Syndax Pharmaceuticals Announces Two Publications in Nature of Data from the Phase 1 Portion of AUGMENT-101 in Acute Leukemia Patients

Syndax Pharmaceuticals, today announced that data from the Phase 1 portion of the ongoing Phase 1/2 AUGMENT-101 trial of revumenib in patients with nucleophosmin mutant (mNPM1) and KMT2A-rearranged (KMT2Ar) relapsed/refractory (R/R) acute leukemia and an analysis describing MEN1 mutations observed in the study have been published in the journal Nature. Revumenib is the Company’s highly selective, oral menin inhibitor.

The Phase 1 publication entitled “The menin inhibitor revumenib in KMT2A-rearranged or NPM1-mutant leukaemia” includes positive data from 68 patients with R/R acute leukemia evaluable for safety, 60 patients of whom had mNPM1 or KMT2Ar acute leukemia and were evaluable for efficacy. In these heavily pretreated patients with a median of four prior therapies, 30% (18/60) experienced a CR/CRh with a median duration of CR/CRh response of 9.1 months. Revumenib was well-tolerated, and there were no discontinuations due to treatment-related adverse events. The Phase 1 data were recently featured in two oral presentations at the 64th American Society of Hematology Annual Meeting.

“We are excited to have our Phase 1 AUGMENT-101 data published in such a prominent peer-reviewed journal. As we continue to deepen our understanding of the tumor biology driven by the menin-KMT2A interaction, we gain more evidence to support the potential of revumenib as a best-in-class treatment for both mNPM1 and KMT2Ar acute leukemias,” said Michael A. Metzger, Chief Executive Officer. “With the expectation of topline data from the pivotal AUGMENT-101 trial beginning in the third quarter of 2023, followed by a potential New Drug Application filing by the end of 2023, revumenib could become the first menin inhibitor approved for patient use.”

A separate companion article published in Nature entitled “MEN1 mutations mediate clinical resistance to menin inhibition” describes somatic mutations in MEN1 that confer resistance to menin inhibitor treatment and further confirm the dependency of mNPM1 and KMT2Ar acute leukemias on the menin-KMT2A interaction. This represents the first report that menin inhibitors exert sufficient selective pressure to drive evolution of escape mutants that confer resistance to all first generation menin inhibitors and impact both mNPM1 and KMT2Ar acute leukemia. These data were highlighted in an oral presentation at the 64th American Society of Hematology Annual Meeting.

“The robust clinical dataset from a heavily pretreated relapsed/refractory patient population demonstrates that revumenib monotherapy was associated with encouraging clinical benefit, including deep molecular remissions and durable responses, with minimal toxicities,” said Ghayas C. Issa, M.D., Assistant Professor, Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center and a corresponding author of the Phase 1 publication. “The identified resistance, a class effect among first-generation menin inhibitors, further validates the menin-KMT2A interaction as the key driver for both mNPM1 and KMT2Ar leukemias. Future and ongoing trials may indicate whether treating patients in earlier settings and in combination would provide higher response rates in mNPM1 or KMT2Ar acute leukemia patients who are less likely to have developed functional mutations.”