- Romaciclib continues to show efficacy in AML: Data from the Phase II RIVER-81 trial suggest that romaciclib restores sensitivity to venetoclax in resistant AML, inducing complete remissions with a favorable safety profile.
- Clinical activity in myelofibrosis (MF): Interim results from the Phase II POTAMI-61 study indicate clinically meaningful spleen volume and symptom reductions, supporting romaciclib’s potential role in the post-JAK inhibitor setting.
- Erythroid response in LR-MDS: In the romaciclib’s Phase II REMARK study, one heavily pretreated patient achieved a major erythroid response.
- Dapolsertib continues evaluation in aggressive lymphomas: The ongoing Phase II JASPIS-01 study represents the first clinical evaluation of dapolsertib in aggressive B-cell lymphomas, exploring dapolsertib both as a single agent and in combination with glofitamab.
KRAKOW, Poland, November 03, 2025 / Biotech Newswire / -- Ryvu Therapeutics (WSE: RVU), a clinical-stage drug discovery and development company focusing on novel therapies that address emerging targets in oncology, today announced it will present data on romaciclib (RVU120) and dapolsertib (MEN1703) at the 2025 American Society of Hematology (ASH) Annual Meeting, December 6-10, 2025, in Orlando, Florida.
Hendrik Nogai, M.D., Chief Medical Officer of Ryvu Therapeutics, said: "We are excited to share the latest data highlighting the breadth and growing maturity of Ryvu’s clinical pipeline. Romaciclib continues to demonstrate meaningful activity across multiple hematologic malignancies, while dapolsertib offers an innovative approach to address treatment resistance in aggressive lymphomas. These results strengthen our confidence in the potential of our targeted therapies to improve outcomes for patients with difficult-to-treat blood cancers."
Details on the abstracts, which were submitted on July 31, 2025, are as follows:
Abstract Title: Preliminary results from RIVER-81, a phase 2 study of romaciclib (RVU120) + venetoclax in patients with acute myeloid leukemia failing first-line venetoclax + hypomethylating agent (HMA)
Session name: 616. Acute myeloid leukemias: Investigational drug and cellular therapies: Poster 2
Session date and time: December 7, 6:00-8:00 PM EST
Poster number: 3424
The Phase II RIVER-81 study evaluates the combination of romaciclib (RVU120), a selective CDK8/CDK19 inhibitor, with venetoclax (VEN) in patients with relapsed or refractory AML following frontline VEN+HMA therapy. As of July 11, 2025, 48 patients with relapsed/refractory AML after VEN+HMA failure were treated in the ongoing RIVER-81 study. No dose-limiting toxicities were observed up to romaciclib 200 mg QD combined with venetoclax 400 mg QD, supporting favorable tolerability across dose levels. Pharmacokinetic analyses confirmed dose-proportional exposure, and pharmacodynamic assessments demonstrated robust inhibition of STAT5 phosphorylation, consistent with on-target CDK8/19 activity. The most common adverse events were low-grade gastrointestinal symptoms, anemia, febrile neutropenia, and pneumonia. Among 28 evaluable patients, composite complete remission (CR + CRi) rates were 23% in Stage 1 of Part 2 and 43% among treated patients in Cohort 4, with several ongoing durable responses. In Cohort 6, two patients were evaluable, with one achieving a CRi and the other patient achieving a substantial blast reduction. Five of eight responding patients remain on therapy, with durations ranging from 0.6 to 7 months. Early efficacy signals suggest romaciclib may restore sensitivity to venetoclax in resistant AML. These findings support continued enrollment and further evaluation of romaciclib + VEN as a potential therapeutic option for patients with poor-prognosis AML.
Ryvu Therapeutics S.A. is implementing a project co-funded by the European Union: "Conducting a multicenter, open-label Phase II clinical trial (RIVER-81) evaluating the safety and efficacy of RVU120 in combination with venetoclax in patients with relapsed/refractory acute myeloid leukemia who have failed prior therapy with venetoclax and a hypomethylating agent." The project is being carried out under grant agreement no. 2022/ABM/06/00002 – 00.
Abstract Title: An open-label, phase I/II clinical trial of wromaciclib (RVU120) as monotherapy and in combination with ruxolitinib in patients with intermediate or high-risk, primary or secondary myelofibrosis (POTAMI-61)
Session name: 634. Myeloproliferative syndromes: Clinical and epidemiological: Poster 1
Session date and time: December 6, 5:30-7:30 PM EST
Poster number: 2045
The Phase II POTAMI-61 study evaluates romaciclib (RVU120), a selective CDK8/19 inhibitor, as monotherapy and in combination with ruxolitinib (RUX) in patients with myelofibrosis (MF) who have failed or shown suboptimal response to JAK inhibitor therapy. As of July 25, 2025, 23 patients were enrolled in Part A (12 monotherapy, 11 combination), with enrollment in Part B ongoing. Romaciclib was administered in 21-day cycles, and treatment was generally well tolerated; the most common adverse events were grade 1–2 nausea (52%) and vomiting (43%). Grade 3 events included anemia, thrombocytopenia, nausea, vomiting, urinary tract infection, and fatigue, each reported in ≤3 patients. Among four evaluable patients, one achieved spleen volume reduction (SVR) ≥20% at 24 weeks, three showed some degree of SVR, and two achieved >50% reduction in total symptom score (TSS). One patient demonstrated complete symptom resolution, and another achieved improvement in bone marrow fibrosis after 12 weeks. Pharmacokinetic results confirmed expected exposure and no drug-drug interaction between romaciclib and RUX. These early data indicate that romaciclib is well tolerated and show initial clinical activity, supporting continued evaluation of romaciclib as a potential therapeutic option for patients with MF.
Abstract Title: REMARK: A phase II, open-label, multicenter study of orally administered romaciclib (RVU120) for the treatment of anemia in patients with lower-risk myelodysplastic neoplasms (LR-MDS)
Session name: 637. Myelodysplastic syndromes: Clinical and Epidemiological: Poster 3
Session date and time: December 8, 6:00-8:00 PM EST
Poster number: 5649
The Phase II REMARK study evaluates romaciclib (RVU120), an oral CDK8/CDK19 inhibitor, in patients with lower-risk myelodysplastic neoplasms (LR-MDS), a disease characterized by anemia and limited treatment options. As of the data cutoff, 42 patients had initiated treatment, of whom 15 remained on therapy. Romaciclib was administered at 150 mg every other day for 13 days in 21-day cycles, with an option to escalate to 250 mg in non-responders or relapsing patients. Preliminary results demonstrated early signs of clinical activity, including one patient with high transfusion burden (≥8 RBC units/16 weeks) who achieved a primary erythroid response (HI-E) per IWG 2018 criteria after 24 weeks of treatment. This responder carried an SF3B1 mutation and had previously failed three standard therapies (ESA, luspatercept, lenalidomide). No new safety signals were identified; the most frequent treatment-related adverse events were nausea, vomiting, asthenia, and decreased appetite. These AEs were predominantly low grade; however, they led to discontinuation in some patients. Ongoing analyses aim to define further romaciclib’s erythroid activity, optimal dosing, and molecular predictors of response in LR-MDS.
Abstract Title: An open-label, phase 2 study of dapolsertib (MEN1703, SEL24) as monotherapy and in combination with glofitamab in patients with relapsed or refractory aggressive B-cell non-Hodgkin lymphoma
Session name: 627. Aggressive lymphomas: Targeted and pharmacologic therapies: Poster 3
Session date and time: December 8, 6:00-8:00 PM EST
Poster number: 5481
The Phase II JASPIS-01 study evaluates dapolsertib (MEN1703), a dual PIM/FLT3 kinase inhibitor, as monotherapy and in combination with the CD20xCD3 bispecific antibody glofitamab in patients with relapsed or refractory (R/R) aggressive B-cell lymphomas who have received at least 2 prior lines of therapy. Dapolsertib targets key oncogenic and survival pathways, including MYC- and BCL6-associated signaling, and has demonstrated preclinical synergy with anti-CD20 antibodies. The study aims to assess the safety, tolerability, and preliminary efficacy of dapolsertib while exploring its potential to overcome resistance associated with CD20 downregulation. In Part 1, patients are enrolled into two groups: bispecific-naïve patients receiving dapolsertib + glofitamab in dose-optimization cohorts, and heavily pretreated patients receiving dapolsertib monotherapy. Two dosing schedules are being explored – 125 mg (2 weeks on/1 week off) and 150 mg (1 week on/2 weeks off) – to identify the optimal therapeutic window. Dose selection for Part 2 will be guided by the Data and Safety Monitoring Board, following safety review after ≥2 treatment cycles. As of July 11, 2025, enrollment in Part 1 is ongoing in France, Poland, Spain, and the UK, with additional site activations planned. This study represents the first clinical evaluation of dapolsertib in B-cell lymphoma and seeks to establish a foundation for novel combination strategies addressing resistance to CD20-targeted immunotherapies.
All abstracts are now available online and can be obtained from the conference site:
https://www.hematology.org/meetings/annual-meeting/abstracts
About Ryvu Therapeutics
Ryvu Therapeutics is a clinical-stage drug discovery and development company focused on novel oncology therapies that address emerging targets in oncology. Internally discovered pipeline candidates at Ryvu use diverse therapeutic mechanisms driven by emerging knowledge of cancer biology, including small molecules and antibody-drug conjugates directed at kinases, synthetic lethality, and immuno-oncology targets.
Ryvu’s most advanced program is romaciclib (RVU120, SEL120), a selective CDK8/CDK19 kinase inhibitor with the potential to treat hematological malignancies. RVU120 is currently in Phase II development (i) in combination with venetoclax for the treatment of patients with r/r AML – the RIVER-81 study, (ii) as a monotherapy for the treatment of patients with lower-risk myelodysplastic syndromes (LR-MDS) – the REMARK study, (iii) as a monotherapy and in combination with ruxolitinib for the treatment of patients with myelofibrosis (MF) – the POTAMI-61 study. Dapolsertib (MEN1703, SEL24) is a dual PIM/FLT3 kinase inhibitor licensed to the Menarini Group that is currently being investigated in a Phase II study in diffuse large B-cell lymphoma (DLBCL) – the JASPIS-01 study. RVU305, a potentially best-in-class, brain-permeable PRMT5 inhibitor aiming to treat multiple solid tumors, is currently in IND/CTA-enabling studies. Ryvu Therapeutics is also engaged in oncology collaborations with BioNTech and Exelixis.
Ryvu was founded in 2007 and is headquartered in Kraków, Poland. It is listed on the Warsaw Stock Exchange and is a component of the sWIG80 index.
Contact
Ryvu Therapeutics
Anna Wilk
+48 532 698 425
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Keywords: Congresses as Topic; Clinical Trials, Phase II as Topic; Clinical Trials, Phase I as Topic; venetoclax; ruxolitinib; Primary Myelofibrosis; glofitamab; Hematologic Neoplasms; Leukemia, Myeloid, Acute; Lymphoma; Lymphoma, Non-Hodgkin; Anemia; Hematology; United States; Poland; Krakow; Ryvu Therapeutics; Romaciclib; RVU120; Dapolsertib; MEN1703; American Society of Hematology; ASH Annual Meeting; Acute Myeloid Leukemia; AML; RIVER-81; CDK8; CDK19; STAT5 phosphorylation; Composite Complete Remission; Myelofibrosis; POTAMI-61; Bone Marrow Fibrosis; Myelodysplastic Neoplasms; LR-MDS; REMARK; Luspatercept; Lenalidomide; Aggressive B-cell Lymphoma; JASPIS-01; PIM kinase; FLT3 kinase; Bispecific antibody; Oncology; Hematologic malignancies; Combination therapy; EU grant
Source: Biotech Newswire