• The primary goal of the study is to evaluate the safety and efficacy of RVU120 in patients with myelofibrosis (MF), both as a single agent and in combination with ruxolitinib (RUX). 

• The study was launched based on RVU120’s activity in the RIVER-51 Phase I study in patients with acute myeloid leukemia (AML) and translational data generated in MF. 

Krakow, Poland – December 5, 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 had been dosed in the POTAMI-61 study, a Phase II clinical trial investigating RVU120 in the treatment of patients with myelofibrosis (MF). 

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

We are excited to announce the initiation of the RVU120 Phase II study, POTAMI-61, the fourth Phase II clinical trial included in the RVU120 development plan that Ryvu presented last year. Based on RVU120’s effect on bone marrow and hematopoietic cells observed in the RIVER-51 study and translational data generated in myelofibrosis with Prof. Raajit Rampal from Memorial Sloan Kettering Cancer Center in New York, we believe there is a strong rationale for RVU120 in the treatment of patients with myelofibrosis, both as a monotherapy and in combination with JAK inhibitors. The favorable RVU120 safety profile may enable targeting patients with unmet medical needs, e.g., patients who are not eligible for or who show a suboptimal response to JAK inhibitor treatment. Additionally, synergy in translational studies indicates potential for use in the frontline setting. 

The POTAMI-61 study is an open-label, multicenter Phase II study of RVU120, a novel small-molecule cyclin-dependent kinase (CDK) 8/19 inhibitor, to treat patients with MF. In the POTAMI-61 study, RVU120 is being explored as a single agent for the treatment of patients with primary or secondary MF previously treated with or ineligible for a JAK inhibitor, e.g. ruxolitynib, or in combination with RUX for patients with suboptimal response to JAK inhibitors. Key endpoints will be spleen volume reduction (SVR), total symptom score (TSS) improvement, and bone marrow fibrosis reduction. 

The study is being initiated based on RVU120’s clinical safety and efficacy data, and strong preclinical and mechanistic rationale. In vivo data demonstrate the beneficial effects of CDK8 inhibition on the improvement of symptoms, i.e., splenomegaly, hepatomegaly, anemia, and thrombopenia. Importantly, disease modification properties of RVU120 were shown by the reduction of mutated allele burden. RVU120 has the potential to become a novel therapeutic strategy in myeloproliferative neoplasms, including MF.  

In the POTAMI-61 study, patients will receive RVU120 until disease progression, withdrawal of consent or other reasons specified in the study protocol. The POTAMI-61 study consists of two parts. Part A of the study with a planned enrollment of approximately 20 patients will comprise two cohorts: 1) single-agent therapy with RVU120 in patients resistant or refractory to prior JAK inhibitor treatment or ineligible for JAK inhibitor treatment, and 2) RVU120 in combination with RUX in patients who experience a suboptimal response to prior JAK inhibitor treatment. Depending on results from Part A, cohorts 1 and/or 2 could be expanded in Part B which will further assess safety, tolerability, and antitumor activity in a larger cohort, totaling up to approximately 230 patients for both Part A and Part B combined. RVU120 could also be investigated in a frontline setting in cohort 3. Ryvu will initially proceed with the execution of Part A of the study, while the decision on the potential initiation of Part B will be based on the outcomes of Part A. 

Initially, Part A of the study will enroll patients at clinical sites in Poland and Italy. If the Ryvu Management Board decides to initiate Part B, the study will expand to include additional sites both in the EU and non-EU countries, totaling approximately 50 clinical sites worldwide. 

POTAMI-61 represents the fourth planned RVU120 Phase II clinical study launched in 2024. Ryvu is already treating patients with acute myeloid leukemia (AML) or high-risk myelodysplastic syndromes (HR-MDS) in the RIVER-52 and RIVER-81 studies, as a single agent or in combination with venetoclax. RVU120 is also being investigated in the REMARK study for the treatment of patients with lower-risk myelodysplastic syndromes (LR-MDS). 

POTAMI-61 is part of RVU120’s Development Plan presented in October 2023 and aligns with the company’s cash runway. 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.