Cogent Biosciences Inc at Citi Biopharma Back to School Conference Transcript

The following is excerpted from the question-and-answer section of the transcript.

Question: David Lebowitz - Citi Infrastructure Investments LLC - Analyst : I guess to start, could we just talk about the mechanism itself of targeting mutant KIT has a long history, a lot of trials through multiple indications. And what about the mechanism itself is attractive for each of these diseases? What have been the challenges that the various competitors have had? And use that to kind of move into bezuclastinib and how that molecule is designed and how it might be different to actually achieve something that some of these other molecules have not been able to achieve. REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies. SEPTEMBER 03, 2025 / 1:00PM, COGT.OQ - Cogent Biosciences Inc at Citi Biopharma Back to School Conference

Question: David Lebowitz - Citi Infrastructure Investments LLC - Analyst : Got it. So let's start diving into systemic mastocytosis. I know that it's really broken down into multiple segments. I know the Street tends to look at it as too advanced and nonadvanced or ISM indolent. Could you tell us about the disease as a whole, the spectrum, frankly, in more detail than we usually get into the Street of what is the mild side of the disease and what is the severe side of the disease? What are the differences?

Question: David Lebowitz - Citi Infrastructure Investments LLC - Analyst : When we drill into the non-advanced side of themselves, there's a whole host of symptoms you start talking about relative to the disease. which are the most problematic -- clearly, skin is the most prevalent, which are the most problematic, which are the symptoms patients to go see doctors and actually begin them within the kind of diagnostic process to be identified as systemic mastocytosis?

Question: David Lebowitz - Citi Infrastructure Investments LLC - Analyst : So if we look historically before avapritinib came out of the market, these patients basically had to run through the antihistamines, some got up to Xolair, which would have been off-label. And of course, avapritinib came along. To this point now, how do you think the market has changed with Ayvakit there versus these other medications, which are almost certainly because they're cheap, probably still easily used. And what is avapritinib done to change it?

Question: David Lebowitz - Citi Infrastructure Investments LLC - Analyst : So SUMMIT Part 2, you announced top line data earlier this year. Could you talk about what you saw in that data versus what we know about avapritinib? And how much closer are we to full symptomatic resolution?

Question: David Lebowitz - Citi Infrastructure Investments LLC - Analyst : Got it. So if you look back at the PIONEER data, they eventually got to start releasing the more details of the data, getting into the actual specific symptoms within the TSS itself, the total symptom score. What were the areas of strength that you saw? I mean, it was hard because you start spreading it out into symptoms, the powering goes way down naturally because of patient numbers. What did you see in there? And where could we see differences once you ultimately get to the more detailed updates?

Question: David Lebowitz - Citi Infrastructure Investments LLC - Analyst : Got it. So I guess, fast forward, specifically with respect to the safety profile, what types of tolerability issues have been observed with bezuclastinib? I know that certainly the Street had concerns about it after the first update, which was, I guess, 1.5 years ago now. What were the expectations originally? What are they now? And how have they evolved?

Question: David Lebowitz - Citi Infrastructure Investments LLC - Analyst : So one more question on non-advanced, and that's regarding the actual process of treatment. Avapritinib, when they go in patients essentially for the first few doses, they have to be -- they're monitored for a period of time. I would expect that you assume that practice would continue at least at the beginning of any prescription and then eventually, that would kind of dissipate once patients are beyond the initial few months.

Question: David Lebowitz - Citi Infrastructure Investments LLC - Analyst : So let's move over to advanced. Tolerability also pops up there, but for different reasons, just like the non-advanced and overall, there's different -- there's a spectrum of disease. Could you talk a little bit about how bezuclastinib can differentiate from what avapritinib has been able to do? And it seems like a lot of that is connected to that tolerability profile.

Question: David Lebowitz - Citi Infrastructure Investments LLC - Analyst : Does this open up the possibility of moving into the associated hematologic neoplasm patients where avapritinib has kind of not been able to get used as much?

Question: David Lebowitz - Citi Infrastructure Investments LLC - Analyst : How much larger would the market be including those patients versus excluding? REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies. SEPTEMBER 03, 2025 / 1:00PM, COGT.OQ - Cogent Biosciences Inc at Citi Biopharma Back to School Conference

Question: David Lebowitz - Citi Infrastructure Investments LLC - Analyst : Got it. And then the readout for that is coming up pretty soon.

Question: David Lebowitz - Citi Infrastructure Investments LLC - Analyst : Got it. Jumping over to GIST. Certainly, there's been a handful of -- I wouldn't call them outright failures. They've had minor successes in areas of GIST for these KIT inhibitors. But you're doing it differently, again, because of differences in the tolerability profile. The kind of stuck to monotherapy later lines, you're actually stepping into combination therapy in the second line. Could you talk to us about the upcoming trial and what the differences are and what we could expect to see?

Question: David Lebowitz - Citi Infrastructure Investments LLC - Analyst : So expectations would be reasonable that efficacy should be improved. The question is, is the tolerability burden acceptable?

Question: David Lebowitz - Citi Infrastructure Investments LLC - Analyst : So the update for that is coming in before the end of this year as well.

Question: David Lebowitz - Citi Infrastructure Investments LLC - Analyst : I know I'm getting ahead of myself here because we have to see this data first. In theory, if it's covering all the mutations, depending on the efficacy data you see. Is this something that could be moved into the combination into a frontline trial against the current standard? Or would that be a heavy lift?

Question: David Lebowitz - Citi Infrastructure Investments LLC - Analyst : Got it. Thank you very much for your time. Appreciate it, and look forward to chatting again soon.