Ryvu Therapeutics has provided an update on its RVU120 Phase II program, a first-in-class dual CDK8/19 inhibitor being developed for hematologic malignancies. The company has successfully launched all four planned Phase II clinical studies for 2024, with efficacy readouts expected in the first half of 2025.
Clinical Trial Progress
As of December 11, 2024, Ryvu has activated 106 clinical sites across Poland, Italy, Spain, France, Germany, and Canada. Enrollment is progressing rapidly, with 78 patients enrolled as of December 11, 2024, and nearly 100 patients expected to be dosed by the end of the year. The pace of recruitment has increased significantly since September 2024, with nearly three times as many patients expected to be treated in Q4 2024 alone compared to the combined total from Q1 to Q3.
"2024 has been transformative for RVU120 development plan in hematologic malignancies, marked by activating over 100 clinical sites across Europe and North America," said Paweł Przewięźlikowski, co-founder and Chief Executive Officer of Ryvu Therapeutics. "As we enter 2025, we are poised to carry strong enrollment momentum and the ambition to generate informative efficacy readouts in the coming months."
RVU120 Clinical Studies
RIVER-81: This Phase II study evaluates RVU120 in combination with venetoclax in patients with relapsed/refractory AML who have failed a previous venetoclax/HMA-based regimen (NCT06191263). Part 1 of the study (combination dose escalation) has been completed, and Part 2 is currently enrolling at the full doses of RVU120 (250 mg) and venetoclax (400 mg). Within eight patients treated with RVU120 at 250 mg (RP2D) that had at least one evaluable post-baseline assessment, one patient achieved a complete remission (CR), and another patient achieved a significant blast reduction.
RIVER-52: This Phase II study investigates RVU120 as a monotherapy in patients with r/r AML and high-risk myelodysplastic syndromes (HR-MDS) (NCT06268574). One of two evaluable patients in cohort 2 (NPM1 mutation) achieved a 50% blast reduction, while disease stabilizations and reduction of peripheral blasts were observed in patients in cohort 3 (DNMT3A mutation).
POTAMI-61: This Phase II study explores RVU120 as a single agent and in combination with ruxolitinib for the treatment of patients with myelofibrosis (MF) (NCT06397313). The first patient in the study was dosed on December 4, 2024, and five more patients were undergoing screening as of December 11, 2024. Initial efficacy data is expected in Q2 2025, based on a 12-week patient observation period.
REMARK: This Phase II study evaluates RVU120 as a single agent for the treatment of patients with lower-risk myelodysplastic syndromes (LR-MDS) (NCT06243458). The first patient in the study was dosed on September 19, 2024, and as of December 11, 2024, 18 patients were treated. Initial efficacy data is expected in Q2 2025, based on a 16-week observation period.
Safety and Efficacy
RVU120 has demonstrated a favorable safety profile compared to other drugs used to treat acute myeloid leukemia (AML). "The growing body of evidence confirms that RVU120 appears to have a favorable safety profile compared to other drugs used for treating similar hematologic malignancies, both in monotherapy and in combination with venetoclax," said Hendrik Nogai, M.D., Chief Medical Officer of Ryvu Therapeutics. Early efficacy signals have been observed in the RIVER-52 and RIVER-81 studies, with further data expected in H1 2025.
About RVU120
RVU120 is a selective, first-in-class dual CDK8/19 kinase inhibitor developed by Ryvu Therapeutics. It has shown clinical activity in a Phase Ib (RIVER-51) study, with 50% of evaluable patients with r/r AML or HR-MDS achieving clinical benefit. RVU120 achieved target engagement of 50-70% at a dose of 250 mg, which was selected as a recommended Phase II dose (RP2D).
