A novel CAR-T cell therapy for the one-time treatment of chronic HIV infection in patients who are not ART suppressed

Abstract Building on our successful primate model studies, we aim to develop a one-time treatment for durable remission of human immunodeficiency virus (HIV) in the absence of antiretroviral therapy (ART). This targeted treatment is an autologous HIV-specific chimeric antigen receptor (CAR)-T cell therapy that employs a CXCR5 “homing device” to direct anti-viral killer T cells into B cell follicles where they can eliminate virus-producing cells. B cell follicles are a “hidden” immune protected site that permit viral replication due to low levels of virus-specific CD8 T cells. Our preclinical CAR/CXCR5-T cell pilot studies in a simian immunodeficiency virus (SIV)-infected rhesus macaque model of HIV indicate that this immunotherapy is safe and effective in ART-treated animals. Our funded STTR Fast Track grant proposed to investigate a similar therapeutic approach in chronically infected non-ART suppressed individuals. In phase I studies, we will modify our original CAR/CXCR5 DNA construct to confer optimized (opt)CAR/CXCR5-T cells with greater persistence, higher anti-viral binding affinity, and resistance to SIV/HIV infection. In Phase II, we will develop a GMP-scalable method to produce human optCAR/CXCR5-T cells for the first-in-human Phase 1 clinical trial, and this method will be used to produce rhesus macaques optCAR/CXCR5-T cells for use in an IND-enabling preclinical study. The IND-enabling study will assess the safety and efficacy of optCAR/CXCR5-T cells in an SIV model of chronic HIV infection. Here, we are proposing to participate in the I-Corp program with a team consisting of: 1) C-level Corporate Officer, Dr. Athanasiou; 2) Scientific Technical Expert, Dr. Sen; and (3) Industry Expert, Janet White. The team will be led by Maria Athanasiou, PhD, co-founder and CEO of MarPam and Principal Investigator on the Parent Award. Dr. Athanasiou has expertise in drug development, having led a team that developed an FDA approved drug for the treatment of depression, managed a $100 M budget, and provided key contributions to market research and marketing activities. Nandini Sen, PhD, Senior Scientist at MarPam, will participate as a technical expert. Having joined MarPam after working as a Senior Scientist at Stanford University, Dr. Sen brings her vast experience gained over a decade working in the laboratory of Dr. Ann Arvin, a renowned infectious disease expert at Stanford. Rounding out the team, Janet White is a seasoned executive and industry expert with over 35 years of experience in international life science companies. In addition to her proven track record for developing and implementing growth strategies and product development, she is a business adviser to entrepreneurs and early-stage companies through accelerator and mentoring programs. All team members are willing to commit at least 20 hours per week for the duration of the program and have a sincere desire to investigate the commercial landscape surrounding the innovation. This team and the company will benefit immensely from the I-Corps program and the MarPam C-level Corporate Officers are committed to incorporate the learnings from this market research to revise its commercialization strategy.