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

• RVU120 Demonstrates Single-Agent Activity with a Complete Response, 4 Blast Reductions, and 4 Erythroid and/or Platelet responses in Patients with Relapsed/Refractory Acute Myeloid Leukemia (AML) or High-Risk Myelodysplastic Syndrome (HR-MDS);

• Preclinical Antitumor Activity of SEL24 (MEN1703) demonstrated in multiple myeloma (MM), Hodgkin’s lymphoma (HL), and diffuse large B-cell lymphoma (DLBCL) as well as in AML in combination with gilteritinib;

• Company to Host Investor Webinar on December 12 at 8 am CET (1 pm CT) to Review Data Presented. To register for the event, please click here.

KRAKOW, Poland, Dec. 11, 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 new data demonstrating clinical and preclinical activity of its selective CDK8/19 inhibitor RVU120 and its selective PIM/FLT3 inhibitor SEL24 (MEN1703) 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.

“The results presented at ASH from the ongoing Phase 1b trial of RVU120 in AML and HR-MDS, are very encouraging. RVU120 demonstrated meaningful clinical activity as monotherapy and was well tolerated across all doses,” said Hendrik Nogai, M.D., Chief Medical Officer of Ryvu. “We are continuing dose escalation and expect responses to deepen at higher levels of target inhibition. The results presented today give us increased confidence in the potential for RVU120 to improve the lives of patients with AML and HR-MDS.”

Phase 1b Interim Efficacy and Safety Results on RVU120 as of a cut-off date of November 11, 2022:

• 16 relapsed/refractory (R/R) acute myeloid leukemia (AML) and 3 high-risk myelodysplastic syndrome (HR-MDS) patients with a median of 3 prior lines of therapy have been treated with RVU120 at doses between 75 and 110 mg;
• Clinical activity was demonstrated in 9 out of 16 evaluable patients, all of them with molecular markers preclinically predicted to respond to CDK8 inhibition;
• One AML patient achieved a complete response;
• 4 patients demonstrated blast reductions;
• 4 patients showed erythroid and/or platelet responses;
• RVU120 was generally well tolerated at all doses;
• Most frequent adverse events were nausea/vomiting, worsening of thrombocytopenia grade 3 to 4, and febrile neutropenia;

After the data cut-off for the poster, dose escalation has continued, and the 110 mg dose cohort has now been fully enrolled. In total, 22 patients have been enrolled in the study through December 7, 2022.

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% in some patients, a threshold, that may be sufficient for robust efficacy in certain groups of super-responder patients. Combined results from the ongoing dose-escalation trials (in 10-135 mg dose range) in AML/HR-MDS and solid tumor patients indicate that pSTAT5 inhibition is dose-dependent.

Ryvu licensee, Menarini Group, and academic collaborators presented new 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 the mechanism of action was also 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. Indeed PIM-dependent oncogenic signaling pathways were also inhibited following SEL24 (MEN1703) treatment of MM cells.

“We are also excited to have SEL24 data featured by our partner Menarini demonstrating preclinical antitumor activity in multiple myeloma, classical Hodgkin lymphoma, diffuse large B-cell lymphoma, and AML in combination with gilteritinib,” added Dr. Nogai. “These presentations provide new insights into the epigenetic function of SEL24 and demonstrate its novel mechanisms of tumor inhibition across multiple blood cancer models.”

Investor Event

Management will host an investor webcast on Monday, December 12 at 8 am Central European Time (1 am Central Time US) to discuss the data presented. To listen to the webcast and view the accompanying slide presentation, please register here: https://ryvu.clickmeeting.com/ryvu-rvu120-clinical-data-ash-2022-posters/register. A replay will be available on the Investors page of the Company’s website.

Details of the poster presentations are as follows:

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 and functions 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 BioNTech, Exelixis, Galapagos, Menarini group 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 sWIG80 index. For more information, please see www.ryvu.com.

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