Krakow, Poland – February 14, 2024 – Ryvu Therapeutics (WSE: RVU), a clinical-stage drug discovery and development company focusing on novel small molecule therapies that address emerging targets in oncology, announced today 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.
• The study is part of RVU120’s Development Plan presented in October 2023 and aligns with the company’s cash runway to Q1 2026.
• In H1 2024, Ryvu plans to launch four Phase II RVU120 clinical studies in r/r AML, HR-MDS, LR-MDS and myelofibrosis, and plans to enroll over 100 patients by the end of the year. Ryvu aims to prioritize further development options in Q1 2025 based on the study outcomes. Clinical trials conducted in various hematological indications and treatment regimens (monotherapy and combination therapy) will contribute to the global RVU120 safety database, supporting potential future regulatory approvals.

 

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.

Hendrik Nogai, M.D., Chief Medical Officer of Ryvu Therapeutics, said:

– We are pleased to announce the initiation of another RVU120 Phase II study, in line with the development plans presented last year. Based on the demonstrated safety profile and observed signs of activity from the Phase Ib study in patients with r/r AML or HR-MDS, we continue to be at the forefront of developing first-in-class CDK8/19 inhibitors. This marks a significant step towards our goal of effectively treating various hematological diseases and providing therapeutic options for patients with unmet medical needs.

Kamil Sitarz, Ph.D., Chief Operating Officer of Ryvu Therapeutics, said:

– With up to 80 clinical sites planned worldwide and a global operational focus, we aim to maximize efficient patient enrollment and ensure the timely execution of the RIVER-52 study, moving RVU120 towards a potential accelerated regulatory approval pathway.

 

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 H1 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).