Kymera Therapeutics, Inc. Common Stock H.C. Wainwright 28th Annual Global Investment Conference

Go ahead. Great. Thanks for the introduction.

Thank you, everyone, for being here. Thanks to those that are listening online. I'm probably going to take just about the next 10 to 15 minutes to give you a quick overview of Kymera, where we've been, and probably more importantly, where we're going. Hopefully, I can get these slides to work, which looks like I can. It's a great time to be here talking about the company. It actually, this year, was the 10-year anniversary of Kymera's founding. The company started back in 2016 with a mission to develop drugs against some of the more intractable challenges in the biotech industry. It was founded around a modality called targeted protein degradation, or TPD.

What made TPD an interesting modality for us was that it had the ability, we thought, to address targets that historically had been undrugged or had been inadequately drugged, and we thought it had great potential across a number of large, important disease areas. We built the company from the beginning with a very strict target selection approach. We are focused really on, as I said, targets that were inaccessible or poorly drugged with conventional technologies for which we thought TPD would be either the best or the only solution. It was, I'd say, an area of focus and target selection that has stayed true to the day. 10 years later, we've built a company that we believe has executed well.

We've taken a number of programs in the clinic, I'll talk to you about that, and I think are well positioned to achieve the mission on which we were founded a decade ago. Moving on to the next slide, I just wanted to spend a minute talking about some of the key capabilities that Kymera has built over the years. One of the areas where we've, I think, become particularly adept and has become an important differentiator for us, is in the area of target selection and hit finding in particular. We have developed what I think is a very strong, I guess I can't say unmatched, but certainly strong capability to find ligands to previously undrugged targets, and we've done that a number of times. Obviously, our STAT6 program that we'll talk about, we believe we were the first to drug that.

IRF5 is another, and the list goes on. We've become, I think, quite adept at finding ligands to hard-to-reach targets. The next step, once you've done that, is to optimize that hit into an advanceable molecule, and I think that skill set in lead optimization is something that has become important capability at Kymera, our ability to quickly turn these hits into drugs that can ultimately be development candidates. We've also seen over the years, I think, very strong translation between the preclinical work we've done and the taking these drugs into the clinic. That's obviously important. You want to be able to reproduce what you see preclinically, and I think we've done that to a great degree, and the result has been a very high level of productivity at Kymera. I think we've been one of the more innovative and productive companies in biotech.

We've taken targets like STAT6, IRF5, and IRAK4 into the clinic. In total, 7 molecules, including some earlier entrants in the oncology industry. We have today what we think is a research engine capable of delivering one new DC annually. Really, foundation has been a very productive research engine. We've lately spent our time building the development organization to prosecute on these opportunities. No presentation would probably be complete without a pipeline swim chart, so this is where we stand today. The top 2 programs, STAT6 and IRF5, are our 2 wholly owned programs, and I'll spend the bulk of the presentation today talking about those, in particular about STAT6. We've also leveraged partnerships in certain instances.

We have a partnership with Sanofi around our IRAK4 program that has a molecule that is currently in phase I studies, both in healthy volunteers and then a group of HS patients. We have a partnership with Gilead as well around a CDK2 molecular glue, which we think has great opportunity in certain oncology settings. I wanted to spend a little more time on our 2 lead wholly owned programs, STAT6 and IRF5. This is, I guess, a bit of a teaser slide. I won't spend too much time here on STAT6 because it'll be the focus of our conversation today, but we do believe this is one of the more exciting targets in biotech. It's a highly validated pathway, really enormous, and I would say untapped market opportunity, and we have a great opportunity to lead the development of this really kind of once-in-a-generation program.

I'll get much more into that as we move through the presentation. IRF5, this will be just the one slide on this before we get to the slide at the end. This is a very exciting program as well. IRF5 is also one of the long sought-after targets in immunology. It's a bit of a master regulator of immune response, and we think degrading this target has the ability to impact many very important pathways, type I interferons, B-cell antibodies, and inflammatory cytokines. There's very strong genetic association between this target and some very important and underserved autoimmune diseases like lupus, like IBD, RA, and others.

This program right now is just finishing up our first healthy volunteer study, first hopefully and only healthy volunteer study with IRF5 KT-579. Our plan is to move that into a lupus study, a phase I-B lupus study, which will start shortly after the healthy volunteer study completes. I will come back to that briefly at the end, but I wanted to really focus our time on the STAT6 program. As I mentioned, STAT6 is a long sought after, probably one of the most highly attractive targets in immunology. It is the specific transcription factor, excuse me, that is responsible for signaling of the IL-4 and IL-13 pathway, which, of course, is a target of the very, very successful drug, dupilumab.

That pathway has been validated both scientifically and commercially by Sanofi and Regeneron with dupilumab, and you can see a list of some of the indications in which dupy is approved: AD, asthma, COPD, EoE, and others. We also have some human biology that gives us additional encouragement about STAT6. Patients who have been identified that have gain of function tend to have basically an allergic disposition or phenotype. There are some loss of function, heterozygous loss of function patients out there who tend to be protected from allergic conditions as well. Good human biology supporting the target, but again, most importantly, what we know from dupy, the importance of this pathway, the safety of this pathway, and the efficacy all gave us great enthusiasm when we started this program, and that has only grown with time.

One of the reasons we are particularly excited about STAT6 is the market opportunity. I mentioned that dupy is approved in, I did not mention all of them, but it is 8 or 9 indications. Taking just one as an example of the opportunity for our STAT6 program, atopic dermatitis, which obviously can be a chronic, debilitating condition for many people. We believe, and based on the literature, there is somewhere between 6 million and 9 million moderate to severe patients in the U.S. Surprisingly, though, only about 400,000 of them are on advanced systemic therapies, which is a surprisingly low penetration rate, both in light of the total number of patients and in light of the fact that dupy itself is in excess of a $20 billion drug.

What that means is of that 6 million to 9 million patient population, there is a large number of patients who are either on topicals or they are completely untreated. Really, that is an enormous opportunity if we can be successful in developing a safe and effective oral medication. Why is penetration not greater? I think it depends on the modality, but there are different reasons. Local therapies, as I mentioned, topicals. They can work in some cases, but they typically do not address the underlying cause of the disease. They also can be messy and really a pain to deal with. There are some oral therapies. You all are probably familiar with JAKs, JAK inhibitors. But those come with, despite the oral convenience, some safety baggage, including black box warnings. That has limited their adoption. Then, of course, there are injectables like dupy, incredibly efficacious drugs, very safe.

They are injectables, and they require as frequent as once a week or once every other week injections. For some patients who are phobic about needles, they may not want to do that. They require cold storage. It also can be a very painful injection as well. I think most importantly from the research we've done, it requires a patient to accept that they have a very severe disease, which some just don't want to accept, and in some cases, taking an injection is that acknowledgment. We think there's just an enormous opportunity here, even if we're not competing, even if we don't take one patient away from biologics to treat this big group of undertreated or untreated patients that are in the middle of this big donut here. What does the data look like for STAT6 for our program, KT-621?