Ryvu Begins POTAMI-61 Phase II Study of RVU120 for Myelofibrosis

Ryvu Therapeutics has commenced the POTAMI-61 study, a Phase II clinical trial to assess the safety and effectiveness of RVU120 in treating myelofibrosis (MF) either as a monotherapy or in combination with ruxolitinib (RUX). This trial follows promising preclinical data and results from the RIVER-51 Phase I study involving patients with acute myeloid leukemia (AML).

Hendrik Nogai, M.D., the Chief Medical Officer of Ryvu Therapeutics, expressed enthusiasm about the launch of POTAMI-61, which marks the fourth Phase II study in the development plan for RVU120 presented last year. Based on RVU120's observed effect on bone marrow and hematopoietic cells, and the translational data generated in collaboration with Prof. Raajit Rampal from Memorial Sloan Kettering Cancer Center, there is significant support for RVU120's use in MF treatment. The safety profile of RVU120 may allow it to address unmet medical needs, especially for patients unresponsive to or ineligible for JAK inhibitor treatments. Additionally, translational studies suggest potential efficacy in frontline treatment settings.

The POTAMI-61 study is an open-label, multicenter Phase II trial investigating RVU120, a novel cyclin-dependent kinase (CDK) 8/19 inhibitor, in patients with MF. The study will evaluate RVU120 as a single agent in patients previously treated with or ineligible for JAK inhibitors like ruxolitinib, and in combination with RUX for patients with a suboptimal response to JAK inhibitors. The primary endpoints include spleen volume reduction, total symptom score improvement, and a reduction in bone marrow fibrosis.

The initiation of this study is grounded in RVU120's clinical safety and efficacy data, with strong preclinical and mechanistic justifications. In vivo studies have shown that CDK8 inhibition can alleviate symptoms such as splenomegaly, hepatomegaly, anemia, and thrombopenia, with notable disease modification indicated by reduced mutated allele burden. RVU120 holds potential as a new therapeutic strategy for myeloproliferative neoplasms, including MF.

Patients in the POTAMI-61 study will receive RVU120 until disease progression or withdrawal of consent. The study has two parts: Part A will involve approximately 20 patients in two cohorts – one receiving RVU120 alone and the other in combination with RUX. Based on Part A's outcomes, Part B may expand the cohorts to further assess safety, tolerability, and anti-tumor activity in a larger group, potentially including up to 230 patients. Additionally, RVU120 could be explored as a frontline treatment in cohort 3.

Initially, Part A will enroll patients in Poland and Italy. Should Part B proceed, the study will expand to include approximately 50 clinical sites globally. POTAMI-61 is the fourth Phase II study for RVU120 initiated in 2024. Ryvu is also conducting studies in patients with AML or high-risk myelodysplastic syndromes (HR-MDS) under the RIVER-52 and RIVER-81 studies, and in lower-risk myelodysplastic syndromes (LR-MDS) in the REMARK study.

POTAMI-61 aligns with the RVU120 Development Plan announced in October 2023 and is supported by Ryvu's financial resources. The clinical trials in various hematological conditions and treatment regimens will enrich the global RVU120 safety database, aiding potential future regulatory approvals.

Ryvu Therapeutics is a clinical-stage company dedicated to developing small-molecule therapies targeting new oncology mechanisms. Their leading program, RVU120, is a selective CDK8/CDK19 inhibitor aimed at treating hematological malignancies and solid tumors. Ryvu has ongoing collaborations with organizations such as BioNTech and Exelixis and is listed on the Warsaw Stock Exchange.