Idorsia Ltd. · SIX:IDIA
Idorsia — Technical Presentation (June 2018)
24 slides from Idorsia's technical presentation, June 2018
Slide 1: Phase 3 investigation of aprocitentan for resistant hypertension management
Phase 3 investigation of aprocitentan for resistant hypertension management Investor Webcast – June 2018
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: More knowledge – Powered by science
More knowledge – Powered by science Jean-Paul Clozel CEO 3 Phase 3 initiation for resistant hypertension management | June 2018
Slide 4: Our Strategic Priorities
Our Strategic Priorities 1 Deliver at least three products to market 5 key priorities to ensure the company’s success 2 Build a commercial organization over the next 5 years 3 Bring Idorsia to profitability in a sustainable manner 4 Create a pipeline with a sales potential of CHF 5 billion 5 Utilize
Slide 5: Aprocitentan: Collaboration with Janssen Biotech, Inc.
Aprocitentan Collaboration with Janssen Biotech, Inc. • Janssen Biotech, Inc. and Idorsia are collaborating in respect of the development and commercialization of aprocitentan and any of its derivative compounds or products • Idorsia has received a one-time milestone payment of USD 230 million • Bot
Slide 6: Phase 3 investigation of aprocitentan for resistant hypertension management
Phase 3 investigation of aprocitentan for resistant hypertension management Guy Braunstein Head of Global Clinical Development 6 Phase 3 initiation for resistant hypertension management | June 2018
Slide 7: Hypertension as a cardiovascular risk factor
Hypertension as a cardiovascular risk factor Hypertension, or high blood pressure, remains the most frequent addressable risk factor of cardiovascular morbidity/ mortality outcomes, ahead of smoking and obesity Reported by the 2015 Global Burden of Disease, Injuries, and Risk Factor Project collabor
Slide 8: What is resistant hypertension?
What is resistant hypertension? Definition Resistant hypertension Patients whose blood pressure remains high, despite receiving at least three antihypertensive medications from different classes, including a diuretic, at Not resistant hypertension maximal tolerated dose Pseudo-resistant hypertension
Slide 9: Resistant hypertension: Clinical phenotypes
Resistant hypertension Clinical phenotypes Typical characteristics of patients Poorer prognosis: higher incidence with resistant hypertension of major cardiovascular events Older age; REACH Registry n = 53,530 High baseline blood especially Excessive pressure and chronicity > 75 years dietary of unc
Slide 10: Resistant hypertension: Therapeutic options
Resistant hypertension Therapeutic options Current (2018) Medical Treatment Principles Pharmacological therapy • Check that each drug is used at the maximum tolerated level • Optimize diuretic treatment • Add antihypertensive drugs with different mechanism of action • Aldosterone receptor antagonist
Slide 11: Aprocitentan in resistant hypertension: Rationale
Aprocitentan in resistant hypertension Rationale Endothelin (ET) System is involved in resistant hypertension ET system is activated in Resistant hypertension is hypertension and especially often a salt- and volume- in salt-and volume- dependent hypertension dependent hypertension ET-1 increase is E
Slide 12: Aprocitentan in resistant hypertension: Rationale
Aprocitentan in resistant hypertension Rationale Orally active Potent dual ETA and ETB receptor antagonist Low potential for drug-drug interaction Synergistic effect with other antihypertensive drugs (RAAS blockers) in Evidence of blockade of both animal models receptors in vivo in humans Demonstrat
Slide 13: Aprocitentan in resistant hypertension: Clinical development
Aprocitentan in resistant hypertension Clinical development • To characterize the RHT SPIRIT patient population survey • To identify sites where these patients are managed Today Clinical Phase 3 Phase 2 pharmacology confirmatory study study • Confirmation of dual ETA and ETB • Clinically relevant, d
Slide 14: Phase 2 study design
Aprocitentan in resistant hypertension Phase 2 study Design Patient population Prospective, multi-center, double-blind, double- • Mild-to-moderate essential hypertension dummy, randomized, monotherapy, placebo- and (Systolic BP/Diastolic BP ≥ 140/90 to < 180/110) active-reference, parallel group, Ph
Slide 15: Aprocitentan dose-dependently decreases blood pressure
Aprocitentan in resistant hypertension Phase 2 study Aprocitentan dose-dependently decreases blood pressure Diastolic Blood Pressure Systolic Blood Pressure -5 -4 Mean change from baseline in DBP (mmHg) Mean change from baseline in SBP (mmHg) -6 -10 -8 -10 -15 -12 -20 -14 5 10 25 50 20 5 10 25 50 20
Slide 16: Phase 2 safety results
Aprocitentan in resistant hypertension Phase 2 study Safety results Placebo Aprocitentan Lisinopril 5 mg 10 mg 25 mg 50 mg 20 mg N 82 82 82 80 81 81 Patients with at least one AE 30 (37%) 18 (22%) 24 (29%) 33 (40%) 22 (27%) 26 (32%) Headache (12) 1 1 2 2 2 4 Nasopharyngitis (10) 1 1 2 2 0 4 Upper re
Slide 17: Phase 2 conclusion
Aprocitentan in resistant hypertension Phase 2 study Phase 2 conclusion Efficacy • Dose response was consistent across all parameters measured • Efficacy observed at 10 and 25 mg, with no additional effect at 50 mg • The effect of aprocitentan covers the 24 h period Safety (in the limit of the study
Slide 18: Phase 3 confirmatory study
Phase 3 confirmatory study Benefitting from consultation with regulatory agencies PRECISION PRECISION will assess the short-term efficacy of aprocitentan as well as the durability of the effect. It will provide replication of clinical evidence in a single study Aprocitentan is investigational, in de
Slide 19: Phase 3 confirmatory study: Study Design
Phase 3 confirmatory study Study Design PRECISION RHT confirmation Efficacy and safety Standardization of aprocitentan Stabilization 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 Standard Stabi
Slide 20: Phase 3 confirmatory study: Objectives
Phase 3 confirmatory study Objectives PRECISION Part I Part II Part III • Double-blind treatment • Single-blind treatment • Double-blind, randomized, • 12.5 mg aprocitentan or 25 mg • 25 mg aprocitentan withdrawal treatment aprocitentan or placebo • Period of 32 weeks • 25 mg aprocitentan or placebo
Slide 21: Phase 3 patient population
Phase 3 confirmatory study Patient population: True resistant hypertension patients on standardized triple therapy PRECISION Entry into screening Entry into run-in Randomization Mean systolic Confirmed diagnosis of Mean systolic blood pressure ≥ 140 mmHg resistant hypertension, mean blood pressure ≥
Slide 22: Phase 3 study endpoints
Phase 3 confirmatory study Study endpoints PRECISION Primary endpoint • Change from baseline to week 4 of double-blind treatment in mean trough sitting systolic blood pressure by AOBPM Key secondary endpoint • Change from week 36 (start of withdrawal period) to week 40 in mean trough sitting systoli
Slide 23: Summary
Summary • Aprocitentan has great potential in difficult to control Resistant hypertension hypertension – resistant hypertension – as an oral, once daily management treatment based on: Compound: Aprocitentan − Pathophysiology of resistant hypertension Mechanism of action: Dual endothelin receptor − M
Slide 24: Physician quote on hypertension research
“Despite hypertension being a serious and growing problem around the world, there is surprisingly little research going on in the field. It has been over 30 years since an anti-hypertensive drug working via a new pathway has been brought to the market.” – Physician 24 Phase 3 initiation for resistan