Ryvu Therapeutics Presents Preclinical Data on RVU120 and Synthetic Lethality Programs at the 2024 AACR Annual Meeting
- Ryvu PRMT5 inhibitors show potential best-in-class profiles, including a strong antiproliferative effect on MTAP-deleted cell lines and a good safety window versus MTAP WT cells.
- Ryvu's WRN inhibitor program has demonstrated target engagement and selective potency with a synthetic lethal effect; in vivo efficacy studies exhibited pronounced tumor growth inhibition in an MSI-H colorectal cancer xenograft model.
- Ryvu's proprietary ONCO Prime discovery platform, which recently received a PLN 26 million (approx.
USD 6.6 million ) grant from thePolish Agency for Enterprise Development , has identified novel drug targets in KRAS-mutant patient-derived cells (PDCs) with therapeutic potential in colorectal cancer; the ONCO Prime platform has broad potential across multiple tumor types. - RVU120 shows efficacy both as a monotherapy and synergistically in combination with ruxolitinib in preclinical models of myeloproliferative neoplasms, including myelofibrosis and polycythemia vera.
- MEN1703 (SEL24), presented by partner
Menarini Group , shows cytotoxic activity in myelofibrosis cell lines as a monotherapy and synergistically in combination with ruxolitinib.
KRAKOW,
"We are excited to present our latest advancements in oncology therapeutics at the AACR Annual Meeting this year. Strong preclinical data from our two lead synthetic lethality programs – PRMT5 and WRN – are encouraging as we make progress toward the identification of competitive clinical candidates," said
Krzysztof Brzózka, Ph.D., Chief Scientific Officer of
Dr. Brzózka added, "We are also proud of our ONCO Prime target discovery platform, which recently received a significant grant from the
The ONCO Prime target discovery platform aims to identify novel drug targets based on patient-derived primary cell cultures, omics characterization, and functional assays. It already supports preclinical development of Ryvu programs, including PRMT5 and WRN. In
AACR 2024 Poster highlights:
Abstract Title: 'Discovery of novel MTA-cooperative PRMT5 inhibitors as targeted therapeutics for MTAP-deleted cancers.'
Session
Session date and time:
Poster Number: 4598
- Ryvu has developed potentially best-in-class MTA-cooperative PRMT5 inhibitors showing favorable drug-like properties and effective PRMT5 inhibition dependent on MTA binding.
- Ryvu PRMT5 inhibitor has a robust antiproliferative effect on MTAP-deleted cell lines and provides a good safety window for MTAP WT cells, as shown in a wide cell line panel.
- Novel Ryvu compounds are characterized by significantly improved PK profile that allow for oral administration.
- I n vitro safety evaluations did not reveal any significant liabilities of the tested compounds.
- The correlation between compound exposure and on-target effect was confirmed in PK/PD and efficacy studies in MTAP-deleted tumor models.
Abstract Title: 'Discovery of WRN inhibitors as targeted therapy in the treatment of microsatellite unstable (MSI-H) tumors.'
Session
Session date and time:
Poster Number: 5942
- Structure-based optimization performed at Ryvu facilitated the rapid expansion and delivery of a compound library with novel intellectual property (IP), demonstrating target engagement in cells and selective potency over other RecQ family members.
- The pharmacokinetic properties of these compounds were favorable, allowing progress to in vivo studies, which confirmed the efficacy of Ryvu's WRN inhibitors in xenograft MSI-H cancer models.
- Data on Ryvu's WRN inhibitors provide pharmacological proof-of-concept with synthetic lethal effect and support WRN inhibition as a new, targeted oncological therapy in MSI-high tumors.
Abstract Title: 'A comprehensive platform for identification of KRAS-specific synthetic lethal targets using patient-derived cells.'
Session
Session date and time:
Poster Number: 4684
- Ryvu's cutting-edge drug discovery platform uniquely combines high throughput capabilities with the precision and translational impact traditionally associated with later, lower throughput stages.
- By leveraging human stem cell-derived model cells (PDC), patient-derived xenografts (PDXs) and clinical samples, we have created a groundbreaking approach to identifying synthetic lethal (SL) targets specific to oncogenic pathways.
- In conjunction with our novel ranking algorithm, these models have successfully identified potential drug targets in KRAS-mutant cells—targets that remained undetected in immortalized CRC cell lines, likely due to genetic and epigenetic alterations accumulated over years of cell culture.
- Chemical compound screening has produced promising results that have been further validated through comparison with a varied collection of patient-derived CRC cultures, ensuring the findings' reliability and clinical relevance.
- These data position Ryvu's primary model platform as an invaluable resource for target discovery research with broad applicability across a variety of tumors.
Abstract Title:
'Combination JAK1/2 and CDK8/19 inhibition demonstrates enhanced efficacy in myeloproliferative neoplasms.'
Session
Session date and time:
Poster Number: 7225
- RVU120, a highly selective and potent CDK8/19 inhibitor, shows potential efficacy as both monotherapy and in combination with ruxolitinib (RUX), a JAK1/2 inhibitor, for the treatment of myeloproliferative neoplasms (MPN) and polycythemia vera (PV).
- In vivo treatment with RVU120/RUX+RVU120 significantly reduced disease manifestation (splenomegaly, WBC, fibrosis scoring, hematopoiesis) compared to VEH/RUX.
- These data suggest that inhibition of JAK1/2 and CDK8/19 could be a novel therapeutic strategy in MPNs.
Abstract Title:
'MEN1703/SEL24 exhibits promising antitumoral activity in preclinical models of myelofibrosis both as a single agent and combined with ruxolitinib.'
Session
Session date and time:
Poster Number: 665
- MEN1703 (SEL24) demonstrates efficacy both as a monotherapy and in combination with the JAK inhibitor ruxolitinib (RUX) in preclinical models of myelofibrosis (MF).
- MEN1703 demonstrated anti-tumoral efficacy in MF preclinical models, exhibiting in vitro activity at clinically relevant concentrations. Notably, the combination of MEN1703 with the standard of care, RUX, exhibited synergistic effects and molecular analyses confirmed the inhibition of downstream targets of PIM.
- The results support the therapeutic potential and relevance of MEN1703 in treating myelofibrosis.
Posters are available on https://ryvu.com/our-research/.
About Ryvu Therapeutics
Ryvu's most advanced programs include RVU120, a selective CDK8/CDK19 kinase inhibitor with the potential to treat hematological malignancies and solid tumors, currently in Phase II development (i) as a monotherapy for the treatment of patients with relapsed/refractory acute myeloid leukemia (r/r AML) and high-risk myelodysplastic syndromes (HR-MDS) as well as (ii) in combination with venetoclax for the treatment of patients with r/r AML. Another clinical program, SEL24 (MEN1703), is a dual PIM/FLT3 kinase inhibitor licensed to the
The Company was founded in 2007 and is headquartered in Kraków,
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