SKY-0515

SKY-0515 is an investigational, orally administered small molecule developed by Skyhawk Therapeutics for the treatment of Huntington’s disease. It acts as an mRNA splicing modulator, designed to reduce levels of both wild-type and mutant huntingtin (HTT) protein by lowering HTT messenger RNA (mRNA) through a splicing mechanism. Additionally, SKY-0515 reduces postmeiotic segregation 1 (PMS1) protein, which is implicated in somatic CAG repeat expansion—a key driver of Huntington’s disease progression. The drug was developed using Skyhawk’s SKYSTAR platform focused on RNA splicing correction and has demonstrated dose-dependent reductions in HTT and PMS1 mRNA levels with favorable safety and tolerability profiles in early clinical studies. SKY-0515 crosses the blood-brain barrier and distributes to peripheral tissues, offering potential benefits via daily oral dosing[1][2][3][4][5][6][8].