Aprocitentan

Multi-phase program to standardize treatment, generate real-world evidence and explore AI-powered tools to improve outcomes for hypertension patients Allschwil, Switzerland & Radnor, Philadelphia – September 5, 2025Idorsia Ltd (SIX: IDIA) announces a first-of-its-kind initiative with the Stanford Hypertension Center and Duke Heart Center to launch IMPACT-HTN, a new three-phase program to transform and modernize the management of difficult-to-control hypertension. Patients requiring multiple medications for difficult-to-control hypertension face increasing challenges with care coordination, evaluation of underlying causes, and worsening outcomes. The initiative, led by Dr. Vivek Bhalla of the Stanford University School of Medicine and Dr. Sreekanth Vemulapalli of Duke University School of Medicine, is expected to generate real-world evidence, standardize clinical decision-making and deliver scalable tools that leverage AI technology to help identify patients with difficult-to-control hypertension who may benefit from innovative therapies that utilize new pathways, including Idorsia's once-daily TRYVIO™ (aprocitentan), the first systemic hypertension treatment to target a new pathway in over 30 years. Sreekanth Vemulapalli, MD, Associate Professor of Medicine, Duke Heart Center, commented:“With novel therapies emerging to improve hypertension control, we are thrilled to work with our esteemed colleagues at Stanford and other hypertension centers to standardize the evaluation, management and access to innovative therapies for our patients with difficult-to-control hypertension. We'll be collaborating with companies to develop high-touch AI tools aimed at supporting the care of our patients to meet people where they are. This is a cross-institutional collaboration which we hope to expand to improve the outcomes of our patients.” Despite progress in improving patient outcomes, hypertension remains a major global health issue, affecting an estimated 50% of adults in the U.S. Patients whose blood pressure that remains above target despite the use of appropriate therapy face significantly higher risks of cardiovascular events, including heart attack, stroke and kidney failure, and are nearly twice as likely to experience premature mortality compared to those with controlled blood pressure. Difficult-to-control hypertension is defined as above-goal elevated blood pressure in a patient despite the concurrent use of multiple antihypertensive drug classes. Vivek Bhalla, MD, Associate Professor of Medicine/Nephrology, Founding Director of the Stanford Hypertension Center, commented: “The IMPACT-HTN program challenges the boundaries of the standard care model for hypertension treatment by building a platform to fundamentally shift how we approach difficult-to-control hypertension. I’m proud to collaborate with Idorsia and Dr. Vemulapalli as well as Dr. Kenneth Mahaffey, the Founding Director of the Stanford Center for Clinical Research for this initiative. By developing and publishing best practices, analyzing real-world data and harnessing emerging technologies, we’re working to deliver impactful solutions that can transform hypertension care and improve lives.”The multi-phased IMPACT-HTN program is expected to deliver actionable tools, data and insights to improve care for those with difficult-to-control hypertension, including: A digital care algorithm to standardize how difficult-to-control hypertension is assessed and managed. Through interactive tools such as patient-facing algorithms, AI chatbots and a program portal, this initiative aims to transform protocols to improve patient care. A personalized hypertension risk score that will build on existing risk scores for prevention to better identify difficult-to-control hypertension patients at risk for negative cardiovascular outcomes so appropriate treatment protocols can be implemented sooner. A prospective early patient experience initiative that will enroll patients from hypertension specialty centers to better understand the treatment obstacles for patients with difficult-to-control hypertension and how newer treatments, like Idorsia's TRYVIO, are impacting the treatment paradigm. Srishti Gupta, MD, CEO of Idorsia, commented: “We are proud to have pioneered the first treatment tackling a new pathway in hypertension in over three decades and as a leader in this area, we understand that our commitment to improving patient outcomes goes beyond the medicine. We are proud to collaborate with two of the world’s leading research institutions, on this exciting new program and believe IMPACT-HTN will help reimagine the pathways of care for hypertension patients who need additional options.” TRYVIO, a dual endothelin receptor antagonist (ERA) is now available to prescribe. It is indicated for the treatment of hypertension in combination with other antihypertensive drugs to lower blood pressure (BP) in adult patients who are not adequately controlled on other drugs. TRYVIO is now included in the American College of Cardiology’s (ACC) and the American Heart Association’s (AHA) new comprehensive clinical practice guidelines for the management of high blood pressure, but many patients remain undiagnosed and undertreated. Important Safety InformationTRYVIO may cause serious side effects, including:TRYVIO can cause major birth defects if used by pregnant patients and has a BOXED Warning for embryo-fetal toxicity. People who can become pregnant must not be pregnant when they start taking TRYVIO or become pregnant during treatment with TRYVIO or for 1 month after stopping treatment with TRYVIO. People who can become pregnant should have a negative pregnancy test before starting treatment with TRYVIO, each month during treatment with TRYVIO, and 1 month after stopping TRYVIO. People who can become pregnant should use acceptable birth control before starting treatment with TRYVIO, during treatment with TRYVIO, and for 1 month after stopping TRYVIO because the medicine may still be in your body. If you are a person who can become pregnant, your healthcare provider will talk to you about pregnancy testing recommendations and the need to use acceptable birth control, the benefits and risks of TRYVIO, and the need to report suspected pregnancy right away to your healthcare provider. What is TRYVIO?TRYVIO is a prescription medicine used to treat high blood pressure (hypertension) in adults who are taking other high blood pressure medicines and whose blood pressure is not well controlled.Do not take TRYVIO if you are pregnant or currently trying to become pregnant. allergic to aprocitentan or any of the ingredients in TRYVIO. Before taking TRYVIO, tell your healthcare provider about all of your medical conditions, including if you: have liver problems have heart failure have anemia have kidney problems or get dialysis are pregnant or plan to become pregnant during treatment with TRYVIO. TRYVIO can cause serious birth defects. are breastfeeding or plan to breastfeed. It is not known if TRYVIO passes into your breastmilk. Do not breastfeed if you take TRYVIO. Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.TRYVIO may cause other serious side effects, including: Liver problems. TRYVIO may cause liver problems. Your healthcare provider should do blood tests to check your liver before starting treatment and as needed during treatment with TRYVIO. Tell your healthcare provider if you have any of the following symptoms of liver problems during treatment with TRYVIO: nausea or vomiting yellowing of your skin or whites of your eyes pain in the upper right stomach dark urine tiredness fever loss of appetite itching Fluid retention. Fluid retention and swelling are common during treatment with TRYVIO and can be serious. Tell your healthcare provider right away if you have any unusual weight gain, trouble breathing, or swelling of your ankles or legs. Your healthcare provider may treat you with other medicines (diuretics) if you develop fluid retention or swelling. Low red blood cell levels (anemia). Anemia is common during treatment with TRYVIO and can be serious. Your healthcare provider will do blood tests to check your red blood cells before starting and as needed during treatment with TRYVIO. Decreased sperm count. TRYVIO may cause decreased sperm counts in males and may affect the ability to father a child. Tell your healthcare provider if being able to have children is important to you. Your healthcare provider may stop treatment with TRYVIO if you develop certain side effects. Tell your healthcare provider if you have any side effect that bothers you or that does not go away.These are not all the possible side effects of TRYVIO. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.For more information see the Full Prescribing Information including BOXED Warning (PI and Medication Guide). Notes to the editor About aprocitentanAprocitentan is Idorsia’s once-daily, orally active, dual endothelin receptor antagonist, which inhibits the binding of ET-1 to ETA and ETB receptors. Aprocitentan is approved as TRYVIO® in the US for the treatment of systemic hypertension in combination with other antihypertensives and has been commercially available since October 2024. Aprocitentan is approved as JERAYGO® for the treatment of resistant hypertension in combination with other antihypertensives in the European Union and the UK and marketing authorization applications are under review in Canada, and Switzerland. About IdorsiaThe purpose of Idorsia is to challenge accepted medical paradigms, answering the questions that matter most. To achieve this, we will discover, develop, and commercialize transformative medicines – either with in-house capabilities or together with partners – and evolve Idorsia into a leading biopharmaceutical company, with a strong scientific core. Headquartered near Basel, Switzerland – a European biotech hub – Idorsia has a highly experienced team of dedicated professionals, covering all disciplines from bench to bedside; QUVIVIQ™ (daridorexant), a different kind of insomnia treatment with the potential to revolutionize this mounting public health concern; strong partners to maximize the value of our portfolio; a promising in-house development pipeline; and a specialized drug discovery engine focused on small-molecule drugs that can change the treatment paradigm for many patients. Idorsia is listed on the SIX Swiss Exchange (ticker symbol: IDIA). For further information, please contact:Investor & Media RelationsIdorsia Pharmaceuticals Ltd, Hegenheimermattweg 91, CH-4123 Allschwil+41 58 844 10 10investor.relations@idorsia.com – media.relations@idorsia.com – www.idorsia.com The above information contains certain "forward-looking statements", relating to the company's business, which can be identified by the use of forward-looking terminology such as “intend”, "estimates", "believes", "expects", "may", "are expected to", "will", "will continue", "should", "would be", "seeks", "pending" or "anticipates" or similar expressions, or by discussions of strategy, plans or intentions. Such statements include descriptions of the company's investment and research and development programs, business development activities and anticipated expenditures in connection therewith, descriptions of new products expected to be introduced by the company and anticipated customer demand for such products and products in the company's existing portfolio. Such statements reflect the current views of the company with respect to future events and are subject to certain risks, uncertainties and assumptions. Many factors could cause the actual results, performance or achievements of the company to be materially different from any future results, performances or achievements that may be expressed or implied by such forward-looking statements. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those described herein as anticipated, believed, estimated or expected. Attachment Press Release PDF Press Release PDF

MADRID — Pivotal data on AstraZeneca’s blood pressure pill baxdrostat look good enough for approval, but competing in the market might be a harder ask as the company prepares for a potential match against another new drug from Mineralys Therapeutics. The three-month blood pressure data presented Saturday showed a strong effect in patients with uncontrolled or resistant hypertension, forms of high blood pressure that do not respond to standard treatment. Patients given the higher dose of baxdrostat in the trial, 2 mg per day, had an absolute reduction in average seated systolic blood pressure of 15.7 mmHg at three months. Adjusted for placebo, the decrease was 9.8mmHg. A lower 1 mg dose of the drug yielded a placebo-adjusted blood pressure drop of 8.7 mmHg. Both differences were good for statistical significance (p=0.001). The data from the BaxHTN study drew applause from delegates at the European Society of Cardiology conference in Madrid, Spain. The results were also published in the NEJM . AstraZeneca needs baxdrostat to be a commercial success, as it paid $1.3 billion upfront for the drug’s originator, CinCor Pharma. The company already toplined the results last month for the pill, an aldosterone synthase inhibitor. But the BaxHTN results appear to lag behind a rival product from Mineralys Therapeutics at the same time point. Mineralys’ pill lorundrostat demonstrated a statistically significant placebo-adjusted blood pressure drop of 11.7 mmHg after three months’ treatment in its pivotal study , with a 50 mg-per-day dose. However, the blood pressure drop at three months was not Mineralys’ trial’s primary endpoint. The study was designed to measure the drop at six weeks, at which point the blood pressure reduction was 9.1 mmHg — slightly less than baxdrostat showed in its trial after patients were treated for twice as long. Mikhail Kosiborod, AstraZeneca’s head of late-stage development of cardiovascular, renal and metabolic drugs, said the crucial data to compare are the trial’s primary goals, even though such comparisons are always imperfect. “Cross-trial comparisons are always problematic, right? But we do them all the time anyway,” he said. Comparing primary endpoint to primary endpoint is “apples to apples,” he said. The 11.7 mmHg finding with lorundrostat was exploratory, he added, and therefore subject to type 1 error, a statistical mistake similar to a false positive. “It’s not a matter of semantics. It’s actually critically important what you define as your primary endpoint,” he said at the meeting, ahead of the data presentation. He argued that the AstraZeneca drug offered “truly clinically meaningful blood pressure reduction in a group of patients that’s very difficult to treat.” That hasn’t stopped Wall Street from making a side-by-side examination anyway. Analysts from Jefferies wrote in an Aug. 18 note that if baxdrostat were to show a blood pressure drop similar to Mineralys’ 11.7 mmHg placebo-adjusted delta — which they define as between 9.7 and 13.7 mmHg — it “should be considered broadly in-line.” And analysts from Goldman Sachs wrote in an Aug. 21 note that “efficacy within 2mmHg of the 11.7mmHg bar set by lorundrostat will represent a strong outcome given nuances in trial design and baxdrostat’s advantages,” which include its longer half-life and lack of drug-drug interactions. Baxdrostat’s safety looked good, with most adverse events being mild. Low rates of confirmed hyperkalemia were seen, with just 1.1% of patients in both dose groups experiencing this closely-watched side effect of high potassium levels (defined as at least 6.0 mmol/L). No cases were seen with placebo. Here, AstraZeneca’s pill is level with lorundrostat. And the UK drugmaker is betting it’s plenty good enough for regulators. “We plan to file for approval before the end of this year, and we hope the regulators will agree with us,” Kosiborod said. The filing will trigger a contingent value right of $10 per share in cash, for a total of $500 million, to former CinCor shareholders. Another drug for resistant hypertension, Idorsia’s endothelin receptor antagonist Tryvio, was approved in the US in 2024 on the strength of a 3.8 mmHg reduction. But Tryvio has a black box safety warning of embryo-fetal toxicity. Editor’s note: This article was updated to add audience reactions from the conference.