Development

Development

BioMarck has completed approximately 13 toxicology studies, including studies in which aerosolized BIO-11006 was given daily for three weeks to rats and dogs. In addition, the potential effects of BIO-11006 on the cardiovascular, respiratory, and central nervous systems were specifically assessed in safety pharmacology studies conducted in rats and dogs. These studies indicated that BIO-11006 is well-suited for clinical studies.

Following a pre-IND meeting in Q1 2005, BioMarck filed an Investigational New Drug (IND) application with the Food and Drug Administration in Q3 of 2005. Following approval of the IND by the FDA, BioMarck initiated its first Phase 1 clinical study in the United States. This study was initiated in January 2006 and completed in March 2006. In this study, 8 subjects (6 BIO-11006 and 2 placebo) were treated with a single 75 mg dose of BIO-11006 Inhalation Solution and monitored for 7 days. The results indicated that a 75 mg dose of BIO-11006 Inhalation Solution is well tolerated.

BioMarck’s second Phase 1 study was initiated in September 2006; this study is a single- and multiple-dose study in which 4 dose levels of BIO-11006 were administered for up to 14 days to healthy individuals. The single dose results indicated excellent tolerability. The results of the multi-dose portion of the study indicated tolerability well above the dose at which maximum efficacy was seen in the mouse efficacy experiments. BioMarck requested and was granted an End-of-Phase 1 meeting with FDA to discuss the entirety of the nonclinical results, the Phase 1 results, and the design of the initial Phase 2 study in COPD patients. FDA reviewed all submitted data as well as the proposed protocol for the Phase 2 clinical study, and indicated that there were no barriers to moving forward with the Phase 2 study. The Phase 2 study, named BREATH 1 (BIO-11006: Respiratory Effectiveness of A Targeted Therapeutic), was initiated in Q3 2008 and completed in Q3 2010.

The BREATH 1 study was designed to evaluate the effectiveness and safety of four dose levels of BIO-11006 Inhalation Solution (75 or 150 mg/kg administered once per day, and 75 or 125 mg administered twice per day) when administered for 21 days to subjects with COPD suffering from chronic bronchitis. The BREATH 1 study enrolled 172 patients with COPD, and evaluated the safety and effectiveness of BIO-11006 Inhalation Solution. The study was double-blinded, placebo-controlled, and assessed the effectiveness of BIO-11006 in improving lung function and symptoms of COPD in patients with moderate COPD. The results of the study demonstrated that lung function and symptoms of COPD were improved in several BIO-11006-treated groups. The safety data from the BREATH 1 study demonstrated adequate tolerability.