Ryvu Therapeutics Presents Data on RVU120 at the 2023 American Society of Hematology (ASH) Annual Meeting

• Clinical activity observed in 50% of evaluable patients with relapsed/refractory acute myeloid leukemia (r/r AML) or high-risk myelodysplastic syndromes (HR-MDS) treated with RVU120 monotherapy, including a complete response.
• Treatment continues to show a favorable safety profile with 50-70% target engagement achieved at a dose of 250 mg.
• The published clinical and non-clinical data strongly support RVU120’s Phase II development plans presented in October.
• A webinar discussing the data presented at the ASH 2023 conference will take place on Sunday, December 10, at 11:00 PM (PST) / Monday, December 11, at 8:00 AM (CET).Registration is available at: ryvu.clickmeeting.com/ryvu-ash-2023-results/register.

KRAKOW, Poland, Dec. 11, 2023 (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, presents clinical and preclinical data on RVU120, a selective CDK8/19 inhibitor, at the 65^th American Society of Hematology (ASH) Annual Meeting & Exposition, which is held on December 9-12, 2023, in San Diego, California.

“The results from the CLI120-001 (RIVER-51) study of RVU120 in patients with r/r-AML and HR-MDS continue to improve over time. RVU120 monotherapy shows signs of clinical activity in 50% of evaluable patients, including a complete response, multiple clinically significant blast reductions, hematologic improvements, and reduction of bone marrow fibrosis. In particular, early signs of efficacy were observed in patients with NPM1 mutation, DNMT3a mutation, and in those with HR-MDS,” said Hendrik Nogai, M.D., Chief Medical Officer of Ryvu Therapeutics. “We are pleased with the 50-70% target engagement achieved at 250 mg dose, which, based on our preclinical data, is anticipated to result in robust antileukemic efficacy in selected settings.”

Dr. Nogai continued: “Given the observed hematologic improvements, particularly the early signs of erythroid responses in seven patients, we believe that RVU120 holds the potential to be a novel erythropoiesis-stimulating agent for patients with LR-MDS and myelofibrosis. Furthermore, the non-clinical study supports RVU120’s development as a frontline targeted therapy in AML, as evidenced by its cytotoxic and differentiating effects on well-characterized leukemic stem cell-like populations. Based on these encouraging results, we plan to initiate Phase II studies in patients with AML, HR-MDS, LR-MDS, and myelofibrosis.”

Posters highlights featured at the Meeting:

Abstract Title: “Safety and Efficacy Results from CLI120-001 a Phase 1 Study in RR-AML and HRMDS: Update from Higher Dose Levels”
Session Name: 616. Acute Myeloid Leukemias: Investigational Therapies, Excluding Transplantation and Cellular Immunotherapies: Poster II
Session date and time: Sunday, December 10, 2023, 6:00 PM - 8:00 PM PST
Poster Number: 2913

Updated Phase I data on RVU120 at higher dose levels in patients with relapsed/refractory (r/r) acute myeloid leukemia (AML) or high-risk myelodysplastic syndromes (HR-MDS) demonstrate clinical activity with a favorable safety profile. As of the data cut-off on November 10, 2023, 38 patients (34 with AML and four with HR-MDS) have been treated in the trial at doses up to 250 mg. Of the 28 evaluable patients, 14 showed clinically relevant benefits, including eight blast reductions to <5% in the bone marrow. Among these, there was one complete response, three marrow complete responses, and four clinically relevant BM blast reductions. Five additional patients achieved transfusion independence, and one achieved an absolute difference of >4 RBC units compared to the baseline, following Cheson 2006 criteria. One patient received a transplant after nearly four months of treatment. The first evaluable patient at 250 mg showed significant blast reduction (64%) at the end of cycle 2. Doses up to 250 mg have shown a favorable safety profile, with 50-70% target engagement achieved at a dose of 250 mg.

Abstract Title: “Preclinical and Clinical Evidence for Erythroid-Stimulating Activity of RVU120 CDK8/19 Inhibitor in AML and MDS”
Session Name: 604. Molecular Pharmacology and Drug Resistance: Myeloid Neoplasms: Poster II
Session date and time: Sunday, December 10, 2023, 6:00 PM - 8:00 PM PST
Poster Number: 2800

RVU120-induced erythroid differentiation was studied in primary malignant stem cells from MDS patients and in a stem cell model. To date, early signs of erythroid response, at the molecular level measured by increased erythroid surface markers CD71 and/or CD235a expression, were observed in seven evaluable patients in the ongoing Phase Ib. Four out of seven patients had a clinically relevant hematological response. Transcriptomic analyses of bone marrow cells in patients treated with RVU120 showed specific induction of gene expression programs leading to the maturation of erythroid cells in two out of four patients, who also exhibited clinical hematologic improvement.

These clinical and preclinical data support further development of RV120 as a novel erythroid stimulating agent. Treatment with RVU120 could be a promising treatment option for patients with lower-risk MDS who are transfusion-dependent and failing previous lines of treatment.

Abstract Title: “Novel Clinically Useful Inhibitor of Mediator Complex, RVU120, Relieves Differentiation Block in MDS/AML”
Session Name: 636. Myelodysplastic Syndromes—Basic and Translational: Poster II
Session date and time: Sunday, December 10, 2023, 6:00 PM - 8:00 PM PST
Poster Number: 3225

Data demonstrate RVU120’s potential for erythroid-stimulating activity in CD34+ primary samples of myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). Treatment with RVU120 in MDS and AML models, including patient-derived sample cultures, resulted in increased erythroid differentiation, as evidenced by increased expression of erythroid surface markers. Additionally, inhibition of CKD8/19 led to transcriptional silencing in MDS-L cells. Notably, RVU120 also inhibits phosphorylation of STAT5 and STAT1, which may represent the underlying mechanism of action. These results provide supporting rationale for further development of RVU120 for transfusion-dependent MDS/AML patients.

Posters are available on Ryvu corporate website.

Additionally, the two posters listed below will be made public on December 11, 2023, at 9:00 AM PST/18:00 CET.

Abstract Title: “Targeting CDK8/CDK19 to Disrupt Leukemic Stem Cell-like Population in Acute Myeloid Leukemia: Exploring RVU120 As a Promising Frontline Therapy”
Session Name: 604. Molecular Pharmacology and Drug Resistance: Myeloid Neoplasms: Poster III
Session date and time: Monday, December 11, 2023, 2023, 6:00 PM - 8:00 PM PST
Poster Number: 4175

Abstract Title: “Mediator Kinase/CDK8 Inhibition as a Strategy to Improve FLT3 Inhibitor Activity in Acute Myeloid Leukemia”
Session Name: 604. Molecular Pharmacology and Drug Resistance: Myeloid Neoplasms: Poster III
Session date and time: Monday, December 11, 2023, 6:00 PM-8:00 PM PST
Poster Number: 4173

Investor Event

Ryvu will host a webinar on Sunday, December 10, at 11:00 PM PST / Monday, December 11, at 8:00 AM CET, to discuss the data presented at the ASH Annual Meeting. To join the webcast, please register here: ryvu.clickmeeting.com/ryvu-ash-2023-results/register.

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 use 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 Ib clinical development for the treatment of acute myeloid leukemia and myelodysplastic syndromes, 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. Ryvu Therapeutics has signed multiple partnering and licensing deals with global companies, including BioNTech, Exelixis, Menarini, 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 mWIG40 index. For more information, please see www.ryvu.com.

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