Epicrispr Biotechnologies Showcases GEMS Epigenetic Editors Data at ESGCT

Epicrispr Biotechnologies, a pioneer in the field of epigenetic editing, recently unveiled new findings on their advanced hypercompact platform for epigenetic editing at the European Society of Gene and Cell Therapy (ESGCT) 31st Annual Congress, held from October 22-25, 2024, in Rome. The company also shared data supporting its investigational therapy for facioscapulohumeral muscular dystrophy (FSHD) and announced plans to commence clinical trials of its leading candidate, EPI-321, in early 2025.

One of the highlights from the presentation was the in vitro study of a new epigenetic modulator designed to reactivate genes that have been silenced through epigenetic mechanisms. This innovative modulator, developed using Epicrispr's rational protein engineering, demonstrated the ability to reactivate a silenced gene to almost 100% of its original expression level, with sustained activity lasting over 75 days, equating to more than 150 cell divisions. This capability is critical in realizing the therapeutic benefits of programmable epigenetic editing.

Moreover, combining this modulator with Epicrispr's previously developed epigenetic activators in a single construct resulted in significantly enhanced gene activation, far surpassing what was achieved by using either component alone. This synergistic effect underscores the potential of Gene Expression Modulation System (GEMS) therapies to robustly reactivate genes to treat various diseases effectively.

The specifics of the presentations at the Congress were meticulously detailed. On October 24, Dan Hart presented a poster titled "Engineered ultracompact epigenetic editors for DNA and histone modifications enable durable epigenetic gene activation and suppression" during Poster Session III. Siddaraju Boregowda kicked off the presentations with "Preclinical data supporting efficacy and safety of EPI-321, an investigational epigenetic editing product treating FSHD" during Poster Session I on October 22. Another poster, "Preclinical in vitro and ex vivo evaluation of EPI-321, an investigational single-dose epigenome editing gene therapy, efficacy for facioscapulohumeral muscular dystrophy (FSHD) treatment," was presented by Abhinav Adhikari on October 24 during Poster Session IV.

EPI-321, the investigational therapy at the center of these presentations, is designed to address the root molecular causes of FSHD. It works by restoring methylation at the D4Z4 region on chromosome 4, effectively stopping the harmful expression of the DUX4 gene. This therapy is delivered to muscle tissue using a single AAV vector (AAVrh74), a method that has been validated in clinical settings for muscle delivery. Preclinical studies have shown that EPI-321 can significantly suppress the pathological expression of the DUX4 gene and decrease muscle cell death, which is a hallmark of FSHD.

Epicrispr Biotechnologies continues to leverage their Gene Expression Modulation System (GEMS), which includes the smallest Cas protein known to function in human cells, allowing for in vivo or ex vivo delivery through a single viral vector. While EPI-321 represents their lead program, the company is also working on developing therapies for other serious conditions like alpha-1 antitrypsin deficiency (A1AD) and heterozygous familial hypercholesterolemia (HeFH).

In summary, Epicrispr Biotechnologies is making significant strides in the field of epigenetic editing, with their latest data showing promising results for gene reactivation and potential therapies for FSHD and other genetic disorders. The company's commitment to pioneering non-cutting CRISPR technology and developing innovative therapeutic platforms positions them at the forefront of the epigenetic editing landscape.