KRAKOW, Poland, June 11,
2021 /PRNewswire/ -- Ryvu Therapeutics (WSE:RVU) today
announced the online publication of two posters and an oral
presentation demonstrating clinical and pre-clinical activity of
its selective CDK8/19 inhibitor RVU120 (previously SEL120) and the
dual PIM/FLT3 inhibitor SEL24 (MEN1703), in-licensed by Menarini
Group from Ryvu Therapeutics, at the Annual European Hematology
Association (EHA) 2021 Virtual Congress.
RVU120: orally available CDK8/19 inhibitor
RVU120 (SEL120) is a highly selective first-in-class CDK8/CDK19
inhibitor, which has demonstrated efficacy in a number of solid
tumor types in in vitro and in vivo models as
well as in onco-hematological malignancies. The first-in-human
(FIH) Phase I study with RVU120, in relapsed or refractory acute
myeloid leukemia (AML) or high-risk myelodysplastic syndromes
(HRMDS), is being conducted at 5 investigational sites in the US
(https://clinicaltrials.gov/ct2/show/NCT04021368).
The data presented at EHA 2021 covers the first four dose
cohorts, in which RVU120 demonstrated favorable safety and PK
profile. No DLTs were observed, and all of the reported SAEs were
assessed as unlikely or not related to study drug.
Results are reported on the first five patients to receive
treatment with RVU120, and the clinically relevant responses were
observed in patients in the two highest dose cohorts reported:
- The Cohort 3 (50mg dose, subsequently escalated to 75 mg)
patient, with HRMDS, demonstrated an erythroid response from Cycle
5 to Cycle 8 and continues on RVU120 treatment in Cycle 13 with
stable disease. An erythroid response reflects a reduction in red
blood cell transfusions vs. baseline.
- The Cohort 4 (75mg dose) patient, with relapsed/refractory AML,
showed a response from C2 with persistence of skin leukemia, which
completely resolved at C7 resulting in a CR. This patient was
previously refractory to venetoclax + HMA, which is a patient
population associated with poor prognosis.
Furthermore, translational data will be presented as part of an
Oral Session and provide a potential linkage between in vitro data
showing erythroid differentiation and erythroid response in the
clinic. In vitro data demonstrate that RVU120 can induce erythroid
cells to differentiate and therefore rescue anemia
in preclinical models.
Presented results indicate strong erythroid differentiation
potential of RVU120 (SEL120) in (Lin-) CD34+, that acquired genetic
abnormalities resulting in arrested erythroid commitment, a
characteristic of many MDS and AML subtypes. Detailed
transcriptomic profiling strongly associated differentiation with
enrichment of genes representing regulators of erythroid commitment
and hemoglobin metabolism. Further studies are warranted to
investigate efficacy of RVU120 (SEL120) in anemias associated with
bone marrow failures in AML and MDS patients.
"We are excited to see early signs of clinical efficacy for
RVU120 in both AML and high risk MDS patients who were previously
treated with multiple lines of therapy. These patients had poor
prognosis prior to treatment with RVU120, so we anticipate that
RVU120 could serve an area of high unmet medical need. The
translation of erythroid differentiation in vitro to potential
erythroid responses in patients is an exciting clinical
benefit as these patients require fewer red blood cell
transfusions" – said Setareh Shamsili, MD, PhD, Chief Medical
Officer and EVP at Ryvu Therapeutics.
Oral Presentation: "RVU120/SEL120 CDK8/19 inhibitor -
a drug candidate for the treatment of MDS can induce erythroid
differentiation in transformed CD34+ hematopoietic progenitor
cells" (S164)
- Presentation ID: p412-5
- Date and Time: on-demand video recording is now available,
followed by a Live Q&A Session on Wednesday, June 16 (13:00
- 13:45 CEST)
Poster Presentation: "CLI120-001 Phase1b Study of
SEL120/RVU120 in patients with AML or High Risk MDS: Preliminary
clinical and PK results from initial dose escalation cohorts"
(EP480)
SEL24/MEN1703: orally available dual PIM/FLT3
inhibitor
A clinical poster on the first-in-human study of SEL24/MEN1703,
the DIAMOND-01 trial conducted by Ryvu's partner Menarini Group,
reports four objective responses across the dose escalation (n=25)
and cohort expansion (n=23) in patients with AML, with 3 of those 4
responders harboring an IDH mutation. Notably, three out of five
patients with IDH mutations treated at doses of 75-125 mg achieved
a CR/CRi, including a patient that relapsed on the IDH-inhibitor
enasidenib. Furthermore, one patient with an IDH1 mutation achieved
a CRi and underwent allogeneic-HSCT.
At the recommended dose (n=30) of 125mg/day as selected in the
dose escalation phase, SEL24/MEN1703 showed a manageable safety
profile. Most Grade 3 or higher treatment-emergent adverse events
(TEAEs) were hematologic or infectious in nature.
"We are thrilled to share encouraging results for SEL24
(MEN1703) in treating patients with Acute Myeloid Leukemia," said
Dirk Laurent, M.D., Global
Therapeutic Area Head – Oncology at Menarini Ricerche,
the R&D division of the Menarini Group. "The data, which
is presented in our posters at both ASCO and EHA annual
meetings, provides a strong rationale for further clinical
development, including the potential to focus on a molecularly
defined subset of patients – AML patients with IDH mutations. This
accomplishment reflects our sustained commitment to improving the
lives of patients with difficult-to-treat cancer and underscores
the value of our precision oncology approach."
Poster Presentation: "Results from DIAMOND-01
(CLI24-001) TRIAL: First in Human Study of SEL24/MEN1703, a
Dual PIM/FLT3 Kinase Inhibitor, in Patients with Acute Myeloid
Leukemia" (EP455)
All presentations and posters are now available online and can
be obtained from conference site: https://eha2021.ehaweb.org/
https://ehaweb.org/
On June 11, at
1:00 PM CEST (7:00 AM ET), Ryvu Therapeutics will hold a
conference call to discuss the data presented at EHA 2021.
Join the call at: live.ryvu.com
(or
https://ryvu.clickmeeting.com/discussion-on-ryvu-data-presented-at-eha-2021)
About RVU120 (SEL120)
RVU120 (SEL120) is a selective first-in-class CDK8/CDK19
inhibitor, which has demonstrated efficacy in a number of
solid tumor types in in vitro and in vivo models as well as in
onco-hematological malignancies. The first-in-human (FIH) phase I
study with RVU120, in relapsed or refractory AML or high-risk
myelodysplastic syndromes (HRMDS), is currently enrolling patients
at 5 investigational sites in USA
(https://clinicaltrials.gov/ct2/show/NCT04021368).
Translational data suggest that RVU120 is particularly effective
in undifferentiated AML STAT5-positive cancers. Administration of
RVU120 in orthotopic AML patient derived xenograft models reduced
tumor burden to the level undetectable in the peripheral blood,
decreased splenomegaly and resulted in partial bone marrow recovery
at well tolerated doses.
In addition, RVU120 has demonstrated single agent efficacy in
multiple solid tumor models. On May 28,
2021, Ryvu's Clinical Trial Application (CTA) to commence a
single-agent, open-label Phase I/II trial, investigating the safety
and efficacy of RVU120 (SEL120) in patients with
relapsed/refractory metastatic or advanced solid tumors, was
approved by the Polish Office for Registration of Medicinal
Products, Medical Devices and Biocidal Products, and the respective
Central Ethics Committee.
On March 25, 2020, the U.S. Food
and Drug Administration (FDA) granted an orphan drug designation
(ODD) to RVU120, for the treatment of patients with acute myeloid
leukemia (AML).
On April 7, 2021, U.S. Food and
Drug Administration, FDA, placed a partial clinical hold on the
first in human Phase Ib, dose escalation clinical trial of RVU120
in patients with relapsed/refractory (R/R) AML and high-risk MDS.
Patients who are currently taking RVU120 may continue treatment.
Ryvu continues to work closely with the FDA to resolve the partial
clinical hold with the objective of resuming enrollment
in the study.
RVU120 (SEL120) has been internally discovered by Ryvu and has
received support from the Leukemia & Lymphoma Society
Therapy Acceleration Program® (TAP), a strategic initiative to
partner directly with innovative biotechnology companies and
leading research institutions to accelerate the development of
promising new therapies for blood cancers.
About SEL24 (MEN1703)
SEL24 (MEN1703), a first-in-class, orally available, dual
PIM/FLT3 kinase inhibitor discovered and initially developed by
Ryvu Therapeutics and licensed to the Menarini Group. SEL24
(MEN1703) is currently evaluated in DIAMOND-01 trial (CLI24-001;
clinicaltrials.gov identifier NCT03008187), a First-in-Human, Phase
I/II, dose escalation and cohort expansion trial, as single agent
for the treatment of patients with Acute Myeloid Leukemia
(AML).
In the dose escalation part of DIAMOND-01 trial, SEL24 (MEN1703)
demonstrated a manageable safety profile up to the recommended dose
(RD) of 125 mg/day, along with initial evidence of anti-leukemic
activity in a single agent setting, particularly in patients with
IDH mutant disease either naïve or previously exposed to IDH
inhibitors, warranting further investigation of the compound in
molecularly defined subset of 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 make use of diverse therapeutic mechanisms
driven by emerging knowledge of cancer biology, including small
molecules directed at kinase, synthetic lethality, and
immuno-oncology targets. RVU120 (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. SEL24
(MEN1703) is a dual PIM/FLT3 kinase inhibitor licensed to the
Menarini Group, currently in Phase II clinical studies in acute
myeloid leukemia.
The Company was founded in 2007 (until 2019 operating under the
name Selvita S.A.) and currently employs over 160 associates,
including more than 80 PhDs. Ryvu is headquartered in Krakow, Poland. Ryvu is listed on the main market of
the Warsaw Stock Exchange, and is a component of sWIG80 index. For
more information, please see www.ryvu.com.
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