Precision BioSciences Presents Preclinical Data Highlighting PBGENE-PMM as a Potential Therapy for Primary Mitochondrial Myopathy

Precision BioSciences, Inc. (Nasdaq: DTIL), an advanced gene editing company utilizing its novel proprietary ARCUS platform to develop in vivo gene editing therapies for sophisticated gene edits, including gene elimination, insertion, and excision, today announced a poster presentation highlighting new data for the Company’s PBGENE-PMM program, evaluating an ARCUS nuclease as a potential treatment for m.3243-associated primary mitochondrial myopathy (PMM). These data are being presented at the Mitochondrial Medicine – Therapeutic Development Annual Conference, being held from March 18-20, 2024 in Hinxton, UK.

“Today’s data from our PBGENE-PMM program further validate our work with ARCUS and continue to demonstrate its ability to make precise edits while avoiding off-target activity,” said Jeff Smith, PhD, Chief Research Officer of Precision BioSciences. “We believe ARCUS is uniquely suited for editing mitochondrial DNA due to its ability to discriminate a single nucleotide difference, making it ideal for editing point mutations such as m.3243. PBGENE-PMM is designed to eliminate mutant mitochondrial DNA leaving normal functioning wild-type mitochondrial DNA intact to repopulate the cell, resulting in a shift in heteroplasmy and improvement in mitochondrial function.”

Smith continued, “Additionally, ARCUS can cross mitochondrial membranes in order to access the mitochondrial DNA. This is possible because ARCUS is a protein-only editor with both recognition and catalytic activity all in one single protein that does not require a guide-RNA. This is not possible for CRISPR-derived editors such as CRISPR-Cas, Base and Prime editors. We look forward to advancing PBGENE-PMM towards clinical readiness this year and anticipate filing a CTA and/or IND submission in 2025.”

Details for the presentation are as follows:

Title: Shifting m.3243A>G heteroplasmy with PBGENE-PMM: Gene editing therapy for primary mitochondrial myopathy
Poster: P22
Presenter: Wendy Shoop, PhD, Research Lead, Precision Biosciences
Date and Time: Tuesday, March 19, 2024, 6:00-7:00 PM GMT
Location: Hinxton Hall Conference Centre, Wellcome Genome Campus, U.K.

In preclinical work presented today, ARCUS demonstrated highly selective elimination of mutant m.3423G mtDNA. PBGENE-PMM, which contains both a mitochondrial targeting sequence and a nuclear export signal, was found to localize exclusively to mitochondria and without any detectable off-target editing in the nuclear genome. As the m.3243A>G mutation only differs from the wild-type sequence by a single nucleotide, PBGENE-PMM was optimized to prevent cutting of wild-type mtDNA while maintaining activity against mutant mtDNA. When evaluated in cells that contain heteroplasmic m.3243A>G mtDNA, PBGENE-PMM-treated cells were found to contain 0.3% mutant mtDNA three days post-transfection, compared to control cells which contained 95% mutant mtDNA. This robust shift in heteroplasmy resulted in a nearly two-fold increase in both basal and maximal respiration. Together, these data support the development of PBGENE-PMM as a single-treatment, in vivo gene editing therapeutic for m.3243-associated primary mitochondrial myopathy.