Kymera Therapeutics, Inc.

Good day and welcome to the Chimera Therapeutics first quarter 2024 results conference call. All participants will be in the listen-only mode. Should you need assistance, please signal a conference specialist by pressing the star key followed by zero. After today's presentation, there will be an opportunity to ask questions. To ask a question, you may press star, then one on a touch-tone phone. To withdraw your question, please press star, then two. Please note that this event is being recorded. I would now like to turn the conference over to Justine Kronisberg. Please go ahead.

Thank you. Good morning, and welcome to Karnera's quarterly update call. Joining me this morning are Nella Manolfi, 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. To have enough time to address everyone's questions, we ask that you please limit your questions to one and a relevant follow-up. 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 FCC. 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'll now turn the call over to Nello.

Thank you, Justine. Good morning, everybody. It's been a very productive beginning of 2024. Starting in January with an extensive update at our Immunology R&D Day, and a subsequent financing to provide capital that we will invest in our expanding clinical development efforts and growing pipeline. Past quarter has been focused on execution on both our preclinical and clinical pipeline, as well as external engagement across a variety of business and medical conferences. Today, our plan is to share a brief update on our programs, as well as timelines for news and catalysts we're expecting through the rest of this year and early 2025. As we shared earlier this year, we believe we have a significant opportunity to address and expand the existing treatment paradigms within immunology by developing compelling oral small molecule degrader medicine with biologics-like activity. Had that been the case all the way back to the founding of the company, we have taken a differentiated approach to target selection and focused on critical molecular pathways that are well validated through human genetics, clinical evidence, and or the success of approved drugs. Many of these pathways play a key role in immune-mediated disease pathology, and while injectable biologics dominate these markets, often due to their strong clinical activity, they're not without limitations, which in many instances can limit penetration. As a result, we believe developing convenient oral options with biologics-like activity and a good safety profile represents an enormous opportunity to expand patient access in many of these markets that are currently dominated by injectable agents. Our IREC4 program, which was our first program to enter clinical development, simplifies a target and a pathway that has the potential for a broad patient impact. We have talked in the past about our reasons for enthusiasm around IREC4 as a target and our rationale for pursuing it. IREC4 is an obligate node in the I1 PLR signaling, and we believe its degradation is the only approach to fully block the pathway, creating multiple development opportunities in large, high-and-mid indications. In the KT474 IREC4 Phase I trial, we observed deep and well-tolerated degradation, early signs of clinical efficacy, and high fidelity of translation from preclinical models to patients. which provide key insights for our growing immunology pipeline and position future programs, such as our STAT6 and TIK2 degraded programs, for success. In March, we had the opportunity to showcase our prototype immunology programs, KT621, our STAT6 degrader, and KT294, our TIK2 degrader, at the American Academy of Dermatology annual meeting. The poster presentations, which mark the first data from a STAT6-targeted agent, and a TIK2 degrader to be shared at a major medical meeting highlighted our robust preclinical passages and support the significant potential of our oral degraders in these pathways. In our KT621 AAP poster, we highlighted the preclinical efficacy studies comparing KT621 to dupilumab in a preclinical atopic dermatitis model. Importantly, KT621 shows robust activity in vivo in this model, equal or superior to dupinamide. KT621's degradation of statics was well-tolerated in multiple preclinical safety studies, and doses had concentrations up to 40-fold above the projected human efficacy concentrations. If we can indeed deliver biologics-like activity, a good safety profile, and oral once-daily dosing, we believe KT621 could change the treatment paradigm of millions of patients suffering from TH2-driven inflammation. In terms of timing, KT621 is currently in 9D laboring studies and is on track to enter Phase I testing in the second half of 2024. It's our intent to conduct a Phase I healthy volunteer study to assess single and multiple ascending doses of KT621 and move quickly from there into patients. We have finalized our clinical development plan and strategy, and we look forward to sharing more details as we move closer into clinical development. Moving to TIK2, we shared a poster AAD that demonstrated picomolar degradation, potency, and low nanomolar inhibition of the L23, L12, and type 1 interferon pathways, showing KT294's potential to recapitulate the biology of human TIK2 loss of function mutations. The biological differentiation of KT294 from allosteric to small molecule inhibitors was demonstrated through isentan sparing compared to DUPRA, which is important in inflammatory bowel syndrome, as well as was shown through superior inhibition of type 1 interferon pathway compared to TAC279, which is relevant for the treatment of several diseases, including interferon-driven diseases. KT294 demonstrated deep and sustained TIK2 knockdown in vivo with low daily oral doses. We believe that this data demonstrates that a TIK2 degrader has the potential to deliver best-in-class TIK2 pathway blockade with productivity across multiple L12, 23, and TIK1 interferon-driven immune inflammatory diseases. We intend to continue to share updates across our pipeline and medical meetings in 2024. In fact, later this month, we present a poster highlighting KT621 and its potential to treat TH2-allergic diseases at both the American Therapeutic Society International Conference in San Diego as well as at the Digestive Disease Week in D.C. These presentations, which build on what was previously shared at R&D, they will include new, exciting additional previews of data. To sum up my intro here, since our funding eight years ago, a milestone which we will commemorate just in a few days, we have demonstrated consistent and scalable innovation, including strongly clinical to clinical translation of degradation, safety, and activity across the whole pipeline. We have also achieved early proof of concept in both immunology and oncology, which we believe is a significant accomplishment for the new modality. As we are transitioning from early to mid-late, development across our pipeline, we remain committed to building on our early success and expanding our team and capabilities to deliver on the substantial clinical and commercial opportunities that our programs offer to ultimately become a global commercial stage medicine company. In the meantime, we look forward to important near-term data redacts this year in oncology and multiple redacts from our immunology pipeline in 2025. I'll pause here and ask Jared to provide an update on our clinical program. Jared?