Inovio achieves strong T cell immune responses in PENNVAX-B Phase I HIV study

Inovio Pharmaceuticals, Inc. (NYSE Amex: INO)  announced today that it has achieved strong T cell immune responses in a Phase I clinical study of PENNVAX®-B, its product for the treatment of the HIV subtype prevalent in North America and Europe, in HIV-positive subjects. These interim results were presented by Dr. Niranjan Y. Sardesai, Inovio's Chief Operating Officer, at the Vaccine World Summit 2012 in Hyderabad, India in a talk titled, "New Development Paradigms and Vaccine Innovation for Infectious Diseases."

"We are particularly excited by the positive interim results of the HIV-001 study in HIV-positive subjects. This data is a first for DNA vaccines by yielding robust T cell immune responses in people chronically infected with HIV. Even though the HIV viral load of these volunteers was suppressed and brought under control by antiretroviral drugs, their immune systems are not normal and would typically have difficulty generating strong T cell responses to any immune stimulating approach. Coupled with positive data from two earlier trials, Inovio's results demonstrate the potency of our synthetic vaccine technology platform and raises the potential for the development of therapeutic vaccines against HIV and other chronic infections," said Dr. J. Joseph Kim, Inovio's President and CEO. "Together with our HIV prophylactic vaccine programs in collaboration with our partners at DAIDS and HVTN, this HIV therapy trial highlights our commitment to addressing one of the foremost global health issues of our time."

The HIV-001 open label, Phase I study enrolled 12 adult HIV-positive volunteers to assess safety and levels of immune responses generated by Inovio's PENNVAX®-B vaccine delivered with its CELLECTRA® electroporation device. PENNVAX®-B consists of SynCon® immunogens targeting HIV gag, pol, and env proteins from HIV subtype B commonly found in North America and Europe.

Study volunteers were required to be on a highly active antiretroviral therapy (HAART) regimen, have undetectable plasma viral load (<75 copies/mL), and have CD4 T lymphocyte counts above 400 cells/µL with nadirs over 200 cell/µL. Twelve (12) eligible subjects were administered a four dose series (day 0, weeks 4, 8 and 16) of PENNVAX®-B containing 3 mg of DNA/dose via intramuscular electroporation.

The study was sponsored by Inovio Pharmaceuticals and conducted at the University of Pennsylvania Medical Center. Dr. Pablo Tebas, Professor of Medicine and Director of AIDS Clinical Trials Unit (ACTU) of the University of Pennsylvania, is the Principal Investigator of the HIV-001 study.

All 12 subjects completed the four dose vaccination regimen. There were no significant adverse events or vaccine related grade 3 or 4 adverse events noted in the study and the vaccine was found to be generally well tolerated. Reported injection site reactions were mild to moderate and did not require treatment to resolve. T-cell responses were measured using a validated ELISpot assay at the U Penn Immunology Core Facility.

Overall, significant vaccine-specific T-cell responses were observed in 75% (9 out of 12) of subjects against at least one of the three vaccine antigens (gag. pol, or env) following vaccination. Fifty percent of the subjects (6 out of 12) had strong vaccine induced antigen-specific responses above the pre-vaccination levels to at least two of the antigens. Importantly, the responses induced by vaccination were predominantly antigen-specific (i.e. gag, pol and env) CD8+ T-cells, which are considered to be paramount in clearing chronic viral infections and an important measurement of the performance of a therapeutic vaccine. These results are in stark contrast to previously reported studies with other DNA vaccines delivered without electroporation that yielded poor overall T cell immune responses.

According to the Joint United Nations Programme on HIV/AIDS (UNAIDS), nearly 30 million people have died from HIV-related causes and roughly 34 million are living with HIV. Although a highly active antiretroviral therapy (HAART) regimen has dramatically transformed the treatment of the disease in developed countries, effective HIV vaccines are needed to stop the spread of disease and perhaps reduce the need for antiretroviral treatments, which generally have harsh side effects and which in many cases lose their efficacy over time. Inovio's PENNVAX®-B HIV vaccine is unique in the field in that it is designed to be used for both treatment and prevention.

Inovio previously reported best-in-class T cell immune responses to the PENNVAX®-B vaccine in healthy adults in a preventive setting. In that study (HVTN-080), three doses of the vaccine delivered together with an IL-12 cytokine plasmid via electroporation resulted in over 89% of the vaccinated subjects mounting an antigen-specific CD4+ or CD8+ T cell response against at least one of the vaccine antigens. The HIV-001 study did not include the IL-12 cytokine plasmid. Inovio plans to further study the impact of cytokines as well as the impact of therapeutic vaccination on HIV viral load in future clinical trials.