The biotech Harness Therapeutics has announced it has nominated HRN001 as its lead drug candidate for Huntington's Disease (HD).
The UK-based company has also established a clinical advisory board to support the programme's progress toward clinical evaluation.
The programme targets somatic CAG-repeat expansion, a key driver of disease progression. This differs from other current approaches, which instead look to lower huntingtin levels.
Despite significant advances in understanding HD disease biology, no disease-modifying treatments are currently approved. HD is caused by the expansion of CAG repeats in the huntingtin (HTT) gene.
Ongoing somatic expansion of these repeats is now recognised as a key driver of disease onset and progression.
FAN1 nuclease has emerged as a compelling target for suppressing somatic expansion, with the strongest genetic association with disease onset in genome-wide association studies.
The first-in-class candidate HRN001 is a potent and specific antisense oligonucleotide targeting FAN1, designed to drive controlled upregulation of this key DNA repair nuclease.
It leverages Harness's proprietary MISBA (microRNA site-blocking ASO) platform, which the company states enables precise upregulation of target protein levels without the risk of overexpression.
HRN001 has demonstrated robust upregulation of FAN1 and slowing of somatic expansion in HD models, as well as favourable PK and tolerability characteristics.
Preclinical development will continue throughout 2026 to support clinical entry in 2027. Harness is exploring the potential of the MISBA platform in other triplet repeat disorders and across a broader pipeline of neurodegenerative disorders.
To support the progression of HRN001 towards the clinic, Harness has established a clinical advisory board (CAB) comprising leading experts in the HD field.
The CAB will provide strategic guidance on clinical development, trial design and translational strategy as the programme advances towards the clinic.
Dr Jan Thirkettle, CEO of Harness Therapeutics, commented: "The nomination of HRN001 represents a pivotal milestone for Harness and underscores our commitment to the Huntington's disease community."
"By precisely upregulating FAN1, 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."
"The formation of a Clinical Advisory Board brings deep clinical and translational expertise to the programme. The CAB will work closely with Harness as we advance HRN001 towards the clinic and seek to deliver a truly disease-modifying therapy for patients and families living with Huntington's disease."
Dr Irina Antonijevic, Chair of Harness Therapeutics' Clinical Advisory Board, added: "FAN1 is one of the most compelling and consistently validated genetic modifiers of Huntington's disease identified to date, with a clear mechanistic link to somatic expansion and disease progression."
"Harness's approach with HRN001 offers a novel and highly targeted way to therapeutically modulate this pathway."
"We look forward to advising the Company, as it advances HRN001 toward the clinic, translating this promising science into a clinical programme that could meaningfully alter the course of this devastating disease."