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 Insights - Idorsia Ltd's novel dual endothelin receptor antagonist, TRYVIO™ (aprocitentan), has been included in the updated clinical practice guidelines for managing systemic hypertension by the American College of Cardiology (ACC) and the American Heart Association (AHA) [1][9] - TRYVIO is recognized as a treatment option for adults with difficult-to-control hypertension, including resistant hypertension, marking it as the first systemic hypertension treatment to target a new pathway in over 30 years [1][9] Company Overview - Idorsia is focused on discovering and developing innovative medicines to improve patient outcomes, with a commitment to addressing unmet medical needs in hypertension management [4][17] - The company has a strong scientific core and aims to evolve into a leading biopharmaceutical company, leveraging its in-house capabilities and partnerships [17][18] Product Information - TRYVIO is indicated for the treatment of hypertension in combination with other antihypertensive drugs, with a recommended dosage of 12.5 mg orally once daily [3][10] - The drug is particularly suitable for patients with hypertension and chronic kidney disease (CKD), as it can be used in patients with an estimated glomerular filtration rate (eGFR) as low as 15 mL/min [3][10] Clinical Evidence - Clinical evidence supports that TRYVIO effectively lowers blood pressure and reduces the risk of cardiovascular events, including strokes and myocardial infarctions [3][9] - Post-hoc analyses presented at the AHA Hypertension Scientific Sessions indicate that aprocitentan provides fast blood pressure control and significant reductions in urinary albumin-to-creatinine ratio (UACR) [6][5] Industry Context - Hypertension is a major global health issue, affecting an estimated 50% of adults in the US, with half of those patients not well controlled despite medication [2][9] - The updated guidelines reflect a shift towards evidence-based practices in managing high blood pressure, emphasizing the importance of new treatment options like TRYVIO [8][9] Recognition - TRYVIO has been nominated for the 2025 Prix Galien USA Awards in the category of "Best Pharmaceutical Product," highlighting its innovative approach in hypertension treatment [7]