SELLAS Reports 100% Response in Phase 2 Trial of SLS009 for r/r AML with ASXL1 Mutation

SELLAS Life Sciences Group, Inc. (NASDAQ: SLS) has announced preliminary data from its Phase 2a trial of SLS009, a selective CDK9 inhibitor, for relapsed/refractory acute myeloid leukemia (r/r AML). The company has also successfully filed a provisional patent application concerning the ASXL1 mutation and SLS009. ASXL1 mutations are commonly associated with poor prognosis in myeloid diseases due to their reduced response to existing treatments.

The trial has shown a high response rate in patients with myelodysplasia-related molecular mutations, as classified by the World Health Organization (WHO). Among these, ASXL1 gene mutations have demonstrated the highest response rates across all dose cohorts. Currently, the ongoing Phase 2 r/r AML study has been expanded to include two additional patient cohorts: one comprising ASXL1 mutated AML patients and another with myelodysplasia-related molecular abnormalities other than ASXL1.

“These early clinical results are very promising and could open up a new avenue in the treatment of AML and potentially beyond,” said Joshua Zeidner, MD, Associate Professor of Medicine and Chief of Leukemia Research at the University of North Carolina Lineberger Comprehensive Cancer Center.

The study highlights significant results up to the April 19, 2024 data cut-off:
- A 57% overall response rate has been achieved with the selected 30 mg BIW dose regimen, surpassing the target of 20%.
- All four r/r AML patients with ASXL1 truncating mutations at the selected dose level achieved an overall response and are alive.
- Across all dose levels, 63% of r/r AML patients with ASXL1 truncating mutations treated with SLS009 achieved an overall response.
- A Phase 1 trial patient with SLS009 monotherapy who had a complete response lasting over 8 months also harbored an ASXL1 mutation.

All patients in the trial were diagnosed with AML that was refractory to or had relapsed after treatments involving venetoclax. The focus will now be on those receiving the 30 mg BIW dose and diagnosed with the ASXL1 mutation.

The strong responses in patients with ASXL1 mutations indicate the transformative potential of SLS009 in addressing unmet medical needs in AML, as well as potentially targeting colorectal and other tumors with this alteration. The enthusiastic participation from clinical sites underscores the promising nature of the study.

SELLAS intends to initiate discussions with the U.S. Food and Drug Administration (FDA) about the potential for an accelerated approval pathway for SLS009 in the ASXL1 molecularly defined r/r AML population and in other indications harboring this mutation.

The Phase 2a clinical trial of SLS009 is an open-label, single-arm, multi-center study designed to evaluate the safety, tolerability, and efficacy of SLS009 in combination with aza/ven at two dose levels, 45 and 60 mg. Patients in the 60 mg dose cohort were randomized to receive either a 60 mg dose once per week or a 30 mg dose twice per week. The target response rate at the optimal dose level is 20%, with a target median survival of over 3 months. Additionally, the study aims to identify biomarkers for the target patient population to enrich further trials.

ASXL1 mutations carry a poor prognosis in all myeloid diseases due to a reduced response to current treatments. In AML, ASXL1 mutations are associated with a lower complete response rate and worse survival outcomes. In myelodysplastic syndromes (MDS), ASXL1 mutations independently predict worse overall survival and higher rates of AML transformation.

SELLAS Life Sciences Group, Inc. is a late-stage clinical biopharmaceutical company developing novel therapeutics for various cancer indications. Its lead product candidate, GPS, is licensed from Memorial Sloan Kettering Cancer Center and targets the WT1 protein present in multiple tumor types. GPS has potential as both monotherapy and in combination with other treatments for a range of hematologic malignancies and solid tumors. Additionally, SELLAS is developing SLS009 (formerly GFH009), a highly selective CDK9 inhibitor licensed from GenFleet Therapeutics (Shanghai) for global use outside Greater China.