Restoring Movement with Ease
NOBLE INVESTOR CONFERENCE PRESENTATION, JANUARY 19, 2015
www.cynapsus.ca
Cautionary Statements
Neither this presentation nor the materials used in this presentations shall constitute an offer to sell or a
solicitation of an offer to purchase securities of Cynapsus Therapeutics Inc. (‘Cynapsus”). This presentation contains
certain “forward-looking statements” within the meaning of applicable securities laws, which have been prepared by
management of Cynapsus without audit or review by independent auditors and is based on management’s judgment of the
anticipated set of industry and economic result and conditions and Cynapsus’ intended course of action under those
conditions as of the date hereof. Generally, these forward-looking statements can be identified by the use of forward-looking
terminology such as “plans”, “expects” or “does not expect”, “is expected”, “budget”, “scheduled”, “estimates”, “forecasts”,
“intends”, “anticipates” or “does not anticipate”, or “believes” or variations of such words and phrases or state that certain
actions, events or results “may”, “could”, “would”, “might” or “will be taken”, “occur” or “be achieved”. Forward-looking
statements are subject to known and unknown risks, uncertainties and other factors that may cause the actual results, level
of activity, performance or achievements of Cynapsus to be materially different from those expressed or implied by such
forward-looking statements, including but not limited to those risks and uncertainties relating to Cynapsus’ business
disclosed under the heading “Risk Factors” in its Annual Information Form dated March 26, 2014 and its other filings with the
various Canadian securities regulators which are available online at www.sedar.com. Although Cynapsus has attempted to
identify important factors that could cause actual results to differ materially from those contained in forward-looking
statements, there may be other factors that cause results not the be as anticipated, estimated or intended.
The assumptions used in the preparation of this presentation, although considered reasonable by Cynapsus at the time of
preparation, may prove to be incorrect. Recipients are cautioned that the information is based on assumptions as to many
factors and that it is likely that actual results will vary significantly from the results projected and such variations may be
material. There is no representation by Cynapsus that actual results achieved during the projection period will be the same in
whole or in part as those projected. Accordingly, readers should not place undue reliance on such projections or on any
forward-looking statements contained herein. Cynapsus does not undertake to update any such projections or forwardlooking statements, except in accordance with applicable securities laws. The information contained herein, while obtained
from sources which we believe to be reliable, is not guaranteed as to its accuracy or completeness.
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Highlights
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Parkinson’s disease “OFF” episodes: significant unmet need
Michael J. Fox Foundation Partnership ($1.5M in grants + recruitment access)
Issued U.S. patents and other pending applications with protection to 2031/33
Human PK Studies (CTH-101, CTH-102, CTH-103, CTH-104)
U.S. Phase 2 Clinical Efficacy Study Under FDA IND (CTH-105)
Modest resources required to U.S. 505(b)2 approval ($25M raised in April
2014)
Experienced Management Team, Directors and Clinical Advisory Board
Only non-injectable delivery of only approved drug for acute rescue of OFF
episodes in PD
Potential for clinically meaningful differentiation to subcutaneous injection
Potential for U.S. NDA approval late 2017
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Parkinson’s Disease and OFF Episodes
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CHRONIC PROGRESSIVE
NEURODEGENERATIVE DISEASE
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Symptoms: Tremor, rigidity, bradykinesia =
impaired movement
Dying cells in
movement control
Centre of the brain
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Restoring Movement with Ease
US = 1 Million patients
WW = 4 to 6 Million patients
2030 = Estimated 2X due to the aging
population
Approx. 50% of PD patients experience OFF
episodes = impaired movement or
emergence of Non-Motor Symptoms
1 to 6 OFF episodes daily in moderate and
severe patients but also seen in mild
patients
Episodes are more frequent over time
Episodes are sporadic and limit ability to
move and engage in daily life
Chronic treatments become less effective
over time as the therapeutic window narrows
Dopamine stimulation, replacement or
breakdown of inhibitors of dopamine =
primary pharmacotherapy patients
4
Apomorphine
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Apomorphine is currently the only
approved drug for the acute, intermittent
management of OFF episodes primarily
used in Advanced PD patients
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Apomorphine is the only member of the
dopamine agonist class that has rapid
onset of activity
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Apomorphine is currently only available
as a subcutaneous injection
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APL-130277 Overview and Expected Attributes
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APL-130277 is a fast-acting, sublingual, thin filmstrip
formulation of apomorphine
Designed to manage all OFF episodes in Parkinson’s patients
of all stages
To date, studied in approximately 110 patients/subjects in five
clinical studies
Most recent result is the CTH-105 Phase 2 study
Safety/Tolerability/Efficacy
Health Economics
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Minimal irritation
Tolerable – few and mild adverse events
Robust & clinically meaningful ∆ in UPDRS
III over 90 minutes & symptomatic relief
Potential impact on levodopa use and
duration of ON
Apomorphine treats all 4 types of OFF
Restoring Movement with Ease
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Freedom of daily living for patient
Ease of opening and administration
Possible measurable benefits to the use of
other medications and their impact on the
patient
6
Past Attempts at Reformulation
Attempts at
Reformulation of
Apomorphine
Could not achieve
minimum plasma
concentration to
allow conversion
from OFF to ON in
less than 30 minutes;
Did not address
acidic nature of API
and irritation of
human tissue; or
Only viable
non-injectable delivery
method
of the only approved drug
(apomorphine)
to provide acute rescue of
OFF episodes in
Parkinson’s Disease
Approach was not
commercially viable.
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APL-130277: Direct Competitors
Company
Product
Pharmacology
Development
Phase
Route of
Administration
Types of OFF
Cynapsus
APL-130277
Apomorphine –
Dopamine Agonist
Phase II
Sublingual
•
•
•
•
Morning Akinesia
End of Dose Wearing OFF
Unpredictable OFF
Latency to ON / Dose
Failure
STADA/
Britannia
Apokyn
Apomorphine –
Dopamine Agonist
Marketed
Subcutaneous
injection
•
•
•
•
Morning Akinesia
End of Dose Wearing OFF
Unpredictable OFF
Latency to ON / Dose
Failure
Jazz,
Mylan,
Schwartz
Parcopa
Levodopa Carbidopa –
Dopamine precursor
and decarboxylase
inhibitor
Marketed
(Brand and
Generic)
Oral disintegrating
tablet
• Morning Akinesia
Acorda /
Civitas
CVT-301
Levodopa –
Dopamine precursor
Phase II
Inhalation
• End of Dose Wearing OFF
• Unpredictable OFF
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APL-130277: Indirect Competitors
Company
Product
Pharmacology
Development
Phase
Route of
Administration
Comments
Merck
Sinemet CR
Levodopa Carbidopa –
Dopamine precursor
and decarboxylase
inhibitor
Market
Extended release
tablet
• Reduces but does not eliminate
OFF time similar to other extended
release LD/CD products
• Requires dosing three times daily
Levodopa Carbidopa –
Dopamine precursor
and decarboxylase
inhibitor
Market (EU)
Approved (US)
Levodopa Carbidopa –
Dopamine precursor
and decarboxylase
inhibitor
Phase II
Levodopa Carbidopa –
Dopamine precursor
and decarboxylase
inhibitor
Approved
Abbvie
Duodopa
Neuroderm ND0612
Impax
Rytary
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Oral
Intestinal gel
Sugically implanted
gastrostomy tube
Microneedle
patch+pump
Subcutaneous
injection
Extended release
tablet
Oral
• Only indicated for very advanced
patients
• Surgical implantation of catheter
• Patients continue to suffer more
than 2 hours OFF daily
• Chronic subcutaneous infusion
results in AEs that limit treatment
to 18 months
• Does not eliminate OFF time
• Likely to be reserved for very
advanced patients
• Reduces but does not eliminate
OFF time similar to other extended
release LD/CD products
• Requires dosing three times daily
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CTH-105 Study Design
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Study Overview
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19 patients dosed (Intent-to-Treat population)
 15 turned from OFF to ON (responders)
 2 were dosed incorrectly (i.e. told to swallow at each dose and did not turn on)
 2 were non-responders (i.e. dosed to 30mg and did not turn on)
Multicenter open-label study
 Sites in Florida (2), Arizona, and Colorado
FPFV: August 2014
LPLV: November 2014
Study protocol
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PD patients with at least 2 hours of OFF daily
Patients pre-treated with Tigan® (trimethobenzamide) for 3 days prior to titration and during dosing
Patients dosed in the morning OFF state (last dose of levodopa no later than 10 PM the night prior)
Escalating doses starting at 10mg up to 30mg, in 5mg increments at a minimum of three hours
between doses, based on response (i.e. change in UPDRS part III, clinician observation, patient
observation)
UPDRS part III was measured at 15, 30, 45, 60 and 90 minutes
Effective dose confirmed at a subsequent visit
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Top-line Results – Change in UPDRS III and ON
Mean Change in UPDRS Part III from Baseline Over Study Period
For Patients Converting from OFF to ON*
A clinically meaningful improvement in motor control
occurred in as early as 10 minutes after administration
of APL-130277 and lasted longer than 90 minutes
Restoring Movement with Ease
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The mean baseline UPDRS III
in an OFF state was 41.4
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The maximum mean change
from baseline UPDRS III was
18.4
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The mean dose used to
convert patients to ON was
18.4mg (over half turned ON
with 10 or 15 mg)
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The reported mean time to
ON was 22 minutes
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Achieved an approximate
45% improvement in motor
function
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Phase 2 Safety Profile
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19 patients dosed
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Treatment with APL-130277 was safe and well tolerated
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There were no related serious adverse events
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Nausea was reported by 3 subjects at doses of 10mg, 15mg and 20mg;
there were no reports of nausea at higher doses
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One of these patients also experienced a mild episode of emesis
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There were no reports of local irritation
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One subject experienced a mild AE of orthostatic hypotension
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505(b)(2) “Efficacy” Path To Anticipated U.S. NDA
2014
2015
2016
CMC
DOE Scale Up
CMC
CTM and Registration batches MFG
Pivotal Safety Study
CMC
Complete 12 months stability
Update CTD
CTH105
Pilot Study in
“APO Naïve”
PD patients
CTH200
Bridging Study
in healthy
Volunteers
U.S. FDA
Meeting
CTH300A
Efficacy in APO
Naïve
PD patients
CTH301
Pivotal Safety Study in Apomorphine
Naïve Parkinson’s Patients
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Prepare and
File US NDA
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Commercial Opportunity
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Market research with physicians, payors, and patients indicate OFF episodes are a
significant unmet need

Recent Michael J. Fox Foundation Survey found that 90% of Parkinson’s patients
suffer OFF episodes and that 65% suffer at least 2 hours OFF daily
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Academic poster presentation by Rizos et. al. found that 48% of mild Parkinson’s
patients, 70% of moderate patients, and 62% of severe patients suffer Early
Morning OFF
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Cynapsus currently estimates APL-130277 may be appropriate treatment for
approximately 1 million Parkinson’s patients worldwide:
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United States = 400,000
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European Union (Largest 5 Countries) = 400,000
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Rest of World = 200,000
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Patients manage one to six OFF episodes per day
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Anticipated product launch in U.S. in 2017; Europe and Japan in 2018
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Recent $25 Million Financing
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On April 15, 2014, completed $25 million short form prospectus financing
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Included commitments from new and existing institutional investors

Included $4 million new commitment from Dexcel Pharma, a strategic
investor that owns approximately 20% of the company
Lead investors were U.S. and International, sophisticated life science
focused specialty funds:
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
$250 million to $6 billion in assets under management
Cynapsus now expects to have sufficient cash to move APL-130277 to a
U.S. NDA submission.
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Research Coverage and Share Capital
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Stock Symbols:
TSX: CTH (Canada); OTCQX: CYNAF (USA)
Market Capitalization*: C$99 Million
Research Coverage: Noble Life Science Partners, M Partners,
Zacks Small Cap Research, SeeThru Equity
Share Capital**:
Common Shares (Basic)
80,225,733
Warrants
Stock Options
TOTAL (Fully Diluted)
60,034,989
5,450,649
145,711,371
*As at January 15, 2015
**As at December 31, 2014
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Management Team and Clinical Advisory Board
Management Team
Clinical Advisory Board
Anthony Giovinazzo, President & CEO
20 yrs. CNS-Parkinson’s, Alzheimer’s, Pain, Anxiety, M&A exits
Dr. Warren Olanow, MD
Henry P. and Georgette Goldschmidt Professor and Chairman
of the Department of Neurology at the Mount Sinai School of
Medicine in New York City. Internationally recognized expert on
movement disorders.
Dr. Albert Agro, PhD, Chief Medical Officer
15 yrs. clinical development of CNS & Parkinson’s specifically
Dr. Thierry Bilbault, Chief Scientific Officer & EVP CMC
20+ yrs. senior management w/ Global large Pharma, 50+ product
launches internationally, 10+ years thin film strip expertise
Andrew Williams, Chief Operating/Financial Officer
15 yrs. finance, operations & consulting, 10 yrs. CNS & Parkinson’s
Dr. Fabrizio Stocchi, MD, PhD
Professor of Neurology and Director of the Parkinson’s Disease
and Movement Disorders Research Centre at the Institute for
Research and Medical Care, IRCCS San Raffaele, Rome, Italy.
Dr. Abraham Lieberman, MD
Director of the Muhammad Ali Parkinson Center and the
Movement Disorder Clinic of Barrow Neurological Institute at St.
Joseph’s Hospital and Medical Center. He is an internationally
recognized expert on Parkinson’s disease.
Dr. Susan Fox, PhD, CCST
Assistant Professor Division of Neurology, Department of
Medicine, University of Toronto and University Health Network.
Member of largest movement disorders clinic in Canada
(Toronto Western).
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Highlights










Parkinson’s disease “OFF” episodes: significant unmet need
Michael J. Fox Foundation Partnership ($1.5M in grants + recruitment access)
Issued U.S. patents and other pending applications with protection to 2031/33
Human PK Studies (CTH-101, CTH-102, CTH-103, CTH-104)
U.S. Phase 2 Clinical Efficacy Study Under FDA IND (CTH-105)
Modest resources required to U.S. 505(b)2 approval ($25M raised in April
2014)
Experienced Management Team, Directors and Clinical Advisory Board
Only non-injectable delivery of only approved drug for acute rescue of OFF
episodes in PD
Potential for clinically meaningful differentiation to subcutaneous injection
Potential for U.S. NDA approval end of 2016 or early 2017
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