Restoring Movement with Ease

Restoring Movement with Ease
TSXV: CTH OTCQX: CYNAF
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 others pending 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. 505b2 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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Parkinson’s
OFF Episodes and
Treatment
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Parkinson’s Disease and OFF Episodes
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CHRONIC PROGRESSIVE
NEURODEGENERATIVE DISEASE
Symptoms: Tremor, rigidity, 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. 25 to 50% of PD patients
experience OFF episodes = impaired
movement or speaking
1 to 6 OFF episodes daily in moderate and
severe 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
Dopamine stimulation, replacement or
breakdown of inhibitors of dopamine =
primary pharmacotherapy patients
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Types of OFF Episodes
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OFF episodes are the result of insufficient dopamine in the brain
1.
Morning Akinesia
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2.
3.
Wearing off
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Sub-therapeutic levels of levodopa prior to next scheduled dose
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Can be treated by re-arranging dose schedule within limits
Unpredictable OFF
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4.
Despite constant levels of levodopa, consumption of dopamine in the
brain varies and depletes dopamine in the brain
Latency to ON (dose failure)
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Lack of dopaminergic drugs overnight results in depleted dopamine
reserves in the brain; the most difficult OFF to treat
Poor absorption of levodopa results in low brain levels of dopamine
Apomorphine rapidly and effectively treats these OFF states
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Apomorphine
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Apomorphine is currently the only
approved drug for the acute
management of OFF episodes
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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 an 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 OFF episodes in Parkinson’s patients
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
Appropriate ∆ in UPDRS III & symptomatic
relief
Potential impact on levodopa use and
duration of ON
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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
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Top-line Phase 2 Results:
CTH-105 Study
Reported on November 19, 2014
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CTH-105 Study Design
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Study parameters
 n=16
 16 patients have completed the dosing regimen
 Due to over enrollment of the study, an additional 3 patients are still in dosing
(Total n=19)
 Multicenter open-label study in patients with Parkinson’s disease
 Subjects required to have a minimum of 2 hours OFF daily
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Study protocol
 Patients pre-treated with Tigan® (trimethobenzamide) for 3 days prior to
titration and during dosing
 Levodopa withheld the morning of dosing to induce OFF
 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
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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
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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
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
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Phase 2 Safety Profile
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16 patients completed with 60 total doses administered
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Treatment with APL-130277 was safe and well tolerated
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There were no 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 or orthostatic hypotension in any
subject treated
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Next Steps and
Additional Information
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Phase 3 Studies Expected to Begin in 2015
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Phase 3 pivotal studies of longer duration and with larger patient
numbers to confirm:
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Efficacy
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Safety
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Details of studies to be confirmed with the U.S. Food and Drug
Administration (“FDA”) during an End of Phase II meeting
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These studies will form the registration package necessary for a
U.S. 505(b)(2) NDA with the FDA expected to be submitted in 2016
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Anticipated 505(B)2 “Efficacy” Path to U.S. NDA
2015
2016
CMC
Clinical Scale Up and
Production (including stability)
CTH200
Bridging Study
in Healthy
Volunteers
U.S.
FDA
Meeting
CTH300
Efficacy
Study in
PD patients
CTH301
Pivotal Safety Study in
Parkinson’s Patients
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Prepare and File U.S. 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
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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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Research Coverage and Share Capital
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Stock Symbols:
TSXV: CTH (Canada); OTCQX: CYNAF (USA)
Market Capitalization: ~$90 Million
Research Coverage: Noble Life Science Partners, Zacks Small Cap Research,
M Partners, SeeThru Equity, Life Science Advisors
Share Capital*:
Common Shares (Basic)
79,068,867
Warrants
61,300,571
Stock Options
TOTAL (Fully Diluted)
4,175,649
144,545,087
*As at November 11, 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. Madhu Hariharan, PhD, Director CMC
18 yrs. drug product expertise and of commercial launches of Rx
(NDA, ANDA) thin film drugs, OTC and confectionary products
Dr. Judi Weissinger, PhD, Regulatory
20 yrs. regulatory, 10 yrs. at US FDA, Director level
Dr. Robin Walker, PhD, Toxicology
20 yrs. toxicology in large Pharma
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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 others pending 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. 505b2 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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