Syndax Pharmaceuticals, Inc.

And welcome to the Sendax First Quarter 2023 Earnings Conference Call. Today's call is being recorded. At this time, I would like to turn the call over to Sharon Clary, Head of Investor Relations at Sendax Pharmaceuticals.

Thank you, Operator. Welcome, and thank you all for joining us today for a review of Sendax's First Quarter 2023 Financial and Operating Results. I'm Sharon Clary, and with me this afternoon's provided update on the company's progress and to discuss financial results are Michael Metzger, Chief Executive Officer, Dr. Neil Gallagher, President and Head of R&D, and Keith Goldan, Chief Financial Officer. Also joining us on the call today for the question and answer session are Dr. Peter Redentlis, Chief Scientific Officer, and Dr. Angelique Angouli, Chief Business Officer. This call is accompanied by a slide deck that has been posted on the investor page of the company's website. You can now turn to our forward-looking statements on slide two. Before we begin, I would like to remind you that any statements made during this call that are not historical are considered to be forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Actual results may differ materially for those indicated by these statements as a result of various important factors. including those discussed in the risk factor section in the company's most recent quarterly report on Form 10Q, as well as other reports filed with the SEC. Any forward-looking statements made represent our views as of today, May 8, 2023 only. A replay of this call will be available on the company's website, www.syndex.com, following its completion. And with that, I'm pleased to turn it over to Michael Metzger, Chief Executive Officer of Syndex.

Thank you, Sharon, and thank you all for joining the webcast. I want to also welcome Dr. Neil Gallagher to be called today as our new president and head of R&D. Neil is a highly accomplished oncology drug developer and his deep experience across all stages of drug development and strong track record of successful drug approvals will be instrumental in driving continued pipeline development and growth at Syndex. You will hear from Neil later in the call. We also welcome Kevin McManus of the company as our new chief people officer. We look forward to benefiting from his extensive experience and vision in building our organization and culture. Now turning to slide three, where we provide a high-level summary of our current corporate priorities. Throughout the first quarter, we continue to execute on our clinical and corporate strategy. We are confident in our ability to deliver pivotal readouts and registration filings for our two lead drug candidates later this year. We are on the cusp of realizing the potential of our science by delivering treatments that provide critical benefit to patients where there is significant unmet medical need. Diving into Revumentiv, our highly selective menin inhibitor. Our pivotal Phase II Augment 101 trial evaluating Revumentiv in patients with relapsed refractory NPM1 mutant or KMT2A rearranged acute leukemia is progressing well. We expect to report data from KMT2A rearranged acute leukemia patients in the Augment 101 Pivotal Trial in the third quarter of this year, which could serve as the basis for a U.S. regulatory filing by year end. We have several additional trials ongoing designed to expand the potential of Revumentiv beyond use as a monotherapy agent in patients with relapsed refractory acute leukemias, including combinations with standard of care regimens to treat these forms of acute leukemia, and we expect to have initial data from several of them by the year end. I will provide details on each of these trials later in the call. Moving to axotilamab, our antibody against CSF1R. We remain on track to report top-line data in mid-2023 from the pivotal Phase II Agave 201 trial evaluating axotilamab in patients with chronic graft-versus-host disease, or CGVHD, and plan to submit a BLA filing by the end of 2023. With Insight, we have the support of a strong pharmaceutical partner to help us advance the development of axotilamab and successfully commercialize once approved. Other trials that we expect to initiate this year include a Phase I-II combination trial of Axotilamab and Jacopi in CGVHD, led by our partner Insight, as well as a Phase II trial of Axotilamab in idiopathic pulmonary fibrosis, or IPF, that will be led by Syndax. As we prepare to become a commercial stage by our pharmaceutical company, delivering two best-in-class products to patients in areas of high unmet medical needs, We continue to take a disciplined and thoughtful approach to building our organization with highly experienced and talented people. We are well funded with $449 million in cash as of March 31st. Our cash balance enables us to expand beyond our core registration indication and provides us flexibility to selectively pursue business development opportunities. As part of that effort, we continue to evaluate earlier stage targeted oncology compounds for potential in licensing. We believe that we have sufficient resources to acquire new early-stage assets that have the potential to become high-value differentiated drugs, but we have, as we have conveyed, a high bar for doing so, as any compound would need to complement our current pipeline and align with our long-term corporate strategy. Let's now turn to slide four, and I'll provide further details on the REVIMED program. The phase two portion of Augment 101 was designed as three single arm pivotal trials with distinct patient populations that enroll independently. These populations include KMT2A rearranged ALL, KMT2A rearranged AML, and MPM1 mutant AML. The primary endpoint of each is the percentage of patients achieving CRCRH with secondary endpoints including durability of CRCRH response, transfusion independence, overall survival, and safety. Patients who undergo transplant also have the opportunity to be retreated with Revumentiv in the phase two portion, which could be an important maintenance option for these patients given that they are at high risk of relapse. Based on the broad breakthrough therapy designation we received in December 2022 and conversations with regulators, we will pool data generated from the AML and ALL KMT2A cohorts into a single NDA filing aimed at an indication to treat adult and pediatric relapse refractory acute leukemia patients with a KMT2A rearrangement. We expect to provide top line data from this pooled population in the third quarter of this year and plan to file an NDA for the treatment of relapse refractory KMT2A acute leukemia in adult and pediatric patients by the end of 2023. Separately, we continue to enroll relapse refractory MPM1 mutant AML patients and expect completion of enrollment of this cohort in the second half of 2023. I'm happy to report that in the first quarter, we completed the clinical pharmacology work that supports a recommended phase two dose in any patient eligible for RevuMentive. We have determined the RP2D in patients who are not on a strong CYP384 inhibitor is 276 milligrams every 12 hours, and now have agency agreement on including this dose in Augment 101. This means that any patient can be treated with Revumentiv, whether or not they are receiving concomitant CYP3A4 inhibitors. We would expect this dose to be incorporated into the Revumentiv label at the time of approval. Moving to slide five, we are excited to now have the Phase I Augment 101 data published in Nature. The work lays out the biology of Revumentiv and provides a thorough review of the data. In these heavily pretreated patients who have received a median of four prior therapies, 30% of the efficacy-evaluable population experienced the CRCRH with an impressive median duration of CRCRH response of 9.1 months as of the data cutoff date. The authors concluded that Revimenib monotherapy was associated with encouraging clinical benefits, including deep molecular remission and durable responses with minimal toxicities in this heavily pre-treated patient population. Turning to slide six. Based on Revumentive's compelling efficacy and safety profile, our clinical strategy is to expand beyond the relapse or refractory setting into earlier settings and post-transplant maintenance, as well as explore the combination of Revumentive with approved therapies. We believe that Revumentive could become the backbone of treatment for patients with KMT2AR and NPM1 mutant acute leukemias, and by unlocking the full potential of Revumentive, meaningful value would be added. There are currently no FDA-approved therapies targeting KMT2AR or MPM1 acute leukemias, a population that together represents up to 40% of AML patients. Including the expansion opportunities, we see the potential to address upwards of 12,000 MPM1 mutant and KMT2AR acute leukemia patients across various settings. Because of this significant unmet medical need, we are committed to bringing encouraging clinical benefits to even more patients. Here we highlight our ongoing trials of Revumenib across the treatment landscape, starting with the Phase 1 Beat AML Umbrella Trial. As part of our collaboration with the Leukemia and Lymphoma Society, Revumenib is being combined with venetoclax and azacitidine to treat newly diagnosed AML patients with an NPM1 mutant or KMT2A rearrangement who are unfit for induction chemotherapy. Revumenib is the first MEN inhibitor to be included in this trial, which will assess safety as well as initial efficacy. Enrollment is ongoing, and we expect to report initial safety data from the trial by year-end 2023. Longer term, we expect that positive beat AML trial results could lead to a Phase 2-3 trial, which could serve as the basis for future regulatory filing. We are also currently enrolling patients in the Augment 102 trial, designed to assess Revimenta in combination with standard salvage chemotherapies for patients with relapse or refractory MPM1 mutant or KMT2A rearranged acute leukemias. We expect to reach a recommended phase 2 dose and report initial data from this trial in 2023. And the Intercept trial continues to enroll patients as part of the master clinical trial led by the Australasian Leukemia and Lymphoma Group. The trial is a creative approach to treating patients early in their disease course as it is focused on investigating novel therapies to target early relapse and clonal evolution as preemptive therapy in AML. It is designed to explore the activity of Revimenib, the first menin inhibitor to be included in this master trial, as monotherapy in patients with NPM1 mutant or KMT2A rearranged AML who have MRD-positive disease following initial treatment. a group of patients at very high risk of relapse. Data from this trial could also provide additional support for use of Revumentiv in a maintenance setting. We also plan to initiate a trial of Revumentiv in combination with standard of care intensive chemotherapy known as 7 plus 3 in the frontline setting in the second half of this year. Turning to slide 7, beyond the market opportunity that we outlined here in acute leukemias, We are also exploring the use of revumenib as a treatment in solid tumors based on compelling preclinical science supporting the role of the menin-MLL1 interaction in beta-catenin-driven tumors. Enrollment is going well in our proof-of-concept signal-seeking phase 1 trial in metastatic colorectal cancer, and we expect to have initial data from this trial by year-end 2023. Now I'd like to turn the call over to Neil to briefly talk about chronic graft-versus-host disease and why we believe axotilamab, our potentially best-in-class monoclonal antibody therapy targeting the CSF1 receptor, could benefit patients diagnosed with this disease. Neil?