Krakow, Poland – October 12, 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 that it will present clinical data on RVU120 in relapsed/refractory metastatic or advanced solid tumors, preclinical data on RVU120 enhancing antibody-dependent cellular cytotoxicity and discovery, and optimization data on novel MTA-cooperative PRMT5 inhibitors at the AACR-NCI-EORTC Molecular Targets and Cancer Therapeutics Symposium taking place on October 26-28 in Barcelona, Spain.
“We are excited to present updated clinical and preclinical data on RVU120 and our novel MTA-cooperative PRMT5 inhibitors at this year’s AACR-NCI-EORTC symposium,” said Hendrik Nogai, M.D., Chief Medical Officer of Ryvu Therapeutics. “RVU120 monotherapy continues to be safe, and dose escalation is progressing. We are also seeing clinical benefits with disease stabilizations in patients with relapsed/refractory metastatic or advanced solid tumors. Beyond single-agent activity, we have also demonstrated in preclinical in-vitro and in-vivo mouse models that RVU120 in combination with a therapeutic antibody enhances NK cell-mediated, antibody-dependent cellular cytotoxicity (ADCC). These findings suggest that RVU120 may increase the therapeutic value of ADCC-promoting drugs, which provides the rationale for exploring RVU120 combination therapies in multiple settings in hematology and solid tumors.”
Details on the poster presentations are as follows:
Abstract Title: “Phase I/II trial of RVU120, a CDK8/CDK19 inhibitor in patients with relapsed/refractory metastatic or advanced solid tumors”
Abstract Number: 67
Session Title: Molecular Targeted Agents 1
Session date: Wednesday, October 26, 2022
Clinical data demonstrate a favorable safety profile at doses of 75 mg, 100 mg, and 125 mg of RVU120 in all 9 patients enrolled to date. None of the patients experienced dose-limiting toxicity (DLT), drug-related serious adverse events (SAE), or drug-related AE of Grade 3 or higher. Disease stabilization was observed in two heavily pretreated patients, one lasting 18 weeks in gastro-esophageal junction cancer, and another, ongoing after 33 weeks in adenoid cystic carcinoma. Two patients are awaiting their first assessment. The most common reason for treatment discontinuation was progressive disease (5 patients). One patient withdrew consent, and 3 patients are ongoing. Available data warrant continuation of dose escalation and collection of additional clinical data.
Abstract Title: “RVU120, a small molecule inhibitor of CDK8/19 kinases, enhances rituximab-driven NK cells-mediated cytotoxicity both in vitro and in vivo”
Abstract Number: 158
Session Title: Combination Therapies
Session date: Thursday, October 27, 2022
Preclinical data demonstrate that treatment with RVU120 in combination with an anti-CD20 antibody causes upregulation of LAMP1 (CD107a) surface level and increases NK cell cytotoxicity against CD20-positive positive diffuse large B-cell lymphoma (DLBCL) cell lines. The combined therapy of RVU120 with rituximab, as a model drug in-vivo was well tolerated and resulted in complete tumor regressions. NK cells isolated from animals treated by the combination confirmed the highest cytotoxic potential on cancer cells ex vivo. This study shows the potential of RVU120 in enhancing antibody-mediated ADCC and 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”
Abstract Number: 45
Session Title: Molecular Targeted Agents 1
Session date: Wednesday, October 26, 2022
Ryvu has identified a series of MTA-cooperative PRMT5 inhibitors with drug-like physicochemical properties that block methyltransferase activity with nanomolar IC50 values. Structurally enabled hit generation and optimization allowed for a rapid expansion and delivery of several generations of compounds with novel IP, high target engagement in cells, and selective potency in MTAP-deleted cell lines. Ryvu compounds selectively inhibit the growth of MTAP-deleted cancer cells in prolonged 3D culture, and efficacy studies with the lead compound resulted in tumor growth inhibition in MTAP -/- model, accompanied by significant inhibition of target proximal PD biomarker.
All abstracts are now available online and can be obtained from the conference site at https://event.eortc.org/ena2022/