Kymera Therapeutics, Inc.

Good day everyone. My name is Sophie and I will be your conference operator today. At this time, I would like to welcome you to the Chimera Therapeutics third 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 would like to ask a question during this time and you have joined via the webinar, please use the raise hand icon, which can be found at the bottom of your webinar application. If you have joined by phone, please dial star nine on your keypad to raise your hand. At this time, I would like to turn the call over to Justine Konigsberg, Vice President of Investor Relations.

Good morning and welcome to Chimera's quarterly update. Joining me this morning are Nello Manolfi, founder, president, and CEO, Jared Golub, our chief medical officer, and Bruce Jacobs, our chief financial officer. Following our prepared remarks, we will open the call to questions from our publishing analysts. If you would like to ask a question, please use the raise hand icon, which can be found at the bottom of your meeting window. And to help us move efficiently through the Q&A session, we ask that you are ready to unmute your line when called on. In addition, we ask that you please limit your question to one and a relevant follow-on to be sure we have enough time to address everyone's questions this morning. Before we begin, I would like to remind you that today's discussion will include forward-looking statements about our future expectations, plans, and prospects. These statements are subject to risks and uncertainties that may cause actual results to differ materially from those projected. A description of these risks can be found in our most recent 10Q filed with the SEC. Any forward-looking statements speak only as of today's date, and we assume no obligation to update any forward-looking statements made on today's call. With that, I would like to turn the call over to Nello.

Thank you, Justine, and thanks, everybody, for joining us this morning. Now, in the final quarter of the year, as we reflect on 2025, I'm happy to say that our team has executed exceptionally well across all parts of our business, and we're very proud of all that we have accomplished this year. We're committed to building a global biopharmaceutical company and have established a strong foundation that will serve us well as we scale an organization and continue to advance our industry-leading oral immunology pipeline. As shown on this slide, I'd like to highlight a few of the key achievements this year that positions us well for important future milestones. In less than two years since unveiling our STAT6 program, we have demonstrated exceptional progress in advancing our first-in-class STAT6 degrader KT621. To recap, we completed a healthy volunteer study ahead of schedule with impressive results. We enrolled and completed dosing in the Phase 1b trial in AD patients, with data coming in December. We initiated a first of two Phase 2b trials, brought in two in AD, and we're on track to start the breath Phase 2b asthma trial in the first quarter of 2026. We were also featuring two recent late-breaking presentations, which have helped us maintain high level of visibility with the medical and scientific communities, where there continues to be a strong interest in oral medicines with potential for biologics-like activity. Beyond STAT6, we unveiled our IRF5 program this spring and presented the robust preclinical data at the American College of Rheumatology annual meeting. just recently. We've also completed the KT579 IND enabling studies and remain on track to initiate the first clinical trial in healthy volunteers early in 2026. In addition to RF5, we continue to advance an earlier stage undisclosed immunology pipeline, and our goal remains to address many of the major immunology indications with oral medicines. Importantly, we believe that synergies across our pipeline provide multiple development opportunities for broad patient populations. We also entered into a new partnership with Gilead outside of immunology. Gilead is an ideal partner to drive forward our CDK2 oncology molecular glue program, which we believe has broad potential in breast cancer and other solid tumors. In summary, it's been a very busy year and a successful one, and we look forward to finishing this year strong as we advance our pipeline towards more and more important milestones. More broadly, we built what I believe is one of the strongest oral immunology pipeline in the industry, where we're well positioned to deliver novel oral treatment options for patients with highly prevalent immune inflammatory diseases. Several years ago, we made a deliberate strategic shift to focus our R&D efforts toward the significant opportunities in immunology. And the reason is quite simple. Within immunology, many pathways have been validated with upstream biologics. Traditional small molecule inhibitors are not able to block the signaling pathways as effective as biologics, given that direct correlation between PK and PD and the need of high drug exposures. As a result of the power of protein degradation, we can now selectively remove disease-causing proteins through a catalytic mechanism and can block pathways completely. which we've consistently demonstrated across all of our programs. This allows us for potential of oral drugs with biologics-like activity for the first time in our industry. And our first-in-class pipeline is a testament to this strategy. If we look specifically at a STAT6 program, KT621 exemplifies this approach. There is a tremendous opportunity for a convenient, safe, and effective oral pill in highly prevalent type 2 diseases like atopic dermatitis, asthma, COPD, EOE, and others. Despite the large size of the patient populations, the penetration of other systemic advanced therapies like injectable biologics is actually quite low. This creates a significant opportunity for safe and effective oral medicines, which we believe would have potential to change the quality of life for many patients and families around the world. We moved our statistics program at a rapid pace from preclinical to IND to initial clinical proof of concept, and we're now embarked on our first global face-to-be trials. In fact, we filed our IND in September of 2024, and by the fourth quarter of 2025, we've already launched our first face-to-be study. This progress is a strong testament to the speed, focus, and execution of excellence of our team in driving this program forward. Looking back at KT621 Phase 1 Healthy Volunteer Study, we demonstrated that at very low doses, we can degrade STAT6 fully and block Th2 disease-relevant cytokines in healthy volunteers as effectively as upstream biologics, and in a well-tolerated manner. We're moving quickly towards completion of the broadened Phase 1b trial, which we initiated in the spring. To remind you, the trial was designed to achieve three important goals. to confirm robust degradation in blood and skin and understand the translation from healthy volunteers to AD patients, to allow us to refine the phase IIb doses based on that translation, and to demonstrate that robust stat6 degradation in AD patients can impact biomarkers and clinical endpoints similar to upstream biologics, specifically dupilumab. Given that the trial is fully enrolled and we plan to share the data next month, I wanted to use this call one last time to reiterate expectations we're setting into the study across the four dimensions we're evaluating KT621 on, degradation, safety, biomarker, and clinical activity. With respect to STAT6 degradation, the goal is to translate in AD patients the robust degradation of STAT6 in blood and skin that we've seen in the phase one healthy volunteer study. The safety profile is paramount, and we hope to continue to see a safety profile in line with what we've seen in both healthy volunteers as well as our preclinical studies. With respect to biomarkers, we plan to look in both blood and skin. In blood, we have highlighted TARC as the most relevant biomarker at the four-week time point. After achieving up to a median reduction of 37% of TARC in healthy volunteers, and given that in atopic dermatitis patients generally have higher baseline TARC levels, our expectation is to show a meaningfully more robust TARC reduction. As a point of reference, in published dupilumab studies where baseline TARC levels were much higher than healthy volunteers, the reduction was in the range of 70% to 80% at four weeks. which is the bar we set for KT621, assuming generally comparable baseline levels. In skin, we also plan to assess KT621's impact on skin transcriptomics, which we have not assessed in the healthy volunteer studies. There, we anticipate changes in downstream genes that aligns with the expected biological effect of this pathway modulation. And finally, in terms of clinical endpoints, we went into the study with a robust body of evidence in all of our experiments demonstrating KT621 blocks IL4N13 as well as dupilumab. And this has resulted in comparable downstream pathway effects in both in vitro and in vivo studies. As a result, we entered the broadened study expecting clinical activity of KT621 to be in the range of what Doopie delivered at four weeks in its published studies, including on both easy score and itch, with all the caveats, small ends, and the lack of a placebo arm. I hope that this is helpful as we approach the data readout next month. Given that we have quite a bit of investor activities planned this month, please understand we will refer back to these key objectives and reserve any additional commentary for the final data presentation in December. So before I hand the call back to Jared, I wanted to take a moment to welcome Brian Adams, our new chief legal officer to Chimera. He's a seasoned life science executive with deep industry experience, bringing more than two decades of experience across legal and compliance, corporate development, strategic planning, and governance. We're thrilled to have him join our team as we enter this next phase of growth and look forward to his contributions as we continue our efforts to building a fully integrated commercial stage company. To wrap up, as I said on the onset of the call, this has been a year of exceptionally strong execution, and we're well-positioned to continue advancing all aspects of our pipeline as we head into 2026. I'm confident that through our expertise, scientific rigor, focused execution, we're building one of the most exciting immunology portfolios in this industry. Let me pause here and turn the discussion over to Jared, who will provide us an update on the pipeline, including additional color on our newly initiated atopic dermatitis study. Jared.