Inovio Pharmaceuticals’ (INO) Optimized DNA Vaccine Demonstrates Significant Advantages

BLUE BELL, Pa.–(BUSINESS WIRE)–Inovio Pharmaceuticals, Inc. (NYSE Amex: INO), a leader in the development of therapeutic and preventive vaccines against cancers and infectious diseases, announced today that the peer-reviewed journal Molecular Therapy has published a paper entitled “Comparative Analysis of Immune Responses Induced by Vaccination With SIV Antigens by Recombinant Ad5 Vector or Plasmid DNA in Rhesus Macaques.” The paper, co-authored by researchers from Merck, University of Pennsylvania School of Medicine, and Inovio Pharmaceuticals, notes that significant advances in the design, formulation, and delivery of DNA plasmid-based vaccines have dramatically increased their ability to induce antigen-specific immune responses. In this head-to-head comparison with an adenovirus serotype 5 (Ad5) vaccine considered to be the most immunogenic among viral vectors, Inovio’s optimized SynCon™ DNA vaccine delivered using its proprietary electroporation technology demonstrated numerous advantages in both magnitude and breadth of immune responses produced in non-human primates.

Compared to Ad5, the SynCon™ DNA vaccine resulted in:

• Significantly stronger antigen-specific cellular immune responses, in particular CD8+ T cells. T cells are considered instrumental in clearing cancerous or infected cells from the body. Such responses are therefore imperative to achieving sufficient potency in new vaccines against cancers and chronic infectious diseases such as HIV and hepatitis C virus. Importantly, Ad5 immunizations failed to boost immune responses following the first immunization, whereas immune responses from DNA vaccination were continually boosted even after four immunizations.
• Increased breadth of T cell-based immune responses. CD4+ and CD8+ T cell immune responses produced with DNA vaccination were broader and produced multiple immune molecules called cytokines (IFNγ, IL-2, TNF-α, and CD107a). Broad immune responses are considered an important potential marker for vaccine efficacy.
• Immune responses that were long-lasting and maintained at high levels.

Dr. David Weiner, Professor, Department of Pathology & Laboratory Medicine and Chair, Gene Therapy and Vaccines Program at the University of Pennsylvania, and the lead author of the paper, commented: “While Ad5 is particularly potent after a single immunization, its apparent susceptibility to pre-existing immune responses is a concerning limitation. We were pleased to see the superior magnitude and quality of immune responses generated by Inovio’s SIV DNA vaccine delivered using electroporation. Moreover, the ability of this technology to continuously boost immune responses after multiple immunizations is an accomplishment that bodes well for the application of this vaccine platform for diseases requiring strong T cell responses, such as HIV, hepatitis C virus, and cancers.” Dr. Weiner is also chairman of Inovio’s scientific advisory board.

Dr. J. Joseph Kim, Inovio’s CEO and also a co-author of the paper, said: “This study highlights that Inovio’s DNA vaccine platform has achieved levels of immune responses previously not achievable and is playing an important role in further advancing this important new generation of vaccines. These results have more recently been supported by the human data reported from our HPV clinical trial, which demonstrated unprecedented levels of cellular and humoral (antibody) responses.”

Inovio’s PENNVAX™-B HIV vaccine is currently being tested in two separate Phase I clinical studies (preventive and therapeutic settings). Inovio is developing two additional globally targeted HIV vaccine candidates, PENNVAX™-G and PENNVAX™-GP, in a collaboration with the US Military HIV Vaccine Research Program and via a multi-year $23.5 million NIAID HIV vaccine development contract, respectively.

SynCon™ DNA Vaccine vs. Ad5 Study Details

Previous studies demonstrated that the most potent recombinant vector system for induction of cellular immune (T cell) responses in macaques and humans is adenovirus serotype 5 (Ad5). However, an Ad5 based vaccine tested in one of the largest HIV clinical trials to date, the Step Study, was halted due to a lack of efficacy. New vaccine approaches must produce more potent immune responses to have a better prospect of succeeding in the clinic. This study compared Merck’s Ad5 SIV vaccine (SIVmac239 gag, nef, and pol immunogens) and Inovio’s optimized electroporation-delivered SIV DNA vaccine (consensus macSIV gag, env, and pol immunogens) in macaques. SIV, the HIV equivalent in non-human primates, is considered an important pre-clinical model for HIV vaccine development. The study compared previously optimized doses and immunization conditions for the two SIV vaccines: animals receiving the Ad5 vaccine were immunized three times; DNA-vaccinated animals were immunized up to four times. The researchers assessed magnitude and quality of the cellular responses induced by each approach. This study was funded in part by a grant from the Division of AIDS, National Institute of Allergy and Infectious Diseases (NIAID).

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™ “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 http://cts.businesswire.com/ct/CT?id=smartlink&url=http%3A%2F%2Fwww.inovio.com&esheet=6336027&lan=en-US&anchor=www.inovio.com&index=1&md5=0007ce70c2f78d805e01e20d1da08040.

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.