Vir Biotechnology Announces AASLD The Liver Meeting® Presentation & New England Journal of Medicine Publication of Phase 2 Data Demonstrating Tobevibart & Elebsiran Combination Deliver High Rates of Undetectable HDV RNA with Favorable Safety Profile




Vir Biotechnology Announces AASLD The Liver Meeting® Presentation & New England Journal of Medicine Publication of Phase 2 Data Demonstrating Tobevibart & Elebsiran Combination Deliver High Rates of Undetectable HDV RNA with Favorable Safety Profile

• SOLSTICE trial data demonstrate that 66% of chronic hepatitis delta participants receiving a monthly dose of tobevibart and elebsiran achieved undetectable HDV RNA at Week 48
• Combination well-tolerated: No grade 3 or higher treatment-related adverse events and no treatment-related discontinuations
• ECLIPSE registrational program evaluating the combination of tobevibart and elebsiran for chronic hepatitis delta fully underway, with topline data expected in the first quarter of 2027
• Data presented at AASLD The Liver Meeting® and simultaneously published in the New England Journal of Medicine

SAN FRANCISCO–(BUSINESS WIRE)–Vir Biotechnology, Inc. (Nasdaq: VIR) today announced that Week 48 endpoint analysis from the Company’s Phase 2 SOLSTICE trial for chronic hepatitis delta (CHD) demonstrated that participants receiving a monthly dose of the combination of tobevibart and elebsiran achieved robust and sustained rates of hepatitis delta virus (HDV) RNA target not detected (TND), including those participants with cirrhosis and high baseline HDV RNA. The combination also showed alanine aminotransferase (ALT) reductions over time and a favorable safety profile. These data were presented in an oral session at the American Association for the Study of Liver Diseases (AASLD) The Liver Meeting ^®, in Washington, D.C., and simultaneously published in the New England Journal of Medicine.

“Achieving undetectable HDV RNA is a key endpoint in clinical trials, and HDV RNA undetectability is associated with better outcomes for people living with chronic hepatitis delta,” said Tarik Asselah, M.D., Ph.D., Professor of Hepatology at the Hôpital Beaujon, APHP, Clichy, France, and at the University of Paris-Cité, and Head of the unit Viral Hepatitis UMR1149 at INSERM, France. “The combination of tobevibart and elebsiran has consistently demonstrated impressive hepatitis delta virologic suppression in the SOLSTICE Phase 2 trial, and these 48-week data are encouraging as they continue to support its potential to deliver meaningful patient benefit.”

Data demonstrate that 66% (21/32) of participants with CHD receiving a monthly dose of the combination of tobevibart and elebsiran achieved and sustained HDV RNA TND at 48 weeks. Additionally, approximately 90% of participants achieved reduction in hepatitis B surface antigen (HBsAg) to values <10 IU/mL by Week 48. HBsAg reduction indicates suppression of the fundamental biologic mechanisms that HDV requires for viral replication. ALT was normalized in 56% (18/32) of participants by Week 48. The combination was well-tolerated, with no grade 3 or higher treatment-related adverse events and no treatment-related discontinuations. Most treatment-related adverse events were generally mild to moderate and transient.

The combination of tobevibart and elebsiran is currently being evaluated in Vir Biotechnology’s ECLIPSE registrational program for the treatment of CHD, which includes three randomized, controlled trials. ECLIPSE 1 has completed enrollment ahead of the Company’s expectations. Topline results from ECLIPSE 1, 2, and 3 are expected in the first quarter of 2027.

“The 48-week data from the SOLSTICE Phase 2 trial presented at AASLD’s The Liver Meeting® reinforce our confidence that a monthly dose of the combination of tobevibart and elebsiran can deliver meaningful patient benefit with convenient dosing, and I am proud to see the caliber of our data recognized by our publication in the prestigious New England Journal of Medicine,” said Marianne De Backer, M.Sc., Ph.D., MBA, Chief Executive Officer, Vir Biotechnology. “We are committed to advancing our registrational ECLIPSE program efficiently with the goal of addressing the critical unmet needs of the hepatitis delta community.”

CHD is the most severe form of chronic viral hepatitis,¹ recently classified as carcinogenic by the International Agency for Research on Cancer.² People living with the disease rapidly progress to cirrhosis, liver failure³ and liver-related death.¹ There are currently no approved treatments in the U.S., and options are limited in the European Union and globally. The objective is to eliminate the virus, and tobevibart in combination with elebsiran offers the potential to achieve this by tackling the viral lifecycle through multiple mechanisms.

The significant unmet need in CHD and the potential for the combination of tobevibart and elebsiran to provide a much-needed treatment option has been recognized by the U.S. Food and Drug Administration (FDA) with Breakthrough Therapy and Fast Track designations, and by the European Medicines Agency (EMA) with Priority Medicines (PRIME) and orphan drug designations.

About the ECLIPSE Registrational Program

ECLIPSE is a registrational program to evaluate the safety and efficacy of tobevibart in combination with elebsiran in patients with chronic hepatitis delta (CHD). ECLIPSE includes three randomized, controlled trials designed to evaluate the combination therapy in comparison to deferred treatment or bulevirtide. ECLIPSE 1 (NCT06903338) is a Phase 3 trial evaluating the safety and efficacy of tobevibart in combination with elebsiran compared to deferred treatment in the U.S. or other regions where bulevirtide use is limited. ECLIPSE 2 (NCT07128550) is a Phase 3 trial that will evaluate the efficacy and safety of switching to tobevibart and elebsiran in people with CHD who have not achieved viral suppression with bulevirtide therapy. ECLIPSE 1 and 2 are designed to provide the registrational efficacy and safety data needed for potential submission to global regulatory agencies. ECLIPSE 3 (NCT07142811) is a Phase 2b head-to-head trial to evaluate tobevibart and elebsiran compared with bulevirtide in bulevirtide-naïve patients, and it is designed to provide important supportive data to help establish access and reimbursement in key markets.

About Tobevibart and Elebsiran

Tobevibart is an investigational broadly neutralizing monoclonal antibody targeting the hepatitis B surface antigen (HBsAg). It is designed to inhibit the entry of hepatitis B and hepatitis delta viruses into hepatocytes and to reduce the level of circulating viral and subviral particles in the blood. Tobevibart was identified using Vir Biotechnology’s proprietary monoclonal antibody discovery platform. The Fc domain has been engineered to increase immune engagement and clearance of HBsAg immune complexes and incorporates Xencor’s Xtend™ technology to extend half-life. Tobevibart is administered subcutaneously, and it is currently in clinical development for the treatment of patients with chronic hepatitis delta.

Elebsiran is an investigational hepatitis B virus-targeting small interfering ribonucleic acid (siRNA) discovered by Alnylam Pharmaceuticals, Inc. It is designed to degrade hepatitis B virus RNA transcripts and limit the production of hepatitis B surface antigen. Current data indicate that it has the potential to have direct antiviral activity against hepatitis B virus and hepatitis delta virus. Elebsiran is administered subcutaneously, and it is currently in clinical development for the treatment of patients with chronic hepatitis delta.

About Vir Biotechnology, Inc.

Vir Biotechnology, Inc. is a clinical-stage biopharmaceutical company focused on powering the immune system to transform lives by discovering and developing medicines for serious infectious diseases and cancer. Its clinical-stage portfolio includes programs for chronic hepatitis delta and multiple dual-masked T-cell engagers across validated targets in solid tumor indications. Vir Biotechnology also has a preclinical portfolio of programs across a range of infectious diseases and oncologic malignancies. Vir Biotechnology routinely posts information that may be important to investors on its website.

References:

¹ NIH National Institute of Diabetes and Digestive and Kidney Diseases Hepatitis D – NIDDK (nih.gov), accessed September 2025

² Karagas, Margaret R et al., Carcinogenicity of hepatitis D virus, human cytomegalovirus, and Merkel cell polyomavirus, The Lancet Oncology, Volume 26, Issue 8, 994 – 995.

³ CDC What is Hepatitis D – FAQ | CDC, accessed September 2025

Forward-Looking Statements

This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Words such as “should,” “could,” “may,” “might,” “will,” “plan,” “potential,” “aim,” “expect,” “anticipate,” “promising” and similar expressions (as well as other words or expressions referencing future events, conditions or circumstances) are intended to identify forward-looking statements. Forward-looking statements contained in this press release include, but are not limited to, statements regarding: the therapeutic potential of the combination of tobevibart and elebsiran to treat CHD and Vir Biotechnology’s belief that monthly dosing of the combination can deliver meaningful patient benefit and address the critical unmet needs of the hepatitis delta community; Vir Biotechnology’s clinical development plans and expectations for the ECLIPSE Phase 3 registrational program, including protocols for and enrollment into ongoing and planned clinical trials, target endpoints and data readouts (including the expectation of topline data for all three trials in the first quarter of 2027); Vir Biotechnology’s strategy and plans; and any assumptions underlying any of the foregoing. Many factors may cause differences between current expectations and actual results, including, without limitation: unexpected safety or efficacy data or results observed during clinical studies or in data readouts, including the occurrence of adverse safety events; risks of unexpected costs, delays or other unexpected hurdles; challenges in accessing manufacturing capacity; clinical site activation rates or clinical enrollment rates that are lower than expected; the timing and outcome of Vir Biotechnology’s planned interactions with regulatory authorities, as well as general difficulties in obtaining any necessary regulatory approvals; successful development and/or commercialization of alternative product candidates by Vir Biotechnology’s competitors, as well as changes in expected or existing competition; geopolitical changes or other external factors; and unexpected litigation or other disputes. In light of these risks and uncertainties, the events or circumstances referred to in the forward-looking statements may not occur. Drug development and commercialization involve a high degree of risk, and only a small number of research and development programs result in commercialization of a product. Results in early-stage clinical studies may not be indicative of full results or results from later stage or larger scale clinical studies and do not ensure regulatory approval. The actual results may vary from the anticipated results, and the variations may be material. You are cautioned not to place undue reliance on any scientific data presented or these forward-looking statements, which are based on Vir Biotechnology’s available information, expectations and assumptions as of the date of this press release. Other factors that may cause Vir Biotechnology’s actual results to differ from those expressed or implied in the forward-looking statements in this press release are discussed in Vir Biotechnology’s filings with the U.S. Securities and Exchange Commission, including the section titled “Risk Factors” contained therein. Except as required by law, Vir Biotechnology assumes no obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise.

Contacts

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Virion Therapeutics Reports Progress Towards HBV Functional Cure with Sustained and Continued HBsAg Declines up to One Year After a Single VRON-0200 Dose From its Phase 1b Study at AASLD’s The Liver Meeting® 2025




Virion Therapeutics Reports Progress Towards HBV Functional Cure with Sustained and Continued HBsAg Declines up to One Year After a Single VRON-0200 Dose From its Phase 1b Study at AASLD’s The Liver Meeting® 2025

Highlights from the Data Presentation

• VRON-0200 was safe and well tolerated, with no serious treatment-related adverse events, treatment discontinuations, or treatment-related clinical laboratory abnormalities reported
• In the majority of patients (83%; 19/23), a single intramuscular VRON-0200 dose, added to standard of care antiviral therapy, induced anti-HBV immune activation and restoration, with HBsAg declines beginning at Day 28; these HBsAg declines were sustained and/or continued to decline up to one year after VRON-0200 treatment, with 47% of patients (9/19) achieving greater than a 50% reduction (4 patients had a 1 log₁₀ IU/mL or greater decline) at Day 360
• A single VRON-0200 prime dose, followed by the addition of monthly doses of investigational antivirals initiated 28 days later, produced rapid and profound HBsAg declines (<2 IU/mL) in all patients (n=7); at Week 20, three of six patients achieved complete HBsAg loss, one within 7 days of the first combination dose
• The “Spark and Fan” model where an upfront VRON-0200 “spark” dose “primes” an anti-HBV immune response which is then “fanned” (aka boosted) by an antiviral regimen that removes the virus (e.g., HBsAg), could make VRON-0200 the foundational backbone agent to a wide range of future Functional Cure treatments

PHILADELPHIA–(BUSINESS WIRE)–Virion Therapeutics, LLC, a clinical-stage biotechnology company, developing novel T cell-based immunotherapies that utilize checkpoint modifiers, today announced at AASLD’s The Liver Meeting^®, in Washington DC, that a single intramuscular dose of VRON-0200, its novel, first-in-class, immunotherapy for HBV Functional Cure, induced HBV-specific immune activation, restoration, and HBsAg declines, that were sustained and/or continued up to one-year post dosing, in the majority of chronically HBV-infected treated patients. The data, presented as an oral presentation, by Dr. Grace Wong, M.D., from the Chinese University of Hong Kong, also highlighted VRON-0200’s ongoing favorable safety and tolerability profile, and rapid and profound HBsAg declines when VRON-0200 was combined with an investigational antiviral regimen.

Professor Grace Wong, M.D., from the Chinese University of Hong Kong, and one of the study investigators commented: “Current and investigational HBV Functional Cure treatments have been limited by their inability to restore a patient’s own immune responses against the virus. As a result, once treatment is discontinued, and the antiviral agents are no longer present, viral rebound typically occurs. What makes these data so exciting is that not only was a single, well tolerated VRON-0200 dose, alone, able to restore broad anti-HBV immune responses in the majority of chronically HBV-infected patients, but these responses were sustained, and/or improved, up to one year after end of treatment. VRON-0200’s ability to restore a patient’s own anti-HBV responses, with the potential for sustained viral control after antiviral treatment ends, is a significant advance for the field and opens up a wide range of possible future Functional Cure treatment options.”

“These new VRON-0200 clinical study data highlight its potential as a key component in future HBV Functional Cure regimens,” said Dr. Sue Currie, COO of Virion, and one of the study authors. “Off treatment viral rebound has been the “Achilles heel” for every HBV Functional Cure regimen to date. A single VRON-0200 dose alone was able to “Spark” a new and sustained anti-HBV response that could offer a solution to treatment rebound. This novel and exciting approach, where a patient’s own immune response is “sparked” (i.e. primed) with VRON-0200, and then “fanned” (aka boosted) by the removal of the HBV virus, position VRON-0200 to be the foundational backbone agent for new combination therapies that could produce meaningful Functional Cure rates for the almost 260 million persons living with chronic HBV worldwide. A Phase 2b SPARK-B trial for HBV Functional Cure is in development and will use the “Spark and Fan” approach to evaluate VRON-0200 in combination with an investigational antiviral.”

Professor Ed Gane, M.D., from the University of Auckland, and one of the study investigators, noted: “Sustained viral control after finite treatment is difficult to achieve with current HBV Functional Cure regimens, including those containing pegylated interferon. What is particularly exciting about these VRON-0200 data are that, in the majority of patients, most infected at birth, VRON-0200 was not only able to activate and restore an HBV-specific immune response, but also, these HBsAg responses were sustained and further reduced even one year after end of VRON-0200 dosing. These sustained anti-HBV immune responses, after finite treatment, could provide a solution for long-term prevention of viral rebound and ultimately get us closer to meaningful Functional Cure rates.”

The presentation is available for download at www.VirionTx.com and more details of this study can be found at ClinicalTrials.gov (Identifier: NCT06070051).

About Chronic Hepatitis B

Despite a preventative vaccine, cases of chronic hepatitis B (CHB) continue to rise, with an estimated 254 million persons infected worldwide and 1.1 million deaths per year from HBV-related liver complications. Chronic HBV remains a global health issue with a high unmet medical need, since there is no cure available. The current standard of care requires lifelong antiviral therapy to maintain control of the virus.

About VRON-0200

VRON-0200 is an investigational therapeutic immunotherapy designed with the goal of providing a functional cure for chronic HBV infection. Clinical data from an ongoing Phase 1b trial have shown VRON-0200 to be safe and well tolerated, and, when given as a single intramuscular dose, was immunogenic, and able to “Spark” anti-HBV activity in chronically HBV-infected patients on nucleos(t)ide therapy alone, and, also, when administered first and given with combination antiviral therapies. These results suggest the potential of VRON-0200 to be the key backbone agent, in combination HBV functional cure regimens.

About Virion Therapeutics (Virion)

Virion Therapeutics, LLC is a clinical-stage company developing novel immunotherapies that utilize proprietary checkpoint modifiers to enhance/restore, broaden, and elicit sustained immune responses, with the goal to cure cancer and chronic infectious diseases. Virion has since developed a robust pipeline, including its lead VRON-0200 clinical program, and several additional IND-enabling programs, such as its VRON-0300 oncology program for advanced solid tumors, leveraging its proprietary platform technologies.

To learn more, visit www.VirionTx.com

Contacts

Virion Therapeutics, LLC, Dr. Sue Currie, Chief Operating Officer

scurrie@viriontx.com
1-800-841-9303

Merck’s Enlicitide Decanoate, an Investigational Oral PCSK9 Inhibitor, Significantly Reduced LDL-C in Adults with Heterozygous Familial Hypercholesterolemia (HeFH) in Phase 3 CORALreef HeFH Trial




Merck’s Enlicitide Decanoate, an Investigational Oral PCSK9 Inhibitor, Significantly Reduced LDL-C in Adults with Heterozygous Familial Hypercholesterolemia (HeFH) in Phase 3 CORALreef HeFH Trial

Enlicitide has the potential to be the first approved oral PCSK9 inhibitor designed to deliver antibody-like efficacy and help address critical unmet needs for patients with HeFH to help combat the ongoing CV epidemic

Results were presented today at AHA Scientific Sessions 2025 and simultaneously published in the Journal of the American Medical Association

RAHWAY, N.J.–(BUSINESS WIRE)–Merck (NYSE: MRK), known as MSD outside of the United States and Canada, today announced the first presentation of results from the pivotal Phase 3 CORALreef HeFH trial demonstrating that treatment with enlicitide decanoate, an investigational, once-daily oral proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor, resulted in a statistically significant and clinically meaningful reduction in low-density lipoprotein cholesterol (LDL-C) of 59.4% compared to placebo at week 24 (95% CI: -65.6, -53.2; p<0.001) in adults with heterozygous familial hypercholesterolemia (HeFH). The effect size and safety profile was comparable to that observed in the pivotal Phase 3 CORALreef Lipids study. These late-breaking data will be presented for the first time today at the American Heart Association (AHA) Scientific Sessions 2025 (Abstract #4391641) and published simultaneously in the Journal of the American Medical Association.

In CORALreef HeFH, enlicitide demonstrated statistically significant and clinically meaningful reductions in LDL-C at week 24 (primary endpoint) and statistically significant reductions in secondary endpoints including LDL-C at one year (week 52), and non-high-density lipoprotein cholesterol (non-HDL-C), apolipoprotein B (ApoB), and lipoprotein(a) (Lp(a)) at week 24, in adults with HeFH receiving stable background lipid-lowering therapy including at least moderate or high intensity statin therapy. The overall safety profile was comparable to placebo. High adherence with study intervention (97%) and dosing instructions (96%) were observed across treatment groups.

“Data from CORALreef HeFH demonstrate the potential for enlicitide to help address critical unmet needs for adults with heterozygous familial hypercholesterolemia are at risk for premature atherosclerotic cardiovascular events yet a significant portion of patients do not achieve guideline-recommended LDL-C level despite available lipid-lowering therapies,” said Dr. Christie M. Ballantyne, a lead author of the CORALreef HeFH study and Professor of Medicine at Baylor College of Medicine. “As the potentially first approved oral PCSK9 inhibitor, enlicitide was designed to provide efficacy similar to anti-PCSK9 monoclonal antibodies and may be an important new treatment option to help adults with heterozygous familial hypercholesterolemia reach their guideline-recommended LDL-C goal. Lowering elevated LDL-C levels helps reduce the risk of atherosclerotic cardiovascular disease.”

“Results from the CORALreef HeFH study demonstrated statistically significant and sustained reductions in LDL-C, ApoB, non-HDL-C, and Lp(a) over one year in a diverse population of adults with heterozygous familial hypercholesterolemia receiving stable background lipid-lowering therapies,” said Dr. Dean Y. Li, president, Merck Research Laboratories. “We look forward to sharing the totality of the results from the CORALreef program presented at AHA with regulatory authorities and progressing enlicitide’s ongoing clinical development program to bring forward the potential first approved oral PCSK9 inhibitor to help address the growing CV epidemic.”

In CORALreef HeFH, LDL-C reductions were observed as early as week 4 and maintained through one year. Treatment with enlicitide resulted in a sustained statistically significant reduction in LDL-C of 61.5% compared to placebo (95% CI: -69.4, -53.7, p<0.001) at one year. At week 24, enlicitide demonstrated statistically significant reductions in non-HDL-C of 53.0% (95% CI: -58.5, -47.4, p<0.001), ApoB of 49.1% (95% CI: -54.0, -44.3, p<0.001) and Lp(a) of 27.5% (-95% CI: -34.3, -20.6, p<0.001) compared to placebo. The study also showed that 67.3% of patients treated with enlicitide achieved at least a 50% reduction in LDL-C along with an LDL-C <55 mg/dL (1.42 mmol/L) compared to 1.0% in the placebo arm at week 24.

Enlicitide had a safety profile similar to placebo. The incidence of adverse events (AEs), serious AEs and discontinuations due to AEs were similar between groups. Discontinuations due to AEs were low and similar between enlicitide (2.0%) and placebo (3.0%).

Merck plans to share data from this trial, along with data from CORALreef Lipids and CORALreef AddOn with regulatory authorities worldwide.

About CORALreef HeFH

CORALreef HeFH (NCT05952869) is a Phase 3, randomized, double-blind, placebo-controlled, multicenter study designed to evaluate the efficacy and safety of enlicitide compared to placebo in adults with HeFH who had a history of or were at risk for a major ASCVD event and received stable background lipid-lowering therapy including at least moderate or high intensity statins. The study enrolled 303 participants who were randomized 2:1 to receive either 20 mg of enlicitide orally once daily or placebo. The primary endpoints were mean percent change in LDL-C from baseline at week 24 versus placebo, number of participants with one or more AEs, and number of participants who discontinued study drug due to an AE. Key secondary multiplicity-controlled efficacy endpoints included change in LDL-C at one year (week 52) and changes in non-HDL-C, ApoB and Lp(a) at week 24. Non-multiplicity-controlled secondary endpoints included LDL-C goal attainment of at least a 50% reduction in LDL-C and an LDL-C <70 mg/dL (1.81 mmol/L) and at least 50% reduction in LDL-C and an LDL-C <55 mg/dL (1.42 mmol/L).

About enlicitide and PCSK9

Enlicitide has the potential to be the first FDA approved oral PCSK9 inhibitor. It is designed to lower LDL-C via the same biological mechanism as currently approved monoclonal antibody, injectable PCSK9 inhibitors but in a daily pill form. Enlicitide is a novel small molecule macrocyclic peptide candidate that binds to PCSK9 and inhibits the interaction of PCSK9 with LDL receptors.

PCSK9 plays a key role in cholesterol homeostasis by regulating levels of the LDL receptor, which is responsible for the uptake of cholesterol into cells. Inhibition of PCSK9 is designed to prevent the interaction of PCSK9 with LDL receptors. This results in greater numbers of LDL receptors available on the cell surface to remove LDL cholesterol from the blood.

About CORALreef Clinical Trial Program

The efficacy and safety profile of enlicitide is being evaluated through the comprehensive CORALreef Clinical Trial program evaluating over 19,000 participants who have hypercholesterolemia. As previously announced, enlicitide demonstrated statistically significant and clinically meaningful reductions in LDL-C in three pivotal Phase 3 studies: CORALreef Lipids (NCT05952856), CORALreef HeFH (NCT05952869) and CORALreef AddOn (NCT06450366). Enlicitide is continuing to be evaluated in the large cardiovascular outcomes trial, CORALreef Outcomes (NCT06008756), which has completed enrollment with over 14,500 participants. Additional CORALreef clinical trials include CORALreef Extension (NCT06492291), CORALreef Pediatric (NCT07058077) and CORALreef Combination (NCT07216482).

About heterozygous familial hypercholesterolemia (HeFH)

Heterozygous familial hypercholesterolemia (HeFH) is a common genetic disorder that affects approximately 1 in 250 individuals and is characterized by elevated levels of LDL-C. Patients with HeFH typically present with substantially elevated LDL-C levels and face an increased risk of premature atherosclerotic cardiovascular disease (ASCVD) due to cumulative lifetime exposure to LDL-C. HeFH cannot be managed through lifestyle and diet changes alone, and cholesterol-lowering medication is typically needed for patients to manage this condition. A large proportion of patients with HeFH fail to achieve guideline-recommended LDL-C goals despite available therapies and have a 13-fold higher risk for coronary artery disease compared with the general population.

About the CV epidemic and atherosclerotic cardiovascular disease

The silent CV epidemic is the leading cause of deaths globally, contributing to the majority of heart attacks and strokes, and deaths related to CV continue to rise. ASCVD accounts for 85% of CV deaths. It is caused by the buildup of plaque within the arteries, leading to narrowed or blocked blood vessels that can result in serious CV events such as heart attacks and strokes as well as coronary artery disease, peripheral artery disease and cerebrovascular disease.

Merck’s focus on cardiovascular disease

Merck has a long history of developing treatments for cardiovascular disease. Nearly 70 years ago, we introduced our first cardiovascular therapy—and our scientific efforts to understand and treat cardiovascular-related disorders have continued. Cardiovascular disease continues to be one of the most serious health challenges of the 21st century and is the leading cause of death worldwide. Approximately 18 million people across the globe die from cardiovascular disease every year; in the United States, one person dies every 36 seconds from cardiovascular disease.

At Merck, we strive for scientific excellence and innovation in all stages of research, from discovery through approval and life cycle management. We work with experts throughout the cardiovascular and pulmonary community to advance research that can help improve the lives of patients globally.

Information for other currently enrolling cardiovascular studies can be found by visiting: https://www.merckclinicaltrials.com/cardiovascular.

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.

Forward-Looking Statement of Merck & Co., Inc., Rahway, N.J., USA

This news release of Merck & Co., Inc., Rahway, N.J., USA (the “company”) includes “forward-looking statements” within the meaning of the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995. These statements are based upon the current beliefs and expectations of the company’s management and are subject to significant risks and uncertainties. There can be no guarantees with respect to pipeline candidates that the candidates will receive the necessary regulatory approvals or that they will prove to be commercially successful. If underlying assumptions prove inaccurate or risks or uncertainties materialize, actual results may differ materially from those set forth in the forward-looking statements.

Risks and uncertainties include but are not limited to, general industry conditions and competition; general economic factors, including interest rate and currency exchange rate fluctuations; the impact of pharmaceutical industry regulation and health care legislation in the United States and internationally; global trends toward health care cost containment; technological advances, new products and patents attained by competitors; challenges inherent in new product development, including obtaining regulatory approval; the company’s ability to accurately predict future market conditions; manufacturing difficulties or delays; financial instability of international economies and sovereign risk; dependence on the effectiveness of the company’s patents and other protections for innovative products; and the exposure to litigation, including patent litigation, and/or regulatory actions.

The company undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise. Additional factors that could cause results to differ materially from those described in the forward-looking statements can be found in the company’s Annual Report on Form 10-K for the year ended December 31, 2024 and the company’s other filings with the Securities and Exchange Commission (SEC) available at the SEC’s Internet site (www.sec.gov).

Contacts

Media Contacts:

Julie Cunningham

(617) 519-6264

Justine Moore

(347) 281-3754

Investor Contacts:

Peter Dannenbaum

(732) 594-1579

Ayn Wisler

(917) 691-6218

Baxdrostat demonstrated a statistically significant and highly clinically meaningful placebo-adjusted reduction of 14.0 mmHg in 24-hour ambulatory systolic blood pressure in patients with resistant hypertension in the Bax24 Phase III trial




Baxdrostat demonstrated a statistically significant and highly clinically meaningful placebo-adjusted reduction of 14.0 mmHg in 24-hour ambulatory systolic blood pressure in patients with resistant hypertension in the Bax24 Phase III trial

Baxdrostat demonstrated a statistically significant placebo-adjusted reduction of 13.9 mmHg in night-time ambulatory systolic blood pressure at 12 weeks with a safety profile consistent with the BaxHTN trial

Full results presented at the American Heart Association Scientific Sessions 2025

WILMINGTON, Del.–(BUSINESS WIRE)–Positive full results from the Bax24 Phase III trial showed baxdrostat demonstrated a statistically significant and highly clinically meaningful reduction in ambulatory 24-hour average systolic blood pressure (SBP) compared with placebo at 12 weeks. Patients with treatment-resistant hypertension (rHTN) received baxdrostat 2mg or placebo on top of standard of care.¹ Efficacy was observed throughout the 24-hour period, including early morning, when patients with hypertension are at a higher risk of cardiovascular events.^2-4

Baxdrostat met the primary endpoint in the Bax24 Phase III trial, delivering clinically meaningful and consistent blood pressure reductions in patients with treatment-resistant hypertension. At 12 weeks, the placebo-adjusted reduction in ambulatory 24-hour average SBP was 14.0 mmHg (95% confidence interval [CI] -17.2, -10.8; p<0.0001).¹ Baxdrostat was generally well tolerated, with a safety profile consistent with the BaxHTN trial.^1,5

Baxdrostat demonstrated statistically significant and clinically meaningful reductions in key secondary endpoints, including ambulatory night-time average SBP (13.9 mmHg placebo-adjusted [95% CI -17.5, -10.3; p<0.0001]) and seated SBP (10.3 mmHg placebo-adjusted [95% CI -14.9, -5.6; p<0.0001]) consistent with data from the BaxHTN trial.^1,5 Significantly more patients treated with baxdrostat (71%) achieved ambulatory 24-hour average SBP of less than 130 mmHg compared with patients receiving placebo (17%) (Odds ratio 15.2 [95% CI 6.6, 35.2; p<0.0001]).¹

Dr. Bryan Williams, Chair of Medicine at University College London, primary investigator, said: “The landmark results from Bax24 Phase III trial demonstrate that patients with the hardest-to-control hypertension treated with baxdrostat achieved a highly clinically meaningful 14 mmHg placebo-adjusted reduction in 24-hour systolic blood pressure, which could transform treatment practice. It’s remarkable to see this magnitude of reduction coupled with the fact that just over 70% of baxdrostat patients achieved guideline targets, consistently over 24 hours.”

Sharon Barr, Executive Vice President, BioPharmaceuticals R&D, said: “The Bax24 data demonstrate the significant impact that baxdrostat’s long half-life and highly selective inhibition of aldosterone synthase can have in improving 24-hour and overnight blood pressure for patients with resistant hypertension. Patients with elevated night-time blood pressure are especially vulnerable to cardiovascular events, including heart attack and stroke. Together with the results from BaxHTN, these findings demonstrate the potential of baxdrostat to redefine what is possible for the millions of patients whose hypertension remains uncontrolled despite current therapies.”

There are 1.4 billion people worldwide living with hypertension.⁶ In the US, approximately 50% of patients living with hypertension on multiple treatments do not have their blood pressure under control.⁷ Consistent 24-hour blood pressure control is an important clinical outcome in patients with hard-to-control hypertension.^8-10 Multiple studies have demonstrated that 24-hour blood pressure is a more powerful predictor of cardiovascular events than a clinic-based measurement.^4,11 When 24-hour average systolic blood pressure rises by 9.5 mmHg, the risk of all-cause mortality increases by 30%.⁴

Full results from the Bax24 trial were presented today at the Emerging Opportunities for Managing Cardiometabolic Syndrome late breaker session at the American Heart Association (AHA) Scientific Sessions 2025. These data will be shared with regulatory authorities around the world.

Baxdrostat is designed to lower blood pressure by specifically inhibiting aldosterone, a key hormone that raises blood pressure and increases the risk of heart and kidney problems. Phase I studies show baxdrostat reached peak levels in the blood within 2 to 4 hours and had a half-life of about 26 to 30 hours.^12,13 Baxdrostat is currently being investigated as a monotherapy for hypertension^13-16 and primary aldosteronism,¹⁷ and in combination with dapagliflozin for chronic kidney disease^18,19 and the prevention of heart failure in high-risk patients.²⁰

Primary and secondary endpoints¹

*The main analyses of ambulatory BP endpoints include patients with valid ambulatory blood pressure monitoring at both baseline and Week 12, without imputation of missing data.

LS, least squares; n Number of subjects in analysis; N Number of subjects per treatment group

Notes

Hard-to-control hypertension

Hypertension is a medical condition characterized by consistently high blood pressure levels, affecting an estimated 1.4 billion people worldwide.^6,21,22 Over time, this can damage blood vessels and vital organs, increasing the risk of serious health problems such as heart attack, stroke, heart failure and kidney disease.^20,21 An observational study of nearly 60,000 patients studied over a median of 9.7 years showed that a 9.5 mmHg increase in 24-hour ambulatory SBP was associated with a 30% increase in risk of all-cause mortality and 41% increase in risk of cardiovascular death.⁴ Studies have shown that increased night-time blood pressure is associated with higher cardiovascular risk,^8,11 and patients with hypertension have a higher risk of cardiovascular events like heart attack, stroke and death around the time of their morning blood pressure surge.^2,3

Hard-to-control (uncontrolled and resistant) hypertension remains a major public health challenge.²³ Despite lifestyle changes and the use of multiple medications, approximately 50% of patients in the US who are being treated for hypertension still do not have their blood pressure under control.⁷ Uncontrolled hypertension refers to persistently elevated blood pressure despite the use of two or more medications, while resistant hypertension, a more severe form, remains elevated despite treatment with three or more medications.^7,21 Guidelines currently recommend that in patients with hypertension, treated BP values should be targeted to 130/80 mmHg or lower in most patients.^21,22

A key contributor to hard-to-control hypertension is aldosterone, a hormone that raises blood pressure by promoting sodium and water retention.^24,25 Elevated aldosterone levels, along with factors such as obesity, high salt intake, and various genetic or secondary conditions,²⁶ are strongly associated with poor blood pressure control. When left untreated, hypertension significantly increases the risk of cardiovascular and kidney-related complications.^21,22

Bax24 trial

The Phase III Bax24 trial¹⁶ is a randomized, double-blind, placebo-controlled, parallel group study to evaluate the effects of 2mg baxdrostat versus placebo, administered once a day (QD) orally, on the reduction of ambulatory SBP, as well as safety and tolerability in participants with resistant hypertension. A total of 218 patients were randomized in a 1:1 ratio to receive baxdrostat 2mg or placebo once daily during a 12-week double blind period. The primary efficacy endpoint was the change from baseline in ambulatory 24-hour average SBP at Week 12.

Additional secondary endpoints include the effect of baxdrostat versus placebo on change from baseline in ambulatory night-time average SBP, change from baseline in ambulatory daytime average SBP, change from baseline in seated SBP, the number of participants achieving ambulatory 24-hour average SBP of less than 130 mmHg , change from baseline in ambulatory 24-hour average diastolic blood pressure (DBP), change from baseline in ambulatory night-time average DBP, change from baseline in the average ambulatory daytime average DBP, change from baseline on seated DBP and the number of participants achieving a nocturnal SBP dipping of greater than or equal to 10%, all measured at Week 12. Occurrence of adverse events was evaluated during the 12-week treatment period as well as during a 2-week safety follow-up period.

Baxdrostat

Baxdrostat is a potential first-in-class, highly selective and potent, oral, small molecule that inhibits aldosterone synthase,¹² an enzyme encoded by the CYP11B2 gene, which is responsible for the synthesis of aldosterone in the adrenal gland.²⁴ In clinical trials, baxdrostat was observed to significantly lower aldosterone levels without affecting cortisol levels across a wide range of doses.^13,27 Baxdrostat is currently being investigated in clinical trials as a monotherapy for hypertension^13-16 and primary aldosteronism,¹⁷ and in combination with dapagliflozin for chronic kidney disease and hypertension,^18,19 and the prevention of heart failure in high-risk patients.²⁰

AstraZeneca acquired baxdrostat through its purchase of CinCor Pharma, Inc. in February 2023.²⁸

AstraZeneca in CVRM

Cardiovascular, Renal and Metabolism (CVRM), part of BioPharmaceuticals, forms one of AstraZeneca’s main disease areas and is a key growth driver for the Company. By following the science to understand more clearly the underlying links between the heart, kidneys, liver and pancreas, AstraZeneca is investing in a portfolio of medicines for organ protection by slowing or stopping disease progression, and ultimately paving the way towards regenerative therapies. The Company’s ambition is to improve and save the lives of millions of people, by better understanding the interconnections between CVRM diseases and targeting the mechanisms that drive them, so we can detect, diagnose and treat people earlier and more effectively.

AstraZeneca

AstraZeneca is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialization of prescription medicines in Oncology, Rare Diseases and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca’s innovative medicines are sold in more than 125 countries and used by millions of patients worldwide. Please visit www.astrazeneca-us.com and follow the Company on social media @AstraZeneca.

References

1. Williams B, et al. Effect of baxdrostat on 24-hour ambulatory blood pressure in patients with resistant hypertension: the Bax24 trial. Presented at: American Heart Association Scientific Sessions 2025; November 7–10, 2025; New Orleans, LA.
2. Renna NF, et al. Morning blood pressure surge as a predictor of cardiovascular events in patients with hypertension. Blood Press Monit. 2023;28(3):149-157
3. Kario K et al. Morning hypertension: the strongest independent risk factor for stroke in elderly hypertensive patients. Hypertens Res. 2006;29(8):581-7.
4. Staplin N, et al. Relationship between clinic and ambulatory blood pressure and mortality: an observational cohort study in 59 124 patients. Lancet. 2023;401(10393):2041-2050.
5. Flack JM, et al. Efficacy and Safety of Baxdrostat in Uncontrolled and Resistant Hypertension. N Engl J Med. 2025. Aug 30:10.1056/NEJMoa2507109. doi: 10.1056/NEJMoa2507109.
6. World Health Organization. Global report on hypertension 2025: high stakes: turning evidence into action. 2025. https://iris.who.int/handle/10665/382841. Accessed September 2025.
7. Carey RM, et al. Prevalence of Apparent Treatment-Resistant Hypertension in the United States. Hypertension. 2019;73(2):424-431.
8. Narita K, et al. Nighttime Home Blood Pressure Is Associated With the Cardiovascular Disease Events Risk in Treatment-Resistant Hypertension. Hypertension. 2022;79(2):e18-e20
9. Kario K, et al. Nighttime Blood Pressure Phenotype and Cardiovascular Prognosis. Circulation. 2020;142(19):1810-1820
10. Williams B, et al. 2018 ESC/ESH Guidelines for the management of arterial hypertension: The Task Force for the management of arterial hypertension of the European Society of Cardiology (ESC) and the European Society of Hypertension (ESH). European Heart Journal. 2018;39(33):3021-3104.
11. Niiranen TJ, Mäki J, Puukka P, Karanko H, Jula AM. Office, home, and ambulatory blood pressures as predictors of cardiovascular risk. Hypertension. 2014 Aug;64(2):281-6.
12. Bogman K, et al. Preclinical and early clinical profile of a highly selective and potent oral inhibitor of aldosterone synthase (CYP11B2). Hypertension. 2017;69(1):189-196.
13. Freeman MW, et al. Results from a phase 1, randomized, double-blind, multiple ascending dose study characterizing the pharmacokinetics and demonstrating the safety and selectivity of the aldosterone synthase inhibitor baxdrostat in healthy volunteers. Hypertens Res. 2023;46(1):108-118.
14. ClinicalTrials.gov.A Study to Investigate the Efficacy and Safety of Baxdrostat in Participants With Uncontrolled Hypertension on Two or More Medications Including Participants With Resistant Hypertension (BaxHTN). Available at: https://clinicaltrials.gov/study/NCT06034743. Accessed October 2025.
15. ClinicalTrials.gov. A Study to Investigate the Efficacy and Safety of Baxdrostat in Participants With Uncontrolled Hypertension on Two or More Medications Including Participants With Resistant Hypertension (BaxAsia). Available at: https://clinicaltrials.gov/study/NCT06344104. Accessed October 2025.
16. ClinicalTrials.gov. A Study to Investigate the Effect of Baxdrostat on Ambulatory Blood Pressure in Participants With Resistant Hypertension (Bax24). Available at: https://clinicaltrials.gov/study/NCT06168409. Accessed October 2025.
17. ClinicalTrials.gov. A Study to Assess Efficacy and Safety of Baxdrostat in Participants With Primary Aldosteronism (BaxPA). Available at: https://clinicaltrials.gov/study/NCT07007793. Accessed October 2025.
18. ClinicalTrials.gov. A Phase III Study to Investigate the Efficacy and Safety of Baxdrostat in Combination With Dapagliflozin on CKD Progression in Participants With CKD and High Blood Pressure. Available at: https://clinicaltrials.gov/study/NCT06268873. Accessed October 2025.
19. ClinicalTrials.gov. A Phase III Renal Outcomes and Cardiovascular Mortality Study to Investigate the Efficacy and Safety of Baxdrostat in Combination With Dapagliflozin in Participants With Chronic Kidney Disease and High Blood Pressure (BaxDuo-Pacific). Available at: https://clinicaltrials.gov/study/NCT06742723. Accessed October 2025.
20. ClinicalTrials.gov. Phase III Study Investigating Heart Failure and Cardiovascular Death With Baxdrostat in Combination With Dapagliflozin (Prevent-HF). Available at: https://clinicaltrials.gov/study/NCT06677060. Accessed October 2025.
21. McEvoy JW, et al. 2024 ESC Guidelines for the management of elevated blood pressure and hypertension. Eur Heart J. 2024;45(38):3912-4018.
22. Jones DW, et al. 2025 AHA/ACC/AANP/AAPA/ABC/ACCP/ACPM/AGS/AMA/ASPC/NMA/PCNA/SGIM Guideline for the Prevention, Detection, Evaluation and Management of High Blood Pressure in Adults: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation 2025;152:e114–e218.
23. NCD Risk Factor Collaboration (NCD-RisC). Worldwide trends in hypertension prevalence and progress in treatment and control from 1990 to 2019: a pooled analysis of 1201 population-representative studies with 104 million participants. Lancet. 2021;398(10304):957-980.
24. Cannavo A, et al. Aldosterone and mineralocorticoid receptor system in cardiovascular physiology and pathophysiology. Oxid Med Cell Longev. 2018;2018:1204598.
25. Inoue K, et al. Serum aldosterone concentration, blood pressure, and coronary artery calcium: The multi-ethnic study of atherosclerosis. Hypertension. 2020;76(1):113-120.
26. van Oort S, et al. Association of cardiovascular risk factors and lifestyle behaviors with hypertension: a mendelian randomization study. Hypertension. 2020;76(6):1971-1979.
27. Freeman MW, et al. Phase 2 trial of baxdrostat for treatment-resistant hypertension. N Engl J Med. 2023;388(5):395-405.
28. AstraZeneca 2023. Acquisition of CinCor Pharma complete. https://www.astrazeneca.com/media-centre/press-releases/2023/astrazeneca-acquires-cincor-for-cardiorenal-asset.html. Accessed October 2025.

Contacts

Media Inquiries
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US Media Mailbox: usmediateam@astrazeneca.com

Vertex Presents Updated Phase 1/2 Data From RUBY-3 Study That Continue to Demonstrate Best-in-Class Potential for Povetacicept in Adults with IgA Nephropathy and Primary Membranous Nephropathy at American Society of Nephrology Kidney Week




Vertex Presents Updated Phase 1/2 Data From RUBY-3 Study That Continue to Demonstrate Best-in-Class Potential for Povetacicept in Adults with IgA Nephropathy and Primary Membranous Nephropathy at American Society of Nephrology Kidney Week

– 48-week data show a 64% decrease from baseline in proteinuria in IgA nephropathy, 82% decrease from baseline in proteinuria in primary membranous nephropathy, and stabilization of estimated glomerular filtration rate across both diseases –

– Vertex on track to initiate rolling submission of Biologics License Application for potential accelerated approval to the U.S. Food and Drug Administration this year; full enrollment completed for Phase 3 RAINIER trial in IgA nephropathy –

– Povetacicept in primary membranous nephropathy granted Fast Track Designation by the U.S. Food and Drug Administration and Phase 2/3 pivotal trial initiated –

BOSTON–(BUSINESS WIRE)–Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) today announced updated data for povetacicept (pove) in IgA nephropathy (IgAN) and primary membranous nephropathy (pMN) from the ongoing RUBY-3 trial at the American Society of Nephrology (ASN) Kidney Week 2025 in Houston, Texas. Pove is an investigational recombinant fusion protein therapeutic and dual inhibitor of the BAFF (B cell activating factor) and APRIL (a proliferation inducing ligand) cytokines. Pove is the only BAFF+APRIL inhibitor in pivotal trials for multiple kidney diseases.

Results were presented today as a late-breaking oral presentation (SA-OR091) and included interim data from the open-label Phase 1/2 RUBY-3 trial, where adults with IgAN and pMN received pove subcutaneously every 4 weeks. The analysis included 21 participants with IgAN and 10 participants with pMN treated with pove at the 80mg dose, of which 17 participants and 5 participants, respectively, completed the Week 48 study visit.

Results in IgAN

In IgAN, key efficacy findings for the pove 80mg cohort at 48 weeks showed a 64% decrease from baseline in mean 24-hour urine protein to creatinine ratio (UPCR), estimated glomerular filtration rate (eGFR) stabilization with change from baseline in eGFR (mean±SE) of 3.3±3.1 mL/min/1.73m², 90% (9/10) of participants achieving hematuria resolution (defined as a decrease to negative or small levels of urine blood in participants with baseline levels of urine blood of moderate or large), and 53% of participants achieving clinical remission (defined as UPCR <0.5 g/g, negative hematuria, and <25% reduction in eGFR vs. baseline).

Results in pMN

In pMN, key efficacy findings for the pove 80mg cohort at 48 weeks showed an 82% decrease from baseline in mean 24-hour UPCR, eGFR stabilization with change from baseline in eGFR (mean±SE) of -0.3±3.4 mL/min/1.73m², and 40% of participants achieving complete clinical remission (defined as UPCR <0.5 g/g).

Pove was generally safe and well tolerated with adverse events (AEs) that were mostly mild or moderate in severity. There were no serious adverse events related to povetacicept. The safety data is consistent with previous interim analyses, and the safety profile is similar between the IgAN and pMN cohorts.

“These impressive data demonstrate the viability of BAFF+APRIL inhibition to transform the treatment of serious kidney diseases such as IgAN and pMN, important areas of high unmet need,” said RUBY-3 Principal Investigator James Tumlin, M.D., Professor, Department of Medicine, Emory University School of Medicine, and Director of Clinical Research at Georgia Nephrology. “In IgAN, it is especially encouraging to see that at 48 weeks of follow up, a full two-thirds of the participants treated with pove achieved a complete response as defined by UPCR <0.5 g/g, which is in line with the most recent KDIGO guidelines.”

“The exceptionally fast pace of enrollment for the Phase 3 RAINIER trial demonstrates the unmet demand to find effective interventions in IgAN,” said RAINIER Steering Committee Member Richard Lafayette, M.D., Professor of Medicine (Nephrology) at the Stanford University Medical Center. “People living with IgAN and pMN indeed need additional disease-modifying treatments that address the specific drivers of nephron loss and will provide lasting disease control. Pove’s data from RUBY-3 in two serious kidney diseases support the utility of a dual BAFF+APRIL approach, and we are increasingly excited awaiting the RAINIER Phase 3 results.”

Next Steps for Pove Development

Vertex recently announced the U.S. Food and Drug Administration (FDA) granted Breakthrough Therapy Designation for pove in IgAN, and the Company expects to submit the first module of the Biologics License Application (BLA) rolling submission this year for potential accelerated approval. Vertex has notified the FDA of its intent to use a priority review voucher to expedite the review of the pove BLA in IgAN from ten months to six months. The Phase 3 RAINIER study is now fully enrolled.

Vertex also received Fast Track Designation from the FDA for pove in pMN, and recruitment for the pivotal Phase 2/3 OLYMPUS trial is currently underway. pMN is the second indication in which pove has demonstrated best-in-class potential.

Investor Event

Vertex will host an investor event at 7:00 p.m. CST (8:00 p.m. EST) in Houston to discuss the updated data for pove in IgAN and pMN and other highlights across its kidney disease portfolio. A live webcast of the presentation and Q&A portions can be accessed through the Investor Relations section of Vertex’s website at https://investors.vrtx.com/. An archived webcast will be available on the company’s website.

Visit news.vrtx.com/asn-kidney-week for more information about Vertex’s presence at ASN Kidney Week 2025.

About Povetacicept (Pove)

Pove is a dual inhibitor of the BAFF and APRIL cytokines, which promote B cell activation, differentiation and/or survival, and provides B cell control by inhibiting the ability of BAFF and APRIL to drive the pathogenesis of multiple autoimmune diseases. Due to its engineered TACI domain, pove has demonstrated greater binding affinity, potency and/or tissue penetration compared to other APRIL, BAFF, and dual BAFF+APRIL inhibitors in preclinical studies. This preclinical data, combined with clinical data observed to date and convenient dosing and administration, give pove best-in-class potential across a number of serious autoimmune diseases driven by uncontrolled B cells. Pove is an investigational agent and has not been approved by health authorities globally.

About IgA Nephropathy (IgAN)

IgAN is a serious, progressive, life-threatening kidney disease driven by uncontrolled autoreactive B cell activity and is the most common cause of primary glomerulonephritis, affecting approximately 300,000 people in the United States and Europe. It is estimated that there are approximately 33,000 diagnosed patients in Japan and approximately 750,000 diagnosed patients in China. IgAN results from the deposition of circulating immune complexes consisting of immunoglobulins and galactose-deficient immunoglobulin A (Gd-IgA1) in the renal glomerular mesangium, triggering kidney injury and fibrosis. Up to 72% of adult IgAN patients progress to end-stage renal disease within 20 years of diagnosis. There are no approved therapies that specifically target the underlying cause of IgAN.

About Primary Membranous Nephropathy (pMN)

pMN is a rare and serious autoimmune glomerular disease, which is driven by uncontrolled autoreactive B cell activity, resulting in autoantibody production against glomerular antigens including protein phospholipase A2 receptor (PLA2R). pMN affects approximately 150,000 people in the United States and Europe. Over-production of these autoantibodies against glomerular antigens results in kidney damage, fibrosis, and renal failure. There are no therapies specifically approved for the treatment of pMN.

About Fast Track Designation

Fast Track Designation is a program administered by the FDA to expedite the development and review of new drugs and biologics that treat serious or life-threatening conditions and have the potential to fill unmet medical needs. This designation is intended to facilitate development and expedite review of qualifying drugs.

About Breakthrough Therapy Designation

The FDA’s BTD is intended to expedite development and review of medicines that aim to address a serious condition with preliminary clinical evidence indicating that the drug may demonstrate substantial improvement over existing treatments on one or more clinically significant endpoints. BTD was granted for pove in IgAN based on data from the Phase 2 RUBY-3 clinical trial.

About RUBY-3

RUBY-3 is an ongoing, multiple-ascending dose, multi-cohort, open label, Phase 1/2 basket study of povetacicept in autoimmune glomerulonephritis, including IgAN, pMN, lupus nephritis and ANCA-associated vasculitis with glomerulonephritis, where povetacicept is being administered subcutaneously for up to 104 weeks.

About RAINIER

RAINIER is a global Phase 3 randomized, placebo-controlled pivotal trial of pove 80 mg administered subcutaneously every four weeks vs. placebo on top of standard of care in approximately 480 people with IgAN. The study is designed to have a pre-planned interim analysis evaluating the percent change from baseline in urine protein to creatinine ratio (UPCR) for the pove arm vs. placebo after a pre-specified number of patients reach 36 weeks of treatment. If positive, the interim analysis may serve as the basis for Vertex to seek accelerated approval in the U.S. Final analysis will occur at two years of treatment, with a primary endpoint of total estimated glomerular filtration rate (eGFR) slope through Week 104. The RAINIER study design was presented as a poster (FR-PO0813) during ASN Kidney Week.

About OLYMPUS

OLYMPUS is a global Phase 2/3 adaptive, randomized, active-controlled pivotal trial of pove in approximately 176 patients with pMN. In the Phase 2 portion, participants will be randomized to receive one of two different doses of pove and after the last participant completes 12 weeks of treatment, the Phase 3 dose will be selected. In the Phase 3 portion, participants will be randomized to receive either the selected dose of pove or a calcineurin inhibitor. Final analysis will occur at two years of treatment, with a primary endpoint of proportion of participants with complete clinical remission at Week 104.

About Vertex

Vertex is a global biotechnology company that invests in scientific innovation to create transformative medicines for people with serious diseases and conditions. The company has approved therapies for cystic fibrosis, sickle cell disease, transfusion-dependent beta thalassemia and acute pain, and it continues to advance clinical and research programs in these areas. Vertex also has a robust clinical pipeline of investigational therapies across a range of modalities in other serious diseases where it has deep insight into causal human biology, including neuropathic pain, APOL1-mediated kidney disease, IgA nephropathy, primary membranous nephropathy, autosomal dominant polycystic kidney disease, type 1 diabetes and myotonic dystrophy type 1.

Vertex was founded in 1989 and has its global headquarters in Boston, with international headquarters in London. Additionally, the company has research and development sites and commercial offices in North America, Europe, Australia, Latin America and the Middle East. Vertex is consistently recognized as one of the industry’s top places to work, including 16 consecutive years on Science magazine’s Top Employers list and one of Fortune’s 100 Best Companies to Work For. For company updates and to learn more about Vertex’s history of innovation, visit www.vrtx.com or follow us on LinkedIn, Facebook, Instagram, YouTube and X.

Special Note Regarding Forward-Looking Statements

This press release contains forward-looking statements as defined in the Private Securities Litigation Reform Act of 1995, as amended, including, without limitation, statements by James Tumlin M.D., and Richard Lafayette, M.D., and statements about the expectations for the Company’s BLA submission for pove in IgAN for potential accelerated approval in the U.S., including expectations for the timing of the submission of the first module and the completion of the full BLA submission, expectations for pove’s best-in-class potential in IgAN and pMN and pipeline-in-a-product potential across a range of diseases, clinical status of and expectations for the OLYMPUS Phase 2/3 trial in pMN, plans for an investor event to discuss updated data for pove in IgAN and pMN and other highlights across the Company’s kidney disease portfolio, expectations for the RAINIER study design and data expectations, including timing of data availability, and expectations that the Company will seek accelerated approval in the U.S., if the RAINIER interim analysis is positive. While Vertex believes the forward-looking statements contained in this press release are accurate, these forward-looking statements represent the company’s beliefs only as of the date of this press release and there are a number of risks and uncertainties that could cause actual events or results to differ materially from those expressed or implied by such forward-looking statements. Those risks and uncertainties include, among other things, that data from a limited number of patients may not be indicative of final clinical trial results, that clinical trial data might not be available on the expected timeline, that data from the company’s research and development programs may not support registration or further development of its compounds due to safety, efficacy, and other risks, that the company may be unable to make the anticipated regulatory submissions on the expected timeline, or at all, and other risks listed under the heading “Risk Factors” in Vertex’s most recent annual report and subsequent quarterly reports filed with the Securities and Exchange Commission at www.sec.gov and available through the company’s website at www.vrtx.com. You should not place undue reliance on these statements or the scientific data presented. Vertex disclaims any obligation to update the information contained in this press release as new information becomes available.

(VRTX-GEN)

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New Post Hoc Analysis from the HELIOS-B Phase 3 Study Shows Vutrisiran Improved Measures of Heart Structure and Function in Patients with ATTR-CM




New Post Hoc Analysis from the HELIOS-B Phase 3 Study Shows Vutrisiran Improved Measures of Heart Structure and Function in Patients with ATTR-CM

− Analyses Presented at the American Heart Association Scientific Sessions 2025 Underscore Vutrisiran’s Differentiated Profile –

− Cardiovascular Magnetic Resonance (CMR) and Echocardiographic Analyses Demonstrate that Treatment with Vutrisiran Resulted in Significant Changes on Multiple Functional and Structural Cardiac Parameters –

– In a Cohort of HELIOS-B Patients, CMR Imaging Showed Amyloid Regression in 22% of Vutrisiran Treated Patients with No Regression Found in Patients Who Received Placebo –

– Treatment with Vutrisiran Preserved Kidney Function in HELIOS-B Patients, and Reduced Risk of Death and Cardiovascular Events in Patients with Advanced Chronic Kidney Disease –

CAMBRIDGE, Mass.–(BUSINESS WIRE)–Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), the leading RNAi therapeutics company, today announced results from new post hoc analyses of the HELIOS-B Phase 3 study of AMVUTTRA^® (vutrisiran), an RNAi therapeutic approved for the treatment of the cardiomyopathy of wild-type or hereditary transthyretin-mediated amyloidosis (ATTR-CM) and the polyneuropathy of hereditary transthyretin-mediated amyloidosis (hATTR-PN) in adults. Data from cardiovascular magnetic resonance (CMR) and echocardiographic imaging as well as renal function analyses were presented at the American Heart Association (AHA) Scientific Sessions 2025 in New Orleans, Louisiana.

As a multisystem disease, ATTR-CM can impact the health and function of organs throughout the body. These analyses evaluated the effect of vutrisiran on critical measures of heart function and structure as well as kidney health, providing deeper insight into its potential impact on key organs affected by the disease.

HELIOS-B Analyses: Cardiac Structure, Function, and Amyloid Burden

In ATTR-CM, amyloid deposits in the heart lead to thickening and stiffening of the ventricles, affecting how well the heart functions and increasing the risk of heart failure and death. Advanced imaging techniques offer insights into structural and functional changes, capturing the overall burden of amyloid deposits and their impact on cardiac function.

• A CMR analysis evaluated a retrospectively identified cohort of HELIOS-B patients from the National Amyloidosis Centre in London who underwent serial CMR scans as part of their routine clinical care at baseline (N=43), Year 1 (N=39), Year 2 (N=26), and Year 3 (N=17).
  • A mixed model analysis that pooled 24- and 36-month data found that treatment with vutrisiran monotherapy was associated with nominally statistically significant and directionally favorable changes in multiple measures of cardiac structure, function, and amyloid burden, including improvements in left and right ventricular ejection fractions as well as stroke volumes and left ventricular mass, compared to placebo.
  • Treatment with vutrisiran also reduced extracellular volume (ECV), which is thought to reflect amyloid buildup in the heart. At Year 3, amyloid regression, as assessed by ECV, was observed in 22% of patients treated with vutrisiran, while no patients who received placebo showed regression; conversely, progression occurred in 63% of patients who received placebo compared to 11% of patients treated with vutrisiran.
  • At Year 3, patients treated with vutrisiran exhibited an absolute mean (standard deviation) reduction in ECV of -0.10% (± 4.72) versus an increase of 7.86% (± 5.67) in the placebo group (p=0.006).
• To further assess cardiac function in patients with ATTR-CM, echocardiographic parameters including left atrial strain (LAS) and right ventricular free wall strain (RVFWS) were evaluated in analyses of the overall HELIOS-B population.
  • The LAS analysis demonstrated that measures of LAS were associated with baseline disease severity, mortality, and cardiovascular (CV) events, and that patients treated with vutrisiran experienced less worsening in LAS at 30 months, compared to those receiving placebo.
  • The RVFWS analysis showed that worse RVFWS was associated with higher risk of adverse outcomes and that treatment with vutrisiran stabilized RVFWS at 30 months, compared to placebo.

“As ATTR-CM progressively damages the heart muscle, making it thicker, stiffer, and less capable of pumping blood effectively, patients experience worsening symptoms, quality of life, and outcomes,” said Marianna Fontana, M.D., Ph.D., HELIOS-B investigator, Professor of Cardiology, University College London, National Amyloidosis Center, Royal Free Hospital, London. “The HELIOS-B CMR analysis provides compelling initial evidence that treatment with vutrisiran can counteract these changes in some patients, as shown by favorable impacts on measures of cardiac structure and function as well as regression of amyloid burden. These results suggest that vutrisiran has the potential not only to slow disease progression, but to reverse some of the structural damage caused by amyloid deposition in the heart in some patients.”

HELIOS-B Analysis: Renal Function and CV Outcomes in Patients with Severe Chronic Kidney Disease (CKD)

Kidney involvement is common in patients with ATTR-CM and is associated with disease progression along with worse patient outcomes as amyloid deposits in the kidneys can lead to a decline in kidney function, indicated by a decreasing estimated glomerular filtration rate (eGFR).

• A post hoc analysis of the HELIOS-B study evaluated the impact of vutrisiran on renal function and assessed the efficacy and safety of vutrisiran in patients who advanced to severe CKD during the double-blind period. Outcomes, including the composite endpoint of all-cause mortality (ACM) and recurrent CV events, as well as safety, were assessed in patients who advanced to CKD Stage 4 or greater (eGFR < 30 mL/min/1.73 m²) in the overall population, vutrisiran monotherapy population, and baseline tafamidis treatment group.
  • In the overall population, treatment with vutrisiran resulted in fewer patients experiencing ≥40% decreases in eGFR from baseline during the double-blind period, compared to placebo (12.7% vs 21.2%).
  • In patients in the overall population who progressed to CKD Stage 4 or greater during the double-blind period, treatment with vutrisiran reduced the risk of ACM and CV events (hazard ratio [HR] 0.47; 95% confidence interval [CI]: 0.26–0.85), compared to placebo.
  • In both analyses, results observed in patients who progressed to CKD Stage 4 or greater were consistent across the overall population, vutrisiran monotherapy, and baseline tafamidis treatment groups, and were also consistent with vutrisiran’s established efficacy profile from the primary HELIOS-B analysis.
  • The safety profile of vutrisiran in patients who advanced to CKD Stage 4 or greater was comparable with that established in the overall population of the HELIOS-B study.

“The new HELIOS-B analyses add depth to the growing body of evidence supporting AMVUTTRA’s first-line potential in ATTR-CM treatment,” said John Vest, M.D., Senior Vice President, TTR Global Clinical Lead, Alnylam. “From heart structure and function to renal health, the benefits observed are consistent across a wide range of measures and analyses, underscoring the potential for protection of the multiple organs impacted by this systemic disease. These findings build on the broadening dataset from HELIOS-B and continue to support the potential of AMVUTTRA to provide meaningful clinical benefit for patients living with this rapidly progressive multisystem disease.”

Data from the HELIOS-B study supported the approvals of AMVUTTRA for the treatment of the cardiomyopathy of wild-type or hereditary ATTR-CM in adults in the United States (US), Brazil, European Union (EU), Japan, United Arab Emirates (UAE), United Kingdom (UK), and Switzerland. AMVUTTRA is an RNAi therapeutic that works upstream to deliver rapid knockdown of transthyretin, addressing the disease at its source, with four subcutaneous doses per year. Collectively, AMVUTTRA has more than 8,000 patient-years of experience worldwide and is the first RNAi therapeutic approved for the treatment of both ATTR-CM and hATTR-PN in adults.

For additional information on Alnylam’s presentations in ATTR-CM at the AHA 2025 Scientific Sessions, please visit Capella.

Indications and Important Safety Information

Indications Approved by the U.S. FDA

AMVUTTRA^® (vutrisiran) is indicated for the treatment of the:

• cardiomyopathy of wild-type or hereditary transthyretin-mediated amyloidosis (ATTR-CM) in adults to reduce cardiovascular mortality, cardiovascular hospitalizations and urgent heart failure visits.
• polyneuropathy of hereditary transthyretin-mediated amyloidosis (hATTR-PN) in adults.

Important Safety Information

Reduced Serum Vitamin A Levels and Recommended Supplementation

AMVUTTRA treatment leads to a decrease in serum vitamin A levels.

Supplementation at the recommended daily allowance (RDA) of vitamin A is advised for patients taking AMVUTTRA. Higher doses than the RDA should not be given to try to achieve normal serum vitamin A levels during treatment with AMVUTTRA, as serum vitamin A levels do not reflect the total vitamin A in the body.

Patients should be referred to an ophthalmologist if they develop ocular symptoms suggestive of vitamin A deficiency (e.g., night blindness).

Adverse Reactions

In a study of patients with hATTR-PN, the most common adverse reactions that occurred in patients treated with AMVUTTRA were pain in extremity (15%), arthralgia (11%), dyspnea (7%), and vitamin A decreased (7%).

In a study of patients with ATTR-CM, no new safety issues were identified.

For additional information about AMVUTTRA, please see the full U.S. Prescribing Information (revised March 2025)

About AMVUTTRA

AMVUTTRA^® (vutrisiran) is an RNAi therapeutic that delivers rapid knockdown of transthyretin (TTR), addressing the underlying cause of transthyretin (ATTR) amyloidosis. It is marketed in more than 15 countries for the treatment of the polyneuropathy of hereditary transthyretin-mediated amyloidosis (hATTR-PN) in adults and it is also approved for the treatment of the cardiomyopathy of wild-type or hereditary transthyretin-mediated amyloidosis (ATTR-CM) in adults in the US, EU, UK, Brazil, Japan, Switzerland, and UAE. In a clinical study, AMVUTTRA rapidly knocked down TTR in as early as six weeks and decreased TTR levels by 87% with two and a half years of treatment. Administered quarterly via subcutaneous injection, AMVUTTRA is the first and only RNAi therapeutic approved for the treatment of both the cardiomyopathy manifestations of ATTR amyloidosis and the polyneuropathy manifestations of hereditary transthyretin-mediated amyloidosis (hATTR).

About ATTR

Transthyretin amyloidosis (ATTR) is an underdiagnosed, rapidly progressive, debilitating and fatal disease caused by misfolded transthyretin (TTR) proteins, which accumulate as amyloid deposits in various parts of the body, including the nerves, heart, and gastrointestinal tract. Patients may present with polyneuropathy, cardiomyopathy, or both manifestations of disease. There are two different forms of ATTR – hereditary ATTR (hATTR), which is caused by a TTR gene variant and affects approximately 50,000 people worldwide, and wild-type ATTR (wtATTR), which occurs without a TTR gene variant and impacts an estimated 200,000 – 300,000 people worldwide.^1-4

About RNAi

RNAi (RNA interference) is a natural cellular process of gene silencing that represents one of the most promising and rapidly advancing frontiers in biology and drug development today.⁵ Its discovery has been heralded as “a major scientific breakthrough that happens once every decade or so,” and was recognized with the award of the 2006 Nobel Prize for Physiology or Medicine.⁶ By harnessing the natural biological process of RNAi occurring in our cells, a new class of medicines known as RNAi therapeutics is now a reality. Small interfering RNA (siRNA), the molecules that mediate RNAi and comprise Alnylam’s RNAi therapeutic platform, function upstream of today’s medicines by potently silencing messenger RNA (mRNA) – the genetic precursors – that encode for disease-causing or disease pathway proteins, thus preventing them from being made.⁵ This is a revolutionary approach with the potential to transform the care of patients with genetic and other diseases.

About Alnylam Pharmaceuticals

Alnylam (Nasdaq: ALNY) has led the translation of RNA interference (RNAi) into a whole new class of innovative medicines with the potential to transform the lives of people afflicted with rare and prevalent diseases with unmet need. Based on Nobel Prize-winning science, RNAi therapeutics represent a powerful, clinically validated approach yielding transformative medicines. Since its founding in 2002, Alnylam has led the RNAi Revolution and continues to deliver on a bold vision to turn scientific possibility into reality. Alnylam’s commercial RNAi therapeutic products include AMVUTTRA^® (vutrisiran), ONPATTRO^® (patisiran), GIVLAARI^® (givosiran), and OXLUMO^® (lumasiran), which are being developed and commercialized by Alnylam, and Leqvio^® (inclisiran) and Qfitlia^™ (fitusiran), which are being developed and commercialized by Alnylam’s partners, Novartis and Sanofi, respectively. Alnylam has a deep pipeline of investigational medicines, including multiple product candidates that are in late-stage development. Alnylam is executing on its “Alnylam P⁵x25” strategy to deliver transformative medicines in both rare and common diseases benefiting patients around the world through sustainable innovation and exceptional financial performance, resulting in a leading biotech profile. Alnylam is headquartered in Cambridge, MA. For more information about our people, science and pipeline, please visit www.alnylam.com and engage with us on X (formerly Twitter) at @Alnylam, or on LinkedIn, Facebook, or Instagram.

Alnylam Forward-Looking Statements

This press release contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. All statements other than historical statements of fact regarding Alnylam’s expectations, beliefs, goals, plans or prospects including, without limitation, Alnylam’s expectations regarding the safety and efficacy of vutrisiran as a treatment for ATTR-CM, including vutrisiran’s impact on measures of cardiac structure and function; the potential for treatment with AMVUTTRA to result in regression of amyloid burden in some patients; the potential of AMVUTTRA to slow disease progression and to reverse some of the structural damage caused by amyloid deposition in the heart in some patients; the potential impact of vutrisiran on key organs affected by ATTR-CM; AMVUTTRA’s potential to be a first-line treatment for ATTR-CM; AMVUTTRA’s potential to protect multiple organs impacted by ATTR-CM and to deliver meaningful clinical benefit for patients living with ATTR-CM; and Alnylam’s ability to execute on its “Alnylam P⁵x25” strategy to deliver transformative medicines in both rare and common diseases benefiting patients around the world through sustainable innovation and exceptional financial performance, resulting in a leading biotech profile should be considered forward-looking statements. Actual results and future plans may differ materially from those indicated by these forward-looking statements as a result of various important risks, uncertainties and other factors, including, without limitation, risks and uncertainties relating to Alnylam’s ability to successfully execute on its “Alnylam P⁵x25” strategy; Alnylam’s ability to discover and develop novel drug candidates and delivery approaches and successfully demonstrate the efficacy and safety of its product candidates; the pre-clinical and clinical results for Alnylam’s product candidates; the possibility of unfavorable new clinical data and further analyses of existing clinical data; interim and preliminary data; the possibility that clinical data are subject to differing interpretations and assessments by regulatory agencies; actions or advice of regulatory agencies and Alnylam’s ability to obtain and maintain regulatory approval for its product candidates, as well as favorable pricing and reimbursement; successfully launching, marketing and selling Alnylam’s approved products globally; delays, interruptions or failures in the manufacture and supply of Alnylam’s product candidates or its marketed products; obtaining, maintaining and protecting intellectual property; Alnylam’s ability to manage its growth and operating expenses through disciplined investment in operations and its ability to achieve a self-sustainable financial profile in the future; Alnylam’s ability to maintain strategic business collaborations; Alnylam’s dependence on third parties for the development and commercialization of certain products; the outcome of litigation; the potential risk of future government investigations; and unexpected expenditures; as well as those risks more fully discussed in the “Risk Factors” filed with Alnylam’s 2024 Annual Report on Form 10-K filed with the Securities and Exchange Commission (SEC), as may be updated from time to time in Alnylam’s subsequent Quarterly Reports on Form 10-Q, and in other filings that Alnylam makes with the SEC. In addition, any forward-looking statements represent Alnylam’s views only as of today and should not be relied upon as representing Alnylam’s views as of any subsequent date. Alnylam explicitly disclaims any obligation, except to the extent required by law, to update any forward-looking statements.

References

¹ Hawkins PN, Ando Y, Dispenzeri A, et al. Ann Med. 2015;47(8):625-638.

² Gertz MA. Am J Manag Care. 2017;23(7):S107-S112.

³ Conceicao I, Gonzalez-Duarte A, Obici L, et al. J Peripher Nerv Syst. 2016;21:5-9.

⁴ Ando Y, Coelho T, Berk JL, et al. Orphanet J Rare Dis. 2013;8:31.

⁵ Elbashir SM, Harborth J, Lendeckel W, et al. Nature. 2001;411(6836):494-498.

⁶ Zamore P. Cell. 2006;127(5):1083-1086.

Contacts

Alnylam Pharmaceuticals, Inc.

Christine Akinc

(Investors and Media)

+1-617-682-4340

Josh Brodsky

(Investors)

+1-617-551-8276

Merck’s Enlicitide Decanoate, an Investigational Oral PCSK9 Inhibitor, Significantly Reduced LDL-C in Phase 3 CORALreef Lipids Trial




Merck’s Enlicitide Decanoate, an Investigational Oral PCSK9 Inhibitor, Significantly Reduced LDL-C in Phase 3 CORALreef Lipids Trial

Enlicitide, designed to deliver antibody-like efficacy, has the potential to be the first approved oral PCSK9 inhibitor to lower LDL-C with a safety profile comparable to placebo

Enlicitide may help address unmet needs in ASCVD, a key driver of the ongoing cardiovascular (CV) epidemic

RAHWAY, N.J.–(BUSINESS WIRE)–Merck (NYSE: MRK), known as MSD outside of the United States and Canada, today announced the first presentation of results from the pivotal Phase 3 CORALreef Lipids trial demonstrating that treatment with enlicitide decanoate, an investigational, once-daily oral proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor, resulted in a statistically significant and clinically meaningful reduction in low-density lipoprotein cholesterol (LDL-C) of 55.8% (primary analysis; 95% CI: -60.9, -50.7; p<0.001) and of 59.7% in a post-hoc reanalysis (95% CI: -62.3, -57.1; p<0.001) compared to placebo at week 24. These late-breaking data will be presented for the first time today at the American Heart Association (AHA) Scientific Sessions 2025 (Abstract #4391578) and were selected for the Late-Breaking Science News Briefing.

In CORALreef Lipids, adults with or at-risk for atherosclerotic cardiovascular disease (ASCVD) on background lipid-lowering therapies or a documented statin intolerance who received once-daily oral enlicitide had statistically significant and clinically meaningful reductions in LDL-C at week 24 (primary endpoint) and statistically significant and sustained reductions in LDL-C through one year (week 52). Enlicitide demonstrated statistically significant reductions in secondary endpoints including non-high-density lipoprotein cholesterol (non-HDL-C), apolipoprotein B (ApoB) and lipoprotein(a) (Lp(a)) at week 24. The overall safety profile was comparable to placebo. High adherence with study intervention (97%) and dosing instructions (≥97%) were observed across treatment groups.

“Enlicitide demonstrated impressive LDL-C reductions with placebo-like safety in the CORALreef Lipids study, underscoring the practice-changing potential of an oral PCSK9 inhibitor,” said Dr. Ann Marie Navar, a lead author of the study and Associate Professor of Medicine in the Division of Cardiology at UT Southwestern Medical Center. “Despite the availability of lipid-lowering therapies such as statins and injectable PCSK9 inhibitors, the majority of patients with atherosclerotic cardiovascular disease do not reach their LDL-C goal. Enlicitide has the potential to help close gaps in achievement of lipid goals in patients with and at risk for cardiovascular events and ultimately help address the ongoing CV epidemic.”

“Enlicitide was designed to deliver PCSK9 antibody-like efficacy and specificity in an easy-to-use pill,” said Dr. Dean Y. Li, president, Merck Research Laboratories. “Enlicitide, if approved, adds to physicians’ armamentarium to lower LDL-C. This moment is the result of Merck’s legacy and commitment to researching ways to help improve ASCVD outcomes for millions worldwide and our strength in medicinal chemistry using our novel macrocyclic peptide platform. Cardiovascular disease is the leading cause of death globally, and we look forward to bringing a potential new option to help address the CV epidemic.”

At one year, enlicitide showed a sustained statistically significant reduction in LDL-C of 47.6% (primary analysis; 95% CI: -52.7, -42.5; p<0.001) and of 52.4% (post-hoc reanalysis; 95% CI: -55.1, -49.7; p<0.001) compared to placebo. At week 24, enlicitide demonstrated reductions in non-HDL-C of 53.4% (95% CI: -55.5, -51.2; p<0.001), ApoB of 50.3% (95% CI: -52.1, -48.5; p<0.001) and Lp(a) of 28.2% (95% CI: -30.3, -26.0; p<0.001) compared to placebo. The study also showed that 67.5% of patients treated with enlicitide achieved the rigorous prespecified goal of at least 50% reduction in LDL-C along with an LDL-C <55 mg/dL (1.42 mmol/L) compared to 1.2% in the placebo arm at week 24.

Enlicitide had a safety profile similar to placebo. There were no apparent differences between the enlicitide and placebo groups in the incidence of any adverse events (AEs), serious AEs or deaths. Discontinuations due to AEs were low and similar between enlicitide (3.1%) and placebo (4.1%).

Merck plans to share data from this trial, along with data from CORALreef HeFH and CORALreef AddOn with regulatory authorities worldwide.

About CORALreef Lipids

CORALreef Lipids (NCT05952856) is a Phase 3 randomized, double-blind, placebo-controlled study designed to evaluate the efficacy, safety and tolerability of enlicitide decanoate in adults with hypercholesterolemia and a history of a major atherosclerotic cardiovascular disease (ASCVD) event or increased risk for a first event. Participants were required to be treated with stable lipid-lowering therapies including at least a moderate or high intensity statin (or have documented statin intolerance). The study enrolled 2,912 participants who were randomized 2:1 to receive either 20mg of once-daily oral enlicitide (n=1,942) or placebo (n=970). The primary endpoints were mean percent change in LDL-C from baseline at week 24 versus placebo, number of participants with one or more AEs, and number of participants who discontinued study drug due to an AE. Multiplicity-controlled secondary efficacy endpoints included: mean percent change from baseline in LDL-C at week 52, mean percent change from baseline in other key atherogenic lipids at week 24 (non-HDL-C, ApoB and Lp(a)).

A post-hoc reanalysis was conducted to revise missing data handling rules that resulted in 5 biologically impossible baseline values being included in the primary analysis. The intent of the reanalysis was to provide a more clinically accurate estimate of the treatment effect.

CORALreef Lipids is the largest completed Phase 3 study evaluating enlicitide in a broad range of participants with elevated LDL-C.

About enlicitide and PCSK9

Enlicitide has the potential to be the first FDA approved oral PCSK9 inhibitor. It is designed to lower LDL-C via the same biological mechanism as currently approved monoclonal antibody, injectable PCSK9 inhibitors but in a daily pill form. Enlicitide is a novel small molecule macrocyclic peptide candidate that binds to PCSK9 and inhibits the interaction of PCSK9 with LDL receptors.

PCSK9 plays a key role in cholesterol homeostasis by regulating levels of the LDL receptor, which is responsible for the uptake of cholesterol into cells. Inhibition of PCSK9 is designed to prevent the interaction of PCSK9 with LDL receptors. This results in greater numbers of LDL receptors available on the cell surface to remove LDL cholesterol from the blood.

About CORALreef Clinical Trial Program

The efficacy and safety profile of enlicitide is being evaluated through the comprehensive CORALreef Clinical Trial program evaluating over 19,000 participants who have hypercholesterolemia. As previously announced, enlicitide demonstrated statistically significant and clinically meaningful reductions in LDL-C in three pivotal Phase 3 studies: CORALreef Lipids (NCT05952856), CORALreef HeFH (NCT05952869) and CORALreef AddOn (NCT06450366). Enlicitide is continuing to be evaluated in the large cardiovascular outcomes trial, CORALreef Outcomes (NCT06008756), which has completed enrollment with over 14,500 participants. Additional CORALreef clinical trials include CORALreef Extension (NCT06492291), CORALreef Pediatric (NCT07058077) and CORALreef Combination (NCT07216482).

About hypercholesterolemia

Hypercholesterolemia, a type of hyperlipidemia, is a disorder in which there are elevated LDL-C levels in the blood. It affects approximately 86 million adults in the U.S. and is a major risk factor for ASCVD. Nearly 70% of people with ASCVD who are treated with lipid-lowering therapies do not reach target LDL cholesterol levels. High LDL-C, if left untreated, can lead to ASCVD events such as heart attacks and strokes.

About the CV epidemic and atherosclerotic cardiovascular disease

The silent CV epidemic is the leading cause of deaths globally, contributing to the majority of heart attacks and strokes, and deaths related to CV continue to rise. ASCVD accounts for 85% of CV deaths. It is caused by the buildup of plaque within the arteries, leading to narrowed or blocked blood vessels that can result in serious CV events such as heart attacks and strokes as well as coronary artery disease, peripheral artery disease and cerebrovascular disease.

Merck’s focus on cardiovascular disease

Merck has a long history of developing treatments for cardiovascular disease. Nearly 70 years ago, we introduced our first cardiovascular therapy—and our scientific efforts to understand and treat cardiovascular-related disorders have continued. Cardiovascular disease continues to be one of the most serious health challenges of the 21st century and is the leading cause of death worldwide. Approximately 18 million people across the globe die from cardiovascular disease every year; in the United States, one person dies every 36 seconds from cardiovascular disease.

Advancements in the treatment of cardiovascular disease can make a critical difference for patients and health systems around the world. At Merck, we strive for scientific excellence and innovation in all stages of research, from discovery through approval and life cycle management. We work with experts throughout the cardiovascular and pulmonary community to advance research that can help improve the lives of patients globally.

Information for other currently enrolling cardiovascular studies can be found by visiting: https://www.merckclinicaltrials.com/cardiovascular.

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.

Forward-Looking Statement of Merck & Co., Inc., Rahway, N.J., USA

This news release of Merck & Co., Inc., Rahway, N.J., USA (the “company”) includes “forward-looking statements” within the meaning of the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995. These statements are based upon the current beliefs and expectations of the company’s management and are subject to significant risks and uncertainties. There can be no guarantees with respect to pipeline candidates that the candidates will receive the necessary regulatory approvals or that they will prove to be commercially successful. If underlying assumptions prove inaccurate or risks or uncertainties materialize, actual results may differ materially from those set forth in the forward-looking statements.

Risks and uncertainties include but are not limited to, general industry conditions and competition; general economic factors, including interest rate and currency exchange rate fluctuations; the impact of pharmaceutical industry regulation and health care legislation in the United States and internationally; global trends toward health care cost containment; technological advances, new products and patents attained by competitors; challenges inherent in new product development, including obtaining regulatory approval; the company’s ability to accurately predict future market conditions; manufacturing difficulties or delays; financial instability of international economies and sovereign risk; dependence on the effectiveness of the company’s patents and other protections for innovative products; and the exposure to litigation, including patent litigation, and/or regulatory actions.

The company undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise. Additional factors that could cause results to differ materially from those described in the forward-looking statements can be found in the company’s Annual Report on Form 10-K for the year ended December 31, 2024 and the company’s other filings with the Securities and Exchange Commission (SEC) available at the SEC’s Internet site (www.sec.gov). 

Contacts

Media Contacts:

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Investor Contacts:

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Groundbreaking pivotal study results of olezarsen for severe hypertriglyceridemia (sHTG) presented as a late breaker at AHA Scientific Sessions




Groundbreaking pivotal study results of olezarsen for severe hypertriglyceridemia (sHTG) presented as a late breaker at AHA Scientific Sessions

– Up to 72% placebo-adjusted mean reduction in fasting triglyceride levels at six months, with reductions sustained through 12 months –

– 86% of olezarsen-treated patients achieved triglyceride levels less than 500 mg/dL, below the risk threshold for acute pancreatitis –

– First and only investigational treatment for sHTG to significantly reduce acute pancreatitis events –

– Data simultaneously published in The New England Journal of Medicine –

– Ionis to host webcast today at 3:00 p.m. ET –

CARLSBAD, Calif.–(BUSINESS WIRE)–Ionis Pharmaceuticals, Inc. (Nasdaq: IONS) today announced positive results from the pivotal Phase 3 CORE and CORE2 studies of olezarsen in people with severe hypertriglyceridemia (sHTG). The studies met the primary endpoint, with olezarsen achieving a highly statistically significant placebo-adjusted mean reduction in fasting triglyceride (TG) levels of up to 72% at six months. The reductions were sustained through 12 months. Olezarsen showed a highly statistically significant 85% reduction in acute pancreatitis events, the first and only time achieved in sHTG. Additionally, 86% of olezarsen-treated patients achieved triglyceride levels less than 500 mg/dL, below the risk threshold for acute pancreatitis. Olezarsen demonstrated favorable safety and tolerability.

These data were presented today during a late-breaking session at the American Heart Association (AHA) Scientific Sessions, taking place November 7-10 in New Orleans, and simultaneously published in The New England Journal of Medicine.

“CORE and CORE2 are the first studies to show a significant reduction in acute pancreatitis events in sHTG, with most patients on olezarsen achieving triglyceride levels below the risk threshold for these potentially life-threatening episodes,” said Nicholas Marston, M.D., M.P.H, presenting author, cardiologist, Brigham and Women’s Hospital, Harvard Medical School. “As a lipid specialist who takes care of sHTG patients, I have seen the major consequences of acute pancreatitis, including cases with recurrent events requiring frequent hospitalizations. Given the modest effects of conventional therapies, these impactful data are a welcome advance and underscore the potential of olezarsen to transform the way we treat sHTG.”

Nearly 1,100 patients were enrolled in the CORE and CORE2 studies, which is the largest pivotal program ever conducted in sHTG, and patients were required to be on standard of care lipid-lowering therapy. The CORE and CORE2 studies met the primary endpoint across doses, with olezarsen demonstrating an up to 72% (p<0.001) placebo-adjusted mean reduction in fasting triglyceride levels at six months. The reductions were sustained through 12 months. Additionally, among patients with baseline levels above these thresholds at 12 months:

• TGs <880 mg/dL: 89% and 88% of patients on olezarsen 50 mg and 80 mg, respectively, achieved triglyceride levels less than 880 mg/dL, the level associated with the highest risk of acute pancreatitis.
• TGs <500 mg/dL: 86% of patients on olezarsen 50 mg and 80 mg achieved triglyceride levels less than 500 mg/dL, below the risk threshold for sHTG and acute pancreatitis.
• TGs <150 mg/dL: 34% and 54% of patients on olezarsen 50 mg and 80 mg, respectively, achieved normal triglyceride levels less than 150 mg/dL.

Olezarsen demonstrated a highly statistically significant 85% reduction in adjudicated acute pancreatitis events at 12 months (p<0.001). These results were based on a total of 22 events in 17 patients in the placebo group, compared to seven events in five patients in the olezarsen group.

• In an overall pooled analysis of the number of patients needed to treat (NNT), treating 20 patients with olezarsen is estimated to prevent one acute pancreatitis event over one year.
• In the highest risk group, patients with triglyceride levels greater than or equal to 880 mg/dL and a history of acute pancreatitis, treating four patients is estimated to prevent one event over one year.

Olezarsen also showed an overall favorable lipid profile, with significant reductions in the secondary endpoints of apoC-III, remnant cholesterol and non-HDL-C.

“Building on olezarsen’s success in treating familial chylomicronemia syndrome, a rare form of sHTG, these groundbreaking results position us to reach a significantly larger patient population who remain at risk of dangerous acute pancreatitis attacks,” said Brett P. Monia, Ph.D., chief executive officer, Ionis. “Olezarsen will be one of two independent launches for Ionis in 2026, our first in a broad population if approved, and is a powerful example of how we are turning groundbreaking science into meaningful medicines that have the potential to change lives.”

Olezarsen demonstrated a favorable safety and tolerability profile in the CORE and CORE2 studies. Adverse events were balanced across treatment arms (75% olezarsen 50 mg; 76% olezarsen 80 mg; 75% placebo). Serious adverse events occurred less frequently in the olezarsen group compared to placebo (9% olezarsen 50 mg; 11% olezarsen 80 mg; 14% placebo). The most common treatment-emergent events were injection site reactions, which were mostly mild and occurred more frequently with olezarsen (10% olezarsen 50 mg; 17% olezarsen 80 mg; 1% placebo).

Several additional parameters were generally consistent with previous study results. At the 80 mg dose, asymptomatic increases in liver enzymes ≥3 times the upper limit of normal occurred in 7% of patients compared to 2% in the placebo group. These were not associated with clinical complications and generally resolved with continued dosing. No cases met the criteria for Hy’s law. Consistent with previously reported results with apoC-III-targeting therapies, small absolute mean elevations in liver fat (2.28% olezarsen 50 mg; 4.18% olezarsen 80 mg; 0.14% placebo) and hemoglobin A1c (HbA1c) (0.25% olezarsen 50 mg; 0.24% olezarsen 80 mg; placebo-adjusted) were observed. Increases in liver fat were not correlated with transaminase elevations and were not associated with clinical sequelae. There were no imbalances in HbA1c in non-diabetic patients.

Ionis is on track to submit a supplemental new drug application for both the 50 mg and 80 mg doses to the FDA by the end of the year. An open-label extension (OLE) study of olezarsen for sHTG is ongoing. More than 90% of patients who completed CORE and CORE2 chose to continue into the OLE.

Webcast

Ionis will host a webcast to discuss the results from the CORE and CORE2 studies on Saturday, November 8 at 3:00 p.m. ET. Interested parties may access the webcast here. A webcast replay will be available for a limited time.

About the CORE and CORE2 Studies

CORE (NCT05079919; n=617) and CORE2 (NCT05552326; n=446), conducted with The TIMI Study Group, are Phase 3 global, multicenter, randomized, double-blind, placebo-controlled trials investigating the safety and efficacy of olezarsen for severe hypertriglyceridemia (sHTG). Participants aged 18 and older with triglyceride levels ≥500 mg/dL were enrolled. Participants were required to be on standard of care therapies for elevated triglycerides. At baseline, 47% and 37% of participants had baseline fasting triglycerides ≥880 mg/dL in CORE and CORE2, respectively. Participants were randomized to receive 50 mg or 80 mg of olezarsen or placebo every 4 weeks via subcutaneous injection for 12 months. The primary endpoint is the percent change from baseline in fasting triglycerides at six months compared to placebo.

About Severe Hypertriglyceridemia

Severe hypertriglyceridemia (sHTG) is defined by severely high triglycerides (≥500 mg/dL) and characterized by an increased risk of acute pancreatitis and other morbidities. Considered a medical emergency, acute pancreatitis causes debilitating abdominal pain that often requires prolonged hospitalization, can lead to permanent organ damage and can become life-threatening. Preventing the first attack is key. In people with a history of acute pancreatitis episodes, the risk of future attacks is even greater. Current standard of care therapies for sHTG and lifestyle modifications (such as diet and exercise) do not sufficiently or consistently lower triglyceride levels or reduce the risks of sHTG in all patients. Approximately 3 million people are living with sHTG in the U.S., including more than 1 million who are considered high risk. High-risk sHTG includes those with triglycerides ≥880 mg/dL or triglycerides ≥500 mg/dL and a history of acute pancreatitis or other comorbidities.

About Olezarsen

Olezarsen is an investigational RNA-targeted medicine being evaluated for the treatment of sHTG. Olezarsen is designed to lower the body’s production of apoC-III, a protein produced in the liver that regulates triglyceride metabolism in the blood. Olezarsen is approved in the U.S. and the European Union as TRYNGOLZA® for adults with familial chylomicronemia syndrome (FCS).

About Ionis Pharmaceuticals, Inc.

For three decades, Ionis has invented medicines that bring better futures to people with serious diseases. Ionis currently has marketed medicines and a leading pipeline in neurology, cardiometabolic disease and select areas of high patient need. As the pioneer in RNA-targeted medicines, Ionis continues to drive innovation in RNA therapies in addition to advancing new approaches in gene editing. A deep understanding of disease biology and industry-leading technology propels our work, coupled with a passion and urgency to deliver life-changing advances for patients. To learn more about Ionis, visit Ionis.com and follow us on X (Twitter), LinkedIn and Instagram.

Ionis Forward-looking Statements

This press release includes forward-looking statements regarding Ionis’ business, the therapeutic and commercial potential of our commercial medicines, olezarsen, additional medicines in development and technologies, and our expectations regarding development and regulatory milestones. Any statement describing Ionis’ goals, expectations, financial or other projections, intentions or beliefs is a forward-looking statement and should be considered an at-risk statement. Such statements are subject to certain risks and uncertainties including those inherent in the process of discovering, developing and commercializing medicines that are safe and effective for use as human therapeutics, and in the endeavor of building a business around such medicines. Ionis’ forward-looking statements also involve assumptions that, if they never materialize or prove correct, could cause its results to differ materially from those expressed or implied by such forward-looking statements. Although Ionis’ forward-looking statements reflect the good faith judgment of its management, these statements are based only on facts and factors currently known by Ionis. Except as required by law, we undertake no obligation to update any forward-looking statements for any reason. As a result, you are cautioned not to rely on these forward-looking statements. These and other risks concerning Ionis’ programs are described in additional detail in Ionis’ annual report on Form 10-K for the year ended December 31, 2024, and most recent Form 10-Q, which are on file with the Securities and Exchange Commission. Copies of these and other documents are available from the Company. In this press release, unless the context requires otherwise, “Ionis,” “Company,” “we,” “our” and “us” all refer to Ionis Pharmaceuticals and its subsidiaries.

Ionis Pharmaceuticals^® and TRYNGOLZA^® are trademarks of Ionis Pharmaceuticals, Inc.

Contacts

Ionis Investor Contact:
D. Wade Walke, Ph.D.

IR@ionis.com 760-603-2331

Ionis Media Contact:
Hayley Soffer

media@ionis.com 760-603-4679

New Data Show Early and Consistent Response to VTAMA® (tapinarof) Cream, 1%, in Children Aged 2+ with Atopic Dermatitis, Including Those With Associated Comorbidities




New Data Show Early and Consistent Response to VTAMA® (tapinarof) Cream, 1%, in Children Aged 2+ with Atopic Dermatitis, Including Those With Associated Comorbidities

• Sub-analysis of children with atopic dermatitis aged 2-17 in pivotal Phase 3 trials revealed early and clinically meaningful improvements in vIGA-AD^™ and EASI-75 (skin clearance and severity), POEM (patient-reported outcomes) and PP-NRS (itch), regardless of comorbidity status, at week 8

JERSEY CITY, N.J.–(BUSINESS WIRE)–Organon (NYSE: OGN), a global independent healthcare company with a focus on women’s health, will present results from a sub-analysis of pooled data from the Phase 3 ADORING 1 and ADORING 2 pivotal trials evaluating VTAMA cream versus vehicle at the 2025 American College of Allergy, Asthma & Immunology (ACAAI) Annual Scientific Meeting in Orlando, Florida, on November 8, 2025. The new data demonstrate that VTAMA cream provided early and consistent response for children aged 2-17 with atopic dermatitis (AD), with or without atopic comorbidities such as asthma, allergic rhinitis and food allergies.

“As many children with atopic dermatitis may also be living with potential comorbidities such as allergies and asthma that may add to their disease burden,¹ it’s important to understand the effects of approved treatments on this population,” said Dr. Luz Fonacier, Professor of Medicine, Section Head of Allergy and Training Program Director, NYU Grossman Long Island School of Medicine. “These reassuring data show tapinarof cream provided early relief, including on bothersome symptoms such as itch, for children as young as 2 years of age with and without comorbidities.”

In the ADORING 1 and ADORING 2 pivotal trials, adults and children (≥2 years; N=813) with moderate to severe AD were randomized to VTAMA cream or vehicle once daily for 8 weeks. The results presented at ACAAI 2025 are from a sub-analysis of the 654 children in the trials aged 2-17, with and without comorbidities associated with AD. The data highlight improvements in clinically relevant patient-reported outcomes, Validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD^™) response, and Eczema Area and Severity Index (EASI) scores in children aged 2-17 years, regardless of comorbidities.

Notable findings include:

• Early improvements in skin clearance were observed, with significant differences in vIGA-AD response rates as early as week 1 and maintained through week 8 in children with or without atopic comorbidities (with comorbidities: 42.3% with VTAMA cream vs. 11.8% with vehicle, p<0.0001; without comorbidities: 49.5% vs. 14.8%, respectively, p<0.0001).
• Improvement in eczema severity, as measured by EASI scores, was observed as early as week 2 and sustained through week 8 (with comorbidities: 54.5% with VTAMA cream vs. 21.8% with vehicle, p<0.0001; without comorbidities: 63.1% vs. 20.4%, respectively, p<0.0001).
• Improvements in patient-reported outcomes, including sleep, as measured by total mean Patient-Oriented Eczema Measure (POEM) and mean POEM sleep scores (based on a single question within the POEM and analyzed separately from the total POEM score), were noted as early as week 1 and maintained through week 8 (total POEM with comorbidities: 6.9 with VTAMA cream vs. 12.0 with vehicle, p<0.0001; total POEM without comorbidities: 6.7 vs. 11.9, respectively, p<0.0001; POEM sleep with comorbidities: 0.9 with VTAMA cream vs. 1.4 with vehicle, p=0.0003; POEM sleep without comorbidities: 0.6 vs. 1.4, respectively, p<0.0001).
• Clinically meaningful improvements in itch (a ≥4-point Peak Pruritus- Numeric Rating Scale [PP-NRS] response) were observed at week 2, based on responder analysis, with continued improvement through week 8 (with comorbidities: 55.6% with VTAMA cream vs. 36.3% with vehicle, p=0.0043; without comorbidities: 63.3% vs. 29.2%, respectively, p<0.0001).

Consistent with the prescribing information, the most frequently reported treatment-emergent adverse events in the sub-analysis of children aged 2-17 in the ADORING 1 and ADORING 2 trials were folliculitis (7.8%), upper respiratory tract infection (4.6%) and headache (3.7%).

“We are proud to announce data from this new sub-analysis demonstrating early and consistent skin clearance with VTAMA cream, as well as other clinically meaningful improvements in key atopic dermatitis measures in children 2 years and older, regardless of comorbidity status,” said Rafael Chaves Cardona, MD, Head of U.S. Medical Affairs and Outcomes Research, Organon. “This study represents the largest pediatric data set to date for VTAMA, and when added to the wealth of data from the pivotal trials, as well as the ADORING 3 open-label, long-term extension trial, these findings support Organon’s commitment to offering treatment options with a favorable safety and efficacy profile for children 2 years and older.”

In December 2024, the U.S. Food and Drug Administration (FDA) approved VTAMA cream for the topical treatment of AD in adults and pediatric patients 2 years of age and older. VTAMA cream was also approved by the FDA in May 2022, for the topical treatment of plaque psoriasis in adults.²

About the Phase 3 Program for VTAMA cream in Atopic Dermatitis

ADORING was the Phase 3 AD clinical development program for VTAMA cream, consisting of two 8-week pivotal trials, ADORING 1 (NCT05014568) and ADORING 2 (NCT05032859), as well as ADORING 3 (NCT05142774), a 48-week, open-label, long-term extension trial.²

INDICATIONS: VTAMA^® (tapinarof) cream, 1% is an aryl hydrocarbon receptor (AhR) agonist indicated for:

• the topical treatment of plaque psoriasis in adults
• the topical treatment of atopic dermatitis in adults and pediatric patients 2 years of age and older

SELECTED SAFETY INFORMATION

Adverse Events: In plaque psoriasis, the most common adverse reactions (incidence ≥1%) were: folliculitis, nasopharyngitis, contact dermatitis, headache, pruritus, and influenza.

Adverse Events: In atopic dermatitis, the most common adverse reactions (incidence ≥1%) were: upper respiratory tract infection, folliculitis, lower respiratory tract infection, headache, asthma, vomiting, ear infection, pain in extremity, and abdominal pain.

Before prescribing VTAMA cream, please read the Prescribing Information.

For more information about VTAMA (tapinarof) cream, 1%, visit www.vtamahcp.com.

About Atopic Dermatitis (AD)

AD, commonly referred to as eczema, is one of the most prevalent inflammatory skin diseases, affecting an estimated 26 million people in the U.S. alone and up to 10% of adults worldwide.^3,4 AD occurs most frequently in children, affecting up to 20% worldwide, including nearly 10 million children in the US.^4,5, The disease results in itchy, red, swollen, and cracked skin, often on the folds of the arms, back of the knees, hands, face, and neck.^3, Itching is an especially bothersome symptom for those with AD, and tends to worsen at night.⁴ Around 90% of children with eczema also have another related condition such as allergies or asthma, according to international survey data.¹

About Organon

Organon (NYSE: OGN) is a global healthcare company with a mission to deliver impactful medicines and solutions for a healthier every day. With a portfolio of over 70 products across Women’s Health and General Medicines, which includes biosimilars, Organon focuses on addressing health needs that uniquely, disproportionately, or differently affect women, while expanding access to essential treatments in over 140 markets.

Headquartered in Jersey City, New Jersey, Organon is committed to advancing access, affordability, and innovation in healthcare. Learn more at www.organon.com and follow us on LinkedIn, Instagram, X, YouTube, TikTok, and Facebook.

Cautionary Note Regarding Forward-Looking Statements

Except for historical information, this press release includes “forward-looking statements” within the meaning of the safe harbor provisions of the US Private Securities Litigation Reform Act of 1995, including, but not limited to, statements about Organon’s expectations about the potential impact of VTAMA as a treatment option for AD. Forward-looking statements may be identified by words such as “potential,” “mission,” “expects,” “will,” or words of similar meaning. These statements are based upon the current beliefs and expectations of Organon’s management and are subject to significant risks and uncertainties. If underlying assumptions prove inaccurate, or risks or uncertainties materialize, actual results may differ materially from those set forth in the forward-looking statements. Factors that could cause results to differ materially from those described in the forward-looking statements can be found in Organon’s filings with the SEC, including Organon’s most recent Annual Report on Form 10-K (as amended), Quarterly Reports on Form 10-Q (as amended), Current Reports on Form 8-K, and other SEC filings, available at the SEC’s Internet site (www.sec.gov). Organon undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise.

© 2025 Organon group of companies. All rights reserved. vIGA-AD is the trademark of Eli Lilly and Co. US-VTA-113019 11/25

¹ Weidinger S, Simpson EL, Silverberg JI, et al. Burden of atopic dermatitis in paediatric patients: an international cross-sectional study. Br J Dermatol. 2024;190(6):846-857. doi:10.1093/bjd/ljad449

² VTAMA (tapinarof) cream, 1%, Prescribing Information. Organon; Revised May 2025.

³ Atopic dermatitis. National Institute of Arthritis and Musculoskeletal and Skin Diseases. November 2022. Accessed August 19, 2025. https://www.niams.nih.gov/health-topics/atopic-dermatitis
⁴ Eczema stats. National Eczema Association. Accessed June 5, 2025. https://nationaleczema.org/research/eczema-facts/
⁵ Global Report on Atopic Dermatitis 2022. International League of Dermatological Societies; 2022. Accessed February 25, 2025. https://www.eczemacouncil.org/assets/docs/global-report-on-atopic-dermatitis-2022.pdf

Contacts

Media Contacts:

Felicia Bisaro

(646) 703-1807

Investor Contact:

Jennifer Halchak

(201) 275-2711

Biomunex to Present Preclinical Data of its MAIT Engager Platform in Immuno-Oncology at 2025 SITC Annual Meeting




Biomunex to Present Preclinical Data of its MAIT Engager Platform in Immuno-Oncology at 2025 SITC Annual Meeting

• Dr. Simon Plyte, Biomunex’s CSO, has been invited to present MAIT engagers preclinical data during an oral communication at 2025 SITC Annual meeting

• With a very attractive safety and efficacy profile, MAIT engagers have a major potential to fuel an innovative portfolio of drug candidates in oncology

• Biomunex’s ambition is to develop the next generation of immunotherapies in oncology: MAIT engagers, bispecific antibodies capable of identifying, mobilizing, and activating MAIT cells, a subpopulation of T cells, to kill cancer cells.

PARIS & CAMBRIDGE, Mass.–(BUSINESS WIRE)–Biomunex Pharmaceuticals, a French biopharmaceutical company specializing in the development of next generation immunotherapies based on the discovery and development of bispecific and multispecific antibodies, today announces presentation of preclinical data from its MAIT engager platform at the Society for Immunotherapy of Cancer’s (“SITC”) 40^th Annual Meeting being held in National Harbor, USA, from November 5th-9th, 2025.

MAIT engagers: a new class of bispecific antibodies for cancer treatment

Invited to present an oral communication on November 8^th, Dr Simon Plyte, Biomunex CSO (Chief Scientific Officer), will make a presentation entitled: “The MAIT Engager platform : rapid generation of several MAIT T cell engagers with significantly improved safety profile and large therapeutic window (Abstract 1197).” He is also presenting a Poster regarding the topic on November 7^th.

Biomunex is developing a large portfolio of MAIT engager drug candidates, a new therapeutic class in immuno-oncology, that is differentiated from classical TCEs (“T cell engagers”). MAIT engagers are bispecific antibodies that identify, mobilize and bridge MAIT cells (Mucosal-Associated Invariant T cells) to cancer cells resulting in MAIT activation and directed killing of tumors; MAIT engagers could become a breakthrough approach in the treatment of many cancers, particularly in solid tumors.

The presentation at SITC Annual meeting will focus on the MAIT engager differentiation from classical CD3+ TCEs and highlight the superior safety of MAIT engagers. MAIT engagers are expected to overcome some of the limitations of current CD3+ TCE therapies, including activation of regulatory T cells (Tregs) and cytokine release syndrome, serious side effects that are difficult to manage for cancer patients.

The Biomunex platform enables rapid generation of several MAIT engagers, that are not only as potent at classical CD3+ T cell engagers but also bring significantly improved safety profile and have the potential to provide a larger therapeutic window in specific tumor types. Moreover, MAIT engagers can effectively induce the “SPARK effect”, enabling long-term durable anti-cancer response.

Based on preclinical data, Biomunex expects the first MAIT engager to enter clinical trials soon. The MAIT engager platform paves the way for a series of innovative new immunotherapeutics targeting many cancers. “MAIT engagers are an attractive approach for the treatment of cancer with breakthrough potential for redefining the standard of care for solid tumors,” comments Dr. Simon Plyte, Biomunex’s CSO. “Presenting those preclinical data as an oral communication and a poster during the 40^th SITC meeting is a unique opportunity in sharing the scientific and medical potential of this innovative approach with the scientific community”.

Biomunex accelerates development of its disruptive immunotherapies pipeline

Biomunex is becoming a major innovative player in oncology. Bi- and multi-specific antibodies and T cell engagers are attracting considerable interest from pharmaceutical companies, with the recent signing of many licensing and partnership agreements, including for Biomunex. “The last few months have marked the beginning of a new chapter in Biomunex’s development with the signing of a major agreement with Ipsen, following other licensing or partnership deals, demonstrating the team’s ability to develop drugs and technologies of interest for the pharmaceutical industry, such as the MAIT engagers presented at 2025 SITC Annual meeting, to treat cancer patients, but also to establish leading licensing agreements and partnerships with the industry,” comments Dr. Pierre-Emmanuel Gerard, Biomunex’s founder and President.

In addition to BMX-502 licensed to Ipsen, Biomunex is developing a portfolio of MAIT engager drug candidates and innovative new therapeutic approaches with high potential, based on its proprietary “Plug-and-Play” BiXAb® platform. This technology enables the generation of breakthrough immunotherapies faster than most other platforms in the field, with excellent drug-like properties and high industrial yield. Biomunex’s first BiXAb drug candidate is currently in Phase 1 clinical development in partnership, as a monotherapy or in combination, in patients with certain solid tumors or hematological malignancies.

***

Details about Biomunex’ presentations at 2025 SITC Annual Meeting

Abstract Title: “The MAIT Engager platform – rapid generation of several MAIT T cell engagers with significantly improved safety profile and large therapeutic window”

Abstract Number: 1197 – Ranked amongst 150 best abstracts.

Poster presentation

Friday 7th Nov, 5:35–7 p.m. ET

Poster Reception | Gaylord National Resort and Convention Center – Lower Level Atrium – Prince George’s ABC

Oral presentation

Saturday 8th Nov, 1:08-1:16 p.m. ET

Concurrent Session 205a: Rapid Oral Abstract Session – Basic

Maryland Ballroom AB

About Biomunex Pharmaceuticals : www.biomunex.com

Biomunex Pharmaceuticals is a biopharmaceutical company based in Paris, France, and Cambridge, MA, USA, specializing in the discovery and development of innovative therapeutic approaches based on solid data and biological and clinical evidence to address unmet medical needs in oncology.

Biomunex has created and developed BiXAb®, a robust, next-generation, plug-and-play technology platform for bi- and multi-specific antibodies, using a proprietary in silico modeling approach, based on a very robust intellectual property and patent portfolio.

The BiXAb platform, which enables the generation of bispecific antibodies from any pair of monoclonal antibodies in a simple, rapid, and cost-effective manner, has been validated through licensing agreements and collaborations with the pharmaceutical and biotechnology industry, including Sanofi, Onward Therapeutics, and most recently Ipsen.

Biomunex is the first company in the world to develop a cancer immunotherapy approach that uses bispecific antibodies from its BiXAb platform to specifically target, engage, and redirect MAIT cells, a subpopulation of T cells naturally present throughout the body, particularly in mucosal and barrier tissues, to kill cancer cells for the treatment of solid tumors.

Contacts

Media:

Biomunex Pharmaceuticals
NewCap Agency – Nicolas Merigeau

nmerigeau@newcap.fr
+33 (0)1 44 71 94 98