This dose escalation study is designed to test the safety and immunogenicity of VGX-3400X. VGX-3400X consists of three distinct DNA plasmids containing a universal consensus hemagglutinin (HA) antigen derived from different H5N1 flu viruses; a universal consensus neuraminidase (NA) antigen encompassing different N1 subtypes such as H5N1 and H1N1; and a universal consensus nucleoprotein (NP) fused to a small portion of the m2 protein (m2E), both also encompassing N1-based viruses. The clinical trial will be conducted at two sites in the U.S. Thirty healthy subjects will be enrolled in three dose groups of 0.2 mg, 0.67 mg, and 2.0 mg of each plasmid delivered via Inovio's proprietary electroporation technology. The primary objectives are to assess safety and tolerability. The secondary objective is to measure antigen-specific antibody and cellular immune responses, in particular hemaglutination inhibition (HI) responses, i.e. a measure of protection, against multiple strains of H5N1 influenza. The company expects to report study results in Q1 2011.
Inovio's SynCon(TM) universal influenza vaccine approach provides "universality" on two levels: within and across different subtypes. SynCon(TM) DNA vaccine "constructs" are designed to provide broad cross-reactive protection against the many existing and potential new strains within each influenza subtype, such as H5N1. Across subtypes, the universal influenza vaccine approach provides protection by combining SynCon(TM) DNA vaccine constructs for targeted subtypes currently posing risk to humans (i.e. H1N1, H2N2, H3N2, and H5N1) to form a single combination vaccine. Cross-reactive protection against multiple unmatched strains has been established in previously reported animal studies and will now be assessed in this Phase I clinical study. Success in this clinical study would allow advancement into clinical studies of SynCon(TM) influenza DNA vaccines encompassing H5N1 and H1N1, and subsequently additional subtypes, to further assess the universal influenza vaccine approach in humans.
Influenza Vaccines for the Future
Dr. J. Joseph Kim, Inovio's President and CEO, said: "We have already demonstrated protection against multiple unmatched as well as newly emergent strains using combination SynCon(TM) vaccines for different influenza subtypes in multiple pre-clinical studies. These studies also indicated that our SynCon(TM) vaccines induced antigen-specific immune responses far exceeding levels that have been correlated with protection in humans. We look forward to human data from this trial and advancing this potentially paradigm-shifting vaccine approach."
As previously published in PLoS ONE, a peer-reviewed, online publication, in an article entitled, "Heterosubtypic Protection against Pathogenic Human and Avian Influenza Viruses via In Vivo Electroporation of Synthetic Consensus DNA Antigens," Inovio's SynCon(TM) H5N1 (avian) influenza DNA vaccine has been shown to provide broad protection against divergent strains of H5N1 influenza in mouse, ferret, and non-human primate models. Responses in all three species demonstrated the ability of SynCon(TM) antigens to induce antibodies capable of providing cross-protection from divergent strains of the H5N1 subtype. In additional testing, ferrets and mice vaccinated with the SynCon(TM) antigens were 100% protected from a lethal influenza challenge, with a concomitant significant reduction in viral shedding and disease progression in the vaccinated animals.
While this first human clinical study is focused on the H5N1 based vaccine, Inovio has also previously demonstrated the efficacy of other components of its SynCon(TM) universal vaccine in relevant animal models. In pre-clinical studies of Inovio's SynCon(TM) H1N1 flu vaccine, vaccinated mice were all protected from the unmatched 1918 "Spanish" H1N1 influenza and did not suffer weight loss. Additionally, ferrets immunized with the vaccine were 100% protected against death and sickness in a challenge with the unmatched A/H1N1 (2009) swine-origin influenza.
About Inovio's SynCon(TM) Universal Influenza Vaccines
Vaccines provide protection against a virus by introducing to the immune system proteins, or antigens, uniquely associated with a virus. The immune system recognizes these antigens as being foreign and mounts a protective response. Unfortunately, conventional influenza vaccines can only provide protection when there is a substantial match with the genetic makeup of the circulating virus strain(s) -- and only one to three specific strains can be included in the vaccine. Therefore current vaccines have limited ability to protect against genetic shifts of the influenza virus within a subtype and no ability to protect against influenza strains from other subtypes. As a result, a new vaccine is created each year to match the anticipated strain(s) of the next flu season. If a significantly different new strain emerges, such as the 2009 H1N1 ("swine flu") strain, then the vaccine will provide little or no protective capability.
Inovio's synthetically derived SynCon(TM)DNA-based influenza vaccines are intended to provide broad protection against unmatched -- known as well as newly emerging, unknown -- seasonal and pandemic influenza strains. Inovio's scientists have designed separate DNA vaccine constructs representing a consensus of the genetic makeup of HA, NA, and m2E-NP proteins from multiple strains of influenza subtypes H1N1, H2N2, H3N2, which are responsible for the majority of the last century's seasonal and pandemic influenza outbreaks, as well as H5N1, which has affected very few humans but been highly lethal to those infected. Animal data shows that Inovio's DNA constructs, which do not match any single influenza strain, provide protection against viruses sharing genetic roots within subtypes. By creating a single vaccine that combines constructs from some or all of the key subtypes, broad protection may be achieved against a multitude of seasonal as well as pandemic strains such as "swine flu" or pandemic-potential strains such as avian influenza.
About Inovio Pharmaceuticals, Inc.
Inovio is developing a new generation of vaccines, called DNA vaccines, to treat and prevent cancers and infectious diseases. The company's SynCon(TM) "universal" vaccines are designed to provide broad cross-strain protection against known as well as newly emergent strains of pathogens such as influenza. When delivered with Inovio's proprietary electroporation delivery devices the vaccines have been shown to be safe and to generate significant immune responses. Inovio's clinical programs include HPV/cervical cancer (therapeutic), avian flu, and HIV vaccines (both preventive and therapeutic). Inovio is developing its universal influenza vaccines in collaboration with scientists from the University of Pennsylvania and National Microbiology Laboratory of the Public Health Agency of Canada. Other partners and collaborators include Merck, ChronTech, University of Southampton, National Cancer Institute, HIV Vaccines Trial Network, and Malaria Vaccine Initiative/PATH. More information is available at www.inovio.com.
This press release contains certain forward-looking statements relating to our business, including our plans to develop electroporation-based drug and gene delivery technologies and DNA vaccines and our capital resources. Actual events or results may differ from the expectations set forth herein as a result of a number of factors, including uncertainties inherent in pre-clinical studies, clinical trials and product development programs (including, but not limited to, the fact that pre-clinical and clinical results referenced in this release may not be indicative of results achievable in other trials or for other indications, that results from one study may not necessarily be reflected or supported by the results of other similar studies and that results from an animal study may not be indicative of results achievable in human studies), the availability of funding to support continuing research and studies in an effort to prove safety and efficacy of electroporation technology as a delivery mechanism or develop viable DNA vaccines, the adequacy of our capital resources, the availability or potential availability of alternative therapies or treatments for the conditions targeted by the company or its collaborators, including alternatives that may be more efficacious or cost-effective than any therapy or treatment that the company and its collaborators hope to develop, evaluation of potential opportunities, issues involving patents and whether they or licenses to them will provide the company with meaningful protection from others using the covered technologies, whether such proprietary rights are enforceable or defensible or infringe or allegedly infringe on rights of others or can withstand claims of invalidity and whether the company can finance or devote other significant resources that may be necessary to prosecute, protect or defend them, the level of corporate expenditures, assessments of the company's technology by potential corporate or other partners or collaborators, capital market conditions, our ability to successfully integrate Inovio and VGX Pharmaceuticals, the impact of government healthcare proposals and other factors set forth in our Annual Report on Form 10-K for the year ended December 31, 2009, our Form 10-Q for the three months ended March 31, 2010, and other regulatory filings from time to time. There can be no assurance that any product in Inovio's pipeline will be successfully developed or manufactured, that final results of clinical studies will be supportive of regulatory approvals required to market licensed products, or that any of the forward-looking information provided herein will be proven accurate.
SOURCE: Inovio Pharmaceuticals, Inc.
