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Inovio Pharmaceuticals HIV Immunotherapy Shows Characteristics Considered Vital to Treating HIV

INO, BIOGY | January 6, 2015

Phase I Trial Reveals DNA Immunotherapy Results Were Similar To HIV-Infected Patients Whose Disease Did Not Progress

PLYMOUTH MEETING, Pa., Jan. 6, 2015 /PRNewswire/ -- Inovio Pharmaceuticals, Inc. (NASDAQ: INO) announced today that results from a 12-patient phase I study of Inovio's HIV immunotherapy, PENNVAX^®-B, in HIV-infected patients revealed that immune response characteristics generated by the immunotherapy were similar to those observed in HIV-infected individuals who without treatment do not progress to further stages of the disease.

These extremely rare individuals who self-regulate their HIV infection are called "long-term non-progressors" and it is believed that part of their ability to control infection may lie in their unique immune responses. In this phase I study, Inovio's HIV immunotherapy, which had been previously tested only in disease prevention, drove the expansion of activated HIV-specific CD8+ T cells with functional characteristics similar to those of long-term non-progressors.

Results from this clinical study appeared in the peer-reviewed journal Molecular Therapy, in the article, "Synthetic consensus HIV-1 DNA induces potent cellular immune responses and synthesis of granzyme B, perforin in HIV infected individuals," authored by Inovio researchers and collaborators.

Dr. J. Joseph Kim, President & CEO of Inovio, said, "These results show the ability of our HIV immune therapy to activate HIV-specific CD8+ T cells in infected patients and the potential to go beyond virus control and reach into reservoirs of the infection to halt progression of HIV. Based on these initial results, Inovio plans to conduct a treatment-focused trial with its lead HIV vaccine, PENNVAX^®-GP, that broadly targets globally significant HIV strains. This therapeutic study will complement our planned phase I vaccine study of PENNVAX^®-GP in healthy subjects."

HIV targets the immune system, specifically CD4+ T cells, which are responsible for activating CD8+ killer T cells that can kill the virus and infected cells. Unfortunately, with fewer CD4+ and CD8+ T cells, most infected individuals are unable to fight the virus. Independent studies have shown, however, that some untreated HIV-infected individuals have controlled viral replication and are long-term non-progressors (up to 30 years). One reason this may occur is due to the presence of CD8+ T cells with particular functional characteristics. While today's commonly used antiviral drugs can control viral replication, they cannot eliminate the virus, their long term effect often diminishes, and they have other associated side effects and disadvantages. Immunotherapies capable of generating antigen (disease)-specific CD8+ killer T cells are therefore considered a promising avenue to achieve long term prevention, viral load control, and elimination of HIV.

Inovio's synthetic immunotherapy technology is very effective at generating disease-specific killer T cells in the body. In this phase I study, HIV-infected individuals whose viral load was already effectively suppressed (below detection level) using a highly active antiviral therapy (HAART) received a four-dose regimen of PENNVAX^®-B. Investigators observed that Inovio's HIV immunotherapy, which in a prior published study in healthy subjects generated best-in-class CD8+ T cell responses, significantly increased antigen-specific CD8+ T-cell responses in all patients.

The investigators also observed that the cell-killing substances granzyme B and perforin (both necessary to kill targeted cells and viruses) produced by activated CD8+ killer T cells were present in quantities and characteristics similar to those of long-term non-progressors. This result mirrors those of the previously published HIV study as well as those of Inovio's HPV immunotherapy, which also generated best-in-class functional T cells in a phase I study and achieved statistically significant clinical efficacy in a phase II study.

Another striking result of this HIV study was that PENNVAX^®-B increased the number of HIV-specific CD8+ killer T cells displaying the receptor integrin, which is associated with the ability to carry T cells to the gastrointestinal tract (GIT). The GIT hosts 40-65% of the body's total immune cells, hence is the most important target organ for HIV, which targets CD4+ T cells and hides in "gut mucosa." The increased presence of integrin suggests the potential of such an immunotherapy to better fight or eradicate these reservoirs of HIV infection in the GIT.

The therapy was well-tolerated and did not result in any adverse events.

About PENNVAX^® HIV Vaccines and Immunotherapies

Human immunodeficiency virus (HIV) is a retrovirus that causes acquired immunodeficiency syndrome (AIDS), a condition in which progressive failure of the immune system allows life-threatening opportunistic infections and cancers to thrive. HIV is classified into clades, sub-types within which the virus has genetic similarities. The most prevalent clades are B (found mainly in North America and Europe), A and D (found mainly in Africa), and C (found mainly in Africa and Asia).

Inovio completed initial clinical studies focused on its HIV immunotherapy PENNVAX®-B, targeting clade B viruses, to achieve proof of principle in generating potent immune responses using its SynCon® vaccine technology. In two published phase I studies, PENNVAX®-B administration has been shown to generate high levels of antigen-specific CD8+ T cells with proper functional characteristics. This ability to generate high level of activated CD8+ killer T cells uniquely positions PENNVAX® as an important product candidate for preventing and treating HIV infections.

Using a $25 million grant from the NIH, Inovio designed its multi-clade PENNVAX®-GP immunotherapy targeting viruses from clades A, B, C and D. PENNVAX®-GP is now Inovio's lead preventive and therapeutic immunotherapy.

A phase I clinical study of PENNVAX®-GP in a preventive setting is planned for the first half of 2015. A phase I clinical study of PENNVAX®-GP as an immune therapy is planned for the second half of 2015.

About Inovio Pharmaceuticals, Inc.

Inovio is revolutionizing the fight against cancer and infectious diseases. Our immunotherapies uniquely activate best-in-class immune responses to prevent and treat disease, and have shown clinically significant efficacy with a favorable safety profile. With an expanding portfolio of immune therapies, the company is advancing a growing preclinical and clinical stage product pipeline. Partners and collaborators include Roche, MedImmune, University of Pennsylvania, DARPA, Drexel University, NIH, HIV Vaccines Trial Network, National Cancer Institute, U.S. Military HIV Research Program, and University of Manitoba. For more information, visit 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, our expectations regarding our research and development programs 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 the studies or trials may not be successful or achieve the results desired, including safety and efficacy for VGX-3100, that pre-clinical studies and clinical trials may not commence or be completed in the time periods anticipated, 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, our ability to support our broad pipeline of SynCon® active immune therapy and vaccine products, our ability to advance our portfolio of immune-oncology products independently, including INO-5150, and to commence a phase I clinical trial for INO-5150 in the first half of 2015, 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, our ability to enter into partnerships in conjunction with our research and development programs, evaluation of potential opportunities, issues involving product liability, 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, 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, 2013, our Form 10-Q for the quarter ended September 30, 2014, 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.

CONTACTS:

Investors: Bernie Hertel, Inovio Pharmaceuticals, 858-410-3101, bhertel@inovio.com
Media: Jeff Richardson, Inovio Pharmaceuticals, 267-440-4211, jrichardson@inovio.com