Excision BioTherapeutics Reports Phase 1/2 EBT-101 Data in HIV and Efficacy in Herpes Virus, Hepatitis B

Excision BioTherapeutics, Inc., a clinical-stage biotechnology firm focused on developing CRISPR-based treatments for latent viral infectious diseases, shared groundbreaking updates from multiple studies during the American Society of Gene and Cell Therapy (ASGCT) meeting. The company's HIV program marked a significant milestone as the first in vivo CRISPR-based systemic treatment evaluated in a U.S. clinical trial.

The EBT-101-001 clinical study was an open-label trial aimed at evaluating the safety and tolerability of systemically administered CRISPR therapy. Daniel Dornbusch, Excision's Chief Executive Officer, emphasized the importance of assessing participant safety when introducing new molecular entities, especially innovative treatment modalities like CRISPR-based therapeutics.

The primary goal of the EBT-101-001 study was to ensure the safety and tolerability of the CRISPR-based treatment. Secondary objectives included evaluating biodistribution and immunogenicity. William Kennedy, M.D., Senior Vice President at Excision, highlighted the necessity of establishing EBT-101's safety as a gene therapy product and the use of CRISPR technology within the field.

Rachel M. Presti, M.D., Ph.D., from Washington University School of Medicine in St. Louis and a Principal Investigator of the Phase 1/2 trial, noted that initial data from the EBT-101-001 trial provided critical clinical evidence demonstrating that a gene editing treatment could be safely administered to target HIV DNA reservoirs in human cells. This study offers invaluable insights for researchers seeking to apply CRISPR technology to infectious diseases, representing a vital step towards optimizing this treatment approach for millions impacted by HIV and other infectious diseases.

Key findings from the EBT-101 clinical trial were promising, with no serious adverse events reported. Only grade 1 adverse events were associated with the therapy. All adverse events, whether associated with the therapy or not, were either grade 1 or 2 and resolved spontaneously without treatment.

In preclinical studies, EBT-104, a CRISPR-based therapy, demonstrated remarkable efficacy in reducing Herpes Virus DNA by over 99.99% in Vero cells and significantly diminished viral shedding in a rabbit keratitis model. Furthermore, EBT-107, another CRISPR-based therapy, showed substantial reductions in Hepatitis B DNA and biomarkers in a mouse model of Hepatitis B. A single dose of lipid nanoparticle (LNP)-delivered CRISPR compound reduced HBV DNA, HBsAg (s-antigen), and HBeAg (e-antigen) by 98%, 97%, and 92%, respectively. The LNP delivery method allows for potential re-dosing to achieve therapeutic target efficacy.

Dr. Jennifer Gordon, Senior Vice President of R&D at Excision, expressed her excitement over the significant and diverse advancements made by the Excision Research and Development team. She underscored the power and potential of CRISPR-based therapies in treating viral infectious diseases.

The EBT-101-001 Clinical Study is a First in Human trial, characterized by an open-label, sequential cohort, single ascending dose design. It involves the intravenous administration of EBT-101 to HIV-1 infected adults on stable antiretroviral therapy (ART). The primary measure of success was to assess the safety and tolerability of a single dose of EBT-101 in participants with undetectable viral loads on ART. The secondary measure involved evaluating EBT-101 biodistribution and immunogenicity.

Excision BioTherapeutics, Inc. is dedicated to developing CRISPR-based medicines aimed at curing serious chronic viral infectious diseases. Their proprietary multiplexed gene editing platform combines next-generation CRISPR nucleases with a novel gene-editing approach, targeting large, underserved markets including herpes virus (HSV-1 and HSV-2), hepatitis B virus (HBV), and human immunodeficiency virus-1 (HIV-1). The company's foundational technologies were developed in collaboration with Dr. Kamel Khalili at Temple University and Dr. Jennifer Doudna at the University of California, Berkeley.