• Ryvu will present 4 posters on: RVU305 (MTA-cooperative PRMT5 inhibitor), demonstrating a potentially best-in-class profile, WRN program, in lead optimization, ONCO Prime platform, highlighting novel target discovery in synthetic lethality and RVU120, with an update from the solid tumor study – AMNYS-51.

 

Krakow, Poland – October 9, 2024 – Ryvu Therapeutics (WSE: RVU), a clinical-stage drug discovery and development company focusing on novel small molecule therapies that address emerging targets in oncology, 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.

“We are thrilled to showcase our latest advancements on RVU120, RVU305, and other synthetic lethality projects at the 2024 EORTC-NCI-AACR Symposium this year. The strong preclinical data from our PRMT5 synthetic lethality program is highly encouraging as we target IND/CTA filing and continue to advance our project toward clinical studies.” – said Krzysztof Brzózka, Ph.D., Chief Scientific Officer. 

 

Poster highlights:

Abstract Title: Discovery of novel MTA-cooperative PRMT5 inhibitors as targeted therapeutics for MTAP-deleted cancers
Abstract Number: ENA24-0205
Session date and time:  Wednesday, October 23 (12:00-19:00 CEST)

Ryvu has developed a potentially best-in-class MTA-cooperative PRMT5 inhibitor, RVU305, demonstrating favorable drug-like properties and effective PRMT5 inhibition dependent on MTA binding. Structure-based optimization has resulted in a compound exerting selective efficacy in MTAP-deleted cell lines and a DMPK profile suitable for oral administration. RVU305 exhibits robust antiproliferative activity in MTAP-null cancer models, with a favorable safety margin in MTAP wild-type cells. Comparative studies against other clinical-stage PRMT5 inhibitors confirmed RVU305’s favorable antitumor activity in vitro and in vivo. Overall, the findings highlight the potential of RVU305 as a promising therapeutic option for patients with MTAP-deleted cancers.

 

Abstract Title:  Discovery of WRN inhibitors as targeted therapy in the treatment of microsatellite unstable (MSI-H) tumors
Number:  ENA24-0364
Session date and time:  Wednesday, October 23 (12:00-19:00 CEST)

Ryvu is developing a series of potent and selective WRN helicase inhibitors that demonstrate pronounced efficacy in tumors with high microsatellite instability (MSI-H). These compounds show nanomolar potency in viability assays in MSI-H cell lines, with excellent selectivity over microsatellite-stable (MSS) cells. In in vivo studies, RVU305 strongly suppressed tumor growth in an MSI-H model (SW48) while not impacting the MSS model (SW620). Additionally, the compounds exhibit favorable pharmacokinetics, achieving optimal exposure and target engagement, further enhancing their therapeutic potential in MSI-H cancers.

Abstract Title:  Exploring synthetic lethality and novel drug combinations in patient-derived cells
Poster Number: ENA24-0395
Session date and time:  Wednesday, October 23 (12:00-19:00 CEST)

Ryvu has developed a proprietary platform, ONCO Prime, to discover novel synthetic lethal (SL) inhibitors targeting key oncogenic drivers such as KRAS and other mutations. Initial data are presented in colorectal cancer (CRC), but the platform has the potential to discover novel SL targets across all tumor types. ONCO Prime uses human intestinal stem cell (hISC)-derived cancer model cells, patient-derived xenografts (PDXs), and clinical samples to conduct genomic and functional analyses. By integrating CRISPR/Cas9 technology and machine learning, Ryvu generated isogenic cancer models, performed high-throughput screenings, and validated the findings through transcriptomic profiling of clinically relevant samples. This approach enabled the identification of essential and tumor suppressor genes critical for CRC and other cancers, focusing on SL targets specific to transformed cells.

Abstract Title: Phase I/II trial of RVU120, a CDK8/CDK19 inhibitor in patients with relapsed/refractory metastatic or advanced solid tumors
Number: 34
Session date and time: Wednesday, October 23 (12:00-19:00 CEST)

RVU120 is being tested in patients with solid tumors in an ongoing Phase I/II clinical trial, AMNYS-51. RVU120 has demonstrated a manageable safety profile across multiple dose levels and dosing schedules in patients with advanced or metastatic solid tumors. No dose-limiting toxicities (DLTs) were observed, and most treatment-emergent adverse events (TEAEs) were mild to moderate, with nausea and vomiting being the most common. Stable disease (SD) was achieved in multiple patients, with tumor size reductions in three patients with adenoid cystic carcinoma (AdCC). The recommended phase 2 dose (RP2D) for the QOD schedule was identified as 250 mg, with dose escalation continuing for the QD schedule. These promising safety and preliminary efficacy results support further clinical investigation of RVU120.

Investor Event:

Ryvu Therapeutics will host a webinar to discuss new data from our latest poster presentations. The date and time of the webinar will be announced soon.