HIV

HIV Gag-Specific, Lentivirus Modified CD4 T Cells for HIV Functional Cure

Status of the Clinical Trial

On August 11, 2020, AGT announced approval by the FDA to begin Phase 1, the first human clinical trial for AGT’s lead HIV program. AGT will conduct its Phase 1 study at clinical sites in the Baltimore/D.C. area. AGT expects that these sites will begin enrollment in the Fall of 2020.

AGT's Phase 1 study clinicaltrials.gov identifier number is NCT04561258 and the study ID is AGT-HC168. For information about the ongoing Phase 1 study of AGT103-T, and information on the trial sites, click the button below.

How AGT103-T Is Intended to Work

CEO Jeff Galvin Provides an Overview of AGT’s HIV Functional Cure Project

A Technical Overview of AGT103-T

Chief Science Officer C. David Pauza, Ph.D. Reviews the Science Behind the Program

The worldwide epidemic of HIV/AIDS caused immeasurable suffering and challenged the biomedical community to create treatments for this devastating disease. A robust response from researchers and pharmaceutical companies led to the development of potent therapies capable of controlling HIV. These treatments were the first medicines designed to slow a viral disease and were proven to extend life span for infected individuals. Despite the remarkable impact on HIV, even decades of treatment failed to cure the disease. The HIV infection rebounds quickly when treatment is interrupted or viral drug resistance arises, and no amount of conventional therapy has overcome this problem. Despite improvements in the medications, it is time for new treatment strategies aimed at eliminating the dependence on antiretroviral therapy. We believe these treatments can rebuild key components of immunity and provide lifelong suppression of HIV with protection against future re-infection. The challenge of rebuilding natural immunity is the inspiration for AGT’s program to develop next generation therapies for HIV disease. Our strategies use the tools of genetic medicine and depend on our deep understanding of key features in HIV disease.

Finding the Achilles Heel of HIV Infection

Many viruses cause short term disease and leave behind a protective immune “memory”. Vaccines mimic this natural event by artificially triggering potent immune responses that will remain as memory for months to years, then reappear and control the infection after a natural virus exposure. For many years researchers have worked toward creating a vaccine against HIV that would trigger natural immunity and prevent infection similar to other vaccines that are critical tools for public health. Sadly, this effort has not yet been successful.

The key to vaccine failure is HIV’s preference for infecting and killing helper T cells, also known as CD4 T cells. True to their designation as “helpers”, these T cells are among the first to respond against new virus infections and they retain a memory of that response. For example, months to years after flu vaccination, any new exposure to the influenza virus activates the memory CD4 T cells and sparks the development of protective immunity and resistance to flu. These influenza-specific CD4 T cells are key to vaccine protection and must be maintained at high levels for months to years after immunization to be ready for quick and potent activation of the protective immune response.

In HIV disease, the HIV-specific CD4 T cells are activated soon after infection similar to other viral diseases. However, HIV targets these cells for destruction because this insidious virus binds to the same CD4 molecule that identifies the helper T cell subset. HIV infection, HIV-specific CD4 T cells are compromised soon after infection, eventually falling below the levels needed to support effective immunity. By that point, only antiretroviral medication is effective for controlling HIV, and infected individuals who seek treatment begin a daily drug regimen that must be continued without interruption for life.

This single feature of HIV disease, that virus depletes the HIV-specific CD4 T cells helper, explains why HIV comes roaring back after years of effective therapy if the treatment is stopped. A key piece of natural immunity to HIV is missing and there is no immune control of the virus.

AGT’s Plan for Immunotherapy of HIV

Our plan is simple. If the HIV-specific CD4 T cells are missing and this explains why treatment must be continued for life, we should replace the missing cells with new ones. When a person has enough of the HIV-specific memory CD4+ cells, natural immune control of HIV should be restored.

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Manufacturing of specific T cells is used increasingly to make treatments for infectious diseases and cancer. In most cases, the processes are straightforward and cells are highly effective after injecting back into the person suffering from disease. A new industry is springing up around the need for cell manufacturing and is providing automation of highly efficient cell processing for T cell-based products. In most cases, specific cells are purified, grown to large numbers outside the body, then injected back in as a living cell therapy using the person’s own cells so there is no risk of rejection.

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AGT is using a process similar to what others are doing but critical changes were needed to generate an HIV therapy. Were we to purify HIV-specific CD4 T cells, grow them to high numbers and inject them back into the body, we would be adding fresh target cells for the virus, in essence adding fuel to the fire. We needed an extra step to protect new cells from infection so that the effects of treatment would be long-lasting and not destroyed by future exposure to HIV. The extra step was to create a viral vector capable of introducing protective genes into the HIV-specific CD4 T cells. Total T cells are purified from blood and stimulated to grow the HIV-specific CD4 T cells which are treated with viral vector (lentivirus vector AGT103) to protect them against HIV infection and destruction. The lentivirus vector inserts genes for HIV protection into the chromosomal DNA of each cell. This process creates a permanent modification capable of reducing cell surface expression of CCR5 protein (a co-receptor for HIV attachment/entry) and attacking HIV RNA in the regions known as Vif or Tat viral genes.

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Manufacturing Cell Products for Treatment of HIV Disease

We developed a highly efficient, cost-effective process for manufacturing large numbers of HIV-specific cells, modifying them with lentivirus vector AGT103, and infusing them back into the body as a single dose, autologous cell therapy. Three key features of the AGT103-T product are:

The lentivirus vector modifies HIV-specific CD4 T cells and: prevents infection by CCR5- or CXCR4-tropic strains of HIV; reduces depletion of CD4 T cells during exposure to HIV; and prevents a latently-infected cell from releasing new HIV virus particles

The process for cell manufacturing is reliable and consistent; this is important for supporting clinical trials

AGT103-T starts with about 1 million HIV-specific CD4 T cells obtained from blood and, by the end of production, delivers about 1 billion HIV-specific CD4 T cells with most of them modified by the AGT103 lentivirus vector

HIV Cell Product Process

By achieving this high dose of HIV-specific CD4 T cells that are protected from attack by HIV, we expect this treatment to reconstitute the immune system and restore an ability to make antiviral immune responses for natural control of HIV. Our upcoming human clinical trials are the first step in testing this concept.

Status of the Clinical Trial

On August 11, 2020, AGT announced approval by the FDA to begin Phase 1, the first human clinical trial for AGT’s lead HIV program. AGT will conduct its Phase 1 study at clinical sites in the Baltimore/D.C. area. AGT expects that these sites will begin enrollment in the Fall of 2020.

AGT's Phase 1 study clinicaltrials.gov identifier number is NCT04561258 and the study ID is AGT-HC168. For information about AGT103-T Phase 1 study, its status, and the clinical site information, view it on clinicaltrials.gov by clicking the button below.

Our Commitment to Developing New Treatments for HIV

Our company is developing genetic medicines for unmet medical needs. First among our priorities is a treatment for HIV that restores natural control of viremia and reduces dependence on antiretroviral therapy. We believe natural virus control will be effective and will reduce the costs and side-effects inherent in life-long use of antiretroviral medication. Please see below, the views of our Chief Science Officer David Pauza, and one of our clinical advisors Dr. Ely Benaim, regarding the importance of AGT’s program for HIV therapy.

Learn Why AGT's Chief Science Officer Is Determined To Cure HIV

Watch The Video Testimony

Dr. David Pauza Video

Learn Why Dr. Ely Benaim Believes In AGT

Watch The Video Testimony

These Two HIV+ Clinical Trial Participants Believe In HIV Cure Research

Watch Their Video Testimony

Our Broader Team of HIV Experts and Advisors

AGT has assembled outstanding internal and external teams who are collaborating to develop this program.

HIV Science Advisory Board

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Shyamasundaran Kottilil, MBBS, PhD

University of Maryland,
School of Medicine

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W. David Hardy, MD, AAHIVS

Johns Hopkins University, School of Medicine

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Ely Benaim, MD

Chief Medical Officer,
Novocure

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John J. Rossi, PhD

Ad Hoc Member

City of Hope,
Duarte, California

Dr. David Pauza

C. David Pauza, PhD

Chief Science
Officer

AGT Analyst Day on HIV Program at The Harvard Club in NYC

Last month American Gene Technologies(AGT) was at the Harvard Club in NYC for Analyst Day on AGT’s HIV Cure project. AGT’s IND is submitted and the FDA is reviewing it. Learn more about HIV treatment and AGT’s unique approach to a potential cure.

American Gene Technologies HIV Cure Program Patents

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Patent No. 10,233,464
HIV pre-immunization and immunotherapy

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Patent No. 10,036,038
HIV pre-immunization and immunotherapy

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Patent No. 10,494,647
HIV pre-immunization and immunotherapy