Welcome, everyone, to the 44th Annual J.P. Morgan Healthcare Conference. My name is Anupam Rama. I'm one of the Senior Biotech Analysts here at J.P. Morgan. I'm joined by my squad, Rathi Phinai , Joyce Zhao, and Priyanka Grover. Our first presenting company of the day is Cogent, and presenting on behalf of the company, we have CEO Andy Robbins. Andy?
Great. Anupam, thanks so much. Thanks for inviting us to the conference. We're happy to be here. My name is Andy Robbins. I'm the CEO of Cogent Biosciences. I'm going to do probably 20, 25 minutes of prepared remarks with a little presentation, and then maybe Anupam will ask some questions. We'll see if anybody in the audience has any questions. Before I get started, just to remind folks, I will be making some forward-looking statements. So we just tell you to take a look at our recent SEC filings for a full disclosure of all the risks associated with the company. Okay, so as much as I want to spend the whole day today reviewing what happened last year, which was certainly a pivotal year in the history of Cogent, we're going to really look forward about what's going to happen with Cogent in 2026 and beyond.
But just to pause, for folks that are new to the story, our lead asset, Bezuclastinib, which is a potent and selective KIT mutant inhibitor, in 2025 read out three pivotal trials, all of which were positive, which was a really exciting year, not just for the company, but obviously for the patients who are fighting these diseases: gastrointestinal stromal tumor and systemic mastocytosis. We're going to spend most, or I'll spend most of the presentation today talking about Bezuclastinib and these three trials. So maybe we'll wait to get into those details. What we're doing this year, really after that success, is focused on as rapid execution as we can to get those three studies filed. So the first NDA for the non-advanced systemic mastocytosis indication, or the SUMMIT trial, was submitted at the end of December.
And the other two NDAs will go in first, the PEAK NDA for the gastrointestinal stromal tumor indication in April of this year, and then followed rapidly in succession by APEX. So in the first half of this year, we'll have all three of our NDAs submitted for Bezuclastinib, and that puts us on track to launch the asset in the U.S. in the second half of the year in at least the Non-advanced Systemic Mastocytosis indication, but as many as all three of those indications commercialized by the end of the year, pending discussions with the agency. The other thing that's important that we did from a corporate perspective, really near the end of the year, was put ourselves in a very strong financial position to build that commercial organization, to file those three trials, and then get ready to launch.
As of the start of 2026, we have about $900 million on the balance sheet, and that will get us deep into 2028 from a cash runway and really get us towards that conversation around profitability, given the timing of these pending commercializations. In kind of the background for what we talk about most of the time is our burgeoning pipeline. So if you remember, Cogent has what I consider to be one of the best research small molecule chemistry teams in the world, a legacy from a past company that I used to work at and now really focused on building Cogent's pipeline of novel agents. I'll go in depth on two of the programs that we're really excited about: our pan-KRAS inhibitor and then our JAK2 V617F inhibitor that we disclosed late last year.
So now coming back to the lead asset, Bezuclastinib and the three pivotal trials. So across just Non-advanced Systemic Mastocytosis and Advanced Systemic Mastocytosis, this represents about an $8 billion annual opportunity. If you get really deep into these diseases, you'll know that there's very limited competition for this $8 billion commercial opportunity. In Systemic Mastocytosis, we're really talking about one company, Sanofi, that owns a drug called Ayvakit and then a backup compound that's in development before us. In GIST, you're really talking about us and us alone. There is really no competition in second-line GIST. We're the first drug ever to show activity against an active comparator in this patient population, first ever, and also plan to be the first drug approved in second-line GIST in over 20 years, hopefully later this year.
The other thing that I think is a little bit misunderstood, and I have a slide on the next slide about this, is our sort of intellectual property position or protection against generics. We see ourselves as having a very long runway of this opportunity into the mid-2040s based on our intellectual property position, and we're continually thinking about ways to enhance that. So here on slide five, you can see from a composition of matter with patent term extension, standard Hatch-Waxman, we'd be protected into 2039. And with our formulation patent, which uses proprietary technology that we're waiting on a pending patent to grant, we would be protected through 2043. So with an approval pending, hopefully later in 2026, you're looking at a 15-18-year runway for Bezuclastinib really around the world to be protected from generics.
Coming back to the GIST indication or the PEAK trial, again, just to reiterate, first time ever in history that a clinical trial in GIST showed an advantage against an active comparator. Every other drug has been approved against placebo. And in the second line, since 2006, first time a trial has been positive with any design. Some of the, I think, key numbers you see here on the slide are 16.5-month median progression-free survival. It's really pushing forward the expected benefit for patients, also matched with a very high response rate, nearing 50% confirmed objective response rate in this patient population when historical drugs are approved with single-digit response rates in imatinib-resistant GIST.
The other thing we pointed out during our study, from an overall survival perspective, way fewer overall survival events occurred at the time of the PFS analysis than we were projecting. So I think it just, from an efficacy perspective, exceeded all expectations across all of the endpoints that we're studying. Again, we're giving formal guidance that we expect to submit the NDA for this trial in April of this year, so not in the not-too-distant future, and then when you think about the size of this market, and I think this is also an area where both the sell side, present company excluded, and the buy side are kind of continuing to learn about what the opportunity here looks like.
What you really need to take away is in our trial, the average duration of therapy, and this continues to evolve because obviously patients remain on the combination. It looks like it's going to be minimally about 19 months of average duration of therapy for these patients. In a rare oncology disease, second-line setting, where the old benchmark was seven, eight months of duration of therapy, this dramatically changes the commercial potential for this patient population. We're looking here across U.S. and Western Europe predominantly with about 6,000 patients becoming resistant to imatinib on an annual basis, with some of the benchmarks on the slide of what other KIT inhibitors have priced at and are priced at in the market today. This could potentially be a $4 billion market alone for second-line GIST. Again, without really any competition.
So we look very well poised to capture a significant proportion of that total available market. Now, pivoting to the other two pivotal trials that read out in 2025, well, first SUMMIT in non-advanced and then APEX in the advanced setting for Systemic Mastocytosis patients. What we demonstrated here is for a KIT inhibitor who can achieve a therapeutic index based on its selectivity and its inability to penetrate the CNS, you can really drive very exciting results in this patient population. So for the first time in the Non-advanced Systemic Mastocytosis patient population, we demonstrated that there is a clear link between hitting the mast cells in the body, the mutant mast cells, and translating that into symptomatic improvement.
For several years, another company said that there was no correlation between those two, but that was likely because they were dosing their drug in a mutant-driven disease at about an IC50 concentration. With our drug, based on its tolerability profile, we could really drive that target engagement up to close to that IC90, more historical full target coverage level. And what that showed from a mast cell burden perspective is rapid and deep reduction in these measures of mast cell burden. You can see here patients achieving at least a 50% improvement across tryptase, variant allele fraction, bone marrow mast cells, all 90% plus. And what that showed is that if you look over on the right side, about 90% of our patients achieved what's known as pure pathologic response, so a measurement of that mast cell objective measures of disease.
And that translates into first at 24 weeks, an outsized improvement in overall symptoms that translates across the domains, across the individual symptoms in noticeably better resolution and symptoms. And then even sort of that preview that we did at ASH of what does this look like at 48 weeks, those symptomatic effects improving even more deeply. So really excited about the potential for Bezuclastinib to become the standard of care in the Non-advanced Mastocytosis setting. And then kind of finishing it off in the advanced setting, again, this matters based on how the competitor has positioned itself. So the standard of care currently is being dosed at that more traditional IC90 type target inhibition.
But with that, for a non-selective CNS penetrant drug for avapritinib, comes a lot of liabilities, high frequency of peripheral and periorbital edema, high frequency of cognitive impacts, and noticeable numbers of patients with intracranial bleeding. What we showed in our study is that you can achieve the same level of potency, drive those deep rapid responses, but spare the liabilities of all of those side effects. And so again, when given a choice for patients, we think that a much, much better tolerated option to drive that same sort of clinical activity is going to be rapidly adopted as a standard of care. And then taken together, we certainly acknowledge the impressive work that Blueprint and now Sanofi has done to drive awareness of this disease, diagnosis of this disease, and the patient population is growing.
The number of patients that are coming forward and being diagnosed with specifically non-advanced systemic mastocytosis, we think will benefit from that because in both of these settings, we have noticeable advantages against the standard of care Ayvakit, and so this $4 billion opportunity, completely distinct from GIST, also is going to be essentially a two-drug battle between Cogent and Sanofi. One thing that I think we want to make clear is that we're not kind of done investing in Bezuclastinib. While there aren't clearly other diseases to pivot into within mastocytosis and gastrointestinal stromal tumors, we are going to generate additional clinical data, which we think can help us expand this market potential, so if you look here on slide 11, the orange is really focused on the GIST, and the sort of more teal colors are focused on systemic mastocytosis.
I think folks are familiar that we had announced a while ago a collaboration with SARC, which is a co-op group in sarcoma, to run a third-line trial to try to investigate the utility of the combination in patients who had progressed on Sutent in the past. So it's not really fair to say that we're going to forget about all those patients who are still fighting GIST. We think that that will be helpful, certainly in the beginning of the launch of Bezuclastinib, to see if those patients have benefit of adding Bezuclastinib, even if they've already progressed on Sutent. Then maybe more excitingly, we haven't presented the full data from the PEAK trial yet, but we plan to do so in the first half of 2026. As part of that, we'll have kind of the full breakdown of the genotype subgroups.
What we've said publicly is that unlike other historical trials that didn't meet the primary endpoint, our trial was not driven to success by an individual genotype subgroup. It looks like patients across genotypes all had very impressive benefit from the combination. But when you think about going into the first line, and we've said this before, imatinib has been established as a standard of care in first-line GIST for a couple of decades. It's a very impressive drug. But there are genotypes in first-line patients, specifically exon 9 patients that don't respond as well to imatinib. So what we're going to do in actually just a few months is initiate a first-line cohort of patients of the Bezuclastinib-sunitinib combination to demonstrate what does that look like in that exon 9 genotype front-line group, which is approximately 15%-20% of newly diagnosed GIST patients.
So this represents an opportunity to kind of migrate upstream from what we expect to be a second-line approval. Now, pivoting to the mastocytosis setting, I think, again, folks are probably aware of that bottom study, the concomitant use, which was part of the APEX design, trying to determine the utilization or the benefit of Bezuclastinib with azacitidine in patients with the associated hematologic neoplasm disease, which is about three quarters of the ASM population. That trial continues to enroll, and we expect to have results from that around the time that we launch. But that kind of darker blue teal study there in the middle, the Switch, we think that this could be really important for the commercialization of the asset. So we're running this phase 2 study in Europe.
We expect to complete enrollment of about 40 patients in the middle of this year, which would put us on track to present that data by the end of the year. And really what this shows is that you find patients who are currently on avapritinib, you get to measure their symptomatic control while on avapritinib, then you run a washout, then you see if Bezuclastinib can deepen the reduction in symptoms. So this will really inform for patients who are the "installed base" on the standard of care, would it be worthwhile trying a new drug when it comes to the market, which we think will be very important.
The other thing, and I think folks are aware of this, but we want to sort of reiterate it, is we have an ongoing expanded access program that provides access to patients in the United States to Bezuclastinib for both gastrointestinal stromal tumors and mastocytosis currently, right now, if they are at an investigational site which is supporting this EAP for free, and so this will get us a lot of experience. It will get the investigators more experience with the drug in advance of the full commercial launch, and so we see this as a really important part of a rare disease launch prior to a full FDA approval. Getting ready in 2026 is going to be one of the most important things for us to have a very successful commercial launch. We have already hired all of the senior commercial executives in the team.
I think the last one we announced in our press release yesterday, their head of sales. We already have, obviously, our Chief Commercial Officer, head of access, head of analytics, head of marketing in place long ago. They are in the process of building out their teams. What we've guided to is that for both of GIST and mastocytosis in the U.S., we see this as about 100 employee or less total buildout, including home office and field-based employees. We're going to be very, very focused in a rare disease fashion on number one, access, ensuring that when a physician decides to prescribe, it is the easiest drug to get their patients on in these two diseases.
Number two, the patient community, again, in these rare diseases, understanding what patients are looking for, how to match them to the drug, how to get them excited about the opportunity to be on Bezuclastinib is going to be critically important to succeeding in the launch. That's kind of where our headspace is at. Certainly through 2026, we'll give more updates as we prepare to launch. Now, just a couple of words about non-Bezuclastinib. You can see here sort of a reimagining of the pipeline splitting into two franchises, two therapeutic areas. A focus on hematology or rare hematology assets and then sort of the more classic solid tumor oncology, really anchored by our lead asset, Bezuclastinib, which is going to have a presence in both of those franchises.
But then in hematology, announcing late in the year that we have what we believe is the most selective JAK2 V617F versus wild type asset with plans to go into the clinic or to IND in 2026. And then coming to oncology, a host of what we believe best-in-class targeted therapies for specific populations from FGF down to ErbB2 down to alpha-selective PI3K, and then maybe highlighted by our pan-KRAS inhibitor that, again, is on track for IND in 2026. So just quickly, obviously, there are other companies that are participating in the KRAS or pan-KRAS field. We presented a poster at the triple meeting in the fall where we use our colleagues at Revolution Medicines as sort of the benchmark for activity in preclinical models. The difference, quite frankly, with our drug and their drug is that we spare activity on HRAS and NRAS.
We see that there is the potential for drugs with HRAS and NRAS to have epithelial toxicity, which may limit their therapeutic index. The hypothesis here is that if you could build a drug that has similar potency on the KRAS variants without that activity on HRAS and NRAS, you could push that therapeutic index. That's really the experiment that we're going to try to judge in our phase one studies. And then looking again very recently at ASH, for the first time we announced we have a JAK2 V617F inhibitor. Again, this is for patients with that mutation across MF, PV, and ET, probably one of the big unmet needs in those MPN indications.
And while a lot of folks also have programs within this umbrella, what they presented is selectivity over wild type of somewhere between three and eight fold, where three to eight X, and we're looking at over 100 fold selectivity over wild type. So again, if you think from a clinical future expectation that selectivity over wild type in this mutant-driven disease is going to be important, that's our opinion, and we're excited to see that hypothesis tested in the clinic. So just to round it out before I let Anupam ask some questions about the company in the future, kind of bringing it back to the high level, what are we going to do in 2026? With Bezuclastinib, we're going to get the two other NDAs filed. So now we would have three NDAs submitted by the first half of the year.
That would lead us into hopefully FDA action, PDUFA dates in the second half of 2026 with a commercial launch. That is the dramatic focus of the company. That's what everybody at Cogent is pulling our oars on. At the same time, the research organization is helping us get by this time next year, hopefully five Cogent-invented assets into the clinic across FGF, ErbB2, PI3K, pan-KRAS, and JAK selective. And then from a corporate perspective, certainly the focus is on finding those excellent new commercial colleagues to help us succeed in our launch, but also at the same time going through a process to figure out exactly how we're going to execute the commercialization of the asset around the world, specifically Europe, which is probably a partner or a build, and then outside Europe, which is definitely a partner from a commercialization perspective.
Just underlining that with a very, very strong balance sheet, we're excited about our opportunity to execute not just in 2026 into the launch, but even further than that without the need to raise additional capital. So maybe I'll pause there and turn it over to Anupam Rama to see if there's anything I didn't cover that would be helpful.
Thanks, Andy. I'll ask the first couple of questions, but then I'll also open it to the audience for questions. Feel free to raise your hand when I do. My first question is on the SUMMIT data in non-advanced. I think you're supposed to give an update in the first quarter. What within that data would you kind of point us to that would continue to kind of underscore the benefit that we're seeing of Bezuclastinib in non-advanced patients?
Yeah.
And they can hear you, right? I don't need to repeat it.
No. That's good.
They can hear you.
Okay. Yes. We do have a plan to share additional data or first data from all three of those pivotal trials within the first half of 2026. So Summit is certainly part of that. For Summit, because we shared the data at ASH about six weeks ago, the next time we share, it'll really be about the longitudinal data. So what do patients look like after 48 weeks when we really did a comprehensive description of what they look like after 24? And what I think is going to be most exciting, and we've already kind of previewed this in some of our corporate decks, is that the symptomatic benefits for Bezuclastinib don't stop after 24 weeks.
So if you look at avapritinib from the Pioneer trial and the long-term follow-up, and they presented, strangely, a poster at ASH that shows the symptomatic benefit at year two and year three is actually worse than at year one. So their effect wanes over time. Our effect is going to continue to deepen. And so I think what we want in a chronic disease therapeutic is that patients continue to get benefit over long periods of time. And so that's really what we're going to try to demonstrate in that presentation of the SUMMIT data.
And Andy, while you're at it, what about the updates for APEX and PEAK? What additional data will we be getting at a medical conference?
Yeah. So I think probably from the PEAK perspective, the most important data, the thing that we get the most questions about is subsetting. I think that there's not a lot of confusion about the excitement of generating a 16-and-a-half-month median progression-free survival as the primary endpoint and nearly a 50% objective response rate. But there are questions about in genotype X or genotype Y, how does your combination look? That'll probably be the highlight of sharing the full results of the PEAK data. From an APEX perspective, I think we did a pretty good job sharing the preliminary data. What we said in December is that the patients on APEX had about nine months of follow-up. I think we'll have an opportunity in a single-arm trial to continue to follow some of these patients and see if the response rates mature over time.
One of the things we said at the top-line results is there are several patients who are either in unconfirmed or still have the potential to become responders on the APEX study, but really, the tolerability of that APEX readout was quite impressive to the mastocytosis community, so even without additional data, I think we're positioned to rapidly become the standard of care in the advanced setting.
Question from the audience? So, just thinking about regulatory dynamics here, you're going to have three filings at the agency basically at the same time. How do you think about the regulatory dynamics there and what has been an unpredictable agency?
Yeah. It's hard for any individual company to predict what's going to happen with a large government agency given the dynamics that are going on today. But what we can do is we can take these three studies, which each have extremely clear results in the case of PEAK and SUMMIT in a randomized fashion against well-documented standards for how you design trials in those patient populations with highly statistically significant primary endpoints and key secondary endpoints and put a package together that is as clear as possible. That really helps the agency, even in a world where there's resource constraints and how do they prioritize.
If you can really put together a story that is for a rare disease patient population, clear outperform against standards of care or well-documented control arms from a regulatory perspective, it gives them an easier file to approve in a rapid basis. So that's kind of our position. The other thing I'll kind of point out, or I will point out, is that we were granted breakthrough designation for a few subgroups of the SUMMIT population. While breakthrough doesn't necessarily confirm that you're going to get a priority review, I think if you look back over the last several years, almost all of the drugs that have breakthrough designation have achieved a priority review.
Questions from the audience? So you've got all this data in hand. And one of your slides kind of broadly touched on this, but maybe I was hoping you could dig into sort of some details on what the key medical initiatives, pre-commercial activities are going to be happening as you look to your first approval towards the end of the year.
Yeah. It's a great question. So the team, both from a commercial and a medical perspective, are already very active. Even at conferences like ASH, we probably had conversations with, I don't know, 100-plus hematologists about the data that we presented across both SUMMIT and then the top-line data for the APEX pivotal trial that was available at that same time. Getting those folks aware of it, getting them activated on the expanded access program, getting them experience treating patients, so obviously, the investigators in the trial already have that, but expanding that into physicians who are interested in treating these patients via the EAP, we think that using Bezuclastinib is the best opportunity to convince people that this is an outcompete against avapritinib in mastocytosis.
In the GIST community, the conversations that we've had with really dozens and dozens of GIST experts have been this combination becomes their standard of care at approval. There's really not a lot of confusion or parsing or comparing. No drug has been approved in 20 years. It's the first time you've ever seen an outcompete in a clinical trial against an active comparator. So the GIST community, both the physicians and the patient groups, are very excited about the combination of Bezuclastinib and sunitinib. It's our job to take these data, communicate them, share it with the physicians in the patient groups, and then make sure that all of the sort of ancillary machine of the U.S. commercialization of pharmaceuticals is teed up and ready to go for our FDA approval.
I've got one more question, but final call for anyone in the audience. One of the most common questions that I get, Andy, is you've got these three positive studies, clearly building out the commercial team, different doses across all of the studies, right? And so how do we think about pricing?
Yeah. We have the luxury of waiting until we're approved to decide what the price is. And of course, given what's going on in the world with geopolitics and most favored nations, other companies pricing their drugs, we're going to use as much information as we can up until that sort of last moment where we set a price. What we can tell you is that in these two patient populations, there have been recently approved KIT inhibitors that have provided benchmarks here in the U.S. So originally Deciphera and now Ono Pharmaceutical with Qinlock or ripretinib, they just took a price increase. So now they're at about a $46,000-a-month wholesale acquisition cost in the U.S. And then Blueprint first, and then obviously they're acquired by Sanofi, is right around $41,000 wholesale acquisition cost. So those provide, I think, interesting benchmarks.
When we do those global commercial opportunity slides, we use 40-0-0-0 as an easy math to get to those numbers. If you were to price higher, obviously the commercial opportunity gets even stronger. So we'll continue to monitor this. Our position is that the results from PEAK, SUMMIT, and APEX put us in best-in-class territory for our drug in the KIT class across all of the diseases as opposed to chopping it up that this drug is for this disease, this one's for another one, this one's for another one. When you have a KIT mutation, we see that Bezuclastinib is going to be the preferred choice across all of the patient populations. And I think that puts us in a very strong position from a pricing perspective. Looks like we have a question in the back.
Yes. Good morning. You're going to have a busy year this year here in the U.S. When do you would consider looking outside of the U.S., please?
Yeah. Just in case folks couldn't hear it, I think the question was very busy year coming up in the U.S., but what about outside the U.S., maybe specifically Europe? So just quickly, outside of Europe, so rest of world outside of Europe, we are definitely exploring actively partnerships from a commercial perspective to find organizations that want to prioritize investment in Bezuclastinib in Asia, South America, Australia, Middle East, et cetera, et cetera. Europe is an interesting question because I would say seven, eight weeks ago, I would have just lumped Europe into that comments I just made that outside the U.S., we're really going to rely on partnerships in order to commercialize.
But with the PEAK data specifically, with the strength of that data and the duration of therapy in an early line setting in a cancer population, it's one of those situations where a U.S. biotech company really can make the numbers work for investing and expanding into Europe itself. So as part of our ongoing partnership discussions around Bezuclastinib outside the U.S., we're going to be very selfish around the U.S. rights and launch that ourselves. As part of those ex-U.S. partnership discussions, we'll determine is there an organization that wants to prioritize Bezuclastinib in Europe and provides the economic terms that make it challenging for us to match that by building it ourselves. But if not, then we would be ready to go ahead and do that ourselves.
Any final questions? All right. Thank you, Andy.
Thanks, Anupam. Appreciate it.