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

  • Poster presentations highlight preclinical data from Ryvu’s PRMT5 program in MTAP-Deficient cancers and its synthetic lethality platform in colorectal cancer models
  • Virtual webinar on PRMT5 data and progress to be held on Monday, October 16, at 9.30 am CEST
  • Preclinical efficacy data of MEN1703 (SEL24) in B-cell lymphomas to be presented by Ryvu’s partner Menarini

Krakow, Poland – October 4, 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, today 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.

“During this year’s AACR-NCI-EORTC conference, we will present data from our most advanced preclinical project on MTA-cooperative PRMT5 inhibitors, representing the flagship initiative within Ryvu’s synthetic lethality platform. Our PRMT5 inhibitors have demonstrated remarkable efficacy and selectivity in preclinical models of tumors with MTAP gene deletion, providing a strong foundation for further development,” said Krzysztof Brzozka, Ph.D., Chief Scientific Officer of Ryvu Therapeutics. “We will also present data on our synthetic lethality platform, highlighting the effective identification of molecular targets and precise optimization of lead molecules in a wide range of cancers.”

Ryvu licensee, Menarini Group, and academic collaborators will present preclinical data on MEN1703 (SEL24), a first-in-class, oral, dual type I PIM/FLT3 inhibitor. MEN1703 demonstrated promising anti-tumor activity across various B-cell lymphomas, highlighting its potential for clinical application.

Details on the poster presentations are as follows:

Abstract Title: Discovery of Novel MTA-cooperative PRMT5 Inhibitors as Targeted Therapeutics for MTAP-deleted Cancers”
Poster Number: C135
Session date and time: Saturday, October 14, 12:30 – 4:00 p.m. EST

Ryvu has developed potentially best-in-class MTA-cooperative PRMT5 inhibitors showing favorable properties and effective PRMT5 inhibition dependent on MTA. Structure-based lead optimization enabled rapid expansion and delivery of a compound library with novel intellectual property, high target engagement in cells, and selective potency in MTAP-deleted cell lines. These compounds have shown over 300-fold selectivity for MTAP-deficient cells compared to WT cells. The inhibitors can be orally administered and have demonstrated efficacy in animal tumor models, supporting their progression towards clinical trials.

Abstract Title:
A Comprehensive Platform for Unraveling the Molecular Mechanisms and Vulnerabilities of Colorectal Cancer: A Step Forward in Target Discovery”
Poster Number: A162
Session date and time:
Thursday, October 12, 12:30 – 4:00 p.m. EST

Colorectal cancer (CRC) is one of the most prevalent and deadly cancers globally. However, molecular mechanisms and vulnerabilities of CRC remain still poorly understood. Ryvu has developed a comprehensive platform using CRC model cells derived from human intestinal stem cells, patient-derived xenografts, and clinical samples. Through transcriptomic and genomic analyses using RNA-seq and whole-exome sequencing and the use of CRISPR/Cas9 system, samples were characterized, and distinct molecular signatures and pathways associated with different mutational variants were identified. Moreover, by utilizing normal intestinal stem cells from a healthy donor, we were able to identify among the essential genes those that are critical only for the transformed cells. This innovative platform provides a powerful tool for target discovery and validation in CRC, with potential applicability to other cancer types and personalized medicine approaches.

Abstract Title:
MEN1703/SEL24, A Potent PIM Inhibitor, Demonstrates Promising Anti-Tumor Activity in Activated B Cell Like DLBCL, Mantle Cell Lymphoma and Marginal Zone Lymphoma Cells”
Poster Number: C144
Session date and time:  Saturday, October 14, 12:30 – 4:00 p.m. EST

PIM kinases have been identified as potential therapeutic targets due to their overexpression and mutations in certain lymphomas. Pharmacological inhibition with MEN1703 (SEL24), a first-in-class, oral, dual type I PIM/FLT3 inhibitor was evaluated across various lymphoma cell lines. MEN1703 demonstrated anti-proliferative effects across a broad range of lymphoma cell lines. Importantly, MEN1703 was effective even in lymphoma cells resistant to other treatments and induced apoptosis in most cell lines. RNA-Seq indicated that the molecule modulates the transcriptome of highly responsive DLBCL cell lines differently from other, poorly responsive cells, providing clues to mechanisms involved in sensitivity to PIM inhibitors and supporting potential in treating B-cell lymphomas.

Ryvu will host a webinar on Monday, October 16, at 9:30 am CEST to discuss the PRMT5 data. To join the webcast, please register here: https://bit.ly/3RL1YWp.