Ryvu Therapeutics has initiated the Phase II trial, POTAMI-61, dosing the first subject with a small-molecule cyclin-dependent kinase (CDK) 8/19 inhibitor, RVU120, for treating myelofibrosis (MF).

This open label, multicentre study will assess the efficacy and safety of the therapy as a single agent and along with ruxolitinib (RUX) in subjects with primary or secondary MF.

It is designed to evaluate key endpoints including bone marrow fibrosis reduction, spleen volume reduction (SVR), and improvement in total symptom score (TSS).

The decision to proceed with this study was influenced by RVU120's efficacy and safety data, as well as its potential disease-modifying properties demonstrated in preclinical studies.

Subjects enrolled in the trial will receive RVU120 until progression of the disease or other specified conditions. Part A of the trial will enrol approximately 20 subjects across two cohorts.

Based on Part A outcomes, these cohorts may be expanded in Part B, which aims to further assess the therapy’s anti-tumour activity, tolerability, and safety in up to nearly 230 subjects.

The first cohort will receive RVU120 as a single-agent therapy, while the second will be treated with a combination of RVU120 and RUX.

The study is the fourth planned Phase II clinical trial for the therapy this year, with trials for acute myeloid leukaemia (AML) and myelodysplastic syndromes (MDS) already underway.

Ryvu Therapeutics chief medical officer Hendrik Nogai 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.”

Earlier this year, the company dosed the first subject in the RIVER-81 Phase II trial for relapsed/refractory AML treatment with RVU120 and venetoclax.