S4, E6: Investor Spotlight: From Cancer Physician to Biotech Investor, with Dr Jakob Dupont of Sofinnova Investments

[00:00:03] Welcome to the Raising Biotech podcast, where we explore the stories, science and strategy behind companies raising impressive funds to develop ambitious medical breakthroughs. I'm your host, Surani Fernando. Normally on Raising Biotech, we dive deep into biotech companies. But from time to time, we'll look at people deciding which companies get their shot.

[00:00:28] The investors, the venture capital firms, the people allocating capital behind the scenes of the biotech innovation. Because in biotech, breakthroughs don't just depend on great science. They also depend on conviction. So today we're getting a unique investor story. We're talking to Dr. Jakob Dupont, executive partner at Sofinnova Investments.

[00:00:51] What intrigued me about Jakob's story and why I wanted to feature him in an episode is that he doesn't have a very linear path towards biotech investing. Before entering the world of biotech, he was actually treating cancer patients.

[00:01:07] Over the course of three decades, he would help develop cancer drugs, lead biotech companies, guide clinical trials and eventually step into some very influential investor shoes to help decide which new medicines receive the capital needed to survive. During this episode, we explore Jakob's origin story all the way up to his current role as a prominent biotech investor.

[00:01:31] We get a glimpse into how Sofinnova Investments typically invests in biotech, what usually piques Jakob's interest when exploring new investment opportunities and how he sees the future of biotech. I hope you enjoy the episode. Hi, Jakob. Thanks for joining the podcast. Yeah, it's great to be here with you. Thank you so much for having me on.

[00:01:54] So just to start off, I'm just really curious about your background, just your personal journey from medicine to industry and then eventually landing at venture investing at Sofinnova. Yeah, absolutely. I actually come from a family of doctors and dinner conversations growing up were always about medicine and research. My father is a cancer researcher.

[00:02:17] So I think I came to this naturally, I would say, worked in my first research laboratory in high school and then went off to college and ultimately ended up going to medical school. By the time Jakob entered medicine, oncology was a very different field. Chemotherapy dominated treatment, outcomes were limited, and for many cancers, doctors simply didn't have enough options.

[00:02:44] But for Jakob, that challenge became part of the fascination. The research world had entered his life early. He started working in labs as a teenager, and over time, cancer became the question he wanted to dedicate his career to finding a solution. That pursuit would take him through medical school, residency, research training, and eventually into an oncology fellowship at Memorial Sloan Kettering in New York, one of the world's leading cancer research centers.

[00:03:14] And it was there that his identity as both a physician and translational scientist fully came together. Came out of fellowship, was actually lucky enough to also get my own immunology, tumor immunology research laboratory at Sloan Kettering, and also continued to see patients in that capacity.

[00:03:34] So really love the concept of taking care of patients, working on things in the laboratory that could be brought to patients as quickly as possible to try to improve that standard of care for patients. And I had an early academic career, my first five, six years, doing the grant funding, running the clinical practice, doing lots of clinical trials, and publications, and the usual activities of a junior faculty member.

[00:04:04] And then I got called by a headhunter to explore industry. And that was back in 2006. That call was from California-based super startup biotech at the time, Genentech. They were interested in bringing Jacob on board to work on its cancer drugs, ranging from small molecules to antibodies to immunotherapies.

[00:04:26] He moved to California for the job, which wasn't hard since his wife was from there, and he was made director of early and late stage development. He managed to see Genentech through a monumental time of growth until it was acquired by Swiss big farmer Roche in 2009 for a whopping $47 billion.

[00:04:46] Over the next decade, DuPont's career would take him from Genentech and Roche to a series of biotech leadership roles at Oncomed, Gossamer Bio, and Atara Biotherapeutics, all pretty serious biotech players. And during his very impressive corporate career, he would lead research and development programs, oversee successful and oversubscribed IPOs.

[00:05:11] He secured major pharmaceutical partnerships, and also eventually contributed to multiple drug approvals. Along the way, his work expanded beyond cancer into autoimmune disease, neurology, pulmonary medicine, and ultimately cell therapy. Now, very few people get to see the drug development process from so many different vantage points, and that experience would eventually shape the way Jacob thought about investing.

[00:05:41] Around 2023, Jacob started getting approached to join Sofanova Investments, a U.S. venture capital firm spun out of Sofanova Partners in France, and an old colleague back from Oncomed had asked him to join as executive partner of the investment team.

[00:05:59] Now, for me, I sort of see academic medicine, clinical trial work, pharma drug development, biotech drug development, venture, and investing as sort of part of the same continuum. You really need all the components in order to successfully develop drugs.

[00:06:22] So over the last seven years, I've been sitting on more and more biotech boards and really getting interested in the strategic directions of companies. How do you fundraise? How do you invest in the most promising programs to ultimately try to get those drugs to patients that need them? So at that point in my career, I'd helped to get 14 drug approvals.

[00:06:46] And, you know, joining Sofanova as an executive partner just felt like a really nice next step in my career to see how could I bring my skills and talents to the team, deploying capital in the most important ways towards high unmet need patient populations, investing in the greatest companies and the greatest teams to try to get important new drugs to patients.

[00:07:15] Looking back at Jacob's career trajectory, at least in hindsight, sounds almost seamless. Academic medicine, cancer research, drug development, biotech leadership, and finally venture investing. But this kind of crossover career is relatively rare. Many physicians and academics remain deeply hesitant to leave academia for the corporate world, even if there is a chunky financial incentive.

[00:07:41] Because academia is seen by many as being closer to the scientific mission itself. And I wondered whether there was a conflict at that time for Jacob, whether he might miss that face-to-face contact with patients. Well, Jacob said it was actually a difficult decision, but he managed to work around to have his cake and eat it too. I have to say I cheated a little bit from the perspective that when I joined Genentech,

[00:08:06] I was fortunate enough to join Stanford University in California as voluntary faculty. So I actually ran a clinic at Stanford for 10 years while I was doing my industry work. So I kind of think of this as having my cake and eat it too, because I got to take care of patients. I got to teach the fellows, the medical students, and the residents in the clinic, be part of tumor board and so forth. But my day job was really doing the drug development.

[00:08:35] So for me, it was this wonderful combination of being able to really work on the breaking edge of getting drugs to patients, but also having that one-on-one patient contact. That was really important. But my biggest decision when I left Sloan Kettering and went to Genentech was following the mission, but following the mission in a different way. It used to be one patient at a time, you know, across the desk for me,

[00:09:04] making decisions about chemotherapy for that patient individually. But when you're working in industry, when you're working in pharma, biotech, and so forth, you're trying to change the standard of care for populations of patients. So, you know, if you change the standard of care for a certain type of breast cancer, it's not just impacting one patient. It's impacting thousands of patients. That said, Jacob never saw himself as a future investor.

[00:09:33] There wasn't a plan per se, but there was a mindset of being open to opportunity. And so I think what I'm doing now on the investment side is just so incredibly exciting because I hear about science. I hear about great teams and innovators and, you know, out-of-the-box thinkers on a daily basis. And it's not just cancer, it's obesity, it's inflammation, it's neurology.

[00:10:02] And it's just endlessly interesting. And for me, I love science and I love new ideas. And it's just so incredible the way that the practice of medicine is just changing right in front of our eyes. It's so exciting. So that brings us to SofaNova Investments. Who are they and what are they investing in? Many in the industry will hear SofaNova and think of Paris. That's SofaNova Partners.

[00:10:32] And while they are connected, they are two separate firms. I would say that we are affectionate cousins, so to speak. It's an old firm. And, you know, we split from our European cousins back in the 1990s. So they're SofaNova Partners. We're SofaNova Investments in the US. But now for SofaNova Investments... The two firms share research and sometimes co-invest. They also do events together. But they are separate funds and they have slightly different investment theses.

[00:11:02] They're more European-focused. They are therapeutic-focused, but they also do devices and diagnostics, whereas we are really only focused on therapeutics. So some slight differences, but we have great relationships. And in some cases, we even invest in the same company as well. SofaNova Investments, based in Menlo Park, California, manages over $5 billion with an elite team of under 50 people.

[00:11:28] They've now raised their 12th fund, around $500 million, mainly backing clinical stage drug startups. SofaNova are well known for bridging the gap between private biotech and public market IPOs. So I'm on the private side. We have the public side. But on the venture side where I sit, we've had a very consistent investment strategy.

[00:11:53] And that has been focus on clinical or near clinical stage companies and make those investments. We'd like to lead or co-lead the investment. We'd like to take a board seat as well. And that has really been the heart and soul of our investment thesis, because we find that once a drug is in the clinic, a lot of de-risking has occurred. You have what looks like a good drug.

[00:12:21] And you're not going to get caught up in some safety issue that's occurring in the GLP tox study. You know a fair amount about drug-drug interaction and so forth. You know a fair amount about the preclinical efficacy of the drug and where the drug may work. So we can really drill down and say, with this clinical asset, how do you maximize it in the clinic to run the right clinical experiments, to have the right regulatory strategy, and to

[00:12:51] address important unmet needs? What also defines Sofanova's investment team is that many of the people making investment decisions have spent decades developing drugs themselves. Former chief medical officers, R&D leaders, and biotech operators sit alongside career investors evaluating not just the science, but the clinical strategy, regulatory path, and ultimately, whether a therapy has a realistic chance of reaching patients.

[00:13:18] And with this type of expertise, Sofanova can make bets earlier in private ventures and take on more risk. 80% of our investments on the Sofanova investments side, the venture firm, are private companies. We can do public pipes as well, but it's really mainly private. And we don't really do seed stage investment. We do Series A. We do Series B. We do Series C. We can do crossovers.

[00:13:46] The nice thing is that we can actually invest on the public side so we can help companies go public. And then other parts of the firm can continue investing on the public side as well. We like to lead or co-lead rounds. So I would say our initial check size is on that order of $20 million to $35 million, and we can do up to $90 million and follow on.

[00:14:12] And in leading or co-leading around, we like to take a board seat and we like to help the companies to be successful. So you asked the question about how do we enable the success of our investments going forward? But we're definitely pretty hands-on. You know, so taking on that board seat will help them, the companies, if they want, you

[00:14:36] know, build the team if they need, help refine the clinical strategy, help them get good sites to work with, you know, give them advice on regulatory strategy and that type of thing. And then when it comes to the next fundraising, we can help them put together the syndicate for the next stage or prepare for going public or even interact with, you know, pharma partners

[00:15:00] where if part of the strategy may be to engage strategics or M&A possibilities, you know, we've got a lot of connections there and we'd like to help in that front as well. As a journalist, I've always wanted to get into the mind of an investor. What typically gets their undivided attention? Are they truly focused on an unmet need or are they swayed by an area of industry hype and blockbuster sales potential?

[00:15:26] And how much weight do they actually put on early clinical data versus its potential? And is there an ick factor with a CEO and executive team that just don't have that spark? Jacob said it was kind of all of the above. The first question, and this goes back to my clinical practice and clinical trial work, is what's the unmet need that's being addressed?

[00:15:50] Is a company going into pancreatic cancer where there's a lot of unmet need or going into a type of lupus, which is very refractory? You know, first and foremost, what is being addressed? If it's a disease state where there really isn't a lot of unmet need, it's hard to gain a lot of interest and conviction there. Then it's about the science. It's an ideally best in class type of profile.

[00:16:18] I think more and more of the competitive landscape really matters, not only in the US, not only Europe, but you got to consider China and Asia and so forth as well. So you really need to understand the positioning of the drug. And then it's about the clinical strategy. One of the dictums of medicine is don't do a test unless you know what you're going to do with the result. I think of it in a very similar way when it comes to biotech or investment is if you're

[00:16:45] going to run a clinical trial, imagine what the results are going to be and what are you going to do with that result? If it turns out you're running a clinical trial and you haven't really advanced your knowledge of the drug or something really defining comes out of it, then are you doing the right clinical trial? So we really scrutinize the trial design, also regulatory interactions. Or is there a regulatory path to get a drug approved in the indication in the way that

[00:17:14] you're thinking about developing? And then you mentioned it as well, but the team really matters. And it matters in a few different ways. Do you have a team that has good leadership? Do you have a team that knows how to raise money? Do you have a board syndicate, which is the right board that's going to be supportive and enabling the success of the company? And then I think it's about the technical experts as well. Because we're clinical stage, we look a lot at the clinical team.

[00:17:44] Do you have a team that knows how to operate? Are they going to be able to run the trials? Are they going to be conducting it with the right sites? Are the investigators going to think of them as credible where they're going to want to work with them and develop this in a very proactive manner? And then do they have disease expertise? If you have an oncology company, has the team had success developing oncology drugs?

[00:18:10] What's happened of late is sometimes teams will shift therapeutic focus. Well, they'll go from cancer to autoimmune. The problem there becomes if you're now pivoting a drug from cancer to autoimmune, do you now have a team and a chief medical officer, chief development officer, clinical lead who understands lupus and autoimmune. If you have an oncologist now running a lupus trial, that's kind of a red flag.

[00:18:37] So I do think that the team really matters. The expertise, the ability to execute, and to some degree track record, you know, really matters to us as well. While those key principles sound relatively straightforward, identifying companies that truly embody them is far more difficult in practice. It really does seem like Sofanova is looking for the cream of the crop of biotech innovators,

[00:19:04] especially those who have already proven themselves. So I asked Jacob which investments stood out as examples of that philosophy in action. And one company that stood out to him was Avenzo Therapeutics, a San Diego-based oncology company developing next-generation cancer therapies. What attracted Sofanova wasn't just the science. It was a combination of experienced leadership, a growing clinical pipeline,

[00:19:31] and a clear strategy in some of the most challenging areas of cancer treatment. It's an amazing leadership team. Athena, Mohamed, the group there. A lot of track record of success. Athena, the CEO, and Mohamed, the chief medical officer, they were at Turning Point previously and got acquired, developed drugs that are going to be meaningful. That leadership team already had a stellar track record at Turning Point Therapeutics,

[00:19:57] which was acquired by Bristol-Myers Squibb for $4.1 billion in 2022. Launching Avenzo in 2022, their initial Series A was almost $200 million, which Sofanova participated in. And by 2026, they had raised a total of $446 million. They built a great support group as well. The board syndicate is terrific now. They have four drugs in the clinic.

[00:20:26] And again, I'm very interested, as you know, in women's cancer. So a couple of these drugs are for breast cancer. So there's a CDK2 inhibitor. There's a CDK4 inhibitor that are both moving forward in the clinic that look like they have really good clinical properties. The strategy is really good to try to combine these in the clinic. That could be a new paradigm shift, especially for hormone receptor positive breast cancer.

[00:20:54] But then they've also brought in a couple of antibody drug conjugates, what are called bispecific ADCs. So one is against the epidermal growth factor receptor and also HER3. So it's a bispecific. That one's moving forward in some solid tumors, including lung cancer and breast cancer. I think that's very promising. There's another bispecific for bladder cancer moving in the clinic.

[00:21:22] So I think that's a team that's executing very well. The trials are going well. They put, you know, four drugs in the clinic. The fundraising's been going well. So you think about the potential with that one. Might they go public? And, you know, I just think the future is very bright. And this example is actually quite timely for this episode, as earlier this week on June 1st, Avenzo announced a reverse merger with Rally Bio,

[00:21:50] which gives Avenzo immediate access to the public markets without going through a costly IPO roadshow. The deal will close in the fourth quarter of this year. But with a fresh cash infusion, the combined company will launch with an estimated value of around $530 million. I think another company that we're very proud of at Sofinova is a company called Capstan.

[00:22:16] This is another San Diego-based company working on a radically different approach to one of biotech's most promising fields, CAR-T therapy. Traditionally, CAR-T treatments require a patient's immune cells to be removed, genetically engineered in a lab, and then infused back into the body, which is complex and expensive. Capstan's vision was simpler. Instead of engineering immune cells outside of the body,

[00:22:43] the company was developing technology designed to reprogram them directly inside the patient. And if this is successful, it could make powerful cell therapies far more accessible at a much larger scale. For Sofinova, it was an early bet on what they believed could become an entirely new therapeutic modality. The company raised $165 million in its Series A in 2022 from an impressive list

[00:23:12] of big pharma venture arms, as well as prominent biotech VCs. And Sofinova came in as a new investor two years later, participating in its $175 million Series B in 2024. The team at Sofinova really scoured the landscape to say, who's got the best technology? Who's on the leading edge here? So we decided to make an investment in Capstan, even before they were in the clinic.

[00:23:42] And lo and behold, they got acquired by AbbVie for a very large sum of money. That acquisition happened almost a year ago in 2025. And that large sum of money was $2.1 billion. And so that was an example where I think we made the right call to say, in vivo, CAR is going to be important. And specifically, Capstan is the group that has some of the best technology that pharma is going to want for merger and acquisition.

[00:24:11] So that's one where, you know, hardly a single patient was even treated in the clinic by the time that AbbVie acquired the company. So that was a great investment success. So that brings us to the future. What is the next five to 10 years going to look like for biotech? What do we have to look forward to? And what potential hurdles are innovators likely to encounter in the next biotech era?

[00:24:38] I think where we're at at this point is medical innovation has never been at a higher point. I was thinking about this when I first started working in oncology over 25 years ago. We were mainly looking at chemo A plus chemo B. And we were seeing a few weeks of improvement. It was not very exciting. Now, if I think about an oncologist, what's in their toolbox?

[00:25:07] There's like 12 different modalities. There are small molecules. There's naked antibodies. There's bispecific antibodies. There's ADCs. There's T cell engagers. There's radioligand therapeutics. There's CAR-T. There's in vivo CAR. I could just go on and on. But it's just amazing to think how much innovation that's gone on. And I think if anything, things are only accelerating when it comes to innovation.

[00:25:35] So I think in the next 10 years, we're going to continue to just see amazing innovation. I do think the bar has been raised so much on the standard of care that we really have to achieve massive benefits there. So yes, innovations is getting greater and greater. But I think that innovation has to produce more than we've ever seen.

[00:26:04] Jacob believes that where new innovators are going to be judged is also the speed to yield results. And that will unveil some unique challenges for future biotech leaders where they will need to prove agility to maintain a competitive edge. AI does help speed up some of the processes around novel drug development. It also speeds up potential recruitment and finding patients and so forth.

[00:26:31] We do have to speed things up when it comes to that innovation. I think the other thing that we're really working against is the patent lifespan, if you will, on innovation as well. And this is one of the problems. I say problems in quotes because it's good for patients. But as the standard of care gets more effective, it takes longer for clinical trials to yield results,

[00:26:58] which means that you're going to have to wait longer to get the readout on some endpoints like progression-free survival or overall survival. And maybe you're going to have to do larger clinical trials because the magnitude of benefit that you're looking for statistically, you're going to need more sample size to prove that, especially against a well-performing standard of care.

[00:27:26] So you've got a logistical problem in terms of effective standard of care, trials taking longer, maybe requiring larger sample size, and still working against a relatively short patent life. And so I think we also have to think about innovating on the clinical trial design where maybe there are earlier endpoints that we can get approval on

[00:27:54] because at some point, you know, the process is going to break if you're going to have to wait that long for trials to read out. Hearing Jacob's story and perspective on the industry is quite unique. Not every investor is fortunate enough to have spent decades developing medicines, running clinical trials, building biotech companies, and seeing patients firsthand. And perhaps that's one of the things that makes biotech different from many other sectors.

[00:28:24] Of course, every investor is looking for returns. I mean, that's the business. But in biotech, many of the people allocating capital have spent their careers much closer to the problems that they're trying to solve. They've experienced how difficult it is to move a promising idea from a lab into a medicine, which means that when they're evaluating a company, they're often looking at much more than just a market opportunity. Looking ahead,

[00:28:52] biotech is entering a period of extraordinary innovation, new modalities, AI-enabled drug development, and entirely new approaches to treating diseases that are emerging at a remarkable pace. But Jacob pointed out, innovation alone isn't enough. The next challenge for the industry will be figuring out how to develop, test, and deliver those medicines faster and more effectively than ever before.

[00:29:22] Thanks to my guest, Dr. Jacob Dupont, for finding the time in his busy schedule to speak with me. It was truly insightful and I hope everyone in the audience also enjoyed it. Remember, if you haven't already, please subscribe to the podcast, hit a five-star review on Apple or Spotify if you enjoyed the episode, and share it around with your network. Thanks everyone for tuning in once again. For now, I'm Sarani Fernando. I'll see you next time on Raising Biotech.