Bristol Myers Squibb Co.

WINREVAIR significantly reduced the risk of major morbidity and mortality events, the primary endpoint, in adults with PAH (Group 1 PH) WHO* functional class (FC) III or IV at high risk of mortality who are on maximum tolerated background PAH therapy ZENITH results presented today at ACC.25 as a late-breaking oral presentation and simultaneously published in the New England Journal of Medicine RAHWAY, NJ, USA I March 31, 2025 I Merck (NYSE: MRK), known as MSD outside of the United States and Canada, today announced the first presentation of results from the Phase 3 ZENITH trial evaluating WINREVAIR™ (sotatercept-csrk) compared to placebo in adults with pulmonary arterial hypertension (PAH, Group 1 PH) WHO* functional class (FC) III or IV at high risk of mortality who were on maximum tolerated background PAH therapy. At a median follow-up of10.6 months (range, 0.3-26.1), WINREVAIR reduced the relative risk of major morbidity and mortality events (the composite of all-cause death, lung transplantation and PAH worsening-related hospitalization of ≥24 hours) by 76% (HR=0.24 [95% CI, 0.13-0.43]; p<0.0001 [1-sided]) compared to placebo.For patients treated with WINREVAIR, 17.4% (n=15/86) experienced one or more major morbidity and mortality events, compared with 54.7% (n=47/86) of patients in the placebo arm. The safety profile of WINREVAIR in ZENITH was generally consistent with that observed in previous studies. These results were presented today as a late-breaking oral presentation at the American College of Cardiology’s Annual Scientific Session and Expo (ACC.25) and simultaneously published in the New England Journal of Medicine . These results follow Merck’s announcement in November 2024 that, based on the recommendation of an independent data monitoring committee, the ZENITH study wasstopping early due to overwhelming efficacy, and study participants were offered the opportunity to receive WINREVAIR through the SOTERIA open-label extension study. “The ZENITH study represents the first PAH clinical trial with a primary endpoint comprised entirely of major outcome measures – all-cause death, lung transplantation and hospitalization for PAH,” said Dr. Marc Humbert, Department of Respiratory and Intensive Care Medicine Hospital Bicêtre (AP-HP), University Paris-Saclay and Inserm Unit 999. “WINREVAIR had a significant and clinically meaningful impact on the composite of these outcomes, and together with the growing body of evidence from the clinical development program, these data support the practice-changing potential of WINREVAIR for a broad range of patients with PAH.” “The impressive results from ZENITH demonstrated that patients on WINREVAIR had a 76 percent risk reduction in the composite of all-cause death, lung transplantation and hospitalization for PAH compared to placebo, with improvement observed early in treatment and increasing benefit throughout the study,” said Dr. Eliav Barr, senior vice president, head of global clinical development and chief medical officer, Merck Research Laboratories. “These results led to the ZENITH study being the first PAH clinical trial stopped early due to overwhelming efficacy, representing an important milestone in clinical research with promise for the PAH community.” In this trial stopped early due to overwhelming efficacy demonstrated in the primary endpoint, the key secondary endpoint of overall survival did not reach the heightened threshold (p<0.0021) that was required to establish statistical significance at the interim analysis (HR=0.42 [95% CI, 0.17-1.07]; p=0.0313]). Subsequent secondary endpoints showed numerical improvements in the WINREVAIR arm, but were not formally tested due to the prespecified hierarchical testing strategy. ZENITH is the second Phase 3 study of WINREVAIR to demonstrate efficacy in adults with PAH. The first was the Phase 3 STELLAR trial previously presented at ACC.23. Results from the ZENITH trial will be shared with regulatory authorities around the world. WINREVAIR is currently approved in more than 40 countries based on the results from the STELLAR trial. Merck announced in January 2025 that the Phase 3 HYPERION study evaluating WINREVAIR when added to background PAH therapy in newly diagnosed patients with PAH FC II or III at intermediate or high risk of disease progression was stopping early and moving directly to final analysis. The decision to stop the HYPERION study prior to its scheduled completion and offer patients the opportunity to receive WINREVAIR through the SOTERIA open-label extension study was based on the positive results from the interim analysis of the ZENITH trial and a review of the totality of data from the WINREVAIR clinical program to date. Findings from the HYPERION study will be available later this year and presented at a future medical congress. Study design and additional data from the ZENITH trial The ZENITH trial ( NCT04896008 ) is a pivotal Phase 3 multicenter, double-blind, placebo-controlled trial evaluating WINREVAIR versus placebo for the treatment of adult patients with WHO FC III or IV PAH at high risk of mortality who were on maximum tolerated background PAH therapy. The primary outcome measure was time to first confirmed morbidity or mortality event, with events defined as all-cause death, lung transplantation or PAH worsening-related hospitalization of ≥24 hours. Secondary outcome measures include overall survival, transplant-free survival and several additional measures. The trial enrolled 172 participants receiving the maximum tolerated background PAH therapy, who were randomized in a 1:1 ratio to receive either WINREVAIR (n=86) once every 3 weeks at a dose of 0.3 mg/kg at visit 1 and a dose of 0.7 mg/kg thereafter or placebo (n=86). The study population characteristics were: mean [±SD] 54.4 ± 14.3 years of age; 87% white; and 77% female. In total, 124 of the randomized patients (72.1%) were receiving triple therapy and 48 patients (27.9%) were receiving double therapy; 102 patients (59.3%) were receiving prostacyclin infusion therapy. Additionally, 25.6% of patients in the WINREVAIR arm and 30.2% in the placebo arm had PAH associated with connective-tissue disease. Demographic and baseline characteristics were similar between the WINREVAIR and placebo groups. When examined as standalone outcomes, each component of the primary composite endpoint was directionally consistent with the overall treatment effect. There were seven deaths in the WINREVAIR arm (8.1%) compared with 13 in the placebo arm (15.1%); lung transplantation occurred in one patient treated with WINREVAIR (1.2%) compared to six patients treated with placebo (7.0%); and hospitalizations for PAH occurred in eight patients in the WINREVAIR arm (9.0%) compared to 43 patients in the placebo group (50.0%). Individual patients could experience one or more component. The safety profile of WINREVAIR was generally consistent with that observed in previous studies. In the ZENITH trial, no patients treated with WINREVAIR discontinued treatment due to an adverse event. Serious adverse events occurred in 53.5% of patients treated with WINREVAIR versus 64.0% in the placebo arm. Treatment-related adverse events (TRAEs) occurred in 65.1% of patients who received WINREVAIR versus 32.6% of patients who received placebo, and serious TRAEs were observed in 3.5% versus 2.3% of patients, respectively. Bleeding events occurred in 62.8% of patients treated with WINREVAIR versus 34.9% treated with placebo (mostly non-serious epistaxis and gingival bleeding). There was a 1.1% difference in the risk of serious bleeding events (5.8% versus 4.7%, respectively), which were similar between treatment groups. Adverse events leading to death occurred in five patients (5.8%) in the WINREVAIR treatment group and 12 patients (14.0%) in the placebo group. Adverse events that occurred more frequently with WINREVAIR versus placebo were cutaneous telangiectasia (25.6% versus 3.5%), increased hemoglobin (12.8% versus 1.2%) and thrombocytopenia (14% versus 8.1%). All participants who have completed the ZENITH trial were offered the opportunity to receive WINREVAIR as part of the open-label, long-term extension trial, SOTERIA ( NCT04796337 ), consistent with that trial’s eligibility criteria. About WINREVAIR ™ (sotatercept-csrk) for injection, for subcutaneous use, 45 mg, 60 mg WINREVAIR is FDA-approved for the treatment of adults with pulmonary arterial hypertension (PAH, WHO Group 1) to increase exercise capacity, improve WHO functional class (FC) and reduce the risk of clinical worsening events. WINREVAIR is the first activin signaling inhibitor therapy approved to treat PAH. WINREVAIR improves the balance between pro-proliferative and anti-proliferative signaling to modulate vascular proliferation. In preclinical models, WINREVAIR induced cellular changes that were associated with thinner vessel walls, partial reversal of right ventricular remodeling, and improved hemodynamics. WINREVAIR is the subject of a licensing agreement with Bristol Myers Squibb. About PAH Pulmonary arterial hypertension (PAH) is a rare, progressive and life-threatening blood vessel disorder characterized by the constriction of small pulmonary arteries and elevated blood pressure in the pulmonary circulation. Approximately 40,000 people in the U.S. are living with PAH. The disease progresses rapidly for many patients. PAH results in significant strain on the heart, leading to limited physical activity, heart failure and reduced life expectancy. The five-year mortality rate for patients with PAH is approximately 43%. About Merck At Merck, known as MSD outside of the United States and Canada, we are unified around our purpose: We use the power of leading-edge science to save and improve lives around the world. For more than 130 years, we have brought hope to humanity through the development of important medicines and vaccines. We aspire to be the premier research-intensive biopharmaceutical company in the world – and today, we are at the forefront of research to deliver innovative health solutions that advance the prevention and treatment of diseases in people and animals. We foster a diverse and inclusive global workforce and operate responsibly every day to enable a safe, sustainable and healthy future for all people and communities. For more information, visit www.merck.com and connect with us on X (formerly Twitter) , Facebook , Instagram , YouTube and LinkedIn . SOURCE: Merck

-- Dr. Bolen has an established track record advancing disruptive medicines from the clinic through approval -- WATERTOWN, Mass., March 31, 2025 /PRNewswire/ -- Orna Therapeutics, a biotechnology company dedicated to engineering immune cells in vivo to treat oncology and autoimmune diseases, today announced the appointment of Joseph Bolen, Ph.D., as Chief Executive Officer. Dr. Bolen most recently served as Orna's Chief Scientific Officer (CSO) and succeeds Amit Munshi who is stepping aside for personal reasons. Orna expects to initiate clinical studies in 2026 for its two wholly owned, potentially best-in-class in vivo panCAR assets, including its CD19 program for B cell-driven autoimmune diseases and a BCMA program for multiple myeloma. In addition to its wholly owned pipeline, Orna has secured two major, potentially multi-billion-dollar pharma partnerships with Merck for the development of vaccines and therapeutics in infectious disease and oncology and with Vertex for next generation approaches to sickle cell disease and transfusion-dependent beta thalassemia. "At its core, Orna is a science driven organization that has greatly benefited from Joe's breadth and depth of drug development expertise," said Ansbert Gadicke, M.D., Chairman of Orna and Managing Partner of MPM BioImpact. "This is the perfect time for Joe to take the helm as Orna advances both its proprietary programs in autoimmune and oncology to the clinic. Joe's scientific expertise and organizational leadership capabilities, in conjunction with the Company's strong cash position, will enable us to achieve key milestones across our wholly owned and partnered programs." Dr. Gadicke continued, "Amit leaves Orna in a strong position and we would like to express our deep appreciation for his commitment and contributions." Dr. Bolen joined Orna through its acquisition of ReNAgade Therapeutics and has served as CSO since November 2024, concurrent to his role as an Entrepreneur Partner at MPM BioImpact. Prior to Orna, Dr. Bolen served in leadership roles at ReNAgade Therapeutics. Previously, he oversaw all aspects of R&D for Moderna Therapeutics as CSO and President of Research and Development. Before Moderna, Dr. Bolen was CSO at Millennium Pharmaceuticals and Global Head of Oncology Research at Takeda Pharmaceutical Company. Earlier in his career, he held senior R&D positions at Hoechst Marion Roussel, Schering-Plough (DNAX) and Bristol Myers Squibb. Dr. Bolen began his career at the National Institutes of Health (NIH). He earned a Ph.D. in Immunology and conducted his postdoctoral training in molecular virology at Kansas State University Cancer Center. He graduated from the University of Nebraska with a B.S. in Microbiology and Chemistry. "I am excited to lead our world-class team, as we advance some of the most transformative science I've seen in my 35-year career in this industry. Our leading circular RNA paired with our potentially best-in-class delivery technologies hold the potential to overcome the limitations of existing ex-vivo technologies and deliver large-scale impact to patients across a range of diseases," said Dr. Bolen. "With robust data in hand demonstrating our ability to deliver and engineer immune cells in vivo, our focus is now on advancing our first two panCAR programs into the clinic in 2026 and continuing to progress our pharma partnerships. I look forward to leading our team through this next exciting chapter of the Company's growth as we unlock the potential of RNA medicines." About Orna Therapeutics Orna Therapeutics is dedicated to designing and delivering a new class of fully engineered circular RNA (oRNA®) therapeutics to unlock the potential of RNA medicine to treat diseases anywhere in the body. Orna's circular RNA transcripts have advantages over traditional mRNA approaches, including simplified production, improved formulation into lipid nanoparticles, and superior protein expression. Its industry-leading LNP-based delivery systems and comprehensive editing programs position Orna to advance novel RNA medicines with vast potential to transform patient care. To learn more, visit and follow Orna Therapeutics on X and LinkedIn. Orna Therapeutics Investor Contact: Alex Lobo Precision AQ [email protected] SOURCE Orna Therapeutics WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Michelle Werner /Courtesy of Alltrna Werner held roles at Bristol Myers Squibb, AstraZeneca and Novartis before landing at Alltrna, where she works to develop tRNA-based treatments for a range of diseases. In the late 1990s, Michelle Werner was a fresh college graduate working as a clinical data manager at Beth Israel Deaconess Medical Center when she met a cancer trial participant whose memory she still carries. “We formed a bond, and then unfortunately he passed away while he was [in] the trial, and I happened to be there when he passed away,” she told BioSpace . “I realized how we really need to do better as an industry to get better medicines out there to patients, because patients are giving their all when they’re fighting some of these diagnoses. . . . I wanted to be part of a movement that was going to hopefully be able to bring some transformative therapies to patients.” Then, in 2020, while Werner was serving as AstraZeneca’s global hematology franchise head, her son was diagnosed with Duchenne muscular dystrophy on his 10th birthday, and her experiences researching care for him only solidified her mission. “The standard of care in Duchenne was and still is basically high dose daily steroids, which really don’t do much for the disease itself and actually have a really horrible side effect profile,” she explained. Werner looked up Duchenne studies on the National Institutes of Health’s clinicaltrials.gov database but found that her son wasn’t eligible for any of them. “That experience really cast a spotlight on . . . the inadequacies of where we are with rare genetic diseases,” she said. Now, as CEO of Alltrna and a CEO-partner at Flagship Pioneering, Werner is working toward developing tRNA-based medications to remedy that problem. Alltrna emerged from stealth in late 2021 with the announcement that Flagship had invested $50 million in the startup, calling it “the first transfer RNA (tRNA) platform company to unlock tRNA biology and pioneer tRNA therapeutics to regulate the protein universe and resolve disease.” Werner took the helm in April 2022. The following year, Alltrna raised $109 million in a Series B. The ambitious aim of developing therapies for multiple untreated diseases comes with corresponding hurdles. No tRNA drugs have so far made it to the market, or even into clinical trials. Earlier this month, fellow startup HC Bioscience abruptly shut down after analyzing preclinical data on a tRNA candidate, with its CEO citing “challenges in targeted delivery and other factors.” From Cancer to Rare Disease Prior to joining Alltrna three years ago, Werner held oncology-related and other roles at not only AstraZeneca, but Bristol Myers Squibb and Novartis. During this time, Werner was focused on aspects of commercialization, sales, marketing and market access, but she wondered whether she had the right skills to lead the Alltrna team, made up mostly of scientists. “I had to really brush [up on] a lot of understanding of basic science research,” she noted. In the end, though, “what I realized is that early- or late-stage, scientists or commercial—really what I think people need is an understanding of the vision and what the strategy needs to be in order to be able to work towards that vision, and to really understand the purpose of the company and what we’re striving to do.” With thousands of known rare genetic diseases and few with approved treatments, Werner said she was drawn by Alltrna’s approach of developing drugs that can be used for multiple conditions. “Even with novel modalities like gene therapy and gene editing and mRNA, each one of those must take a disease-by-disease strategy, or gene-by-gene or protein-by-protein, so in essence we’re really tackling them one at a time,” she explained. Alltrna’s approach is different. As its name suggests, Alltrna is developing drugs based not on genes, proteins or mRNA but on tRNA, the macromolecules known for ferrying amino acids to ribosomes to be added to new proteins during translation. Multiple genetic diseases can be traced to stop codon errors, in which a DNA sequence that should code for an amino acid instead tells the ribosome to prematurely terminate the build, resulting in a protein that’s ineffective or missing altogether. Alltrna is developing an engineered tRNA to correct these stop codon errors, allowing translation to continue despite the error. Since Werner took the helm at Alltrna, the company has gone from having some promising in vitro and cell culture data to “a much more robust preclinical proof of concept with our engineered tRNAs across, now, not just one but three different disease mouse models,” she said, as well as some work in nonhuman primates. Alltrna is now conducting investigational new drug-enabling work toward launching clinical trials of an engineered tRNA in several rare liver diseases using a concept called a basket trial that’s borrowed from oncology, Werner said. The idea is to enroll patients with multiple diseases stemming from the same underlying mutation into the trial and treat them all with the same engineered tRNA, which would be delivered to hepatocytes via lipid nanoparticles. “I’m really excited about the possibility . . . if what we’re seeing in mice translates into humans, this could be really profound, and I’m really eager to demonstrate that.” A Patient Focus Based on her personal experience, Werner brings to her CEO role an appreciation for the importance of the patient’s perspective. “As I joined Alltrna it’s something that I made a priority from within my first month or two, to start engaging with patient groups. Because I know that they really are the keepers of the most up-to-date information about what the standard of care is and what innovations are being explored there.” She added that the groups can provide “incredible insights” about what they think are the important endpoints for a therapy to achieve. That way, “as we think about putting clinical trials together . . . we start planning for what the patient expectations are already from day one,” she said. In addition to her enthusiasm about Alltrna’s science, Werner sees reasons to be excited about the rare disease space as a whole. “I think that we’re really approaching the golden age of drug development for rare diseases because of the work that’s been done over the course of the last decade to really understand DNA and RNA and how all these might translate into new approaches for genetic diseases,” she said. “The science is possible, the tools are there, but really what we need to do as a field and an industry is work with a sense of urgency that we’ve never had before. Because patients do not have time to wait.”