Pearl Therapeutics Inc. announced the advancement of its dual combination product candidate, PT003 and its individual components, PT001 and PT005 into a series of planned phase II studies in patients with moderate-to-severe COPD. PT003 (GFF MDI) is an investigational inhaled combination bronchodilator product comprising glycopyrrolate (GP), a Long-Acting Muscarinic Antagonist (LAMA), and formoterol (FF), a well-known, established, Long-Acting Beta-2 Agonist (LABA), delivered together for the first time via a Hydrofluoroalkane Metered Dose Inhaler (HFA MDI), using a proprietary cosuspension formulation approach.

These phase II studies are designed to expand findings from the Company’s recently concluded phase II b study of PT003 and strengthen the safety and efficacy foundation of the company’s phase III programme, which is expected to start in late 2012. Specifically they will provide further insight into the individual component doses, compare clinical activity to that of a short-acting anticholinergic agent and assess any cardiovascular effects.

The phase II studies in this series include: a randomized, double-blind study of four doses of PT001 (GP MDI) compared to placebo and Atrovent HFA inhalation aerosol, a short-acting muscarinic antagonist; a randomized, double-blind study of three doses of PT005 (FF MDI) compared to placebo and Foradil Aerolizer; a randomized, double-blind cardiovascular safety study of PT003, PT005, PT001 and Foradil Aerolizer; and a randomized, double-blind study of four doses of PT003 compared with its components, PT001 and PT005.

“With the success of our first phase II b study behind us, we are advancing PT003 and its components without delay into this planned series of four phase II studies,” said Chuck Bramlage, Pearl’s chief executive officer. “Pearl has instituted an iterative and integrated clinical and product development process that allows us to conduct clinical studies rapidly while maintaining a high level of rigour. Combining our novel scientific platform with our unique operational construct, we were able to complete an eight-arm, randomized, active- and placebo-controlled phase II b study of PT003 in fewer than nine months. We anticipate completing the four new phase II studies in about 12 months, making top-line results available by mid 2012. Following the conclusion of these studies, we will meet with the U.S. Food and Drug Administration to review plans for a registrational Phase 3 program of PT003.”

With the exception of the cardiovascular safety study, the primary endpoints of the phase II studies will be improvement in bronchodilation as assessed by change in FEV1 (forced expiratory volumes in one second)  AUC0-12 relative to baseline. The cardiovascular safety study will measure the change in mean heart rate averaged over 24 hours following chronic administration of PT003, PT005, PT001 or Foradil compared to baseline obtained during the screening period. Heart rate will be evaluated using Holter monitoring. More than 500 patients with moderate-to-severe COPD will be enrolled in these four studies.

“The insights we gained from our first phase II b study, and those from the forthcoming phase II studies will provide a strong foundation for selecting the most effective and safe doses of GP and FF in PT003 for phase III trials,” added Colin Reisner, chief medical officer and executive vice president of clinical development and medical affairs at Pearl Therapeutics. “We are building additional confidence in our dose selection by comparing GP efficacy with that of a short-acting muscarinic antagonist, Atrovent, in our phase II study of PT001 before progressing into phase III. This will strengthen our GP clinical experience beyond our already completed assessment of GP against a long-acting muscarinic antagonist, Spiriva.”

Pearl’s new phase II studies follow the successful conclusion of the company’s first phase II b study, in which patients administered PT003 experienced superior bronchodilation compared to those administered the individual components, PT001 and PT005, in a head-to-head comparison following the expectations set under FDA's combination rule.

Further, PT003 also showed superior bronchodilation compared to active comparators, Spiriva HandiHaler and Foradil Aerolizer. This assessment was based on the primary endpoint of FEV1 AUC0-12 after one week, as well as secondary endpoints, peak FEV1 after one and seven days, and trough FEV1. Primary and secondary endpoints from this phase II b study were presented in May 2011 at the American Thoracic Society annual meeting. This poster may be downloaded from the Publications page of the Pearl website. The five studies in Pearl’s phase II programme are fully funded by proceeds of the company’s 2010 Series C financing.

Since its inception in 2007, Pearl has completed four early stage clinical trials on PT003, PT001 and PT005, along with a suite of non-clinical toxicology studies, and generated comprehensive data on product design and robustness, to boost its confidence in the scientific and clinical merit of the four new phase II b studies.

Chronic Obstructive Pulmonary Disease (COPD) is a preventable and treatable lung disease that is the fourth leading cause of death in the United States. Each year 12 million Americans are diagnosed with COPD and an additional 12 million Americans may have COPD but remain undiagnosed. Research shows that many do not get optimal treatment.

Bronchodilator medications are central to symptom management and are prescribed on an as-needed or regular basis to prevent or reduce symptoms. Long-acting inhaled bronchodilators have been shown to be most effective and convenient. Combining bronchodilators of different pharmacological classes, as recommended by The Global Initiative for Chronic Obstructive Lung Diseases (GOLD), has been shown to improve efficacy and may decrease the risk of side effects compared to increasing the dose of a single bronchodilator. As the course of COPD progresses, regular treatment with inhaled glucocorticosteroids may be added to bronchodilator treatment. Pearl is developing inhaled combination products designed to optimize the treatment of COPD.

Pearl Therapeutics is a privately held company developing combination therapies for the treatment of highly prevalent respiratory diseases, including chronic obstructive pulmonary disease and asthma.