SEL-120

Ryvu Therapeutics has announced the dosing of the first patient in the REMARK Phase II study of RVU120. The primary goal of the REMARK study is to evaluate the safety and efficacy of RVU120 in patients with lower-risk myelodysplastic syndromes (MDS). The study is conducted as an investigator-initiated study through the European Myelodysplastic Neoplasms Cooperative Group (EMSCO) network with Prof. Uwe Platzbecker, a globally renowned expert in the field of LR-MDS, as the Coordinating Principal Investigator. The REMARK study has already received approval from the Competent Authorities and Ethics Committees of Germany, Spain, Poland, Italy, and France under the European Union Clinical Trial Regulation (EU-CTR) 2023-509947-29. It will cover up to 25 clinical sites globally. The planned overall enrollment is up to approximately 40 patients. KRAKOW, Poland, Sept. 19, 2024 /PRNewswire/ -- Ryvu Therapeutics (WSE: RVU), a clinical-stage drug discovery and development company focusing on novel small molecule therapies that address emerging targets in oncology, announced today that the first patient has been dosed in the REMARK study, a Phase II clinical trial investigating RVU120 as a monotherapy for the treatment of patients with LR-MDS. "We are glad to announce the initiation of the REMARK study for RVU120, which can potentially help patients with lower-risk MDS. This study builds upon the promising results from our Phase Ib study in patients with AML and high-risk MDS, where we observed hematologic improvement in several patients, including cases of transfusion independence. The objective is to further assess the safety and efficacy of RVU120 in patients with lower-risk MDS, underpinned by robust preclinical and mechanistic evidence. We believe this represents a significant advancement toward our objective of developing effective treatments for hematological diseases and offering therapeutic options for patients. I am delighted that we can count on the support of the EMSCO network and Prof Uwe Platzbecker in this endeavor." - said Hendrik Nogai, M.D., Chief Medical Officer of Ryvu Therapeutics. REMARK is an open-label, multicenter Phase II study of RVU120, a novel small-molecule cyclin-dependent kinase (CDK) 8/19 inhibitor. The study aims to treat anemia in patients with lower-risk myelodysplastic syndromes (MDS). In REMARK, RVU120 is being explored as a single agent in patients with LR-MDS who have exhausted available treatment options. The REMARK study is being conducted as an investigator-initiated study through the EMSCO network with Prof. Uwe Platzbecker, a globally renowned expert in the field of LR-MDS, as the Coordinating Principal Investigator. "I am proud that we could start the REMARK study in line with our ambitious plans. RVU120 has shown promising hematologic improvement in patients with off-hematologic impaired bone marrow function. I am optimistic that this clinical evidence will translate into a positive outcome of the REMARK study. RVU120 has important features that should be considered a potential new treatment option for patients with LR-MDS. It may aid in achieving our ultimate aim to alleviate the need for red blood cell transfusions in these patients." - said Uwe Platzbecker, M.D., Director of the Clinic and Poliklinik for Hematology, Cell Therapy and Hemostaseology at the Leipzig University Hospital. REMARK is being initiated based on the clinical safety and efficacy data gathered so far, as well as strong preclinical and mechanistic rationale. MDS pathogenesis is influenced by gene expression alterations that hinder the maturation of hematopoietic cells. RVU120 triggers erythroid gene expression programs orchestrated by STAT5 and GATA1 in aberrant stem cells from MDS patients. Importantly, RVU120's activity does not lead to significant toxicity in the hematopoietic system. As a result, RVU120 emerges as a promising drug candidate for treating transfusion-dependent MDS patients. In REMARK, patients will receive RVU120 for at least 8 complete cycles (24 weeks). The primary goal is to achieve hematologic improvement in the form of an erythroid response (HI-E), with secondary goals including independence from RBC transfusions, improvement in hemoglobin levels, quality of life, disease progression, and analysis of specific gene mutations. REMARK represents the third of four planned RVU120 Phase II clinical studies scheduled for launch in 2024. Ryvu has already started patient treatment in the RIVER-52 and RIVER-81 studies in AML, and the fourth Phase II trial is the planned to be initiated shortly POTAMI-61 study, evaluating both monotherapy and combination therapy for the treatment of patients with myelofibrosis (MF). About Ryvu Therapeutics Ryvu Therapeutics is a clinical-stage drug discovery and development company focused on novel small-molecule 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 directed at kinases, synthetic lethality, and immuno-oncology targets. Ryvu's most advanced program is RVU120, a selective CDK8/CDK19 kinase inhibitor with the potential to treat hematological malignancies and solid tumors. RVU120 is currently in Phase II development (i) as a monotherapy for the treatment of patients with relapsed/refractory acute myeloid leukemia (r/r AML) and high-risk myelodysplastic syndromes (HR-MDS) – the RIVER-52 study, (ii) in combination with venetoclax for the treatment of patients with r/r AML – the RIVER-81 study, and (iii) a monotherapy for the treatment of patients with lower risk myelodysplastic syndromes (LR-MDS) – the REMARK study. SEL24 (MEN1703) is a dual PIM/FLT3 kinase inhibitor licensed to the Menarini Group that is expected to start a Phase II study in diffuse large B-cell lymphoma (DLBCL) in Q4 2024. RVU305, a potentially best-in-class PRMT5 inhibitor aiming to treat multiple solid tumors, is currently undergoing IND/CTA-enabling studies. Ryvu Therapeutics has signed 11 partnering and licensing deals with global companies, including BioNTech and Exelixis. The Company was founded in 2007 and is headquartered in Kraków, Poland. Ryvu is listed on the Warsaw Stock Exchange and is a component of the mWIG40 index. For more information, please visit About EMSCO The European Myelodysplastic Neoplasms Cooperative Group (EMSCO) serves as a platform to foster academic clinical research, cooperation and education in the field of myelodysplastic syndromes (MDS). EMSCO is administered by GWT-TUD GmbH and was founded in 2013 upon an initiative of the European Leukemia Network (ELN). Originally founded to facilitate European MDS-specific trials, EMSCO soon also became active in organizing indication-specific conferences and in serving as a platform for education and outreach in MDS. SOURCE Ryvu Therapeutics WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

The total operating revenues in H1 2024 amounted to USD 12.1 million and increased by USD 4.2 million compared to H1 2023. As of September, 5 2024, Ryvu's cash position was USD 65.3 million. Together with other already secured funding sources, this cash position provides a runway through Q1 2026. On September 5, 2024, Ryvu received the third and final tranche of financing under the agreement with the European Investment Bank, amounting to EUR 6 million. The Management Board decided to advance Ryvu's potentially best-in-class PRMT5 inhibitor RVU305 to further steps of preclinical development, including toxicology and API/IMP manufacturing, targeting IND/CTA filing in H2 2025. KRAKOW, Poland, Sept. 12, 2024 /PRNewswire/ -- Ryvu Therapeutics (WSE: RVU), a clinical-stage drug discovery and development company focusing on novel small molecule therapies that address emerging targets in oncology, today reported financial results for the half year ended June 30, 2024, and provided a corporate update. Pawel Przewiezlikowski, Chief Executive Officer of Ryvu Therapeutics, said: - We are progressing with enrollment in two already launched RVU120 Phase II studies and expect to present the initial data update in December at the ASH 2024 conference. We are also close to launching two additional Phase II studies. By the end of the year, we should be enrolling patients across four independent development paths in hematologic malignancies. The next few quarters will be an important period of data generation for RVU120 and progress in the preclinical pipeline. H1 2024 SUMMARY AND RECENT CORPORATE EVENTS RVU120 clinical development plan progress In early 2024, Ryvu launched two Phase II studies with RVU120: (i) the RIVER-52 study investigating RVU120 as monotherapy in two genetically defined cohorts of patients with r/r AML and in a cohort of patients with HR-MDS, and (ii) the RIVER-81 study investigating RVU120 in combination with venetoclax in patients with AML. The RIVER-52 study was initially launched at clinical sites in Poland and Italy, and as of August 31, 16 sites had been activated for enrollment in these two countries. Starting from September 2024, Ryvu will activate additional clinical sites in Spain, France, and Canada, targeting the activation of a total of 46 sites by the end of 2024. The RIVER-81 study was initially launched at clinical sites in Poland and Italy, followed by the activation of additional sites in Spain and France. As of August 31, 27 sites had been activated for enrollment across all four countries, with a total of 34 sites planned to be activated by the end of 2024. POTAMI-61, a Phase II study evaluating the efficacy of RVU120 as a monotherapy and combination therapy in patients with myelofibrosis (MF), is expected to begin enrollment shortly, initially in Poland and Italy. REMARK, a Phase II study of RVU120 in patients with low-risk myelodysplastic syndromes (LR-MDS), will enroll patients across five countries: Poland, Germany, France, Spain, Italy, and is also expected to start enrollment shortly. REMARK will be conducted as an investigator-initiated study through the EMSCO network with Prof. Uwe Platzbecker, a globally renowned expert in the field of LR-MDS, as the Coordinating Principal Investigator. At the 2024 European Hematology Association (EHA) Congress (June 13-16, Madrid, Spain) Ryvu presented clinical and preclinical data from RVU120 program. Key takeaways: RIVER-52 had immature data for efficacy assessment in the target population, even though preliminary signs of clinical benefit had been observed in ongoing patients. Initial data from the RIVER-81 study demonstrated the safety of RVU120 in combination with venetoclax at the initial dose level. Translational data support the synergistic combination of RVU120 and venetoclax in patients with AML, including RVU120's potential to overcome resistance to venetoclax treatment. Translational data underscores RVU120's potential in myeloproliferative neoplasms (MPNs) phenotypes (single-agent or combined with ruxolitinib (RUX)) partly through downregulation of pro-inflammatory cytokines. Additionally, RVU120 exhibits synergy with a whole class of JAK inhibitors and the BET inhibitor pelabresib which support CDK8 inhibition as a potential novel therapeutic strategy in MPNs, with a focus on myelofibrosis (MF). Preclinical Pipeline updates PRMT5 On September 9, 2024, the Management Board decided to advance Ryvu's potentially best-in-class PRMT5 inhibitor RVU305 to further steps of preclinical development, including toxicology and API/IMP manufacturing, targeting IND/CTA filing in H2 2025. RVU305 has a potentially best-in-class profile with favorable drug-like properties, including oral administration, a strong antiproliferative effect on MTAP-deleted cell lines, and a good safety window for MTAP WT cells. Data on Ryvu's PRMT5 inhibitors were presented at AACR 2024 in April. WRN Ryvu's WRN inhibitor program demonstrates target engagement and selective potency with a synthetic lethal effect, providing pharmacological proof-of-concept; in vivo efficacy studies exhibited pronounced tumor growth inhibition in an MSI-H colorectal cancer xenograft model and support WRN inhibition as a new, targeted cancer therapy. Data were presented at AACR 2024 in April. The company is targeting preclinical candidate selection in the upcoming quarters. Key business events From March to September 2024, Ryvu fulfilled conditions for the disbursement of all three tranches of financing from the EIB and received a total amount of EUR 22 million. In June 2024, Ryvu concluded a funding agreement with the Polish Agency for Enterprise Development ("PARP") and expects to receive approximately USD 6.6 million (PLN 26.3 million) in grant funding over five years to support its proprietary ONCO Prime discovery platform. In May 2024, Ryvu obtained the status of Associate Partner within the IPCEI Med4Cure program with its PANACEA-NOVO project – a unique platform for the discovery of new therapeutic targets with potential in the treatment of rare cancers, combined with several early discovery campaigns for innovative drugs. Ryvu expects that potential future grant funding may cover 75-80% of the total costs, which are PLN 142.5 million. In February 2024, Ryvu announced that it had achieved the second milestone under the license agreement with Exelixis and received a USD 2.0 million (PLN 7.9 million) payment. UPCOMING INDUSTRY AND INVESTOR EVENTS 6th Annual RAS-Targeted Drug Development Summit, September 24-26. Krzysztof Brzozka, Chief Scientific Officer of Ryvu Therapeutics will showcase ONCO Prime, Ryvu's discovery platform that uses isogenic primary cells and patient-derived cells to identify novel cancer targets. Dr. Brzozka's presentation on September 25, at 4:45 PM ET (Boston), will highlight ONCO Prime's application in the identification of KRAS-specific synthetic lethal targets. Trigon BioTech & MedTech Conference 2024 (online), October 2. Ryvu will host investor meetings during the conference. Erste Finest CEElection Investor Conference 2024 (Vienna, Austria), October 8-9. Ryvu will host investor meetings during the conference. ENA Symposium 2024 (Barcelona, Spain), October 23-25. Ryvu will share its scientific achievements. LSBC 2024 Central European Life Science Investment Conference (Krakow, Poland), October 23-25. Pawel Przewiezlikowski will be a panelist at the discussion titled "Poland's top Biotech Executives discuss today's challenges and the influence of AI" and will host investor and partnering meetings during the conference. H1 2024 FINANCIAL UPDATE Cash Position – On June 30, 2024, Ryvu Therapeutics held USD 63.9 million in cash, cash equivalents, and bonds, compared to USD 63.7 million on December 31, 2023. On September 5, 2024, Ryvu Therapeutics held USD 65.3 million in cash, cash equivalents, and bonds, including the third tranche of venture debt from the EIB, amounting to EUR 6 million. Operating Revenues – In H1 2024, Ryvu recognized total operating revenues (including grants) of USD 12.1 million, compared to USD 7.9 million in H1 2023. Operating costs, related primarily to research and development expenditures, excluding the valuation of NodThera shares and non-cash cost of valuation of the Incentive Program in H1 2024, amounted to USD 25.4 million, compared to USD 17.7 million in H1 2023. Net Loss Attributable to Common Shareholders – In H1 2024, the net loss attributable to common shareholders, excluding the non-cash cost of the Incentive Program valuation, amounted to USD 11.9 million, compared to USD 9.4 million in the previous year. About Ryvu Therapeutics Ryvu Therapeutics is a clinical-stage drug discovery and development company focused on novel small-molecule therapies that address emerging targets in oncology. Internally discovered pipeline candidates use diverse therapeutic mechanisms driven by emerging knowledge of cancer biology, including small molecules directed at kinase, synthetic lethality, and immuno-oncology targets. Ryvu's most advanced programs include RVU120, a selective CDK8/CDK19 kinase inhibitor with the potential to treat hematological malignancies and solid tumors, currently in Phase II development (i) as a monotherapy for the treatment of patients with relapsed/refractory acute myeloid leukemia (r/r AML) and high-risk myelodysplastic syndromes (HR-MDS) as well as (ii) in combination with venetoclax for the treatment of patients with r/r AML. Another clinical program, SEL24 (MEN1703), is a dual PIM/FLT3 kinase inhibitor licensed to the Menarini Group. Ryvu Therapeutics has signed multiple partnering and licensing deals with global companies, including BioNTech and Exelixis. The Company was founded in 2007 and is headquartered in Kraków, Poland. Ryvu is listed on the Warsaw Stock Exchange and is a component of the mWIG40 index. For more information, please see . 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