Slide 1: The first and only hypertension therapy targeting the endothelin pathway
The first and only hypertension therapy targeting the endothelin pathway TRYVIO in the difficult-to-control treatment landscape | August 2025
Slide 2: TRYVIO: The only approved therapy for difficult-to-control hypertension
TRYVIO (aprocitentan): The only approved therapy for difficult-to-control hypertension 1 Difficult-to-control hypertension 2 The optimal endothelin blocker 3 Compelling efficacy & safety data 4 Differentiated profile in high-risk populations 5 Strong advocacy – ready to launch 2 TRYVIO in the diffic
Slide 3: Forward-looking statements
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", "s
Slide 4: TRYVIO: The only approved therapy for difficult-to-control hypertension
TRYVIO (aprocitentan): The only approved therapy for difficult-to-control hypertension 1 Difficult-to-control hypertension 2 The optimal endothelin blocker 3 Compelling efficacy & safety data 4 Differentiated profile in high-risk populations 5 Strong advocacy – ready to launch 4 TRYVIO in the diffic
Slide 5: Difficult-to-control hypertension
1 Difficult-to-control hypertension Hypertension is the number one modifiable risk factor of cardiovascular morbidity and premature death – Risk is even greater in patients whose blood pressure is difficult-to-control The Global Burden of Disease 2021, The Lancet 2024 5 TRYVIO in the difficult-to-co
Slide 6: Difficult-to-control versus resistant hypertension
Difficult-to-control versus resistant hypertension Hypertension guidelines Resistant hypertension recommend less than Patients whose blood pressure remains high, despite receiving at 130/80 mmHg2 least three antihypertensives of different pharmacological classes, as a blood pressure goal including a
Slide 7: Morbidity and mortality risk is greater in difficult-to-control hypertension
Morbidity and mortality risk is greater in patients whose hypertension is difficult-to-control Increased risks when comparing individuals with vs. without difficult-to-control hypertension Peripheral artery disease 23% All-cause mortality 30% Coronary heart disease 44% Stroke 57% Heart failure 88% E
Slide 8: Significant medical need in difficult-to-control hypertension
Significant medical need in difficult-to-control hypertension Total drug treated patients in the US* 40.2 million ~26 million US patients are not adequately L3/4+ million *1 12.9million 12.7 L1 controlled on other drugs 16 million 14.4million despite treatment and are amenable to TRYVIO L2 15 millio
Slide 9: TRYVIO: The only approved therapy for difficult-to-control hypertension
TRYVIO (aprocitentan): The only approved therapy for difficult-to-control hypertension 1 Difficult-to-control hypertension 2 The optimal endothelin blocker 3 Compelling efficacy & safety data 4 Differentiated profile in high-risk populations 5 Strong advocacy – ready to launch 9 TRYVIO in the diffic
Slide 10: The optimal endothelin blocker
2 The optimal endothelin blocker Aprocitentan targets the endothelin system and represents the first drug from the established ERA class – optimized for patients with difficult-to-control hypertension 10 TRYVIO in the difficult-to-control treatment landscape | August 2025
Slide 11: The endothelin system
The endothelin system Aldosterone Salt Increased expression of ETB in smooth muscle cells amplifies vasoconstriction effects of endothelin ET-1 ETB ET-1 ETB ETB ETB VASODILATION Hypertension Cell proliferation and Fibrosis and ETA ETB ETB ETA Vascular hypertrophy inflammation ETB ETB ETA ETA END-ORG
Slide 12: Endothelin is the key driver of difficult-to-control hypertension
Endothelin is upregulated and it is the key driver of difficult-to-control hypertension in these patients Comorbidities that are at high Consequently, patients are at risk for difficult to control significant risk of several life- hypertension threatening diseases High body weight Chronic Black kidn
Slide 13: Blockade of the RAAS pathway is the focus of current therapies
Blockade of the RAAS pathway is the focus of current marketed and developmental therapies Endothelin System RAAS System PreProET-1 Angiotensinogen RI Renin Big ET-1 Angiotensin I ACEi or Converting enzyme Endothelin-1 ERA ARB Angiotensin II Stimulation of aldosterone • Vasoconstriction MRA secretion
Slide 14: TRYVIO: The only approved therapy for difficult-to-control hypertension
TRYVIO (aprocitentan): The only approved therapy for difficult-to-control hypertension 1 Difficult-to-control hypertension 2 The optimal endothelin blocker 3 Compelling efficacy & safety data 4 Differentiated profile in high-risk populations 5 Strong advocacy – ready to launch 14 TRYVIO in the diffi
Slide 15: Compelling efficacy & safety data
3 Compelling efficacy & safety data Aprocitentan demonstrated compelling efficacy, safety and tolerability in difficult-to-control / resistant hypertension 15 TRYVIO in the difficult-to-control treatment landscape | August 2025
Slide 16: Aprocitentan as monotherapy in systemic hypertension
Aprocitentan as monotherapy in systemic hypertension Phase 2 trial in patients with essential hypertension Aprocitentan Placebo 5mg 10mg 25mg 50mg Lisinopril N=66 N=68 N=71 N=67 N=68 N=69 149.2/97.5 149.4/97.8 149.8/97.7 151.2/97.8 148.6/98.2 149.8/96.8 SBP DBP SBP DBP SBP DBP SBP DBP SBP DBP SBP DB
Slide 17: PRECISION: Investigated onset and durability of blood pressure reduction
PRECISION: Investigated onset and durability of blood pressure reduction Selection of patients with uncontrolled hypertension on Efficacy and safety of aprocitentan over 48 weeks existing therapy confirmation Up to 8 weeks 4 weeks 4 weeks 4 weeks 32 weeks 12 weeks 30 days Screening Screening Run-in
Slide 18: PRECISION population mirrors clinical reality of resistant hypertension
PRECISION population mirrors clinical reality of resistant hypertension with comorbidities and lack of response to prior therapies Older patients High-risk and patients with comorbidities • ≥65 years old (34%) • North America origin (29%) − Of which, 10% were ≥75 years old − Of which 38.9% were Blac
Slide 19: Rapid double-digit reduction in BP
Rapid double-digit reduction in BP seen as early as 2 weeks with continued benefit over time On top of three antihypertensives: valsartan, amlodipine and hydrochlorothiazide 160 Triple combination + Placebo Sitting systolic blood pressure (mmHg) Triple combination + Aprocitentan 12.5 mg 155 150 145
Slide 20: Double-digit BP decrease was sustained
Double-digit BP decrease was sustained BP reduction confirmed up to 48 weeks Randomization Re-randomization PART 1 PART 2 PART 3 155 Double- Single-blind Double-blind blind withdrawal 150 SiSBP (mm Hg) +/- SE 145 140 135 -15.3 mmHg -17.7 mmHg -19.2 mmHg 130 0 4 8 12 16 20 24 28 32 36 40 44 48 Time (
Slide 21: Major night-time BP decrease
Major night-time BP decrease Daytime Nighttime 0 0 • Insufficient BP decrease at night is a very strong predictor of poor outcome in hypertension. systolic blood pressure (mmHg) -2 -2.3 -2 -2.6 • Unique nighttime efficacy of aprocitentan is an important feature and may be due to Change in ambulatory
Slide 22: US Prescribing Information
US Prescribing Information Broader indication – difficult-to- control hypertension – compared to the resistant hypertensive patients included in PRECISION 22 TRYVIO in the difficult-to-control treatment landscape | August 2025
Slide 23: Edema: mild, peripheral, early and transient
Edema: mild, peripheral, early and transient Edema discontinuation rate <1% over 48 weeks Pre-randomization (switched to SBAT) 10% Aprocitentan 12.5 mg -> 25 mg fluid retention events 8% New edema and/or 6% After 8 weeks of treatment, incidence returns to levels observed before randomization 4% 2% 0
Slide 24: Demonstrated safety and tolerability profile
Demonstrated safety and tolerability profile No hypotension, No increased No drug-drug No heart rate incidence interactions increase, of hyperkalemia No headaches Very low overall discontinuation rate Half-life of 41 hours with or without food due to adverse events over 48 weeks: One dose can be mis
Slide 25: TRYVIO: The only approved therapy for difficult-to-control hypertension
TRYVIO (aprocitentan): The only approved therapy for difficult-to-control hypertension 1 Difficult-to-control hypertension 2 The optimal endothelin blocker 3 Compelling efficacy & safety data 4 Differentiated profile in high-risk populations 5 Strong advocacy – ready to launch 25 TRYVIO in the diffi
Slide 26: Differentiated profile in high-risk populations
4 Differentiated profile in high-risk populations The blood pressure-lowering effect of TRYVIO was consistent among subgroups – defined by age, sex, race, body mass index, baseline eGFR, baseline UACR, and medical history of diabetes 26 TRYVIO in the difficult-to-control treatment landscape | August
Slide 27: Unprecedented BP reduction in CKD 3/4 patients
Unprecedented BP reduction in CKD 3/4 patients (n = 162) SiSBP Ambulatory SBP 0.0 4.0 2.2 -2.0 2.0 pressure from baseline to W4 (mmHg) Mean change in sitting systolic blood systolic blood pressure (mmHg) Mean change in ambulatory -4.0 0.0 -6.0 -2.0 -5.9 -8.0 -4.0 -3.4 -6.0 -10.0 -6.9 -8.0 -12.0 -10.
Slide 28: Major reduction of UACR at week 36
Major reduction of UACR at week 36 Microalbuminuria Macroalbuminuria UACR 30-300 mg/g UACR >300 mg/g 0% UACR change from baseline -10% -20% to Week 36 -30% Aprocitentan 25 mg -40% -50% -60% -56% -70% -67% UACR: Urine Albumin-to-Creatinine Ratio -80% Schlaich MP, et al. The Lancet, 2022; Data on file
Slide 29: Stable eGFR in CKD 3/4 over 48 weeks
Stable eGFR in CKD 3/4 at 25 mg over 48 weeks 50 48 46 Mean values in eGFR 44 (mL/min/1.73mˆ2) 42 40 38 36 34 32 30 28 26 24 22 20 0 4 8 12 16 20 24 28 32 36 40 44 48 Time (weeks) eGFR mean observed values for patients treated with aprocitentan 25 mg over Aprocitentan 25 mg 48 weeks – CKD stage 3/4
Slide 30: TRYVIO: The only approved therapy for difficult-to-control hypertension
TRYVIO (aprocitentan): The only approved therapy for difficult-to-control hypertension 1 Difficult-to-control hypertension 2 The optimal endothelin blocker 3 Compelling efficacy & safety data 4 Differentiated profile in high-risk populations 5 Strong advocacy – ready to launch 30 TRYVIO in the diffi
Slide 31: Strong advocacy – ready to launch
5 Strong advocacy – ready to launch Prescribers are seeing the benefits of TRYVIO in real-world practice. 31 TRYVIO in the difficult-to-control treatment landscape | August 2025
Slide 32: Commercially available in the US and ready for launch with the right partner
Commercially available in the US and ready for launch with the right partner 32 TRYVIO in the difficult-to-control treatment landscape | August 2025
Slide 33: Early positive outcomes with TRYVIO in US
Early positive outcomes with TRYVIO in US Strong advocacy and interest for patients with difficult-to-control hypertension We continue to “Resistant hypertension • ~10 to 15 mmHg drop in BP • Well tolerated, plans to expand build advocacy and has complexities... One patient had a clear need use with
Slide 34: TRYVIO: first systemic hypertension treatment to target a new pathway in over 30 years
TRYVIO: first systemic hypertension treatment to target a new pathway in over 30 years TRYVIO is the first and only dual endothelin receptor antagonist (ERA) approved for systemic hypertension The endothelin pathway is a key driver in difficult-to-control hypertension TRYVIO is well tolerated and de