Kymera Therapeutics, Inc.

Good morning, and welcome to the Chimera Therapeutics first quarter 2023 earnings conference call. All participants will be in a listen-only mode for the duration of the call, and should you need any assistance during that time, 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 your telephone keypad. And to withdraw your question, please press star, then two. Please note that this event is being recorded today. I would now like to turn the conference over to the Chief Financial Officer, Bruce Jacobs. Please go ahead, sir.

Good morning, everyone, and welcome to the Chimera Therapeutics Quarterly Conference Call. I'm Bruce Jacobs, Chief Financial Officer at Chimera, and I'll be joined today by Nella Manolfi, Founder, President, and CEO, and Jared Golub, our Chief Medical Officer. After our prepared remarks, we will open the call to your questions. To ask a question at that time, please press star 1 on your telephone keypad. And if any time you'd like to withdraw from the queue, you can press star 2. Before I get started, I'd like to remind everyone that some of the comments that management may make on this call include forward-looking statements, as outlined in the press release. Actual events and results could differ materially from those expressed or implied by any forward-looking statements as a result of various risks, uncertainties, and other factors, including those set forth in Chimera's most recent findings with the SEC and any other future findings that the company may make with the SEC. You are cautioned not to place any undue reliance on those forward-looking statements, and Chimera disclaims any obligation to update such statements except as required by law. With that said, I'll now hand the call over to Nello.

Thanks, Bruce, and thank you, everybody, for joining us today. This month marks the seven-year anniversary of our founding. And as Chimera reaches this milestone, I thought I would spend a few minutes reflecting on the progress we've made on our ambitious plans to build the best-in-class, fully integrated global medicines company. Since our funding, we have focused on a target selection strategy that would allow us to use this novel drug modality in target areas that would uniquely benefit from it, and on evolving the platform to reach novel therapeutic hypotheses. Over that time, we've continued to enhance our platform capabilities and advance programs in areas of significant patient needs that cannot be meaningfully addressed by conventional medicines, building a high-value pipeline and demonstrating our ability to design molecules that have the potential to transform disease treatment. Our first-in-class ARAC4 degrader program, KT474, is a molecule we've discovered and developed through Phase I, and its plan to start phase 2 trials conducted by our partner Sanofi. In December of last year, we shared positive early data in both hydrotonitis separativa and atopic dermatitis patients that demonstrated strong translation of our preclinical PKPD and safety models into the clinic. With this program, we have seen for the first time clinical benefits of a hetero-bifunctional degrader in inflammation and immunology indications for the first proof of concept of clinical differentiation of a degrader compared to a small molecule inhibitor. This is a substantial accomplishment for a company that is pioneering a new modality. Sanofi expects to initiate the first phase two study of KT474 in HS this year, followed by a study in AD. Our three oncology programs continue to make progress. Of note, we have initiated the phase one clinical trial of our MDM2 degrader, KT253. The clinical effects of stabilizing P53 and P53 wild-type tumor is a concept that has been pursued extensively in the biopharma industry. There are a handful of MDM2 small molecule inhibitors in the clinic with some activity in a variety of tumor types. Unfortunately, the activity has been limited, given the inhibition of MDM2 leads to a transcriptional feedback loop, which creates more protein that makes it harder for occupancy-driven small molecule inhibitors to block, leading to reduced therapeutic indices. We believe KT253, on the other hand, has the potential to overcome that feedback loop because it removes the protein and does so in a catalytic manner. This makes KT253 a highly effective potent candidate that may be able to induce an irreversible acute apoptotic response with brief exposure while allowing time for the recovery of any normal cells which may be affected, creating an improved therapeutic index. With KT253, we believe we have a degrader that can remove MDM2, stabilize P53, and overcome the feedback loop generated by MDM2 reduction giving us the opportunity to explore the clinical potential of such a powerful mechanism fully. We look forward to sharing more updates as the trial advances, including safety and proof of mechanism data later in the year. Nearer term, we plan to present additional preclinical data on KT253's pharmacological profile at the European Hematology Association Congress next month. Our Arachimid program, KT413, targets Arach4 and the imid substrates, Igoros and Nylos, with a single small molecule and has the potential to be the first precision medicine to treat a genetically defined subset of tumors. KT413 has been designed to target mighty 88 mutant lymphomas, and we're currently in dose escalation of the phase 1 trial in B-cell lymphomas, including BLBCL. We shared some initial data from the trial in December showing that we engaged the target without any dose-limiting toxicities. Our third oncology program, KT333, target STAT3, which has been linked to numerous cancers and inflammatory and autoimmune diseases, and is the first degrader against an undrugged transcription factors to enter the clinic. We're currently in dose escalation of the phase one trial in a broad subset of liquid and solid tumor patients where we've also shown early proof of mechanisms. Our focus in 2023 for both KT413 and KT333 will be the degradation profile and evaluating their biological and clinical impact in the appropriate target patient populations. As discussed today, we plan to provide a clinical update focused on degradation and safety. for KT413 and KT333 at the International Conference on Malignant Lymphoma, or ICML, in June. We intend to present data evaluating anti-tumor activity in the target patient populations for both programs later in the year. In addition, we continue to push the science of TPD forward and identify best and first in class opportunities to transform the treatment of disease. We have several exciting programs in our preclinical pipeline that are designed to address well-validated immunology and oncology pathways in areas of significant patient need and commercial opportunity. These include developing tissue-selective restricted E3 ligase-driven programs, as well as a new generation of molecular glues, exploiting newly identified diagram motifs to expand the reach to high-value undrugged and non-legandable targets. We hope to be able to share more on these efforts later this year or early next. Jared will now cover in more detail the recent progress for each of our disclosed programs before turning the call over to Bruce for a financial update. I will then finish with some concluding remarks before handing the call to the operator for a Q&A session in which Jared, Bruce, and I will be available. Jared?