Harness Therapeutics Advances HRN001 Toward the Clinic for Huntington’s Disease

Harness Therapeutics has reached an important milestone in its mission to tackle neurodegenerative disease. The biotechnology company has officially nominated HRN001 as its lead development candidate for Huntington’s disease (HD) and announced the formation of a Clinical Advisory Board (CAB) to guide the programme toward clinical evaluation.

This development signals a significant step forward—not only for the company, but for the broader Huntington’s community, where the need for disease-modifying treatments remains urgent.

Understanding the Unmet Need in Huntington’s Disease

Huntington’s disease is a devastating, inherited neurodegenerative disorder characterised by progressive cognitive decline, psychiatric symptoms, and worsening motor dysfunction. Symptoms typically lead to severe disability, with death often occurring within 15 years of onset.

The condition is caused by an expansion of CAG repeats in the Huntingtin (HTT) gene. In recent years, research has shown that ongoing somatic expansion of these repeats—where repeat lengths continue to increase in certain tissues over time—is a major driver of disease onset and progression.

Despite significant advances in understanding the biology of HD, there are currently no approved therapies that modify the underlying disease process.

Targeting FAN1: A Genetically Validated Approach

Among the most compelling targets emerging from genome-wide association studies is FAN1, a DNA repair nuclease strongly associated with delayed disease onset in Huntington’s patients. Genetic data consistently show that higher FAN1 activity correlates with reduced somatic expansion and slower disease progression.

Harness Therapeutics’ lead candidate, HRN001, is designed to harness this insight.

HRN001 is a first-in-class antisense oligonucleotide (ASO) that specifically targets FAN1. Rather than suppressing a protein, it is engineered to precisely upregulate FAN1 levels, enhancing the body’s own DNA repair mechanisms. The drug leverages Harness’ proprietary MISBA (microRNA site blocking ASO) platform, which enables controlled increases in protein expression without risking excessive overexpression.

In preclinical models of Huntington’s disease, HRN001 has demonstrated:

• Robust upregulation of FAN1
• Slowing of somatic CAG repeat expansion
• Favourable pharmacokinetic properties
• Encouraging tolerability profiles

Preclinical development is expected to continue throughout 2026, with clinical entry targeted for 2027. Beyond Huntington’s disease, Harness is exploring the broader potential of the MISBA platform across other triplet repeat disorders and additional neurodegenerative indications.

Building Clinical Expertise: Formation of the Advisory Board

To support HRN001’s advancement into the clinic, Harness has established a Clinical Advisory Board comprising internationally recognised leaders in Huntington’s disease research and care. The CAB will provide strategic guidance on trial design, translational strategy, and overall clinical development.

The board includes:

• Dr. Irina Antonijevic (Chair), Chief Medical Officer at Trace Neuroscience
• Dr. Anne Rosser, Professor of Clinical Neuroscience at Cardiff University
• Dr. Jeffrey Long, Professor of Psychiatry and Biostatistics at University of Iowa Health Care
• Dr. Ralf Reilmann, Founding Director and CEO of the George-Huntington-Institute
• Dr. Roger Barker, Professor of Clinical Neuroscience at the University of Cambridge
• Dr. Sarah Tabrizi, Professor of Clinical Neurology at University College London
• Dr. William Gray, Professor of Functional Neurosurgery at Cardiff University

Collectively, the group brings decades of expertise in HD clinical care, biomarker development, trial design, gene therapy, statistical modelling, and translational neuroscience.

Dr Jan Thirkettle, CEO of Harness Therapeutics, described the nomination of HRN001 as a “pivotal milestone” for the company, highlighting the strong genetic validation of FAN1 and the differentiated nature of the therapeutic approach. He emphasised the company’s commitment to delivering a truly disease-modifying therapy for patients and families affected by Huntington’s disease.

Dr Irina Antonijevic, Chair of the CAB, underscored FAN1’s importance as one of the most consistently validated genetic modifiers of HD identified to date. She noted that HRN001 offers a novel and highly targeted strategy to modulate this pathway and expressed enthusiasm about translating the science into a meaningful clinical programme.

Showcasing the Science at CHDI 2026

Further insights into the HRN001 programme will be shared at the annual CHDI Huntington’s Disease Therapeutics Conference in Palm Springs, California, taking place 23–26 February.

Dr Andy Billinton, Chief Scientific Officer of Harness Therapeutics, will present:

• Title: Upregulation of FAN1 with ASOs as a potential therapeutic strategy for triplet repeat disorders
• Session: Somatic Instability/Mismatch Repair
• Date: Tuesday, 24 February

The presentation will highlight the scientific rationale behind targeting FAN1 and outline the preclinical progress achieved to date.

A Precision Strategy for Disease Modification

Harness Therapeutics was founded with the goal of unlocking previously “undruggable” targets in neurodegeneration. Through its MISBA platform, the company is pursuing a novel therapeutic strategy: precise upregulation of beneficial proteins rather than simply suppressing harmful ones.

By targeting somatic expansion—one of the fundamental drivers of Huntington’s disease progression—HRN001 represents a mechanistically differentiated approach that could meaningfully alter the disease course.

While clinical validation still lies ahead, the nomination of HRN001 and the assembly of a world-class advisory board mark an important step toward translating genetic insight into therapeutic reality for Huntington’s patients.

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