Harness Therapeutics Advances First-in-Class Huntington's Disease Drug HRN001 Toward Clinical Trials
核心洞察
Harness Therapeutics (搜索) has nominated HRN001, a first-in-class antisense oligonucleotide targeting FAN1 (搜索) nuclease, as its lead drug candidate for Huntington's disease (搜索) treatment.
The company established a clinical advisory board comprising seven leading Huntington's disease (搜索) experts to guide HRN001's progression toward first-in-human studies planned for 2027.
HRN001 leverages Harness' proprietary MISBA® platform to precisely upregulate FAN1 (搜索) protein levels, addressing somatic expansion which drives Huntington's disease (搜索) progression.
Harness Therapeutics (搜索) announced the nomination of HRN001 as its lead drug candidate for Huntington's disease (搜索) and the formation of a clinical advisory board to support the program's advancement toward clinical evaluation. The Cambridge, UK-based biotechnology company plans to initiate first-in-human studies in 2027.
HRN001 represents a first-in-class therapeutic approach targeting FAN1 (搜索) nuclease, a genetically validated target in Huntington's disease (搜索). The antisense oligonucleotide is designed to drive controlled upregulation of FAN1, which has emerged as one of the most compelling targets to suppress somatic expansion—a key driver of disease onset and progression.
Novel Mechanism Addresses Disease Driver
Huntington's disease (搜索) is caused by the expansion of CAG repeats in the huntingtin (搜索) (HTT (搜索)) gene, with ongoing somatic expansion now recognized as a fundamental driver of disease onset and progression. FAN1 (搜索) nuclease has demonstrated the strongest genetic association to disease onset in genome-wide association studies, making it an attractive therapeutic target.
HRN001 leverages Harness' proprietary MISBA® (microRNA site blocking ASO) platform, which enables precise upregulation of target protein levels without risk of over-expression. In preclinical studies, HRN001 has demonstrated robust upregulation of FAN1 (搜索) and slowing of somatic expansion in models of Huntington's disease (搜索), as well as favorable pharmacokinetic and tolerability characteristics.
"By precisely upregulating FAN1 (搜索), a target with compelling genetic validation in delaying disease onset, HRN001 represents a differentiated, first-in-class therapeutic approach for addressing somatic expansion, a fundamental driver of disease progression," said Dr. Jan Thirkettle, CEO of Harness Therapeutics (搜索).
Expert Advisory Board Established
To support HRN001's progression toward the clinic, Harness has established a clinical advisory board comprising seven leading experts in the Huntington's disease (搜索) field. The board is chaired by Dr. Irina Antonijevic, Chief Medical Officer at Trace Neuroscience (搜索), and includes prominent researchers from Cardiff University, University of Iowa Health Care, George-Huntington-Institute (搜索), University of Cambridge, and University College London.
"FAN1 (搜索) is one of the most compelling and consistently validated genetic modifiers of Huntington's disease (搜索) identified to date, with a clear mechanistic link to somatic expansion and disease progression," said Dr. Antonijevic. "Harness' approach with HRN001 offers a novel and highly targeted way to therapeutically modulate this pathway."
The clinical advisory board will provide strategic guidance on clinical development, trial design, and translational strategy as the program advances toward clinical evaluation.
Addressing Significant Unmet Need
Huntington's disease (搜索) is a devastating, inherited neurodegenerative disorder that leads to progressive cognitive, psychiatric and motor decline, with death often occurring within 15 years of symptom onset. Despite significant advances in understanding the disease biology, there are currently no approved disease-modifying treatments available.
Preclinical development of HRN001 will continue throughout 2026 to support clinical entry in 2027. Harness is also exploring the potential of the MISBA® platform in other triplet repeat disorders and across a broader pipeline of neurodegenerative disorders, including programs addressing targets for ALS (搜索), Alzheimer's disease (搜索), and Parkinson's disease (搜索).
Scientific Presentation Planned
Dr. Andy Billinton, Chief Scientific Officer of Harness Therapeutics (搜索), will present the company's work in Huntington's disease (搜索) at the upcoming annual CHDI Huntington's Disease Therapeutics Conference in Palm Springs, California, February 23-26. The presentation, titled "Upregulation of FAN1 (搜索) with ASOs as a potential therapeutic strategy for triplet repeat disorders," will provide further insights into the scientific rationale and development progress for HRN001.
The company's investors include Takeda Ventures (搜索), SV Health Investors' Dementia Discovery Fund, Epidarex Capital, and Ono Ventures Investment.