As reported on PharmaBiz, Harness Therapeutics has selected HRN001 as its lead therapeutic candidate for Huntington’s disease (HD), marking a major milestone for the company as it prepares to transition the program toward clinical development. Alongside the nomination, the company has assembled a high‑profile clinical advisory board (CAB) to guide strategy, trial design, and translational planning.
HD is a rare, inherited neurodegenerative disorder characterized by progressive cognitive decline, psychiatric disturbances, and motor impairment. Although the genetic cause—a CAG repeat expansion in the HTT gene—has been well understood for decades, no approved therapies have been shown to slow or alter disease progression. Increasing evidence points to ongoing somatic expansion of the CAG tract as a key accelerant of disease onset and severity.
FAN1, a DNA repair nuclease, has emerged as one of the strongest genetic modifiers of HD. Enhancing FAN1 activity may help stabilize repeat length and delay disease progression, making it one of the most promising therapeutic targets in the field.
HRN001 is an antisense oligonucleotide designed to precisely elevate FAN1 levels using Harness’ proprietary MISBA (microRNA site blocking ASO) technology. This platform upregulates specific proteins by targeting microRNA binding sites without inducing harmful overexpression. In preclinical studies, HRN001 increased FAN1 expression and reduced somatic repeat expansion in HD models, while demonstrating promising pharmacokinetics and tolerability. The company expects to complete remaining preclinical work in 2026 and begin clinical testing in 2027.
Harness is also evaluating additional MISBA‑based programs targeting other triplet repeat disorders and neurodegenerative conditions.
Expert Clinical Advisory Board Established
To support the transition toward clinical evaluation, Harness has convened a CAB composed of leading HD researchers and clinicians:
- Dr. Irina Antonijevic (Chair) – Chief medical officer, Trace Neuroscience
- Dr. Anne Rosser – Professor of Clinical Neuroscience, Cardiff University
- Dr. Jeffrey Long – Professor of Psychiatry and Biostatistics, University of Iowa Health Care
- Dr. Ralf Reilmann – CEO and founding director, George‑Huntington‑Institute
- Dr. Roger Barker – Professor of Clinical Neuroscience, University of Cambridge
- Dr. Sarah Tabrizi – Professor of Clinical Neurology, University College London
- Dr. William Gray – Professor of Functional Neurosurgery, Cardiff University
These advisors bring deep expertise across clinical neurology, neurogenetics, biostatistics, trial design, and advanced surgical and gene therapy approaches.
Leadership Perspectives
Jan Thirkettle, CEO of Harness Therapeutics, described HRN001’s nomination as a significant step forward, emphasizing the therapeutic potential of precisely boosting FAN1 to address a core mechanism of disease progression. Antonijevic highlighted FAN1’s strong genetic validation and expressed optimism about translating the approach into a program capable of altering long‑term outcomes for patients.
Upcoming Scientific Presentation
Dr. Andy Billinton, the company’s chief scientific officer, will present new data on FAN1 upregulation using antisense technology at the CHDI Huntington’s Disease Therapeutics Conference (Palm Springs, February 23–26). His session, scheduled for February 24, will explore FAN1‑targeting ASOs as a therapeutic strategy for triplet repeat disorders.
Harness Therapeutics continues to focus on unlocking previously inaccessible biological pathways to develop disease‑modifying treatments for neurodegeneration. The advancement of HRN001 marks one of the most targeted efforts to date aimed at slowing the genetic mechanism that drives Huntington’s disease.
