Ryvu Therapeutics is making strides in its oncology-focused drug development programs, highlighted by the advancement of its PRMT5 inhibitor, RVU305, into further preclinical development. This decision, announced on September 9, 2024, aims for an Investigational New Drug (IND) or Clinical Trial Application (CTA) filing in the second half of 2025. The company also reported positive financial results for the first half of 2024 and provided updates on its ongoing clinical trials with RVU120.
RVU305: A Potentially Best-in-Class PRMT5 Inhibitor
RVU305 is distinguished by its favorable drug-like properties, including oral administration, strong antiproliferative effects on MTAP-deleted cell lines, and a good safety window for MTAP WT cells. Preclinical data presented at AACR 2024 support its potential as a best-in-class PRMT5 inhibitor. PRMT5 inhibition represents a promising therapeutic strategy in cancers with MTAP deletions, offering a targeted approach to address this genetic vulnerability.
RVU120 Clinical Trial Updates
Ryvu is actively enrolling patients in two Phase II studies with RVU120: RIVER-52 (RVU120 as monotherapy in r/r AML and HR-MDS) and RIVER-81 (RVU120 in combination with venetoclax in AML). Enrollment is progressing across clinical sites in Poland, Italy, Spain, France, and Canada, with plans to activate a total of 46 sites for RIVER-52 and 34 sites for RIVER-81 by the end of 2024. Initial data from these studies are anticipated to be presented at the ASH 2024 conference in December.
Two additional Phase II studies, POTAMI-61 (RVU120 in myelofibrosis) and REMARK (RVU120 in low-risk myelodysplastic syndromes), are expected to begin enrollment shortly. The REMARK study will be conducted through the EMSCO network, with Prof. Uwe Platzbecker as the Coordinating Principal Investigator.
Data presented at the 2024 European Hematology Association (EHA) Congress highlighted preliminary signs of clinical benefit in ongoing RIVER-52 patients and demonstrated the safety of RVU120 in combination with venetoclax in the RIVER-81 study. Translational data suggest a synergistic effect between RVU120 and venetoclax, potentially overcoming resistance to venetoclax treatment. RVU120 also shows promise in myeloproliferative neoplasms, potentially through downregulation of pro-inflammatory cytokines and synergy with JAK inhibitors and the BET inhibitor pelabresib.
Financial Highlights and Corporate Developments
Ryvu reported total operating revenues of USD 12.1 million for H1 2024, compared to USD 7.9 million in H1 2023. As of September 5, 2024, the company's cash position was USD 65.3 million, providing a financial runway through Q1 2026. This includes the final tranche of financing from the European Investment Bank (EUR 6 million).
Ryvu also secured approximately USD 6.6 million in grant funding from the Polish Agency for Enterprise Development to support its ONCO Prime discovery platform and obtained Associate Partner status within the IPCEI Med4Cure program for its PANACEA-NOVO project. Additionally, Ryvu achieved a milestone under its license agreement with Exelixis, receiving a USD 2.0 million payment.
WRN Inhibitor Program
Ryvu's WRN inhibitor program has demonstrated target engagement and selective potency, with in vivo efficacy studies showing pronounced tumor growth inhibition in an MSI-H colorectal cancer xenograft model. The company is targeting preclinical candidate selection in the upcoming quarters, supporting WRN inhibition as a new, targeted cancer therapy.
