Skyhawk Therapeutics has expanded its global pivotal Phase 2/3 clinical trial of investigational Huntington’s disease therapy SKY-0515 into the USA, UK and Canada following additional regulatory approvals and encouraging Phase 1/2 clinical data.

The expansion means more than 10 countries and over 20 clinical sites are now participating in the FALCON-HD programme, with more than 175 patients enrolled across the global study. The company also confirmed that enrolment has been completed in its Phase 1/2 trial, where SKY-0515 has demonstrated sustained reductions in key disease biomarkers and early improvements in clinical measures after 12 months of treatment.

Huntington’s disease is a rare inherited neurodegenerative disorder caused by a mutation in the huntingtin gene, resulting in the production of a toxic mutant huntingtin (mHTT) protein that progressively damages nerve cells in the brain. The condition affects movement, cognition and behaviour, and currently there are no approved therapies proven to slow or stop disease progression.

SKY-0515 is an investigational oral RNA splicing modifier designed to reduce production of mutant huntingtin protein while also lowering levels of PMS1, a DNA repair protein believed to play a role in disease progression. By targeting both proteins, researchers hope the therapy may slow the underlying disease process rather than simply treating symptoms.

The company reported that after 12 months of treatment, SKY-0515 reduced mutant huntingtin protein levels by 69% and PMS1 by 26%. Participants also demonstrated improvements from baseline in the composite Unified Huntington’s Disease Rating Scale (cUHDRS), whereas natural history studies would typically be expected to show gradual clinical decline over the same period.

The Phase 1/2 programme has now completed enrolment and has shown SKY-0515 to be generally well tolerated across the doses studied.

Sergey Paushkin, head of Skyhawk R&D, said: “We are excited to now begin enrolling patients in our pivotal trial for Huntington’s in the United States, the United Kingdom and Canada.

“Clinician and Patient assessments done at twelve months of treatment support what the SKY-0515’s compelling and consistent effects on critical biomarkers and cUHDRS scores demonstrate—the exciting possibility that SKY-0515 may offer Huntington’s patients a type of therapy they have long deserved, in a convenient daily pill.”

The FALCON-HD programme consists of two complementary studies evaluating the safety, efficacy and pharmacodynamic effects of SKY-0515 in people with Stage 2 and early Stage 3 Huntington’s disease.

The Australian and New Zealand component of the programme has completed enrolment with 144 participants, while the international Phase 2/3 study plans to recruit up to 400 additional patients across more than 40 sites worldwide. Following regulatory clearances, recruitment will now expand into the USA, UK and Canada.

Unlike many investigational therapies for Huntington’s disease that require administration directly into the spinal fluid, SKY-0515 is being developed as a once-daily oral treatment. If future studies confirm its safety and effectiveness, the approach could offer a less invasive treatment option for patients living with the progressive neurological condition.

The expansion of the pivotal programme represents another step forward for RNA-targeted therapies in neurodegenerative diseases, an area attracting growing interest as researchers seek disease-modifying treatments capable of slowing or preventing neuronal damage rather than managing symptoms alone.