Inovio achieves best-in-class immune responses in PENNVAX-B HIV vaccine Phase I study

Inovio Pharmaceuticals, Inc. (NYSE Amex: INO), a leader in the development of synthetic immunogens against cancers and infectious diseases, announced today that it has achieved best-in-class immune responses in a Phase I clinical study of PENNVAX™-B, its product for the prevention of the HIV sub-type prevalent in the US and Europe. These end of study results were presented at the AIDS Vaccine Conference in Bangkok, Thailand.

Dr. Spyros Kalams, Associate Professor of Medicine Vanderbilt University Medical Center and principal investigator of Vanderbilt's HIV Vaccine Trials Unit and of this clinical study, said, "These data show for the first time that HIV-specific immune responses may be enhanced with DNA and a plasmid cytokine adjuvant (IL-12) delivered via electroporation. The results of this study represent a significant advance for the ability of a DNA based vaccine to generate high levels of immune responses against HIV antigens and is transformative for DNA vaccination."

The HVTN-080 Phase I study enrolled 48 healthy, HIV-negative 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. This randomized, double-blind, multi-center study was sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), an agency of the National Institutes of Health, and conducted by the NIAID-funded HIV Vaccine Trials Network (HVTN) at several clinical sites.

Of the 48 total volunteers, eight subjects received a placebo, 10 subjects received a 3 mg dose (1 mg dose of each of three DNA plasmids – gag, pol, env) of Inovio's SynCon® PENNVAX™-B vaccine, and 30 subjects received a 3 mg dose of PENNVAX™-B along with 1 mg of GENEVAX™IL-12 DNA. All volunteers received vaccine or placebo administered via intramuscular injection with electroporation at months 0, 1, and 3. The T-cell immune responses were detected using a validated flow cytometry-based intracellular cytokine staining (ICS) assay at the HVTN core immunology laboratory at the Fred Hutchinson Cancer Research Center (Seattle, WA).

These data indicate that antigen-specific T-cell responses were generated by the vaccine in a majority of subjects. Overall, either CD4+ or CD8+ or both T-cell responses were observed against at least one of the vaccine antigens in 83.3% (30 of 36) of evaluated subjects after three vaccinations using electroporation. The response rate increased to 88.9% (24 of 27) of evaluated subjects after three vaccinations with electroporation plus the IL-12 cytokine gene adjuvant. The investigators in this study concluded that PENNVAX™-B + IL-12 plasmid delivered via electroporation led to frequencies and magnitudes of cellular immune responses equal to or greater than those reported from current vector-based HIV vaccines such as adenovirus or traditional DNA vaccination without electroporation. Further trials delivering an HIV DNA vaccine using electroporation with or without IL-12 as a vaccine strategy are merited.

Specifically, after three vaccinations with the PENNVAX™-B vaccine given with IL-12 and electroporation:

• Antigen-specific CD4+ T-cell responses were generated by the vaccine in 80.8% of evaluated vaccine recipients (21 of 26).
• Significantly strong antigen-specific, CD8+ T-cell responses were also generated by the vaccine in 51.9% of evaluated vaccine recipients (14 of 27).
• In an assessment of immune response durability out to six months post dose 3, 53.6% (15 of 28) of the subjects maintained positive CD4+ T-cell responses and 42.9% (12 of 28) of the subjects maintained positive CD8+ T-cell responses out to six months.
• Compared to the previously conducted HVTN 070 Phase I study, which assessed PENNVAX™-B with cytokine adjuvant IL-12 at double the dose, with four vaccinations, but without electroporation delivery, response rates in HVTN 080 with electroporation were significantly higher for both CD4+ responses (40.7%) and CD8+ T cell responses (3.6%).
• Samples from eight placebo recipients and pre-vaccine samples from vaccine recipients were also tested and were negative for both CD4+ T-cell responses and CD8+ T-cell responses.
• PENNVAX™-B delivered using the CELLECTRA® intramuscular electroporation delivery device with or without IL-12 was safe and generally well tolerated. There were no vaccine-related serious adverse events. Reported adverse events and injection site reactions were mild to moderate and required no treatment.

Dr. J. Joseph Kim, Inovio's President and CEO, said: "We are excited by the final results of the HVTN-080 study. These data are consistent with the previously announced interim results and unequivocally demonstrate the impact electroporation has on improving the immune potency of DNA vaccination. We appreciate the close collaboration with the NIH DAIDS and HVTN groups to systematically evaluate the immunogenicity of DNA immunogens together with cytokine adjuvants and delivery systems. We look forward to a continuing fruitful partnership with the HVTN and the DAIDS/NIH to further develop our HIV vaccine products to the next level."