CTH Cotec Holdings Corp

Cynapsus Therapeutics Inc. (TSX: CTH) (OTCQX: CYNAF), a specialty Central Nervous System (CNS) pharmaceutical company developing and preparing to commercialize a fast-acting, easy-to-use sublingual thin film for the on-demand management of debilitating OFF episodes associated with Parkinson's disease (PD), today announced financial results for the three months ended March 31, 2015. Unless specified otherwise, all amounts are in Canadian dollars.

"In the first three months of 2015, we have made significant progress advancing our strategic plan, including work related to the commencement of Phase 3 clinical trials for APL-130277. Importantly, we also raised gross proceeds of approximately $21 million through a private placement, which we expect will fund APL-130277 development through to a New Drug Application (NDA) submission with the U.S. Food and Drug Administration (FDA) in 2016, initial commercialization studies and preparation for a U.S. product launch, as well as planning for clinical studies in the European Union," stated Anthony Giovinazzo, President and Chief Executive Officer of Cynapsus.

Financial Highlights

• On March 31, 2015, the Company announced that it completed private placement offering of common shares for aggregate gross proceeds of $20,981,579. The financing was led by funds associated with OrbiMed, Aisling Capital and Venrock, with participation from various other institutional investors, including existing shareholders Broadfin Capital, Sphera Funds Management, Pura Vida Investments, DAFNA Capital Management and Dexcel Pharma Technologies Ltd./Dexxon Holdings Ltd.
• Cash as of March 31, 2015 of $36,661,012 (December 31, 2014: $17,448,497).
• Cash used in operating activities of $5,689,901 for the three months ended March 31, 2015 (three months ended March 31, 2014: $1,676,386).
• Net loss of $5,094,432 for the three months ended March 31, 2015 (three months ended March 31, 2014: $1,210,272).
• Reported 110,311,428 common shares outstanding as of March 31, 2015 (December 31, 2014: 80,334,449 common shares).

Operational Highlights

• Completed End-of-Phase 2 Meeting with the U.S. FDA. On February 4, 2015, Cynapsus held its End-of-Phase 2 meeting with the FDA. For development of APL-130277 in the U.S., the Company will follow Section 505(b)(2) of the FDCA. The drug substance (apomorphine) in APL-130277 is identical to the active pharmaceutical ingredient in the FDA approved subcutaneous injection, Apokyn®, and APL-130277 is designed for similar usage but potentially for a broader range of PD patients. The Section 505(b)(2) regulatory pathway will require the Company to provide statistically significant clinical evidence that PD patients experience improvement in their motor function as a result of delivery of apomorphine via the sublingual thin film route compared to placebo.
• Reported details for the Company's Phase 3 pivotal program. On March 11, 2015, following the End-of-Phase 2 meeting with the U.S. FDA, the Company announced that an agreement was reached on the design, duration and size for the Phase 3 program clinical studies, as well as for primary and key secondary endpoints. As a result, the Company has initiated a pivotal Phase 3 program evaluating the safety and efficacy of APL-130277 in PD patients.
  • Appointed a new Director to the Board of Directors. On March 12, 2015, Tamar Howson was appointed to the Board of Directors. Ms. Howson is a seasoned business development executive within the pharmaceutical industry, having formerly served as Senior Vice President at both Bristol-Myers Squibb and SmithKline Beecham. Ms. Howson currently serves as a business development and strategy consultant to biopharmaceutical companies and she also serves as a director at Oxigene Pharmaceuticals and Organovo. She has formerly served as a director at several biotechnology companies, including Actavis, Ariad, Idenix Pharmaceuticals, NPS Pharmaceuticals, SkyePharma and Warner Chilcott.
  • Presented Data from a Pharmacokinetic Subgroup of the Phase 2 CTH-105 Study at the American Academy of Neurology (AAN) Annual Meeting. On April 22, 2015, the Company presented data at AAN that demonstrated that a minimum efficacious plasma threshold of apomorphine was required to convert a patient from the OFF state to the ON state. APL-130277 reached this threshold in as early as 10 minutes and levels were maintained over this threshold through 90 minutes after dosing. This translated to clinically meaningful improvement in motor function as assessed by the MDS-UPDRS Part III score.

Upcoming Clinical Studies

Following the progress made in the first quarter of 2015, the Company currently plans to complete the following clinical studies:

• CTH-200 Bridging Study. A single-dose, crossover comparative bioavailability and pharmacokinetic study in healthy volunteers. This study is designed to allow the Company to use the safety and efficacy data for Apokyn® in our NDA submission to the FDA. This study is planned to commence in the second quarter of 2015.
• CTH-300 Efficacy Study. A double-blind, placebo-controlled, parallel-design study with an estimated 126 PD patients who have at least one OFF episode every 24 hours, with total OFF time of at least two hours per day. The objective is to evaluate the efficacy and safety of APL-130277 versus placebo in patients with PD. Sites will recruit patients over several months. The 126 patients will each be observed for 12 weeks, with dosing at home and in clinic. Patients will be evaluated every four weeks in clinic. The primary end point will be measured at week 12 in clinic. The primary endpoint will be the mean change in the MDS-UPDRS Part III score at 30 minutes after dosing.   This study was initiated in the second quarter of 2015.  
• CTH-301 Safety Study. A long-term open-label, single arm safety study in PD patients who have at least one OFF episode every 24 hours, with total OFF time of at least two hours per day. The objective is to evaluate the safety and tolerability of APL-130277 in patients with PD over 6 months of treatment. Sites will recruit patients over several months, with each patient being evaluated for six months. An estimated 226 patients will be enrolled, including up to 126 who had been enrolled in the CTH-300 efficacy study and rolled over to this study, plus an additional 100 new patients.  The CTH-301 protocol has a built-in adaptive component potentially allowing the open label titration procedure to be modified to at-home titration. This change will be based upon the safety assessment completed by a Drug Safety Monitoring Board ("DSMB") in the CTH 300 study.  This study is planned to commence in the third quarter of 2015.

In parallel, the Company will continue to perform the necessary development activities, including process validation and stability studies as part of the chemistry, manufacturing and controls, or CMC, requirements for the filing of the NDA. The Company expects that all development will be performed according to current Good Manufacturing Practices methodology.

Upon completion of the efficacy and safety studies, as well as the CMC requirements, the Company intends to prepare and submit a Section 505(b)(2) NDA to the FDA in 2016.

About Cynapsus

Cynapsus is a specialty CNS pharmaceutical company developing and preparing to commercialize a Phase 3, fast-acting, easy-to-use, sublingual thin film for the on-demand turning ON of debilitating OFF episodes associated with Parkinson's disease, or PD. PD is a chronic, progressive neurodegenerative disease characterized by motor symptoms including tremor at rest, rigidity and impaired movement as well as significant non-motor symptoms such as cognitive impairment and mood disorders. The re-emergence of PD symptoms is referred to as an OFF episode.  The Company recently successfully completed a Phase 2 clinical trial for its product candidate, APL-130277, a sublingual formulation of apomorphine hydrochloride, or apomorphine. Apomorphine is the only molecule approved for acute, intermittent treatment to provide rapid turning ON and relief from OFF episodes, but is currently only approved in the United States as a subcutaneous injection, which poses a number of problems. APL-130277 is a "turning ON" medication designed to rapidly, safely and reliably convert a PD patient from the OFF to the ON state while avoiding many issues associated with subcutaneous delivery of apomorphine. It is designed to convert all types of OFF episodes, including morning OFF episodes, often considered the most difficult to treat. The Company has initiated our Phase 3 clinical program for APL-130277, relying on the abbreviated Section 505(b)(2) regulatory pathway in the United States, and intends to submit an NDA in 2016.

 

PD is the second most common neurodegenerative disease worldwide. Over one million people in the United States and between four and six million people worldwide suffer from PD.  There is no known cure or disease modifying treatment currently available for PD. Current medications and treatments only control the major symptoms of the disease, with most drugs becoming less effective over time as the disease progresses. Cells that die in PD produce dopamine, a neurotransmitter critical to the signaling for movement. These current drugs and therapies either aim to supplement dopamine levels in the brain, mimic the effect of dopamine in the brain by stimulating dopamine receptors, referred to as dopamine agonists, or prevent the enzymatic breakdown of dopamine, prolonging its effect. The standard of care for the treatment of symptoms of PD remains oral levodopa, a drug approved nearly 50 years ago.  While oral levodopa is efficacious, there are significant challenges for physicians in creating a dosing regimen of oral levodopa that consistently maintains levodopa levels within a patient's therapeutic range. Over time, the response to levodopa becomes less reliable and predictable and levodopa often cannot turn a patient from the OFF to the ON state. As a result, the majority of PD patients experience OFF episodes despite taking PD medications.

 

OFF episodes are thought to occur when brain dopamine levels fall below a critical threshold to sustain relatively normal motor function, or ON. It can be a period of time when a patient's PD medication is not working adequately to alleviate the patient's PD symptoms, when the medication has a delayed effect or does not work at all. When experiencing an OFF episode, a PD patient is unable to perform simple daily tasks such as eating, bathing and dressing, thus becoming increasingly dependent on caregivers. OFF episodes are considered one of the greatest unmet medical needs facing PD patients. The Company believes the current addressable market for its product candidate, APL-130277, in the United States alone is approximately 400,000 patients.

More information about Cynapsus (TSX: CTH) (OTCQX: CYNAF) is available at www.cynapsus.ca and at the System for Electronic Document Analysis and Retrieval (SEDAR) at www.sedar.com.

Contact Information

Cynapsus Therapeutics

Anthony Giovinazzo

President and CEO

(416) 703-2449 x225

ajg@cynapsus.ca

Andrew Williams

COO & CFO

(416) 703-2449 x253

awilliams@cynapsus.ca

Forward-Looking Statements

This announcement contains "forward-looking statements" within the meaning of applicable securities laws. 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 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 to be as anticipated, estimated or intended. There can be no assurance that such statements will prove to be accurate, as actual results and future events could differ materially from those anticipated in such statements. Accordingly, readers should not place undue reliance on forward-looking statements. Cynapsus does not undertake to update any forward-looking statements, except in accordance with applicable securities laws.

Neither the TSX nor the OTCQX International has approved or disapproved of the contents of this press release.

HUG#1920313