Ryvu Therapeutics announced that the first patient has been dosed with the study drug in a Phase II clinical trial investigating RVU120 as a monotherapy for the treatment of patients with relapsed/refractory acute myeloid leukemia (r/r AML) and high-risk myelodysplastic syndromes (HR-MDS) ? the RIVER-52 study. The primary goal of the RIVER-52 study will be to evaluate safety and efficacy of RVU120 in a larger population of patients with genetically defined subtypes of AML, including NPM1 mutations, as well as with HR-MDS.

The evaluation will be conducted at the dose level of 250 mg EOD (Every Other Day), identified in the Phase Ib clinical study, where numerous signs of clinical activity have been observed. The RIVER-52 study is initially launching at clinical sites in Poland and Italy. Ultimately, the study will expand to other EU and non-EU countries, covering up to 80 clinical sites globally.

The planned overall enrollment is up to approx. 140 patients. RVU120 is a selective, first-in-class dual CDK8/19 kinase inhibitor developed by Ryvu Therapeutics.

RVU120 monotherapy has demonstrated clinical activity in a Phase Ib study, where 50% of evaluable patients with r/r AML or HR-MDS achieved clinical benefit, including a complete response, a morphologic leukemia-free state, transition to a bone-marrow transplant, two-year disease stabilization, multiple clinically significant blast reductions, hematologic improvements, and reduction of bone marrow fibrosis. RIVER-52 is a multicenter, open-label clinical trial designed to evaluate RVU120 in adult patients with r/r AML and HR-MDS, without alternative therapies. The study aims to assess the safety, tolerability, anti-tumor activity (efficacy), pharmacokinetics (PK), and pharmacodynamics (PD) of RVU120 as a monotherapy in the above-mentioned patient populations.

The study is divided into two parts. Part 1 aims to assess the level of anti-tumor activity in patients with genetically defined subtypes of AML, including NPM1 mutations, and in patients with HR-MDS. Based on the outcomes of Part 1, Part 2 will further evaluate the safety, tolerability, and anti-tumor activity in a larger group of patients within the subtypes that exhibit the highest sensitivity to RVU120.

The study has received approval from the Competent Authorities in Poland and Italy following a clinical trial application under the European Union Clinical Trial Regulation (EU-CTR) 536/2014, as well as positive opinions from the respective Ethics Committees, enabling patient enrollment in both countries. Start-up activities in other EU and non-EU countries are currently in progress. RIVER-52 represents the second of the four planned RVU120 Phase II clinical studies scheduled for launch in first half 2024.

In addition to RIVER-52, Ryvu has already started patient treatment in the RIVER-81 study (evaluating RVU120 in combination with venetoclax for treating r/r AML patients). Upcoming plans also include the initiation of the REMARK study (conducted as an investigator-initiated trial, exploring RVU120 as a monotherapy for the treatment of patients with low-risk myelodysplastic syndromes; LR-MDS) and the POTAMI-61 study (evaluating both monotherapy and combination therapy for the treatment of patients with myelofibrosis; MF).