Developing an HIV Cure With Gene Therapy: AGT103-T

A Life Without HIV

Addimmune™ is Changing the Way We Treat HIV

Addimmune is building on the gene therapy research pioneered by American Gene Technologies®, so that one day HIV may no longer be a lifelong sentence
— but a curable illness.

Only Targeting Diseased Cells

Addimmune's gene therapy allows us to "edit" a cell's operating system (its DNA) to insert or delete commands, targeting diseased cells while avoiding healthy tissue.

We no longer have to just imagine a world without HIV. We believe it could be a reality.

Gene Therapy is the Future

Gene therapy enables us to develop more specific and directed treatments and cures with fewer side effects because the drugs target diseased cells and avoid healthy tissue. Addimmune is making great progress in our ongoing clinical trial where we are testing a gene therapy treatment that could potentially cure HIV.

HIV depletes the HIV-specific CD4 T cell responsible for a potent immune response, necessitating lifelong antiretroviral therapy. If the depleted cells are replaced by durable T cells, natural immune control of HIV should be restored.

Rationale for AGT103-T

The 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 being injected back into the person suffering from a 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.

HIV infection depletes virus-specific CD4 T cells that are not reconstituted despite years of ART.

The critical CD4 T cell subset is the Gag-specific CD4 T call population (around 10-4 frequency in persons with chronic, progressive HIV and virus suppressed by ART).

Elite controllers (EC) and long-term non-progressors (LTNP) are distinguished by much higher levels of Gag-specific CD4 T cells.

Our gene therapy raises Gag-specific CD4 T cell levels in patients with chronic, progressive disease and mimics the condition of EC and LTNP individuals.

Reconstituted Gag-specific CD4 T cells may support durable immunity to HIV and reduce or eliminate the need for ART.

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Patented Lentivirus Vector AGT103-T

AGT103-T is intended to give CD4 T cells the ability to survive attack by HIV and support effective antiviral immune response.

Efficient transduction of primary CD4 T cells

Blocks HIV infection by CCR5- and CXCR4-tropic viruses

Prevents HIV replication in latently infected reservoir cells

Manufacturing Cell Products to Treat HIV

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

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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.

Three Key Features of the AGT103-T Product Are:

1
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.
2
The process for cell manufacturing is reliable and consistent; this is important for supporting clinical trials.
3
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-T lentivirus vector.

HIV Clinical Trial Progress

Addimmune completed our Phase 1 clinical trial and we have submitted the final report to the FDA. In the meantime, we are designing the Phase 2 clinical trial protocol and working to identify manufacturers and trial sites.

Seven patients received AGT103-T and have experienced no serious adverse events, thereby demonstrating the therapy’s safety.

Blood markers in the treated patients have provided a view into how the cell therapy is responding in their bodies.

So far, the data has confirmed that the cells are properly engrafting, persisting, and seem to be remaining uninfected while reacting to, and likely fighting, HIV the way scientists expected.