Ryvu Therapeutics announced the online publication of two posters and an oral presentation demonstrating clinical and pre-clinical activity of its selective CDK8/19 inhibitor RVU120 and the dual PIM/FLT3 inhibitor SEL24, in-licensed by Menarini Group from Ryvu Therapeutics, at the Annual European Hematology Association 2021 Virtual Congress. RVU120 is a highly selective first-in-class CDK8/CDK19 inhibitor, which has demonstrated efficacy in a number of solid tumor types in vitro and in vivo models as well as in onco-hematological malignancies. The first-in-human Phase I study with RVU120, in relapsed or refractory acute myeloid leukemia or high-risk myelodysplastic syndromes, is being conducted at 5 investigational sites in the US. The data presented at EHA 2021 covers the first four dose cohorts, in which RVU120 demonstrated favorable safety and PK profile. No DLTs were observed, and all of the reported SAEs were assessed as unlikely or not related to study drug. Results are reported on the first five patients to receive treatment with RVU120, and the clinically relevant responses were observed in patients in the two higher dose cohorts reported: The Cohort 3 patient, with HRMDS, demonstrated an erythroid response from Cycle 5 to Cycle 8 and continues on RVU120 treatment in Cycle 13 with stable disease. An erythroid response reflects a reduction in red blood cell transfusions vs. baseline. The Cohort 4 patient, with relapsed/refractory AML, showed a response from C2 with persistence of skin leukemia, which completely resolved at C7 resulting in a CR. This patient was previously refractory to venetoclax + HMA, which is a patient population associated with poor prognosis. Furthermore, translational data will be presented as part of an Oral Session and provide a potential linkage between in vitro data showing erythroid differentiation and erythroid response in the clinic. In vitro data demonstrate that RVU120 can induce erythroid cells to differentiate and therefore rescue anemia in preclinical models. Presented results indicate strong erythroid differentiation potential of RVU120 in CD34+, that acquired genetic abnormalities resulting in arrested erythroid commitment, a characteristic of many MDS and AML subtypes. Detailed transcriptomic profiling strongly associated differentiation with enrichment of genes representing regulators of erythroid commitment and hemoglobin metabolism. Further studies are warranted to investigate efficacy of RVU120 in anemias associated with bone marrow failures in AML and MDS patients. A clinical poster on the first-in-human study of SEL24/MEN1703, the DIAMOND-01 trial conducted by Ryvu's partner Menarini Group, reports four objective responses across the dose escalation and cohort expansion in patients with AML, with 3 of those 4 responders harboring an IDH mutation. Notably, three out of five patients with IDH mutations treated at doses of 75-125 mg achieved a CR/CRi, including a patient that relapsed on the IDH-inhibitor enasidenib. Furthermore, one patient with an IDH1 mutation achieved a CRi and underwent allogeneic-HSCT. At the recommended dose of 125mg/day as selected in the dose escalation phase, SEL24/MEN1703 showed a manageable safety profile. Most Grade 3 or higher treatment-emergent adverse events were hematologic or infectious in nature.