Ryvu Therapeutics Presents Positive Phase I Data for RVU120 at the Virtual 26th Annual Congress of the European Hematology Association. Phase I/II Data for SEL24 (MEN1703) presented by development partner Menarini

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)

• Poster ID: 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)

• Poster ID: 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.

SOURCE Ryvu Therapeutics

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