Increasing Our PoS On GTX-102 After Significant Diligence on the Angelman Syndrome Space

Research evidence excerpt

Increasing Our PoS On GTX-102 After Significant Diligence on the Angelman Syndrome Space

May 20, 2026

the Phase 3 trial is the placebo response rate, which, based on our

diligence, we believe has been substantially mitigated.

●Another important factor is that very little has changed from the

Phase 1/2 protocol to the Phase 3 one.

●Based on our diligence, placebo response is likely to be limited in

the Phase 3 trial because the Bayley-4 scale used in the study is

a standardized, physician-administered assessment with a binary

scoring structure, whereby patients either demonstrate a skill or they

do not, helping to mitigate potential placebo effects.

●Experts consulted during our diligence noted that placebo response

rates are more commonly observed in assessments that rely

heavily on caregiver-reported outcomes, given the well-documented

phenomenon of caregiver optimism. However, RARE’s Phase 3 primary

endpoints are not solely dependent on caregiver-based measures.

●Additionally, experts we consulted this week expressed skepticism

that placebo response would be a meaningful issue given the severe

nature of AS, noting that many patients are unlikely to fully understand

whether they are receiving active treatment.

●AS is also a neurodevelopmental disorder, meaning patients are not

expected to naturally acquire new skills over time, and the KOLs we

consulted during our diligence saw no reason to believe patients in the

placebo arm would demonstrate meaningful skill gains in the absence

of GTX-102 treatment.

Support From Experts:

●Anecdotally, during our conversation with a KOL who served as a

principal investigator for prior AS trials conducted by Ionis (NC), Oak Hill

Bio (private), and Ultragenyx, we asked whether he believed antisense