ACI-7104.056's Phase 2 Part 1 final data will determine whether active alpha-synuclein immunotherapy can demonstrably slow early Parkinson's progression

Bull

A positive outcome would show durable alpha-synuclein-specific antibody responses through week 104, statistically or clinically meaningful slowing of UPDRS III motor decline, favorable trends in DaT-SPECT striatal binding, and continued normalization of CSF alpha-synuclein and NfL relative to placebo. This would establish proof-of-concept for active immunotherapy as a disease-modifying strategy in early PD, validate the VacSYn platform, and provide the regulatory basis to advance into a powered Part 2 efficacy trial.

Bear

The most likely failure modes are an attenuation of the interim biomarker signals at full follow-up — particularly if DaT-SPECT or UPDRS III trends do not hold or widen versus placebo — or an inability to distinguish drug effect from natural disease variability in a small Phase 2 Part 1 cohort. Secondary failure modes include immunogenicity that is robust but not translating to clinical benefit, or safety signals emerging during the extended observation period that complicate the benefit-risk profile for Part 2.