TRYVIO Overview - TRYVIO (aprocitentan) is the only approved therapy for difficult-to-control hypertension [3, 8, 22, 39, 71, 84] - It is the first hypertension therapy targeting the endothelin pathway [1] - TRYVIO represents the first drug from the established ERA class optimized for patients with difficult-to-control hypertension [28] Market Need and Patient Population - Approximately 26 million US patients are not adequately controlled on other drugs and are amenable to TRYVIO [21] - Morbidity and mortality risks are increased in patients with difficult-to-control hypertension, including a 30% increased risk of all-cause mortality, a 44% increased risk of coronary heart disease, a 57% increased risk of stroke, an 88% increased risk of heart failure, and a 95% increased risk of end-stage renal disease [17] Clinical Efficacy and Safety - Aprocitentan demonstrated a rapid double-digit reduction in blood pressure as early as 2 weeks, with a 15.4 mmHg reduction at 4 weeks on top of three antihypertensives [50, 51] - The blood pressure reduction was sustained up to 48 weeks, with a 19.2 mmHg reduction [55, 56] - A major night-time blood pressure decrease was observed with aprocitentan, with an 8.1 mmHg reduction in ambulatory systolic blood pressure [58, 59] - In a phase 2 trial, aprocitentan demonstrated dose-dependent reductions in systolic and diastolic blood pressure, with a maximum reduction of 18.5 mmHg in systolic blood pressure at the 50mg dose [43] - The most common adverse reaction was edema/fluid retention, reported in 9.1% of TRYVIO-treated patients compared to 2.1% in placebo-treated patients [64] High-Risk Populations - In patients with CKD 3/4, aprocitentan showed a 13.4 mmHg reduction in sitting systolic blood pressure and a 10.7 mmHg reduction in daytime ambulatory systolic blood pressure [76] - Aprocitentan 25 mg showed a 56% reduction in microalbuminuria (UACR 30-300 mg/g) and a 67% reduction in macroalbuminuria (UACR >300 mg/g) at week 36 [79]

Core Viewpoint - Idorsia Ltd, in collaboration with Stanford Hypertension Center and Duke Heart Center, has launched the IMPACT-HTN program aimed at modernizing the management of difficult-to-control hypertension through a multi-phase initiative that incorporates AI technology and real-world evidence [2][3][4]. Group 1: Program Overview - The IMPACT-HTN program consists of three phases designed to standardize treatment protocols and improve patient outcomes for those with difficult-to-control hypertension [2]. - The initiative will generate real-world evidence and develop scalable AI-powered tools to assist in identifying patients who may benefit from innovative therapies, including Idorsia's TRYVIO™ [2][5]. Group 2: Collaboration and Goals - The program is led by Dr. Vivek Bhalla from Stanford and Dr. Sreekanth Vemulapalli from Duke, emphasizing a cross-institutional collaboration to enhance care coordination and access to new therapies [3][4]. - The goal is to standardize evaluation and management practices for hypertension, ultimately improving patient outcomes and addressing the global health issue of hypertension, which affects approximately 50% of adults in the U.S. [3][4]. Group 3: Tools and Innovations - The program will introduce a digital care algorithm to standardize assessment and management of difficult-to-control hypertension, utilizing interactive tools such as AI chatbots and patient-facing algorithms [6]. - A personalized hypertension risk score will be developed to better identify patients at risk for negative cardiovascular outcomes, allowing for timely intervention [6]. Group 4: TRYVIO™ Overview - TRYVIO, a dual endothelin receptor antagonist, is now available for prescription and is indicated for patients whose hypertension is not adequately controlled with other medications [7][18]. - It has been included in the new clinical practice guidelines from the American College of Cardiology and the American Heart Association, highlighting its significance in the treatment landscape [7].

Core Insights - Idorsia will host a live investor Q&A webcast and conference call to discuss the role of TRYVIO™ (aprocitentan) in treating difficult-to-control hypertension, marking it as the first and only therapy targeting the endothelin pathway [1] Group 1 - The event is scheduled for September 8, 2025, at 16:00 CEST / 15:00 BST / 10:00 EDT, starting with a presentation by senior management followed by a Q&A session [1] - The live webcast will be accessible via the Idorsia website, providing both audio and slides for participants [2] - Analysts wishing to ask questions must register in advance through a specified link, and a replay of the webcast will be available approximately 60 minutes after the call [3]

Core Insights - Idorsia Ltd has introduced TRYVIO™ (aprocitentan), the first hypertension therapy targeting the endothelin pathway, addressing the need for novel treatments in difficult-to-control hypertension [1][2][3] - TRYVIO is the only endothelin receptor antagonist included in the ACC/AHA clinical practice guidelines, highlighting its significance in hypertension management [2][9] Company Overview - Idorsia aims to challenge medical paradigms by discovering, developing, and commercializing transformative medicines, positioning itself as a leading biopharmaceutical company [19][21] - The company is headquartered in Allschwil, Switzerland, and is listed on the SIX Swiss Exchange under the ticker symbol IDIA [21] Product Details - TRYVIO is a once-daily, orally active dual endothelin receptor antagonist approved in the US for systemic hypertension treatment in combination with other antihypertensives since October 2024 [11] - The drug targets a significant patient population, with approximately 26 million patients in the US potentially eligible for treatment under TRYVIO's indication [3][4] Market Opportunity - The hypertension market presents a substantial opportunity, particularly for patients with difficult-to-control hypertension, which is defined as elevated blood pressure despite the use of multiple antihypertensive drug classes [5][6] - Nearly half of US adults, around 120 million people, have hypertension, with 40 million currently treated with antihypertensive drugs [3] Clinical Insights - Patients with difficult-to-control hypertension face higher risks of cardiovascular events and premature mortality, emphasizing the need for effective treatment options [5] - Idorsia will present scientific findings at the AHA Hypertension Scientific Sessions, showcasing the efficacy of aprocitentan in achieving rapid blood pressure control and reducing urinary albumin-to-creatinine ratio (UACR) [7] Recognition - TRYVIO has been nominated for the 2025 Prix Galien USA Awards in the "Best Pharmaceutical Product" category, reflecting its innovative approach in the pharmaceutical landscape [8]

Core Insights - Idorsia Ltd has reported a significant operational turnaround driven by the commercial acceleration of QUVIVIQ and financial discipline, aiming for overall profitability by the end of 2027 [2][3][4] Commercial Operations - QUVIVIQ generated total product sales of CHF 56 million in the first half of 2025, representing over a 140% increase compared to the same period in 2024 [5] - In the EUCAN region, QUVIVIQ net sales reached CHF 44 million, nearly four times the CHF 9 million recorded in the first half of 2024 [6] - QUVIVIQ is positioned to become the standard of care for insomnia in Europe, with a focus on securing public reimbursement and expanding promotional efforts [7] Financial Performance - Total net revenue for H1 2025 was CHF 131 million, significantly up from CHF 26 million in H1 2024, driven by QUVIVIQ sales and contract revenues [24][25] - US GAAP operating income for H1 2025 was CHF 64 million, compared to an operating loss of CHF 64 million in H1 2024 [24] - Net income for H1 2025 was CHF 52 million, a substantial improvement from a net loss of CHF 79 million in H1 2024 [27][28] Funding and Liquidity - The company secured a new money facility of CHF 150 million, extending its cash runway through the end of 2026 [4][32] - At the end of H1 2025, Idorsia's liquidity amounted to CHF 72 million, with total indebtedness of CHF 1.37 billion [33][34] Research and Development - Idorsia is advancing multiple investigational clinical assets, including a Phase 2 study for daridorexant in pediatric insomnia and ongoing discussions with the FDA regarding lucerastat for Fabry disease [15][17][19] - The company is also developing a bacterial vaccine targeting Clostridioides difficile, with initial data showing positive results [23] Financial Guidance - For 2025, Idorsia expects continued acceleration of QUVIVIQ with net sales around CHF 130 million and anticipates a non-GAAP operating loss of approximately CHF 175 million [35][36]

Core Insights - Idorsia Ltd reported significant financial improvements in Q1 2025, with net revenue reaching CHF 59 million, a substantial increase from CHF 10 million in Q1 2024, driven by strong sales of QUVIVIQ and a one-off exclusivity fee [4][6][11] - The company has streamlined its R&D organization and focused on its promising pipeline, which includes QUVIVIQ and TRYVIO, positioning itself for growth in 2025 [3][20] Financial Highlights - Q1 2025 net revenue was CHF 59 million, compared to CHF 10 million in Q1 2024, with QUVIVIQ product sales contributing CHF 25 million [4][6] - Operating income for Q1 2025 was CHF 67 million, up from CHF 31 million in Q1 2024, while net income increased to CHF 63 million from CHF 30 million [4][6][8] - Non-GAAP operating loss for Q1 2025 was CHF 17 million, a significant improvement from a loss of CHF 85 million in Q1 2024 [10][11] Product Performance - QUVIVIQ demonstrated strong performance with net sales of CHF 25 million in Q1 2025, and demand in Europe and Canada grew by 50% from Q4 2024 to Q1 2025 [5][31] - In France, QUVIVIQ's market share increased significantly, with a new-to-brand share growing from 1.1% in September 2024 to 9.3% in January 2025 [25] - TRYVIO received FDA approval and had its REMS requirement removed, allowing for broader distribution in retail pharmacies [3][38] Strategic Developments - Idorsia restructured its convertible bond debt and secured a CHF 150 million new money facility to alleviate short- to mid-term debt overhang [16][20] - The updated agreement with Viatris reduced Idorsia's development cost contributions and expanded territorial rights, enhancing financial flexibility [14][20] - The company aims for continued growth in 2025, projecting QUVIVIQ net sales of around CHF 110 million and a non-GAAP operating loss of approximately CHF 215 million [18][19] Research and Development - Idorsia is focusing its drug discovery efforts on fewer active projects, preparing some for out-licensing while developing others to the next inflection point [41][42] - Recent publications highlighted the efficacy of daridorexant in treating chronic insomnia and nocturia, supporting its market potential [44][45] Liquidity and Indebtedness - As of March 31, 2025, Idorsia's liquidity stood at CHF 51 million, down from CHF 106 million at the end of 2024 [21][22] - Total indebtedness remained stable at CHF 1.322 billion, with convertible loans and bonds unchanged [22][23]