- Ryvu presents four posters at the 2024 ENA Symposium: (a)
RVU305 (MTA-cooperative PRMT5 inhibitor), demonstrating a
potentially best-in-class profile, (b) WRN program, in lead
optimization, (c) ONCO Prime platform, highlighting novel target
discovery in synthetic lethality and (d) RVU120, with an update
from the solid tumor study - AMNYS-51.
- Upcoming events:
- R&D Update at ENA 2024: webinar on Friday, October 25 at
11:00 AM CET. Link below.
- RVU120 Program Progress and Data Update: webinar on Thursday,
December 12 at 10:00 AM CET.
KRAKOW, Poland,
Oct. 23, 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, presents
four posters with clinical and preclinical data from RVU305
(MTA-cooperative PRMT5 inhibitor), WRN program, ONCO Prime, and
RVU120 at the 2024 EORTC-NCI-AACR Symposium (ENA), October 23-25,
Barcelona, Spain.
"It is an exciting time for Ryvu's pipeline as we advance a
potentially best-in-class PRMT5 inhibitor, RVU305, through
IND-enabling studies. We are pleased to highlight data from this
program, with expected initiation of clinical development in Q4
2025, and other Ryvu projects at the EORTC-NCI-AACR Symposium this
year. We are especially proud of our ONCO Prime target discovery
platform, which demonstrates the progress of our scientific efforts
on novel synthetic lethal (SL) inhibitors targeting key oncogenic
drivers such as KRAS and other mutations." - said
Krzysztof Brzózka, Ph.D., Chief Scientific
Officer.
Upcoming Events
- R&D Update at ENA 2024: webinar on Friday, October 25 at 11:00 AM CET to discuss the data presented at the
ENA Symposium. To join the webcast, please register here:
https://ryvu.clickmeeting.com/ryvu-ena-2024-results/register
- RVU120 Program Progress and Data Update: webinar on
Thursday, December 12, 10:00
AM CET to discuss the ongoing RVU120 Phase II
studies.
Poster highlights:
Poster
Title: Discovery of novel MTA-cooperative PRMT5
preclinical candidate as targeted therapeutics for MTAP-deleted
cancers
Poster Number: 32
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.
- RVU305 exhibits robust antiproliferative activity in
MTAP-null cancer models, including over 100% tumor growth
inhibition (TGI) at several dose levels and multiple complete
remissions (CRs) at several dose levels in a DoHH2 MTAP-deleted
model.
- Tolerability and selectivity towards MTAP-deleted cells
was also demonstrated in in vitro and in vivo
preclinical models.
- Overall, the findings highlight the potential of RVU305
preclinical candidate as a promising therapeutic option for
patients with MTAP-deleted cancers.
Poster Title: Exploring synthetic lethality and
novel drug combinations in patient-derived cells
Poster Number: 417
Session date and time: Friday, October 25
(09:00-15:00 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.
- Ryvu generated isogenic cancer models and validated them
through transcriptomic profiling of patient-derived xenografts
(PDXs) and patient-derived cell cultures to ensure clinical
relevance.
- The data presented in this poster highlights the outcomes of
chemical compound and CRISPR/Cas9 screenings, confirming the
reliability and relevance of our model for identifying new
therapeutic targets in oncology.
Poster Title: Discovery of WRN inhibitors as
targeted therapy in the treatment of microsatellite unstable
(MSI-H) tumors
Poster number: 107
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).
- Ryvu WRN inhibitors show nanomolar potency in viability assays
in MSI-H cell lines, with excellent selectivity over
microsatellite-stable (MSS) cells.
- In in vivo studies, Ryvu inhibitor strongly
suppressed tumor growth in an MSI-H model (SW48) while not
impacting the MSS model (SW620).
- The compounds exhibit favorable pharmacokinetics,
achieving optimal exposure and target engagement, further enhancing
their therapeutic potential in MSI-H cancers.
Poster Title: Phase I/II trial of RVU120, a
CDK8/CDK19 inhibitor in patients with relapsed/refractory
metastatic or advanced solid tumors
Poster 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.
- 6/8 patients with adenoid cystic carcinoma achieve a longer
duration of treatment on RVU120 compared with their most recent
prior line of therapy. A reduction of 20% of target lesions was
observed in 2 patients with adenoid cystic carcinoma.
- The recommended phase 2 dose (RP2D) for the QOD schedule
was identified as 250 mg and remains the primary dosing schedule in
clinical studies, but a continuous dosing schedule was explored and
could offer an alternative to patients: continuous every day
administration (QD) of RVU120 at doses of 100 mg and 150 mg is
considered safe and may improve tolerability of RVU120 compared
with 250 mg every other day.
Links to the presented posters can be found here:
https://ryvu.com/investors-media/publications/
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. MEN1703 (SEL24) 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
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