Kymera Therapeutics, Inc.

Good day, everyone. My name is Kahayalani, and I will be your conference operator today. At this time, I would like to welcome you to the Chimera Therapeutics fourth quarter 2025 results call. All lines have been placed on mute to prevent any background noise. After the speaker's remarks, there will be a question and answer session. If you'd like to ask a question during this time, and if you've joined via the webinar, please use the raise hand icon, which can be found at the bottom of your webinar application. If you've joined by phone, please dial star 9 on your keypad to raise your hand. At this time, I'd like to turn the call over to Justine Konigsberg, Vice President, Investor Relations.

Good morning and welcome to Chimera Therapeutics quarterly update conference call. Joining me today are Noah Meinolfi, our founder, president, chief executive officer, Jared Golub, our chief medical officer, and Bruce Jacobs, our chief financial officer. Following our prepared remarks, we will open the call for questions from our publishing analysts. Please use the raise hand icon to indicate that you'd like to ask a question, and we ask that you limit your question to one and a brief follow-up so we can accommodate everyone. Before we begin, I would like to remind you that today's discussion will include forward-looking statements subject to risks and uncertainties described in our most recent Form 10-K filed with the SEC. Please note that any forward-looking statements speak only as of today's date. And with that, I will now turn the call over to Nello.

Thank you, Justine, and thank you, everybody, for joining us this morning. As this is our year-end 2025 call, I wanted to spend a few minutes recapping what was an incredible year for Chimera. Those of you that know us well appreciate the fact that we're always forward-looking, highly focused on what's in front of us, and the bulk of the call would fissure just that. But given how important our 2025 accomplishments were, I'm hoping that a quick reflection on the year would provide some context for the foundation we have set for 2026 and beyond. Before we start, I would like to mention that this year we will celebrate our 10th year anniversary since Chimera's founding in May of 2016. Over the past decade, we've executed on our strategy and have built the capabilities, the platform, and the team to deliver on our goal to develop the next generation breakthrough immunology medicines. We've accomplished so much in our short history, but arguably 2025 was truly a breakout year. I'll start with the significant progress in our first-and-best-in-class STAT6 Degrader program. We shared outstanding results from both our Phase 1 Healthy Volunteer Study and our Phase 1b study in AD patients. In the Healthy Volunteer Study, KT621 demonstrated robust STAT6 degradation with excellent safety and tolerability. That was followed by a highly encouraging impact on efficacy endpoints in Phase 1b that supports our view that KT621 has the potential to deliver robust efficacy in line with pathway biologics with the convenience of oral daily dosing. On the strengths of these two studies, we launched our first Phase 2b study in atopic dermatitis patients last fall and started the asthma Phase 2b early this year. Jared will talk more about our KT621 clinical development plans, but both studies are benefiting from the awareness of and appreciation for the data we have recently shared, as well as from clear enthusiasm from clinicians and patients around promising oral options. We were busy advancing the rest of our pipeline as well. In May, we unveiled our first-in-class RFI program, supported by a compelling preclinical profile and validating human genetics. Last year, we completed IND-enabling studies, and we're excited to announce this morning that after IND clearance from the FDA, we recently initiated dosing in the Phase I Healthy Volunteer Study with KT579. Finally, we're building on the success of our internal pipeline by advancing our existing collaborations with Sanofi around IREC4, and by signing a new partnership last year with Gilead around our first-in-class CDK2 molecular glue program. Bruce will provide an update later in the call on the potential upcoming collaboration milestones, which would be incremental to our financial position. Speaking of finances, in 2025, we raised almost a billion dollars, bringing our year-end cash balance to $1.6 billion. We believe that this amount of capital, which extends our runway into 2029, will enable us to execute on our broad development plans that are designed to realize the full potential of our wholly-owned programs while maintaining the productivity of our discovery engine, which we expect will expand our innovative pipeline. Now, with 2025 behind us, our focus is squarely on 2026 and beyond and the multiple milestones we plan to achieve. For KTE 621, we expect to complete enrollment in the AD study this year and share data by mid-2027. The first patient was those in the asthma trial last month, and we expect to share that data in late 2027. In the meanwhile, we're planning to report scientific publication and presentation to continue to build awareness of this exciting program. This is an important year for KTE 579, our lead IRA 5D grader. We expect to complete the recently started phase one healthy volunteer study and share the data later this year. And the next step will be to advance the program into a patient proof of concept study, which we expect to bin lupus soon after that. Our partner Sanofi is expected to start healthy volunteer phase one trial with KT485 this year. We also hope to be able to advance our CDK2 program in partnership with Gilead into further development. Finally, our goal continues to be to announce at least one new program annually, and we're targeting the second half of this year to share our new development candidate program. We clearly have a busy 2026 planned, which makes me particularly happy to announce the most recent addition to Chimera's leadership team, Neil Graham, who joined us as Chimera's chief development officer. Neil is a seasoned life sciences executive with more than 30 years' experience in global drug development in both early and late-stage clinical trials across a wide therapeutic spectrum, including dermatology, allergy, rheumatology, virology, and pulmonology. Neil has led several groundbreaking programs, including the development of dupilumab at Regeneron. We're thrilled to have him join our team as we enter the next phase of our growth and look forward to his contributions as we continue our efforts to build a fully integrated commercial company. Now, before I turn the call over to Jared, I wanted to spend the remainder of my remarks speaking in more details of the unprecedented market opportunity of our STAT6 program. I can't overstate the opportunity we had to significantly increase the number of patients who are treated effectively. We hear overwhelmingly from both physicians and patients that current advanced therapies, including biologics, just aren't sufficient. There is a palpable excitement for the potential of a simple and convenient oral therapy for type 2 diseases that doesn't compromise on safety or efficacy. We have cited these numbers in the past. We believe there are about 140 million diagnosed type 2 patients in the U.S., five major EU countries, and Japan. Of this total, about 50 million patients are estimated to be in the moderate to severe category. Yet, despite this significant need, only an estimated 2 million patients are treated with advanced systemic therapies, mostly biologics, and overwhelmingly with dupiluma. So the question is, why are so many patients not treated with advanced systemic therapies? The gap is clearly not due to lack of need, but it reflects barriers built into the current treatment paradigm. There are many patients who rely on local therapies, most often topical or inhalers, depending on the diseases. However, most of these treatments do not address the underlying drivers of type 2 diseases, and as a result, do not deliver adequate treatment for many moderate to severe patients. There are existing oral systemic therapies in both asthma and AD, for example, but those can be limited by efficacy and certainly, for example, in the case of JAKs, safety concerns, including box warning and the requirements from blood monitoring and initiation and or during treatment. Finally, injectable biologics have delivered important advances and now account for the majority of systemic therapy use. actually more than 75%. However, they're associated with significant treatment burden, injection site pain, needle fatigue, burdensome loading regimens, often four to five injections in the first month, cold stain storage requirements, and ultimately with high drop-off rates over time. So, When we ask why so many moderate to severe patients remain untreated with advanced therapies, the answers lie in the limitation in efficacy for some, safety concerns for others, and very real convenience and access hurdles built into the system. The consequence is that millions of patients who would benefit from more effective therapies remain untreated, cycling through suboptimal options and living with inadequately controlled disease. This is the unmet need, and this is the opportunity in front of us. Going from patient numbers and unmet needs to market opportunities, the gap is even larger. As previously mentioned, about 2 million patients are currently receiving advanced systemic therapies for type 2 diseases. This segment represents an annual market value of about $20 billion, with dupilumab serving as the predominant drug. Although this is already a significant figure, the broader market opportunity is much larger, given that there's tens of millions of patients that are not reached by current approved drugs. In fact, I would characterize the current type 2 market as very early in its development. Historically, the introduction of new products and mechanisms has expanded immunology markets by enabling access to additional patient populations. In addition, an oral therapy that overcomes many limitations associated with existing treatments while maintaining safety and efficacy could, for the first time, provide a viable alternative for millions of patients across all age groups. It is reasonable to assume, in my opinion, that the current market for type 2 diseases is positioned for substantial expansion well beyond the current $20 billion. In fact, a comparable example can be found in the psoriasis market, which has experienced a five-fold growth over the past decade, mostly thanks to new drugs and oral therapies. I think this all comes well together when we consider the limitation of existing therapies and what KT621 has to offer, a drug that has the potential to deliver biologics like efficacy and safety without requiring patients to compromise efficacy and safety for convenience. a drug that has the potential to change the way patients are treated around the world. How will we do so? In two important ways. One, expand the existing treatment treated patient population, which for us is the number one goal. Second, provide an easy and convenient alternative to patients currently on injectable biologics, many of whom, based on our market analysis and industry survey data, are eagerly waiting to switch to an oral therapy. So then, how might this paradigm shift look, and what will it mean for patients with type 2 diseases? Our goal and the cornerstone of our development plan is to position KT621 as the product of choice for this large underserved or inadequately-deserved patient population. In many inflammatory diseases, advanced systemic treatments are typically reserved for patients with failed conventional therapies, which in turn are typically biologics. We believe having an effective safe oral medicine, we can fundamentally change the treatment paradigm, making it practical to intervene earlier in the disease course rather than waiting for significant progression or treatment failure. If successful, we believe KT621 has the potential to shift advanced therapy from being a last resort for a small subset of patients to a mainstream option for millions and improve standard of care. I hope that context around the market opportunity makes it clear why we believe that KT621 has the potential to be one of the biggest programs in the biotechnology and pharma industry. With that context, let's turn the call over to Jared and discuss clinical progress with KT621 and KT579, our IR5 degrader. Jared?