Skyhawk Therapeutics Reports 72% Huntingtin mRNA Reduction in Phase 1 SKY-0515 Trial for Huntington's Disease

Skyhawk Therapeutics, Inc., a clinical-stage biotech firm, recently shared promising results from parts A and B of its Phase 1 clinical trial for SKY-0515, a potential treatment for Huntington’s disease (HD). This small molecule RNA splicing modifier demonstrated a significant reduction in huntingtin (HTT) mRNA levels, achieving a 72% reduction at the highest dose tested in healthy volunteers.

SKY-0515 was developed using Skyhawk’s proprietary RNA-splicing platform and aims to reduce HTT protein levels as well as PMS1 protein, which is also implicated in HD pathology. Professor Ed Wild from University College London emphasized the significance of these findings, noting that the dual reduction of HTT and PMS1 could offer more therapeutic benefits than targeting HTT alone. Wild highlighted that Huntington’s disease, a rare neurodegenerative condition affecting over 40,000 people in the U.S., currently has no approved treatments to slow or reverse its progression.

The trial for SKY-0515 is divided into three parts. Parts A and B focused on evaluating the drug in healthy volunteers while Part C will extend the study to patients with early-stage Huntington's disease. In Part A, a double-blind, placebo-controlled single ascending dose study was conducted. Healthy adult volunteers were divided into five cohorts and administered single doses of SKY-0515 ranging from 1mg to 16mg or a placebo. The impact of food on the drug’s pharmacokinetics was also studied in a separate cohort.

Part B involved a double-blind, placebo-controlled multiple ascending dose study. Three cohorts of participants received daily doses of SKY-0515 ranging from 1mg to 9mg or a placebo over 14 days. The dose levels identified in these trials will be used in Part C, which will assess the drug in early-stage HD patients.

Commenting on the trial’s progress, Skyhawk’s Chief Medical Officer, Dr. Douglas V. Faller, expressed optimism about the drug’s potential. He noted that the Safety Review Committee found SKY-0515 to be generally well tolerated across all tested doses, with a dose-proportional increase in systemic exposure. This positive safety profile has paved the way for the study to progress into the patient arm, with recruitment already underway and topline data expected by the second quarter of 2025.

CEO Clint Musil praised the speed and success of the trial so far. He highlighted that the topline data underscore the potential of Skyhawk’s platform to address diseases with no current disease-modifying therapies. The Phase 1 trial, initiated in late 2023, marks a significant milestone for SKY-0515 and the company’s broader efforts in disease treatment innovation.

Skyhawk Therapeutics is committed to discovering and developing novel therapies targeting critical RNA structures. The company’s proprietary platform has enabled the identification and testing of RNA splicing modifiers across various therapeutic areas, including neurodegenerative diseases, autoimmune disorders, and cancer. Skyhawk has also established collaborations with multiple pharmaceutical partners to leverage its platform across these diverse disease areas.