Ryvu Therapeutics Presents New Clinical Data from RIVER-81 and POTAMI-61 Studies of Romaciclib (RVU120)

Ryvu Therapeutics Presents New Clinical Data from RIVER-81 and POTAMI-61 Studies of Romaciclib (RVU120) at the 2025 American Society of Hematology (ASH) Annual Meeting

* Phase II RIVER-81 Study in acute myeloid leukemia (AML): in two dose optimization cohorts, romaciclib demonstrated clinical activity in AML with a 43% (3 of 7 patients) CR/CRi rate(1) at 150mg QD (once daily) and 28% (2/7) CR/CRi rate at 200mg QD romaciclib in combination with venetoclax (VEN), suggesting that romaciclib may help restore venetoclax sensitivity in relapsed/refractory AML following first-line VEN+HMA.
* Phase II POTAMI-61 Study in myelofibrosis (MF): romaciclib demonstrated encouraging signals of activity in MF with 7 of 14 patients evaluable for spleen volume demonstrating a reduction in spleen size of at least 10%, supporting romaciclib’s potential in patients with MF who have failed or shown suboptimal response to JAK inhibitors.
* Two additional posters will be presented on December 8, covering the investigator-initiated Phase II REMARK trial of romaciclib in lower-risk myelodysplastic syndromes (LR-MDS) and the Phase II JASPIS-01 study of dapolsertib (MEN1703, SEL24) in diffuse large B-cell lymphoma (DLBCL).
* Ryvu management will host a webinar on Sunday, December 7, at 5:30 PM CET. Details below.

KRAKOW, Poland, December 07, 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, is presenting new clinical results from the RIVER-81 and POTAMI-61 studies evaluating romaciclib (RVU120), a first-in-class selective CDK8/19 inhibitor, 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: "The updated romaciclib data presented at ASH 2025 strengthen our confidence in its broad therapeutic potential across hematologic cancers with limited treatment options. We are particularly encouraged by complete remissions in post-venetoclax relapsed/refractory AML, as well as early signs of meaningful reductions in spleen volume in patients with myelofibrosis. These results support our belief that romaciclib can become an important component of future treatment strategies in AML and MF."

Pau Montesinos, MD, PhD, Head of the Leukemia Unit of the Department of Hematology at the University Hospital La Fe in Valencia, Spain, said: "Patients who have failed venetoclax-azacitidine treatment in AML need better therapeutic options. The clinical data generated with the romaciclib-venetoclax combination so far are promising and supportive of further investigation in this setting and should be confirmed in a larger group of patients."
 
Raajit K. Rampal, MD, PhD, Director, MPN and Rare Hematologic Diseases, Memorial Sloan Kettering Cancer Center, said: "Romaciclib has shown clinically meaningful activity in patients with myelofibrosis. The reported data support further development of romaciclib and point to a potential path to approval."
 
Ryvu will host a webinar to discuss data on RIVER-81 and POTAMI-61, December 7 at 5:30 PM CET: here
 
Clinical updates from RIVER-81 and POTAMI-61 studies of romaciclib (RVU120):

The posters will be showing data with a cut-off of September 22, 2025, but more recent data is available and is summarized below:

Poster 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
Poster number: 3424

The Phase II RIVER-81 study evaluates the combination of romaciclib (RVU120), a selective CDK8/CDK19 inhibitor, with venetoclax (VEN) in unfit patients with relapsed or refractory AML following frontline VEN+HMA therapy, a patient population of high unmet need with no approved therapies. A total of 58 patients have been dosed with romaciclib and venetoclax combination (median age 76 years), and 31 patients were evaluable for response across cohorts. Romaciclib in combination with VEN demonstrated promising anti-leukemic activity in patients with a historically poor prognosis.

* In two dose cohorts testing doses of 150 mg QD and 200 mg QD, 3 of 7 treated patients (43%) achieved CR/CRi (CRx) and 2 of 7 patients (28%) achieved CRx, respectively. In the subgroup of patients who achieved a durable response to venetoclax in the first-line (defined as a CR in first-line, and remaining on treatment for at least five cycles), representing a patient population of high unmet need after initial response to VEN, the CRx rate was 50% (5 of 10 patients) in the two dose cohorts combined.
* Overall, the mean duration of response is 141 days at 150 mg QD and 55 days at 200 mg QD.
* The observed complete remissions suggest that romaciclib may help overcome venetoclax resistance.
* Romaciclib in combination with venetoclax was generally tolerated in this difficult-to-treat population. No dose-limiting toxicities were observed up to romaciclib 200 mg QD combined with venetoclax 400 mg QD, and no new safety signals were identified.
* A dose of 250 mg QD was tested but was associated with poor tolerability.
* These data support continuation of the RIVER-81 study and present opportunities for investigation in additional AML settings – including the frontline setting – and for future evaluation of the romaciclib-venetoclax doublet and potential triplet combinations with SOC.

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.

Poster Title: An open-label, phase I/II clinical trial of romaciclib (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
Poster number: 2045

The Phase II POTAMI-61 study evaluates romaciclib as monotherapy and in combination with ruxolitinib (RUX) in patients with myelofibrosis (MF) who have failed or shown suboptimal response to JAK inhibitor therapy.

Overall, 25 patients were treated (13 in Cohort 1 as monotherapy and 12 in Cohort 2 in combination with RUX), of which 14 patients completed at least 12 weeks of treatment for preliminary spleen volume assessment (as of today and updated from the poster data cut-off).

* Of the 14 patients evaluable for spleen volume at 12 weeks or more, 9 achieved spleen volume reduction, with 7 achieving SVR10 or better. One patient achieved a 59% reduction in spleen volume at week 36.
* Patients with a high-risk mutation in ASXL1 derived clinical benefit from romaciclib.
* Significant and durable TSS improvement was achieved in patients in both cohorts.
* Romaciclib was found to be safe and tolerated by the majority of patients with MF, when used either as a single agent or in combination with RUX. No dose-limiting toxicities were observed.
* These early data indicate that romaciclib is well tolerated and shows initial clinical activity, supporting continued evaluation of romaciclib as a potential therapeutic option for patients with MF.

Posters are now available online and can be downloaded from Ryvu website: https://ryvu.com/publications  as well as from the conference website: https://www.hematology.org/meetings/annual-meeting

Upcoming poster sessions:
Additional updates, including data from romaciclib’s ongoing REMARK study in lower-risk MDS and dapolsertib (MEN1703) in aggressive B-cell lymphomas, will be shared on December 8, 2025.

Poster 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
Poster 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

Semantic keywords: Hematology, Primary Myelofibrosis, Leukemia, Myeloid, Acute, Myelodysplastic Syndromes, Janus Kinase Inhibitors, venetoclax, United States, Ryvu Therapeutics, RIVER-81, POTAMI-61, romaciclib, RVU120, American Society of Hematology, ASH 2025, acute myeloid leukemia, relapsed AML, refractory AML, JAK inhibitors, Phase II REMARK trial, LR-MDS, JASPIS-01, dapolsertib, MEN1703, SEL24, selective CDK8/CDK19 inhibitor, ruxolitinib, RUX, primary myelofibrosis, secondary myelofibrosis
 
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.