Pearl Therapeutics' Bronchodilator Combination PT003 Provides Superior Inspiratory Capacity Compared to Spiriva®

REDWOOD CITY, Calif., Sept. 26, 2011 /PRNewswire/ -- Pearl Therapeutics Inc. presented additional positive results from its  Phase 2b study (NCT01085045) demonstrating that the dual bronchodilator combination product, PT003 (GFF MDI) provides superior inspiratory capacity (IC) compared to Spiriva® HandiHaler® (tiotropium bromide inhalation powder). IC is a lung function measurement that has been shown to be predictive of improvement in exercise performance in patients with COPD. PT003 is a proprietary fixed-dose combination of glycopyrrolate (GP), a long-acting muscarinic antagonist (LAMA) and formoterol fumarate (FF), a long-acting beta-2 agonist (LABA) delivered via a pressurized hydrofluoroalkane metered dose inhaler (HFA MDI). In a separate analysis, the Company also confirmed the comparability of their monotherapy, PT001 (GP MDI) to Spiriva. Both PT003 and PT001 products are based on Pearl's novel cosuspension formulation platform for metered dose inhalers. These data are being presented at the 2011 European Respiratory Society (ERS) annual meeting, which is being held in Amsterdam.

"It has recently been shown that the progressive reduction of resting IC is associated with the development of an increasingly shallow, rapid breathing pattern and worsening shortness of breath during exercise," explained Colin Reisner, Pearl's chief medical officer and executive vice president of clinical development. "Improvement in IC correlates well with improvement in dyspnea at rest and with exercise, as well as overall exercise endurance. PT003 provided substantial improvement in IC relative to Spiriva after the initial dose, with further improvements following chronic dosing. These data suggest that PT003 may provide significant improvements in symptomatic benefits and exercise performance and supports further evaluation."

In this Phase 2b study, patients with moderate-to-very severe COPD were randomized to receive one of two doses of PT003, PT001, one of two doses of PT005, Spiriva, Foradil® Aerolizer® (formoterol fumarate inhalation powder), or placebo. The two doses of PT003 (72 mcg GP/9.6 mcg FF and 36 mcg GP/9.6 mcg FF) and Spiriva provided statistically significant improvements in IC compared to placebo on day one (p<0.0001 all comparisons) and on day seven (p<0.0004 all comparisons). Both doses of PT003 provided a benefit on day one relative to Spiriva, with the higher dose showing statistical difference vs Spiriva (p<0.05). Further improvement was observed with chronic dosing, with both doses of PT003 providing a statistically significant benefit on day seven pre-dose and two hours post-dose relative to Spiriva (p<0.05).

"These results provide important early evidence of the broad clinical promise inherent in Pearl's fixed-dose bronchodilator combination, PT003 for patients suffering from debilitating effects of COPD," said Chuck Bramlage, Pearl's CEO. "These results strengthen our confidence in sustaining PT003's rapid progress towards late stage clinical development in 2012."

Pearl will also present at ERS an analysis of the efficacy of the two LAMAs studied in this trial, PT001 (36 mcg, BID) and Spiriva (18 mcg, QD). Both PT001 and Spiriva were shown to provide superior bronchodilation compared to placebo, yielding mean improvements in FEV1 (AUC 0-12) of 189 mL and 195 mL, respectively (p<0.0001 for both). The difference between these values was 6 mL, demonstrating that PT001 is statistically similar (non-inferior) to Spiriva (95% confidence interval -49; 38).

Poster Details
Date & Time: Sunday, September 25, 2011; 12:50pm – 2:40pm
Thematic Poster Session: Bronchodilators in asthma and COPD; Session 96
Title: "Fixed combination of glycopyrrolate and formoterol MDI (GFF MDI) demonstrates superior inspiratory capacity (IC) compared to tiotropium DPI (Tio) following 7 days dosing, in a randomized, double-blind, placebo-controlled Phase 2b study in patients with COPD"

Date & Time: Tuesday September 27, 2011; 12:50pm – 2:40pm
Thematic Poster Session: Drug delivery and pharmacokinetics II; Session 414
Title: "Glycopyrrolate MDI Demonstrates Comparable Efficacy and Safety to Tiotropium Dry Powder Inhaler in a Randomized, Double-Blind, Placebo-Controlled Phase 2b Study in Patients with Moderate to Very Severe Chronic Obstructive Pulmonary Disease"

Reproduction of these posters may be retrieved from the Publications page of the Pearl website.

About COPD

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.

About Pearl Therapeutics

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. Pearl is rapidly advancing a pipeline of products including PT003, an inhaled, fixed-dose combination bronchodilator product comprised of a long-acting muscarinic antagonist (LAMA) and a long-acting beta-2 agonist (LABA) delivered via a metered dose inhaler (HFA MDI); and PT010, a triple-combination product that combines the LAMA and LABA components of PT003 with an inhaled corticosteroid (ICS) for twice-daily administration from an HFA MDI for the treatment of severe COPD. Both PT003 and PT001 are developed with Pearl's proprietary porous particle cosuspension technology, which allows the formulation of multiple products in the MDI format, with highly stable, robust and aerodynamically efficient drug delivery. Founded in 2006, Pearl Therapeutics is privately held and backed by 5AM Ventures, Clarus Ventures, New Leaf Ventures and Vatera Healthcare. For more information, please visit www.pearltherapeutics.com.

* FEV1 (forced expiratory volumes in one second) is a common measurement of lung function in patients with asthma, cystic fibrosis, and COPD and is typically used to predict the severity of pulmonary disease. AUC (area under the curve) is a measure of therapeutic benefit over a period of time.

Editor's note: Spiriva® HandiHaler® (tiotropium bromide inhalation powder) is a registered trademark of Boehringer Ingelheim Pharmaceuticals; Foradil® is a registered trademark of Astellas Pharma; and Aerolizer® is a registered trademark of Novartis AG.

SOURCE Pearl Therapeutics Inc.