SEL-120

RVU120 as a single agent showed clinical benefit in heavily pretreated patients with AML and HR-MDS in the Phase 1 RIVER-51 study (CLI120-001). The strongest evidence of benefit was observed in patients with NPM1 and/or DNMT3A mutations and in patients with HR-MDS. 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. Preclinical results strongly support RVU120 as a candidate for venetoclax relapsed/refractory and frontline AML therapy. New data in myelofibrosis models show that RVU120 acts synergistically with JAK inhibitors and BET inhibitor – pelabresib. These data support new potential therapeutic options for patients with myelofibrosis. Based on compelling preclinical results, Ryvu plans to launch the clinical study POTAMI-61 (NCT06397313). A webinar covering the latest data in AML, MDS, and MF will be held on Friday, June 14, at 9:30 (CET). Registration is available at: KRAKOW, Poland, June 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, presents clinical and preclinical data from RVU120 at the 2024 European Hematology Association Congress (EHA), June 13-16, Madrid, Spain. "We are thrilled to share the advancements in RVU120 research and its clinical development, emphasizing its significant potential in addressing unmet needs in hematologic malignancies.", states Dr. Hendrik Nogai, Chief Medical Officer, Ryvu Therapeutics. "We are proud of the successful initiation of our Phase II studies. It is reassuring that the initial clinical safety data of RVU120 in combination with venetoclax, allow us to continue testing the compelling preclinical evidence of synergism in patients. Beyond AML and HR-MDS, we continue to work hard on new therapeutic strategies for patients with myeloproliferative neoplasms. Over the upcoming months, we are expecting a ramp up of patient enrollment and data readouts, and we remain committed to developing innovative treatments that can provide improved outcomes for patients in need." – underlines Dr. Hendrik Nogai, Chief Medical Officer, Ryvu Therapeutics. Poster highlights: Poster 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. Poster Number: P600 Session date and time: Friday, June 14 (9:00 CET on the online platform, 18:00 CET for the poster presentation) The poster includes data on 30 evaluable patients out of 38 total dosed patients in the Phase I trial (RIVER-51) and initial data from the Phase II trial (RIVER-52). RVU120 as single agent showed clinical benefit in heavily pretreated patients with AML and HR-MDS in the Phase I trial CLI120-001 (RIVER-51). The strongest evidence of benefit was observed in patients with NPM1 and/or DNMT3A mutations, and in patients with HR-MDS. At the poster presentation's cut-off date, the data from the Phase II RIVER-52 trial of RVU120 as a monotherapy for patients with relapsed/refractory AML and HR-MDS were not yet mature enough for efficacy assessment in the target population, but preliminary signs of clinical benefit have been observed in ongoing patients. The safety and tolerability of RVU120 at the RP2D of 250 mg administered every other day was confirmed in patients treated in both trials, with mild or moderate gastrointestinal events being the most frequently reported. Poster Title: Synergistic potential of RVU120, a first-in-class CDK8/CDK19 inhibitor, with venetoclax in AML: preclinical and initial clinical insights. Poster Number: P525 Session date and time: Friday, June 14 (9:00 CET on the online platform, 18:00 CET for the poster presentation) Ryvu presents a mechanism of synergy between RVU120 and venetoclax in preclinical models of acute myeloid leukemia (AML). The combination of RVU120 and venetoclax leads to caspase-dependent degradation of MCL-1 protein and represses inflammatory and AML oncogenic pathways at the transcriptomic level in AML cells. RVU120, when combined with venetoclax, exerts cytotoxic and differentiating effects on leukemic stem cells (LSCs) from a hierarchical AML model, exceeding the efficacy of venetoclax alone. By countering therapeutic failure caused by persistent LSCs and MCL-1-mediated venetoclax resistance, this combination offers hope to patients with AML in both the refractory and the frontline setting. Initial data from the ongoing Phase II study RIVER-81 demonstrate the safety of RVU120 in combination with venetoclax at the initial dose level in patients with relapsed/refractory AML. Enrollment is currently ongoing in Cohort 2. Poster Title: CDK8/19 Inhibition: A Promising Therapeutic Strategy in Myeloproliferative Neoplasms. Poster Number: P1018 Session date and time: Friday, June 14 (9:00 CET on the online platform, 18:00 CET for the poster presentation) In murine models of disease, RVU120 effectively attenuates myeloproliferative neoplasms (MPN) phenotypes (single-agent or combined with ruxolitinib (RUX)) partly through downregulation of pro-inflammatory cytokines. RVU120 exhibits synergy with JAK inhibitors as a class and BET inhibitor – pelabresib. These findings open new potential therapeutic options for MPN patients, including myelofibrosis. The combination of RVU120 and RUX acts synergistically by downregulating JAK/STAT signaling and inflammatory pathways at the transcriptomic level. Based on compelling preclinical results, Ryvu is launching the clinical study POTAMI-61 (NCT06397313), evaluating RVU120 as a single agent or in combination with ruxolitinib in patients with myelofibrosis. Investor Event: Ryvu will host a webinar on Friday, June 14, at 9:30 CET, covering the latest data and potential of RVU120. 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

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