Sellas Life Sciences announces data from preclinical studies of SLS009

SELLAS Life Sciences (SLS) 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, 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 with high level microsatellite instability and non-small cell lung cancer; 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 exposing them to SLS009 at various concentrations and determining the inhibitory concentration for each cell line. All cell lines were analyzed for presence of ASXL1 mutations and other genetic markers. High efficacy was prespecified as IC50 less than 100 nM, significantly lower than the standard threshold definition for an effective compound. 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. Positive controls involved cell lines treated with staurosporine at different concentrations. The results were as follows: In CRC MSI-H, ASXL1 mutations were observed in 7/12 of PDCs, aligning with predicted frequency of ~55%. In NSCLC, ASXL1 mutations occurred in 2/6 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 was observed in 6/9 solid cancer cell lines and in non-ASXL1 mutated cancer high SLS009 efficacy was observed in 0/9 of studied solid cancer cell lines. In CRC MSI-H, high efficacy was observed in 4/7 of ASXL1 mutated cell lines and in 0/5 of non-ASXL1 mutated cell lines. In NSCLC, high efficacy was observed in 2/2 of ASXL1 mutated cell lines and in 0/4 of non-ASXL1 mutated cell lines. No activity was observed in any of the studied cell lines with revumenib at any concentration. Staurosporine activity was confirmed, but interestingly and importantly, SLS009 outperformed positive control staurosporine in 5/9 cell lines.