SEL-120

Total operating revenues in Q1 2024 amounted to $6.4M, compared to $4.3M in Q1 2023. As of May 9, 2024, Ryvu's cash position was $59.0M, inclusive of the first tranche of €8M in venture debt from the EIB, obtained in March. This cash position, and other secured funding sources, provide a runway through Q1 2026. In Q1 2024, Ryvu announced the initiation of two Phase II studies of RVU120 in relapsed/refractory acute myeloid leukemia (r/r AML) and high-risk myelodysplastic syndromes (HR-MDS). Updated clinical data on RVU120 in patients with r/r AML/HR-MDS as well as preclinical data in myelofibrosis (MF) will be presented at the upcoming 2024 EHA Congress, June 13-16. Additionally, a webinar highlighting RVU120's potential in myelofibrosis (MF) will take place on Friday, May 17, at 3:00 PM (CEST). In February 2024, Ryvu announced that it had achieved the second milestone under the license agreement with Exelixis and received $2.0M. In March 2024, Ryvu announced that it would receive a approximately $6.6M (26 million PLN) in grant funding over five years from the Polish Agency for Enterprise Development (PARP) to support Ryvu's proprietary ONCO Prime discovery platform. KRAKOW, Poland, May 15, 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 first quarter, ended March 31, 2024, and provided a corporate update. Pawel Przewiezlikowski, co-founder, largest shareholder, and Chief Executive Officer of Ryvu Therapeutics, said: "We are progressing rapidly with our clinical and preclinical pipeline programs and expect several key milestones in 2024. With RVU120 now in Phase II, we have achieved our development goals established last year. By the end of this year, we anticipate RVU120, our first-in-class CDK8/19 inhibitor, enrolling patients across four independent and potentially high-value development paths. We are well-positioned with a cash runway through Q1 2026 and numerous potential non-dilutive capital sources ahead of us." Q1 2024 SUMMARY AND RECENT CORPORATE EVENTS RVU120 clinical development plan progress In early 2024, Ryvu launched two Phase II studies with RVU120: the RIVER-52 study investigating RVU120 as monotherapy in two genetically defined cohorts of patients with r/r AML or HR-MDS, and the RIVER-81 study investigating RVU120 in combination with venetoclax in patients with AML. POTAMI-61, a Phase II study evaluating the efficacy of RVU120 in patients with myelofibrosis (MF), is expected to initiate in Q3 2024. On March 28, Ryvu signed an agreement with Fortrea for the operational execution of POTAMI-61 clinical study. REMARK, a Phase II study of RVU120 in patients with low-risk myelodysplastic syndromes (LR-MDS), is expected to initiate in mid-2024. 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. The company plans to enroll approximately 100 patients across all RVU120 Phase II studies this year and aims to present initial Phase II data by the end of 2024. Preclinical updates At the 2024 American Association for Cancer Research (AACR) Annual Meeting (April 5-10, San Diego, California), Ryvu presented preclinical data from its synthetic lethality pipeline and RVU120: Ryvu's PRMT5 inhibitors have potentially best-in-class profiles and favorable drug-like, oral administration properties, including a solid antiproliferative effect on MTAP-deleted cell lines and a good safety window for MTAP WT cells. Ryvu anticipates nominating a PRMT5 clinical candidate and initiation of IND-enabling studies in 2024. 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 showed pronounced tumor growth inhibition in an MSI-H colorectal cancer xenograft model and supported WRN inhibition as a new, targeted oncological therapy. RVU120 shows efficacy both as a monotherapy and synergistically in combination with ruxolitinib in preclinical myeloproliferative neoplasms models (MPN), including myelofibrosis (MF) and polycythemia vera. UPCOMING INDUSTRY AND INVESTOR EVENTS Myelofibrosis Webinar, Friday, May 17 at 3:00 PM CEST: Ryvu will host a webinar discussing RVU120 and spotlighting MF. Registration is available at: 10th Annual Oncology Innovation Forum, Chicago, May 31: Ryvu will give a corporate presentation and conduct investor/partner meetings. Pekao I Technology & Consumer Conference, Warsaw, June 3: Ryvu will conduct investor meetings Erste | CEE Consumer & Technology Conference 2024, Warsaw, June 4: Ryvu will conduct investor meetings EHA Congress, Madrid, June 13-16: Ryvu will present clinical and preclinical data from RVU120 and host an exhibition booth; three posters will be presented on RVU120: Updated data from the Phase Ib trial of RVU120 in patients with relapsed/refractory acute myeloid leukemia (r/r AML) or high-risk myelodysplastic syndromes (HR-MDS) demonstrate promising clinical activity. Preclinical data support the synergistic combination of RVU120 and venetoclax in patients with AML, including RVU120's potential to overcome resistance to venetoclax treatment. In vivo data further supported CDK8 inhibition as a potential novel therapeutic strategy in myeloproliferative neoplasms (MPNs), focusing on myelofibrosis (MF). Q1 2024 FINANCIAL UPDATE Cash Position – On March 31, 2024, Ryvu Therapeutics held $62.7M in cash, cash equivalents, and bonds, compared to $63.7M on December 31, 2023. On May 9, 2024, Ryvu Therapeutics held $59.0M in cash, cash equivalents, and bonds, including €8M of venture debt from the EIB, received on March 13. 2023. Operating Revenues— In Q1 2024, Ryvu recognized total operating revenues (including grants) of $6.4M, compared to $4.3M in Q1 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 ($0.3M) in Q1 2024, amounted to $11.7M, compared to $7.5M in Q1 2023. Net Loss Attributable to Common Shareholders – In Q1 2024, the net loss attributable to common shareholders, excluding the non-cash cost of valuation of the Incentive Program, amounted to $4.6M compared to $3.3M in the same period last 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 . SOURCE Ryvu Therapeutics

Updated data from the Phase I trial of RVU120 in patients with relapsed/refractory acute myeloid leukemia (r/r AML) or high-risk myelodysplastic syndromes (HR-MDS) demonstrate promising clinical activity. Preclinical data support the synergistic combination of RVU120 and venetoclax in patients with AML, including RVU120's potential to overcome resistance to venetoclax treatment. Combination data of RVU120 with other drug candidates in vitro support potentially new therapeutic options for patients with myeloproliferative neoplasm (MPN). In vivo data further support CDK8 inhibition as a potential novel therapeutic strategy in MPNs, particularly myelofibrosis (MF). A webinar with Professor Raajit Rampal covering the myelofibrosis landscape, latest data, and potential of RVU120 in MF. The webinar will be held on Friday, May 17, at 3:00 PM (CET). Registration is available at: KRAKOW, Poland, May 14, 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, will present clinical and preclinical data from RVU120 at the 2024 European Hematology Association Congress (EHA), June 13-16, Madrid, Spain. "At this year's EHA conference, we proudly unveil the latest advancements in RVU120 research and clinical development, illuminating its potential in addressing the unmet need in hematologic malignancies. RVU120 has demonstrated clinical activity as a single agent in 15 of 29 evaluable patients with AML and HR-MDS at tolerated doses. Furthermore, our preclinical data demonstrate the synergistic potential of RVU120 in combination with venetoclax, representing a promising strategy against resistance in AML. We are also excited about the emerging data in MPN models, where combination regimens with RVU120 could represent a new treatment paradigm." – Dr. Hendrik Nogai, Chief Medical Officer, Ryvu Therapeutics. Based on these data and in line with prior guidance, Ryvu's development plan for RVU120 includes four Phase II studies: the RIVER-52 study in patients with AML/HR-MDS as monotherapy, the RIVER-81 study in combination with venetoclax in patients with r/r AML, the POTAMI-61 study in patients with myelofibrosis, and the REMARK study, an investigator-initiated trial in patients with LR-MDS. Poster highlights: Abstract Title: RVU120, a first-in-class CDK8 inhibitor for the treatment of relapsed/refractory AML and high-risk MDS: preliminary results from two ongoing studies. Number: 6466 Session date and time: Friday, June 14 (18:00-19:00 CEST) The abstract includes data on 29 evaluable patients out of 38 total dosed patients. In the Phase I trial CLI120-001, RVU120 shows promising clinical activity in patients with AML or HR-MDS. 15 out of 38 patients experienced clinical benefit with RBC transfusion independence and/or blast reduction. A complete remission (CR) was achieved in a patient with NPM1 and DNMT3A mutations as well as 3 marrow CRs in patients with HR-MDS. Relevant target inhibition was achieved at a dose of 110 mg or higher, supporting a recommended Phase II dose (RP2D) of 250mg. The follow-on Phase II RIVER-52 study investigates RVU120 as a monotherapy in patients with genetically defined AML or HR-MDS and is currently recruiting. Abstract Title: Synergistic potential of RVU120, a first-in-class CDK8/CDK19 inhibitor, with venetoclax in AML: preclinical and initial clinical insights. Abstract Number: 6720 Session date and time: Friday, June 14 (18:00-19:00 CEST) The abstract presents updated preclinical data supporting the synergistic combination of RVU120 and venetoclax in AML, including RVU120's potential to overcome resistance to venetoclax treatment. Ongoing preclinical research and an ongoing Phase II clinical study seek to refine patient stratification and enhance therapeutic outcomes, with initial safety profiles appearing favorable. The Phase II RIVER-81 study investigates RVU120 in combination with venetoclax in patients with AML and is currently recruiting. Abstract Title: CDK8/19 Inhibition: A Promising Therapeutic Strategy in Myeloproliferative Neoplasms. Poster Number: P1018 Session date and time: Friday, June 14 (18:00-19:00 CEST) The presentation, prepared in collaboration with Prof. Raajit Rampal's group from Memorial Sloan Kettering Cancer Center, includes the assessment of RVU120 as a monotherapy and in combination with JAK inhibitors and other drug candidates for the treatment of myeloproliferative neoplasms (MPN). Analysis of the effects from combinations of RVU120 with other compounds in vitro has revealed potentially new therapeutic options for patients with MPN sensitivity and resistance to ruxolitinib (RUX). In vivo data further support CDK8 inhibition as a potential novel therapeutic strategy in MPNs. Additional mechanistic work will potentially elucidate disease mechanisms and therapeutic action independent of JAK-STAT attenuation. This work has led to a Phase II clinical study ( POTAMI-61) for RVU120 as a monotherapy in patients with myelofibrosis patients not eligible for RUX or in combination with RUX for those patients with myelofibrosis and suboptimal RUX response. The final posters that will be presented on June 14th will contain additional information. Investor Event: Ryvu will host a webinar on Friday, May 17, at 3:00 PM CET with Professor Raajit Rampal, who will present the myelofibrosis landscape, the latest data and the potential of RVU120 in MF. To join the webcast, please register here: 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