SELLAS Announces Positive Data from Preclinical Studies Indicating ASXL1 Mutations as Predictor of Response to SLS009 in Solid Cancers

- Preselection Method for Cancers Responding to SLS009: High Efficacy of SLS009 Observed in 67% of ASXL1 Mutated Solid Cancers vs 0% in Non-ASXL1 Mutated Cancers –

- ASXL1 Mutations Predictably Identified in Colorectal Cancer (CRC MSI-H) and Non-Small Cell Lung Cancer (NSCLC) in Addition to Hematologic Malignancies -

- Existing Clinical Data Demonstrating SLS009 Efficacy in ASXL1 mutated AML and Safety Across Multiple Cancer Types Lay Foundation for Targeted SLS009 Clinical Trial in Selected Solid Cancers -

NEW YORK, Nov. 27, 2024 (GLOBE NEWSWIRE) -- SELLAS Life Sciences Group, Inc. (NASDAQ: SLS) (“SELLAS’’ or the “Company”), a late-stage clinical biopharmaceutical company focused on the development of novel therapies for a broad range of cancer indications, today announced data from preclinical studies identifying ASXL1 mutation as key predictor of SLS009, a highly selective CDK9 inhibitor, response in solid cancers.

Based on elucidated biology of ASXL1 mutations, results from SELLAS’ clinical trials in acute myeloid leukemia (AML), and reports of common occurrence of ASXL1 mutations in some solid cancers, the Company performed experiments and analyses to explore the following:

• The frequency of ASXL1 mutations in certain solid cancers, including colorectal carcinomas (CRC) with high level microsatellite instability (MSI-H) and non-small cell lung cancer (NSCLC)
• Whether ASXL1 mutations in solid cancers may predict as high SLS009 efficacy as the efficacy exhibited in AML where ASXL1 and similar mutations demonstrated high response rates in SELLAS’ clinical trials

SELLAS performed experiments in patient derived cell lines (PDCs) exposing them to SLS009 at various concentrations and determining the inhibitory concentration (IC50) for each cell line. All cell lines were analyzed for presence of ASXL1 mutations and other genetic markers. High efficacy was prespecified as IC50 < 100 nM, significantly lower than the standard threshold definition for an effective compound (IC50 < 1,000 nM). This threshold was chosen based on the observed long-lasting concentrations of SLS009 observed in patients, which were ~400 nM.

Negative controls consisted of untreated cell lines, while active negative control varying concentrations of revumenib (drug used in hematologic malignancies). Positive controls involved cell lines treated with staurosporine at different concentrations (staurosporine is a standard control compound for kinase inhibitors due to its high broad-spectrum potency in inhibiting most protein kinases at sub-micromolar concentrations).

The results were as follows:

• In CRC MSI-H, ASXL1 mutations were observed in 7/12 (58%) of PDCs, aligning with predicted frequency of ~55%
• In NSCLC, ASXL1 mutations occurred in 2/6 (33%) studied cell lines, higher than predicted 2.6%
• Overall, in 18 studied solid cancer cell lines, ASXL1 mutations were recorded in 9 cell lines and no ASXL1 mutations were recorded in 9 cell lines which were designated as control
• In ASXL1 mutated cell lines, high SLS009 efficacy (IC50