SBIR-STTR Award

This Phase I SBIR application is presented by Bistech, Inc. of Woburn, MA. It will test the feasibility of using a new inhaled pharmaceutical agent, pneumoreductive surfactant (PRS), to treat pulmonary emphysema, a progressive and disabling disease that affects millions of individuals throughout the world. Existing medical therapies for emphysema, such as bronchodilators and anti-inflammatory drugs, are of limited benefit since they do not address the fundamental physiological defect in this disease: loss of elastic recoil caused by destruction of the collagen and elastin fibers of the lung. Two factors determine lung elastic recoil: 1) stretching of the tissue fiber network and 2) surface tension generated by the surface film at the alveolar air-liquid interface. In, theory, elastic recoil could be restored in emphysema either by repairing the tissue fiber network or by increasing surface tension. While medical therapies cannot readily accomplish the former, they may be able to accomplish the latter. Prototype formulations of pneumoreductive surfactant have been developed by Bistech. In preliminary in vitro testing and short term in vivo testing, these formulations appear to increase recoil effectively and safely. The studies proposed here will extend these preliminary observations, and examine whether PRS can be developed for clinical testing. The specific aim of this proposal is to evaluate short and long term physiological and biological responses to PRS administration in an experimental model of emphysema that accurately represents the disease as it presents in humans. The studies are designed to provide detailed information about the effects of PRS on lung function in vivo, and to identify any potential toxic effects of prolonged PRS exposure. If Phase I proves successful, a Phase II application will be filed to complete preclinical animal testing and product formulation, initiate pharmacology-toxicology studies, develop a manufacturing plan, and begin the planning of a Phase 1 clinical trial in human patients.

Thesaurus Terms:
drug screening /evaluation, emphysema, nonhuman therapy evaluation, respiratory disorder chemotherapy, surfactant disease /disorder model, drug adverse effect, inhalation drug administration, surface property laboratory ray

Aeris therapeutics is developing a novel medical treatment for patients with advanced emphysema known as Pneumoreductive Surfactant (PRS). PRSs are inhaled drugs that increase lung recoil by safely altering the surface tension properties of native lung surfactant. Unlike existing medical therapies for chronic obstructive pulmonary disease, PRS is the only medical therapy designed specifically to treat emphysema by improving lung recoil and decreasing hyperinflation. During Phase I SBIR funding (9/2004 to 3/2005), Aeris identified two PRS formulations that favorably alter lung surfactant function in vitro, and effectively increase lung recoil in emphysema models in vivo. The best of these preparations has been selected for product development. Dose-response and dose delivery studies demonstrate that PRSs can be effectively delivered to the lung using conventional nebulizer systems. Repeat dosing studies confirm the safety of PRS administration, out to two weeks. GMP sources of raw materials for manufacturing PRS have been identified, and a manufacturing protocol, clinical plan, and regulatory strategy have been developed for advancing this product into clinical testing. Aeris is requesting Phase II SBIR support to advance the development of this exciting new therapeutic product