Ryvu Therapeutics announced that new data demonstrating clinical and preclinical activity of its selective CDK8/19 inhibitor RVU120 and its selective PIM/FLT3 inhibitor SEL24 (MEN1703) will be presented at the 64thAmerican Society of Hematology (ASH) Annual Meeting & Exposition, which is being held on December 10 –13, 2022, in New Orleans, Louisiana. Updated Phase 1b efficacy and safety data will be presented for RVU120 at doses between 75 and 110 mg in patients with relapsed/refractory (R/R) acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome (HR-MDS). As of the cut-off date of July 25, 2022, 17 patients have been treated with RVU120.

One patient achieved a complete response and 10 patients achieved disease stabilization. RVU120 demonstrated a manageable safety profile. Additionally, the on-target activity of RVU120 was evaluated in AML and HR-MDS patient samples by measuring changes in pSTAT5 levels.

As of the cut-off date, the inhibition of pSTAT5 reached >50%, a threshold that based on preclinical predictions is sufficient for robust efficacy in certain groups of super-responder patients. Ryvu licensee, Menarini Group, and academic collaborators will present data on SEL24 (MEN1703), a first-in-class, oral, dual type I PIM/FLT3 inhibitor. Combination therapy of SEL24 (MEN1703) with gilteritinib, a highly potent and selective oral FLT3 inhibitor, induces strong tumor regression and complete responses in-vivo, demonstrating the potential of concomitant FLT3 and PIM inhibition kinases in AML.

SEL24 (MEN1703)-induced PIM inhibition and mechanism of action will also be demonstrated in-vitro in multiple myeloma (MM), classical Hodgkin lymphoma-tumor-associated macrophages (cHL-TAMs), and diffuse large B-cell lymphoma (DLBCL) models. In multiple myeloma preclinical models, SEL24 (MEN1703) induces cytotoxicity of MM cell lines, disrupts MM endothelial cell vessel formation, and decreases the activity of several pathways essential for myeloma cell survival. This study demonstrates the promising therapeutic potential of SEL24 (MEN1703) in MM and reveals the underlying mechanism of PIM inhibition.