SEL-120

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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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