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DYNAVAX PRESENTS DATA FROM FIRST HUMAN TRIAL OF INHALED ISS FOR ASTHMA AT AAAAI
Contact:
Dino Dina, M.D.
President and Chief Executive Officer
Dynavax Technologies Corporation
(510) 848-5100
Denver, CO (March 7, 2003) � Dynavax Technologies today reported Phase I clinical data demonstrating the safety and biological activity of its inhaled ISS (immuno-stimulatory DNA sequence) for the treatment of asthma. The results were presented here at the 60th annual meeting of the American Academy of Allergy, Asthma & Immunology (AAAAI), along with preclinical data on mechanisms of action of ISS. Asthma is a major health problem affecting an estimated 17 million Americans and more than 100 million individuals worldwide. As in other developed countries, the prevalence and severity of asthma in the U.S. are increasing, with significant impact both in terms of quality of life and in the total costs associated with the disease.
�We were pleased to find that 1018 ISS delivered by inhalation is safe at doses that produce readily measurable biological responses,� said Dino Dina, M.D., president and chief executive officer of Dynavax. �In addition, the biological activity we�re seeing in humans is consistent with that shown in animals. Were hopeful that this will translate into clinical efficacy in our ongoing Phase II trials, initiated one month ago in asthmatic patients.�
Robert Coffman, Ph.D., and Edith Hessel, Ph.D., of Dynavax presented results from the randomized, placebo-controlled, Phase I clinical study evaluating the effects of an inhaled formulation of 1018 ISS in healthy volunteers. In Part 1 of the study, 21 volunteers were exposed to one of three doses of nebulized 1018 ISS at four weekly intervals. All treatments proved to be safe and well tolerated. In Part 2 of the study, a separate group of 18 volunteers was given a single exposure to 1018 ISS. The biological response to these doses was evaluated by comparing gene expression patterns in samples of airway cells taken before and after ISS treatment. Dose-related biological responses were measured in genes that had previously been defined as inducible by 1018 ISS. In this way, it was determined that the compound was active in the respiratory tract, and information was obtained about mechanisms of action, suggesting possible clinical activity in asthmatic patients.
Drs. Coffman and Hessel also reported the results of preclinical mechanism studies demonstrating that Dynavax�s 1018 ISS can reprogram the immune response, reducing inflammatory immune responses provoked by Th2 cells (T helper type 2 cells) in response to allergens. Using both mouse and primate models of allergic asthma, the researchers showed that a single intrapulmonary dose of 1018 ISS could substantially block the activation of Th2 lymphocytes to a subsequent challenge with inhaled allergen. This rapid inhibition of Th2 activation in the lung correlated with a marked reduction in airway hyper-reactivity and eosinophilia � responses that are characteristic of human asthma.
Asthma is a chronic lung disease characterized by inflammation of the airways typically driven by inflammatory Th2 responses to common environmental allergens. The possibility of inhibiting the inflammation by provoking a concomitant Th1 response provides a strong rationale for developing an ISS-based product for the treatment of asthma. ISS therapy is expected to alleviate the symptoms associated with asthmatic reactions and create mechanisms within the body for preventing future attacks.