BELLUS Health and NEOMED Institute Transaction Licensing of BLU-5937 for Chronic Cough

Transcription

1 BELLUS Health and NEOMED Institute Transaction Licensing of BLU-5937 for Chronic Cough February 28, 2017 r

2 Investment Thesis BLU-5937: potential to be best-in-class drug addressing high unmet need Orally bioavailable small molecule Superior potency and P2X3 selectivity Potential for improved efficacy and safety profile Clear and efficient development path & value creation P2X3: validated target in emerging drug class for chronic cough Merck acquired a P2X3 antagonist program in 2016 for US$500M based on positive Phase II data in chronic cough Potential multi billion dollar drug class in therapeutic indication lacking innovation Right-sized transaction for BELLUS Attractive financial terms Leverages core competencies: clinical, BD, financing Experienced, motivated team to drive project to success Fast follower with best-in-class potential for large market with high unmet medical need 2

3 Chronic Cough Characteristics Cough lasting > 8 weeks, associated with: Pulmonary diseases (asthma, COPD, lung cancer, IPF) Extra-pulmonary disorders (post-nasal drip, gastro-oesophageal reflux) Use of certain drugs (ACE inhibitors) No identifiable cause (unexplained chronic cough) Implications Time and resource intensive for healthcare system Responsible for 30M physician visits per year in U.S. 38% of pulmonologist outpatient practice Unexplained and refractory chronic cough require time and resource intensive differential diagnosis 3

4 Major Impact on Patients Social complications Physical complications Psychosocial complications Embarrassment of coughing in public Interference with lifestyle, work & leisure Difficulty speaking Social exclusion Exhaustion Sleep deprivation Retching/vomiting Incontinence Headache Hoarse voice Chest pain Rib fracture Distress Anger Anxiety Depression Chronic cough has significant impact on patient quality of life 4

5 Few Treatment Options Opioids Some efficacy but cause sedation/confusion Constipation and nausea Potential for addiction Gabapentin/Pregabalin Centrally acting Some efficacy demonstrated in small studies High incidence of adverse effects OTC Products Very limited efficacy No novel approach approved to address chronic cough in 40 years 5

6 Pathophysiology: Hypersensitivity of Cough Reflex Coughing trigger (ex. asthma attack) Cellular damage causes ATP release in respiratory tract ATP activates P2X3 receptors on airway sensory neurons ATP and Cytokines Cell injury Airway hyper-excitability ATP Primary afferent (Aδ or C-fiber) Receptors P2X3 Chronic Cough P2X3-containing Primary afferent ATP Drug targeting P2X3 has strong mechanistic rationale for reducing cough frequency 6

7 Clinically Validated Molecular Target Weakly selective P2X3 antagonist use in chronic cough patients results in: 50 to 75% reduction in cough frequency 50 to 100% of patients experience taste disturbance Problematic taste side effect likely due to lack of high selectivity for P2X3 Adbulqawi et al., P2X3 receptor antagonist (AF-219) in refractory chronic cough: a randomised, double-blind, placebo-controlled phase 2 study. Lancet. Vol 385, No 9974 pp Kitt et al., A Phase 2 Dose-Escalation Study with AF-219, a P2X3 Antagonist for the Treatment of Chronic Cough. American Thoracic Society 2016 International Conference - San Francisco. Opportunity for highly selective P2X3 antagonist with better efficacy/safety profile ratio to become class leader 7

8 P2X3 Family Involved in Taste Perception Taste stimuli ATP release from taste buds mouse tongue Knockout Mice P2X3 & P2X2 Double knockout Taste loss Legend P2X3 P2X2 P2X3 Antagonist ATP activates P2X3 and P2X2 receptors on taste sensory neurons P2X3 Single knockout Mild taste alteration P2X2 Single knockout Mild taste alteration Drug Approach Taste perception P2X3 Highly Selective Antagonist Expected mild/no taste alteration P2X3 Mildly Selective Antagonist Significant taste alteration Kinnamon et al., A Taste for ATP: neurotransmission in taste buds. Frontiers in Cellular Neuroscience. Vol 7, Article 264 pp Drug with high selectivity for P2X3 could limit or eliminate taste alteration side effect without compromising effect on cough 8 8

9 BLU-5937 Profile Orally bioavailable small molecule High Potency (low nm) and Selectivity for P2X3 Zero safety findings of concern to-date Broad and comprehensive IP to 2034 Kg scale CMC Strong drug candidate profile with potential to be best in P2X3 class 9

10 Preclinical Efficacy: Cough Response Total coughs (average) Control BLU * * 0 Control 0.3 mg/kg p.o. 3 mg/kg p.o. 30 mg/kg p.o. Treatments (control, BLU-5937) were administered orally (p.o.) two hours prior to tussive agent exposure: citric acid (0.1 M, aerosol) and histamine (0.6 mm, aerosol); n=6 animals (guinea pig) per group *p<0.05 Oral administration of BLU-5937 dose-dependently reduced the frequency of cough in a guinea pig model 10

11 Competitive Landscape TRP modulators Novel target, TRPM8, is in the exploratory stage with limited mechanistic understanding Ax-8 Alveonix TRPM8 agonist AF-219 Afferent/Merck BLU-5937 BELLUS Health Acquired by Merck in 2016 (US$500M upfront, US$750M in milestones) following positive Phase II data P2X3 antagonists NK1 antagonists Repurposed class initially developed for depression Also target sensory nerve signaling Limited clinical validation in chronic cough Overpitant NeRRe Therapeutics Repurposed class SCH Opko Health Repurposed class Inhibit respiratory tract sensory pathway signals Most promising and competitive novel class of anti-tussive Registration Late clinical Early clinical Preclinical 11

12 Large Addressable Market 2.75M Unexplained/ refractory patients 10-40% patients with refractory / unexplained chronic cough 27.5M U.S. chronic cough patients 10% of US adult population has chronic cough 275M U.S. adults Estimated addressable patients in major pharma markets: 6.3M Major pharma markets include the U.S., Europe top five countries and Japan Song et al., The global epidemiology of chronic cough in adults: a systematic review and meta-analysis. Eur Respir J. Vol 55 pp Zanasi et al., Chronic and unexplained cough. (Published online) Vol 4, No 3 pp

13 Key Development Milestones /2020 IND-enabling studies Phase I: assess dose and taste effect Phase II: demonstrate antitussive effect Complete IND preclinical study package Assess safety, tolerability, PK, effect on taste in healthy subjects Single ascending dose and multiple ascending dose studies Assess safety, PK and antitussive effects in patients suffering from chronic refractory cough Dose response study with crossover design Value creating milestones throughout development path 13 13

14 Key Transaction Terms Scope: exclusive worldwide license for all indications Upfront Fee: $1.7M cash; $1.5M equity Royalty Rate: Low single digit tiered Revenue Sharing: Very low double digit revenue sharing expected Milestone Payments: None Significant upside potential for BELLUS investors 14 14