-  LETI-101 has demonstrated therapeutically relevant reductions of mutant huntingtin (HTT) protein, exceeding 80%, while preserving essential wild-type HTT in a clinically relevant Huntington’s disease mouse model

-  Administration of LETI-101 in nonhuman primates was well-tolerated and showed the potential for therapeutically relevant nuclease and guide RNA expression across critical brain regions affected by Huntington's disease

-  LETI-101 results and regulatory feedback support advancement into clinical development through ElevateBio’s partnership business model

WALTHAM, Mass., Feb. 24, 2025 (GLOBE NEWSWIRE) -- ElevateBio, a technology-driven company focused on powering the creation of life-transforming genetic medicines, announced the presentation of new preclinical data from LETI-101, the Huntington's disease (HD) program developed by its gene editing and R&D technology business, ElevateBio Life Edit. LETI-101 combines Life Edit's proprietary CRISPR nuclease with AAV5 delivery to selectively target the T allele of an exonic SNP in the HTT gene to treat HD. In preclinical studies, LETI-101 has demonstrated selective reduction of disease-causing mutant huntingtin (mHTT) protein, supporting its selection as Life Edit’s lead development candidate. These data will be presented at the 20th Annual Huntington's Disease Therapeutics Conference being held February 24-27, 2025, in Palm Springs, CA.

LETI-101 has demonstrated robust, therapeutically relevant reductions of mHTT protein levels exceeding 80% in a clinically relevant Huntington's disease transgenic mouse model (BACHD), while preserving wild-type protein, which is essential for cellular functions and physiological health. LETI-101 was well-tolerated with a no observed adverse effect level (NOAEL) obtained for the highest evaluated dose in nonhuman primates (NHPs). Additionally, Life Edit has gained alignment on a CMC and development path with the UK’s Medicines and Healthcare Products Regulatory Agency (MHRA), further supporting its continued development as a potential therapy for HD.

“The advancement of LETI-101 validates our gene editing technology and showcases ElevateBio's ability to power the development of genetic medicines. Combination of our robust tech stack at Life Edit and end-to-end manufacturing capabilities at BaseCamp enables us to add value throughout the entire drug development lifecycle,” said David Hallal, Chairman and CEO of ElevateBio. “The progression of LETI-101 from concept to a partnership-ready development candidate poised to begin IND-enabling studies demonstrates the potential of this integrated approach, connecting technology, manufacturing, and therapeutics to change the future of medicine.”

Huntington’s disease is a rare, inherited, neurodegenerative genetic disorder that affects motor function and leads to behavioral symptoms and cognitive decline in mid-adulthood, resulting in physical and mental deterioration. HD is 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, which aggregates within the brain, causing damage to neurons and leading to progressive neurodegeneration.

Life Edit has demonstrated the ability to selectively target disease-associated genetic factors to treat life-threatening diseases. The Company's extensive collection of nucleases with diverse protospacer adjacent motifs (PAMs) – short DNA sequences required for nuclease binding that determine where gene editing can occur – enables precise targeting of specific genetic sequences, making this selective approach possible. In addition, these potent nucleases are easily packaged into an AAV delivery vector due to their small size.

"The compelling preclinical results being presented along with recent favorable feedback from the UK’s MHRA represent significant milestones in advancing LETI-101 as we explore partnership opportunities to accelerate the program’s progress," said Tedd Elich, Ph.D., Chief Scientific Officer at Life Edit. "Our unique approach to selectively target the mHTT protein while preserving wild-type is a clear example of the value of our diverse PAMs and robust collection of nucleases and demonstrates the broader capabilities of our platform to address other challenging genetic diseases."

Preclinical studies evaluating LETI-101 have demonstrated:

• Dose-dependent editing of the targeted mHTT exon 50 site, leading to potentially therapeutically relevant reductions of mHTT protein in the striatum, cortex, and thalamus at clinically relevant dose levels evaluated in BACHD transgenic mice
• Bilateral intrastriatal administration of LETI-101 in NHPs was well-tolerated with a NOAEL obtained for the highest evaluated dose
• Therapeutically relevant vector copy number and nuclease and guide expression were observed across brain regions that are critically vulnerable in HD
• No change in immune response to the nuclease and minimal systemic vector distribution were observed

These data will be presented in a poster presentation titled "AAV5-delivered Life Edit CRISPR system results in broad CNS biodistribution and allele selective editing and reduction of mutant HTT protein in critical HD brain regions" at the Huntington's Disease Therapeutics Conference on Wednesday, February 26, 2025, at 1 p.m. PT.

About ElevateBio
ElevateBio is a technology-driven company built to power transformative genetic medicines today and for many decades to come. The Company commercializes its enabling technologies, manufacturing capabilities, and industry-leading expertise through partnerships to accelerate development across a breadth of therapeutic approaches and modalities. The ElevateBio ecosystem combines Life Edit, its gene editing and R&D technology business – which includes a full-spectrum gene editing platform, cell and RNA engineering technologies, and a viral and non-viral therapeutic delivery platform – with BaseCamp^®, its end-to-end genetic medicine cGMP manufacturing and process development business, to accelerate the discovery and development of advanced therapeutics.

ElevateBio aims to be the dominant engine inside the world’s greatest scientific advancements harnessing human cells and genes to alter disease. For more, visit www.elevate.bio or follow ElevateBio on LinkedIn or X.

Investor contact:
Catherine Hu
chu@elevate.bio

Media contact:
DJ Webster
dwebster@elevate.bio

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