Krakow, Poland – October 23, 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, announced today updated clinical Phase I data from RVU120 Phase I/II study in patients with relapsed/refractory metastatic or advanced solid tumors, presented at the European Society for Medical Oncology (ESMO) Congress 2023, taking place October 20-24 in Madrid, Spain. The Company has also provided an update on the progress of the ongoing Phase Ib study in patients with acute myeloid leukemia (AML) and high-risk myelodysplastic syndromes (HR-MDS), and presented the updated RVU120 program development plan.
Based on the recently updated Phase I study results in patients with solid tumors presented at ESMO, along with data from patients with AML/HR-MDS, the company has updated the development plan for RVU120:
- Both Phase I studies of RVU120 in patients with solid tumors (AMNYS-51) and AML/HR-MDS (RIVER-51) have provided convincing RVU120 safety data, effectively reducing the risk associated with both the target and the molecule as a first-in-class CDK8/19 inhibitor.
- Both studies have demonstrated relevant levels of target inhibition at safe doses.
- Meaningful signs of clinical activity have been reported in patients with AML and HR-MDS, including a complete remission in a patient with NPM1 and DNMT3 mutations, in line with the preclinical data first published by Ryvu in 2019. The Phase II development in AML/HR-MDS is planned to be initiated in Q4 2023 with two cohorts of genetically defined patients with AML or HR-MDS as a single agent (RIVER-52) and in combination with venetoclax (RIVER-81).
- Induction of erythropoiesis in multiple patients in RIVER-51, consistent with RVU120’s mechanism of action, encouraged Ryvu to financially support a dedicated Phase II clinical trial in patients with low-risk myelodysplastic syndromes (LR-MDS) – the REMARK study. REMARK will be conducted as an investigator-initiated study through the EMSCO network, with Uwe Platzbecker, a globally renowned expert in the field of LR-MDS, taking on the role of Coordinating Principal Investigator. Start-up activities for the study are scheduled to commence later this year, and patient enrollment is planned to start in H1 2024.
- RVU120’s effect on bone marrow and hematopoietic cells observed in RIVER-51, supported by the translational data generated with Prof. Rajit Rampal as part of a scientific collaboration established in 2021, encouraged Ryvu to initiate a new, previously unplanned study in patients with myelofibrosis (MF) – the POTAMI-61 study. Start-up activities for the study are scheduled to commence this year, with patient enrollment planned to begin in Q2 2024.
- Even though AMNYS-51 study has provided signs of RVU120 single-agent activity in solid tumors, including long-term disease stabilizations in patients with adenoid cystic carcinomas (AdCC) and evidence of on-target activity in a patient with pancreatic cancer, Ryvu will not immediately open any tumor type-specific cohorts in AMNYS-51 study. However, considering the attractive development opportunities in hematologic malignancies, Ryvu will focus its efforts on the aforementioned RIVER-52, RIVER-81, REMARK and POTAMI-61 clinical studies.
- Translational research in solid tumors will be ongoing, including combination studies in multiple solid tumor types, as well as academic collaborations on medulloblastoma and sarcoma.
- The updated RVU120 clinical development plan includes studies that may lead to three approvals in 2026-2027.
- The total budget for Phase II clinical development of RVU120, aimed at enrollment of over 270 patients across four Phase II clinical studies (RIVER-52, RIVER-81, REMARK and POTAMI-61), is approximately €68M. This budget also includes necessary drug manufacturing activities required for the approval pathway, translational research, and internal costs related to RVU120 clinical development. The total budget for the Phase II clinical development of RVU120 aligns with the estimates initially announced in the Ryvu Development Plans for 2022-2024.
- The current Ryvu cash runway extends through Q1 2026.
Hendrik Nogai, MD, Chief Medical Officer at Ryvu commented:
– We are very close to completing RVU120 Phase I development in 2023, including determining a safe dose in the pharmacologically active range. Based on the convincing safety data and observed signs of activity, we plan to initiate the first Phase II efficacy study in Q4 2023, pioneering the development of CDK8/19 inhibitors.
– We are privileged to have attracted the interest of globally recognized researchers. With their invaluable support, we have identified an attractive development plan for RVU120. During the next few months, we expect the launch of four Phase II efficacy studies in hematologic malignancies: AML/HR-MDS, LR-MDS, and myelofibrosis.
Paweł Przewięźlikowski, co-founder, largest shareholder and Chief Executive Officer at Ryvu said:
– Based on clinical data analysis, our internal Clinical Committee, strengthened by numerous international opinion leaders and medical experts, has supported the update of the clinical development plan for RVU120, prioritizing multiple hematologic indications. We have also given more attention to a fast-to-market strategy, now pursuing three development paths aimed at generating clinical data supporting potential approvals in 2026-2027.
– Over the last few months, we have successfully extended our cash runway to Q1 2026. The presented RVU120 development plan aligns with the budget outlined in Ryvu Development Plans for 2022-2024 and targets multi-billion-dollar market potential.
At the ESMO Congress 2023, Ryvu announced updated clinical Phase I data from Phase I/II study of RVU120 in relapsed/refractory metastatic advanced solid tumors.
- RVU120 achieved 12 disease stabilizations with a good safety profile in unselected and heavily pretreated patients.
- The dose of 250 mg is safe and tolerated, results in exposure in the pharmacologically active range, and is expected to result in robust efficacy in selected patients. Further dose optimization is ongoing, and the final results may be used in future additional solid tumor clinical studies, depending on translational data in different indications.
With a data cutoff of September 26, 2023, the results are featured in a poster presentation entitled, “Phase I/II trial of RVU120, a CDK8/CDK19 inhibitor, in patients with relapsed/refractory metastatic or advanced solid tumors”.
Hendrik Nogai, MD, Chief Medical Officer at Ryvu said:
– We are excited to share positive, updated results from the Phase I/II trial of RVU120 in patients with advanced solid tumors at this year’s ESMO Congress. RVU120 monotherapy continues to demonstrate a favorable safety profile in a heavily pretreated all-comer patient population. Disease stabilization was observed in 12 patients with previously progressing disease, with RVU120 treatment durations exceeding the most recent prior therapy in 8 patients.
Results as of the Data Cut-Off Date of September 26, 2023:
- 39 patients with metastatic or locally advanced solid tumors received treatment distributed across 8 cohorts, with doses ranging from 75 to 400 mg of RVU120.
- Median patient age is 58 years, and median prior lines of therapy is 5 (heavily pre-treated).
- 12 patients achieved stable disease (SD), and 8 out of 12 patients had a duration of therapy on RVU120 longer than the prior line of therapy. A trend of a longer treatment duration was observed in patients with adenoid cystic carcinoma (AdCC).
- RVU120 was generally well tolerated. Most common adverse events (AEs) were GI-related (nausea/vomiting) and occurred shortly after initial RVU120 dosing (average time to onset of slightly over 1 hour).
- A robust relationship between exposure to RVU120 and inhibition of PD marker was observed:
- Analysis of cells exposed to patient plasma samples after treatment with RVU120 revealed that inhibition of pSTAT5 closely correlated with achieved exposures (Cmax, AUC), reaching a biologically significant range of more than 50% at doses 250 mg and above.
A presentation will be available on the “Publication” section of the Ryvu website.
Webinar on RVU120 development plan
Ryvu will host a webinar today (Monday, October 23) at 9:00 am CEST to discuss further RVU120 development plans. To join the webcast, please register here: https://ryvu.clickmeeting.com/ryvu-esmo-2023-results-rvu120-development-plans/register.