Cogent Biosciences Inc at Stifel Targeted Oncology Days (Virtual) Transcript

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

Question: Brad Canino - Stifel Financial Corp. - Analyst : Greg, let's kick it off with maybe a few quick questions on bezu in GIST because there were those mutational subgroup data presented by Deciphera in January from that company's failed second line GIST trial with ripretinib. How to like contextualize those learnings from those data in relation to bezuclastinib, sunitinib, the combination that you have in development for second line GIST?

Question: Brad Canino - Stifel Financial Corp. - Analyst : Yeah, now you're doing the combo with sunitinib that does have a defined toxicity profile, but it's been used for decades and can be managed. I guess the question is how much data do you have to support high confidence in the combo safety profile such that those doses can be maintained at a high enough intensity and to ensure that [pancake] coverage that you mentioned?

Question: Brad Canino - Stifel Financial Corp. - Analyst : Okay. There are a few questions come in from the audience about the Phase 3 study, particularly around the trial design and the analysis plan around specific mutations. Deciphera ended up doing a cut looking at empowering for exon 9 versus exon 11. Are you doing more of an all -comer approach? Or will you have some statistical analysis around specific mutations as well?

Question: Brad Canino - Stifel Financial Corp. - Analyst : Okay. Now bezuclastinib monotherapy for advanced systemic mastocytosis, you shared first data last year at ASH '22. I guess what would you highlight is the differential findings from that data set relative to the approved avapritinib for that setting?

Question: Brad Canino - Stifel Financial Corp. - Analyst : Yeah. How should I read the result that you didn't report responses post avapritinib at least not yet in the data today?

Question: Brad Canino - Stifel Financial Corp. - Analyst : Okay, very helpful context. You just announced that Part 2, when the studies is opened with the 150 milligram optimized dose of bezuclastinib, so congrats on the progress there. I guess just help us understand the clin pharm you had completed and how this new dose relates to those doses used and that ASH cohort that we just saw.

Question: Brad Canino - Stifel Financial Corp. - Analyst : Okay. Right now thinking about the market potential here ASM, if we look at Blueprint as a comp, it's grown to about 100 million annually in the US, still it's getting some mid-teens growth from it, but you've got guidance out there that you think this should be a $300 million US market. What are either the drug property or label considerations that actually get you there tripled what we've got today and how are you designing that into Part 2 to capture this opportunity?

Question: Brad Canino - Stifel Financial Corp. - Analyst : Okay. And moving to ISM, any different competitive differentiation to note versus the ASM difference between avapritinib here would be helpful. And then I guess point us to some of the biomarker data in ASM that are going to reinforce your ISM strategy.

Question: Brad Canino - Stifel Financial Corp. - Analyst : Yeah, because it sounds like avapritinib is inert in the ISM population. You look at the impact it has on the mast cell biomarkers. So I think the question is why do you believe that that incremental improvement and stuff like tryptase suppression, mutant KIT fraction is going to translate into a further symptom benefit in 24 weeks because you're not measuring those biomarkers as a part of response like you are in ASM?

Question: Brad Canino - Stifel Financial Corp. - Analyst : Yeah. And now you mentioned the dance between dose intensity and the clinical benefit, which is going to be measuring symptoms and not wanting to offset that with the avapritinib development, and it sounds like you're comfortable with the mutant selectivity for your molecule that will allow you to push dose without generating some of those nuisance side effects that would be marked as symptom scores. But you did have hair color changes that you reported in the ASM data. So it seems like there is some wild-type KIT inhibition that's going on. And in a disease where you're measuring quality of life, what is your confidence that that will be an accepted adverse event?

Question: Brad Canino - Stifel Financial Corp. - Analyst : Yeah. And what data do you plan to show for ISM in second half '23 and to what degree do you believe it will be sufficient data to prove some of the competitive differentiation theses that you've been discussing today?

Question: Brad Canino - Stifel Financial Corp. - Analyst : Yeah. And now there's a debate between the correlation of tryptase reduction and symptoms. Are you going to be able to show that much in your data? And by that, I mean, are you going to be starting at doses that are going to have not full tryptase reduction and then dose escalate or kind of all patients going to be at potent doses here?

Question: Brad Canino - Stifel Financial Corp. - Analyst : Okay, great. Well, Andy, we've squeezed a lot in for just one molecule. So it's fun to have three separate programs baking in once for one molecule. I look forward to all the updates for the rest of this year, and thank you so much for joining us on the fireside chat.