Pipeline :: Flu Vaccine

Our novel Universal Flu vaccine entered clinical development in June 2010. In late September, we initiated a Phase 1b study to evaluate the safety of the combination of N8295, the novel component of Dynavax's Universal Flu vaccine candidate, and Novartis' investigational H5N1 avian influenza vaccine. 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 Phase 1b study was initiated six months ahead of schedule based on preliminary Phase 1a safety data on N8295 alone.

In mid-February, 2011, in Geneva, Switzerland at the World Health Organization 7th Meeting on Evaluation of Pandemic Influenza Prototype Vaccines in Clinical Trials, we reported new Phase 1a and Phase 1b safety and immunogenicity data for our universal flu candidate vaccine. In an oral presentation, Dynavax's Robert Janssen, M.D., Senior Director, Clinical Research, described new findings for N8295 in combination with an investigational H5N1 avian influenza vaccine. The study evaluated 54 subjects, including 39 from the Phase 1a dose escalation study of N8295 and 15 from the Phase 1b dose escalation study of H5N1/N8295.

Data from the Phase 1a and the Phase 1b study showed:

N8295 alone or combined with H5N1 vaccine was very safe and generally well tolerated;
The most common adverse events were mild, self-limited injection site reactions;
There were no SAEs;
All N8295 dose groups had an antibody response to M2e, and the placebo group did not;
All N8295 dose groups had an antibody response to NP, and the placebo group did not;
All N8295 dose groups had a cellular immune response to NP, and the placebo group did not;
The addition of N8295 to a non-immunogenic dose of H5N1 vaccine resulted in H1 responses in all N8295 dose groups.

Establishing the safety -- first, of the novel component, N8295, and now, of the combination -- is key to the continued development of Dynavax's Universal Flu Vaccine. By assessing N8295 in combination with H5N1 vaccine, Dynavax expects to improve its understanding of the immunologic properties of the company's universal flu vaccine candidate in the absence of pre-existing immunity to the H5N1 flu strain in human subjects. With positive data from the completed Phase 1a and 1b studies, Dynavax plans to design a proof-of-concept study to generate data that could trigger Novartis' option on joint development and commercialization of the product.

Principal Investigator, Dr. John E. Ervin, will conduct the study at The Center for Pharmaceutical Research in Kansas City, MO. A total of 15 subjects will be divided into three different dose groups of N8295, each dose of which will be combined with the same amount of H5N1 vaccine. All subjects will receive two immunizations, separated by one month. Preliminary data is expected to be available early in 2011. Subjects will continue to be monitored for approximately one year.

Under a 2008 agreement Novartis Vaccines and Diagnostics is providing Dynavax with influenza vaccine for both clinical trial use and potential vaccine sales. Novartis has an exclusive option to negotiate a Joint Development and Commercialization agreement with Dynavax pending proof-of-concept data.

Commercial Opportunity

Human viral influenza is an acute respiratory disease with high morbidity and mortality that occurs in annual epidemics worldwide. There are an estimated 30,000 to 40,000 viral influenza-associated deaths per year in the United States, primarily in those over 65 years of age. Influenza pandemics occur infrequently, on average every 30 to 40 years, but the next pandemic could result in millions of deaths worldwide. Analysts estimate the current worldwide market opportunity for seasonal influenza vaccines to be approximately $3 billion annually.

Standard flu vaccines can provide protection against the influenza strains predicted to be prevalent during a season. The efficacy of these vaccines is often decreased by unpredictable changes in the actual strains causing influenza. Current vaccines are also least effective in those who need prevention the most, the elderly and others with weaker immune systems. Pandemic vaccination is further complicated by the need to produce large quantities of vaccine in a short time period.

Our Universal Flu vaccine is designed to offer protection against divergent influenza strains, increase the efficacy of standard vaccines, and potentially reduce the dose of vaccine to extend the quantity available during a pandemic.