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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

Ryvu PRMT5 inhibitors show potential best-in-class profiles, including a strong antiproliferative effect on MTAP-deleted cell lines and a good safety window versus MTAP WT cells. Ryvu's WRN inhibitor program has demonstrated target engagement and selective potency with a synthetic lethal effect; in vivo efficacy studies exhibited pronounced tumor growth inhibition in an MSI-H colorectal cancer xenograft model. Ryvu's proprietary ONCO Prime discovery platform, which recently received a PLN 26 million (approx. USD 6.6 million) grant from the Polish Agency for Enterprise Development, has identified novel drug targets in KRAS-mutant patient-derived cells (PDCs) with therapeutic potential in colorectal cancer; the ONCO Prime platform has broad potential across multiple tumor types. RVU120 shows efficacy both as a monotherapy and synergistically in combination with ruxolitinib in preclinical models of myeloproliferative neoplasms, including myelofibrosis and polycythemia vera. MEN1703 (SEL24), presented by partner Menarini Group, shows cytotoxic activity in myelofibrosis cell lines as a monotherapy and synergistically in combination with ruxolitinib. KRAKOW, Poland, April 10, 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, presents preclinical data from its synthetic lethality pipeline, RVU120, and MEN1703 (SEL24) at the 2024 AACR Annual Meeting, April 5-10 in San Diego, California. "We are excited to present our latest advancements in oncology therapeutics at the AACR Annual Meeting this year. Strong preclinical data from our two lead synthetic lethality programs – PRMT5 and WRN – are encouraging as we make progress toward the identification of competitive clinical candidates," said Krzysztof Brzózka, Ph.D., Chief Scientific Officer of Ryvu Therapeutics. Dr. Brzózka added, "We are also proud of our ONCO Prime target discovery platform, which recently received a significant grant from the Polish Agency for Enterprise Development, giving validation and financial support to our innovative drug discovery efforts. At AACR, we present promising data in KRAS-mutant patient-derived colorectal cancer cells, where the ONCO Prime platform has identified promising novel drug targets. With these initial data, we continue to expand the platform's potential to discover novel anticancer targets across various tumor types." The ONCO Prime target discovery platform aims to identify novel drug targets based on patient-derived primary cell cultures, omics characterization, and functional assays. It already supports preclinical development of Ryvu programs, including PRMT5 and WRN. In March 2024, the Polish Agency for Enterprise Development (PARP) recommended awarding a PLN 26 million (approx. USD 6.6 million) grant to Ryvu to cover five years of ONCO Prime research activities retroactive to May 2023. The ONCO Prime platform covers a broad spectrum of tumor types, and data from colorectal cancer are presented in AACR Poster No. 4684, 'A comprehensive platform for identification of KRAS-specific synthetic lethal targets using patient-derived cells.' AACR 2024 Poster highlights: Abstract Title: 'Discovery of novel MTA-cooperative PRMT5 inhibitors as targeted therapeutics for MTAP-deleted cancers.' Session Name: HDAC and Methyltransferase Inhibitors Session date and time: Tuesday, April 9, 9:00 AM - 12:30 PM PST Poster Number: 4598 Ryvu has developed potentially best-in-class MTA-cooperative PRMT5 inhibitors showing favorable drug-like properties and effective PRMT5 inhibition dependent on MTA binding. Ryvu PRMT5 inhibitor has a robust antiproliferative effect on MTAP-deleted cell lines and provides a good safety window for MTAP WT cells, as shown in a wide cell line panel. Novel Ryvu compounds are characterized by significantly improved PK profile that allow for oral administration. In vitro safety evaluations did not reveal any significant liabilities of the tested compounds. The correlation between compound exposure and on-target effect was confirmed in PK/PD and efficacy studies in MTAP-deleted tumor models. Abstract Title: 'Discovery of WRN inhibitors as targeted therapy in the treatment of microsatellite unstable (MSI-H) tumors.' Session Name: Novel Antitumor Agents 4 Session date and time: Tuesday, April 9, 1:30 PM – 05:00 PM PST Poster Number: 5942 Structure-based optimization performed at Ryvu facilitated the rapid expansion and delivery of a compound library with novel intellectual property (IP), demonstrating target engagement in cells and selective potency over other RecQ family members. The pharmacokinetic properties of these compounds were favorable, allowing progress to in vivo studies, which confirmed the efficacy of Ryvu's WRN inhibitors in xenograft MSI-H cancer models. Data on Ryvu's WRN inhibitors provide pharmacological proof-of-concept with synthetic lethal effect and support WRN inhibition as a new, targeted oncological therapy in MSI-high tumors. Abstract Title: 'A comprehensive platform for identification of KRAS-specific synthetic lethal targets using patient-derived cells.' Session Name: New Targets, Technologies, and Drug Delivery Systems Session date and time: Tuesday, April 9, 9:00 AM - 12:30 PM PST Poster Number: 4684 Ryvu's cutting-edge drug discovery platform uniquely combines high throughput capabilities with the precision and translational impact traditionally associated with later, lower throughput stages. By leveraging human stem cell-derived model cells (PDC), patient-derived xenografts (PDXs) and clinical samples, we have created a groundbreaking approach to identifying synthetic lethal (SL) targets specific to oncogenic pathways. In conjunction with our novel ranking algorithm, these models have successfully identified potential drug targets in KRAS-mutant cells—targets that remained undetected in immortalized CRC cell lines, likely due to genetic and epigenetic alterations accumulated over years of cell culture. Chemical compound screening has produced promising results that have been further validated through comparison with a varied collection of patient-derived CRC cultures, ensuring the findings' reliability and clinical relevance. These data position Ryvu's primary model platform as an invaluable resource for target discovery research with broad applicability across a variety of tumors. Abstract Title: 'Combination JAK1/2 and CDK8/19 inhibition demonstrates enhanced efficacy in myeloproliferative neoplasms.' Session Name: Targeted, Combination, and Differentiation Therapies Session date and time: Wednesday, April 10, 9:00 AM - 12:30 PM PST Poster Number: 7225 RVU120, a highly selective and potent CDK8/19 inhibitor, shows potential efficacy as both monotherapy and in combination with ruxolitinib (RUX), a JAK1/2 inhibitor, for the treatment of myeloproliferative neoplasms (MPN) and polycythemia vera (PV). In vivo treatment with RVU120/RUX+RVU120 significantly reduced disease manifestation (splenomegaly, WBC, fibrosis scoring, hematopoiesis) compared to VEH/RUX. These data suggest that inhibition of JAK1/2 and CDK8/19 could be a novel therapeutic strategy in MPNs. Abstract Title: 'MEN1703/SEL24 exhibits promising antitumoral activity in preclinical models of myelofibrosis both as a single agent and combined with ruxolitinib.' Session Name: Novel Antitumor Agents 2 Session date and time: Sunday, April 7, 01:30 AM – 05:00 PM PST Poster Number: 665 MEN1703 (SEL24) demonstrates efficacy both as a monotherapy and in combination with the JAK inhibitor ruxolitinib (RUX) in preclinical models of myelofibrosis (MF). MEN1703 demonstrated anti-tumoral efficacy in MF preclinical models, exhibiting in vitro activity at clinically relevant concentrations. Notably, the combination of MEN1703 with the standard of care, RUX, exhibited synergistic effects and molecular analyses confirmed the inhibition of downstream targets of PIM. The results support the therapeutic potential and relevance of MEN1703 in treating myelofibrosis. Posters are available on . 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 . SOURCE Ryvu Therapeutics