CRISPR-Editing EBT-101 Therapy Safe, Temporarily Suppresses HIV Infection


Excision is evaluating a higher dose in a second cohort as well as exploring alternative, potentially redosable, delivery methods.

Excision BioTherapeutics’ EBT-101-001 phase 1/2 trial (NCT05144386) of EBT-101 CRISPR-based gene editing therapy has met its primary safety endpoint and its secondary biodistribution/immunogenicity endpoint.1

Data from the trial were presented at the American Society of Gene & Cell Therapy (ASGCT) 27th Annual Meeting, held May 7 to 10, 2024, in Baltimore, Maryland by principal investigator Rachel M. Presti, MD, PhD, Professor of Medicine, Washington University School of Medicine, St. Louis.

“Initial data from the EBT-101-001 trial provides important clinical evidence that a gene editing treatment modality can be safely delivered for targeting the HIV DNA reservoirs in human cells. This study provides researchers with invaluable insights for how CRISPR technology can be applied for addressing infectious disease and was an important first step towards additional programs designed to optimize this treatment modality for treating the millions of individuals who are impacted by HIV and other infectious disease,” Presti said in a statement.2

Investigators observed no serious adverse events (AEs), grade 1 AEs related to the therapy, and grade 1 or 2 AEs that resolved without treatment. Of the 5 participants who received a single infusion of the initial dose of EBT-101, 3 stopped antiretroviral therapy, experienced viral rebound, and had to restart antiretrovirals. One participant maintained viral suppression for 16 weeks after treatment discontinuation.1

“We know that many people were hopeful that a first trial could provide evidence of a possible cure for HIV because the field has been waiting over 20 years for a cure. However, it was essential that this clinical trial establish safety for EBT-101 as a gene therapy product as well as safety related to the use of CRISPR for the field,” William Kennedy, MD, Senior Vice President, Clinical, Excision, added.2

EBT-101-001 is a first in human, open-label, sequential cohort, single ascending dose study enrolling adults with HIV-1 on stable antiretroviral therapy (ART). The trial is primarily assessing the safety and tolerability of a single dose of EBT-101 in study participants with undetectable viral load on ART. The secondary endpoint is assessing EBT-101 biodistribution and immunogenicity. Excision is evaluating a higher dose of EBT-101 in a second cohort as well as exploring new delivery methods, including lipid nanoparticles, which would allow redosing of the therapy.

“Evaluating any new molecular entity begins by first and foremost assessing participant safety, and this is particularly true when exploring the potential of new treatment modalities such as CRISPR-based therapeutics,” Daniel Dornbusch, Chief Executive Officer, Excision, added.2

Excision also presented data on other CRISPR-based editing candidates for other latent infections. In a preclinical study evaluating EBT-104, a CRISPR-editing therapy for herpes simplex, investigators found that a single dose of therapy reduced Herpes Virus DNA by over 99.99% in Vero cells and nearly eliminated (11 out of 12) viral shedding in the rabbit keratitis model. In another preclinical study on EBT-107, a CRISPR-editing therapy being developed for hepatitis B, investigators found that a single dose of a lipid nanoparticle delivered CRISPR compound reduced HBV DNA by 98%, HBsAg (s-antigen) by 97%, and HBeAg (e-antigen) by 92 in a mouse model of HBV.

1. Presti RM. EBT-101: First-in-human clinical trial of systemic CRISPR-Cas9 multiplex targeting of latent HIV. Presented at: ASGCT 27th Annual Meeting, May 7-10; Baltimore, Maryland. Poster #2122
2. Excision BioTherapeutics Announces Data from the Phase 1/2 Trial of EBT-101 in HIV And In Vivo Efficacy Data in Herpes Virus and Hepatitis B. News release. Excision BioTherapeutics. May 13, 2024.
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