Skyhawk Therapeutics has reported encouraging 12-month results from its ongoing Phase 1/2 study of SKY-0515, an investigational oral therapy for Huntington’s disease, showing sustained reductions in disease-driving proteins alongside positive trends in clinical measures.

The company announced interim findings demonstrating that patients receiving SKY-0515 achieved reductions of up to 69% in mutant huntingtin protein (mHTT), the toxic protein responsible for Huntington’s disease pathology. The treatment also reduced PMS1 messenger RNA by up to 26%, targeting a second pathway associated with disease progression.

Huntington’s disease is a rare inherited neurodegenerative disorder affecting more than 40,000 symptomatic individuals in the United States and many more worldwide. There are currently no approved therapies proven to slow or stop disease progression.

Clinical outcomes reported after 12 months showed mean improvements from baseline in Composite Unified Huntington’s Disease Rating Scale (cUHDRS) scores ranging from +0.31 to +0.38 points. Skyhawk compared these findings with propensity score-weighted analyses based on the Enroll-HD and TRACK-HD natural history datasets, which suggested an expected decline of 0.92 points over the same period in symptomatic patients.

Positive trends were also reported across individual components of the cUHDRS assessment, including motor function, functional capacity and cognitive measures.

The company said SKY-0515 demonstrated strong central nervous system exposure and was generally safe and well tolerated across all dose levels evaluated.

Bill Haney, co-founder and chief executive officer of Skyhawk Therapeutics, said: “The increasing separation of the clinical trajectories of treated participants from natural history expectations at the twelve-month timepoint suggests exciting and sustained benefits for Huntington’s patients.”

He added: “The magnitude and durability of lowering of critical biomarkers mHTT and PMS1, as well as encouraging twelve-month clinical findings across all four of the critical cUHDRS subcomponents, reinforce our confidence in SKY-0515’s differentiated mechanism and potential for dramatic therapeutic impact for patients.”

SKY-0515 is an orally administered small molecule RNA splicing modifier developed using Skyhawk’s proprietary platform. Unlike some Huntington’s disease programmes that focus solely on lowering mutant huntingtin, SKY-0515 is designed to reduce both mHTT and PMS1, potentially targeting two mechanisms involved in disease progression.

Ed Wild, professor of neurology at University College London, said: “SKY-0515 continues to reduce mHTT protein to the greatest extent demonstrated in patients, with clinical and biomarker data showing the drug is well tolerated at all doses tested.”

He added: “These Phase 1/2 trial results, due to be validated in the ongoing Phase 2/3 FALCON-HD pivotal program, give an expectation of meaningful therapeutic impact for people living with HD across the world.”

Alongside the clinical update, Skyhawk announced that the Australia and New Zealand portion of its Phase 2/3 FALCON-HD programme completed enrolment six months ahead of schedule, recruiting 144 patients. The global FALCON-HD study has now expanded to eight countries and plans to enrol approximately 400 participants.

More than 175 patients have now been enrolled across the SKY-0515 clinical development programme.

While the findings require confirmation in larger pivotal studies, the combination of substantial huntingtin lowering, favourable safety data and positive clinical trends positions SKY-0515 among the more closely watched programmes in Huntington’s disease development.