#Poland #Ryvu Therapeutics #RVU120 #Myelofibrosis #Kraków

Ryvu Therapeutics Begins Dosing in POTAMI-61 Phase II Study

On December 5, 2024, Ryvu Therapeutics announced a significant milestone in their clinical research. The company revealed that the first patient has been dosed in the POTAMI-61 Phase II study, which evaluates the efficacy and safety of RVU120 in patients diagnosed with myelofibrosis (MF). This endeavor reflects Ryvu's commitment to advancing innovative treatments in the field of oncology.

The Aim of the POTAMI-61 Study

The primary objective of the POTAMI-61 study is to assess the safety and effectiveness of RVU120, both as a standalone treatment and in conjunction with ruxolitinib (RUX) for treating myelofibrosis. The groundwork for this study stemmed from promising results observed during the RIVER-51 Phase I trial, which involved patients suffering from acute myeloid leukemia (AML). In this earlier study, RVU120 demonstrated notable activity and provided valuable translational data pertaining to the myelofibrosis population.

Hendrik Nogai, M.D., Chief Medical Officer at Ryvu Therapeutics, expressed enthusiasm about launching the RVU120 Phase II trial. He highlighted that this is the fourth Phase II clinical study associated with RVU120, showcasing the company’s strategic focus on this therapeutic agent. Dr. Nogai elaborated that the clinical observations regarding RVU120's impact on bone marrow and hematopoietic cells from the RIVER-51 study, alongside the translational data accrued with experts such as Prof. Raajit Rampal from Memorial Sloan Kettering Cancer Center, support RVU120's potential in addressing unmet needs in myelofibrosis treatment.

Study Design and Key Endpoints

POTAMI-61 is an open-label, multicenter study focusing on RVU120, which acts as an inhibitor for cyclin-dependent kinases 8 and 19. Participants suffering from either primary or secondary myelofibrosis, who have previously received treatment with or are unsuitable for JAK inhibitors, will be enrolled. Moreover, the study explores RVU120 in combination with RUX for those demonstrating inadequate responses to prior treatments.

The key endpoints for the trial will encompass spleen volume reduction (SVR), improvement of total symptom score (TSS), and the reduction of bone marrow fibrosis. These measures are critical to gauge the overall benefits of RVU120 in enhancing patient outcomes.

Encouraging Preclinical Evidence

The decision to initiate the POTAMI-61 study was backed by robust preclinical data underscoring the drug's safety and efficacy profiles. Moreover, in vivo studies have signaled the potential of CDK8 inhibition in alleviating symptoms such as splenomegaly, hepatomegaly, anemia, and thrombocytopenia. Another pivotal aspect is RVU120's ability to reduce the mutated allele burden, which marks a significant step towards modifying the disease's trajectory.

Study Structure and Future Outlook

Patients in this trial will continue to receive RVU120 until disease progression or other withdrawal criteria are met. The study is bifurcated into two parts: Part A aims to enroll approximately 20 participants, which consists of two cohorts. The first cohort will explore RVU120 as a single-agent therapy for patients resistant or refractory to previous JAK inhibitor treatments, while the second cohort will focus on the combination therapy with RUX.

Following the results from Part A, there is potential for an extension into Part B, which could enroll up to 230 patients across various clinical sites in Poland, Italy, and potentially extend to additional European and non-European sites, pending positive results from Part A.

Broader Implications of RVU120 Development

The initiation of POTAMI-61 represents a critical addition to Ryvu Therapeutics' ambitious clinical program. RVU120 is currently undergoing evaluation in multiple hematological indications and could serve as a valuable treatment option. The cumulative data from these clinical trials will contribute to an expansive safety database, enhancing the prospects for future regulatory approvals.

As Ryvu Therapeutics continues its pioneering efforts, the advancement of RVU120 underscores the dynamic landscape of oncology and the importance of innovative therapies in addressing significant medical needs in the treatment of myelofibrosis and beyond.