^Ad hoc announcement pursuant to Art. 53 LR * Idorsia receives a positive opinion from the Committee for Medicinal Products for Human Use for JERAYGO(TM) (aprocitentan) as the first and only endothelin receptor antagonist for the treatment of resistant hypertension in adult patients in combination with at least three antihypertensive medicinal products. * A CHMP positive opinion is one of the final steps before marketing authorization can be granted by the European Commission - a final decision is expected in approximately two months. Allschwil, Switzerland - April 26, 2024 Idorsia Ltd (SIX: IDIA) announced today that the Committee for Medicinal Products for Human Use (CHMP), the scientific committee of the European Medicines Agency (EMA), adopted a positive opinion for the use of JERAYGO(TM) (aprocitentan) for the treatment of resistant hypertension in adult patients in combination with at least three antihypertensive medicinal products. The CHMP has adopted a positive opinion for the use of 12.5 mg JERAYGO orally once daily. The dose can be increased to 25 mg once daily for patients tolerating the 12.5 mg dose and in need of tighter blood pressure (BP) control. Detailed recommendations for the use of JERAYGO will be described in the summary of product characteristics (SmPC), which will be published in the European public assessment report (EPAR) and made available in all official European Union languages after the marketing authorization has been granted by the European Commission, expected in approximately two months. Hypertension is one of the leading causes of cardiovascular disease worldwide, impacting an estimated 1.3 billion people globally.(1) Approximately 10% of these people have uncontrolled BP, despite receiving at least three antihypertensive medications from different classes, at optimal doses and they are categorized in hypertension guidelines(2,3) as having resistant hypertension. Compared with adults whose hypertension is well controlled, adults with uncontrolled hypertension have greater risk of heart attack, heart failure, stroke, end-stage renal disease and death.(4) Jean-Paul Clozel, MD and Chief Executive Officer of Idorsia commented: "Uncontrolled hypertension, particularly resistant hypertension, where blood pressure remains uncontrolled despite the use of multiple antihypertensive therapies, affects millions of Europeans and is a major public health issue leading to a high risk of heart attack, heart failure, stroke and renal disease, not to mention the increased risk of death. Idorsia has tackled this need by developing aprocitentan, or JERAYGO, the brand name in Europe, an endothelin receptor antagonist discovered by our team and optimized for the treatment of resistant hypertension. As a result of our efforts, physicians and patients in Europe are one step closer to having a new oral antihypertensive therapy - the first in almost 40 years - that is working via a new therapeutic pathway." The positive CHMP opinion is supported by a comprehensive clinical and non- clinical development program. Aprocitentan was evaluated as a monotherapy in a Phase 2 study in patients with hypertension,(11) and as an add-on therapy in a Phase 3 study called PRECISION in patients with confirmed resistant hypertension.(12) In the Phase 3 registration study, PRECISION, aprocitentan showed statistically significant and clinically meaningful reduction in blood pressure (BP) which was maintained for up to 48 weeks when added to a combination of background antihypertensive therapies in patients with resistant hypertension. In PRECISION, aprocitentan was generally well tolerated with no major safety concerns. The most frequent adverse event with aprocitentan was mild-to-moderate edema/fluid retention. The team at Idorsia has been working on the research and development of endothelin receptor antagonists for more than 30 years, successfully bringing three other molecules from this class to patients in different indications. Endothelin (ET)-1, via its receptors (ET(A) and ET(B)), mediates a variety of effects such as vasoconstriction, fibrosis, cell proliferation, inflammation, aldosterone production(7) and is upregulated in hypertension. Aprocitentan is a dual ERA that inhibits the binding of ET-1 to ET(A) and ET(B) receptors and hence the effects mediated by these receptors.(5) The effects of ET-1 bear many similarities with the pathophysiology of hypertension,(6)(,8) and the resistance to other antihypertensive drugs in some patients (often with risk factors such as obesity, sleep apnea, older age, kidney failure, type 2 diabetes, and African Americans), can be explained by an endothelin-dependent hypertension(8). This is now confirmed by the efficacy of aprocitentan in the PRECISION study. About the Phase 3 PRECISION study (NCT03541174 (https://classic.clinicaltrials.gov/ct2/show/NCT03541174))(12) PRECISION was a multicenter, blinded, randomized, parallel-group, Phase 3 study, which was performed in hospitals or research centers in Europe, North America, Asia, and Australia. Patients were eligible for randomization if their sitting systolic blood pressure (SBP) was 140 mm Hg or higher despite taking standardized background therapy consisting of three antihypertensive drugs, including a diuretic. The study consisted of three sequential parts: Part 1 was the 4-week double-blind, randomized, and placebo-controlled part, in which 730 patients were randomized to aprocitentan 12.5 mg (n=243), aprocitentan 25 mg (n=243), or placebo (n=244) in a 1:1:1 ratio; Part 2 was a 32-week single (patient)-blind part, in which all patients received aprocitentan 25 mg (n=704); and Part 3 was a 12-week double-blind, randomized, and placebo-controlled withdrawal part, in which patients were re-randomized to aprocitentan 25 mg (n=307) or placebo (n=307) in a 1:1 ratio. The primary and key secondary endpoints were changes in unattended office SBP from baseline to week 4 and from withdrawal baseline to week 40, respectively. Secondary endpoints included 24-h ambulatory blood pressure changes. At baseline, 69.2% of patients were obese or severely obese, 54.1% had diabetes, 22.2% had stage 3-4 chronic kidney disease and 19.6% had congestive heart failure. At screening, 63% of all patients who were randomly assigned were prescribed four or more antihypertensive drugs. Key PRECISION findings(13) The least square mean change in office SBP at 4 weeks was -15.3 mmHg for aprocitentan 12.5 mg, -15.2 mmHg for 25 mg, and -11.5 mmHg for placebo, for a difference versus placebo of -3.8 mmHg (p=0.0042) and -3.7 mmHg (p=0.0046), respectively (the primary endpoint). Office diastolic blood pressure (DBP) also decreased with both aprocitentan doses compared to placebo (-3.9 mmHg for the 12.5 mg dose and -4.5 mmHg for the 25 mg dose). Office SBP and DBP were maintained during Part 2 in patients previously receiving aprocitentan and decreased within the first 2 weeks of Part 2 before stabilizing in those previously receiving placebo. In Part 3, office SBP after 4 weeks of withdrawal (week 40) (the key secondary endpoint) increased significantly with placebo compared to aprocitentan (5.8 mmHg; p= 75 years), sex, race (including patients with Black or African American origin), BMI, baseline urine albumin-to-creatinine ratio (UACR), baseline estimated Glomerular Filtration Rate (eGFR) and medical history of diabetes, and was consistent with the effect in the overall population. Treatment-emergent adverse events (TEAEs) during the 4-week double-blind study period (Part 1) were reported in 27.6% and 36.7% of the patients treated with 12.5 and 25 mg aprocitentan, respectively, versus 19.4% in the placebo group. The most frequent adverse event with aprocitentan was mild-to-moderate edema/fluid retention leading to discontinuation in seven patients during the study. Edema/fluid retention was reported more frequently with aprocitentan than with placebo in a dose-dependent fashion (9.1%, 18.4%, and 2.1% for patients receiving aprocitentan 12.5 mg, 25 mg and placebo, during Part 1, respectively; 18.2% for patients receiving aprocitentan 25 mg during Part 2; and 2.6% and 1.3% for patients on aprocitentan 25 mg and placebo, during Part 3, respectively). Regulatory status of aprocitentan The positive opinion recommending JERAYGO, is a scientific recommendation issued by the EMA's CHMP, which is sent to the European Commission (EC) for the adoption of a decision on an EU-wide marketing authorization. An EC marketing authorization through the centralized procedure is valid in all European Union Member States, as well as the European Economic Area countries Iceland, Liechtenstein and Norway, and Northern Ireland under the Northern Ireland Protocol. In March, TRYVIO(TM) (aprocitentan) was approved by the US Food and Drug Administration (FDA). Notes to the editor References 1. 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; 398:957-80. 2. Noubiap JJ, et al. Global prevalence of resistant hypertension: a meta- analysis of data from 3·2 million patients. Heart 2019; 105: 98-105. 3. Williams B, et al. 2018 ESC/ESH guidelines for the management of arterial hypertension. Eur Heart J 2018; 39: 3021-104. 4. Daugherty SL, et al. Incidence and prognosis of resistant hypertension in hypertensive patients. Circulation. 2012 Apr 3;125(13):1635-42. 5. Trensz F, et al. Pharmacological characterization of aprocitentan, a dual endothelin receptor antagonist, alone and in combination with blockers of the renin angiotensin system, in two models of experimental hypertension. J Pharmacol Exp Ther. 2019 Mar; 368(3):462-473. 6. Iglarz M, et al. At the heart of tissue: endothelin system and end-organ damage. Clin Sci 2010; 119:453-63. 7. Rossi GP, et al. Endothelin-1 stimulates steroid secretion of human adrenocortical cells ex vivo via both ETA and ETB receptor subtypes. J Clin Endocrinol Metab. 1997, 82: 3445-3449 8. Clozel M. Aprocitentan and the endothelin system in resistant hypertension. Can J Physiol Pharmacol 2022; 100:573-83. 9. Whelton P.K., et al. 2018. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ ASH/ASPC/NMA/PCNA 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 Task Force on clinical practice guidelines. Hypertension, 71: e13-e115. 10. Williams B, et al. 2018 ESC/ESH guidelines for the management of arterial hypertension. Eur Heart J 2018; 39: 3021-104. 11. Verweij P. et al. Randomized Dose-Response Study of the New Dual Endothelin Receptor Antagonist Aprocitentan in Hypertension. Hypertension. 2020;75:956-965 12. Danaietash P et al. Identifying and treating resistant hypertension in PRECISION: A randomized long-term clinical trial with aprocitentan. J Clin Hypertension 2022 Jul;24(7):804-813. 13. Schlaich MP, et al. A randomized controlled trial of the dual endothelin antagonist aprocitentan for resistant hypertension. The Lancet, 2022; Dec 3;400(10367):1927-1937. About Idorsia Idorsia Ltd is reaching out for more - We have more ideas, we see more opportunities and we want to help more patients. In order to achieve this, we will develop Idorsia into a leading biopharmaceutical company, with a strong scientific core. Headquartered near Basel, Switzerland - a European biotech-hub - Idorsia is specialized in the discovery, development and commercialization of small molecules to transform the horizon of therapeutic options. Idorsia has a 25-year heritage of drug discovery, a broad portfolio of innovative drugs in the pipeline, an experienced team of professionals covering all disciplines from bench to bedside, and commercial operations in Europe and North America - the ideal constellation for bringing innovative medicines to patients. Idorsia was listed on the SIX Swiss Exchange (ticker symbol: IDIA) in June 2017 and has over 750 highly qualified specialists dedicated to realizing our ambitious targets. For further information, please contact Investors & Media Andrew C. Weiss Senior Vice President, Head of Investor Relations & Corporate Communications Idorsia Pharmaceuticals Ltd, Hegenheimermattweg 91, CH-4123 Allschwil +41 58 844 10 10 investor.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 "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 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. °

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