Ryvu Therapeutics Announces Dosing of the First Patient in the REMARK Phase II Study of RVU120 for the Treatment of Anemia in Patients with Lower-Risk Myelodysplastic Syndromes (LR-MDS)

• Ryvu Therapeutics has announced the dosing of the first patient in the REMARK Phase II study of RVU120. The primary goal of the REMARK study is to evaluate the safety and efficacy of RVU120 in patients with lower-risk myelodysplastic syndromes (MDS). 
• The study is conducted as an investigator-initiated study through the European Myelodysplastic Neoplasms Cooperative Group (EMSCO) network with Prof. Uwe Platzbecker, a globally renowned expert in the field of LR-MDS, as the Coordinating Principal Investigator.
• The REMARK study has already received approval from the Competent Authorities and Ethics Committees of Germany, Spain, Poland, Italy, and France under the European Union Clinical Trial Regulation (EU-CTR) 2023-509947-29. It will cover up to 25 clinical sites globally. The planned overall enrollment is up to approximately 40 patients. 

KRAKOW, Poland, Sept. 19, 2024 /PRNewswire/ -- 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 has been dosed in the REMARK study, a Phase II clinical trial investigating RVU120 as a monotherapy for the treatment of patients with LR-MDS.

"We are glad to announce the initiation of the REMARK study for RVU120, which can potentially help patients with lower-risk MDS. This study builds upon the promising results from our Phase Ib study in patients with AML and high-risk MDS, where we observed hematologic improvement in several patients, including cases of transfusion independence. The objective is to further assess the safety and efficacy of RVU120 in patients with lower-risk MDS, underpinned by robust preclinical and mechanistic evidence. We believe this represents a significant advancement toward our objective of developing effective treatments for hematological diseases and offering therapeutic options for patients. I am delighted that we can count on the support of the EMSCO network and Prof Uwe Platzbecker in this endeavor." - said Hendrik Nogai, M.D., Chief Medical Officer of Ryvu Therapeutics.

REMARK is an open-label, multicenter Phase II study of RVU120, a novel small-molecule cyclin-dependent kinase (CDK) 8/19 inhibitor. The study aims to treat anemia in patients with lower-risk myelodysplastic syndromes (MDS). In REMARK, RVU120 is being explored as a single agent in patients with LR-MDS who have exhausted available treatment options.

The REMARK study is being conducted as an investigator-initiated study through the EMSCO network with Prof. Uwe Platzbecker, a globally renowned expert in the field of LR-MDS, as the Coordinating Principal Investigator.

"I am proud that we could start the REMARK study in line with our ambitious plans. RVU120 has shown promising hematologic improvement in patients with off-hematologic impaired bone marrow function. I am optimistic that this clinical evidence will translate into a positive outcome of the REMARK study. RVU120 has important features that should be considered a potential new treatment option for patients with LR-MDS. It may aid in achieving our ultimate aim to alleviate the need for red blood cell transfusions in these patients." - said Uwe Platzbecker, M.D., Director of the Clinic and Poliklinik for Hematology, Cell Therapy and Hemostaseology at the Leipzig University Hospital.

REMARK is being initiated based on the clinical safety and efficacy data gathered so far, as well as strong preclinical and mechanistic rationale. MDS pathogenesis is influenced by gene expression alterations that hinder the maturation of hematopoietic cells. RVU120 triggers erythroid gene expression programs orchestrated by STAT5 and GATA1 in aberrant stem cells from MDS patients. Importantly, RVU120's activity does not lead to significant toxicity in the hematopoietic system. As a result, RVU120 emerges as a promising drug candidate for treating transfusion-dependent MDS patients.

In REMARK, patients will receive RVU120 for at least 8 complete cycles (24 weeks). The primary goal is to achieve hematologic improvement in the form of an erythroid response (HI-E), with secondary goals including independence from RBC transfusions, improvement in hemoglobin levels, quality of life, disease progression, and analysis of specific gene mutations.

REMARK represents the third of four planned RVU120 Phase II clinical studies scheduled for launch in 2024. Ryvu has already started patient treatment in the RIVER-52 and RIVER-81 studies in AML, and the fourth Phase II trial is the planned to be initiated shortly POTAMI-61 study, evaluating both monotherapy and combination therapy for the treatment of patients with myelofibrosis (MF).

About Ryvu Therapeutics 

Ryvu Therapeutics is a clinical-stage drug discovery and development company focused on novel small-molecule therapies that address emerging targets in oncology. Internally discovered pipeline candidates at Ryvu use diverse therapeutic mechanisms driven by emerging knowledge of cancer biology, including small molecules directed at kinases, synthetic lethality, and immuno-oncology targets. Ryvu's most advanced program is RVU120, a selective CDK8/CDK19 kinase inhibitor with the potential to treat hematological malignancies and solid tumors. RVU120 is currently in Phase II development (i) as a monotherapy for the treatment of patients with relapsed/refractory acute myeloid leukemia (r/r AML) and high-risk myelodysplastic syndromes (HR-MDS) – the RIVER-52 study, (ii) in combination with venetoclax for the treatment of patients with r/r AML – the RIVER-81 study, and (iii) a monotherapy for the treatment of patients with lower risk myelodysplastic syndromes (LR-MDS) – the REMARK study. SEL24 (MEN1703) is a dual PIM/FLT3 kinase inhibitor licensed to the Menarini Group that is expected to start a Phase II study in diffuse large B-cell lymphoma (DLBCL) in Q4 2024. RVU305, a potentially best-in-class PRMT5 inhibitor aiming to treat multiple solid tumors, is currently undergoing IND/CTA-enabling studies. Ryvu Therapeutics has signed 11 partnering and licensing deals with global companies, including BioNTech and Exelixis. The Company was founded in 2007 and is headquartered in Kraków, Poland. Ryvu is listed on the Warsaw Stock Exchange and is a component of the mWIG40 index. For more information, please visit www.ryvu.com 

About EMSCO

The European Myelodysplastic Neoplasms Cooperative Group (EMSCO) serves as a platform to foster academic clinical research, cooperation and education in the field of myelodysplastic syndromes (MDS). EMSCO is administered by GWT-TUD GmbH and was founded in 2013 upon an initiative of the European Leukemia Network (ELN). Originally founded to facilitate European MDS-specific trials, EMSCO soon also became active in organizing indication-specific conferences and in serving as a platform for education and outreach in MDS.

SOURCE Ryvu Therapeutics