- Data from the Phase 1 “HIV Cure” Study as published in Nature Medicine showed that Anktiva (N-803) stimulates latent HIV replication in CD4+ cells (the kick) and increases immune cell activation (the kill)
- Activated CD4, CD8, and NK immune cells are necessary for finding and killing HIV-infected cells
- No treatment-related serious adverse events were reported
- Multiple Phase 1 and 2 trials with Anktiva in patients with HIV are ongoing
- The need for this therapeutic approach is significant: Globally there are an estimated 38 million people living with HIV; in the US, with 1.2 million people living with HIV, the average annual cost of antiretrovirals is $36,000, while nearly $2 billion is spent on those therapies in developing countries1 & 2
ImmunityBio, Inc. (NASDAQ: IBRX), a clinical-stage immunotherapy company, today announced promising study results that demonstrate the activation of CD4+ and CD8+ T cells and natural killer (NK) cells in people living with HIV by ImmunityBio’s IL-15 superagonist Anktiva (N-803). Anktiva stimulates latent HIV replication (the “kick”) in CD4 memory cells allowing the previously hidden infected cells to be revealed and eliminated (the “kill”) by CD8 and NK cells. This mechanism is key for killing cells that harbor latent virus, thereby reducing viral reservoirs in antiretroviral (ART)-suppressed HIV patients and ultimately ridding the body of the virus and the threat of re-activation. These positive clinical findings support ImmunityBio’s “Kick-and-Kill” strategy to cure HIV.
The study was conducted by Timothy W. Schacker, M.D., a leading HIV researcher and Vice Dean for research at the University of Minnesota Medical School, and the results were published today in Nature Medicine. The goal of the Phase 1 study was to assess the effects of Anktiva on these viral reservoirs, along with safety and tolerability, as a precursor to larger human studies.
“Today there are 38 million people living with HIV in every corner of the world, and most of them depend on a daily cocktail of antiretroviral drugs to keep the virus at bay. These can cost thousands of dollars a month, a huge cost in wealthy countries and unaffordable for people in poorer nations,” said Patrick Soon-Shiong, M.D., Executive Chairman and Global Chief Scientific and Medical Officer at ImmunityBio. “This study is one of several ImmunityBio is undertaking to validate the potential role of Anktiva in activating the innate (NK) and adaptive (T cell) immune system to attack and kill cancerous or virus-infected cells. In this case, the target is HIV, and our ultimate goal is to develop our immunotherapy platforms of IL-15 fusion proteins combined with NK cell therapy as a therapeutic approach to rid the body of the virus for good and eliminate the need for antiretroviral therapy. The company is pursuing multiple studies in patients with HIV in hopes of meeting this goal of curing the disease.”
Study Adds to Existing Results
In both pre-clinical and clinical research, ImmunityBio’s IL-15 superagonist Anktiva has exhibited three activities that could potentially help the immune system eliminate HIV reservoirs and control virus rebound. First, Anktiva has been shown to reverse HIV latency—whereby genetic code for the virus persists, but virus is not made, allowing the infected cells to evade detection and elimination by the immune system—by stimulating HIV replication within long-lived immune cells such as memory CD4 cells, allowing the infected cells to be recognized and cleared. Second, it activates NK cells and CD8+ T cells, two elements of the immune system that specialize in killing virus-infected cells. Third, it enables NK cells and CD8+ T cells to move to lymphoid tissues where they will encounter and have an increased likelihood of eliminating HIV-infected cells.
Study Details (NCT02191098)
ART-suppressed individuals were enrolled into a dose-escalation study of N-803 in four different cohorts (0.3, 1.0, 3.0, and 6.0 mcg/kg). Each cohort received three doses total, separated by at least one week. The study enrolled 16 individuals, of which 11 completed all three doses. The maximum tolerated dose was 6.0 mcg/kg. The primary clinical adverse events (AEs) reported were an injection site rash and adenopathy and four participants experienced a grade 1 or 2 QTc prolongation, which was deemed unrelated to the N-803 administration. There were no significant laboratory AEs attributable to N-803. In exploratory analyses, N-803 was associated with proliferation and/or activation of CD4+ and CD8+ T cells, and NK cells, that peaked at four days post dosing. IFN, IP10, MCP-1, and IL-15 increased during treatment. HIV transcription in memory CD4 T cells and intact proviral DNA initially increased after N-803 treatment and there was a small but significant decrease in the frequency of PBMCs with an inducible HIV provirus that persisted for up to six months post therapy.
Additional HIV-related studies involving N-803
The ACTG A5386 trial is studying whether Anktiva can control HIV alone or together with combination broadly neutralizing antibodies (bNABs) after participants stop their antiretroviral therapy (ART) and they are carefully monitored. The “HIV Cure” study is sponsored by the National Institute of Allergy and Infectious Diseases (NIAID) and conducted by the AIDS Clinical Trials Group (ACTG), the largest global HIV research network.
A second study, which is in Phase 2, will evaluate Anktiva in combination with antiretroviral therapy during acute HIV infection. This study is being conducted by the Walter Reed Army Institute of Research’s U.S. Military HIV Research Program (MHRP) at the Thai Red Cross AIDS Research Centre in Bangkok. Both studies were announced in 2021.
ImmunityBio is a leading late-clinical-stage immunotherapy company developing next-generation therapies that drive immunogenic mechanisms for defeating cancers and infectious diseases. The company’s broad immunotherapy and cell therapy platforms—including Antibody cytokine fusion proteins, synthetic immunomodulators, vaccine technologies (hAd5 viral vector, mRNA, recombinant protein, and adjuvant), and genetically-modified, off-the-shelf natural killer cells (autologous and allogenic cytokine-enhanced memory NK cells)—activate both the innate (natural killer cell and macrophage) and adaptive (T cell) immune systems to create long-term “immunological memory.”
ImmunityBio’s clinical pipeline consists of 21 clinical trials—13 of which are in Phase II or III development—across 12 indications in solid and liquid cancers (including bladder, pancreatic, and lung cancers) and infectious diseases (including SARS-CoV-2 and HIV). Anktiva™, ImmunityBio’s lead cytokine infusion protein, is a novel interleukin-15 (IL-15) superagonist complex and has received Breakthrough Therapy and Fast Track Designations from the U.S. Food and Drug Administration (FDA) for BCG-unresponsive CIS non-muscle invasive bladder cancer (NMIBC).
The company has established GMP manufacturing capacity at scale with cutting-edge cell manufacturing expertise and ready-to-scale facilities, as well as extensive and seasoned R&D, clinical trial, and regulatory operations, and development teams. For more information, please visit: www.immunitybio.com.
- Clinton Health Access Initiative, 2021 HIV Market Report
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