ASH 2024 | SLS009, a CDK9 inhibitor, with azacitidine and venetoclax for R/R AML after prior venetoclax therapy

SLS009 is an investigational CDK9 inhibitor and we’ve been very interested in this compound, especially in patients who have progressed on venetoclax. Venetoclax is a BCL2 inhibitor as we all know and one of the main mechanisms of resistance to a venetoclax-based strategy is the upregulation of MCL1 which can lead to resistance and low activity of venetoclax. So we’ve been developing a study where we add SLS as a CDK9 inhibitor to azacitidine and venetoclax in patients who have had previous treatment with venetoclax with the intention that the addition of the SLS agent might mitigate the resistance seen and lead to clinical activity in these patients. 

So this was initially a Phase I dose escalation and an expansion where we’re studying three different dose levels and we wound up escalating to 30 milligrams twice a week IV of this SLS CDK9 inhibitor compound that’s in combination with azacitidine and venetoclax in a relapsed/refractory patient population. We reported results in a poster presentation of 30 patients treated with this combination and at that 30 milligram twice weekly dose level which is now our kind of recommended Phase II dose, we’ve seen 50% response rates, particularly high responses in a cohort of patients with AML with myelodysplasia-related changes. And in particular, those with an ASXL1 mutation seem to have a predilection for response, 56% overall response in ASXL1 mutation. So this is really exciting for us, expanding the study to only assess patients with AML myelodysplasia-related and this is an agent that we’re excited about for further development specifically in that kind of post-venetoclax treated patient population.

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