- 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, Oct. 9, 2024
/PRNewswire/ -- 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.
About Ryvu Therapeutics
Ryvu Therapeutics is a
clinical-stage drug discovery and development company focused on
novel small-molecule therapies that address emerging targets in
oncology. Internally discovered pipeline candidates at Ryvu
use diverse therapeutic mechanisms driven by emerging
knowledge of cancer biology, including small molecules directed
at kinases, synthetic lethality, and
immuno-oncology targets.
Ryvu's most advanced program is RVU120, a selective CDK8/CDK19
kinase inhibitor with the potential to treat hematological
malignancies and solid tumors. RVU120 is 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) – the RIVER-52 study,
(ii) in combination with venetoclax for the treatment of patients
with r/r AML – the RIVER-81 study, (iii) as a monotherapy for
the treatment of patients with lower-risk myelodysplastic syndromes
(LR-MDS) – the REMARK study. SEL24 (MEN1703) is a dual PIM/FLT3
kinase inhibitor licensed to the Menarini Group that is expected to
start a Phase II study in diffuse large B-cell lymphoma
(DLBCL) in Q4 2024. RVU305, a potentially best-in-class
PRMT5 inhibitor aiming to treat multiple solid tumors, is currently
undergoing IND/CTA-enabling studies. Ryvu Therapeutics is also
engaged in oncology collaborations with BioNTech and Exelixis.
The Company was founded in 2007 and is headquartered in Kraków,
Poland. Ryvu is listed on the
Warsaw Stock Exchange and is a component of the mWIG40 index. For
more information, please visit www.ryvu.com, X.com,
linkedin.com
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