Harness Therapeutics has named HRN001 as its lead Huntington’s disease drug candidate and set out plans to advance the programme towards clinical trials.
Huntington’s disease is an inherited neurodegenerative condition that causes progressive problems with movement, thinking and mental health, with death often occurring within 15 years of symptoms starting. There are currently no approved disease-modifying treatments.
The condition is caused by expansion of CAG DNA repeats in the huntingtin gene. Continued expansion of these repeats within cells is now recognised as a key driver of disease onset and progression.
HRN001 is designed to increase levels of FAN1, a DNA repair protein that has shown the strongest genetic association with delayed disease onset in genome-wide studies.
By boosting FAN1, the therapy aims to suppress further repeat expansion and slow disease progression.
The drug is a first-in-class antisense oligonucleotide developed using the company’s MISBA platform, which is designed to precisely raise protein levels without overexpression.
In preclinical models of Huntington’s disease, HRN001 increased FAN1 levels and slowed somatic repeat expansion, while also showing favourable pharmacokinetic and tolerability profiles. Preclinical development is due to continue through 2026, with clinical entry targeted for 2027.
Harness is also exploring the MISBA platform in other triplet repeat and neurodegenerative disorders.
To support progression towards the clinic, the company has formed a clinical advisory board made up of Huntington’s disease specialists from institutions including Cardiff University, University College London, the University of Cambridge and the University of Iowa.
Dr Jan Thirkettle, chief executive of Harness Therapeutics, said: “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 board 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 the 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’ 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 towards the clinic, translating this promising science into a clinical programme that could meaningfully alter the course of this devastating disease.”
