Kymera Therapeutics, Inc.

Welcome to the Chimera Therapeutics quarterly conference call. Leading the call for management are Nello Malby, founder and CEO, Jareb Golub, chief medical officer, and Bruce Jacobs, chief financial officer. After management's prepared remarks, we will open the call to your questions. To ask a question, please press star one on your telephone keypad. If at any point you would like to withdraw from the queue, please press star one again. Before we get started, I would like to remind everyone that some of the comments that management 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 filings with the SEC and any other future filings that the company may make with the SEC. You are cautioned not to place any undue reliance on these forward-looking statements, and Chimera disclaims any obligation to update such statements. I will now hand the call to Nello Manolfi, Founder President, and CEO.

Thank you, Operator, and thank you, everybody, for joining us today. We're very excited to share with you the progress we've made over the last quarter and how it contributes to achieving our mission to building best-in-class, fully integrated, global, the greater medicine company. We recently completed the patient cohort portion of our KT474 phase one clinical trial, which concludes the phase one campaign for this drug. Jared will share more details in his remarks, but with the study completed, we're currently in the process of collecting and analyzing all the data. We plan to share, as we always do, the data and the analysis of the data with our partner Sanofi. And as announced, we will subsequently share the data publicly on a company webcast on the morning of December 14th, 2022. As we have reiterated in the past, the objective of the patient cohort is to confirm that PKPD and safety in patients with AD and HS is consistent with what was demonstrated in the healthy volunteers, the SAD and MAD cohorts. As we announced last month, We plan to update investors also in our clinical oncology pipeline on the December 14th call. I believe you all know we have two clinical stage programs, the RACIMED KT413 and STAT3 KT333, and one program that we expect to enter the clinic soon, which is our MDM2 degrader KT253. With respect to the ongoing trials, the KT413 and KT333, they're both in those escalating stages of our phase one portion. As a reminder, the objective in these early dose cohorts is to demonstrate what we call a proof of mechanism. which we define as the ability to degrade the proteins of interest, which obviously is STAT3 for 333 and then for 413 is IRAC4 and even substrates, ECOROS and ILOS, with an advanceable safety profile. Again, Jared will share more here as we go into the call. Along with our clinical progress, we continue to work to ensure that we have the resources to build our company in a sustainable way and continue to invest in our clinical programs, discovery pipeline, platform, and teams. To this end, in August, we raised an additional $150 million through a private placement equity financing, which was led by a broad group of really committed, strategically aligned, and long-term oriented investors, each of which demonstrated their confidence in the team and share our optimism in Pemera's future. As a result, we ended the third quarter in a very solid financial position with approximately $596 million in cash. Before I turn the call over to Jared, I also wanted to take a moment to recognize the change we announced today on our board of directors. As many of you have heard me say, we aspire to build Chimera into a fully integrated biotech company and to sustain a leadership position in both PPD as well as in biotech. As we work to achieve this mission, we obviously will continue to build both an employee base as well as a board of directors that bring all the requisite knowledge and experiences to support our success. To that end, we're pleased to announce that Dr. Victor Sandor has joined our board of directors. For those of you who don't know Victor, he has deep expertise in global clinical development of medicines that have significantly impacted lives of patients, especially in oncology. He was most recently the CMO at RA Biopharma prior to his acquisition by Pfizer and has had an impressive career in the biopharmaceutical industry. Importantly, at the same time, I also would like to recognize and thank another director, Don Nicholson, who will be leaving Chimera as director after having served for the past five years and having started just shortly after the company's formation. Don is one of our longest-tenured directors and has been an important contributor to Chimera's growth and success over the last five years. We're very thankful for all of his important contributions and wishing the best. With that said, Jared will now cover in greater details a 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 back to the operator for a Q&A session in which Jared, myself, and Bruce will be available. Jared?

Thanks, Noah. I'm excited to share updates on our three clinical programs. I'll begin with our IRAC-IV program, AT474 is a potentially first-in-class oral degrader of IRAC4, a key protein involved in inflammation mediated by the activation of toll-like receptors in IL-1 receptors. AT474 is being developed for the treatment of TLR, IL-1R-driven immune and inflammatory diseases, such as hydradenitis suppurativa, atopic dermatitis, and potentially others. As you may recall, Part C is an open-label study of KD474 administered daily on an outpatient basis for 28 days with patients followed through day 42. As we shared last month, we've completed dosing in the patient cohort or Part C of our phase one trial for KD474. Additionally, we can confirm today that all patients have completed their last visit or day 42 of the study. The Part C patient cohort followed the dosing of over 100 healthy volunteers in the single ascending dose and multiple ascending dose portions of the Phase I trial. In the SAD and MAD studies, we demonstrated near-complete IRAC4 degradation in peripheral blood mononuclear cells and skin, robust inhibition of multiple ex vivo stimulated disease-relevant cytokines, and a favorable safety profile. Part C includes patients with either moderate to severe hydradenitis suppurativa or atopic dermatitis, and is examining the safety, pharmacokinetics, and pharmacodynamics of KT474, while also exploring early signs of clinical activity. Patients received a daily dose of 75 milligrams of KT474 in the fed state. This dose is expected to provide a plasma exposure that is approximately equivalent to that achieved with a 100 milligram per day dose in the facet state in healthy volunteers in the MAD portion of the trial, which showed maximal or close to maximal degradation in blood and skin and broad disease-relevant cytokine inhibition ex vivo. As previously mentioned, the goal for this study is to confirm that our PK, PD, and safety profile in patients is in line with what we have seen in healthy volunteers. In December, we plan to share data on the impact of KT474 on IRAC4 levels in PBMC and in active HS and AD skin lesions, as well as on the expression of pro-inflammatory gene transcripts in skin lesions and on plasma biomarkers of inflammation. We are also undertaking an exploratory assessment of early impact on clinical endpoints, including eczema area and severity index, or EZ for AD, total abscess, and inflammatory nodule counts, or HS, as well as symptom scores and global assessments of disease severity for both AD and HS. As we have noted in the past, it is important to consider that this is an open-label study without placebo in a small number of patients, and one in which we do not expect to reach steady-state IRAC4 degradation in skin until the second half of the four-week dosing period. And as a result, the data on early signs of clinical activity should be viewed through that lens. We will also be following safety and tolerability in Part C. And as a reminder, in our SAD and MAD studies, KT474 demonstrated no serious adverse events and only a few mild to moderate adverse events. Our December update will include a similar safety analysis including whether the modest non-adverse QTC prolongation that we observed with multi-dosing in healthy volunteers that plateaued after seven days continues to show evidence that it is self-limited, but in this case, out to 28 days. Before I conclude my remarks, I will update everyone on our disclosed oncology pipeline, which includes our SAS3, Arachamid, and MDM2 degraders, the first two of which are in the dose escalation stage of their ongoing phase one trials. As mentioned, our December webcast will include an update on our pipeline. As a quick reminder, STAT-3 is a transcriptional regulator that has been linked to numerous cancers and other inflammatory and autoimmune diseases. Our Phase I clinical trial is evaluating KT333's potential in hematological malignancies and solid tumors. Specifically, the trial is evaluating the safety, tolerability, PKPD, and clinical activity of KT333 in adult patients with relapse and or refractory lymphomas in solid tumors. We have been recruiting broadly in Phase Ia dose escalation across solid and liquid tumors in order to reach pharmacologically active doses as soon as possible, before then focusing on patient populations where we expect to see clinical activity, either as a monotherapy or in combination with other agents. The trial's second stage will consist of four Phase Ib expansion cohorts to further characterize the safety, tolerability, PKPD, and antitumor activity of KT333 in relapsed and or refractory peripheral T cell lymphoma, cutaneous T cell lymphoma, large granular lipocytic leukemia, and solid tumors. In September, KT333 was granted its second orphan drug designation by the U.S. Food and Drug Administration for the treatment of cutaneous T cell lymphoma, following its orphan drug designation for peripheral T cell lymphoma earlier this year. Our arachnid program, KT413, is a novel hetero-bifunctional degrader that targets degradation of both IRAC4 and the imid substrate icorose and ilose with a single small molecule. KT413 was designed to address both the IL-1R, TLR, and the type 1 interferon pathways synergistically to broaden activity against mighty 88 mutant B-cell malignancies. KT413 is on a similar timeline as STAT3 and is currently in the dose escalation stage of the Phase 1 trial, evaluating the safety, tolerability, PKPD, and clinical activity of KT413 in patients with relapsed and or refractory B-cell non-Hodgkin's lymphomas. Similar to the strategy I just described for the KT333 Phase 1, we are enrolling a broad population of B-cell lymphoma patients after which we will focus on patients in whom we expect to see the most substantial clinical activity. Specifically, the second stage will consist of two Phase 1B expansion cohorts in DLBCL to further characterize safety, tolerability, PKPD, and antitumor activity of KT413 in relapsed refractory, MI-D88 mutant, and MI-D88 wild-type DLBCL. Finally, KT253, our MDM2 degrader, has completed IMD-enabling studies and is on track to achieve IMD clearance by year end. MDM2 is the crucial regulator of the most common tumor suppressor, P53, which remains intact in more than 50% of cancers. Chimera is developing a highly potent MDM2 degrader that, unlike small molecule inhibitors, has been shown preclinically to have the ability to suppress the MDM2 feedback loop and rapidly induce apoptosis, even with brief exposures. KT253 has the potential to be effective in a wide range of hematological malignancies and solid tumors with functioning or wild-type P53. We look forward to updating investors on our pipeline in December. I will now hand the call to Bruce Jacobs, our Chief Financial Officer, who will share some brief comments on our financial results for the first quarter.