Daridorexant hydrochloride

High-dose cohort confirms the favorable safety pro the dose-dependent immune response against Clostridioides difficile bacteria and spores Allschwil, Switzerland – June 1, 2026 Idorsia Ltd (SIX: IDIA) today announced additional positive clinical results for IDOR-1134-2831, its vaccine targeting Clostridioides difficile ( C. difficile ) in a Phase 1 clinical pharmacology trial. The glycan target of this vaccine is present on both bacteria and spores – the transmissible form of the pathogen responsible for spreading infection – of the most clinically relevant C. difficile strains, including hypervirulent variants. Following initial results in June 2025, which provided the first clinical validation for Idorsia’s synthetic glycan vaccine technology, the company advanced the program with a higher-dose cohort. Results from healthy participants receiving the high dose confirmed that the vaccine is safe and well-tolerated. The vaccine induced a dose-dependent IgG response, with all participants receiving the high dose showing immunogenicity. In further exploratory tests, the dose-dependent response was particularly pronounced for IgG1, a subclass known to play a key role in opsonization, marking the pathogen for rapid identification and destruction by the immune system. Idorsia’s vaccine is intended to be developed for the prevention of C. difficile infection (CDI) in patients at risk in both hospital and community settings, with the aim of providing broad protection against circulating strains. Martine Clozel, MD, Chief Scientific Officer & Head of Research at Idorsia, commented: “These new results from the high-dose cohort mark an important step forward for our synthetic glycan vaccine platform and reinforce our conviction that we are pioneering a fundamentally new approach to vaccination. The dose-dependent responses against the glycan target present on both C. difficile bacteria and spores, underscore the potential of this vaccine to go beyond traditional strategies and target the full life cycle of the pathogen. Beyond C. difficile , this technology has the potential to transform the landscape of vaccines, allowing prophylaxis against multiple bacteria and more. The fact that the antigens are synthesized in a chemistry laboratory offers immense opportunity. To fully realize this potential and accelerate development, we intend to advance this program in partnership.” C. difficile infection C. difficile is a spore-forming and toxin-producing bacterium. It is the leading cause of antibiotic-associated diarrhea in developed countries. It infects the gastrointestinal tract, often following disruption of the gut microbiota, for example due to antibiotic use. CDI symptoms can range from mild diarrhea to pseudomembranous colitis, which in some cases – particularly in the elderly – can lead to death. CDI is a major public health threat, particularly because recurrences are frequent, and is increasing with the aging population. In the US, C. difficile is estimated to cause almost 400,000 infections each year. One in eleven people over 65 diagnosed with healthcare-associated CDI die within one month. C. difficile infections cause more than 25,000 deaths each year in the US alone. CDI places a significant economic burden on the healthcare system. The acute care direct costs of CDI are estimated to be $5–6 billion per year in the US and €3 billion per year in Europe. Standard treatments of CDI are efficacious in clearing primary CDI. However, CDI recurs in up to 25% of treated patients. The C. difficile vaccine identified by Idorsia targets both spores and vegetative C. difficile bacteria and, therefore, could prevent not only colonization but also transmission. Frail patients, elderly persons, persons in nursing homes, receiving antibiotic treatment, who are hospitalized, or expected to be hospitalized, represent target populations for this prophylactic vaccine. A unique approach to vaccination – w hat is a synthetic glycan vaccine? Pathogenic bacteria like C. difficile express carbohydrates (glycans) on their surface which are recognized by the host’s immune system, leading to the production of glycan-specific antibodies. This makes glycans on the surface of pathogens attractive candidates for vaccine development. The synthetic glycan in Idorsia’s C. difficile vaccine is synthesized in a carefully designed chemical process. This transforms a complex biochemical extraction, which is associated with heavy investment, into a purely chemical process driven by medicinal chemistry. Idorsia’s C. difficile synthetic glycan vaccine has the advantage of being stable, immunogenic, fully characterizable, and the process has the potential to enable scalable and cost-efficient manufacturing. About the Phase 1 trial The Phase 1 clinical pharmacology trial is a double-blind, randomized, placebo-controlled, two-part trial to assess the safety, tolerability, and immunogenicity of up to 4 ascending dose levels of the IDOR-1134-2831 vaccine in healthy participants aged 18 to 49 years. About Idorsia’s vaccine portfolio In addition to the C. difficile vaccine that is in Phase 1 clinical development, Idorsia is also developing synthetic glycan vaccines for infections caused by Klebsiella pneumoniae and Neisseria gonorrhoeae . Notes to the editor About Idorsia The purpose of Idorsia is to discover, develop and commercialize innovative medicines to help more patients. 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 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 Relations Idorsia Pharmaceuticals Ltd, Hegenheimermattweg 91, CH-4123 Allschwil +41 58 844 10 10 investor.relations@idorsia.com – media.relations@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

The findings demonstrate that aprocitentan may help reduce the risk of kidney disease progression, cardiovascular events, and mortality in patients with resistant hypertension. Allschwil, Switzerland – June 01, 2026 Idorsia Ltd (SIX: IDIA) announces new analyses from the Phase 3 PRECISION study demonstrating that aprocitentan, Idorsia’s dual endothelin receptor antagonist, significantly reduces albuminuria and improves albuminuria risk categories in patients with resistant hypertension. The data were presented by Prof. Markus Schlaich at the 35th Congress of the European Society of Hypertension (ESH). The oral presentation, entitled “ Effect of the Dual Endothelin Receptor Antagonist Aprocitentan on Albuminuria ”, underscores the role of endothelin pathway inhibition not only in blood pressure control, but also in addressing kidney-related risk in this high-risk population, further supporting the evidence presented in Hypertension titled “ Aprocitentan in Patients with Chronic Kidney Disease and Resistant Hypertension ”. Addressing a critical unmet need in resistant hypertension Hypertension remains the leading modifiable risk factor for cardiovascular disease and premature death, with patients whose blood pressure is difficult to control facing even higher risks of stroke, myocardial infarction, heart failure, and kidney disease. In resistant hypertension in particular, chronic kidney disease and type 2 diabetes are common and contribute to poor long-term outcomes. Albuminuria, measured as urine albumin-creatinine ratio (UACR), is a well-established biomarker of kidney damage and is strongly associated with increased cardiovascular morbidity and mortality, and more rapid progression towards kidney failure. Albuminuria is more commonly observed in conditions such as Type 2 diabetes and hypertension, as well as older age. Changing to a lower risk category, as a result of lowering albuminuria is therefore an important therapeutic objective beyond blood pressure lowering. Potential to improve long-term renal and cardiovascular outcomes By lowering albuminuria and shifting patients to lower risk categories, aprocitentan may help reduce the risk of kidney disease progression and cardiovascular risk in patients with difficult-to-control hypertension. Prof. Markus Schlaich, MD, FAHA, FESC, ISHF, The University of Western Australia, Perth, and lead investigator in the PRECISION study commented: “These data represent a major step forward in the management of difficult-to-control hypertension. By targeting the endothelin pathway, aprocitentan not only delivers robust and sustained blood pressure reductions, but also drives clinically meaningful improvements in albuminuria – an established marker of kidney and cardiovascular risk. The ability to lower albuminuria risk category in nearly half of these high-risk patients underscores the potential of aprocitentan to change the treatment paradigm and deliver tangible long-term benefits for patients who remain inadequately controlled on current therapies, particularly those in whom treatment decisions are complicated by the risk of hyperkalemia.” New PRECISION analysis: meaningful reductions in albuminuria The new analysis evaluated the effect of aprocitentan in 730 patients with confirmed resistant hypertension receiving at least three antihypertensive agents, including a diuretic. Key findings include: Rapid and substantial reductions in UACR: In patients with baseline microalbuminuria (UACR 30–300mg/g) and macroalbuminuria (UACR >300mg/g), aprocitentan significantly reduced UACR at Week 4 compared with minimal changes on placebo. Sustained long-term effects: By Week 36, treatment with aprocitentan 25 mg reduced mean UACR: From 77.5 mg/g to 34 mg/g in patients with microalbuminuria From 860.2 mg/g to 286.7 mg/g in patients with macroalbuminuria Early improvement/normalization in albuminuria risk category: As early as Week 4: Up to 45% of patients with microalbuminuria achieved normal albumin levels with aprocitentan Up to 39% of patients with macroalbuminuria improved to a lower risk category At Week 36, approximately 46% of patients with baseline micro- or macroalbuminuria achieved a lower albuminuria risk category Stable eGFR in both microalbuminuria and macroalbuminuria eGFR did not decline but remained stable, confirming the renal protective effect of aprocitentan Preservation of normal kidney status: More than 92% of patients with normal albumin levels at baseline remained within the normal range during treatment. Targeting endothelin: a novel and clinically meaningful mechanism Idorsia’s Chief Scientific Officer & Head of Research, Martine Clozel, also spoke at the event with a presentation entitled “From dream to reality: improving lives though endothelin-related innovations”. Aprocitentan, Idorsia’s dual endothelin receptor antagonist approved as TRYVIO™ in the US and as JERAYGO™ in Europe, is the first therapy of its kind to target the endothelin pathway in systemic hypertension. Endothelin is a key driver of vasoconstriction, inflammation, fibrosis, and organ damage, and is often upregulated in patients with resistant hypertension and kidney disease. The findings from this analysis reinforce the central role of endothelin in both the development and consequences of hypertension, including the potential to reduce kidney damage progression and long-term cardiovascular risk. Unlike therapies targeting the renin–angiotensin–aldosterone system (RAAS) pathway, which may be associated with electrolyte disturbances such as hyperkalemia, endothelin receptor antagonism with aprocitentan has not demonstrated an increased risk of hyperkalemia. Building on proven blood pressure efficacy The albuminuria data complement previously reported results from PRECISION, where aprocitentan demonstrated: Rapid, double-digit reductions in systolic blood pressure Sustained efficacy over 48 weeks Consistent effects across office and ambulatory measurements Consistent blood pressure reductions across key patient subpopulations, including those with high-risk comorbidities Importantly, the treatment effect was maintained in patients with common and clinically relevant comorbidities, including type 2 diabetes, obesity (including severe obesity), chronic kidney disease, and congestive heart failure, as well as across demographic subgroups such as older patients and those with higher cardiovascular risk pro Aprocitentan has also shown a manageable safety profile, with mild and transient edema as the most commonly observed treatment-related effect and no significant drug–drug interactions – an important consideration in patients with complex regimens. Importantly, no signal for hyperkalemia or hyponatremia was observed, supporting its use in patients with resistant and difficult-to-control hypertension, including those with chronic kidney disease, even with an eGFR (estimated glomerular filtration rate) as low as 15ml/min/1.73m 2 , diabetes, or heart failure, without additional electrolyte monitoring burden. About aprocitentan 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. 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. Aprocitentan is approved as JERAYGO ® for the treatment of resistant hypertension in combination with other antihypertensives in the European Union, the UK, and Switzerland, and a marketing authorization application is under review in Canada. Notes to the editor About Prof. Markus Schlaich, MD Markus Schlaich is a nephrologist and a European Society of Hypertension (ESH) accredited hypertension specialist. He is a Fellow of the American Heart Association (FAHA), the European Society of Cardiology (FESC), and the International Society of Hypertension (ISHF). He served as an Executive Committee of the ISH from 2018-2020 and is currently on the Management Board of the global ISH May Measurement Month campaign. Markus is President of Hypertension Australia and a Trustee of the Foundation for High Blood Pressure Research. Markus has a strong background in clinical research with a focus on the pathophysiology of hypertension, involvement of the kidneys, and hypertension mediated organ damage. He has a specific interest in treatment modalities targeting the sympathetic nervous system and other relevant pathways such as the endothelin system to improve BP control and thereby outcomes for patients with difficult-to-control hypertension. For his work he received the Björn Folkow Award from the European Society of Hypertension (ESH) and the Arthur C. Corcoran Award from the AHA Hypertension Council, both in 2021. He has authored more than 450 articles in peer-reviewed journals and serves on the Editorial Board of Hypertension and Journal of Hypertension. Prof. Schlaich serves as a consultant to Idorsia. Key literature 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. 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. Rossignol P, et al. Aprocitentan in Patients With Chronic Kidney Disease and Resistant Hypertension. Hypertension. Online ahead of print, December 2025, doi.org/10.1161/HYPERTENSIONAHA.125.25563 Iglarz M, et al. At the heart of tissue: endothelin system and end-organ damage. Clin Sci 2010; 119:453-63. Clozel M. Aprocitentan and the endothelin system in resistant hypertension. Can J Physiol Pharmacol 2022; 100:573-83. About Idorsia The purpose of Idorsia is to discover, develop and commercialize innovative medicines to help more patients. 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 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 Relations Idorsia Pharmaceuticals Ltd, Hegenheimermattweg 91, CH-4123 Allschwil +41 58 844 10 10 investor.relations@idorsia.com – media.relations@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