E25: Jeff Galvin, CEO of Addimmune on Finding a Cure for HIV

Episode Summary

Executive Summary: Jeff, CEO of Adimmune, discusses the potential of gene and cell therapy, particularly for HIV. He details the company's phase one trial of AGT103, a gene therapy that showed safety and promising efficacy signals, including an effective immune response in six out of six patients during an analytical treatment interruption. Jeff also shares his personal journey from tech to biotech, drawing parallels between computing and programmable biology.

Main Topics: Gene and Cell Therapy Revolution: Jeff explains the concept of gene therapy using the metaphor of an 'organic computer,' where viruses are used as vectors to deliver therapeutic genes. He highlights the potential to cure diseases by modifying DNA at its root. HIV Mechanism and Challenges: Jeff describes HIV as a '007 super spy' virus that integrates into the host DNA and infects CD4+ T cells, the 'generals' of the immune system, making it difficult for the body to mount an effective immune response. AGT103 Gene Therapy for HIV: The therapy aims to knock out the CCR5 receptor on T cells, making them resistant to HIV, inspired by the 'Berlin patient' cure. Phase one results showed safety and efficacy signals. Phase One Trial Results: Seven patients were treated with AGT103, showing zero serious adverse events. Blood markers indicated engraftment, persistence, and functionality of modified T cells. Analytical Treatment Interruption (ATI) Study: Six patients underwent ATI, showing characteristics of an effective immune response: stable CD4 counts and rising CD8 counts. Four patients had a second ATI with multi-log reductions in viremia. Jeff's Background and Journey: Jeff shares his early passion for technology, teaching at MIT as a teen, working at Apple, and eventually retiring before being drawn back to biotech by the potential of gene therapy. Future Plans and Call to Action: Adimmune plans a 24-patient study to gain statistical power. Jeff encourages listeners to learn about gene therapy and consider contributing to the field.

Key Arguments: Gene therapy is a revolution in pharmaceuticals that can cure diseases by modifying DNA, analogous to how software controls computers. HIV is a uniquely insidious virus that integrates into host DNA and disables the immune system's command structure (CD4+ T cells). AGT103, a gene therapy that knocks out the CCR5 receptor, has shown safety and promising efficacy in phase one trials, including effective immune responses during treatment interruption. The success of the 'Berlin patient' (cured via bone marrow transplant from a CCR5-negative donor) provides a proof-of-concept for this approach. Gene and cell therapies, while initially expensive, offer high value by providing cures rather than just treatments, potentially reducing long-term healthcare costs.

Data Points: Patients treated in phase one: 7 - HIV patients on antiretrovirals treated with AGT103. Serious adverse events: 0 - No serious adverse events observed in phase one. Patients showing effective immune response in first ATI: 6 out of 6 - All six patients who underwent analytical treatment interruption showed characteristics of an effective immune response. Patients agreeing to second ATI: 4 out of 6 - Four patients agreed to a second treatment interruption. Viremia reduction in second ATI: Multi-log reductions - All four patients in the second ATI showed marked reductions in viral load. Approved gene and cell therapies: 30 - Number of approved gene and cell therapies currently on the market. People with HIV in North America and Europe: 5 million - Estimated number of people living with HIV in these regions.

Pivotal Quotes: "What we saw was zero serious adverse events. So that's about as good as you can do in safety." — Jeff (CEO of Adimmune): Describing the safety results of the phase one trial for AGT103. "Boy, did they! Six out of six patients, okay, showed what looks like the characteristics of an effective immune response." — Jeff (CEO of Adimmune): Describing the results of the analytical treatment interruption study. "We're going to start curing disease. Diseases with gene and cell therapy." — Jeff (CEO of Adimmune): Expressing the transformative potential of gene and cell therapy.

Implications: AGT103 could offer a functional cure for HIV, reducing lifelong antiretroviral dependence. Success would validate gene therapy for infectious diseases, potentially transforming HIV treatment and inspiring similar approaches for other chronic viral infections.