INFLUENZA
In 2005, we applied our DNA delivery technology towards the development of an influenza vaccine. Our approach is to include vaccine components which we believe will provide potential cross strain protection, particularly against severe disease and mortality, unlike conventional influenza vaccines which provide symptomatic relief through antibodies alone and are unlikely to protect against severe disease and mortality if the strain match is not correct. Our lead influenza vaccine candidate uses pDNA encoding two highly-conserved influenza virus proteins—nucleoprotein (NP) and ion channel protein (M2)—plus the H5 (hemagglutinin) avian influenza virus surface protein, and is formulated with our patented Vaxfectin® adjuvant.
In 2005, we received a $2.9 million challenge grant from the NIAID to support the development of a DNA vaccine against naturally emerging or weaponized strains of influenza and a two-year, $0.5 million challenge grant from the NIAID to support the development of a DNA vaccine against seasonal influenza. Funding under the challenge grant was released in stages upon the achievement of development milestones. In the initial activities covered by the challenge grant, we collaborated with St. Jude Children’s Research Hospital, a world-renowned center of expertise in influenza research, including pandemic influenza research.
In 2005, we achieved the first milestone in this challenge grant which was based on the successful design, manufacturing, and initial immunogenicity testing of an H5-based influenza vaccine. We showed that our influenza H5 HA DNA vaccine is immunogenic in animals.
During the second quarter of 2006, we achieved the second milestone under the pandemic influenza challenge grant which included challenging DNA-vaccinated animals with a virulent Vietnam strain (A/Vietnam/1203/04) of H5N1 avian influenza virus. The data showed that our DNA vaccine provided complete protection of mice and ferrets against lethal challenges with the H5N1 avian influenza virus as well as protection of mice against multiple human influenza strains.
Data from subsequent studies demonstrated that a single injection of our lead influenza vaccine candidate provided 100% protection in ferrets against lethal challenge from the H5N1 virus. Conventional vaccines under development for pandemic influenza typically have required two or more doses in humans, even with novel adjuvants, to produce the immunogenicity levels expected to provide protection.
In 2007, we initiated a Phase 1 trial of our pandemic influenza candidate. The double-blind, placebo-controlled trial was designed to evaluate safety, tolerability and immune responses in up to 60 healthy volunteers age 18 to 45 at three U.S. clinical sites. Later in 2007, we implemented a planned expansion of the Phase 1 study to allow comparison of vaccination with needle and syringe to vaccination with the Biojector® 2000 needle-free injection system. The Biojector® 2000 needle-free injection system has been shown to enhance the immunogenicity of pDNA vaccines in previous animal studies, and has demonstrated encouraging safety and immunogenicity data in multiple human pDNA vaccine studies. The expanded Phase 1 study was designed to evaluate needle-free testing in up to 50 subjects. All tests were double-blind and placebo-controlled, and were designed to evaluate safety, tolerability and immune responses.
In July 2008, we announced preliminary clinical trial data demonstrating that DNA vaccines can safely achieve significant immune responses against H5N1 pandemic influenza in humans. Preliminary human safety and immunogenicity data obtained in our 100-subject Phase 1 trial of Vaxfectin®-formulated H5N1 pandemic influenza DNA vaccines demonstrated for the first time that DNA vaccines have achieved potentially protective levels of antibody responses in up to 67% of evaluable subjects in the higher dose cohorts. No significant safety issues were observed at any of the doses tested. These results support further development of Vaxfectin®-formulated DNA vaccines, and could position them as potential alternatives to conventional vaccines. Expanded data presented in October 2008 showed that in the highest dose cohorts, responses peaked by Day 56 and were sustained in 80% to 100% of the responders through the end of the study at Day 182.
We announced in October 2008 that AnGes has signed a non-binding letter of intent with us indicating its mutual interest to license the development and marketing rights for our pandemic influenza DNA vaccines in Japan. AnGes plans to conduct due diligence on the pandemic influenza DNA vaccines, and both parties intend to negotiate terms and conditions potentially leading to a license.
About Influenza
Pandemic influenza is virulent human influenza that causes a global outbreak, or pandemic, of serious illness. A pandemic could begin if the H5N1 virus or another avian influenza virus strain changes to a form that can spread easily from person to person. Avian influenza is caused by influenza A viruses that occur naturally among wild birds. Most of the hundreds of strains of avian influenza virus remain in birds and cause only mild disease symptoms. Some strains of H5N1 avian influenza virus have become highly pathogenic in recent years and can be deadly to domestic poultry as well as certain wild birds. Certain strains can also be transmitted from birds to humans. Most cases of H5N1 influenza infection in humans have resulted from contact with infected poultry or surfaces contaminated by infected birds. The spread of H5N1 virus from person to person has been limited, but continued changes to the H5N1 virus could result in a strain that is more easily spread from person to person. Because humans have no prior exposure to H5, they have no immunity. Symptoms of avian influenza in humans have ranged from typical human influenza-like symptoms to pneumonia, severe respiratory complications, and death.
Seasonal influenza is a respiratory illness that can be transmitted person to person. It is caused by one of two currently circulating influenza A virus HA subtypes (H1 and H3), which originated in other species before spreading to humans, or by an influenza B virus, which affects only humans. Other influenza A strains also might change over time to infect and spread among humans. Most people have some immunity through prior exposure and/or vaccination. Because influenza A viruses are constantly changing, new vaccines are required each year. Seasonal influenza can cause mild to severe illness with symptoms typically including fever, headache, severe fatigue, cough, sore throat, and muscle aches. The elderly, young children and others with chronic health problems are at high risk for more serious influenza complications. Each year in the United States, between 5% and 20% of the population gets influenza, more than 200,000 are hospitalized for complications, and about 36,000 people die from influenza.