Waltham, MA and Durham, NC – April 25, 2023 – Life Edit® Therapeutics Inc., an ElevateBio® company focused on next-generation gene editing technologies and therapeutics, today announced the presentation of the first preclinical data from the company's Huntington's disease program across three presentations at CHDI’s 18th Annual Huntington’s Disease Therapeutics Conference taking place April 24-27, 2023, in Dubrovnik, Croatia.
Life Edit’s presentations underscore the ability of its gene editing platform to selectively target disease-associated genetic factors to treat life-threatening diseases. Huntington’s disease is an inherited neurodegenerative disorder caused by a mutation in the huntingtin gene as a result of a cytosine-adenine-guanine (CAG) trinucleotide expansion. This results in a mutant form of the huntingtin protein (mutHTT) that damages brain cells. Wild-type HTT protein is purported to be physiologically critical, hence selective editing of the mutant HTT (mutHTT) protein is necessary for therapeutic benefit.
Life Edit has generated new, small RGNs with expanded protospacer adjacent motif (PAM) diversity that can separately target both the T and C alleles of an exonic SNP in the HTT gene. The small size of Life Edit’s nucleases also enabled packaging and delivering in a single AAV vector. Life Edit evaluated preclinical development candidates in clinically relevant YAC128 and BACHD transgenic murine disease models that contain a full-length human mutant HTT gene. AAV5-delivered Life Edit gene editing systems enabling allele-specific targeting of mutant HTT demonstrated dose-response reductions in striatal mutHTT protein with clinically meaningful reductions of >50% observed. Dose-dependent increases in insertions and deletions (INDELs) correlated with reductions in mutHTT levels. High vector copy numbers were detected in the striatum and cortex up to 12-weeks post injection (furthest time point tested). These results support continued evaluation and identification of a development candidate.
"These exciting preclinical data underscore the enormous therapeutic potential of our gene editing systems to deliver a life-transforming therapy for patients suffering from Huntington’s disease, a debilitating genetic disease with no approved therapies," said Mitchell Finer, Ph.D., Chief Executive Officer, Life Edit Therapeutics, and President, R&D, ElevateBio. "The PAM diversity of Life Edit's proprietary RNA-guided nucleases allows us to target virtually any genomic site, including those enabling editing of both T and C SNP alleles as demonstrated in these data. Our mission to make any edit, anywhere possible can transform how we approach new treatments for the most challenging genetic disorders.”
Date and Time: Tuesday, April 25, 2023: 11:55 a.m. – 12:20 p.m. CEST
Session 1: DNA Structure-Function of mHTT: Pathogenesis and Opportunities for Intervention
Presentation Title: Allele-selective SNP editing utilizing AAV5-delivered Life Edit nuclease and guide RNA resulting in meaningful reduction of mutant HTT protein
Date and Time: Wednesday, April 26, 2023; 1:00 p.m. – 2:30 p.m. CEST
Poster #16: Group A: Huntingtin Lowering
Poster Title: Allele selective SNP editing utilizing AAV5-delivered Life Edit nuclease and guide RNA resulting in meaningful reduction of mutant HTT protein
Date and Time: Wednesday, April 26, 2023; 1:00 p.m. – 2:30 p.m. CEST
Poster #26: Group A: Huntingtin Detection/Quantification
Poster Title: Mutant and wildtype huntingtin protein quantitation utilizing automated capillary electrophoresis
Life Edit's gene editing platform offers a large and diverse library of RNA-guided nucleases (RGNs), base editors, and reverse transcriptase editors, making it one of the most flexible gene editing technology platforms available. The RGNs are smaller in size when compared to conventional nucleases, potentially enabling greater versatility for delivery. Life Edit's nuclease collection features a range of Protospacer Adjacent Motifs (PAMs), short sequences that determine the DNA segments in the genome to which a nuclease can bind. The diversity of Life Edit's PAM collection offers unprecedented access to the genome to treat and cure genetic diseases.
The platform has achieved several key milestones over the past year, including the generation of new base editors and RNA-guided nucleases with expanded PAM diversity towards making any edit, anywhere possible. Additionally, the platform has demonstrated multiplex base editing of up to five genes, simultaneous knock-in/knock-out in primary T-cells, and in vivo editing in the liver and brain.
"Next-generation gene editing capabilities are central to our ecosystem as we power the cell and gene therapy industry," said David Hallal, Chairman and Chief Executive Officer of ElevateBio. “Our partners recognize the immense value of our library of novel genome editing systems and its potential to enable them to develop a broad array of advanced therapies. Our recent technology advancements will help us to further power the Life Edit gene editing platform, support our partners, and selectively build out our pipeline of innovative therapeutic candidates."
Life Edit Therapeutics, an ElevateBio company, is a next-generation genome editing company that has built a highly innovative platform with one of the world's largest and most diverse collections of novel RNA-guided nucleases (RGNs) and base editors. The platform allows Life Edit to target any genomic sequence and develop novel human therapeutics for the most challenging genetic diseases by enabling ex vivo engineering for cell therapies and regenerative medicines and in vivo delivery of gene therapies. In addition to developing its own pipeline of cell and gene therapies, Life Edit Therapeutics will continue to strengthen its platform of genome-editing enzymes, provide gene editing expertise to strategic partners, and form other third-party partnerships to discover and develop new therapies.
ElevateBio is a technology-driven company built to power the development of transformative cell and gene therapies today and for many decades to come. The company’s integrated technologies model offers turnkey scale and biotechnological capabilities to power cell and gene therapy processes, programs and companies to their full potential. The ElevateBio ecosystem combines multiple R&D technology platforms – including Life Edit, a next-generation, full-spectrum gene editing platform; a proprietary induced pluripotent stem cell (iPSC) platform; and an RNA, cell, protein, and vector engineering platform – with BaseCamp®, its end-to-end genetic medicine cGMP manufacturing and process development business, to power the discovery and development of advanced therapeutics.
In addition to enabling a broad breadth of biopharmaceutical companies in the development of their novel cell and gene therapies, ElevateBio is also building a highly innovative pipeline of cellular, genetic, and regenerative medicines. ElevateBio aims to be the dominant engine inside the world’s greatest scientific advancements harnessing human cells and genes to alter disease. For more information, visit us at www.elevate.bio, or follow Elevate on LinkedIn, Twitter, or Instagram.