Slides
Page 1
Unlocking the value of TRYVIO/JERAYGO Investor presentation
Page 2
Forward-looking statements The information in this presentation contains certain "forward-looking statements", relating to the company's business or aprocitentan, 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, milestones, product , market opportunity, business development activities and anticipated expenditures in connection therewith, descriptions of 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. Rounding differences in the numbers presented may occur. Idorsia has transferred its rights for aprocitentan, cenerimod and selatogrel to Idorsia Investments SARL to allow the repayment of existing notes issued in connection with the repurchase offer completed in August 2025. More details on the transfer can be found in the latest financial report from Idorsia Investments SARL. There can be no assurance that the required consents for the creation of the news notes will be obtained or that the proposed transaction will be completed on the terms described or at all. This presentation does not constitute an offer to sell or a solicitation of an offer to buy any securities. The securities have not been and will not be registered under the U.S. Securities Act of 1933, as amended, and may not be offered or sold in the United States absent registration or an applicable exemption. Unlocking the value of TRYVIO/JERAYGO | 04 Nov 20262
Page 3
Advancing key value drivers for Idorsia Roland Wandeler Chief Executive Officer Unlocking the value of TRYVIO/JERAYGO | 04 Nov 20263
Page 4
Unlocking the value of TRYVIO/JERAYGO | 04 Nov 20264 Advancing the key drivers of growth and value creation Accelerate QUVIVIQ Maximize the current QUVIVIQ opportunity in insomnia • Accelerate demand • Expand reach • Broaden patient access • Increase penetration into primary care • Advance lifecycle expansion opportunities TRYVIO / JERAYGO Advance pipelineDevelop Daridorexant in ASD Unlock the value of TRYVIO / JERAYGO • Large medical need • Highly identifiable patients • Differentiated product with compelling clinical data • Encouraging early commercial adoption • Focused specialty strategy Expand the long-term value of daridorexant beyond insomnia • Dedicated program in Autism Spectrum Disorder • Based on Phase 2 data in pediatric population, internal research, external scientific evidence Advance innovation and the pipeline • Advancing a pipeline of first- or best-in-class assets • Potential to change treatment paradigms • Phase 3 program for lucerastat in Fabry disease Clear focus on execution to drive progress Focus today
Page 5
Unique opportunity to unlock the value of TRYVIO/JERAYGO MomentumAssetMarket High unmet needs • Large medical need in difficult-to- control hypertension • 36 million highly identifiable patients • Significant proportion of patients with comorbidities such as CKD 3b/4, diabetes, and obesity Differentiated, 1st-in-class • Compelling clinical data • Distinct pathway: 1st and only treatment to address the endothelin pathway • Proven efficacy: Double-digit BP lowering on top of ≥3 antihypertensives • Well tolerated safety profile without monitoring requirements Increasing awareness • Encouraging early commercial adoption in the US • Broad availability & growing access • New market entrants increasing awareness of the urgent medical need Focused specialty strategy gives clear path to blockbuster status Unlocking the value of TRYVIO/JERAYGO | 04 Nov 20265
Page 6
Four perspectives on the opportunity for TRYVIO/JERAYGO Today’s presentation Market feedback Martine Clozel, Chief Scientific Officer & Head of Research Importance of endothelin pathway in the treatment of hypertension Amer Joseph, Chief Medical Officer & Head Global Clinical Development Implications for the treatment of patients with uncontrolled hypertension Rudy Sharan, Head of Commercial, US Early experience strengthens confidence in the opportunity Arno Groenewoud, Chief Financial Officer A mechanism to realize the TRYVIO/JERAYGO opportunity Clinical practiceScientific foundation Funding approach Unlocking the value of TRYVIO/JERAYGO | 04 Nov 20266
Page 7
Importance of endothelin pathway in the treatment of hypertension Martine Clozel, MD, Chief Scientific Officer & Head of Research Unlocking the value of TRYVIO/JERAYGO | 04 Nov 20267
Page 8
Endothelin via both ETA and ETB receptors reproduces all features of hypertension and correlates with end-organ damage ET-1 Endothelial cells - Endothelial dysfunction - Vascular permeability Smooth muscle cells – Vasoconstriction – Proliferation – Cardiovascular remodeling – Baroreceptor function – Catecholamine production Fibroblasts – Proliferation – Collagen deposition – Interstitial fibrosis Macrophages - NF-κB activation - Cytokine release Adrenal cortex – Aldosterone production Sympathetic nervous system TrpIleIleAspLeuHisCysTyrVal PheCys CysCys Ser Glu Ser SerLeu Met Asp Lys N C Heart - Cardiomyocyte hypertrophy - Cardiac fibrosis Unlocking the value of TRYVIO/JERAYGO | 04 Nov 20268
Page 9
Endothelin is a distinct novel pathway, untapped up to TRYVIO / JERAYGO Unlocking the value of TRYVIO/JERAYGO | 04 Nov 20269 Established mechanism Increased risks of: + Hyperkalemia + Hyponatremia + Acute renal failure + Hypotension RAAS pathway Hypertension Angiotensinogen Angiotensin I Angiotensin II Aldosterone Increased blood volume Vasoconstriction RNAi RI ACEi ARB MRA Recent/under development Older drugs ASI Upregulated endothelin system independent of RAAS Aprocitentan Endothelin pathway PreProET-1 Big ET-1Endothelin-1 Inflammation / Fibrosis Proliferation / Hypertrophy Sympathetic activation Vasoconstriction Aldosterone
Page 10
Endothelin upregulation is the key driver of difficult-to-control hypertension Type 2 diabetes Chronic kidney disease Difficult-to- control hypertension Chronic kidney disease Heart failure Strokes Upregulated endothelin system Increased risks for patients Unlocking the value of TRYVIO/JERAYGO | 04 Nov 202610 Post-menopausal women Obesity Elderly African Americans Obstructive sleep apnea
Page 11
Aprocitentan was selected for its efficacy, safety and practical use Unlocking the value of TRYVIO/JERAYGO | 04 Nov 202611 Dual ETA and ETB antagonism Drug properties Relevance for clinical practice Once daily oral dosing with or without food Elimination independent of kidney function Long half-life No known drug-drug interaction Expectation of better efficacy, safety profile and organ protection Straightforward addition to existing treatments No dose adjustment needed for mild to severe renal impairment Sustained effect throughout the day and night and resilience if a dose is missed Highly relevant for a heavily poly-medicated population
Page 12
Schlaich MP, et al. The Lancet, 2022; Data on file Response to aprocitentan 12.5 mg Patients were allowed to stay on beta-blockers (58 to 85% depending on sub- groups) SBAT: Standard Background Antihypertensive Therapy Data as mean±SEM ≥ 4 antihypertensive medications ≥ 5 antihypertensive medications ≥ 3 antihypertensive medications In PRECISION, TRYVIO 12.5 mg decreased BP when all combinations had failed, including 17% of patients on MRAs Unlocking the value of TRYVIO/JERAYGO | 04 Nov 202612 Switch to SBAT Aprocitentan -15.5 mmHg -2.9 mmHg Switch to SBAT Aprocitentan -14.7 mmHg -1.9 mmHg Switch to SBAT Aprocitentan -17.1 mmHg -0.5 mmHg
Page 13
Implications for the treatment of patients with uncontrolled hypertension Amer Joseph, MD, Chief Medical Officer & Head of Global Clinical Development Unlocking the value of TRYVIO/JERAYGO | 04 Nov 202613
Page 14
Uncontrolled hypertension remains a key unmet need in clinical practice Ettehad D, et al. Lancet. 2016;387(10022):957-967. doi:10.1016/S0140-6736(15)01225-8; Muntner P, et al. Hypertension. 2014;64(5):1012-1021; World health organization. Hypertension is a key driver of mortality and comorbidity 1,000+ deaths every hour Well-established impact of lowering BP on outcomes Every 10 mmHg of lower systolic BP leads to… 36M remain above target BP despite lifestyle changes and taking guideline-directed treatments as prescribed +95% +88% +57% of which ~4M US patients have CKD 3b/4−20% major CV events Stroke Heart failure Kidney failure Resistant hypertension is associated with higher risk of: Adjusted hazard ratios, ALLHAT, n = 14,684 Unlocking the value of TRYVIO/JERAYGO | 04 Nov 202614 −27% Stroke events −28% Heart failure However, 36 million patients remain above target BP
Page 15
Benefits of a new ERA Unlocking the value of TRYVIO/JERAYGO | 04 Nov 202615 Why TRYVIO/JERAYGO will matter for physicians 15.4 mmHg absolute SBP reduction at Week 4 on top of standardized therapy Durable BP lowering over 48 weeks Efficacy eGFR ≥15 Usable across almost the entire CKD spectrum Studied in patients with multiple medications and comorbidities Patient population Safe and tolerable No hyperkalemia No hyponatremia No hypotension No electrolyte monitoring required Safety Once daily one 12.5 mg dose in the US No drug-drug interactions Ease of administration Schlaich MP, et al. Lancet. 2022;400(10367):1927-1937.
Page 16
Double-digit SBP reduction consistent across subgroups -15.7 -17.9 -16.2 -16.4 -18.0 -17.3 -18.8-20 -15 -10 -5 0 Mean absolute change in office SBP from baseline to Week 36 (mm Hg) All patients CKD Stage 3–4 Type 2 diabetes Black race Age ≥65 years CKM Stage 2 CKM Stage 4a Unlocking the value of TRYVIO/JERAYGO | 04 Nov 202616 Schlaich MP, et al. Lancet. 2022;400(10367):1927-1937. Efficacy maintained regardless of CKD stage, diabetes, age, race or disease severity
Page 17
TRYVIO/JERAYGO shows effects beyond office BP, across ambulatory BP and kidney measures Greatest lowering at night Night-time Placebo −2.6 Aprocitentan −8.1 Daytime Placebo −2.3 Aprocitentan −6.2 • Ambulatory systolic BP, mmHg, week 4, 12.5 mg • Nocturnal BP is a strong predictor of CV outcomes UACR more than halved Annualized chronic eGFR slope (mL/min/1.73m2) was stable in patients with and without CKD stage 3/4 +0.27 in CKD 3/4 UACR: Urine Albumin-to-Creatinine Ratio Unlocking the value of TRYVIO/JERAYGO | 04 Nov 202617 −56% Micro-albuminuria at baseline (30–300 mg/g) −67% Macro-albuminuria at baseline (>300 mg/g) Change from baseline to week 36, 25 mg Schlaich MP, et al. Lancet. 2022;400(10367):1927-1937. Rossignol P et al. Hypertension. 2026;83:448-460. Providing 24-hour BP control Lowering albuminuria Stabilizing kidney function
Page 18
Edema is early, transient, mild to moderate, and peripheral 0% 2% 4% 6% 8% 10% -8 -4 0 4 8 12 16 20 24 28 32 36 40 44 48 New edema and/or fluid retention events Weeks Pre-randomization (switched to SBAT) Part 1 Part 2 (all patients received aprocitentan 25 mg) Part 3 After 8 weeks of treatment, incidence returned to levels observed before randomization Part 1: 12.5 mg Part 2: 25 mg Schlaich MP, et al. The Lancet, 2022 Edema rarely led to treatment discontinuation (<1% over 48 weeks) Unlocking the value of TRYVIO/JERAYGO | 04 Nov 202618
Page 19
Early experience strengthens confidence in the opportunity Rudy Sharan, Head of US Commercial Unlocking the value of TRYVIO/JERAYGO | 04 Nov 202619
Page 20
TRYVIO approved with broad and differentiated US label TRYVIO (aprocitentan) [prescribing information]. Radnor, PA: Idorsia Pharmaceuticals US Inc; 2025. Unlocking the value of TRYVIO/JERAYGO | 04 Nov 202620 Inclusive indication statement which includes the outcome benefits INDICATION AND USAGE TRYVIO is an endothelin receptor antagonist indicated for the treatment of hypertension in combination with other antihypertensive drugs, to lower blood pressure in adult patients who are not adequately controlled on other drugs. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions. Safety profile No incidence of hyperkalemia, hyponatremia, nor hypotension reported No clinically relevant DDIs Edema/fluid retention was generally mild-to- moderate, transient, and primarily observed early in PRECISION. In patients with an eGFR of 15-60 ml/min/1.73 m2, eGFR remained stable
Page 21
Early market feedback aligned with clinical evidence U.S. Key Opinion Leaders identify several key value drivers EFFICACY SAFETY AND TOLERABILITY SIMPLICITY AND NOVELTY INITIAL FEEDBACK – WHAT RESONATES BY SPECIALTY 4 Cardiologists More aware of ERAs as a mechanism for hypertension Nephrologists Drawn to no hyperkalemia and UACR reductions in CKD IM / PCPs Interested in the new pathway ↓15.4 mm Hg • Double-digit reductions in the overall PRECISION population† • Studied in patients on 3 or more antihypertensive medications and eGFR ≥15 mL/min/1.73m 2 48 weeks Once daily • No increased incidence of hyperkalemia, hypotension, or hyponatremia • No clinically relevant drug-drug interactions Use with common comorbidities • Double-digit reductions in patients with CKD stage 3 and 4 • Can be used in patients with diabetes, in obese and elderly No dose adjustment • No dose-adjustment needed according to PI • Most common adverse reactions: edema/fluid retention and anemia † • 12.5 mg once daily • Long t½: Sustained efficacy over 24-hour or if one dose missed • No electrolyte monitoring required • Only approved dual ERA for difficult-to-control hypertension • First agent in nearly 40 years targeting a new pathway in systemic hypertension *TRYVIO 12.5 mg + SOC. †Efficacy and adverse reaction rates reflect the 4- week placebo-controlled period.1,2 CKD = chronic kidney disease; eGFR = estimated glomerular filtration rate; ERA = endothelin receptor antagonist; SOC = standard of care; DDI = drug-drug interaction; CKD = chronic kidney disease; UACR = urine albumin- to- creatinine ratio. References: 1. TRYVIO (aprocitentan) [Prescribing Information]. Radnor, PA: Idorsia Pharmaceuticals US Inc; 2025. 2. Schlaich MP, et al. Lancet. 2022;400(10367):1927 -1937. 3. Rossignol P, et al. Hypertension. 2026;83(2):e25563. 4. US HCP feedback A new pathway for systemic HTN Unlocking the value of TRYVIO/JERAYGO | 04 Nov 202621
Page 22
1H24 2H24 1H25 2H25 1H26 2H26 1H27 With the major foundations now in place, the next phase is disciplined execution to convert growing market readiness into adoption. A market ready for expanded TRYVIO adoption Unlocking the value of TRYVIO/JERAYGO | 04 Nov 202622 FDA Approval March 2024 REMS removed; March 2025 Guideline Inclusion; August 2025 Expand retail distribution Increasing recognition of uncontrolled hypertension and appropriate patients Increasing Reach Decision to have a specialty- led salesforce Focused Deployment Priority hypertension centers with 6 KAMs Light-touch availability Specialty-led sales force IMPACT-HTN; Flagship partnership with Duke & Standford Specialty Pharmacy Walgreens distribution established
Page 23
Early experience supports efficacy in practice, safety profile and willingness to prescribe. Access and distribution remain the key unlocks. “ “ “ “Now with TRYVIO we have for the first time the option to treat patients down to an eGFR of 15 and not worry about hyperkalemia” “I’m seeing ~10 to 15 mmHg drops in BP. Patients on multiple other medications are tolerating TRYVIO well” “One patient had a clear need for another medication; he normalized after adding TRYVIO.” Unlocking the value of TRYVIO/JERAYGO | 04 Nov 202623 Cardiologist Nephrologist Hypertension specialist Early TRYVIO experience at Top HTN centers validates the differentiated profile
Page 24
Unlocking the value of TRYVIO/JERAYGO | 04 Nov 202624 Strengthened confidence in the clinical profile and commercial strategy Limited awareness and availability Early market experience reinforces differentiation Specialist focused launch will unlock broad adoption • Limited experience • Uncertain reimbursement • Limited physician familiarity • Theoretical target population • Unproven commercial strategy • Strong real-world experience at top HTN Centers • Established specialist awareness • Clear and viable patient identification • Broad availability and growing access • Focused specialty strategy to drive adoption • Targeted deployment of capital aligned with high-value opportunities NEXT TODAY AT APPROVAL
Page 25
Targeting specialists in key centers • “Fast follower" strategy, leveraging new market entrant investment in developing the market • Targeting the Top 50 centers and 300 affiliates of care • Significant concentration of cardiologists and nephrologists at 1000+ Top Neph and Card Group Practices • Reaching 5000+ HCPs or 17% of the market • Large medical need with highly identifiable patients who benefit most • Such as patients with CKD 3b/4 − 4M patients with limited treatment options − Proven safety and efficacy − Supports nephrologist discussions − Compelling target for physician first experience Unlocking the value of TRYVIO/JERAYGO | 04 Nov 202625 US | Targeted approach while leveraging Idorsia US commercial platform Targeting specific populations
Page 26
Aligning the interest of all stakeholders Arno Groenewoud, Chief Financial Officer Unlocking the value of TRYVIO/JERAYGO | 04 Nov 202626
Page 27
CHF 120 m committed funding to reach expected break-even in 2029 (1) SPV: Special Purpose Vehicle (Idorsia Investments SARL) - upside value from cenerimod, selatogrel, and aprocitentan once debt in the SPV has been fully paid back. (2) 30% on net sales | 30% on net licensing revenue after contingent liability to Johnson&Johnson (3-5% of aprocitentan net sales, 10% of contract revenue for cenerimod and selatogrel, and 30% of contract revenue for aprocitentan to be paid to Johnson & Johnson for contingent liability to up to CHF 269 m (as of September 30, 2026)). investment in the TRYVIO / JERAYGO launch in 2027 & 2028 SPV noteholders Idorsia earn-out on SPV upside value(1) share in global revenue(2) of upside value in the SPV(1) sit economically between existing A and B notes CHF 72 million new 12% contribution to the TRYVIO / JERAYGO launch in 2027 & 2028 new Notes in the SPV CHF 48 million 30% maintaining 88% Unlocking the value of TRYVIO/JERAYGO | 04 Nov 202627
Page 28
New notes to be issued by the SPV --> consent solicitation to be launched in coming weeks (1) Remains subject to achieving the required noteholder approvals and completion of final documentation CHF 72 m Pay-as-you-can notes in Idorsia Investments SARL (“SPV”) B noteholders offered first opportunity to subscribe, then A noteholders 12% earn-out to be distributed by the SPV to: noteholders who backstop the funding existing noteholders as a consent fee buyers of the new notes Fully backstopped by a group of noteholders representing a significant majority of notes(1) 6% Interest rate 2050 Maturity Ranking Will rank between A1/A2 and B notes Unlocking the value of TRYVIO/JERAYGO | 04 Nov 202628
Page 29
Strong alignment of interests between Idorsia and SPV noteholders over the lifecycle of the SPV assets (1) 3-5% of aprocitentan net sales, 10% of contract revenue for cenerimod and selatogrel, and 30% of contract revenue for aprocitentan to be paid to Johnson & Johnson for contingent liability to up to CHF 269 m (as of September 30, 2026) Unlocking the value of TRYVIO/JERAYGO | 04 Nov 202629 Net Sales 3% to J&J1) 30% to Idorsia 67% to SPV (70% after J&J) Simplified illustrative example of how aprocitentan net sales could be allocated to stakeholders After paying back all notes in the SPV 88% of net proceeds to Idorsia 12% of net proceeds to Earn-out holders Before paying back all notes in the SPV Net proceeds distributed by SPV based on Waterfall to Noteholders
Page 30
The path forward: disciplined execution Unlocking the value of TRYVIO/JERAYGO | 04 Nov 202630
Page 31
Path to unlock the value of TRYVIO/JERAYGO MomentumAssetMarket High unmet needs Differentiated, 1st-in-class Increasing awareness Focused specialty launch strategy gives clear path to blockbuster status Unlocking the value of TRYVIO/JERAYGO | 04 Nov 202631 Drive uptake in the US Tied to market access and adoption Co-promotion opportunities as the market develops Phased approach to EUCAN Out-license opportunities Targeting specialists in key centers Targeting specific populations Additional high-value growth opportunities China Japan