KRAKOW, Poland, Dec. 1,
2020 /PRNewswire/ -- Ryvu Therapeutics (WSE: RVU), a
clinical-stage biopharmaceutical company developing novel small
molecule therapies that address emerging targets in oncology,
announced today the positive results of the pharmacodynamic assay
demonstrating target engagement in the dose escalation part of the
DIAMOND-01 trial (CLI24-001; clinicaltrials.gov identifier
NCT03008187), a study investigating SEL24/MEN1703, a
first-in-class, orally available, dual PIM/FLT3 inhibitor as single
agent in acute myeloid leukemia (AML).
The poster entitled "SEL24/MEN1703 provides PIM/FLT3
Downstream Pathway Inhibition in Acute Myeloid Leukemia (AML) Blast
Cells: Results of the Pharmacodynamic (PD) Assay in the Dose
Escalation Part of First-in-Human DIAMOND Trial" will be
presented at the 62nd American Society of Hematology
(ASH) Annual Meeting and Exposition, which will take place
virtually on December 5-8.
"We are very happy to see SEL24/MEN1703 progressing through
clinical development. The positive preliminary data from the dose
escalation phase of DIAMOND-01 trial shows a manageable safety
profile, signs of efficacy and a meaningful target engagement in
peripheral blood and bone marrow blast cells of AML patients
treated with SEL24/MEN1703," said Setareh Shamsili, MD, PhD,
Chief Medical Officer of Ryvu Therapeutics. "At the same time,
we are delighted to see that further research performed on PIM
kinases inhibition as a potential therapeutic strategy in other
hematologic malignancies – such as diffused large B-cell lymphoma
and multiple myeloma – is ongoing in cooperation with our global
development partner and trial sponsor Menarini and our academic
partners, and results show promising potential for targeting PIM
kinases in other hemato-oncology indications. Together with
Menarini, we are fully focused on delivering the most effective and
safe treatment options to cancer patients worldwide."
DIAMOND-01 is the First-in-Human, Phase I/II dose escalation and
cohort expansion trial of SEL24/MEN1703, in-licensed from Ryvu
Therapeutics by Menarini, in AML. The study has completed the dose
escalation part showing a manageable safety profile up to the
recommended dose of 125 mg/day, with initial evidence of
anti-leukemic activity in a single agent setting.
The objective of the pharmacodynamic assessment was to
investigate the degree of target engagement achieved at different
doses of SEL24/MEN1703, by evaluating the phosphorylation of S6
(pS6), a downstream effector of the PIM/FLT3 signaling pathway. In
addition, the correlation between pS6 levels and the anti-leukemic
effect of SEL24/MEN1703 was assessed in samples collected from
patients enrolled in the dose escalation part of the DIAMOND-01
trial. The quantitative assessment of pS6 at a single-cell level
was performed both on peripheral blood (PB) and bone marrow (BM)
blast cells samples.
The results of this assay confirmed that meaningful target
engagement has been achieved, both in PB and BM blast cells, in
patients treated with SEL24/MEN1703 at 100 mg/day (one dose level
below the recommended dose) and at 125 mg/day. Moreover,
preliminary data suggest that the PIM/FLT3 pathway inhibition might
be associated with blast count reduction, particularly in those
patients showing high phosphorylation of S6 at baseline.
Longitudinal monitoring of PD will be continued in the cohort
expansion part of the DIAMOND-01 trial, which is currently
recruiting patients with relapsed or refractory AML in both the EU
and the US.
Two additional posters regarding the potential therapeutic
effect of PIM kinases inhibition – in both cases carried out using
SEL24/MEN1703 - in other hematological cancers, namely diffuse
large B-cell lymphoma and multiple myeloma, will also be published
at the 62nd American Society of Hematology (ASH) Annual Meeting and
Exposition; :
- "Inhibition of PIM Kinases in Diffuse Large B-Cell Lymphoma
Cells Targets MYC-Dependent Transcriptional Program, Increases CD20
Expression and Augments the Efficacy of Anti-CD20 Antibodies,"
characterizing a PIM-MYC regulatory circuit promoting DLBCL growth
and resistance to anti-CD20 antibody, as well as demonstrating that
PIM inhibition exhibits pleiotropic effects that combine direct
cytotoxicity with increased surface CD20 levels and increased
susceptibility to anti-CD20 antibody-based therapies;
- "PIM Kinase Inhibition Decreases the Proangiogenic
Properties of Multiple Myeloma Cells and Affects the Metabolic
State of the Vascular Endothelium," which demonstrates
that PIM inhibition induces MM cell death and abolishes important
tumor cell-ECs interactions. In addition, research shows that PIM3
is overexpressed in MM tumor endothelial cells and PIM inhibition
disrupts the activation state in in vitro cultured ECs.
Hence, targeting PIM kinases may represent an efficient approach to
induce tumor cell death and to block angiogenesis in MM.
About Ryvu
Ryvu Therapeutics is a clinical stage drug discovery and
development company developing novel small molecule therapies that
address emerging targets in oncology. Pipeline candidates make use
of diverse therapeutic mechanisms driven by emerging knowledge of
cancer biology, including small molecules directed at kinase,
synthetic lethality, immuno-oncology and cancer metabolism targets.
SEL120 is a selective CDK8/CDK19 kinase inhibitor with potential
for the treatment of hematological malignancies and solid tumors
currently in Phase 1b clinical
development for the treatment of acute myeloid leukemia and
myelodysplastic syndrome. The second clinical program of Ryvu is
SEL24/MEN1703, a dual PIM/FLT3 kinase inhibitor licensed to the
Menarini Group, currently in Phase II clinical studies in acute
myeloid leukemia.
Other Ryvu programs developed through internal discovery
platform are focused on new oncology targets.
The Company was founded in 2007 (until 2019 operating under the
name Selvita S.A.) and currently employs more than 150 associates,
including more than 80 PhDs. Ryvu is headquartered in Krakow, Poland.
Ryvu Therapeutics is listed on the main market of the Warsaw
Stock Exchange, and has been a component of sWIG80 index since
March 2017. For more information,
please see www.ryvu.com.
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