NIAID-Sponsored Study Shows N-803 Combined with Neutralizing Antibodies Could Lead to Sustained HIV Viral Control After Discontinuation of Antiretroviral Therapy

ImmunityBio (NASDAQ: IBRX), a clinical-stage immunotherapy company, today announced the recent publication of preclinical data in the online issue of Science, First Release indicating that combination therapy with N-803, an IL-15 superagonist, and broadly neutralizing antibodies may potentially enable the immune system to manage human immunodeficiency virus (HIV) without the need for antiretroviral treatment.

In the preclinical non-human primate study, researchers led by Dr. James Whitney, Ph.D. and funded by the National Institutes of Health and the National Institute of Allergy and Infectious Diseases (NIAID) demonstrated that using N-803, in combination with broadly neutralizing antibodies (bNAbs), led to sustained viral control after discontinuation of antiretroviral therapy (ART) in ART-suppressed rhesus macaques infected with simian-human immunodeficiency virus AD8 (SHIV-AD8). Treatment with N-803 and bNAbs led to immune activation and transient viremia, but only limited reductions in the SHIV reservoir. Upon ART discontinuation, all animals experienced viral rebound, followed by long-term virus control for up to 10 months in approximately 70% of those treated with N-803 and bNAbs.

"The viral reservoir in people with HIV is established within the first few days of infection and cannot be eliminated by the body’s immune system or currently available treatments, representing a significant obstacle in curing an established HIV infection,” said James B. Whitney, M.D., study author and researcher at the Center for Virology and Vaccine Research at Beth Israel Deaconess Medical Center and Harvard Medical School. “When combined with broadly neutralizing antibodies, N-803 has the potential to provide viral control without significant reduction in the viral reservoir, which further suggests that the complete eradication of this reservoir may not be required to induce sustained remission after discontinuing antiretroviral therapy."

Following on from and directly attributable to these preclinical results, two clinical trials were designed to investigate the ability of N-803 and bNAbs to reduce viral loads in HIV-infected individuals on antiretroviral therapy. These Phase 1 clinical trials are investigating N-803 in combination with bNAbs in HIV-infected individuals and will include an analytical treatment interruption (ATI) to determine the effect of the immunotherapies on post therapy viral loads. (ACTG A5386, NCT04340596: and NCT05245292 at the Rockefeller University). The studies are actively enrolling participants.