Idorsia Ltd. · SIX:IDIA
Idorsia — Investor Presentation (October 2017)
71 slides from Idorsia's investor presentation, October 2017
Slide 1: Idorsia – Reaching out for more
Idorsia – Reaching out for more
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: The purpose of Idorsia
Idorsia – Reaching out for more The purpose of Idorsia is to discover, develop and bring more, innovative medicines to patients. Jean-Paul Clozel Chief Executive Officer 3 Idorsia - Reaching out for more | October 2017
Slide 4: Developing Idorsia into a leading European biopharma
Idorsia – Reaching out for more To achieve this, we aim to develop Idorsia into one of Europe’s leading biopharmaceutical companies, with a strong scientific core. Guy Braunstein Head of Global Clinical Development 4 Idorsia - Reaching out for more | October 2017
Slide 5: Idorsia at a glance
Idorsia at a glance 5 Idorsia - Reaching out for more | October 2017
Slide 6: New biopharmaceutical company
New biopharmaceutical company • Fully functional since 15 June 2017 Listed on SIX Swiss Exchange • Started with CHF 1 billion in cash • Total employees: > 600 • 10 compounds in pipeline: key candidates moving into Phase 3 in near future • Guidance: For 2017, we expect non-GAAP operating expenses to
Slide 7: Idorsia's strengths
Idorsia’s strengths The crucial elements for bringing R&D to successful medicines An experienced A full CHF 1 billion team of research and State-of-the-art in cash highly development facilities from Day 1 qualified pipeline professionals 7 Idorsia - Reaching out for more | October 2017
Slide 8: Idorsia's strategic priorities
Idorsia’s strategic priorities To ensure company success over the next 5 years: 1 Deliver at least three products to market 2 Build a commercial organization 3 Bring Idorsia to profitability in a sustainable manner 4 Create a pipeline with a sales potential of CHF 5 billion 5 Integrate state-of-the-
Slide 9: More in the pipeline – Promising compounds
More in the pipeline – Promising compounds 9 Idorsia - Reaching out for more | October 2017
Slide 10: Idorsia's Clinical Development Pipeline
Idorsia’s Clinical Development Pipeline Status Compound Mechanism of Action Target indications Aprocitentan* Endothelin receptor antagonist Resistant hypertension ACT-541468 Dual orexin receptor antagonist Insomnia Phase 2 Cenerimod S1P1 receptor modulator Systemic lupus erythematosus Clazosentan**
Slide 11: Aprocitentan in resistant hypertension
Aprocitentan in resistant hypertension. Aprocitentan is investigational, in development and not approved or marketed in any country. 11 Idorsia - Reaching out for more | October 2017
Slide 12: Resistant hypertension – Medical need
Resistant hypertension – Medical need • Resistant hypertension is defined by uncontrolled hypertension despite three antihypertensive drug therapies from different classes at optimal doses including a diuretic • Represents a small sub-set of hypertensive population • High cardiovascular risk factor
Slide 13: Aprocitentan
Aprocitentan A novel dual ETA and ETB ERA • Oral, potent, once-a-day drug for control of blood pressure • Evaluated in a dose-finding study to explore the effects of aprocitentan (ACT-132577) – at different dose levels – on the efficacy, safety and tolerability in 490 patients with essential hyperte
Slide 14: Aprocitentan dose-finding study
Aprocitentan Dose-finding study Placebo Aprocitentan 5 mg Aprocitentan 10 mg Aprocitentan 25 mg Aprocitentan 50 mg Lisinopril 20 mg Period I Period II Period III SB Placebo Run-in DB-treatment SB Placebo WD FU Randomization DB-EOT WD-EOT EOS Week -6 -4 -1 Day 1 2 4 8 10 Visit 1 2 3 4 5 6 7 8 Phone c
Slide 15: Aprocitentan efficacy results
Aprocitentan Phase 2 efficacy results • In the per-protocol, primary population (410 patients) after 8 weeks of treatment • Mean reduction from baseline in diastolic blood pressure: − 6.3 - 12.0 mmHg in aprocitentan groups (statistically significant dose-dependent manner) − 4.9 mmHg in the placebo g
Slide 16: Aprocitentan safety results
Aprocitentan Phase 2 safety results Placebo group Aprocitentan group Lisinopril group Safety population / in patients 82 327 81 Discontinuation from study 6.1% 1.2% – 3.7% 3.7% treatment due to an adverse event Cases of increased liver enzymes 1 1 – above three times the upper limit of the normal ra
Slide 17: Aprocitentan conclusion from the study
Aprocitentan Conclusion from the study • The effect of aprocitentan observed is clinically relevant • The effect of aprocitentan covers the 24 h period • Aprocitentan was well tolerated across all four doses in this patient population • The overall frequency of adverse events was similar on aprocite
Slide 18: Aprocitentan Phase 3 plans
Aprocitentan Phase 3 plans • Clinical development program in resistant hypertension will be discussed with the health authorities • The proposed program will consist of two studies evaluating the effect of aprocitentan on systolic and diastolic blood pressure in patients with true resistant hyperten
Slide 19: Collaboration with Janssen Biotech, Inc.
Aprocitentan Collaboration with Janssen Biotech, Inc. • Janssen Biotech, Inc. and Idorsia have entered into a collaboration agreement in respect of the development and commercialization of aprocitentan and any of its derivative compounds or products • Following completion of the Phase 2 study, Janss
Slide 20: ACT-541468 (DORA) in insomnia
ACT-541468 (DORA) in insomnia ACT-541468 is investigational, in development and not approved or marketed in any country. 20 Idorsia - Reaching out for more | October 2017
Slide 21: Insomnia – Medical need
Insomnia – Medical need • Around 10% of adults report daytime impairment as result of insomnia • Insomnia is associated with an increased risk of psychiatric disorders − Depression, Anxiety, Alcohol abuse, Drug abuse • Insomnia increases the risk of accident and injury • Insomnia is a leading cause
Slide 22: Insomnia – Medical need: unmet patient needs
Insomnia – Medical need Most existing sleep-promoting agents do not induce natural sleep Leading to unmet patient needs • Lack of continued benefit over time • Lack of sustained effect through the night • Impacted next day performance (residual effect) 22 Idorsia - Reaching out for more | October 20
Slide 23: Insomnia – Medical need: physician concerns
Insomnia – Medical need Most existing sleep-promoting agents have significant limitations Leading to physician concerns • Insufficient acute & long-term efficacy • Abuse potential and withdrawal effect • Problematic side effects − Next day residual effect (balance, ambulation, psychomotor response,
Slide 24: ACT-541468: a novel dual orexin receptor antagonist
ACT-541468 (DORA) A novel dual orexin receptor antagonist Desired profile • High in vitro and in vivo potency and efficacy • Fast onset of action • Appropriate duration of action • No deterioration of next day performance • No unmanageable drug-drug interaction • No safety issue ACT-541468 is invest
Slide 25: Rat EEG data: sleep efficacy / architecture
ACT-541468 (DORA) Rat EEG data: sleep efficacy / architecture ACT-541468 (mg/kg) Active wake Quiet wake non-REM sleep REM sleep Vehicle 39.9 35.9 18.0 6.2 * Active 10 35.3 35.5 21.7 7.4 phase dosing *** *** ** 30 31.1 35.1 24.0 9.8 *** *** *** 100 27.3 34.2 27.5 11.0 Rest phase 15.3 33.5 40.4 10.8 T
Slide 26: ACT-541468 Phase 1 program
ACT-541468 (DORA) Phase 1 program Single-ascending dose study in healthy young male adults • Doses evaluated from 5 mg to 200 mg 3-part study in male and female young adults and elderly • Multiple-ascending dose in adults • Single-ascending dose in elderly • Multiple night-time dosing in adult and e
Slide 27: Ideal pharmacokinetic profile
ACT-541468 (DORA) Ideal pharmacokinetic profile for an insomnia medication 1000 800 Dose: 25 mg for 600 5 days 400 200 ACT-541468 (ng/ml) 0 0 24 48 72 96 120 144 168 ACT-541468 is investigational, in development and not approved or marketed in any country. 27 Idorsia - Reaching out for more | Octobe
Slide 28: Pharmacodynamic profile: fast onset of action
ACT-541468 (DORA) Pharmacodynamic profile Fast onset of action in adult & elderly Adult Healthy Volunteer – Daytime dosing Elderly Healthy Volunteer – Daytime dosing Person performing eye movement test Reduced speed of eye movements ACT-541468 is investigational, in development and not approved or m
Slide 29: Pharmacodynamic profile: duration of action
ACT-541468 (DORA) Pharmacodynamic profile Appropriate duration of action in adult & elderly Adult Healthy Volunteer – Daytime dosing Elderly Healthy Volunteer – Daytime dosing Person performing adaptive tracking test Reduced tracking performance ACT-541468 is investigational, in development and not
Slide 30: Next-day pharmacodynamic profile
ACT-541468 Next-day pharmacodynamic profile No sleepiness reported on next morning Healthy adult with night-time administration Karolinska Sleepiness Scale Score 9 Very sleepy 8 Sleepy, but no effort 7 keeping awake 6 Neither 5 alert nor sleepy 4 Alert, 3 normal level 2 1 Very alert ACT-541468 is in
Slide 31: Initial safety profile from Phase 1 program
ACT-541468 (DORA) Initial safety profile from Phase 1 program • No SAEs, no unexpected AEs after 110 healthy adults and elderly exposed • Starting at 25 mg, transient AEs of mild to moderate intensity were observed such as: Disturbance of attention, somnolence, fatigue, headache and dizziness • No s
Slide 32: Phase 2 program overview
ACT-541468 (DORA) Phase 2 program overview • Two dose-response studies to evaluate the safety and efficacy of DORA in adult and elderly patients with insomnia • Adult study with zolpidem as an active reference − Study 1: 360 adult insomnia patients − Study 2: 58 elderly insomnia patients ACT-541468
Slide 33: Phase 2 results in adult patients
ACT-541468 (DORA) Phase 2 results in adult patients, announced in July 2017 • Study in adults showed a significant dose dependent decrease in WASO (average decrease of wake-time after sleep onset) at Day 1 & 2 • ACT-541468 also significantly decreased LPS (latency to persistent sleep) at Day 1 & 2 i
Slide 34: Phase 2 results in elderly patients
ACT-541468 (DORA) Phase 2 results in elderly patients, announced in July 2017 • Positive results of the study confirm the efficacy and safety profile of ACT- 541468 in this population • Results of this study also showed significant decrease in WASO and LPS at Day 1&2 in a dose-dependent manner ACT-5
Slide 35: ACT-541468 summary
ACT-541468 (DORA) Summary • Idorsia has significant expertise in the discovery and development of DORAs • DORAs have the potential to promote sleep and maintain a natural sleep architecture • PK/PD profile of ACT-541468 suggests an optimal combination of effect on the CNS and low residual concentrat
Slide 36: Cenerimod in systemic lupus erythematosus
Cenerimod in systemic lupus erythematosus Cenerimod is investigational, in development and not approved or marketed in any country. 36 Idorsia - Reaching out for more | October 2017
Slide 37: Systemic lupus erythematosus – Medical need
Systemic lupus erythematosus – Medical need • Complex, systemic, autoimmune disease of unknown etiology • Characterized by tissue damage across multiple organ systems • Severe organ damage and significant mortality in subset of patients • Limited treatment options with a high need for a new approach
Slide 38: Cenerimod: a novel S1P1 receptor modulator
Cenerimod A novel S1P1 receptor modulator O N • Very potent, highly selective, S1P1 receptor modulator • Prevents lymphocytes from leaving lymph nodes and reaching target tissues N O N • Induces rapid and reversible, dose-dependent blood lymphocyte count reduction • Pharmacokinetic profile suitable
Slide 39: Cenerimod Phase 2 study
Cenerimod Phase 2 study Phase 2 randomized, double-blind, placebo-controlled, dose-response study to investigate the biological activity, safety, and tolerability of cenerimod in adult patients with systemic lupus erythematosus 67 patients were enrolled to receive either placebo or 0.5, 1, 2 or 4 mg
Slide 40: Cenerimod Phase 2 study design
Cenerimod Phase 2 study Randomization EOT EOS Placebo 12 pts Part A Cenerimod 0.5 mg 12 pts Cenerimod 1.0 mg 12 pts Cenerimod 2.0 mg 12 pts Visit 1 2 3 4 5 6 7 8 9 Week Day -30 Day 1 2 4 8 12 18 23 28 Screening Treatment period Follow-up Phone calls FU 30 days 12 weeks 6 weeks 10 weeks Randomization
Slide 41: Cenerimod study results
Cenerimod Study results • A dose-response relationship for cenerimod was demonstrated, based on circulating lymphocyte counts • Cenerimod was well tolerated at all dose levels • The occurrence of adverse events was similar in all five treatment groups • As a result, cenerimod is ready to move into a
Slide 42: Clazosentan in cerebral vasospasm post-aSAH
Clazosentan in cerebral vasospasm post-aneurysmal subarachnoid hemorrhage Clazosentan is investigational, in development and not approved or marketed in any country. 42 Idorsia - Reaching out for more | October 2017
Slide 43: Vasospasm post-aSAH – Medical need
Vasospasm post-aSAH – Medical need aSAH is a sudden, life-threatening bleeding in the space around the brain caused by the rupture of an aneurysm 43 Idorsia - Reaching out for more | October 2017
Slide 44: Clazosentan: highly soluble ETA selective ERA
Clazosentan Highly soluble ETA selective ERA • Ideal for intravenous administration • >1’500 patients treated with clazosentan providing significant experience in vasospasm post aSAH and a well documented safety profile • CONSCIOUS-2 aneurysm secured by clipping • CONSCIOUS-3 aneurysm secured by coi
Slide 45: CONSCIOUS-3 results
Clazosentan CONSCIOUS-3 results – event rate for the components of the 1o composite endpoint RRR 35% -21% 15% 29% (95% CI) (-79 to 76%) (-97 to 26%) (-28 to 44%) (-9 to 54%) -34% 44% 54% 65% (-211 to 42%) (-5 to 70%) (22 to 72%) (38 to 80%) 25 21 21 20 18 Placebo 16 Event rate (%) Clazosentan 5 mg/h
Slide 46: Clazosentan Phase 3 REVERSE study
Clazosentan Phase 2 REVERSE study • REVERSE: Phase 2 study to evaluate whether clazosentan has a rapid effect in reversing angiographically-confirmed cerebral vasospasm in patients with aSAH treated by endovascular coiling or surgical clipping • Results are expected to be discussed with health autho
Slide 47: Lucerastat in Fabry disease
Lucerastat in Fabry disease Lucerastat is investigational, in development and not approved or marketed in any country. 47 Idorsia - Reaching out for more | October 2017
Slide 48: Fabry disease – Medical need
Fabry disease – Medical need Fabry disease is a rare X-linked genetic disorder in which patients have a deficiency or dysfunction of the enzyme alpha-galactosidase A Standard treatment approach for Fabry disease is Enzyme Replacement Therapy (ERT), which supplies recombinant GLA to the cells 48 Idor
Slide 49: Lucerastat current status
Lucerastat Current status • Lucerastat is a small molecule iminosugar that inhibits glucosylceramide synthase and has the potential to provide substrate reduction therapy for the oral treatment of certain lysosomal storage disorders • In an exploratory clinical study in patients with Fabry disease t
Slide 50: Vamorolone in Duchenne Muscular Dystrophy
Vamorolone in Duchenne Muscular Dystrophy 50 Idorsia - Reaching out for more | October 2017
Slide 51: Vamorolone
Vamorolone • Vamorolone is a novel compound for the treatment of Duchenne Muscular Dystrophy • It holds potential to better preserve muscle function and prolong ambulation for the patient, without some of the side effects associated with glucocorticoid therapy • A Phase 2a program is currently under
Slide 52: Idorsia's Phase 1 clinical development pipeline
Idorsia’s Phase 1 clinical development pipeline 52 Idorsia - Reaching out for more | October 2017
Slide 53: ACT-246475 – P2Y12 receptor antagonist
ACT-246475 – P2Y12 receptor antagonist in acute coronary syndrome • In development for the prevention of myocardial damage in acute coronary syndrome • Targeted for individuals at risk of a myocardial infarction • Meets a very specific pharmacokinetic profile, which requires the product to be well-
Slide 54: ACT-539313 – selective orexin 1 receptor antagonist
ACT-539313 – selective orexin 1 receptor antagonist (SORA) In anxiety disorders • In development for the potential treatment of anxiety disorders • Potent antagonist, brain-penetrating • Shown anxiolytic (anxiety inhibiting) effects after oral administration in four different preclinical models repr
Slide 55: ACT-774312 – CRTH2 receptor antagonist
ACT-774312 – CRTH2 receptor antagonist in asthma and allergy disorders • In development for the treatment of asthma and allergy disorders for patients whose disease is not fully controlled with conventional therapies • Current evidence suggests that treatment with a CRTH2 receptor antagonist can con
Slide 56: ACT-709478 – T-type calcium channel blocker
ACT-709478 – T-type calcium channel blocker in epilepsy • In development for certain forms of generalized epilepsy • ACT-7091478 is a selective, orally available triple T-type calcium channel blocker. • The compound exhibits good tolerability after single-dose administration in humans and PK propert
Slide 57: More science – Bursting with ideas
More science – Bursting with ideas 57 Idorsia - Reaching out for more | October 2017
Slide 58: Idorsia's drug discovery approach
Idorsia’s drug discovery approach Single-center approach Few platforms of expertise Fully integrated research informatics Multiple therapeutic areas Focus on High medical input small molecules 58 Idorsia - Reaching out for more | October 2017
Slide 59: Key financials
Key financials 59 Idorsia - Reaching out for more | October 2017
Slide 60: Operating results
Operating results Financial results as of 30 September 2017 Non-GAAP US-GAAP -34 -71 -79 -23 -14 -5 -3 Revenues Research Development G&A Non-GAAP D&A SBC US-GAAP Operating Operating results results 60 Idorsia - Reaching out for more | October 2017
Slide 61: Net results
Net results Financial results as of 30 September 2017 Non-GAAP US-GAAP -71 -73 -2 +1 -79 -4 -82 Operating results Financial Income Tax Non-Controlling Interests Net results results results 61 Idorsia - Reaching out for more | October 2017
Slide 62: Cash flow
Cash flow Financial results as of 30 September 2017 +22 +2 - 72 1,000 952 Cash at Funds from Working Capital Capex / Liquidity as of Demerger Operations Requirements Other 30 Sep 2017 62 Idorsia - Reaching out for more | October 2017
Slide 63: Liquidity
Liquidity Financial results as of 30 September 2017 952 250 Cash deposits > 3 months Cash deposits 150 < 3 months 1,000 Cash and Cash Equivalents 552 Liquidity at Liquidity as of demerger 30 Sep 2017 63 Idorsia - Reaching out for more | October 2017
Slide 64: Convertible bond
Convertible bond Financial results as of 30 September 2017 580 135 445 Equity component 82 Debt component 445 363 Convertible Bond Convertible Bond at demerger as of 30 Sep 2017 64 Idorsia - Reaching out for more | October 2017
Slide 65: Potential issued shares
Potential issued shares Financial results as of 30 September 2017 Issued common shares = 119.1 million Potential issued shares = 162.7 million 157.8 162.7 4.9 50.5 38.7 Equity instruments Equity derivatives 119.1 Issued common 107.3 shares Potential shares Potential shares at demerger as of 30 Sep 2
Slide 66: Financial Guidance for 2017
Financial Guidance for 2017 As of 24 October 2017 -10 • Non-GAAP Operating Expenses = CHF -160 / -170 million -61 • 2017 = 6 ½ months activity since demerger from Actelion -89 -99 -160 -170 Q2 2017 Q3 2017 Q4 2017 FY 2017 (Actual) (Actual) (Estimate) (Estimate) 66 Idorsia - Reaching out for more | O
Slide 67: More experience – Driving innovation
More experience – Driving innovation 67 Idorsia - Reaching out for more | October 2017
Slide 68: Idorsia's leadership team
Idorsia has a strong and visionary leadership team with the power and drive to create more remarkable innovations and more new medicines 68 Idorsia - Reaching out for more | October 2017
Slide 69: Idorsia management team
Idorsia management team Jean-Paul Clozel Martine Clozel Guy Braunstein André C. Muller Chief Executive Officer Chief Scientific Officer Head of Global Clinical Development Chief Financial Officer Andrew C. Weiss Head of Investor Relations & Alex Khatuntsev Oliver Peinelt Olivier Lambert Corporate Co
Slide 70: Idorsia Board of Directors
Idorsia Board of Directors Jean-Pierre Garnier Robert J. Bertolini Jean-Paul Clozel Chairman of the board of directors Member of the board of directors Chief Executive Officer John J. Greisch David Stout Herna Verhagen Member of the board of directors Member of the board of directors Member of the b
Slide 71: Be prepared for more
Be prepared for more 71 Idorsia - Reaching out for more | October 2017