- Updated data from Phase I/II dose-escalation study of RVU120 show four disease stabilizations in advanced solid tumor patients,
- RVU120 was well tolerated across all doses evaluated,
- Preclinical data demonstrate the potential of combination therapy with RVU120 and
- Novel MTA-cooperative PRMT5 inhibitors show preclinical antitumor efficacy and target engagement in MTAP-deleted cancers.
Krakow, Poland – October 26, 2022 – 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 updated clinical data on RVU120 in relapsed/refractory metastatic or advanced solid tumors, preclinical data on RVU120 enhancing antibody-dependent cell-mediated cytotoxicity (ADCC) and discovery, and 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.
“The data presented today at the EORTC-NCI-AACR meeting further support the growing body of clinical evidence of RVU120’s potential therapeutic benefits for patients with metastatic or advanced solid tumors,” said Hendrik Nogai, M.D., Chief Medical Officer of Ryvu Therapeutics. “To date, we have observed four disease stabilizations in this heavily pre-treated patient group with three of those lasting more than 4 months. RVU120 monotherapy continues to be safe, well-tolerated and the dose escalation has now progressed to a dose of 175mg. Additionally, we presented data from our preclinical studies showing that RVU120 enhances the therapeutic potential of ADCC-promoting drugs in-vivo and in-vitro. The combination therapy resulted in complete tumor regressions in these models, providing a strong rationale for further exploration of RVU120 combination therapies in multiple settings in hematology and solid tumors.”
Dr. Nogai continued, “We also presented preclinical data with our proprietary MTA-cooperative PRMT5 inhibitors that selectively target MTAP deficiency which occurs in 10-15% of all tumors. These compounds showed antitumor efficacy and target engagement in-vivo showing best-in-class potential.”
Poster presentations featured at the Symposium:
Abstract Title: “Phase I/II trial of RVU120, a CDK8/CDK19 inhibitor in patients with relapsed/refractory metastatic or advanced solid tumors”
Updated data from the ongoing dose-escalation Phase I/II trial in relapsed/refractory metastatic or advanced solid tumors include newly enrolled patients at doses of up to 175mg. RVU120 is administered orally, every other day for a total of 7 doses, in 3-week treatment cycles. Patients’ median age is 61 years and the median of previous therapy lines is 5. Out of 17 patients that received at least one dose of RVU120, 11 were evaluable for efficacy. One patient withdrew consent prior to the first post-baseline assessment and 5 patients are ongoing and awaiting their first assessment. Disease stabilization was observed in 4 heavily pretreated patients, and 7 progressed. Three patients achieved a disease stabilization for more than 4 months. None of the patients experienced dose-limiting toxicity (DLT), drug-related serious adverse events (SAEs), or drug-related AEs of Grade 3 or higher. Data at 135mg indicate a target inhibition of more than 60%. These data support the continuation of dose escalation of RVU120 currently at 175mg.
Abstract Title: “RVU120, a small molecule inhibitor of CDK8/19 kinases, enhances rituximab-driven NK cells-mediated cytotoxicity both in vitro and in vivo”
Preclinical data demonstrated RVU120’s potential in enhancing the therapeutic value of antibody-dependent cell-mediated cytotoxicity (ADCC)-promoting drugs. Combination with rituximab, an anti-CD20 antibody, resulted in upregulation of lysosomal-associated membrane protein 1 (LAMP1) surface level and increased NK cell cytotoxicity against CD20-positive positive diffuse large B-cell lymphoma (DLBCL) cell lines. The combination treatment in mice was well tolerated and resulted in complete tumor regressions. This study reinforces the rationale for the development of RVU120 combination therapies.
Abstract Title: “Discovery of novel MTA-cooperative PRMT5 inhibitors as targeted therapeutics for MTAP deleted cancers”
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.
All posters are now available for download from Ryvu corporate website: https://ryvu.com/investors-media/publications/