Syndax Pharmaceuticals Announces Preclinical Profile and Initial Phase 1 Data Demonstrating Clinical Activity of Menin Inhibitor SNDX-5613 in Adults with Relapsed/Refractory Acute Leukemias

Publisher: The Insight Partners

Syndax Pharmaceuticals, Inc., a clinical stage biopharmaceutical company developing an innovative pipeline of cancer therapies, presents preclinical and initial clinical data for SNDX-5613, the Company's potent, highly selective oral menin inhibitor. The oral presentation will be featured during the New Drugs on the Horizon session at the 2020 American Association for Cancer Research (AACR) Virtual Annual Meeting I. The New Drugs on the Horizon session will take place today at 4:50 p.m. ET and features discussions of innovative small molecules and biologics that have recently entered Phase 1 clinical trials.

"Within months of initiating the Phase 1/2 AUGMENT-101 trial, we are excited to present to the cancer research community the first clinical evidence that disrupting the interaction between menin and MLL1 with our potent and selective inhibitor, SNDX-5613, can induce response in patients with genetically-defined acute leukemias," said Briggs W. Morrison, M.D., Chief Executive Officer of Syndax. "Notably, clinical activity was achieved rapidly after a single, 28-day cycle, a highly encouraging sign in this population of patients who face a particularly poor prognosis with few effective treatment options. We look forward to presenting additional findings from this trial in the fourth quarter."

The Company also announced today that SNDX-5613 was recently granted Orphan Drug Designation for the treatment of adult and pediatric acute myeloid leukemia (AML) by the U.S. Food and Drug Administration (FDA).

Preliminary AUGMENT-101 Data

As of the April 17th data cutoff date, a total of six patients have been treated in the Phase 1 portion of the ongoing open-label AUGMENT-101 trial at increasing dose levels of SNDX-5613. Responses were observed in two of three patients harboring an MLL rearrangement. This included one patient, whose drug exposure was consistent with that needed for activity in preclinical models, who had a complete response  with incomplete blood count recovery (CRi) after 28 days of therapy and subsequently improved to a complete response (CR). The second patient achieved a partial response with incomplete blood count recovery (PRi) after 28 days of therapy. Both patients continue to receive SNDX-5613. A third patient harboring an MLL rearrangement did not achieve drug exposure levels consistent with that needed for activity in preclinical models and was removed from the trial due to progressive disease. Treatment with SNDX-5613 has been tolerated well, with no dose limiting toxicities reported. One patient experienced a Grade 2 QTc prolongation but remains on treatment. Additional details regarding all six patients are available in the AACR presentation.

"Three decades of scientific research exploring the menin-MLL-r interaction and its importance in this subset of leukemias have helped establish our confidence in the therapeutic potential of SNDX-5613 for leukemia patients harboring MLL-r and NPM1 mutations," said Jerry McGeehan, Ph.D., Vice President, Menin Program at Syndax Pharmaceuticals. "Following the recently published preclinical studies in Cancer Cell and Science magazine highlighting the activity of menin inhibition in genetically-defined leukemias, we are thrilled to demonstrate in the clinical setting that SNDX-5613 could serve as a targeted agent with the potential to deliver durable benefit to a severely underserved patient population."

The Company's presentation also highlighted preclinical data supporting the potential of single-agent menin-MLL inhibition to serve as an effective intervention for both NPM1 mutant AML and MLL-r acute leukemias.

The AUGMENT-101 trial is a Phase 1/2 open-label trial designed to evaluate the safety, tolerability, pharmacokinetics and efficacy of orally administered SNDX-5613. The Phase 1 dose escalation portion of AUGMENT-101 was recently separated into two cohorts based on concomitant treatment with a strong CYP3A4 inhibitor. Arm A will enroll patients not receiving a strong CYP3A4 inhibitor, while Arm B will enroll patients receiving a strong CYP3A4 inhibitor. The Phase 1 dose escalation portion of AUGMENT-101 is currently enrolling adults with R/R acute leukemias including MLL-r and nucleophosmin (NPM1) mutant acute leukemias and is expected to establish a recommended Phase 2 dose for both cohorts by the fourth quarter of 2020. The Phase 2 portion will evaluate efficacy, as defined by CR rate (per International Working Group response criteria), across three expansion cohorts: MLL-r acute lymphoblastic leukemia (ALL), MLL-r AML and NPM1 mutant AML. MLL rearrangements are seen in 5-10% of AML and ALL, while NPM1 mutations are seen in 30% of adult AML cases. The Company expects to present additional results from AUGMENT-101 at a medical conference in the fourth quarter of 2020.

Additional AACR Presentations

In addition to the SNDX-5613 presentation, data from the Phase 1 trials of the Company's anti-CSF-1R monoclonal antibody, axatilimab, both as a monotherapy and in combination with IMFINZI® (durvalumab) in patients with locally-advanced or metastatic solid tumors, were summarized in two oral presentations. These data indicate that axatilimab is tolerated well in solid tumor patients, generated a recommended Phase 2 dose for axatilimab for the treatment of patients with solid tumors, and provided evidence of its ability to deplete circulating pro-inflammatory monocytes.