Idorsia Reaching out for more

Transcription

1 Idorsia Reaching out for more

2 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, pending or anticipates or similar expressions, or by discussions of strategy, plans or intentions. Such statements include descriptions of the company s investment and research and development programs and anticipated expenditures in connection therewith, descriptions of new 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. 2

3 15 June

4 The purpose of Idorsia is to discover, develop and bring more, innovative medicines to patients. We have more ideas, we see more opportunities and we want to help more patients. 4

5 Highlights Pipeline Results Substantial progress with the pipeline productive discussions with health authorities Idorsia is born Idorsia created and listed pipeline advanced without missing a beat Partnerships Development partnership with Janssen Biotech to advance aprocitentan Research collaboration with Roche in the field of cancer immunotherapy 5

6 Idorsia Today >650 Highly qualified professionals 11 Compounds in the pipeline, with four progressing to late-stage development in the year ahead >1 bn Swiss francs in cash > 550 State-of-the-art laboratory workspaces 6

7 Our Strategic Priorities 1 5 key priorities to ensure the company s success over the next 5 years 2 Deliver at least three products to market Build a commercial organization 3 Bring Idorsia to profitability in a sustainable manner 4 5 Create a pipeline with a sales potential of CHF 5 billion Utilize state-of-the-art technologies 7

8 More in the pipeline Promising compounds Diversified and balanced pipeline: CNS, cardiovascular and immunological disorders & orphan diseases Asthma and allergy disorders ACT CRTH2 receptor antagonist Status: Phase 1 Duchenne muscular dystrophy Vamorolone Dissociative steroid Status: Phase 2 Idorsia has an exclusive option to the worldwide rights for ReveraGen's vamorolone Anxiety Resistant hypertension Management Aprocitentan Dual endothelin receptor antagonist Status: Advancing to Phase 3 ACT Selective orexin 1 receptor antagonist Status: Phase 1 Insomnia Acute Coronary Syndrome ACT P2Y12 receptor antagonist Status: Phase 2 Fabry disease ACT Dual orexin receptor antagonist Status: Advancing to Phase 3 Epilepsy Lucerastat Glucosylceramide synthase inhibitor Status: Advancing to Phase 3 ACT T-type calcium channel blocker Status: Phase 1 Systemic lupus erythematosus Cenerimod S1P 1 receptor modulator Status: Phase 2 Orphan CNS diseases Vasospasm associated with aneurysmal subarachnoid hemorrhage (asah) Clazosentan Endothelin receptor antagonist Status: Advancing to Phase 3 ACT GBA2/GCS inhibitor Status: Phase 1 8

9 Lucerastat in Fabry disease Lucerastat is investigational, in development and not approved or marketed in any country. 9

10 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 10

11 Lucerastat 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 treated with ERT, treatment with lucerastat showed a marked decrease in the plasma levels of metabolic substrates thought to be related to the development of the disease Lucerastat is investigational, in development and not approved or marketed in any country. 11

12 Summary Fabry disease is a rare genetic disorder involving deficiency or dysfunction of an enzyme that breaks down fatty waste products in body Lucerastat oral monotherapy offers new treatment approach with potential to alleviate symptoms of Fabry disease Phase 3 study to assess effects of compound on neuropathic pain and gastrointestinal symptoms and safety and tolerability to start in first half of 2018 Lucerastat has orphan drug status in US and EU Fabry disease Compound: Lucerastat Mechanism of action: Glucosylceramide synthase inhibition Status: Advancing to Phase 3 Lucerastat is investigational, in development and not approved or marketed in any country. 12

13 Aprocitentan in resistant hypertension management. Aprocitentan is investigational, in development and not approved or marketed in any country. 13

14 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 in comparison to non-resistant hypertension Evidence supports ERAs as a therapeutic strategy in systemic hypertension with the appropriate product Renal denervation studies continue despite initial failure, exemplifying medical need in resistant hypertension 14

15 Aprocitentan A novel dual ET A and ET B 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 ) at different dose levels on the efficacy, safety and tolerability in 490 patients with essential hypertension Aprocitentan is investigational, in development and not approved or marketed in any country. 15

16 Aprocitentan Dose-finding study Placebo Aprocitentan 5 mg Aprocitentan 10 mg Aprocitentan 25 mg Aprocitentan 50 mg Lisinopril 20 mg Period I SB Placebo Run-in Period II DB-treatment Period III SB Placebo WD FU Week Randomization DB-EOT WD-EOT EOS Day Visit Phone call/visit Aprocitentan is investigational, in development and not approved or marketed in any country. 16

17 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: mmhg in aprocitentan groups (statistically significant dose-dependent manner) 4.9 mmhg in the placebo group 8.4 mmhg in the lisinopril group Mean reduction from baseline in systolic blood pressure : 10.3 to 18.5 mmhg in the aprocitentan groups (statistically significant dose-dependent manner) 7.7 mmhg in the placebo group 12.8 mmhg in the lisinopril group Findings confirmed in all randomized patients (Intent-to-Treat principle) and by 24 hours Ambulatory Blood Pressure Monitoring Aprocitentan is investigational, in development and not approved or marketed in any country. 17

18 Aprocitentan Phase 2 safety results Placebo group Aprocitentan group Lisinopril group Safety population / in patients Discontinuation from study treatment due to an adverse event Cases of increased liver enzymes above three times the upper limit of the normal range 6.1% 1.2% 3.7% 3.7% 1 1 Dose 5 mg 10 mg 25 mg 50 mg 20 mg Cases of peripheral edema 2 2 Change of mean body weight / in kg Dose related change from baseline in the hemoglobin concentration Increase 2.2 g/l Expected decrease 1.3 to 6.7 g/l Increase 0.1 g/l Aprocitentan is investigational, in development and not approved or marketed in any country. 18

19 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 aprocitentan to placebo It is anticipated that the results can be extrapolated to resistant hypertension The study provides the necessary information for moving into a pivotal registration program Aprocitentan is investigational, in development and not approved or marketed in any country. 19

20 Aprocitentan Phase 3 plans Based on the positive dose-finding results and following feedback from health authorities, Idorsia is currently finalizing the design of a Phase 3 study The study will evaluate the initial and long-term effect of aprocitentan on systolic and diastolic blood pressure in patients requiring resistant hypertension management (RHM) The program will also provide long-term safety information If successful, the study will constitute the basis for registration of the product Significant potential to expand indications to related populations Aprocitentan is investigational, in development and not approved or marketed in any country. 20

21 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 Both parties will have joint development rights over aprocitentan, while Janssen Biotech, Inc will have the sole manufacturing and commercialization rights The development costs will be shared equally between both partners Idorsia will oversee Phase 3 development and regulatory submission for the treatment of patients with hypertension that is not controlled by at least three therapies Janssen will oversee the Phase 3 development and submission for any additional indications Aprocitentan is investigational, in development and not approved or marketed in any country. 21

22 Summary Aprocitentan has great potential in resistant hypertension management as an oral, once daily treatment with potent, long lasting hypertensive effects We are collaborating with Janssen Biotech to jointly develop and commercialize product Phase 3 study to evaluate initial and long-term effects on systolic and diastolic blood pressure in patients requiring resistant hypertension management expected to start in first half 2018 This registration program is based on feedback from health authorities Resistant hypertension management Compound: Aprocitentan Mechanism of action: Dual endothelin receptor antagonism Status: Advancing to Phase 3 Aprocitentan is investigational, in development and not approved or marketed in any country. 22

23 ACT in insomnia ACT is investigational, in development and not approved or marketed in any country. 23

24 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 of absenteeism and reduced productivity at work Estimated global cost around USD 100 billion each year 24

25 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) 25

26 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, etc.) Rebound insomnia upon attempted discontinuation Memory disorders (including anterograde amnesia) Parasomnias 26

27 ACT (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 is investigational, in development and not approved or marketed in any country. 27

28 ACT (DORA) Rat EEG data: sleep efficacy / architecture ACT (mg/kg) Active wake Quiet wake non-rem sleep REM sleep Vehicle Active phase dosing * *** *** ** *** *** *** Rest phase Time spent in sleep and wake stages (% of total time) over the first 6h of the active phase following administration ACT is investigational, in development and not approved or marketed in any country. 28

29 ACT (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 elderly ACT is investigational, in development and not approved or marketed in any country. 29

30 ACT (DORA) Ideal pharmacokinetic profile for an insomnia medication Dose: 25 mg for 5 days ACT (ng/ml) ACT is investigational, in development and not approved or marketed in any country. 30

31 ACT (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 is investigational, in development and not approved or marketed in any country. 31

32 ACT (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 is investigational, in development and not approved or marketed in any country. 32

33 ACT Next-day pharmacodynamic profile No sleepiness reported on next morning Healthy adult with night-time administration Karolinska Sleepiness Scale Score Very sleepy Sleepy, but no effort keeping awake Neither alert nor sleepy Alert, normal level Very alert ACT is investigational, in development and not approved or marketed in any country. 33

34 ACT (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 significant effect on vital signs, ECG, and laboratory parameters ACT is investigational, in development and not approved or marketed in any country. 34

35 ACT (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 is investigational, in development and not approved or marketed in any country. 35

36 ACT (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 also significantly decreased LPS (latency to persistent sleep) at Day 1 & 2 in a dose-dependent manner Treatment with ACT was generally well tolerated - no reports of serious AEs related to treatment ACT is investigational, in development and not approved or marketed in any country. 36

37 ACT (DORA) Phase 2 results in elderly patients, announced in July 2017 Positive results of the study confirm the efficacy and safety profile of ACT 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 is investigational, in development and not approved or marketed in any country. 37

38 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 suggests an optimal combination of effect on the CNS and low residual concentration next-day for a sleep medication Both Phase 2 studies, in adult and elderly patients, meet their primary endpoints Registration program based on feedback from health authorities Insomnia Compound: ACT Mechanism of action: Dual orexin receptor antagonism Status: Advancing to Phase 3 ACT is investigational, in development and not approved or marketed in any country. 38

39 Clazosentan in cerebral vasospasm post-aneurysmal subarachnoid hemorrhage Clazosentan is investigational, in development and not approved or marketed in any country. 39

40 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 40

41 Clazosentan Highly soluble ET A 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 CONSCIOUS-3 aneurysm secured by clipping aneurysm secured by coiling Clazosentan is investigational, in development and not approved or marketed in any country. 41

42 Clazosentan CONSCIOUS-3 results event rate for the components of the 1 o composite endpoint RRR (95% CI) 35% (-79 to 76%) -21% (-97 to 26%) 15% (-28 to 44%) 29% (-9 to 54%) Placebo Clazosentan 5 mg/h Clazosentan 15 mg/h Event rate (%) % (-211 to 42%) % (-5 to 70%) % (22 to 72%) % (38 to 80%) 7 DIND = Delayed ischemic neurological deficits; Macdonald R et al. Stroke Death (within 6 weeks) New cerebral infarct DIND Vasospasm-related Rescue therapy Clazosentan is investigational, in development and not approved or marketed in any country. 42

43 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 authorities by the end of 2017 In Japan, a Phase 2 study that evaluated the efficacy, pharmacokinetics, and safety of clazosentan against cerebral vasospasm after clipping surgery in Japanese and Korean patients with asah was completed in Market registration trials have started Baseline Vasospasm 2 days of treatment Clazosentan is investigational, in development and not approved or marketed in any country. 43

44 Summary Developed as intravenous infusion for prevention and treatment of cerebral vasopasms in patients who have suffered an asah Has potential to prevent ischemic complications of cerebral vasoconstriction and to decrease the need for invasive intervention Registration studies in Japan expected to complete in second half of 2018 Phase 3 study evaluating the safety and efficacy of clazosentan in an enriched asah population to start later in 2018 Cerebral vasospasm Compound: Clazosentan Mechanism of action: Endothelin receptor antagonism Status: Advancing to Phase 3 Clazosentan is investigational, in development and not approved or marketed in any country. 44

45 Cenerimod in systemic lupus erythematosus Cenerimod is investigational, in development and not approved or marketed in any country. 45

46 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 approaches Scientific rationale for S1P 1 receptor modulation in SLE: T and B cells play a key role in pathogenesis S1P 1 receptor modulators have shown efficacy in different preclinical models of SLE: MRL/lpr and BXSB mice 46

47 Cenerimod A novel S1P 1 receptor modulator Very potent, highly selective, S1P 1 receptor modulator O N Prevents lymphocytes from leaving lymph nodes and reaching target tissues Induces rapid and reversible, dose-dependent blood lymphocyte count reduction N N O Pharmacokinetic profile suitable for once-daily oral dosing with no need for initial up-titration regimen Potential in multiple autoimmune diseases HO OH O Cenerimod is investigational, in development and not approved or marketed in any country. 47

48 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/day of cenerimod over a treatment period of 12 weeks Cenerimod is investigational, in development and not approved or marketed in any country. 48

49 Cenerimod Phase 2 study Part A Randomization EOT EOS Placebo 12 pts Cenerimod 0.5 mg 12 pts Cenerimod 1.0 mg 12 pts Cenerimod 2.0 mg 12 pts Visit Week Day -30 Day Screening 30 days Treatment period 12 weeks Follow-up 6 weeks Phone calls FU 10 weeks Part B Safety interim review (IDMC) Randomization Placebo Cenerimod 4.0 mg 4 pts 12 pts EOT EOS Visit Week Day -30 Day Screening 30 days Treatment period 12 weeks Follow-up 6 weeks Phone calls FU 10 weeks Cenerimod is investigational, in development and not approved or marketed in any country. 49

50 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 an exploratory, dose-finding study to deliver all the information required to design the Phase 3 program Cenerimod is investigational, in development and not approved or marketed in any country. 50

51 Vamorolone in Duchenne Muscular Dystrophy 51

52 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 underway to investigate the safety and efficacy of vamorolone in 4-7 year old steroid-naïve boys with Duchenne (patients that have not taken prednisone or deflazacort) Idorsia has the option to obtain the exclusive worldwide license rights on vamorolone from ReveraGen 52

53 Idorsia s other clinical development assets 53

54 ACT P2Y12 receptor antagonist for 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 wellabsorbed subcutaneously after self-administration Rapid onset of action and 3 to 4 hours duration of action ACT has completed Phase 1, and a Phase 2 study was initiated in January 2018 ACT is investigational, in development and not approved or marketed in any country. 54

55 ACT selective orexin 1 receptor antagonist (SORA) for 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 representing different sub-types of anxiety disorders In these models, it did not induce sleep at anxiolytic doses Phase 1 trials are ongoing ACT is investigational, in development and not approved or marketed in any country. 55

56 ACT CRTH2 receptor antagonist for 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 contribute to the better management of these conditions Phase 1 trials are ongoing ACT is investigational, in development and not approved or marketed in any country. 56

57 ACT T-type calcium channel blocker for epilepsy In development for certain forms of generalized epilepsy ACT is a selective, orally available triple T-type calcium channel blocker. The compound exhibits good tolerability after single-dose administration in humans and PK properties that warrant further investigations. A study was initiated to evaluate the effect of ACT in photosensitive epilepsy patients following single dose administration. ACT is investigational, in development and not approved or marketed in any country. 57

58 More science Bursting with ideas 58

59 Idorsia s drug discovery approach Single-center approach Fully integrated research informatics Focus on small molecules Few platforms of expertise Multiple therapeutic areas High medical input 59

60 More joy Transforming the horizon Our drug discovery process Preclinical Development Clinical Development Registration Launch Molecular-Biology (Target Finding) Biochemistry (High Throughput Screening) Structural Biology And Molecular Modeling Targets Hits Compound Library Research Information Management Medicinal Chemistry Chemistry Process R&D Pharmacokinetics & Metabolism 60 Pharmacology

61 Financial information 61

62 Operating results Non-GAAP US-GAAP Revenues Research Development G&A Non-GAAP Operating results D&A SBC US-GAAP Operating results 62 Financial results as of March 31, 2018

63 Net results Non-GAAP US-GAAP Operating results Financial results Income Tax results NonControlling Interests Net Results 63 Financial results as of March 31, 2018

64 Cash flow '091 1'016 Dec 31, 2017 Funds from operations Working capital requirements Capex / other Mar 31, Financial results as of March 31, 2018

65 Liquidity 1' ' Cash deposits > 12 months Cash deposits > 3 < 12 months Cash and cash equivalents Dec 31, 2017 Mar 31, Financial results as of March 31, 2018

66 Convertible bond CB - Equity component CB - Debt component Convertible Dec 31, 2017 Convertible Mar 31, Financial results as of March 31, 2018

67 Potential issued shares Equity instruments Equity derivatives Issued common shares Potential Dec 31, 2017 Potential Mar 31, Financial results as of March 31, 2018

68 Financial Guidance 2018 Unforeseen events and potential milestone expenses excluded, we expect non-gaap operating expenses for 2018 to be around 390 million Swiss francs. 68

69 More experience Driving innovation 69

70 Idorsia has a strong and visionary leadership team with the power and drive to create more remarkable innovations and more new medicines 70

71 Idorsia management team Jean-Paul Clozel Chief Executive Officer Martine Clozel Chief Scientific Officer Guy Braunstein Head of Global Clinical Development André C. Muller Chief Financial Officer Andrew C. Weiss Head of Investor Relations & Corporate Communications Alex Khatuntsev Head of Human Resources Oliver Peinelt General Counsel Olivier Lambert Head of Pharmaceutical Development Thomas Weller Head of Drug Discover Chemistry Ulrich Mentzel Head of Pharmacology & Preclinical Development Markus Riederer Head of Drug Discovery Biology 71

72 Idorsia Board of Directors Jean-Pierre Garnier Chairman of the board of directors Robert J. Bertolini Member of the board of directors Jean-Paul Clozel Chief Executive Officer John J. Greisch Member of the board of directors David Stout Member of the board of directors Herna Verhagen Member of the board of directors 72

73 Be prepared for more 73