NodThera Ltd.

For the past few years, Sanofi has stayed out of the obesity drug development bonanza, taking a wait-and-see approach while keeping an eye on potential next-generation therapies. On Monday, however, the French pharma giant made what could be an early move: a $27 million investment in small, San Diego-based Ventyx Biosciences. The deal comes with exclusive right of first negotiation on the biotech’s drug VTX3232, an NLRP3 inhibitor being tested in obesity as well as neuroinflammatory conditions. Ventyx’s shares $VTYX were up about 16% before the opening bell. In many ways, VTX3232’s development program matches up nicely with Sanofi’s current focus. The French drugmaker has turned much of its attention to inflammation and immunology, as well as CNS diseases like multiple sclerosis . Ventyx expects Phase 2a data on the drug in early Parkinson’s disease and Phase 2 data in obesity and cardiometabolic risk factors next year. In Parkinson’s, Sanofi has an early-stage experimental medicine in development with collaborator ABL Bio. Ventyx’s oral, CNS-penetrant drug also has potential in Alzheimer’s, multiple sclerosis and other areas, the company has said. Sanofi’s announcement says the deal comes with “certain VTX3232 program rights,” but the company didn’t immediately respond to an Endpoints News inquiry Monday about which indications it’s interested in. Sanofi’s VC arm is an investor in another NLRP3 inhibitor biotech named NodThera , which is also exploring the mechanism’s potential in obesity. Novo Nordisk, meanwhile, is looking at NLRP3 for MASH and other cardiometabolic uses . Executives at Sanofi have previously said they don’t want to be involved in “me-too” obesity drugs. Getting into the GLP-1 space would take years of R&D and significant manufacturing expenses, executives have said. But they’ve signaled interest in next-generation approaches. “There are genetic signals on where to dig for obesity drugs 2.0,” Sanofi’s head of R&D Houman Ashrafian said at the JP Morgan Healthcare Conference in January. During the company’s annual general meeting in April, CEO Paul Hudson defended Sanofi’s emphasis on inflammation and immunology, comparing it to the level of investment that other drugmakers have made in obesity. “I can tell you that almost every other major company sees what we’re doing in immunology as the level of obesity,” Hudson said. “They’re being asked by their own shareholders, ‘Why did you miss immunology of the scale that Sanofi is going after?’ You have to pick your areas where you think you can win, where you have expertise.” If Sanofi moves forward with VTX3232 in obesity, it could mark its first significant foray into the area in many years. The company had an obesity drug in the 2000s, snagging an approval in Europe for a CB1 drug called Acomplia, but the company pulled the medicine because of concerning psychiatric side effects. Other drugmakers are testing next-generation CB1-targeting medicines for obesity, aiming to stave off those concerning side effects, but Novo Nordisk’s attempt in the area ran into hurdles in a Phase 2 study last Friday. For Ventyx, the move comes two months after its TYK2 inhibitor failed a Crohn’s disease Phase 2 trial, leading the company to shelve the asset known as VTX958.

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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The trial enrolled patients with obesity and elevated baseline C-reactive protein, a biomarker of chronic inflammatory diseases such as coronary artery disease. NodThera’s NLRP3 inhibitor has already proved its worth against Novo Nordisk’s blockbuster obesity drug in preclinical trials. Now, an early readout from a study in humans with obesity has again demonstrated the drug’s anti-inflammatory potential. The phase 1b/2a trial saw patients with obesity and elevated baseline C-reactive protein (CRP)—a biomarker of chronic inflammatory diseases such as coronary artery disease—receive either NT-0796 or placebo over 28 days. The data demonstrated a “highly statistically significant and rapid” reduction in CRP among patients who received NT-0796 compared to the placebo cohort, hitting the study’s primary endpoint. In addition, more than 75% of the NT-0796 cohort achieved a CRP reduction of 2mg/L or more—considered a threshold for reducing cardiovascular risk—compared to less than 25% of those on placebo, NodThera noted in a June 12 release. The biotech also pointed to reductions in other additional pro-inflammatory and cardiometabolic biomarkers, which it said built on its weight loss studies in mice as well as a phase 1b/2a study in patients with Parkinson’s disease. “While all subjects lost weight due to calorie restriction in both the active and placebo groups, the most pronounced placebo-adjusted reductions in body weight were among high-risk subgroups of NT-0796 dosed subjects, and, with the company’s earlier preclinical data, support the anti-obesity potential of the molecule,” NodThera said in the release. The company is now preparing to launch a 26-week phase 2 study in obesity alongside other mid-stage studies ranging from additional cardiometabolic diseases to Parkinson’s disease. Today’s readout builds on the promise demonstrated by NT-0796 in both preclinical and clinical studies so far this year. In February, the company showed that NT-0796 caused weight loss at nearly the same rate as Wegovy in mice. The results demonstrated that NLRP3 inhibitors are “uniquely positioned” over GLP-1 receptor agonists to block the initiation of cellular inflammatory responses to obesity-related damage-associated molecular patterns, researchers wrote in an article (PDF) published at the time in the Journal of Pharmacology and Experimental Therapeutics. Last month, a phase 1b/2a study showed that NT-0796 resulted in mean reductions of key pro-inflammatory biomarkers in Parkinson’s patients. NodThera President and Chief Scientific Officer Alan Watt, Ph.D., described today’s results as “an impressive data set, made all the more remarkable by being achieved within 28 days.” “In addition to the profound anti-neuroinflammatory effects in Parkinson’s disease patients demonstrated previously, the data generated in this study of NT-0796 show improvements in inflammatory and metabolic biomarkers of CV risk that go beyond that seen with antibody and peptide therapies,” Watt added in the release. “With additional reductions in body weight that should be enhanced with longer-duration dosing, NT-0796 is confirmed as a highly promising therapeutic agent for chronic inflammatory indications,” Watt said.