Ryvu Announces Dosing of the First Patient in the RIVER-81 Phase II Study of RVU120 in Combination with Venetoclax for the Treatment of Patients with Relapsed/Refractory AML

Krakow, Poland – January 31, 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 drugs in a Phase II clinical trial investigating RVU120 in combination with venetoclax for the treatment of patients with relapsed/refractory acute myeloid leukemia (r/r AML) – the RIVER-81 study (NCT06191263).

  • The primary goal of the RIVER-81 study will be to evaluate safety and efficacy of RVU120 in combination with venetoclax in r/r AML patients who have failed prior venetoclax treatment.
  • The RIVER-81 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 50 clinical sites globally. The planned overall enrollment for the study is up to approx. 98 patients.
  • The study is part of the RVU120 Development Plan presented in October 2023 and aligns with the company’s cash runway to Q1 2026. Execution of the RIVER-81 study is supported with a PLN 62.3 mln grant from the Polish Medical Research Agency (ABM).
  • In H1 2024, Ryvu plans to launch four Phase II RVU120 clinical studies and enroll over 100 patients across the studies 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, which would support potential future regulatory approvals.

RVU120 is a selective, first-in-class dual CDK8/19 kinase inhibitor developed by Ryvu Therapeutics. RVU120 monotherapy has demonstrated positive 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, multiple clinically significant blast reductions, hematologic improvements, and reduction of bone marrow fibrosis.

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

  • Considering the encouraging results from the Phase Ib study of RVU120 as monotherapy for patients with r/r AML and HR-MDS, along with compelling translational evidence of synergistic activity with venetoclax, we have launched the Phase II RIVER-81 study with optimism. AML patients who fail the current standard of care, consisting of venetoclax and a hypomethylating agent, have very few alternative treatment options and a poor prognosis. We are delighted to commence the new Phase II RVU120 study in Poland and Italy, with plans to expand to up to 50 clinical sites Our goal is to bring meaningful clinical benefits to AML patients.

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

  • We have successfully confirmed the safety profile of RVU120, and our focus is now on substantiating its efficacy signals. With the activation of dozens of clinical sites globally, we aim to dose over 100 patients across four RVU120 Phase II studies by the end of 2024. Subsequently, and based on treatment outcomes, we will strategically prioritize further development paths. This progress aligns with the RVU120 development plan unveiled in October 2023, supported by secured financing until Q1 2026.

RIVER-81 is a multicenter, open-label clinical trial that aims to assess the safety, tolerability, efficacy, pharmacokinetics (PK), and pharmacodynamics (PD) of RVU120 when administered in combination with venetoclax to adult patients with AML who are relapsed or refractory to prior therapy with venetoclax and a hypomethylating agent.

The study is divided into two parts. Part 1 aims to identify safe and tolerated doses of RVU120 and venetoclax when used in combination, through dose escalation of both study drugs. In Part 2, the selected doses will be evaluated for both safety and efficacy in a larger group of patients.

The study has received approval from the Competent Authorities in Poland and Italy following a clinical trial application in accordance with 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-81 marks the commencement of the first of four planned RVU120 Phase II clinical studies, scheduled to launch in H1 2024. Following RIVER-81, Ryvu intends to initiate the RIVER-52 study (evaluating RVU120 as a monotherapy in patients with genetically defined subtypes of AML and in patients with HR-MDS). 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).