Dapolsertib

Three romaciclib (RVU120) abstracts and one dapolsertib (MEN1703) abstract were accepted for poster presentation at the 2025 American Society of Hematology (ASH) Annual Meeting in December. Romaciclib continues to demonstrate meaningful activity in the Phase II study across multiple hematologic malignancies, including AML and myelofibrosis, while dapolsertib offers an innovative approach to address treatment resistance in aggressive lymphomas. Ryvu presented new preclinical data on RVU305 (brain-penetrant, MTA-cooperative PRMT5 inhibitor) and the ONCO Prime novel target discovery platform at the 2025 AACR-NCI-EORTC Conference in October. As of November 11, 2025, Ryvu’s cash position was €28.2 million. In addition, Ryvu has secured approximately €18.5 million in non-dilutive grant funding. Krakow, Poland – November 20, 2025 – Ryvu Therapeutics (WSE: RVU), a clinical-stage drug discovery and development company focusing on novel therapies that address emerging targets in oncology, today reported financial results for the third quarter ended September 30, 2025, and provided a corporate update. Pawel Przewięźlikowski, co-founder and Chief Executive Officer of Ryvu Therapeutics, said: – We are excited to present Phase II clinical data at the ASH conference in December, with three abstracts on romaciclib and one on dapolsertib. Romaciclib continues to show meaningful activity across multiple hematologic malignancies, and dapolsertib is being tested as an innovative option for aggressive lymphomas. Q3 2025 SUMMARY AND RECENT CORPORATE EVENTS Romaciclib (RVU120): In the third quarter of 2025, Ryvu advanced romaciclib, its selective CDK8/CDK19 inhibitor, across three Phase II clinical studies in hematologic malignancies. Three abstracts were accepted for presentation at the 2025 American Society of Hematology (ASH) Annual Meeting (December 6-9), highlighting continued progress and clinical activity across AML, myelofibrosis, and lower-risk MDS. Acute myeloid leukemia (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. 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. Lower-risk myelodysplastic syndrome (LR-MDS): In the Phase II REMARK study, one heavily pretreated patient achieved a major erythroid response. New IIT Phase I study: on September 9, Ryvu announced the initiation of a collaboration with the Children’s Memorial Health Institute as part of the MEDWAY project – a new, investigator-initiated Phase I clinical study aimed to evaluate romaciclib in combination with everolimus in children with recurrent or progressive Group 3 or 4 medulloblastoma. Dapolsertib: a dapolsertib abstract was accepted for presentation at the 2025 ASH Annual Meeting, reflecting growing clinical experience with the program. The ongoing Phase II JASPIS-01 study is evaluating dapolsertib in aggressive B-cell lymphomas, both as a single agent and in combination with glofitamab.  RVU305: In October 2025, Ryvu presented preclinical data on RVU305, a brain-permeable MTA-cooperative PRMT5 inhibitor, at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics, showcasing a potentially best-in-class profile in MTAP-deleted cancers. IND/CTA-enabling studies are planned to be completed in H2 2025. ONCO Prime platform: At the same event (AACR-NCI-EORTC), Ryvu also presented data from ONCO Prime, its proprietary, integrated synthetic lethality discovery platform leveraging patient-driven models, engineered systems, and high-throughput CRISPR/omics analytics – uncovers the identification of novel targets across various cancer types, including colorectal cancer (CRC) in genetically defined patient populations. Ryvu continues to advance its dual-pronged preclinical discovery strategy built around the ONCO Prime platform, focused on novel small-molecule precision medicine, including synthetic lethality targets and ADCs (antibody-drug conjugates) with novel payloads. New strategic agreement with BioNTech: on September 2, Ryvu announced an expansion of its collaboration with BioNTech. Based on the new agreement, Ryvu will support BioNTech in accelerating site activation and patient enrollment for several of BioNTech’s priority oncology clinical programs in Poland, including indications such as lung, breast, and colorectal cancers. Ryvu is progressing R&D partnerships with BioNTech, Exelixis, and Menarini. Ryvu is fully reimbursed for its expenses in these collaborations and has the potential to achieve multiple financial milestones. UPCOMING INDUSTRY AND INVESTOR EVENTS Life Science Open Space (Krakow, Poland), November 27-28: Paweł Przewięźlikowski, CEO of Ryvu, will deliver a presentation entitled: “From Ryvu labs in Krakow to AML patients worldwide – the story of romaciclib”. 2025 American Society of Hematology Annual Meeting (Orlando, US), December 6-9: Ryvu will present four abstracts on romaciclib and dapolsertib and host scientific and partnering meetings. DM BOŚ Investor Conference – Business Outlook for 2026 (online), January 8, 10:00 AM CET: Ryvu will host investor presentation. 11th Oncology Innovation Forum (San Francisco, US), January 10: Ryvu will host partnering and investor meetings. Biotech Showcase (San Francisco, US), January 12-14: Ryvu will host partnering and investor meetings. BIO Partnering at JPM (San Francisco, US), January 12-15: Ryvu will host partnering and investor meetings. Q3 2025 FINANCIAL UPDATE Cash Position – On September 30, 2025, Ryvu Therapeutics held €32 million in cash, cash equivalents, and investment funds, compared to €52.7 million on December 31, 2024. On November 11, 2025, the Company held €28.2 million in cash, cash equivalents, and investment funds. In addition, Ryvu has secured approximately €18.5 million in non-dilutive grant funding. Operating Revenues – In the first three quarters of 2025, Ryvu recognized total operating revenues (including grants) of €14.6 million, compared to €17.1 million in the corresponding period of 2024. Operating costs, primarily related to research and development expenditures, excluding the valuation of NodThera shares and non-cash cost of valuation of the Incentive Program for the first three quarters of 2025, amounted to €33 million, compared to €35.1 million for the same period last year. Thanks to the cost discipline and strategic reorganization announced in February 2025 Ryvu reduced its operating loss in Q3 2025 by €0.2 million (3%) yoy. Net Loss Attributable to Common Shareholders – In the first three quarters of 2025, the net loss attributable to common shareholders, excluding the non-cash cost of the Incentive Program, amounted to €19.1 million, compared to €17.1 million in the same period of the previous year.

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 3, 2025 – 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