- Company to host a virtual webinar on PRMT5 data and the synthetic lethality pipeline, including WRN and novel target discovery, today, Monday, October 16, at 9.30 am CEST
- Presentations include updated data from the lead preclinical program on MTA-cooperative PRMT5 inhibitors
- Preclinical studies highlight the potential of Ryvu’s synthetic lethality platform based on primary cells
- Ryvu’s partner Menarini presented preclinical data on MEN1703 (SEL24) showing promising anti-tumor activity in B-cell lymphomas, supporting the Phase II clinical program
Krakow, Poland – October 16, 2023 – Ryvu Therapeutics (WSE: RVU), a clinical-stage drug discovery and development company focusing on novel small molecule therapies that address emerging targets in oncology, today announced presentations of preclinical data from the PRMT5 program and synthetic lethality platform, as well as preclinical data on MEN1703 (SEL24) in B-cell lymphomas, at the 2023 AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics, taking place in Boston, Massachusetts.
“We are pleased with preclinical data underscoring the promise of our synthetic lethality platform, as highlighted by our leading preclinical program on PRMT5 inhibitors,” said Krzysztof Brzózka, Ph.D., Chief Scientific Officer of Ryvu Therapeutics. “With the growing evidence of the potential of PRMT5 as a cancer therapeutic target, we are excited to share updated data on our MTA-cooperative PRMT5 inhibitors showing high selectivity and efficacy in animal tumor models. Our potentially best-in-class MTA-cooperative PRMT5 inhibitors exhibit significantly improved pharmacokinetics relative to other PRMT5 inhibitors currently in development. Given their in vivo target engagement and remarkable anti-tumor efficacy, we anticipate further development and progression to IND-enabling studies in 2024. In addition, we presented our comprehensive primary colorectal cancer (CRC) cell models that not only mirror the molecular profile seen in patient-derived specimens but also surpass industry benchmarks in screenings, making them invaluable for future drug discovery.”
Ryvu licensee, Menarini Group, and academic collaborators presented preclinical data on MEN1703 (SEL24), a first-in-class, oral, dual type I PIM/FLT3 inhibitor in B-cell lymphomas, where MEN1703 demonstrated promising anti-tumor activity. These data support the Phase II clinical program of MEN1703 in diffuse large B-cell lymphoma (DLBCL).
Details on the poster presentations are as follows:
Abstract Title: “Discovery of Novel MTA-cooperative PRMT5 Inhibitors as Targeted Therapeutics for MTAP-deleted Cancers”
Ryvu has developed potentially best-in-class MTA-cooperative PRMT5 inhibitors with outstanding drug-like physicochemical properties and the ability to block methyltransferase activity of PRMT5 with nanomolar IC50 values. The novel, optimized inhibitors exhibit a significantly improved PK profile, and in addition, the compounds show antitumor efficacy and target engagement in vivo, providing a strong foundation for further development.
Abstract Title: “A Comprehensive Platform for Unraveling the Molecular Mechanisms and Vulnerabilities of Colorectal Cancer: A Step Forward in Target Discovery”
Ryvu has pioneered an extensive platform that employs primary colorectal cancer (CRC) models, originated from human intestinal stem cells. This innovative approach enables high-throughput phenotypic assays and CRISPR/Cas9 genomic screenings, surpassing conventional industry standards. The robustness of these models has been confirmed through Ryvu’s proprietary ranking algorithm, which identifies potential synthetic lethal drug targets, particularly in KRAS-driven cells.
Abstract Title: “MEN1703/SEL24, A Potent PIM Inhibitor, Demonstrates Promising Anti-Tumor Activity in Activated B Cell Like DLBCL, Mantle Cell Lymphoma and Marginal Zone Lymphoma Cells”
Pharmacological inhibition with MEN1703 (SEL24), a first-in-class, oral, dual type I PIM/FLT3 inhibitor shows anti-proliferative effects in B cell lymphomas of various histotypes. Importantly, MEN1703 was effective in lymphoma cells resistant to other treatments inducing apoptosis in most cell lines. RNA-Seq indicated that the molecule modulates the transcriptome of highly responsive DLBCL cell lines differently from other, poorly responsive cells, providing clues to mechanisms involved in sensitivity to PIM inhibitors and supporting potential in treating B-cell lymphomas.
Posters are available on the Ryvu corporate website.
Webinar on PRMT5 and synthetic lethality pipeline, including WRN project and target discovery efforts
Ryvu will host a webinar today at 9:30 am CEST to discuss the PRMT5 data. To join the webcast, please register here: https://bit.ly/3RL1YWp. A recording from the webinar will be available on the ‘Presentations’ section of the Ryvu website.