Targeted Genetics Corporation announced final results of its Phase II clinical trial in patients with cystic fibrosis. The product candidate, tgAAVCF, met its primary endpoint demonstrating safety and tolerability in this first ever repeat dosing study. Positive trends in pulmonary function, inflammatory cytokine (IL-8) levels and gene transfer were also observed.

tgAAVCF, Targeted Genetics' lead gene therapy product candidate for the treatment of cystic fibrosis, was tested in a randomized, double-blind, placebo-controlled clinical trial that included 37 patients with mild cystic fibrosis. Patients were monitored for approximately five months. The complete data analysis confirmed preliminary results presented at the 16th Annual North American Cystic Fibrosis Conference in October of 2002. Data highlights are as follows:

-- A clean safety profile was sustained over the entire 150-day study period. No clinically significant differences in adverse events between the product candidate and placebo were observed.

-- Statistically significant improvements in lung function (FEV1) were observed after 30 days. In addition, positive trends were observed in various measurements of lung function after 60 and 90 days in the treated population, compared to the placebo group.

-- A statistically significant decrease in IL-8 levels (a cytokine associated with inflammation) was observed after 14 days compared to placebo.

-- Excellent gene transfer was observed in all patients tested.

After complete data analysis, additional data highlights included:

-- Chest computerized tomography (CT) scans utilized to measure additional safety showed no statistically significant changes in CT scores between days 0 and 90, further supporting a strong safety profile associated with tgAAVCF.

-- 22 percent of patients treated with tgAAVCF sustained a 5 percent or greater improvement in lung function at 90 days, while no patients receiving placebo achieved this response.

-- 17 percent of patients treated with tgAAVCF sustained a 10 percent or greater improvement in lung function at 90 days, while no patients receiving placebo achieved this response.

-- No correlation was observed between the levels of AAV neutralizing antibodies and patients' FEV1 measurements, suggesting that antibodies to the AAV vector do not appear to impact the therapeutic profile of tgAAVCF when administered via repeat dosing.

This phase II clinical trial involved 37 CF patients with mild lung disease, 17 who received placebo and 20 who received tgAAVCF. The mean age in this study was 24 years. Following approvals from an independent data safety monitoring board, patients as young as 12 years of age were included in the clinical trial. Patients were randomized to receive three doses at 30-day intervals of tgAAVCF, 1013 DNAse resistant particles (DRP) per dose, or placebo. Patients were followed for 90 days after receiving their last dose. The primary endpoint of this study was the safety and tolerability of repeat dosing with tgAAVCF. Activity measures included lung function (FEV1 - a standard measurement of lung function), inflammation and microbiology. In a subset of six patients undergoing bronchoscopy one to two months after last dosing, gene expression, measured by determining levels of mRNA, was not demonstrated in cells brushed from the largest airways within the limit of detection of the assay. Over the course of the clinical trial, AAV neutralizing antibody response occurred systemically and locally, although no correlation was noted between the levels of AAV neutralizing antibodies and patients' change in lung function (FEV1).