Current Report ESPI 13/2025

The Management Board of Ryvu Therapeutics S.A. with its registered office in Krakow, Poland (“Company”, “Ryvu”) announces that it will present clinical and preclinical data from RVU120 at the 2025 European Hematology Association Congress (EHA), June 12-15, Milan, Italy. 

 

Details on the abstract presentations are as follows (cut-off date February 2025):  

Abstract Title (oral presentation): RVU120 enhances erythroid potential in MDS patient-derived cells: preclinical mechanistic insights into CDK8/CDK19 inhibition and potential patient stratification   

Session date and time: 12 June 2025, 17:00 – 18:15 CEST   

Session title: s450 MDS cellular and molecular therapeutic targeting   

RVU120, a selective inhibitor of CDK8 and CDK19, demonstrates significant potential in enhancing erythroid differentiation in MDS patient-derived cells. Data show that RVU120 promotes erythropoiesis in CD34+ bone marrow cells derived from MDS patients, particularly benefiting those with differentiation defects. Transcriptomic analysis confirms RVU120’s mechanism via CDK8/CDK19 inhibition and indicates potential patient stratification based on ASXL1 mutations. These findings support RVU120 as a promising therapeutic candidate in the REMARK Phase II clinical study in patients with low-risk myelodysplastic syndromes (LR-MDS).   

   

Abstract Title (poster presentation): Preliminary results from RIVER-81, a Phase 2 study of RVU12+VEN in patients with AML failing first-line VEN+HMA   

Session date and time: 14 June 2025, 18:30 – 19:30 CEST  
Poster Number: PS1509   

Preliminary results from the open-label RIVER-81 Phase II clinical study demonstrate that RVU120, when combined with venetoclax (VEN), shows promising anti-leukemic activity in patients with relapsed or refractory acute myeloid leukemia (r/r AML) who failed first-line VEN-based treatment. As of February 25, 2025, 36 patients had been treated. 20 patients were evaluable for response across Parts 1 and 2. One out of two evaluable patients from Cohort 2 achieved a complete remission (CR). Three out of thirteen (23%) evaluable patients from stage 1 of Part 2 achieved a complete remission with incomplete count recovery (CRi), suggesting that RVU120 may help overcome VEN resistance. The study, which continues enrolling patients, supports further exploration of RVU120+VEN as a potential therapeutic strategy for AML with poor prognosis. The combination has been well tolerated, with nausea as the most common adverse event.   

   

Abstract Title (poster presentation): An Open-Label Clinical Trial of RVU120 as Monotherapy and in Combination with Ruxolitinib in Patients with Intermediate or High-Risk, Primary or Secondary Myelofibrosis (POTAMI-61)   

Session date and time: 13 June 2025, 18:30 – 19:30 CEST   

Poster Number: PF861   

The open-label POTAMI-61 Phase II clinical trial evaluates RVU120, a selective CDK8/19 inhibitor, as a monotherapy and in combination with ruxolitinib (RUX) for patients with intermediate or high-risk myelofibrosis (MF). As of February 6, 2025, 12 patients were treated. The median time on treatment was four weeks, and no patient had met the follow-up for the primary endpoint due to insufficient time on the study. The ongoing trial aims to assess spleen volume reduction, symptom burden, and safety over 24 weeks. Early results show that RVU120, alone or with RUX, is well tolerated, with three patients showing early signs of clinical improvement, including improved hematologic parameters and an indication of a reduced spleen size. These early findings support further investigation of RVU120 as a potential treatment for MF for patients who have not responded adequately to JAK inhibitors.   

  

Abstract Title (poster presentation): RIVER-52: A Multicenter, Open-Label Clinical Trial of RVU120 in Patients with Relapsed or Refractory High-Risk Myelodysplastic Syndrome or Acute Myeloid Leukemia  
Session date and time: 13 June 2025, 18:30 – 19:30 CEST   

Poster Number: PF548   

The open-label RIVER-52 Phase II clinical study evaluated RVU120 monotherapy in patients with AML or relapsed or refractory high-risk MDS (HR-MDS). 39 patients received RVU120 (27 AML and 12 HR-MDS patients). RVU120 demonstrated a manageable safety profile, with gastrointestinal and infectious adverse events being the most common. While two patients with NPM1 and DNMT3A mutations showed >50% reduction in bone marrow blasts, no CRs were observed. As predefined efficacy criteria were not met, the trial did not advance to Part 2, and enrollment was suspended.  
  
Abstract Title (poster presentation): Overcoming venetoclax resistance: synergistic potential of RVU120, a CDK8/CDK19 inhibitor, in combination treatment   

Session date and time: 13 June 2025, 18:30 – 19:30 CEST   

Poster Number: PF415   

RVU120 demonstrates strong synergy when combined with venetoclax (VEN) to overcome resistance in the treatment of acute myeloid leukemia (AML). Preclinical studies reveal that RVU120+VEN effectively targets key resistance pathways, including IL6/JAK/STAT3, TGF-β, and PI3K/AKT/mTOR, which are implicated in venetoclax resistance. The combination also retains efficacy in models of bone marrow stroma-mediated resistance, a common mechanism of therapy failure. These findings support the ongoing Phase II RIVER-81 trial, exploring RVU120+VEN in patients with AML who have failed prior VEN-based treatments. This research underscores RVU120’s potential to improve treatment outcomes by overcoming venetoclax resistance in AML.   

All abstracts are now available online and can be obtained from the conference site:   
https://ehaweb.org/congress/eha2025-congress/   

 

Disclaimer: This English language translation has been prepared solely for the convenience of English-speaking readers. Despite all the efforts devoted to this translation, certain discrepancies, omissions or approximations may exist. In case of any differences between the Polish and the English versions, the Polish version shall prevail. Ryvu Therapeutics S.A., its representatives and employees decline all responsibility in this regard. 

 

Legal basis: Article 17.1 of MAR 

Representatives of the Issuer: 

• Paweł Przewięźlikowski – President of the Management Board 

• Hendrik Nogai – Member of the Management Board