SKY-0515

No placebo-controlled efficacy results are available for SKY-0515. In the SKY-0515-001 Part C study, 26 participants with HD were randomized to 3 mg (10 participants), 9 mg (10), or placebo (6) for 84 days and then received blinded 4 mg or 9 mg SKY-0515 for an additional 12 months. At day 84, blood mHTT protein was reduced by 62% with 9 mg and by 29% with 3 mg, and blood HTT and PMS1 mRNA were reduced by 62% and 26% with 9 mg. Reductions in blood mHTT of up to 69% were reported at 12 months, and average reductions of more than 60% in mHTT and 25% in PMS1 mRNA at 9 mg were reported through 15 months. In healthy volunteers, blood HTT mRNA was reduced by up to 67% after a single 16 mg dose and by 72% after 14 days of 9 mg daily.

Clinical outcomes have been compared only with overlap-weighted external natural-history controls from the Enroll-HD, 2CARE, and CREST-E datasets, not with placebo. At month 15, the designated primary timepoint (15 treated participants), cUHDRS changed by +0.94 points with SKY-0515 and by -0.65 points in the external control (difference +1.59; 95% CI 1.09 to 2.09; p<0.001), with differences favoring SKY-0515 on TFC (+0.98), TMS (-9.38), SDMT (+4.15), and SWRT (+4.18). The cUHDRS differences at month 3 (+0.66; p=0.191) and month 6 (+0.78; p=0.051) were not statistically significant. The sources also disagree on the month 12 result and on which timepoint is primary. The September 2026 fifteen-month announcement reports a month 12 cUHDRS difference of +0.79 (18 treated participants; 95% CI 0.11 to 1.48; p=0.023) and designates month 15 as the primary timepoint. The June 2026 poster reports a difference of +1.25 at "the primary 12-month endpoint" versus propensity score-weighted natural-history controls, pooling the 4 mg and 9 mg groups and including participants who switched from placebo (15 participants at month 12). Because the two analyses use different weighting methods and participant sets, their estimates are not directly comparable. These results are reported only in company announcements and congress posters.

In participants with HD, the most common related TEAEs (reported by two or more participants) were headache, diarrhea, and nausea, with the majority mild or moderate. The sources differ on serious adverse event attribution. A February 2026 poster listed four severe or serious events and described one, a prolonged headache, as "possibly drug related". A June 2026 poster reported that three participants had at least one serious adverse event (grade 3 mania; grade 3 tooth infection; grade 3 pneumonia and pleural effusion), none considered related to study drug, and the fifteen-month announcement reported no treatment-related SAEs. Plasma NfL through 12 months and CSF NfL through 9 months were reported as generally stable. In healthy volunteers, no severe or serious adverse events were observed at single doses up to 16 mg or multiple doses up to 9 mg/day for 14 days.

The randomized, placebo-controlled phase 2/3 FALCON-HD trials have not reported results. FALCON-HD 004-ANZ enrolled 144 participants in Australia and New Zealand. Planned enrollment in FALCON-HD 004-WW is 400 participants in the registry record and in a July 2026 company announcement ("up to an additional 400"), and approximately 600 participants in the September 2026 fifteen-month announcement.