RYVU Therapeutics S.A.

Regulatory Filings • Dec 7, 2025

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

The Management Board of Ryvu Therapeutics S.A. with its registeredoffice in Krakow, Poland ("Company", "Ryvu") announces the latest dataon romaciclib (RVU120), will be presented during the 2025 Annual Meetingof the American Society of Hematology (ASH), which is being held onDecember 6-10, 2025, in Orlando, USA.

Details on the data to be presented on December 7, 2025, are as follows:

- Phase II RIVER-81 Study in acute myeloid leukemia (AML): in two doseoptimization cohorts, romaciclib demonstrated clinical activity in AMLwith a 43% (3 of 7 patients) CR/CRi rate (including both CR - completeremission, and CRi - complete remission with incomplete blood countrecovery) at 150mg QD (once daily) and 28% (2/7) CR/CRi rate at 200mg QDromaciclib in combination with venetoclax (VEN), suggesting thatromaciclib may help restore venetoclax sensitivity inrelapsed/refractory AML following first-line VEN+HMA.

- Phase II POTAMI-61 Study in myelofibrosis (MF): romaciclibdemonstrated encouraging signals ofactivity in MF with 7 of 14 patientsevaluable for spleen volume demonstrating areduction inspleen size ofat least 10%, supporting romaciclib's potential in patients with MFwhohave failed or shown suboptimal response to JAK inhibitors.

- Two additional posters will be presented on December 8, covering theinvestigator-initiated Phase II REMARK trial of romaciclib in lower-riskmyelodysplastic syndromes (LR-MDS) and the Phase II JASPIS-01 study ofdapolsertib (MEN1703, SEL24) in diffuse large B-cell lymphoma (DLBCL).

Ryvu will host a webinar to discuss data on RIVER-81 and POTAMI-61,December 7 at 5:30 PM CET:https://events.teams.microsoft.com/event/e50deb06-b3d4-44dd-9eda-780d63d070dd@412e0527-92cc-4f1b-a2d5-9692a763df44

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 ofromaciclib (RVU120) + venetoclax in patients with acute myeloid leukemiafailing first-line venetoclax + hypomethylating agent (HMA)

Session name: 616. Acute myeloid leukemias: Investigational drug andcellular 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) inunfit patients with relapsed or refractory AML following frontlineVEN+HMA therapy, a patient population of high unmet need with noapproved therapies. A total of 58 patients have been dosed withromaciclib and venetoclax combination (median age 76 years), and 31patients were evaluable for response across cohorts. Romaciclib incombination with VEN demonstrated promising anti-leukemic activity inpatients with a historically poor prognosis.

- In two dose cohorts testing doses of 150 mg QD (once daily) and 200 mgQD, 3 of 7 treated patients (43%) achieved CR/CRi (CRx; CRx - compositecomplete remission, including both complete remission (CR) and completeremission with incomplete blood count recovery (CRi)) and 2 of 7patients (28%) achieved CRx, respectively. In the subgroup of patientswho achieved a durable response to venetoclax in the first-line (definedas a CR in first-line, and remaining on treatment for at least fivecycles), representing a patient population of high unmet need afterinitial response to VEN, the CRx rate was 50% (5 of 10 patients) in thetwo dose cohorts combined.

- Overall, the mean duration of response is 141 days at 150 mg QD and 55days at 200 mg QD.

- The observed complete remissions suggest that romaciclib may helpovercome venetoclax resistance.

- Romaciclib in combination with venetoclax was generally tolerated inthis difficult-to-treat population. No dose-limiting toxicities wereobserved 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 poortolerability.

- These data support continuation of the RIVER-81 study and presentopportunities for investigation in additional AML settings - includingthe frontline setting - and for future evaluation of theromaciclib-venetoclax doublet and potential triplet combinations withSOC.

Poster Title:An open-label, phase I/II clinical trial of romaciclib(RVU120) as monotherapy andincombination with ruxolitinib in patientswith intermediate or high-risk, primary or secondary myelofibrosis(POTAMI-61)

Session name: 634. Myeloproliferative syndromes: Clinical andepidemiological: Poster 1

Poster number: 2045

The Phase II POTAMI-61 study evaluates romaciclib asmonotherapy and incombination with ruxolitinib (RUX) in patients with myelofibrosis (MF)whohave failed or shown suboptimal response to JAK inhibitor therapy.

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

- Of the 14 patients evaluable for spleen volume at 12 weeks or more, 9achieved spleen volume reduction, with 7 achieving SVR10 or better. Onepatient achieved a 59% reduction in spleen volume at week 36.

- Patients with a high-risk mutation in ASXL1 derived clinical benefitfrom romaciclib.

- Significant and durable TSS improvement was achieved in patients inboth cohorts.

- Romaciclib was found to be safe and tolerated by the majority ofpatients with MF, when used either as a single agent or in combinationwith RUX. No dose-limiting toxicities were observed.

- These early data indicate that romaciclib is well tolerated and showsinitial clinical activity, supporting continued evaluation of romaciclibas a potential therapeutic option for patients with MF.

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

Upcoming poster sessions:

Additional updates, including data from romaciclib's ongoing REMARKstudy in lower-risk MDS and dapolsertib (MEN1703) in aggressive B-celllymphomas, will be shared on December 8, 2025.

Poster Title:REMARK: A phase II, open-label, multicenter study oforally administered romaciclib (RVU120) for the treatment of anemia inpatients with lower-risk myelodysplastic neoplasms (LR-MDS)

Session name: 637. Myelodysplastic syndromes: Clinical andEpidemiological: 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 andincombination with glofitamab in patientswith relapsed or refractory aggressive B-cell non-Hodgkin lymphoma

Session name: 627. Aggressive lymphomas: Targeted and pharmacologictherapies: Poster 3

Session date and time:December 8, 6:00-8:00 PM EST

Poster number: 5481

Disclaimer: This English language translation has been prepared solelyfor the convenience of English-speaking readers. Despite all the effortsdevoted to this translation, certain discrepancies, omissions orapproximations may exist. In case of any differences between the Polishand the English versions, the Polish version shall prevail. RyvuTherapeutics S.A., its representatives and employees decline allresponsibility in this regard.