook. Now you can build a biotech dream team in a fraction of that time. Find out how. Visit Chlora.com. Chlora. Talent optimized. Marshall seems to have certainly been a very busy and productive in the two plus years since we last spoke. And during that time, you've raised some additional financing, nearly 4x your market cap, and now have market cap north of $2 billion. With under 100 employees, all this during a period within our biotech ecosystem where there's been quite a bit of capital constraints, we've been facing a correction for quite some time, but you've been able to do quite a bit while keeping fixed costs low and accelerated your path into the clinic and late-stage clinical development. I'd love to hear from you how one, you view the current landscape within biotech and how that informed your operating model at Vera. - Question, and I think the best way I can answer that is good ideas get funded even when the capital markets are challenging, private and public. So good ideas get funded. And I think anyone with decades experience and biotech or outside of biotech would say the same thing, good ideas get funded. And so that's the number one thing, is come up with a good idea that will be robust enough to withstand a challenging market. And I think we're able to do that by number one, picking an important problem to solve. We think iGAM really isn't unmet need and really does support a large commercial opportunity. So that has to be the case in anything you work on. That's the reason why the lead program exists. This solution has to be meaningful and move the needle enough. And that should be a story that's relatively easy to tell. When we began on this journey, we didn't know if a drug could get approved on a nine-month protonuria endpoint. So if evaluated a surrogate endpoint, there were certain risks that we had to take. And I remember trying to convince investors that, hey, you know, FD is going to say yes to a nine-month surrogate endpoint. And that unfolded in the right way. We now have two drugs approved with that out there. So some cards fell in our favor because we took very calculated bets on the various risks ahead for us. That's a very bullish response to your question, Rahul, 'cause it's really hard to raise money, both privately and publicly. And I think it creates a discipline for executive teams, for CEOs in the operating model. Our operating model was disciplined once we transitioned from the true code model, which was all preclinical. For example, we had lab space. That was expensive real estate. And it was not simple to sublease our lab space in the time of COVID to a willing sub lieutenant. So there were lots of challenges, but we had to be disciplined, you know, we'd just say, look, we would love to run a fully integrated clinical and preclinical company right now. We had exciting science. We had really good scientists in the company. And we had to apply the discipline and say, you know what, for where we are today and the capital constraints, let's focus our energy on where we're going to drive value. And that's a tacky-cept. And we got rid of our labs. We had to downsize our team. We currently have a very light operating model where it's development only. We do not have preclinical science active and company. And that's why we can leverage the model that you just described. Being judicious about who's full-time and how do you outsource both contractors and consultants is an active area for us on the leadership team at Vera and making sure you do that really judiciously. Of course, if you're too far leveraged outsource, you end up losing a certain amount of accountability and ownership. That's critical for success and quality results. And I think we've been navigating that really successfully going forward. So those are the some of the general things that we've had to deal with. But at the end of the day, good ideas get funded and the investment dollars are out there. This is still an incredibly healthy sector. And I think you see that happen. On the other hand, there has to be an appreciation that better financing environments enable us to have more aspirational shots. And I think all of us need that. Without a doubt, we all prefer healthier constructive times than the leaner times. - Yeah, Marshall, you mentioned something about accountability, particularly in late-stage clinical development, where oftentimes the operating model is, hey, let's outsource quite a bit of operational activity in late-stage clinical development. How have you been approaching that? And what's the operating model where you've been able to thread that needle where it's high-degree of control and accountability, but yet still staying lean? - It's all about good people. I've had amazing development partners are head of operations and development. We've really had people who know how to put money within a predictable frame. So bear us a little bit of an outlier and actually delivering on what we say we're gonna do. And without delays, it's been an amazing thing to say, running a global top clinical trials in the time of COVID and even war in Ukraine. Those are all deeply across the sector. So having good people who can have good estimates for cost and time and making sure that team dynamic is constructive and there's good communication so that the outward facing part of the company, the CEO and CFO has really good communication with the development, CMO in making those forward looking statements that you can actually deliver on. So that's been pretty key for us. And then accountability in making sure that your partners deliver. That's a matter of experience and making sure that you got people who know how to do that. And I've been focusing my comments on the clinical regulatory side. Of course, the same is true for product development and CMC. And that's increasingly in focus for a company like ours in phase three and getting ready for commercialization in two years. There's a lot of focus on making sure that you're ready for commercial launch with respect to regulatory alignment, quality and scale. And I would say that's probably the number one reason why companies like ours run into delays is on the product development side 'cause they're big dollars and they're long lead times. And that's probably the most challenging component of a company in a format like ours. And I think that's something that we've managed well that I think will put us in a strong position. - And Marshall, I'm sure your role has changed quite a bit from the early days of Vera to where you are now. How do you think about the evolution of your role and the CEO's role during these exciting periods of late stage clinical development? And what advice would you give to folks that are going through perhaps similar periods of growth and at an inflection point to make sure you're doing what the company needs? - Great question. I could answer it in so many ways, Raghuul. I feel so privileged that this has been an opportunity for my learning and growth. And I'm pleased that things are going well. I explained it to my 15 year old this morning 'cause we're really into the NHL playoffs like incredibly exciting period of hockey right now. I'm a New York Rangers fan. And so it looks pretty good this year. And I said, Caleb, it's like starting a hockey team. You start with one player. So the founder needs to be the goalie, the defense, and the offense, pull at the same time and you gotta play all the positions. And then you might hire a goalie and that would free you up a little bit. And then finally, you've got five guys on the ice and then you can get off the ice and into the box. And then eventually you got a second line, a third line. And that really describes my journey over the last seven or eight years. It's been a movement from having to do the work to hiring great people. And I've been incredibly fortunate to have great colleagues along the way and now I get to be a coach. And I get to top grade my team and I get to expect my team to top grade their teams. And that's not a nice to have. It's an absolute necessity. Number one, to make sure you're early and appreciate that your early hires are critical. The impact of a hire when your end is five or 10 of FTEs, it's a huge impact. And that's been a live part of our conversation whole time. And now that we're getting into the 100 range, it's just as important. And I bring a perspective of what was it like to lose a key player at Gilead in those days when we were 5,000 employees in big impact. And just imagine that the impact scale, how big an impact it is if you have someone who isn't the right person or think of the impact when you have an absolutely outstanding hire. And what that does for the company, what it does for their teammates. So to me, that's been the biggest part of the journey as a message to those who are in the early stages or looking at those early stages, core asset of your biotech company are your people. And you've got to know that. - Yeah, really well said. I love the hockey analogy. I hadn't heard that before. I really like it and resonated. - If I could go on to that, it's all about digging it out of the corner. You see those guys working for the puck in the corner of the hole. I chuckle every time I see one of these camps and like, that's what you got to do. Whether you're trying to get work out of your CRO or you're trying to work hard to get an investor understanding the story. It's all about digging the puck out of the corner. It takes summer sweat to do what we did in this industry. - Yeah, totally agree. Particularly early stage startups with that digging mentality. Yeah, certainly love that analogy. Marshall, zooming out a little bit, there's been an increasing interest in the autoimmune space over the last few years, now coupled with obviously additional financing into the area. I'd love to hear your perspective being in your seat now on why you think that shift has occurred and also what you're most excited about moving forward as it relates to that space. - I take a bit of a historical perspective on what's most interesting in biotech and therapeutics and it go all the way back to the last 75 years or so of biomedical research. Remember, we had 75 years ago, we were just discovering the chemical basis of heredity and structured DNA and that led to a molecular biology route. And suddenly we have a much better understanding of mechanics, both biology and chemistry. And one way to say it is it's now harvest time. And by the way, let's not forget to continue to invest as a country and as a world in basic biomedical research. I'm passionate about that. I think we should massively increase our NIH budget, but it is harvest time. So we have learned a lot about the mechanisms to a high level of resolution. And there was this wave of immuno oncology that has really moved the needle forward for cancer patients. It's not rocket science to move from immuno oncology to the flip side of that and take advantage of what we know about the immune system for patients without immune disease. So from a biology and mechanistic perspective, this makes all the sense in the world where I see the field a little bit struggling as appreciating the clinical science. It's very different to test your new mechanism and a patient who's on a background of steroids and microfennel and is broadly immunopressed. And then you're going to tweak one little piece in the immune system, which is what was attempted with the tachycept early on. It was tachycept 300 weekly was thrown on top of hydro steroids. That's one way to test a mechanism. The other is to take it and die again and say, we're going to very finely tune and immunomodulate this patient with by down-regulating an exuberant bath April signal in these patients. So I think the key to making real progress in autoimmune disease is being thoughtful about the clinical science and the clinical context. And I think that requires a medical and clinical perspective that is often lost on biotech. You can often have science plus money, but you forget about the medical side. And remember, if you're a therapeutic company, every business needs a reason to exist and you exist to solve a medical problem. So you better understand your patient, your ultimate customer. And I think that's really what needs to happen as this field evolves. The other is therapeutic modality. And I would put there's a lot of excitement around cell therapy for autoimmune disease. I think anyone who has read the New England Journal Medicine article about cell therapy in a case series giving remissions to patients with systemic autoimmune disease, it's wildly exciting. And as a business, you need to be able to reproduce that in very, very difficult, in very difficult ways. And you need to be able to achieve that in a way that's very difficult to do. And you need to be able to be able to do that in a way that's very difficult to do. And you need to be able to do that in a way that's very difficult to do. And you need to be able to do that in a way that's very difficult to do. And you need to be able to do that in a way that's very difficult to do. And you need to be able to do that in a way that's very difficult to do. So there hasn't been a wild run in the biologic spades that erodes a leadership position quickly. So we really like the fusion protein biologic space a lot. So I think getting the modality in clinical science, right, is going to help unlock a higher resolution of modulating the immune system. And Vera is in the midst of giving patients an opportunity to maintain their normal immune response while dialing down the exuberant response that puts them at risk of bad outcomes in the future. So I think when you're wiping out the immune system, we know how to do that in a lot of ways, but can you tune it in the right way so that it's safe and works over time? I think we're going to see that happen in spades in the future. - And Marshall, zooming out now, even further, you know, we're recording this in Q2 of 2024. You were a founder entrepreneur with Vera. I'm curious what your feelings are about the entrepreneurship ecosystem in biotech right now. And perhaps for folks that are listening that are either aspiring entrepreneurs or in the earliest stages of kind of company formation, how they should be thinking about value creation at those nascent stages of company creation. - I think everyone who's got the energy and then know how should be an entrepreneur. I want all my kids to grow up to be entrepreneurs. I think that's what the world needs. And so I'm extremely energetic about thinking that this is the right path. Got to go in and it's a very challenging path, but the world needs entrepreneurs and the opportunities are out there. I do think that it's important to have meaningful insights into the problem or the solution or how to get there. And that's why you see CEOs who have insights into the problem. And I would say that's my profile. The problem is medical and as a physician, I'm aware of how the dimensions of that problem. And that's why you see CEOs who are PhDs, they know the solution, they know the science well. If you have an insight into formulations that gives you a chance to improve and reposition therapeutics, that's an incredibly valuable set of insights. And then on how to do it, that's the business profile of a biotech CEO. And I think that's critical as well. I think it's pretty exciting when you sit in the CEO, entrepreneur COC to pull those three elements together. The medical problem, scientific solution and the business, a way of making that happen. There's nothing more exciting in my mind. So how does the ecosystem look? There's exuberance. Sometimes people are rushing into it and I don't think there's enough thought. And then there are people who really should do it, who need the stimulus to say, "Hey, you know, stitch those things together." Insight into the medicine and where we need improvement. Insight into the science and why we can really create a step forward and do it smart, get the right business mind focused on that so that it's a shame when the problem is big, solution is great, but it failed because of somewhat overbuilt or underbuilt or the like. Many ways to fall down, of course, but I'm incredibly fortunate to be in this position. And I love being an entrepreneur. I think anyone who thinks they've got the pieces to put together for it should do it. - Yeah, great. Marshall, I certainly echo your exuberance with regards to entrepreneurship and particularly in our space, given the impact on human health. Marshall was wonderful having you back on the podcast again today after quite some time. Congratulations on all the amazing progress you and your colleagues at Vera have made. And look forward to having you back on after you have an approved product knock on with. - Absolutely, a whole thanks for the opportunity and yeah, I feel so fortunate to be part of the team that's been able to make this happen. And we ultimately do have a mission. We're looking to improve standard of care. And we now have a lot of confidence. We can get there in the near turn on what a fantastic journey. So thanks so much for the opportunity, Rahul, and let's stay in touch. I'd love to share the next chapter when it happens. - Sounds great, Marshall. Thank you. (upbeat music) Thank you for listening to this episode of biotech 2050. This episode is hosted by me, Rahul Chaturvedi and Alok Taiyi. If you enjoyed this episode of biotech 2050, please subscribe to our podcast and leave us a review. Also follow us on Twitter and Instagram and biotech 2050 pod. Again, that's biotech 2050 POD. Until next time. (upbeat music) (upbeat music) (upbeat music) [BLANK_AUDIO]