RVU305 / Ryvu Therap - LARVOL DELTA

RVU305, a brain-penetrant MTA-cooperative PRMT5 inhibitor, shows efficacy in GBM preclinical models (AACR-NCI-EORTC 2025) - "In vivo, RVU305 displayed signs of antitumor activity in an orthotopic U87MG GBM mouse model. Taken together, these studies confirm that RVU305 is a potent, brain-penetrant MTA-cooperative PRMT5 inhibitor which induces a strong synthetic lethal phenotype in MTAP-deleted cancers, including GBM, offering an exciting therapeutic opportunity for a large patient population and potentially addressing an unmet clinical need."

Preclinical • Glioblastoma • Oncology • MTAP

RVU305: (Ryvu Therapeutics Press Release) - "IND/CTA-enabling studies are planned to be completed in H2 2025."

Clinical • Solid Tumor

Ryvu Therapeutics presents preclinical data on RVU305…at AACR and ADC payload summit (Ryvu Therapeutics Press Release) - "We are excited to showcase continued progress across our preclinical pipeline. In particular, we are rapidly advancing RVU305....with IND/CTA-enabling studies on track for completion in H2 2025....RVU305, a potentially best-in-class, brain-permeable MTA-cooperative PRMT5 inhibitor, demonstrates significant potential in targeting MTAP-deleted cancers. In preclinical studies, RVU305 effectively inhibited tumor growth in MTAP-null cancer models without affecting normal cells. RVU305 also demonstrated CNS penetration with predicted efficacious exposure in the brain in cynomolgus monkeys....In CNS cell lines, RVU305 exhibited high potency and efficacy. Furthermore, co-treatment with an anti-PD-1 antibody was well tolerated and resulted in antitumor activity in an MTAP-deleted model resistant to immune checkpoint inhibitors (ICI)."

Preclinical • Oncology

Preclinical candidate RVU305, an MTA-cooperative PRMT5 inhibitor, shows activity in MTAP-deleted tumors resistant to immune checkpoint treatment (AACR 2025) - "Immunomodulatory effects of RVU305, both alone and in combination with anti-PD-1, were supported by pharmacodynamic changes observed in tumor tissue. Taken together, these studies confirm that MTA-cooperative PRMT5 inhibitors induce a strong synthetic lethal phenotype in MTAP-deleted cancers, offering an exciting therapeutic opportunity for a large patient population and potentially addressing an unmet clinical need when combined with immunotherapy."

Preclinical • Colon Cancer • Colorectal Cancer • Oncology • Solid Tumor • CDKN2A • IFNG • MTAP

Ryvu Therapeutics announces strategic reorganization to extend the cash runway for the development of RVU120 and the preclinical pipeline (PRNewswire) - "RVU120: emphasis on rapid study enrollment and quality data generation in 2025 - Three Phase II studies of RVU120 are in progress as planned: RIVER-81 (combination study with venetoclax in patients with AML), POTAMI-61 (monotherapy/combination study with ruxolitinib in patients with myelofibrosis) and REMARK (monotherapy study in patients with LR-MDS). The Phase II RIVER-52 study of RVU120 monotherapy in patients with AML or HR-MDS, will not enroll new patients to focus investment on the other RVU120 development paths. Currently enrolled patients will continue to receive treatment per protocol. The decision to progress RIVER-81 and suspend enrollment in RIVER-52 was based on data analysis and feedback from advisory boards in February 2025. The next data update for RVU120 is planned in Q2 2025. RVU305: IND/CTA-enabling studies are ongoing and planned to be completed in H2 2025."

Clinical data • Preclinical • Trial status • Acute Myelogenous Leukemia • Myelodysplastic Syndrome • Myelofibrosis

Discovery of novel MTA-cooperative PRMT5 preclinical candidate as targeted therapeutics for MTAP-deleted cancers (PRNewswire) - "RVU305 exhibits robust antiproliferative activity in MTAP-null cancer models, including over 100% tumor growth inhibition (TGI) at several dose levels and multiple complete remissions (CRs) at several dose levels in a DoHH2 MTAP-deleted model. Tolerability and selectivity towards MTAP-deleted cells was also demonstrated in in vitro and in vivo preclinical models. Overall, the findings highlight the potential of RVU305 preclinical candidate as a promising therapeutic option for patients with MTAP-deleted cancers."

Preclinical • Oncology • Solid Tumor

Ryvu Therapeutics to present clinical and preclinical data on RVU120, RVU305, and novel synthetic lethality programs at the 2024 EORTC-NCI-AACR Symposium (PRNewswire) - "Ryvu Therapeutics...will present four posters with clinical and preclinical data from RVU120 (CDK8/19 inhibitor), RVU305 (MTA-cooperative PRMT5 inhibitor), WRN and novel synthetic lethality programs at the 2024 EORTC-NCI-AACR Symposium (ENA), October 23-25, Barcelona, Spain."

Clinical data • Preclinical • Oncology • Solid Tumor

Preclinical Pipeline updates (PRNewswire) - "On September 9, 2024, the Management Board decided to advance Ryvu's potentially best-in-class PRMT5 inhibitor RVU305 to further steps of preclinical development, including toxicology and API/IMP manufacturing, targeting IND/CTA filing in H2 2025."

IND • Preclinical • Solid Tumor

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

Ryvu Therapeutics Presents Preclinical Data on PRMT5 and its Synthetic Lethality Platform at the 2023 AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics (PRNewswire) - "Ryvu Therapeutics...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....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....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."

Preclinical • Colorectal Cancer • Diffuse Large B Cell Lymphoma • Gastrointestinal Cancer • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Marginal Zone Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor

Ryvu Therapeutics to Present Preclinical Data on PRMT5 and its Synthetic Lethality Platform at the 2023 AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics (GlobeNewswire) - "Ryvu Therapeutics...announced that preclinical data from its PRMT5 program and synthetic lethality platform as well as preclinical data on MEN1703 (SEL24) in B-cell lymphomas will be presented at the 2023 AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics, October 11-15 in Boston, Massachusetts....Poster presentations highlight preclinical data from Ryvu’s PRMT5 program in MTAP-Deficient cancers and its synthetic lethality platform in colorectal cancer models....Preclinical efficacy data of MEN1703 (SEL24) in B-cell lymphomas to be presented by Ryvu’s partner Menarini."

Preclinical • Colorectal Cancer • Non-Hodgkin’s Lymphoma

Ryvu Therapeutics Reports Fourth Quarter and Full Year 2022 Financial Results and Provides Corporate Update (GlobeNewswire) - "Upcoming clinical and corporate milestones... (i) SEL24 (MEN1703): Updates from the Phase I/II study of SEL24/MEN1703, a first-in-class dual PIM/FLT3 kinase inhibitor, in patients with IDH1/2-mutated acute myeloid leukemia expected in 2023; (ii) Synthetic lethality: Updated in vivo data for the MTA-cooperative PRMT5 inhibitors will be presented at the upcoming 2023 AACR Annual Meeting in Orlando, Florida."

P1/2 data • Preclinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

Ryvu Therapeutics Presents Updated Clinical and Preclinical Data on RVU120 at the AACR-NCI-EORTC Molecular Targets and Cancer Therapeutics Symposium (GlobeNewswire) - "Ryvu Therapeutics...announced...optimization data on novel MTA-cooperative PRMT5 inhibitors at the 34th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics, taking place on October 26 - 28 in Barcelona, Spain....Structurally enabled hit generation and optimization allowed for a rapid expansion and delivery of potentially best-in-class MTA-cooperative PRMT5 inhibitors that exhibit drug-like physicochemical properties and selective, nanomolar growth inhibition in MTAP-deleted cell lines in prolonged 3D culture. In the in-vivo responder model, the lead compound demonstrated antitumor efficacy and target engagement showing a promising strategy for targeted therapy for MTAP deficiency that occurs in 10-15% of all tumors."

Preclinical • Oncology

Ryvu Therapeutics Reports 2022 Half-Year Financial Results and Provides Corporate Update (PRNewswire) - "UPCOMING CLINICAL AND CORPORATE MILESTONES: RVU120: Data update from the ongoing Phase I clinical study in acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (HR-MDS) and the ongoing Phase I clinical study in solid tumors will be presented in Q4 2022; Data on Ryvu's novel MTA-cooperative PRMT5 inhibitors as targeted therapeutics for MTAP deleted cancers to be presented in Q4 2022."

Clinical data • P1 data • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology

Ryvu Therapeutics Announces Presentations at the AACR 2022 Annual Meeting (PRNewswire) - "Ryvu Therapeutics...announced presentations from its most advanced oncology program RVU120 and MTA-cooperative PRMT5 inhibitor program at the American Association for Cancer Research (AACR) Annual Meeting, taking place April 8-13 in New Orleans, U.S."

Preclinical • Trial status • Breast Cancer • Oncology • Solid Tumor