Current Report ESPI 17/2025

The Management Board of Ryvu Therapeutics S.A. with its registered office in Krakow, Poland (“Company”, “Ryvu”) announces that the Company will be presenting data on RVU120 at the 2025 European Hematology Association Congress (EHA), which takes place from June 12 to June 15 in Milan, Italy.

 

Details on the oral and poster presentations are described below. The presentation related to the presented posters is attached to this report.

 

# RVU120 in combination with venetoclax in AML

Poster PS1509: Preliminary results from RIVER-81, a Phase II study of RVU120+VEN in patients with AML failing first-line VEN+HMA

Session date and time: 14 June 2025, 6:30 pm – 7:30 pm CEST

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 May 14, 2025, 43 patients had been treated, of which 27 patients were evaluable for response across exploratory Parts 1 and 2. In total, 7 out of 27 evaluable patients (26%) achieved a complete remission with or without incomplete hematologic recovery (CR/CRi). One out of three evaluable patients from Cohort 2 achieved a complete remission (CR). 3 out of 13 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. With optimized dosing in Cohort 4 (150mg of RVU120 QD + 400mg VEN), the efficacy results have further improved – the CR rate in the evaluable population in this cohort was 50% (3 out of 6 patients. As of June 6, 2025, 4 patients who have achieved a CR/CRi across all cohorts remain in remission on study treatment. The study continues enrollment in Cohort 6 at a dose of 200mg of RVU120 QD + 400mg VEN, with the potential to maximize the duration of response. The study supports further exploration of RVU120+VEN as a potential therapeutic strategy for AML with poor prognosis. The combination has been tolerated, with nausea as the most common adverse event.

Poster PF415: Overcoming venetoclax resistance: synergistic potential of RVU120, a CDK8/CDK19 inhibitor, in combination treatment

Session date and time: 13 June 2025, 6:30 pm – 7:30 pm CEST

RVU120 demonstrates strong synergy when combined with venetoclax (VEN) to overcome resistance to VEN in the treatment of AML. Preclinical studies reveal that RVU120+VEN effectively targets key VEN resistance pathways, including IL6/JAK/STAT3, TGF-β, and PI3K/AKT/mTOR. 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.

 

# RVU120 as a monotherapy and in combination with RUX in MF

Poster PF861: 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, 6:30 pm – 7:30 pm CEST

The open-label POTAMI-61 Phase II clinical trial evaluates RVU120 as a monotherapy and in combination with ruxolitinib (RUX) for patients with intermediate or high-risk myelofibrosis (MF). As of May 14, 2025, 21 patients were treated, completing the enrollment in the exploratory part. The median time on treatment was 10 weeks, with 8 patients completing at least 12 weeks of treatment, but no patient had met the follow-up for the primary endpoint at 24 weeks due to insufficient time on study. The ongoing trial is assessing spleen volume reduction, symptom burden, and safety over a 24-week period. Initial signs of clinical activity were observed in selected patients: TSS improvement was noted in 3 out of 4 patients at week 12; initial changes in spleen size reduction were observed in 4 out of 8 patients. Considering the early read-out after only 12 weeks, the data are encouraging and warrant further exploration of RVU120 in patients with MF. RVU120 was found to be tolerated by patients with MF, both when used as a single agent or in combination with RUX. The full week 24 data are anticipated in Q4 2025.

 

# RVU120 in MDS

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, 5:00pm – 6:15pm CEST

Session title:  s450 MDS cellular and molecular therapeutic targeting

RVU120 demonstrates significant potential in enhancing erythroid differentiation in MDS patient-derived cells confirmed by transcriptomic and functional analysis. Data show that RVU120 promotes erythropoiesis in CD34+ bone marrow cells derived from MDS patients, particularly benefiting those with differentiation defects. Results from multiple patient-derived samples indicate 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).

 

# RVU120 as a monotherapy in AML

Poster PF548: 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, 6:30 pm – 7:30 pm CEST

The open-label RIVER-52 Phase II clinical study evaluated RVU120 monotherapy in patients with acute myeloid leukemia (AML) or relapsed or refractory high-risk myelodysplastic syndrome (HR-MDS). As of May 14, 2025, 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. Two patients, one NPM1-mutated and one DNMT3A-mutated, showed more than 50% bone marrow blast reduction at their C2D13 disease assessment. A patient with HR-MDS achieved a CR but was lost to follow-up. Despite relevant blast reductions in some patients, no durable CRs were observed, and enrollment was suspended. The data collected will be used to support the RVU120 safety and efficacy database.

Posters are now available through the EHA Congress platform or through the Ryvu website: https://ryvu.com/publications.

Ryvu Management will host a webinar to discuss these data on Thursday, June 12 at 9:45 CEST: https://ryvu.clickmeeting.com/ryvu-eha-2025-results/register

 

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