Inovio Pharmaceuticals Inc., a company revolutionizing vaccines to prevent and treat today's cancers and challenging infectious diseases, has reported interim results of a phase I trial that showed that a single dose of its H1N1 universal SynCon flu vaccine followed with a dose of a seasonal flu vaccine generated protective immune responses in 40 per cent of trial subjects compared with a 20 per cent response rate in elderly patients who received the seasonal flu vaccine alone. This interim data is a significant step in developing a more effective flu vaccine for the most vulnerable segment of our population.

People over 65 years of age represent about 90 per cent of annual influenza deaths in the US. Older people's immune systems typically mount much weaker protective immune responses to seasonal vaccines, often in only 10 to 20 per cent of this population. In younger adults, the same flu vaccines generate protective immune responses in at least 65 per cent of the vaccine recipients. Other approaches, such as the use of higher vaccine doses and novel adjuvants, have not significantly improved the seasonal vaccine's impact in the older population. Thus, there is a significant need for a new approach to provide better protection in this more vulnerable population.

With the vulnerability of the elderly in mind, this phase I study is evaluating the ability of Inovio's SynCon vaccine alone, as well as in combination with the 2012 seasonal influenza vaccine, to generate protective levels of antigen-specific antibody immune responses in a greater proportion of the elderly population as well as to assess the potential for more universal protection against both matched and unmatched seasonal influenza strains.

In the trial, 50 healthy elderly patients have been divided into three groups: one group of 20 subjects received a two-dose regimen of Inovio's H1N1 universal SynCon flu vaccine delivered using Inovio's proprietary CELLECTRA intradermal electroporation device 16 weeks apart; a second group of 20 subjects received one dose of Inovio's SynCon vaccine delivered using electroporation followed by a dose of seasonal flu vaccine 16 weeks later; a third group of 10 subjects received placebo delivered by electroporation followed by a dose of the seasonal flu vaccine 16 weeks later. The study's objectives are to assess the tolerability, safety, and immune responses of these different vaccination regimens. Today's interim results report on the last two arms in the influenza study. The phase I open label study is ongoing at the University of Manitoba in Winnipeg, Canada. See the clinical study protocol.

Serum samples from the vaccinated subjects were used to assess the generation of hemagglutination inhibition (HAI) titers meeting or exceeding a dilution of 1:40 to the current H1N1 seasonal flu strain (A/California/07/09). An HAI titer of 1:40 is the level recognized as a protective immune response against influenza in humans. Because of generally high HAI titer background rates to the A/California/07/09 strain, vaccine-specific, protective response rates were determined by assessing the number of patients in each group who had HAI titers greater than 1:40 and HAI titers at least 4-fold higher than the background value at the start of the trial. Vaccination with the H1N1 universal SynCon® flu vaccine followed with a dose of a seasonal flu vaccine generated protective immune responses in 40 per cent (8 of 20) of trial subjects compared with a 20 per cent (two of 10) response rate in elderly patients who received the seasonal flu vaccine alone.

Dr Gary P Kobinger, Professor, University of Manitoba, and a principal investigator of this study, said, "These early results indicate the potential to significantly expand the protection of this at-risk population of elderly subjects against flu. With limited evidence of other innovations enhancing protection against influenza, this technology could potentially lead to a breakthrough vaccine."

Dr J Joseph Kim, Inovio's President and CEO, said, "Today's results provide evidence of the power of our DNA vaccine approach to generate protective antibodies in this vulnerable age group. They also show how our vaccines can increase the potency and coverage of existing therapies."

The need for a new vaccine approach that can stimulate a protective immune response in a greater proportion of people and a broader immune response that is capable of protecting against influenza strains not specifically matched to the strain(s) represented in the vaccine is even greater in the elderly population because they are most at risk for death and illnesses by influenza infection. In addition to improving the immune response and patient response rate against the matched seasonal strain in the older population, all patient serum samples will also be analyzed against other important H1N1 strains to assess the prime-boost regimen's ability to generate universal cross-strain protection and will be reported in 2013.

Inovio also reports that enrollment is complete for a phase II trial of a DNA vaccine for hepatitis C administered by Inovio's proprietary electroporation delivery technology. Researchers are currently analyzing levels of immune response and HCV viral load in trial subjects. Inovio will report preliminary results in the first quarter of 2013. The trial is being conducted by Inovio's partner, ChronTech Pharma AB.

The strategy to combine an influenza DNA vaccine prime with a conventional seasonal vaccine boost is based on the idea that combining the different modalities of Inovio's SynCon flu vaccine's ability to generate cross-protective antibody responses with the conventional seasonal flu vaccine in a prime-boost regimen could generate a stronger and broader antibody response in the elderly.

Inovio's SynCon influenza vaccine approach provides "universality" within and across subtypes. Individual SynCon DNA vaccine "constructs" are designed to provide broad cross-strain protection against existing and potential new strains of influenza within key branches (clades) of subtypes of greatest concern to humans, including H1N1, H3N2 and Type B as well as H5N1. Inovio combines multiple DNA constructs into a universal influenza vaccine potentially able to provide broad protection against the targeted subtypes. Such preemptive protection against new strains could be particularly important to the elderly.