Kymera Therapeutics, Inc.

Good day and welcome to the Chimera Therapeutics third quarter 2023 results call. All participants will be in listen-only mode. If 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. Please note that this event is being recorded. I'd like to turn the conference over to Ms. Justine Collinsberg, Vice President of Investor Relations. Please go ahead.

Good morning, and welcome to Chimera's quarterly update. Joining me on this morning's call are Nello Manolfi, founder, president, and CEO, Jared Golub, our chief medical officer, and Bruce Jacobs, chief financial officer. Following our remarks and presentation, we will open the call to questions. During the Q&A portion of the call, please limit your question to one and a related follow-up so that we will have enough time to address everyone's questions. Please note that we will be referencing slides in our corporate presentation during Jared's remarks. The slides can be accessed in the investor section of our website under events and presentations and will be shown during the call for those on the webcast. Before we begin, 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 now like to turn the call over to Nello.

Thank you, Justine, and thanks, everybody, for joining us today. We're excited to review our recent progress and several critical milestones that the company has achieved. As we are near the end of 2023, I'm extremely proud of the strong execution by our team that has led to continued progress in our clinical studies across multiple programs, along with innovative pipeline advancements to support our future growth. Before we detail that progress, I want to share a few thoughts on where Chimera is in our mission to building a best-in-class, fully integrated global degrader medicine company. In doing so, I hope to provide you with an important lens through which you can view our achievements and our strategic decisions regarding the portfolio. Our unique approach to developing a new generation of medicines using TPD has resulted in a robust pipeline, both in the clinic and on the way to the clinic, highlighted by multiple programs that are guided by and consistent with our goal of creating groundbreaking medicines. I hope there is broad appreciation for all that Chimera has accomplished since our founding only seven years ago. We have taken four programs in the clinic, demonstrating fidelity of translation of PK, PD, and safety across each of those programs. We have shown early clinical proof of concept for three of them, as you will hear soon. Our unique strategy has allowed us to achieve multiple TPD firsts, including conducting the first INI study in healthy volunteers and patients with KT474 targeting IRAC4. In addition, we've been the first to degrade an elusive transcription factor like STAT3. More strategically, for KT474, we formed a critical collaboration with Sanofi, one of the leaders in the INI space. And that program is now advancing in Phase II development, with the first patient in the first trial just recently dosed. We have built industry-leading knowledge and capabilities that we're leveraging each and every day, and we have developed a best-in-class pipeline of innovative and highly valuable programs, some of which we would be excited to share with you over the coming months. An important cornerstone of Chimera's success has been our unique approach to target selection, which has several key tenets that guide our strategy and, of course, our research and development efforts. Our focus is and has always been on genetically validated targets that are either undrugged or inadequately drugged within pathways with clear validation and where TPD is the best or only solution. Importantly, we target large market opportunities where the unmet needs are significant and where we believe that there is a greater probability and opportunity for significant commercial success. With regards to therapeutic areas, our programs have progressed over the last several years. And as you can see from the pipeline slide on our website and in our corporate presentation slide six, our portfolio has increasingly leaned towards immunology. This is a purposeful strategy orientation guided by several factors that have influenced our strategic and investment decisions. You will hear a more complete overview of this focus at our R&D day on January 4th, but today I'd like to highlight a few. First, it is clear that INI is an area where the understanding of the underlying biology has increased dramatically. Second, the large commercial opportunities within INI are mostly dominated by biologics that have helped validate key pathways and targets, but also create an opportunity for other more convenient modalities. And at last, at least for today, to that point, we believe that TPD can provide a unique solution with strong efficacy and biologics-like specificity, but with the flexibility of oral small molecules. Importantly, we hope you all appreciate that we have demonstrated early but convincing evidence of our potential in INI with KT474. In fact, we believe strongly that the success we've had with our IRAC4 program will help shape how we approach these new opportunities. We have countless learnings from that program, starting with the development of the molecule itself, including our extensive preclinical work and the key insight we've gained from running what we believe is the largest safety volunteer subsequent patient study in the TPD space. And now KT474 is undergoing phase two studies with our partner Sanofi. This wealth of experience and knowledge gives us high degree of confidence in our ability to execute on many new opportunities, some of which we will be sharing with all of you in the coming months. We've also made important progress in the clinic with KT333, which targets STAT3, and KT253, our MDM2 degrader. Jared will provide updates on both programs later during the call. At high level, we're very excited that KT333 will appear in an ASH abstract later this morning and will be featured in a poster presentation with updated clinical data at the ASH meeting in December. It's important to note that we're seeing early signs of clinical activity, even at those levels that were not predicted to be clinically active, but where we are nonetheless seeing robust STAT3 degradation. Jared will share a few highlights on this call. And we'll be able to say more once the accepted abstract is publicly released, which should be shortly after our call concludes this morning. We're also excited about early data emerging from KT253 Phase 1 dose escalation study. We've demonstrated both proof of mechanism and early signs of clinical activity in the initial dose levels, even earlier than we expected. The early clinical activity, lack of thrombocytopenia neutropenia in the presence of anti-tumor activity makes us optimistic about the translation of our degrader rationale of increased therapeutic index and full realization of P53 pathway potential. With regards to KT413, our arachnid degrader, we have decided to discontinue the program. Let me first say that this decision is not driven by any clinical data or safety concerns that we have with the program. We are degrading the targets in blood as we had expected, and we have not experienced those limiting toxicities. Rather, our decision to discontinue KT413 reflects our commitment to the program that more closely fit the previously mentioned strategic focus of the company. More specifically, when we evaluate the evolving healthcare landscape, especially in oncology, and the market opportunity and the competitive landscape in in diffuse large B-cell lymphoma and juxtapose that with the enormous opportunities we have in our emerging pipeline, we have decided the right strategic decision is to focus our resources on those high-value programs. It should also be noted that we did not take this decision lightly, nor did we make it without thinking about the potential impact on patients. But as many of you already know, the DLBCL market is well served today with numerous active agents, And we believe promising therapies will continue to emerge in the relapsed refractory and frontline settings. Ultimately, we believe that Chimera can have the greatest impact by focusing on areas of significant unmet patient need where TPD can have the greatest impact. We've built a team with leading expertise in drug discovery and development capabilities, which we believe provides Chimera with a strong competitive advantage. And perhaps most importantly, as I have already highlighted, we have shown our ability to execute with the development of KT474, which has achieved another significant milestone with the dosing of the first patient in the Phase II study. At our Immunology R&D Day in January, we will provide an even clearer picture of the strategic focus that we're outlining today, highlighted by what we believe are both important and exciting pipeline disclosures. We're confident then when we share the details around our next programs and our strategies for building Chimera into an industry-leading, fully integrated biotech company, you will appreciate our enthusiasm for the enormous opportunities those programs represent. I can tell you now, and I will likely repeat this when we gather in January, I've never been more encouraged and excited by the pipeline opportunities on which Chimera is poised to capitalize. Finally, Chimera remains very well capitalized, which puts us in a strong position to execute on the opportunities our pipeline presents. As we noted in today's press release, we have extended our runway into the first half of 2026. This takes us well beyond several key catalysts and data readouts that we expect to be important de-risking events for our clinical and preclinical pipeline, including face-to-date on KT474, further POC readouts for our oncology programs, and important updates on our pipeline, more details about which will be shared at our upcoming Immunology R&D Day. Let me pause here and turn the discussion to Jared.