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: 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
Airway hyper-excitability
Chronic Cough
Cell injury
Drug targeting P2X3 has strong mechanistic rationale for reducing cough
frequency
6
ATPand
Cytokines
Primaryafferent
(A𝛿 or C-fiber)
ATP
ATP
Receptors
P2X3
P2X3-containing
Primaryafferent
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
Knockout Mice
Drug Approach
P2X3 Mildly
Selective Antagonist
Significant taste 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 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
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
• Inhibit respiratory 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., Europe top five countries and Japan
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
