Inovio Pharmaceuticals, has announced that its academic and industry collaborators received a multi-year $6.95 million grant from the NIH’s National Institute of Allergy and Infectious Diseases to develop a single or combination therapy using Inovio’s Pennvax-GP with the goal of attaining long-term HIV remission in the absence of antiviral drugs.

Although current antiretroviral therapy can reduce the amount of circulating HIV in the blood to an undetectable level, latent cellular reservoirs of HIV continue to exist in the body such that when therapy is discontinued, these cells begin to produce HIV again. This proof-of-concept clinical program will test whether enhancing anti-HIV specific CD8 killer T cell immune responses alone or in combination with other products can influence the size of the viral reservoir pool, potentially resulting in reducing or eradicating the virus.

This is a two-step clinical study in HIV-positive subjects to assess Inovio’s HIV immunotherapy Pennvax-GP with INO-9012 (an IL-12 immune activator) alone and with the addition of a PD-1 checkpoint inhibitor.

All trials will be randomized, double-blind, placebo-controlled assessments of Pennvax-GP. They will be conducted at the University of California in San Francisco and Los Angeles.

PD-1 checkpoint inhibitors have proven effective in treating cancer and may have a role in the management of chronic infectious diseases. This trial seeks to demonstrate that an in vivo immunotherapy combining a PD-1 inhibitor and Pennvax-GP will enhance the CD8 killer T cell response to HIV infected cells.

Development of Inovio’s Pennvax-GP immunotherapy, which widely targets multiple major clades of HIV — providing global coverage — has been funded through a $25 million NIAID contract awarded to Inovio and its collaborators. In addition, Inovio and its collaborators were awarded a five-year $16 million Integrated Preclinical/Clinical AIDS Vaccine Development (IPCAVD) grant in 2015 from NIAID.

Pennvax-GP is currently being studied in a phase I trial (HVTN-098) to evaluate safety and immunogenicity in 94 healthy volunteers. In this study, Pennvax-GP is being evaluated as a preventive vaccine. The newly funded study will assess the impact of this vaccine approach in a therapeutic setting.

Steven G. Deeks, MD, the grant and clinical trial’s Principal Investigator, and Professor of Medicine in Residence at the University of California, San Francisco, said, “There is growing recognition that we will need to generate powerful CD8+ T cells that target vulnerable regions of the virus and which can migrate to the tissues where the virus hides. The preliminary data from other Inovio-sponsored studies makes me enthusiastic that this vaccine might fill an important niche in future curative strategies.”

Dr. J. Joseph Kim, Inovio's president and chief executive officer, said, "We are thrilled to receive this NIH funding to test the combination of Inovio’s HIV immunotherapy with a PD-1 inhibitor. Similar to what we are doing in the cancer field with INO-3112 and INO-5401, we believe that the one-two punch of generating potent killer T cells with our immunotherapies combined with PD-1/PDL-1 checkpoint therapies could be an important step in generating functional cure for these diseases.”