Kymera Therapeutics, Inc. Common Stock Wells Fargo 21st Annual Healthcare Conference

Yeah. Thanks for the invite, and great to be here in Boston sometimes. Maybe let's take a step back, just a minute on Kymera for people that don't follow the company closely. We're a company that was founded about 10 years ago with the goal of using and building and evolving and advancing a new drug modality called targeted protein degradation to deliver a whole new generation of medicines. These are small molecule oral drugs that can degrade targets with the efficiency, the specificity that you can see in, for example, oligo-based therapeutics, but with obviously the convenience of oral small molecules. As part of our target selection strategy, we have really focused on pathways with high degree of validation targets that have strong human genetics, but undrugged or poorly drugged.

STAT6, coming back to your question, STAT6 is, we believe, one of the perfect targets for protein degradation. Is a transcription factor traditionally difficult to drug. It's in a pathway that has been extensively validated by multiple agents, but most importantly by dupilumab, which is an IL-4 receptor alpha monoclonal antibody. Again, a pathway and a target that would potentially give the first oral drug in this space. We have generated a plethora of preclinical data demonstrating that targeting STAT6 can block IL-4 and 13 just as effectively as an upstream biologics. We've generated early clinical data that confirmed that KT-621 is a potent, specific, and highly effective STAT6 degrader. Again, a first-in-class degrader. Also we've shown in a small Phase 1b AD trial that the level of STAT6 degradation lead to a deep the level of degradation that we achieved, which was very robust lead to a very robust impact on type 2 downstream biomarkers, which eventually correlate to meaningful improvements in signs and symptoms of atopic derm, comorbid asthma, comorbid allergic rhinitis.

All of this data, all of this 2 minutes or 3 minutes of my talk, has given us the confidence and the excitement to initiate two global Phase 2b studies. One, BROADEN2 that you mentioned. This is a global dose-ranging placebo controlled study in moderate to severe atopic dermatitis patients. Another study is BREATH, which is a global dose-ranging Phase 2b study in eosinophilic, actually I should say, in type 2 asthma patients, so patients with high eosinophils and high FeNO.

I think as you said, and I completely agree, I think it's one of the most exciting programs, our STAT6 program, and namely with the acceleration of enrollment, we have been able to move up the data readout from middle of next year to, as we said, by the end of 2026. That's where we are today. The goal of the study is, number one, to evaluate the safety and efficacy of KT-621 in a much bigger study, and just as importantly, to select dose for our Phase III program.

Yeah. I would start by saying that our projections were based on general execution of any atopic dermatitis studies in this day and age, and also included what we expected the timeline would be in a study that is set up to ensure that quality and speed are equally important, and not speed is the most important parameter. I guess we expected that because of some of the measures that we had put in place to control, let's call it patient quality, that that would have impact enrollment. What we've learned that while all those measures that we put in place obviously were not changed alongside the execution of the study, they actually did not impact enrollment. The enrollment went at least as well, if not actually way better than we anticipated.

Mostly, I think because there is a big desire from the AD community to have an oral drug. I think there is a level of comfort that investigators and eventually patients, I assume, have in this pathway, and also the appreciation of the data that we've generated so far.

Yeah. I think we have seen, I would say more recently, the placebo responses have been generally within, let's say, the historical range. Yes, higher, but not dramatically higher than historical rates. We have had, maybe 2 and a half years ago or so, a couple of really, really bad placebo rates that I think spooked everybody.