N8295 is a fusion protein comprised of NP and M2e, two highly conserved influenza antigens covalently linked to Dynavax's proprietary second-generation TLR9 agonist. The trial assessed three dose levels of N8295 in a total study population of 39 subjects. The Phase 1a data showed:
• All doses were very safe and generally well tolerated;
• No dose limiting toxicities;
• Positive antibody responses to M2e; and
• Positive T-cell mediated responses to NP.
Based on preliminary safety data, Dynavax initiated a Phase 1b study in September 2010 to evaluate the safety of the combination of N8295, the novel component of Dynavax's Universal Flu vaccine candidate, and an investigational H5N1 avian influenza vaccine. Detailed results of the Phase 1a and 1b studies will be reported at the World Health Organization 7th Meeting on Evaluation of Pandemic Influenza Prototype Vaccines in Clinical Trials in Geneva, Switzerland in February 2011.
Dr. J. Tyler Martin, M.D., Dynavax President and Chief Medical Officer, said, "Now that we have completed the safety assessment of the novel component, N8295, we are eager to assess the combination of N8295 with an avian flu vaccine. Those data are expected to improve our understanding of the immunologic properties of our universal flu vaccine candidate in the absence of pre-existing immunity to the H5N1 flu strain in human subjects. These are key achievements in the continued development of Dynavax's Universal Flu Vaccine as they should allow us to design a proof-of-concept study."
Dynavax's Universal Flu Vaccine is designed to offer protection against divergent influenza strains as well as to increase the efficacy of a conventional influenza vaccine. Preclinical data have confirmed the expected immunogenicity and mechanistic effects of the vaccine candidate's novel components. The production of cytotoxic T-cells by NP and cytotoxic antibodies by M2e have been demonstrated in preclinical studies, as has an increase in neutralizing antibodies provided by a co-administered conventional influenza vaccine. A GLP toxicity study demonstrated that this Universal Flu vaccine candidate is well-tolerated.