Pearl advances PT003 dual combination drug candidate into Phase 2 studies for treatment of COPD

Pearl Therapeutics Inc. today announced the advancement of its dual combination product candidate, PT003 and its individual components, PT001 and PT005 into a series of planned Phase 2 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 2 studies are designed to expand findings from the Company's recently concluded Phase 2b study of PT003 and strengthen the safety and efficacy foundation of the Company's Phase 3 program, 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 2 studies in this series include:

1. 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;
2. A randomized, double-blind study of three doses of PT005 (FF MDI) compared to placebo and Foradil® Aerolizer®;
3. A randomized, double-blind cardiovascular safety study of PT003, PT005, PT001 and Foradil® Aerolizer®; and
4. A randomized, double-blind study of four doses of PT003 compared with its components, PT001 and PT005.

"With the success of our first Phase 2b study behind us, we are advancing PT003 and its components without delay into this planned series of four Phase 2 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 rigor. Combining our novel scientific platform with our unique operational construct, we were able to complete an eight-arm, randomized, active- and placebo-controlled Phase 2b study of PT003 in fewer than nine months. We anticipate completing the four new Phase 2 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 2 studies will be improvement in bronchodilation as assessed by change in FEV1 (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 2b study, and those from the forthcoming Phase 2 studies will provide a strong foundation for selecting the most effective and safe doses of GP and FF in PT003 for Phase 3 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 2 study of PT001 before progressing into Phase 3. 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 2 studies follow the successful conclusion of the Company's first Phase 2b 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 2b 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 2 program 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 2b studies.