Kymera Therapeutics Inc Q1 2025 Earnings Call Transcript

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

Question: Jeet Mukherjee - BTIG - Analyst : Hey. Good morning. Maybe just one question around the decision not to advance the TYK2 program. You obviously talked about the decision in the context of being capital conscious in the macro backdrop. But it appears you've swapped TYK2 for perhaps IRF5. So was there anything there in terms of the molecule's profile or just the evolving competitive landscape that influenced your decision? Thanks. REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies. MAY 09, 2025 / 2:00PM, KYMR.OQ - Q1 2025 Kymera Therapeutics Inc Earnings Call

Question: Marc Frahm - TD Cowen - Analyst : Thanks for taking my questions. On the IRF5 burn that you disclosed today. Just as you get into the clinic, what does that minimum kind of target profile in terms of degradation look like? And as we get to clinical data, as you highlighted with your kind of intro Nello, the bar in some of these other diseases where you started going after orals, things like psoriasis, like is extremely high. There really isn't much room even there or to some extent, AD to push efficacy higher. But some of these diseases you're talking about for IRF5, there's certainly much more room for clinical -- for efficacy improvement. How important is that to ultimately show versus just kind of matching available therapies but offering oral convenience?

Question: Eliana Merle - UBS Securities LLC - Analyst : Hey, guys. Just on IRF5, just a quick search. There's obviously a lot of literature showing that this plays a critical role in a lot of diseases. But curious how you're thinking about balancing the safety here. It looks like there's some data showing that IRF5 can act as a tumor suppressor. I mean, obviously, we're new to this target, and it seems like it's involved in a lot of diseases. But just can you explain why you're comfortable with the safety here? And I know in the last question, you mentioned that you can even get disease protection or modification perhaps with the 50% degradation, just from a clinical development perspective. Even if early on 90% degradation is safe, would you also explore moving forward with, say, 50% degradation, 90% with multiple dose levels and thinking about the long-term safety profile? Thanks.

Question: Sudan Loganathan - Stephens Inc. - Analyst : Hi, good morning. And thank you, this morning, again for this detailed presentation and for taking my questions. My first one is on the IRF5 program. In your preclinical work or any of the literature out there, did the degradation of IRF5 trigger any feedback mechanisms that may have activated IRAK4, MYD88, [Nak1, 2] or any other IRFs that could be a means of causing like an untargetable relapse in a disease state whenever treated in humans going forward?

Question: Sudan Loganathan - Stephens Inc. - Analyst : Great. I appreciate that. And just if I can squeeze in a follow-up, just in regards to the STAT6 program and the degradation. I think you've mentioned before, obviously, also achieving a pretty high level of STAT6 degradation, hopefully, in the human population as well in your trial. Between the REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies. MAY 09, 2025 / 2:00PM, KYMR.OQ - Q1 2025 Kymera Therapeutics Inc Earnings Call different indications you're going after with STAT6 degradation, does the level of that degradation need to be exceeding 90% for all the indications? Or is it different between each ones to get a clinical benefit specific to each type, for instance, with AD in the skin and blood, are there kind of targets between the two different tissue types there when it comes to looking at the STAT6 degradation to form a clinical benefit?

Question: Vikram Purohit - Morgan Stanley & Co. LLC - Analyst : Great, good morning. Thanks for taking the questions and for the presentation. We had a follow-up question on IRF5. I mean you've alluded to how challenging this target has been through your prepared remarks and also through the responses to the last few questions. But we were wondering if you could speak in a bit more detail about prior competitive approaches that may have been attempted for IRF5 and where specifically these approaches may have faltered and how 579 has been engineered specifically to address some of the missteps that others in the space may have faced in the past. And I have a follow-up, but I'll save that for post your response.

Question: Vikram Purohit - Morgan Stanley & Co. LLC - Analyst : Great And then as a follow-up, on the development program, how broad of an initial development plan do you think you will end up pursuing for 579? Is it reasonable to expect something like 621 where you started with the two sentinel indications and then go from there? And relatedly, you mentioned a mid-2028 runway. How far in development do you think you could get with 579 through that time point? Thanks.

Question: Eric Joseph - J.P. Morgan Securities LLC - Analyst : Thanks for taking the questions. Just on IRF5, can you talk a little bit about the relative infection risk given the broader or more pan pro-inflammatory cytokine suppression profile here? To what extent are you able to model that preclinically perhaps? And then in what sounds like lupus or SLE being one of the lead -- one of the focal indications with this approach, have you preclinically looked at the comparative efficacy of 579 versus some of the B-cell depleting or modulating approaches to the extent that this is also feasible to do in mice models? Thanks.

Question: Eric Joseph - J.P. Morgan Securities LLC - Analyst : No. I appreciate you taking the questions. Thanks for the update.

Question: Faisal Khurshid - Leerink Partners LLC - Analyst : Hey, guys. Good to see you. Thanks for taking the question. So we're still early in our few days of work, I think you said now to understand the target. But I saw that there is one other kind of disclosed development program for IRF5. That's an allosteric modulator. Can you talk a little bit about how you kind of see the potential benefits of a degrader approach over an allosteric modulator?

Question: Michael Schmidt - Guggenheim Securities, LLC - Analyst : Hey, guys. Good morning. I just wanted to come back to KT-621 and STAT6, especially sort of heading to the June update coming up here very soon. How important will be interpretation of some of the PD marker analysis in this Phase 1 healthy volunteer study, especially given that, as you mentioned earlier, the biomarkers in healthy is really very low at baseline. And also asking because there was a lot of variability, especially with TARC, in some of the Dupi studies. So how meaningful is interpretation of these biomarkers in the June data set? And perhaps then following up on your upcoming Phase 1b study in patients, so what are some of the things that you're trying to address in this study ahead of starting your randomized Phase 2 trial later this year? Are there any particular outcomes or questions you're trying to answer in patients before starting the Phase 2? Thanks.

Question: Michael Schmidt - Guggenheim Securities, LLC - Analyst : And maybe just a quick follow-up. Can I ask a follow-up? So on dosing in particular, Dupixent is typically given at a high initial loading dose and then there's a lower maintenance dose. How do you think about that in context of the sort of KT-621 dynamics? Is that something that you're evaluating to for the Phase 2 perhaps? REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies. MAY 09, 2025 / 2:00PM, KYMR.OQ - Q1 2025 Kymera Therapeutics Inc Earnings Call

Question: Yifan Xu - Jefferies LLC - Analyst : Hi. This is Yifan from Jeffrey for Kelly. Thank you for taking my question. Maybe another question on the STAT6 program. Could you please provide some additional color on the dose level used in the Phase 1b trial because this is a single-arm trial. How does it compare to the highest dose tested in the healthy volunteer studies? And how might it relate to the potential dose that you are going to use in the upcoming Phase 2b trials? Thank you.

Question: Andy Chen - Wolfe Research Securities - Analyst : Hey. Thank you for taking the question. On IRF5, do you see this as a conceptual equivalent to a combo therapy, including [ipilimumab] and anifrolumab and perhaps also Humira? Is this like a dual biologic or maybe triple biologic? So in terms of the studies that you have done in vivo, do we have reasons to believe that your -- it would act like a dual drug or even a triple drug? So I noticed that in the mouse model, you tested deucravacitinib and if not, separately, but can you combine them in mice? And would you see better efficacy that way? Thank you.

Question: Kalpit Patel - B. Riley Securities, Inc. - Analyst : Yeah, hey. Good morning and thanks for squeezing me in here. Now, I just had one question on the degradation kinetics that you may show here with the STAT6 degrader in patients by the year-end. For the IRAK4 program, previously, in that paper that was published, there was a rebound of the protein between day 14 to day 28, which you attributed to the variability in the method used, the testing method used and the storage conditions. So I guess, going forward, what steps are you taking to ensure that the kinetics will more accurately reflect the true target knockdown rather than any measurement or sampling handling issues?