Dapolsertib

Results presented at the American Society of Hematology (ASH) Annual Meeting in December 2025 confirmed the clinical activity of romaciclib (RVU120) in patients with relapsed/refractory acute myeloid leukemia (r/r AML), who have historically poor outcomes following venetoclax-based therapy. In the Phase II RIVER-81 study, complete and incomplete remission rates reached 43% in the 150 mg once-daily cohort, with a favorable safety profile. Romaciclib Phase II POTAMI-61 study in myelofibrosis (MF), which included patients previously exposed or refractory to JAK inhibitors, brought early signals of spleen volume reduction (SVR) and symptom improvement (total symptom score; TSS) without significant myelosuppression. SVR rate of at least 25% (SVR25) was met by 4 out of 14 evaluable patients (29%). At the same time SVR10 was achieved by 7 patients (50%). The Company is progressing research and clinical collaborations with BioNTech, Exelixis, and Menarini Group, as well as strengthening its long-term value drivers with progress in fully owned early pipeline projects. Total operating revenues for the full year 2025 were €20.7 million, compared to €23.7 million for the same period in 2024. EBITDA loss was reduced to €23.2 million, compared to €25.9 million in the previous year. For Q4 alone, those figures were €3.5 million and €8.8 million, respectively. As of March 9, 2026, Ryvu’s cash position was €20.7 million. In addition, Ryvu has secured approximately €20.9 million in non-dilutive grant funding. Krakow, Poland – March 19, 2026 – Ryvu Therapeutics (WSE: RVU), a clinical-stage drug discovery and development company focusing on novel therapies that address emerging targets in oncology, reports its financials for the 2025 fiscal year and provides a corporate update. Pawel Przewiezlikowski, co-founder and Chief Executive Officer of Ryvu Therapeutics, said: – In 2025, we continued to focus on disciplined execution across our clinical programs while maintaining strict cost control. Our priority remains the efficient advancement of romaciclib (RVU120), for which we presented positive Phase II clinical data demonstrating efficacy in difficult-to-treat hematologic malignancies, including acute myeloid leukemia and myelofibrosis. At the same time, we continued to prepare RVU305 for clinical development and to advance multiple early pipeline programs. Thanks to ongoing partnerships and strategic reorganization implemented in Q1 2025, we are generating stable revenue streams and have significantly reduced operating costs. Importantly, we entered 2026 with new grant funding to support our preclinical discovery and research. Krzysztof Brzozka, Ph.D., Executive Vice President and Chief Scientific Officer, said: – Our discovery and research strategy continues to generate promising opportunities in precision oncology. The ONCO Prime platform remains a key engine of innovation, enabling the identification of novel precision oncology targets, including synthetic lethal approaches, in genetically defined cancers. In parallel, we continue to explore next-generation ADC payloads leveraging both synthetically lethal and immunocytotoxic mechanisms. Together with new projects – such as our PERO project (Predictive Engineering for Rational Oncology), which secured significant grant funding in March 2026 – these initiatives are designed to drive the development of future oncology therapies that address high unmet medical needs. 2025 SUMMARY AND RECENT CORPORATE EVENTS Romaciclib (RVU120) clinical development plan progress Ryvu continued to advance the clinical development of romaciclib (RVU120), a first-in-class selective CDK8/CDK19 inhibitor, across multiple hematologic malignancies. Current data support continued development of romaciclib in AML and MF, including further exploration of combination strategies. Throughout 2025, three Phase II studies continued as planned: RIVER-81 (combination with venetoclax in r/r AML), POTAMI-61 (monotherapy and combination with ruxolitinib in MF), and REMARK (monotherapy in LR-MDS; investigator-initiated trial). Ryvu generated further clinical insights and presented updated clinical data from the RIVER-81 and POTAMI-61 studies at the American Society of Hematology (ASH) Annual Meeting. RIVER-81 The Phase II RIVER-81 study evaluates the combination of romaciclib (RVU120), a selective CDK8/CDK19 inhibitor, with venetoclax (VEN) in unfit patients with r/r AML following frontline VEN plus hypomethylating agent (HMA) therapy, a patient population of high unmet need with no approved therapies. In the cohort testing romaciclib dose of 150 mg QD (once daily) and VEN 400 mg , 3 of 7 treated patients (43%) achieved CR/CRi (CRx) and 2 of 7 patients (28%) achieved CR. Overall, the mean duration of response at 150 mg QD was 141 days.   These data support expansion of the RIVER-81 study and present opportunities for investigation in additional AML settings, including the frontline setting. In January 2026, the U.S. Food and Drug Administration (FDA) held the Type C meeting requested by Ryvu. The FDA raised no objections to opening the expansion cohort in the United States with romaciclib at 150 mg QD in combination with VEN. POTAMI-61 The Phase II POTAMI-61 study evaluates romaciclib as monotherapy and in combination with ruxolitinib (RUX) in patients with MF who have failed or shown suboptimal response to JAK inhibitor therapy. Of the 14 patients evaluable for spleen volume evaluation at 12 weeks or more, 9 achieved spleen volume reduction, with 7 (50%) achieving at least SVR10 and 4 (29%) achieving SVR25 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.  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. In September 2025, Ryvu announced the initiation of a collaboration with the Children’s Memorial Health Institute as part of the MEDWAY project, an investigator-initiated Phase I clinical study evaluating romaciclib in combination with everolimus in children with recurrent or progressive Group 3 or 4 medulloblastoma. FPFV (First Patient, First Visit) is expected in Q2 2026. Dapolsertib (MEN1703, SEL24): The JASPIS-01 Phase II study evaluates dapolsertib in patients with relapsed/refractory diffuse large B-cell lymphoma (r/r DLBCL) as a monotherapy and in combination with glofitamab. The first patient was dosed in March 2025. JASPIS-01 is fully funded by the Menarini Group and operationally executed by Ryvu. RVU305: Ryvu continues development of RVU305, its potentially best-in-class brain-permeable, MTA-cooperative PRMT5 inhibitor, which is completing IND/CTA-enabling studies in preparation for clinical development. In October 2025, the Company presented preclinical data on RVU305 at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics, highlighting its brain-permeable profile and potential in MTAP-deleted cancers. Ryvu continues to advance its dual-pronged preclinical discovery and research strategy, focused on the ONCO Prime platform (novel small-molecule precision medicine, including synthetic lethality targets) and ADCs (antibody-drug conjugates) with novel payloads. Grant funding for the ADCraft project: on April 23, 2025, Ryvu announced signing a grant agreement with the Medical Research Agency (in Polish: Agencja Badań Medycznych, “MRA”) for the “ADCraft – next-generation small-molecule payloads for antibody-drug conjugates in oncology” project. The aim of the Project is to develop methods for discovering and testing a new generation of ADC payloads along with a portfolio of R&D activities focused on new therapeutic modalities used in oncology. The Company expects to receive PLN 9.9 million to support the project of a total net value of PLN 13.2 million. Grant funding for the PERO project: on March 11, 2026, the Company signed the grant agreement with the National Centre for Research and Development (in Polish: Narodowe Centrum Badan I Rozwoju; NCBR) for the PERO (“Predictive Engineering for Rational Oncology”) project. The objective of PERO is to establish an innovative technological platform for the functional validation of structural protein pockets of potential therapeutic targets in oncology. The project addresses a significant technological gap by enabling an in-depth, currently unavailable level of functional target validation based on integrated genomic, structural, and pharmacological data. The funding, PLN 20.0 million of a PLN 32.4 million project, will significantly fund the development of an innovative platform for functional target validation in oncology. Ryvu continues to advance partnerships with Menarini Group, BioNTech, and Exelixis, under which the Company is fully reimbursed for its expenses and has the potential to receive multiple financial milestones. Clinical collaboration with BioNTech: on September 2, 2025, Ryvu announced an expansion of its collaboration with BioNTech. Based on the new agreement, Ryvu supports 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. Extension of the research collaboration with BioNTech: on March 16, 2026, Ryvu informed about amending its research collaboration option exclusive license agreement with BioNTech, originally disclosed in November 2022. Under the amendment, the parties agreed to extend its research collaboration by an additional period of one year – until November 2028. KEY UPCOMING INDUSTRY AND INVESTOR EVENTS Ryvu will host partnering and investor meetings at all of the below conferences, with scientific presentations where noted: BIO-Europe Spring (Lisbon, Portugal), March 23-25 LSX World Congress (Lisbon, Portugal), March 24-25 AACR Annual Congress (San Diego, CA), April 17-22: Data to be presented on the ONCO Prime platform BIO Equity Europe (Prague, Czech Republic), May 4-6 ASCO Annual Meeting (Chicago, IL), May 29 to June 2 EHA Annual Congress (Stockholm, Sweden), June 12-15 BIO International Convention (San Diego, CA), June 22-25 2025 FISCAL YEAR FINANCIAL UPDATE Cash Position – On December 31, 2025, Ryvu Therapeutics held €25.5 million in cash, cash equivalents, and investment funds, compared to €52.7 million at the end of 2024. On March 9, 2026, the Company held €20.7 million in cash, cash equivalents and investment funds. In addition, Ryvu has secured approximately €20.9 million in non-dilutive grant funding. Operating Revenues – In 2025, Ryvu recognized total operating revenues (including grants) of €20.7 million, compared to €23.7 million in 2024. Operating costs, related primarily to research and development expenditures, excluding the valuation of NodThera shares and the non-cash cost of valuation of the Incentive Program for 2025, amounted to €43.0 million, compared to €51.1 million in 2024. EBITDA result – EBITDA loss for full-year 2025 was reduced to €23.2 million, compared to €25.9 million in the previous year. EBITDA loss in Q4 2025 was €3.5 million, compared to €8.8 million in the previous year. Net Loss Attributable to Common Shareholders – In 2025, the net loss attributable to common shareholders, excluding the non-cash cost of the Incentive Program, amounted to €23.2 million, compared to €24.9 million in the previous year. RYVU Therapeutics Leona Henryka Sternbacha 2 30-394 Kraków, Poland