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Bellus Health Neomed Presentation
- 1. BELLUS Health and NEOMED Institute Transaction Licensing of BLU-5937 for Chronic Cough February 28, 2017 r
- 2. Investment Thesis Fast follower with best-in-class potential for large market with high unmet medical need 2 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 Orally bioavailable small molecule Superior potency and P2X3 selectivity Potential for improved efficacy and safety profile Clear and efficient development path & value creation Attractive financial terms Leverages core competencies: clinical, BD, financing Experienced, motivated team to drive project to success Right-sized transaction for BELLUS BLU-5937: potential to be best-in-class drug addressing high unmet need P2X3: validated target in emerging drug class for chronic cough
- 3. Chronic Cough 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) 3 ImplicationsCharacteristics 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
- 4. Major Impact on Patients 4 Exhaustion Sleep deprivation Retching/vomiting Incontinence Headache Hoarse voice Chest pain Rib fracture Embarrassment of coughing in public Interference with lifestyle, work & leisure Difficulty speaking Social exclusion Distress Anger Anxiety Depression Psychosocial complications Social complications Physical complications Chronic cough has significant impact on patient quality of life 4
- 5. Few Treatment Options 5 Gabapentin/PregabalinOpioids Centrally acting Some efficacy demonstrated in small studies High incidence of adverse effects Very limited efficacySome efficacy but cause sedation/confusion Constipation and nausea Potential for addiction OTC Products No novel approach approved to address chronic cough in 40 years 5
- 6. Pathophysiology: Hypersensitivityof Cough Reflex Coughing trigger (ex. asthma attack) Cellular damage causesATP release in respiratory tract ATP activates P2X3 receptors on airway sensory neurons Airway hyper-excitability Chronic Cough Cell injury Drug targeting P2X3 has strong mechanistic rationale for reducing cough frequency 6 ATP and Cytokines Primary afferent (A𝛿 or C-fiber) ATP ATP Receptors P2X3 P2X3-containing Primary afferent
- 7. Problematic taste side effect likely due to lack of high selectivity for P2X3 Clinically Validated Molecular Target Opportunity for highly selective P2X3 antagonist with better efficacy/safety profile ratio to become class leader 7 50 to 75% reduction in cough frequency 50 to 100% of patients experience taste disturbance Adbulqawi et al., 2016. P2X3 receptor antagonist (AF-219) in refractory chronic cough: a randomised, double-blind, placebo-controlled phase 2 study. Lancet. Vol 385, No 9974 pp. 1198-1205. Kitt et al., 2016. 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. Weakly selective P2X3 antagonist use in chronic cough patients results in:
- 8. P2X3 Family Involved in Taste Perception 8 Taste stimuli ATP release from taste buds ATP activates P2X3 and P2X2 receptors on taste sensory neurons Taste perception Drug with high selectivity for P2X3 could limit or eliminate taste alteration side effect without compromising effect on cough 8 Kinnamon et al., 2013. A Taste for ATP: neurotransmission in taste buds. Frontiers in Cellular Neuroscience. Vol 7, Article 264 pp. 1-7. mouse tongue Legend P2X3 P2X2 P2X3 Highly Selective Antagonist P2X3 & P2X2 Double knockout Taste loss P2X3 Single knockout P2X2 Single knockout Mild taste alterationMild taste alteration Expected mild/no taste alteration P2X3 Antagonist KnockoutMice Drug Approach P2X3 Mildly Selective Antagonist Significanttaste alteration
- 9. Strong drug candidate profile with potential to be best in P2X3 class BLU-5937 Profile 9 Kg scale CMC Broad and comprehensive IP to 2034 High Potency (low nM) and Selectivity for P2X3 Orally bioavailable small molecule Zero safety findings of concern to-date
- 10. Preclinical Efficacy: Cough Response * Treatments (control, BLU-5937) were administeredorally (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 0 5 10 15 20 25 30 Control 0.3 mg/kg p.o. 3 mg/kg p.o. 30 mg/kg p.o. Total coughs (average) Control BLU-5937 *
- 11. Competitive Landscape 11 Preclinical Early clinical Late clinical Registration TRP modulators • Novel target, TRPM8, is in the exploratory stage with limited mechanistic understanding NK1 antagonists • Repurposed class initially developed for depression • Also target sensory nerve signaling • Limited clinical validation in chronic cough P2X3 antagonists • Inhibitrespiratory tract sensory pathway signals • Most promising and competitive novel class of anti-tussive BLU-5937 BELLUS Health AF-219 Afferent/Merck Overpitant NeRRe Therapeutics Repurposed class SCH 900978 Opko Health Repurposed class Ax-8 Alveonix TRPM8 agonist Acquired by Merck in 2016 (US$500M upfront, US$750M in milestones) following positive Phase II data
- 12. 10-40% patients with refractory / unexplained chronic cough 10% of US adult population has chronic cough Estimated addressable patients in major pharma markets: 6.3M Large Addressable Market 12 275M U.S. adults 27.5M U.S. chronic cough patients 2.75M Unexplained/ refractory patients Major pharma markets include the U.S., Europetop five countries andJapan Song et al., 2015. The global epidemiology of chronic cough in adults: a systematic review and meta-analysis. Eur Respir J. Vol 55 pp. 1479-1481 Zanasi et al., 2014. Chronic and unexplained cough. (Published online) Vol 4, No 3 pp. 159-164
- 13. Key Development Milestones 13 Value creating milestones throughout development path 2017 2018 2019/2020 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 13
- 14. Key Transaction Terms 14 Significant upside potential for BELLUS investors 14 Milestone Payments: None Revenue Sharing: Very low double digit revenue sharing expected Upfront Fee: $1.7M cash; $1.5M equity Scope: exclusive worldwide license for all indications Royalty Rate: Low single digit tiered