APL-130277

Overview

Cynapsus is a clinical-stage, specialty pharmaceutical company developing a convenient and easy to use sublingual thin film strip to manage OFF episodes associated with Parkinson’s disease. Our drug candidate, APL-130277, is an easy-to-administer, fast-acting reformulation of apomorphine, which is the only approved acute drug (in the United States, Europe, Japan, and other countries) to rescue patients from OFF episodes.

Over one million people in the United States and an estimated 4 to 6 million people globally suffer from Parkinson’s disease, and its prevalence is expected to increase with the general aging of the population. Parkinson’s disease is a chronic and progressive neurodegenerative disease that impacts motor activity resulting from the gradual loss of certain neurons responsible for producing dopamine. It is characterized by symptoms including tremor at rest, rigidity and impaired movement and ability to communicate. 

Based on a recent studies, it is estimated that between 25 percent and 50 percent of patients experience OFF episodes in which they have impaired movement and/or communication capabilities, with such patients having between one to six OFF episodes daily. OFF episodes are considered one of the greatest unmet medical needs facing Parkinson’s disease patients as they often result in patients’ inability to perform simply daily tasks such as eating, bathing and dressing. As Parkinson’s disease progesses, patients are often forced to leave the workforce early and become increasingly dependent on care-givers.

To date, Cynapsus has studied approximately 110 subjects / patients in five clinical studies, with the most recent result being our CTH-105 Phase 2 clinical trial, which had 16 people with Parkinson's disease who completed the dosing regimen. Out of 16 patients, 14 converted from OFF to ON with clinically meaningful improvement in motor control in as early as 10 minutes after administration of APL-130277 and lasted longer than 90 minutes. The maximum mean change from baseline UPDRS III was 18.4, which is a large clinically important difference.  The CTH-105 Phase 2 clinical trial results showed the APL-130277 treatment was safe and well-tolerated, with no local irritation, no postural hypotension and a low number of nausea events.

Cynapsus expects to initiate Phase 3 clinical trials in 2015, which will be of longer duration and with larger patient numbers to confirm the efficacy and safety of APL-130277. The details of these trials will form the basis for the registration package necessary for a 505(b)(2) New Drug Application, or NDA, with the United States Food and Drug Administration, or the FDA, expected to be submitted to the FDA in 2016.

Through surveys and commercial and competitive assessments that we’ve had conducted by third-parties, we estimate APL-130277 may be an appropriate treatment for up to 1 million Parkinson’s patients worldwide, with 800,000 being located in the United States and Europe.

Regulatory Plan

On February 4, 2015, Cynapsus held its End-of-Phase 2 meeting with the FDA. For development of APL-130277 in the United States, Cynapsus will follow section 505(b)(2) of the FFDCA. Specifically, Cynapsus is pursuing a novel formulation of apomorphine that is a convenient, tolerable and safe sublingual thin filmstrip. The drug substance (apomorphine) is identical to the active pharmaceutical ingredient (“API”) in the FDA approved SC injection, Apokyn®. APL-130277 is being developed as an adjunctive therapy for the on-demand management of OFF episodes (i.e., predictable wearing OFF, morning akinesia (or morning OFF), delayed ON (or dose failure), and unpredictable OFF) in patients with PD, similar to the description of usage in the FDA approved Apokyn® label.

The 505(b)(2) regulatory pathway will require Cynapsus to provide statistically significant clinical evidence that PD patients experience resolution of their OFF episodes as a result of delivery of apomorphine via the sublingual thin filmstrip route.

To achieve this, Cynapsus currently plans to complete the following clinical studies:

• CTH-200 Bridging Study. A single-dose, crossover comparative bioavailability and PK study in healthy volunteers. This study is designed to allow Cynapsus to use the safety and efficacy data for the Reference Listed Drug (“RLD”) (Apokyn®) in its NDA submission to the FDA. This study is planned to start in Q2 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 over a 12 week period. The primary end point will be the mean change in the UPDRS III score at 30 minutes after dosing. This study is planned to start in Q2 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 a six-month period. 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. This study is planned to start in Q3 2015.

In parallel to these studies, Cynapsus will be performing the necessary scale-up, process validation and stability as part of the Chemistry, Manufacturing and Controls (“CMC”) requirements for the filing of the NDA. All development will be performed according to current Good Manufacturing Practices (“cGMP”) methodology.

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

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