- Updated data from the Phase I trial of RVU120 in
relapsed/refractory acute myeloid leukemia (r/r AML) or
high-risk myelodysplastic syndromes (HR-MDS) demonstrate clinically
relevant benefit in 50% of evaluable patients
- Preclinical data support RVU120 as a novel agent for the
treatment of patients with lower-risk MDS (LR-MDS) and show
cytotoxic and differentiating effects on leukemic stem
cells
- The published data strongly supports the RVU120 Phase II
development plans presented in October
KRAKOW, Poland, Nov. 2, 2023
/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,
today announced that clinical and preclinical data on RVU120, a
selective CDK8/19 inhibitor, will be presented on four posters at
the 65th American Society of Hematology (ASH) Annual
Meeting & Exposition, which is being held on December 9 –12, 2023 in San Diego, California.
"At this year's ASH conference, we are pleased to present
updated clinical and preclinical data that highlight the
potential of RVU120 to address hematologic malignancies," said
Hendrik Nogai, M.D., Chief Medical
Officer of Ryvu Therapeutics. "RVU120 continues to show
single-agent clinical activity in patients with AML and
HR-MDS, along with a tolerable safety profile. Notably, several
patients achieved a reduction of blasts in the bone marrow
including one complete response. We also observed hematologic
improvement supporting RVU120's further development as a treatment
for patients with LR-MDS and myelofibrosis. In addition,
evidence that RVU120 has cytotoxic and differentiating effects on
leukemic stem cells highlight its potential as frontline therapy in
AML."
Based on these data and in line with prior guidance, Ryvu's
development plan for RVU120 includes initiation of Phase II studies
in AML/HR-MDS as a monotherapy and in combination, in
myelofibrosis, and an investigator-initiated trial in LR-MDS.
Initiation of Ryvu-sponsored studies in AML is planned in Q4 2023,
and in the LR-MDS and myelofibrosis studies in H1 2024.
"Our internal Clinical Committee and a global network of
external experts have thoroughly assessed the clinical and
preclinical results of RVU120, and have recognized its significant
potential in the treatment of multiple hematological diseases. This
recognition is a crucial element in the recently presented RVU120
development plans," added Hendrik
Nogai.
Details on the poster presentations are as follows:
Abstract Title: "Safety and Efficacy Results from
CLI120-001 a Phase 1 Study in RR-AML and HR-MDS: Update from
Higher Dose Levels"
Session Name: 616. Acute Myeloid Leukemias: Investigational
Therapies, Excluding Transplantation and Cellular Immunotherapies:
Poster II
Session date and time: Sunday,
December 10, 2023, 6:00 PM - 8:00 PM
PST
Poster Number: 2913
Updated higher dose level Phase I data on RVU120 in patients
with relapsed/refractory (r/r) acute myeloid leukemia (AML) or
high-risk myelodysplastic syndrome (HR-MDS) demonstrate clinical
activity with a tolerable safety profile. 12 of 24
evaluable patients showed clinically relevant benefit, including
four blast reductions to <5% in the bone marrow: one complete
response and three marrow complete responses in patients with
HR-MDS. Three additional patients treated across different dose
levels experienced a sustained BM blast reduction, and five
patients achieved hematologic improvements. Dose-escalation data
continues to demonstrate relevant target inhibition at doses of 110
mg and higher.
Abstract Title: "Preclinical and Clinical Evidence for
Erythroid-Stimulating Activity of RVU120 CDK8/19 Inhibitor in AML
and MDS"
Session Name: 604. Molecular Pharmacology and Drug
Resistance: Myeloid Neoplasms: Poster II
Session date and time: Sunday,
December 10, 2023, 6:00 PM - 8:00 PM
PST
Poster Number: 2800
RVU120-induced erythroid differentiation was studied in primary
malignant stem cells from MDS patients and in a stem cell model. To
date, erythroid improvement has been observed in five evaluable
patients in the ongoing Phase Ib study. Bulk RNA-seq analysis
confirmed broad transcriptomic changes in the bone marrow (BM) of
selected patients after treatment compared to the pre-dose baseline
levels. Robust induction of genes involved in erythroblast
differentiation and hemoglobin metabolism genes were observed in
two AML with myelodysplasia-related changes (AML-MRC) and two AML
patients. These clinical and preclinical data strongly support the
further development of RVU120 as a novel agent for patients
with LR-MDS who are transfusion-dependent and failing first-line
therapy.
Abstract Title: "Targeting CDK8/CDK19 to Disrupt Leukemic
Stem Cell-like Population in Acute Myeloid Leukemia: Exploring
RVU120 As a Promising Frontline Therapy"
Session Name: 604. Molecular Pharmacology and Drug
Resistance: Myeloid Neoplasms: Poster III
Session date and time: Monday,
December 11, 2023, 6:00 PM - 8:00 PM
PST
Poster Number: 4175
Leukemic stem cells (LSC) are a small subset of AML cells that
can resist therapy and cause relapse. To achieve a cure for
patients, it is essential to eliminate LSCs. In preclinical models,
RVU120 displayed cytotoxic and differentiating effects on
well-characterized LSC populations. Single-cell studies further
revealed RVU120's ability to inhibit LSC-enriched populations and
induce differentiation. In summary, RVU120 emerges as a frontline
candidate in AML treatment, addressing therapeutic failures caused
by persistent LSCs.
Abstract Title: "Novel Clinically Useful Inhibitor of
Mediator Complex, RVU120, Relieves Differentiation Block in
MDS/AML"
Session Name: 636. Myelodysplastic Syndromes—Basic and
Translational: Poster II
Session date and time: Sunday,
December 10, 2023, 6:00 PM - 8:00 PM
PST
Poster Number: 3225
Data demonstrate the potential of inhibiting overexpressed
mediator complex proteins, including CDK8, to address
differentiation blocks and resulting anemias in MDS/AML. Treatment
of primary cells in bone marrow collected from MDS and AML patients
with RVU120 led to increased erythroid differentiation, as
evidenced by changes in the expression of erythroid differentiation
markers, including increased CD71 and Glycophorin A expression.
These studies provide supportive evidence for RVU120 as a drug
candidate in transfusion-dependent MDS/AML patients.
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 use diverse therapeutic mechanisms driven by
emerging knowledge of cancer biology, including small molecules
directed at kinase, synthetic lethality and immuno-oncology
targets.
Ryvu's most advanced programs are RVU120 — a selective
CDK8/CDK19 kinase inhibitor with potential
for the treatment of hematological malignancies and solid
tumors currently in phase I clinical development
for the treatment of acute myeloid leukemia and
myelodysplastic syndromes, and phase I/II for the treatment
of r/r metastatic or advanced solid tumors — and SEL24
(MEN1703), a dual PIM/FLT3 kinase inhibitor licensed to
the Menarini Group. Ryvu Therapeutics has signed multiple
partnering and licensing deals with global companies, including
BioNTech, Exelixis, Menarini and Merck.
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 see www.ryvu.com.
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