Ryvu Therapeutics Starts Dosing in Phase II REMARK Study of RVU120 for LR-MDS Anemia

Ryvu Therapeutics has announced the commencement of the REMARK Phase II clinical trial focusing on RVU120, following the dosing of the first patient. The primary goal of the trial is to assess the safety and efficacy of RVU120 in patients with lower-risk myelodysplastic syndromes (LR-MDS). This trial is being conducted through the European Myelodysplastic Neoplasms Cooperative Group (EMSCO) network, with Prof. Uwe Platzbecker, a renowned expert in LR-MDS, serving as the Coordinating Principal Investigator.

The REMARK study has obtained necessary approvals from Competent Authorities and Ethics Committees in Germany, Spain, Poland, Italy, and France in accordance with the European Union Clinical Trial Regulation (EU-CTR). The study aims to enroll up to 40 patients across approximately 25 clinical sites worldwide.

Ryvu Therapeutics, a clinical-stage company specializing in novel small molecule therapies for oncology, announced the dosing milestone on September 19, 2024. The REMARK trial will investigate RVU120 as a monotherapy for patients with LR-MDS. The company aims to build on promising results from a previous Phase Ib study in acute myeloid leukemia (AML) and high-risk myelodysplastic syndromes (HR-MDS), where RVU120 demonstrated hematologic improvements in several patients, including cases of transfusion independence. The goal is to further validate the safety and effectiveness of RVU120 in LR-MDS patients, supported by strong preclinical data.

Dr. Hendrik Nogai, Chief Medical Officer of Ryvu Therapeutics, expressed optimism about the REMARK study, emphasizing its potential to advance treatments for hematological diseases and provide new therapeutic options for patients. He also acknowledged the significant support from the EMSCO network and Prof. Uwe Platzbecker.

The REMARK study is designed as an open-label, multicenter Phase II trial focusing on RVU120, a novel inhibitor of cyclin-dependent kinase (CDK) 8/19. The trial specifically targets anemia in patients with LR-MDS who have exhausted other treatment options. Prof. Uwe Platzbecker highlighted the potential of RVU120, noting its promising hematologic improvements in patients with impaired bone marrow function. He expressed confidence that the trial could yield positive outcomes, potentially reducing the need for red blood cell transfusions in these patients.

The initiation of REMARK is based on promising clinical safety and efficacy data, as well as robust preclinical evidence. Altered gene expression affecting hematopoietic cell maturation is a key factor in MDS pathogenesis. RVU120 promotes erythroid gene expression programs mediated by STAT5 and GATA1 in abnormal stem cells from MDS patients. Importantly, RVU120 has not shown significant toxicity in the hematopoietic system, making it a promising candidate for treating transfusion-dependent MDS patients.

Participants in the REMARK study will receive RVU120 for at least 24 weeks, covering eight complete cycles. The primary objective is to achieve hematologic improvement in the form of an erythroid response (HI-E). Secondary objectives include achieving independence from RBC transfusions, improving hemoglobin levels, enhancing the quality of life, monitoring disease progression, and analyzing specific gene mutations.

The REMARK study is one of four planned Phase II trials for RVU120 set to launch in 2024. Ryvu Therapeutics has already initiated two other Phase II trials, RIVER-52 and RIVER-81, focusing on AML. Another upcoming trial, POTAMI-61, will evaluate both monotherapy and combination therapy for myelofibrosis (MF).

Ryvu Therapeutics, based in Kraków, Poland, is a clinical-stage company dedicated to discovering and developing small-molecule therapies for oncology. The company's diverse pipeline targets emerging cancer biology mechanisms, including kinases, synthetic lethality, and immuno-oncology. RVU120, their most advanced program, targets CDK8/CDK19 and is being developed for various hematological malignancies.