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TOPIGEN Initiates Expanded Phase II Trial of Inhaled TPI ASM8 in Patients With Asthma

09 Mar 2007

Leading RNA-Targeting Drug to Treat Respiratory Disease Progresses in Development

MONTREAL, Canada | Mar 08, 2007 | TOPIGEN Pharmaceuticals Inc., an emerging biopharmaceutical company specializing in

developing treatments for respiratory diseases, today announced it has commenced a second, expanded, 14-day Phase II clinical trial with one of its leading product candidates, inhaled TPI ASM8. TOPIGEN believes TPI ASM8 to be the first RNA-targeting drug with demonstrated efficacy in respiratory patients. This Phase II study is commencing as a result of initial positive Phase II results announced in July 2006 indicating that TPI ASM8 demonstrated protection in early and late stage allergic responses in patients with allergic asthma.

The initial Phase II trial conducted last year was a 17-patient trial designed to assess overall safety and tolerability and to demonstrate 'proof-of-principle' that inhaled TPI ASM8 would show pharmacological activity in the respiratory tract of patients with mild-to-moderate asthma. The study results announced in July 2006 validated TOPIGEN's proprietary multi-targeted therapeutic approach, demonstrating the drug candidate works effectively in the respiratory tract of patients with asthma and that it is safe and effective in this patient population. The study also served as validation of TOPIGEN's receptor targets in patients with asthma. Specifically, the study results indicated that inhaled TPI ASM8 is safe and well tolerated and it demonstrated significant pharmacological activity in study subjects, including substantial reductions of eosinophil cell levels and suppression of target gene expression. Eosinophils are cells that are recognized as key contributors to inflammation and airway destruction in all grades of asthma and other respiratory diseases.

The second, expanded Phase II study is being conducted to evaluate the effects of TPI ASM8 given for a longer duration and to confirm efficacy at different doses. This Phase II study will assess and compare the safety, tolerability and efficacy of inhaled TPI ASM8 at nominal dosages of 250µg and 500µg with a placebo administered once a day for fourteen days in adult patients of chronic allergic asthma. The 60-patient randomized, parallel-group, placebo-controlled, double-blinded study will be conducted at the Firestone Institute for Respiratory Health in Ontario, Canada. Three groups of 20 subjects will be evaluated (two groups will receive active drug and one group will receive placebo of a sterile, buffered saline solution delivered via identical nebulizer). The primary objective of the study is to compare the efficacy of the two dosages of inhaled TPI ASM8 against placebo at reducing sputum eosinophils in subjects with asthma, as well as to assess safety and tolerability.

Dr. Paolo Renzi, Chief Scientific Officer and Founder of TOPIGEN, commented, "We remain excited about the therapeutic potential of TPI ASM8 following the positive results from our previous Phase II study. As a result of its highly specific mechanism of action on multiple targets of inflammation, TPI ASM8 should have improved anti-inflammatory properties for targeting the source of lung inflammation, beyond the anti-inflammatory properties of today's current therapies, but with minimal systemic side-effects. We also believe that TPI ASM8 has the potential to treat allergic disorders in sites other than the lung such as allergic conjunctivitis of the eye, allergic rhinitis, and allergic dermatitis and there is long-term potential for expanded indications."

Paul K. Wotton, Ph.D., President and Chief Executive Officer of TOPIGEN, added, "Our last study provided strong validation of TOPIGEN's novel multi-targeted approach as evidenced by the substantial knockdown in eosinophil cells in patients with asthma. Results from this study evaluating TPI ASM8 in an expanded patient study population will bring us closer to developing a meaningful therapeutic alternative for patients with asthma, as well as towards our goal of building TOPIGEN as a leading biopharmaceutical company focused on developing innovative treatments for respiratory diseases."

About Inhaled TPI ASM8

TPI ASM8 is a first-in-class, inhaled RNA-targeting drug candidate currently in Phase II clinical development for the treatment of asthma. TPI ASM8 is based on TOPIGEN's proprietary RNA-targeting chemistry and consists of two modified RNA-targeting oligonucleotides designed specifically to reduce the recruitment and persistence of chronic inflammatory cells and their associated release of cytokines -- all key components underlying the cause of the disease. TPI ASM8 targets two distinct cellular pathways involved in allergic airway inflammation by inhibiting the recruitment of allergic inflammatory cells, called eosinophils, via an effect on the CCR3 receptor, and also reducing the persistence of allergic inflammatory cells via interference with a common beta sub-unit for the receptors of interleukin (IL) 3, 5 and GM-CSF. This pioneering multi-targeted approach of blocking the expression of specific genes with RNA-antagonists is expected to have advantages over current medications through providing broader pharmacological activity with limited systemic availability.

About Asthma

Asthma is a chronic inflammatory disease of the airways in which many cells and cellular elements play a role -- in particular, mast cells, eosinophils and T-lymphocytes. In susceptible individuals, this inflammation causes recurrent episodes of wheezing, breathlessness, chest tightness and coughing, particularly at night and/or in the early morning. The inflammation also causes an associated increase in the airway hyperresponsiveness to a variety of stimuli. Symptoms are usually associated with widespread but variable airflow obstruction that is at least partly reversible with treatment. Allergic asthma accounts for most cases of the disease and afflicts people who are predisposed to developing hypersensitivity to environmental allergens.

About TOPIGEN

TOPIGEN is a privately held, clinical-stage biopharmaceutical company focused on developing new classes of inhaled drugs for respiratory diseases such as asthma, COPD and allergic rhinitis. TOPIGEN's pipeline includes small molecule and RNA-targeting therapeutics. The Company has two lead product candidates, inhaled TPI ASM8 for the treatment of asthma and inhaled TPI 1020 for the treatment of Chronic Obstructive Pulmonary Disease (COPD), both currently undergoing Phase II trials. By topically targeting multiple affected airway receptors, the Company expects to improve outcomes for many patients with respiratory diseases. This specific approach has shown promising preclinical and clinical results in inhibiting the underlying inflammation associated with many pulmonary conditions. Current venture investors include CDP Capital - Technology Ventures, Desjardins Venture Capital, T2C2 / BIO, Fonds de solidarité FTQ, BDC Venture Capital and Multiple Capital Inc. For more detailed information on TOPIGEN visit www.topigen.com.

SOURCE: TOPIGEN

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