Kymera Therapeutics, Inc. Common Stock Morgan Stanley 24th Annual Global Healthcare Conference

Yeah. First of all, thanks for having us. Yes, the idea when we started Kymera in May of 2016 was there is tons of biological data tying a disease-causing protein to diseases. We have really lacked the right technology to address many of them. While we make so much progress with oligo-based therapeutics and obviously injectable biologics and traditional small molecules, there was still a big gap, and I would argue there is still a big gap. Only, I think, 20%-25% of the proteome has been drugged. We saw this new small molecule-based modality called targeted protein degradation as a mean to expand the number of targets we can go after, and ideally, obviously, fulfill some of the key unmet needs that are still out there.

As people that might have heard about protein degradation, this is modality that uses the ubiquitin-proteasome system, which is the cellular machinery responsible for protein homeostasis and directs it against disease-causing proteins. We have focused in the past, over the course of the company, in different areas across initially oncology and immunology. In the past 6 years, focused really almost solely in immunology. The idea was, again, at the high level, quite simple. Lots of pathways have been validated in immunology. Lots of extremely successful drugs have changed lives of millions of patients around the world. These are almost only, if not mostly, injectable biologics.

We found these opportunities to go downstream of these biologics intracellularly with oral degrader molecules to provide what we believe is, for the first time, really specific-directed therapies that could deliver the best risk-reward profile for patients with immune-inflammatory diseases. Our wholly owned programs are a STAT6 degrader, which is downstream of IL-4 receptor alpha, the target of Dupixent, which is, I believe today, the number one prescribed drug in immunology. Another program that we are very excited about is IRF5 with KT-579, which is another undrugged transcription factor downstream of highly validated pathways in many immune-inflammatory diseases. We have many other preclinical programs that we have not disclosed yet, and we have a couple of partnership, one in immunology with Sanofi and one in oncology with Gilead.

Well, I haven't started IRAK4 since 2023, so that's a very interesting, exciting way to start. We started with the program with the idea of going after one of these key, again, undrugged nodes in immune inflammatory diseases. In this case, IL-1, IL-17 biology, a pathway that had actually upstream extensive validation. We had IL-1 biologics even more recently from AbbVie that had some exciting data in HS. We had initially back then IL-18 had some mixed data, but more recently we've seen some interesting data from IL-18 in AD. We have recently seen some really amazing data of IL-33 from AstraZeneca in COPD. Probably one of the most exciting data set of the year, I believe, in that area. Again, between then and now, we've seen these cytokines have impact across many diseases. IRAK4 is the central node downstream of those cytokines responsible for the signaling.

It was actually an obvious target that has been pursued by many in the industry going after the catalytic function. We demonstrated that there was a scaffolding function that required a degrader instead of a small molecule inhibitor. Obviously we advanced our first generation degrader, KT-474, through phase II, and then as a part of the collaboration with Sanofi, we decided to focus on the second generation degrader, which is a superior molecule that now entered recently phase I.

Yeah. I would say the biggest learning, and actually one of the reasons why we have decided to invest further and if not almost solely in immunology, was driven by the early translation of IRAK4 degradation in healthy volunteers. We saw that what we had studied preclinically, kinetics of degradation, safety, predictability of safety, predictability of degradation kinetics across different tissue types gave us the confidence that one can develop reliably degraders. In immunology, we were the first company to do so back then. That's, I think, a big learning, even the, let's call it, the platform translation and fidelity thereof. The second part was actually how important specificity is to successful drugs in this space, how important dose selection becomes, how important the distribution of the molecule and the impact of that distribution has on the profile of the drug.

This allowed us to develop this new generation of degraders. I would call KT-474 a first-generation degrader molecule with pros and cons and things that we learned from. This allowed us to invest and learn and optimize these degraders. I think KT-621, KT-579, and even KT-485, which is our second-generation IRAK4 degrader, have benefited from what we learned, and these are way better molecules than our first molecule.

Yeah. There's not a ton we can disclose.

given that this is a program run by Sanofi, but I think it's also, I believe, on ClinicalTrials.gov by now. It's actually a quite creative phase I study that has healthy volunteers and HS patients. The healthy volunteer portion is a more traditional SAD and MAD study with some interesting biomarkers. Again, we unfortunately can't go into it. Then there is an HS, let's say, proof of mechanism- portion at the back of it that obviously we look forward to seeing the data when they are generated.