Generate Biomedicines, Inc. (GENB) November 9, 2026 Conference Transcript

Good to get started here. Thanks, everybody, for joining us. We've made it to the afternoon of day one of the Guggenheim Healthcare Innovations Conference. It's 2026, and, you know, we're all looking forward to more great company data ahead. I'm thrilled to have Generate Biomedicines with us here today, CEO Mike Nally, President and CFO Jason Silvers, to my left sequentially. And, you know, earlier this year, the company came public via a $400 million IPO in February 2026. A lot of progress along the way. So, Mike, I'll just turn it over to you to, you know, maybe give us the lay of the land of where Generate sits today, what you're seeking to accomplish in the next, you know, 12 to 18 months, and then beyond.

Yeah, well, first and foremost, thanks, Seamus, for the opportunity. It's always great to be here. You know, generate... It's been really fun being at Generate. You know, I've now been at Generate almost six years after having spent 18 years at Merck. And when I joined the company, it was going after a premise that nobody in the world believed in, that generative AI could actually design protein therapeutics. And, you know, at that time, when I joined, there were no pipeline programs at all. And what we've been able to see over the past, you know, five plus years is not only does the technology work, but it translates really, really quickly. And, you know, our first asset, our lead asset's now in phase three of development. It's going after severe asthma. You know, the early data is suggestive that it will be dosed every six months. It reduces, you know, key biomarkers at least as well, if not better, than what we saw with tezapelumab. And so, you know, we're really encouraged by not only the state of the technology, but also its ability to translate into meaningful therapeutics. We've now put five molecules into the clinic. You know, behind our asthma drug is there are a couple of oncology assets that I'm sure we'll talk more about. But I think, you know, what's really exciting for us is, you know, we're just scratching the surface of the potential of this sort of a technology. And while I think there's a lot of noise in this kind of tech-bio intersection with some people saying we're going to cure cancer in five years, others saying it's not going to have any impact, inevitably the answer sits certainly well in between. We're on the more optimistic side, and we're already starting to see the very tangible markers that these technologies are helping us understand biology in really extraordinary ways. And I think we're just, you know, at the early days of the impact. Right.

And so maybe talk about your first program, you know. I think you've taken a bold approach to the development. A lot of folks would say, you know, that it was a risky approach. Our view is, is that few answers, few incremental answers could have been gained by running a phase two here. So can you just help us understand what brought you to phase three so quickly with the Solaria program?

Yeah, well, I think, you know, Seamus, this concept of risk, like, We're in a high-risk business, right? 95% of things fail when you start a program. We thought this was a really sound bet, and we still, to this day, our conviction in that bet has only grown. You know, our choice to skip phase two was predicated on a series of very measurable facts. We know we bind the same epitope as tezapelumab. We know in the phase one trial, we saw the same or better biomarker reduction as tezapelumab on highly correlative biomarkers, including EOS, FENO, IL-5, IL-13. We know there was a regulatory precedent for pursuing this sort of pathway. Depomocumab has been approved in both the U.S. and the EU using this sort of an approach. We know based on our modeling that our target engagement is at the same level or better than tezapelumab at every time point. So 99.9% target engagement. And so the leap that we made was with that body of evidence, we could effectively select. The dose using the phase one data. And the other thing that was very evident in the data was that you saw no additional biomarker reductions when you dose beyond the 300 milligrams that we've ultimately selected. And so for us, you know, if you go back and look at the tezapelumab phase two dose finding study, they studied three doses, there was an eightfold difference in dose, and they showed no statistically significant difference in asthma exacerbation rate. So you would ultimately make a pragmatic choice. You'll spend $50 million and take two years, or you just make the dose selection choice based on the evidence that you have. And so for us, this was clearly the opportunity was obviously a lot more sizable if we were the first long acting to make it to the market. We think we have the best in class candidate given both the half life and the bio physical characteristics. And we think the dosing data actually was pretty robust when you actually look at it. Great.

When you think about the build up of a development organization around that, so there's, you know, we've seen a lot of rapid advancement, particularly at Generate into phase one. You know, we're now talking about a large phase three development organization that you're extending into this. Can you just help us understand what Generate has built there to, you know, extend into successful phase threes?

Well, certainly, you know, Shaman, as I go back a long time, you know, one of the things Merck taught me really well is how important extraordinary clinical development organizations are. You know, we've been really fortunate to be able to hire some of the best asthma developers in the world, people that have licensed key products for GSK, for instance, who are leading this sort of program. We feel really good that really quickly we were able to assemble a world-class team across clinical development, clinical pharmacology, stats, regulatory, all the really key functions to making a clinical development program work. And what's been exciting for them is I think they're in this kind of technology-first organization that's actually helping us solve some of the, you know, kind of longstanding challenges around, you know, patient recruitment. You know, can we use these sort of digital technologies to identify patients, to identify sites, to, you know, drive regulatory reporting? And so they feel like they're actually sitting at the precipice of the future of drug discovery and development, and that's been a huge attraction for a lot of key talent within the industry. Great.

So let's extend that to COPD and, you know, decisions that need to be made on COPD and, you know, the choice of COPD versus perhaps other potential indications.

Yeah, so, um... The beautiful thing about TSLP is it has a lot of potential application, right? You know, we can count five, six different indications that could actually have, you know, very sizable potential, including obviously severe asthma, COPD, EOE, chronic rhinocitis with nasal polyps, food allergy. There's some, you know, a lot of people that still think there's utility in atopic derm. So a huge array of potential opportunities. When we step back and we think about the data we've seen to date, we think about the unmet medical need, we think about how TSLP positions itself versus other choices in these different domains, we feel really good about COPD for a few reasons. Number one, COPD is one of the top five burdens of disease, of any disease globally. And if you think about biologics penetration in COPD, you're talking low single-digit biologics usage. So the unmet medical need and the burden to the health care system and to patients is extraordinary in COPD. And we think, based on the data we saw earlier with tezapelumab, there's a really strong utility in that domain where, you know, if you look at the approved therapies in COPD, you saw Dupixent have roughly a 30% COPD exacerbation rate reduction. Nucala had about a 20%. In the TESI Phase II study, albeit with small numbers, you saw a mid-40%. Reduction in the greater than 300 EOS. You saw a 37% reduction in the greater than 150 EOS. So this is a really meaningful potential therapy for COPD patients. And given the medical need, we think there's a really good thesis to go after COPD as the next entrant. Plus, it has a shared commercial infrastructure with asthma. Yep. EOE, I think the data that we saw in August was super encouraging from TESI as well. You know, we think of that as a frontier that has been probably underserved by biologics therapies. Obviously, Dupixin has had, you know, some really good success there. But we think, you know, TSLP could be the mechanism of choice in EOE as well. I think there's a slightly different customer set in terms of the physician population that you'd be working with, but we think it's a great opportunity in the future as well, and so our orientation is let's get the asthma trials done. COPD probably will be the next one. I think if you were to go rank order based on what we know today, EOE would probably be the third choice in terms of the indications.

And there are... Two, I think, factors in COPD that are worth talking about. One is, do you feel confident that you can move forward into phase three? The second is confidence to move forward with a single dose. And then the third is, is confidence to move forward with a single trial.

Two out of three isn't bad. Okay. Yes on the first two, no on the third. Okay, got it. Um, you know, uh... We know there's a pathway, but we've had regulatory engagement across the world. We know there's a path forward in COPD. We have seen GSK take a very aggressive stance where they basically have gone straight into phase three with no data in COPD. As you know, we presented our 1B data in COPD that showed there was no difference between our 300 and 600 milligram doses, and you saw comparable levels of biomarker reduction that you saw in asthma in COPD. The single trial, we did ask the FDA. And we said, you know, given Dr. Macri's proclamation in the New England Journal, would a single trial be acceptable? And they said, we think two is the right way to go. And so very clearly, we think that's the best path forward, given the regulatory feedback we received to date. Got it. Great to know.

You know, beyond now, you know, we can move to sort of the next program. That's, I think, really an exciting update. But in terms of the next programs, one program that our team is really focused on is the MMA Neutralizer. You know, maybe you can just kind of set the stage for what the MMA neutralizer is seeking to accomplish. And then, you know, beyond that, any learnings from... Both ASCO and then subsequently ESMO as it relates to the opportunity for an MA neutralizer.

I mean, we share your excitement here. You know, I still remember the ESMO where the original padsev data was presented, and my jaw. Hit the table because, you know, for patients with urothelial cancer, the unmet medical need was just so profound. And to see the survival rates that were, you know, coming with this sort of a medicine was transcendent for so many patients. You know, having spent a lot of time and members of my team having spent a lot of time developing PAD-7 in combination with Keytruda, we also recognized there was a major liability with the therapy. Two-thirds of patients suffered from peripheral neuropathy that was leading to discontinuations, down-dosing, dose holidays, and ultimately affecting survival rates. And, you know, one of the gentlemen who's on our team, you know, is one of the preeminent clinical pharmacologists in the industry. He asked, you know, could we use these new computational tools to design a molecule that selectively binds the cleave-pave load? Without interrupting the intact ADC, because what's happening, you know, with PAD-SEV is you have this premature cleavage of the payload that's driving these high rates of peripheral neuropathy, upwards of two-thirds of patients, and importantly, once you get to grade two peripheral neuropathy, it's an irreversible side effect. So you have this tension in the treatment landscape where you'd love to use this medicine earlier and earlier in the treatment continuum. However, you have this irreversible side effect that is really harmful to patients in their long-term quality of life. And so we've been able to design a molecule that just selectively binds, it clears it, and it opens up the therapeutic window in a very, very meaningful way. And so for us, the opportunity here is, you know, to drive an endpoint toward peripheral neuropathy, but we think the long-term benefits here inevitably will be positively, will positively affect survival. And, you know, you mentioned the data at ASCO. What we saw at ASCO was, you know, Pfizer presented some brilliant data based on how long you survive on drug is purely correlated with overall survival. And so if you can get people, you know, past these sort of side effects, we think it has that long-term potential benefit, which is really, really exciting. And then, you know, I think as we've come through ESMO, clearly, you know, there's a whole range of other payloads that are being developed. But I think what would, you know, it's going to be hard to displace a drug like Padsev if You can alleviate the side effect. And so for us, a lot of our focus is, let's generate the proof of concept. Let's show that in the phase one data, we can select the dose that allows us to reduce 50 to 80% of the circulating MMAE. And then go into a rapid proof of concept study where we're going to look at can we stop or slow the progression from grade one to grade two neuropathy. And we should have that data next year.

And then in terms of just, you know, separating out metastatic disease versus, you know, whether it be neoadjuvant or even ultimately adjuvant, we'll see if that opportunity really is opened up. You know, what about the Volga study? You know, we saw a shortening of pad set utilization that was claimed to have comparable results. But I guess the question is, is, well, what if you'd been able to treat with? How bad salve longer in vulga would you have different results?

Well, I think it's inevitable that, you know, in all of these studies, survival rates are still way too low, right? And so you know there's an unmet medical need that is not being addressed. And you know, given the nature of the chemotoxin, that if you can persist long enough on it, ultimately it's going to provide better and better survival rates. And so I think to your point, Seamus, I think, you know, the ideal for us is... Passive is underutilized today for the survival benefits it's shown. You can see that very clearly if you look at the data between academic medical centers and the community. You know, you have 80, 90% utilization at academic medical centers. You have 50% utilization in the community. The opportunity for this sort of an agent is ultimately to make sure that everyone who needs. A drug like PADSF can get it to ultimately drive the best survival rates for patients with urothelial cancer.

And let's talk, so proof of principle or what proof of concept would be from, you know, once you've kind of dose selected, what does that look like? And then what does the regulatory path look like after that?

Yeah, so we think, you know. By the end of this year, we should have an ability to understand what dose gets us that 50% reduction. We will quickly go into an expansion cohort of the study, you know, maybe, you know, about 40 subjects, where we think we can look at patients with grade one neuropathy. Based on the PADSA level label, 70% of those patients progress to grade two. Our ability to slow or reduce that number. Based on that evidence, you'd go into probably somewhere between 100 and 200 patient study that we think would be potentially registrational, where you'd look at your ability to stop or slow the progression of neuropathy overall. Okay, got it.

Is there an opportunity, I mean, is it possible? What is the duration of a program like that? Is that kind of a two-year duration for registrational 200 patients? Doesn't sound like a huge number.

I think it could be approved before TSLP.

Okay, got it. Um, let's go to the, uh, armored car program. Um, you know, what do we know today? How far along are we in the armored car program? And, um, you know, what are you specifically looking for in, you know, at least the early data? What would the number of patients be, uh, where you would say, we feel confident that this is the right time to, you know, share the data and make, and start making decisions?

Yeah, so this is a program we've partnered with Roswell Park on, and so this is an armored car for ovarian cancer, MUC-16 being the target. These are patients who are kind of a solid tumor, obviously has not been very successful with these types of treatments. What our technology was able to do in working with some of the premier folks there, Rainier Brenchens being one of them at Roswell Park, It's an IL-18 armored car, but we changed the way that these actually bind to the target such that we can bind in a way that makes it highly, extraordinarily potent, one of the more potent cars, and according to Ranieri, you'd say probably the most potent car. And so using that technology to do that, what we believe is we will have a better impact on these. Solid tumors, to the point where these are not, they're not expecting to lymphodeplete for these patients. Where we are in that trial now is the first patient's been dosed. We believe that this is probably somewhere between 10 to 15 or so patients in a phase one trial. In this, we'll learn very quickly, we think, based on the mechanism here for these patients, how successful it is in terms of leading to better outcomes for the patients. And then ultimately, we'll decide what the right path is for this program if this is successful. We don't plan to be a car T company longer term with regard to autologous cars like this. And ultimately, therefore, we would think about whether it makes sense to spin on a new company or partner it with somebody else. But that's the status of where we are there.

Got it. All right. Super helpful. And then just in terms of the data that we saw at ESMO, again, ovarian cancer, lots of ADC data were emerging there. Can you just, what is sort of a realistic bar for a CAR-T therapy from your perspective?

Well, I think the data that's actually been most encouraging to me has actually been the data out of Regeneron on the TCE side. And I think what you saw there was a very high rate of partial responses. You know, the ideal for a CAR-T therapy would be, can you turn those PRs into CRs? Got it. Okay, great.

The, you know. Partnerships have definitely been a vehicle to continue interrogating the technology, expanding the technology. What are you doing? How far along are the individual partnerships? And, you know, as those progress, what is that opening up for the organization?

Yeah, so we have three large pharma partnerships with Novartis, Amgen, and now Zeeland Pharmaceuticals, which we announced about a month ago or a few weeks ago. We are basically, they're target-specific partnerships in which we work on, for Amgen, it's about six targets. For Novartis, it's three targets. And for Zeeland, it's initially two targets. And so the real estate that we are focused on here is really, is target-specific. What's great about it is you're talking about some of the best protein engineers in the industry who are asking us to help solve challenges that they've been working on sometimes over a decade. And so there are two critical pieces for us. Number one, it really allows us to direct our platform to some of the most challenging areas and give us insight into what are those challenging areas relative to what has been successful in traditional drug discovery, point number one. And number two is it allows us to utilize what we learn from those challenges to apply them to a broader swath of real estate, let's say, based on what we learn from each of those. I'd say we've had really strong success across the first two. Zealand is new at this point and takes us into obesity. But around the Amgen partnership was originally a five-target deal. Each one of these is structured very similarly in that they pay us an amount of cash up front to access the technology. Both Novartis and Amgen took small equity investments in the company. Each one of these are somewhere between mid and high $300 million of milestones over time, and then royalties that reach up to the double digits or the structure. With Amgen, it was originally a five-target deal, signed in 2021. They opted into a six-target. We've already been paid a first milestone on the first target. We believe we're... Going to be very successful in achieving other milestones, but that is actually getting toward the end of the program. Novartis was a three-target deal. We've done also very successful or had successful results there already. One of those programs they've announced they've moved into their preclinical pipeline. We believe we will receive at least one, if not multiple, milestones on those as well, and those are much faster now that our organization has kind of grown and matured since the original 2021 deal with Amgen, and now we're kicking off the Zeeland partnership as we speak. Got it.

Great. Well, we only have 42 seconds left. So I guess in the context of just capital allocation in general, you know, can you just remind us how much cash runway you have? And, you know, what should we be looking for from the company to continue to fund a lot of this, you know, certainly aggressive clinical development that's moving forward, but a lot of the early discovery that has actually continued to bubble up through the company.

So in 11 seconds, our cash runway is basically into early 2028. We are exploring a range of capital opportunities, including additional partnerships like the Zeeland partnership. You'll see those accelerate over time. We now have more capacity as we've kind of gotten to the end of the partnership with Amgen and Novartis. We certainly Secondly, we'll look at product-specific financing. We are looking at debt financing. We're looking at equity financing and even, frankly, licensing opportunities for some of the portfolio that we have taken to almost proof of concept. And ultimately, we think we can create value from that. And ultimately, we may think about commercial partnerships for even the lead asset. We don't intend probably to globally commercialize that. And whether that's a global commercial partnership or an OUS partnership, we're going to explore all those alternatives.

Lots of opportunity and a lot of product coming out of the Generate platform. So congrats on all the progress, and thanks again for joining us. Again, your first Guggenheim HIC conference as a public company.

Thanks, James.