Restoring Movement with Ease
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. Restoring Movement with Ease 2 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 late 2017 Restoring Movement with Ease 3 Parkinson’s Disease and OFF Episodes CHRONIC PROGRESSIVE NEURODEGENERATIVE DISEASE Symptoms: Tremor, rigidity, bradykinesia = impaired movement Dying cells in movement control Centre of the brain 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 Apomorphine is currently the only approved drug for the acute, intermittent management of OFF episodes primarily used in Advanced PD patients Apomorphine is the only member of the dopamine agonist class that has rapid onset of activity Apomorphine is currently only available as a subcutaneous injection Restoring Movement with Ease 5 APL-130277 Overview and Expected Attributes 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 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 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. Restoring Movement with Ease 7 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 Restoring Movement with Ease 8 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 Restoring Movement with Ease 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 9 CTH-105 Study Design Study Overview 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 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 Restoring Movement with Ease 10 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 The mean baseline UPDRS III in an OFF state was 41.4 The maximum mean change from baseline UPDRS III was 18.4 The mean dose used to convert patients to ON was 18.4mg (over half turned ON with 10 or 15 mg) The reported mean time to ON was 22 minutes Achieved an approximate 45% improvement in motor function 11 Phase 2 Safety Profile 19 patients dosed Treatment with APL-130277 was safe and well tolerated There were no related serious adverse events Nausea was reported by 3 subjects at doses of 10mg, 15mg and 20mg; there were no reports of nausea at higher doses One of these patients also experienced a mild episode of emesis There were no reports of local irritation One subject experienced a mild AE of orthostatic hypotension Restoring Movement with Ease 12 505(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 Restoring Movement with Ease Prepare and File US NDA 13 Commercial Opportunity 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 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 Cynapsus currently estimates APL-130277 may be appropriate treatment for approximately 1 million Parkinson’s patients worldwide: United States = 400,000 European Union (Largest 5 Countries) = 400,000 Rest of World = 200,000 Patients manage one to six OFF episodes per day Anticipated product launch in U.S. in 2017; Europe and Japan in 2018 Restoring Movement with Ease 14 Recent $25 Million Financing On April 15, 2014, completed $25 million short form prospectus financing 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: $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. Restoring Movement with Ease 15 Research Coverage and Share Capital 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 Restoring Movement with Ease 16 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). Restoring Movement with Ease 17 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 Restoring Movement with Ease 18
© Copyright 2024