Ryvu Therapeutics Announces Multiple Presentations of Clinical and Translational Data of RVU120 and SEL24 (MEN1703) at the 2022 American Society of Hematology (ASH) Annual Meeting

• Six Presentations Highlight the Clinical and Preclinical Activity of RVU120 and SEL24 (MEN1703)

• RVU120 Demonstrates Single-Agent Activity with a Complete Response and Disease Stabilization in 10 Patients with Relapsed/Refractory Acute Myeloid Leukemia (AML) or High-Risk Myelodysplastic Syndrome (HR-MDS)

• Preclinical Models Show Potential for Clinical Efficacy of SEL24 (MEN1703) in multiple myeloma (MM), Hodgkin’s lymphoma (HL), anddiffuse large B-cell lymphoma (DLBCL)

KRAKOW, Poland, Nov. 03, 2022 (GLOBE NEWSWIRE) -- 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 new data demonstrating clinical and preclinical activity of its selective CDK8/19 inhibitor RVU120 and its selective PIM/FLT3 inhibitor SEL24 (MEN1703) will be presented at the 64^th American Society of Hematology (ASH) Annual Meeting & Exposition, which is being held on December 10 –13, 2022, in New Orleans, Louisiana.

Updated Phase 1b efficacy and safety data will be presented for RVU120 at doses between 75 and 110 mg in patients with relapsed/refractory (R/R) acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome (HR-MDS). As of the cut-off date of July 25, 2022, 17 patients have been treated with RVU120. One patient achieved a complete response and 10 patients achieved disease stabilization. RVU120 demonstrated a manageable safety profile.

Additionally, the on-target activity of RVU120 was evaluated in AML and HR-MDS patient samples by measuring changes in pSTAT5 levels. As of the cut-off date, the inhibition of pSTAT5 reached >50%, a threshold that based on preclinical predictions is sufficient for robust efficacy in certain groups of super-responder patients.

Ryvu licensee, Menarini Group, and academic collaborators will present data on SEL24 (MEN1703), a first-in-class, oral, dual type I PIM/FLT3 inhibitor. Combination therapy of SEL24 (MEN1703) with gilteritinib, a highly potent and selective oral FLT3 inhibitor, induces strong tumor regression and complete responses in-vivo, demonstrating the potential of concomitant FLT3 and PIM inhibition kinases in AML.

SEL24 (MEN1703)-induced PIM inhibition and mechanism of action will also be demonstrated in-vitro in multiple myeloma (MM), classical Hodgkin lymphoma-tumor-associated macrophages (cHL-TAMs), and diffuse large B-cell lymphoma (DLBCL) models. In multiple myeloma preclinical models, SEL24 (MEN1703) induces cytotoxicity of MM cell lines, disrupts MM endothelial cell vessel formation, and decreases the activity of several pathways essential for myeloma cell survival. This study demonstrates the promising therapeutic potential of SEL24 (MEN1703) in MM and reveals the underlying mechanism of PIM inhibition.

“We look forward to presenting updated, positive data from our ongoing Phase 1b trial of RVU120 in both AML and HR-MDS, demonstrating clinical activity and manageable safety profile,” said Hendrik Nogai, M.D., Chief Medical Officer of Ryvu Therapeutics. “Dose-escalation data continues to achieve target inhibition at the current doses, and we expect increased inhibition as the study progresses. We are also proud that our partner Menarini will showcase multiple preclinical data on SEL24 showing potential efficacy across multiple blood cancer models. These presentations mark the growth of our understanding of the role of CDK8/19 and PIM/FLT3 in tumorogenesis and continued progress in clinical and preclinical development.”

CDK8/19 Kinase Inhibitor RVU120 in Patients with AML or Higher-Risk MDS: Safety and Efficacy Results from New Dose Escalation Cohorts (Publication Number: 2771), Camille Abboud, MD (Washington University in Saint Louis/ Washington University School of Medicine) et al.

• Session Name: 616. Acute Myeloid Leukemias: Investigational Therapies, Excluding Transplantation and Cellular Immunotherapies: Poster II
• Date: Sunday, December 11, 2022
• Presentation Time: 6:00 PM - 8:00 PM

Multiomics Analysis Confirms Effective Target Engagement for RVU120 – a First-in-class CDK8/19 Kinase Inhibitor in AML and MR-MDS Patients and Reveals the Mechanism of Action (Publication Number: 2642), Tomasz Rzymski, Ph.D. (Ryvu Therapeutics) et al.

• Session Name: 604. Molecular Pharmacology and Drug Resistance: Myeloid Neoplasms: Poster II
• Date: Sunday, December 11, 2022
• Presentation Time: 6:00 PM - 8:00 PM

PIM Inhibition by SEL24 (MEN1703) Combines Synergistically with gilteritinib in FLT3-ITD Preclinical Models of Acute Myeloid Leukemia (Publication Number: 1333), Daniela Bellarosa (Menarini Group) et al.

• Session Name: 604. Molecular Pharmacology and Drug Resistance: Myeloid Neoplasms: Poster I
• Date: Saturday, December 10, 2022
• Presentation Time: 5:30 PM - 7:30 PM

Super-enhancer-driven PIM Kinase Upregulation in Multiple Myeloma Maintains the Plasma Cell-specific Oncogenic and Microenvironmental Circuits and Can Be Efficiently Targeted by the Pan-PIM Inhibitor MEN1703 (Publication Number: 1822), Filip Garbicz (Institute of Hematology and Transfusion Medicine, Warsaw, Poland) et al.

• Session Name: 651. Multiple Myeloma and Plasma Cell Dyscrasias: Basic and Translational: Poster I
• Date: Saturday, December 10, 2022
• Presentation Time: 5:30 PM - 7:30 PM

PIM Kinases Regulate Super-Enhancer-Dependent Gene Expression In Diffuse Large B-Cell Lymphoma (Publication Number: 1310), Sonia Debek, (Institute of Hematology and Transfusion Medicine, Warsaw, Poland) et al.

• Session Name: 603. Lymphoid Oncogenesis: Basic: Poster I
• Date: Saturday, December 10, 2022
• Presentation Time: 5:30 PM - 7:30 PM

MEN1703-mediated PIM kinases inhibition impairs protumoral and immunosuppressive phenotype andfunctions of macrophages in classical Hodgkin Lymphoma, (Publication Number: 2867), Maciej Szydlowski (Institute of Hematology and Transfusion Medicine, Warsaw, Poland) et al.

• Session Name: 622. Lymphomas: Translational–Non-Genetic: Poster II
• Date: Sunday, December 11, 2022
• Presentation Time: 6:00 PM - 8:00 PM

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.

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 syndrome, 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, currently in phase II clinical studies in acute myeloid leukemia. Ryvu Therapeutics has signed multiple partnering and licensing deals with global companies, including Merck, Menarini Group, Galapagos 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 sWIG80 index. For more information, please see www.ryvu.com.

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