Idorsia Ltd. · SIX:IDIA
Idorsia — Technical Presentation (May 2022)
37 slides from Idorsia's technical presentation, May 2022
Slide 1: PRECISION: Phase 3 study of aprocitentan for patients with resistant hypertension
PRECISION: Phase 3 study of aprocitentan for patients with resistant hypertension Investor webcast – May 2022
Slide 2: Forward-looking statements
The following 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 “estimates”, “believes”, “expects”, “may”, “are expected to”, “will”, “will continue”, “should”, “would be”, “seeks”,
Slide 3: CEO quote: Idorsia at the forefront of medical research
“I am very proud that Idorsia is once again at the forefront of medical research.” Jean-Paul Clozel Chief Executive Officer 3 Investor webcast – PRECISION results | May 2022
Slide 4: CSO quote: result more than 30 years in the making
“This outstanding result has been more than 30 years in the making!” Martine Clozel Chief Scientific Officer 4 Investor webcast – PRECISION results | May 2022
Slide 5: Endothelin-1 identified as a target
Endothelin-1 identified as a target 1988 Endothelin-1 identified 1990 ETA and ETB receptors identified 5 Investor webcast – PRECISION results | May 2022
Slide 6: First antagonists of the endothelin system
First antagonists of the endothelin system 1988 Endothelin-1 identified 1990 ETA and ETB receptors identified 1993 First orally available Endothelin Receptor Antagonist (ERA) published in Nature 6 Investor webcast – PRECISION results | May 2022
Slide 7: Advancing the potential of the endothelin system
Advancing the potential of the endothelin system 1988 Endothelin-1 identified 1990 ETA and ETB receptors 2022 1998 Aprocitentan identified 2007 First evidence of successfully 1993 dual ERA effect in Failed attempt investigated for hypertension in resistant resistant First orally published in New hyp
Slide 8: Resistant hypertension
Resistant hypertension 8 Investor webcast – PRECISION results | May 2022
Slide 9: What is resistant hypertension?
What is resistant hypertension? Resistant hypertension Patients whose blood pressure remains high, despite receiving at least three antihypertensives of different pharmacological classes, including a diuretic, at optimal dose. 9 Investor webcast – PRECISION results | May 2022
Slide 10: Risk factors for resistant hypertension
Risk factors for resistant hypertension Older age; especially > 75 years Ethnicity Post-menopausal (higher prevalence in women African Americans) High Body Mass Obstructive Sleep Index (BMI) Apnea (OSA) High baseline blood pressure and chronicity of uncontrolled hypertension 10 Investor webcast – PR
Slide 11: Disease burden when hypertension is uncontrolled
Disease burden when hypertension is uncontrolled Increased risk of certain health Higher incidence of major 95% cardiovascular events outcomes compared to those with 88% controlled essential hypertension REACH Registry n = 53,530 57% 44% 30% 23% Medication usage: Peripheral All-cause Coronary Stroke
Slide 12: Estimated resistant hypertensive patient population in 2025
Estimated resistant hypertensive patient population in 2025 US breakdown of projected number of resistant hypertensive patients (patients in millions, 2025) 122.4 35.0 87.4 77.4 10.0 Prevalence of Untreated Treated Treated Uncontrolled BP (clinic BP hypertension1 hypertension hypertension 1+ hyperte
Slide 13: Endothelin-1 and resistant hypertension
Endothelin-1 and resistant hypertension 13 Investor webcast – PRECISION results | May 2022
Slide 14: Endothelin system is (until now!) untargeted in systemic hypertension
Endothelin system is (until now!) untargeted in systemic hypertension Dates of Discovery of Antihypertensive Drugs or Drug Classes Year(s) Antihypertensive Agent(s) 1900 Sodium thiocyanate 1930 Reserpine 1947-1950 Ganglion blocking drugs 1958 Thiazide-type diuretics 1950s Hydralazine 1950s Guanethid
Slide 15: Endothelin system in resistant hypertension
Endothelin system in resistant hypertension Salt Risk factors ET-1 Endothelial dysfunction Hypertrophy and Inflammation Hypertension Aldosterone release Hypervolemia proliferation and fibrosis END-ORGAN DAMAGE 15 Investor webcast – PRECISION results | May 2022
Slide 16: Aprocitentan for resistant hypertension
Aprocitentan for resistant hypertension Aprocitentan is investigational, in development and not approved or marketed in any country. 16 Investor webcast – PRECISION results | May 2022
Slide 17: Aprocitentan in resistant hypertension
Aprocitentan in resistant hypertension Orally-active, potent dual ETA and ETB receptor antagonist Low potential for drug-drug Synergistic effect with interaction other antihypertensive drugs (RAAS blockers) in animal models Demonstrated efficacy of aprocitentan Demonstrated blood pressure on blood p
Slide 18: PRECISION is positive! (quote)
“PRECISION is positive! Primary and key secondary endpoints are statistically significant and clinically meaningful.” Alberto Gimona Head of Global Clinical Development 18 Investor webcast – PRECISION results | May 2022
Slide 19: Aprocitentan clinical development overview
Aprocitentan clinical development overview • To characterize the resistant hypertension patient population SPIRIT survey* • To identify sites where these patients are managed Clinical Phase 2 Phase 3 pharmacology study confirmatory study • Confirmation of dual ETA and ETB • Clinically relevant, dose
Slide 20: PRECISION Phase 3 study objectives
PRECISION Phase 3 study Primary objective Demonstrate the blood pressure lowering effect of aprocitentan in patients with confirmed resistant hypertension Secondary objectives Demonstrate that the effect of aprocitentan on blood pressure is durable in patients with confirmed resistant hypertension T
Slide 21: PRECISION study design
PRECISION study design Patient population with established Efficacy and safety resistant hypertension of aprocitentan 1 to 8 weeks 4 weeks 4 weeks 4 weeks 32 weeks Withdrawal 12 weeks 30 days Safety Screening Screening Run-in Part I Part II Part III Follow-up Individual Standardized Stabilization on
Slide 22: Patient population with established resistant hypertension
Patient population with established resistant hypertension Standardized background Stabilization on standardized Individual background antihypertensive therapy background antihypertensive antihypertensive therapy therapy 1 to 8 weeks 4 weeks 4 weeks Randomization Antihypertensive medication of ≥ 3 G
Slide 23: Patient disposition
Patient disposition Randomized N = 730 Aprocitentan 12.5 mg Aprocitentan 25 mg Placebo N = 243 N = 243 N = 244 Double- blind Prematurely discontinued 11 (4.5%) 9 (3.7%) 6 (2.5%) (Part 1) Treated Aprocitentan 25 mg N = 704 Single- blind Prematurely discontinued 91 (12.9%) (Part 2) Re-randomized N = 6
Slide 24: Patient demographic and disease characteristics
Patient demographic and disease characteristics – in line with resistant hypertension population Demographic characteristics Total Variable Statistic N = 730 [n (%)] Age at screening (years) Mean (SD) 61.7 (10.6) Sex n = 730 Male 434 (59.5) Female 296 (40.5) Race White 605 (82.9) Black or African Am
Slide 25: Patient demographic and disease characteristics
Patient demographic and disease characteristics – in line with resistant hypertension population Demographic characteristics Total Disease characteristics Total Variable Statistic N = 730 Variable Statistic N = 730 [n (%)] [n (%)] Age at screening (years) Main anti-hypertensive therapies present at
Slide 26: Patient demographic and disease characteristics
Patient demographic and disease characteristics – in line with resistant hypertension population Demographic characteristics Total Disease characteristics Total Demographic characteristics Total Variable Statistic N = 730 Variable Statistic N = 730 Variable Statistic N = 730 [n (%)] [n (%)] [n (%)]
Slide 27: PRECISION – Part 1
PRECISION – Part 1 Part 1 Double-blind 25 mg aprocitentan Randomization (1:1:1) 12.5 mg aprocitentan placebo Treatment 4 weeks Continue standardized background antihypertensive therapy Aprocitentan is investigational, in development and not approved or marketed in any country. 27 Investor webcast –
Slide 28: Primary endpoint results
Primary endpoint results Randomized N = 730 Aprocitentan 12.5 mg Aprocitentan 25 mg Placebo N = 243 N = 243 N = 244 After 4 weeks of treatment, a statistically significant and clinically meaningful reduction in the primary endpoint measure of systolic blood pressure – assessed by measurement at trou
Slide 29: PRECISION – Part 2
PRECISION – Part 2 Part 1 Part 2 Double-blind Single-blind 25 mg aprocitentan Randomization (1:1:1) 12.5 mg aprocitentan 25 mg aprocitentan placebo Treatment 4 weeks 32 weeks Continue standardized background antihypertensive therapy Aprocitentan is investigational, in development and not approved or
Slide 30: Effect maintained through Part 2
Effect maintained through Part 2 Aprocitentan 25 mg N = 704 In patients who received aprocitentan during Part 1 the mean reduction from baseline in systolic blood pressure was maintained Patients switching from placebo to aprocitentan rapidly achieved the same blood pressure reduction as seen in Par
Slide 31: PRECISION – Part 3
PRECISION – Part 3 Part 1 Part 2 Part 3 Double-blind Single-blind Double-blind withdrawal End of treatment Re-randomization (1:1) 25 mg aprocitentan 25 mg aprocitentan Randomization (1:1:1) 12.5 mg aprocitentan 25 mg aprocitentan placebo placebo Treatment Withdrawal Safety 4 weeks 32 weeks 12 weeks
Slide 32: Key secondary endpoint result
Key secondary endpoint result Re-randomized N = 614 Aprocitentan 25 mg Placebo N = 307 N = 307 After 4 weeks in the withdrawal period, systolic blood pressure increased significantly on placebo compared to aprocitentan 25 mg (p<0.0001) This provided replication of the treatment effect of aprocitenta
Slide 33: Consistent efficacy across multiple endpoints
Consistent efficacy across multiple endpoints Double-blind Double-blind withdrawal at week 4 at week 40 Aprocitentan Aprocitentan Aprocitentan 12.5 mg 25 mg 25 mg AOBP systolic BP(mmHg) √ √ √ AOBP diastolic BP (mmHg) √ √ √ ABPM 24-h mean systolic BP √ √ √ ABPM 24-h mean diastolic BP √ √ √ ABPM night
Slide 34: Top-line safety results
Top-line safety results Double-blind 4 weeks • Aprocitentan was generally well Aprocitentan Aprocitentan Placebo tolerated with no major safety 12.5 mg 25 mg concerns in this patient population Treatment-emergent 27.6% 36.7% 19.4% adverse events (TEAEs) at both doses discontinuation due to 2.5% 2.0%
Slide 35: PRECISION Phase 3 study topline conclusion
PRECISION Phase 3 study Topline conclusion Aprocitentan reduces blood pressure compared to placebo by week 4 of treatment, the effect is maintained and confirmed over a period of 48 weeks, and is generally well tolerated with no major safety concerns Primary and key secondary endpoints were met with
Slide 36: CEO quote: collected safety and efficacy information
“We have collected information on safety and efficacy which will allow us to fully characterize the benefit of aprocitentan.” Jean-Paul Clozel Chief Executive Officer Aprocitentan is investigational, in development and not approved or marketed in any country. 36 Investor webcast – PRECISION results
Slide 37: Aprocitentan for difficult-to-control hypertension: next steps
Aprocitentan for difficult-to- control hypertension New mode of action in systemic hypertension Next steps • Discuss the results with health authorities with the aim to file the NDA with the US FDA by the end of 2022 – closely followed by other health authorities • Share data through scientific pres