Undisclosed WRN inhibitor / Ryvu Therap - LARVOL DELTA

Discovery of WRN inhibitors as targeted therapy in the treatment of microsatellite unstable (MSI-H) tumors (EORTC-NCI-AACR 2024) - "This selectivity was also proven in in vivo CDX experiment, where strong TGI was observed in MSI CDX model (SW48) but had no impact on MSS CDX model (SW620). Top compounds demonstrate favorable pharmacokinetic properties, achieving optimal exposure and target engagement, resulting in strong tumor growth inhibition.Taken together, these studies demonstrate that WRN inhibitors induce a strong synthetic lethal phenotype in MSI-H cancers, presenting an exciting therapeutic potential for oncology patients."

Endometrial Cancer • Microsatellite Instability • Oncology • Ovarian Cancer • MSI • WRN

Discovery of WRN inhibitors as targeted therapy in the treatment of microsatellite unstable (MSI-H) tumors (PRNewswire) - "Ryvu WRN inhibitors show nanomolar potency in viability assays in MSI-H cell lines, with excellent selectivity over microsatellite-stable (MSS) cells. In in vivo studies, Ryvu inhibitor strongly suppressed tumor growth in an MSI-H model (SW48) while not impacting the MSS model (SW620). The compounds exhibit favorable pharmacokinetics, achieving optimal exposure and target engagement, further enhancing their therapeutic potential in MSI-H cancers."

Preclinical • Microsatellite Instability • Oncology • Solid Tumor

Discovery of WRN inhibitors as targeted therapy in the treatment of microsatellite unstable (MSI-H) tumors (AACR 2024) - "The correlation between compound exposure and on-target effect was confirmed in PK/PD and efficacy studies in xenograft MSI-H cancer models. These data provide pharmacological proof-of-concept for the synthetic lethal effect of our inhibitors and support WRN inhibition as a new oncological therapy."

Endometrial Cancer • Microsatellite Instability • Oncology • Ovarian Cancer • Solid Tumor • MSI • WRN

Ryvu Therapeutics Presents Preclinical Data on RVU120 and Synthetic Lethality Programs at the 2024 AACR Annual Meeting (PRNewswire) - "Ryvu has developed potentially best-in-class MTA-cooperative PRMT5 inhibitors showing favorable drug-like properties and effective PRMT5 inhibition dependent on MTA binding. Ryvu PRMT5 inhibitor has a robust antiproliferative effect on MTAP-deleted cell lines and provides a good safety window for MTAP WT cells, as shown in a wide cell line panel....Data on Ryvu's WRN inhibitors provide pharmacological proof-of-concept with synthetic lethal effect and support WRN inhibition as a new, targeted oncological therapy in MSI-high tumors....In conjunction with our novel ranking algorithm, these models have successfully identified potential drug targets in KRAS-mutant cells—targets that remained undetected in immortalized CRC cell lines, likely due to genetic and epigenetic alterations accumulated over years of cell culture."

Preclinical • Colorectal Cancer • Gastrointestinal Cancer • Microsatellite Instability • Oncology • Solid Tumor