Early Phase 2 results: ACI-7104 vaccine safe and immunogenic in people with early Parkinson’s

# What the study tested

ACI-7104 is an active immunotherapy designed to train a person's immune system to make antibodies that target aggregated forms of alpha-synuclein, the protein that forms toxic clumps implicated in Parkinson's disease. The vaccine is an optimized version of an earlier candidate, Affitope PD01A, and is intended to preferentially bind oligomers and fibrils rather than single alpha-synuclein molecules.

# Who was enrolled and how the trial ran

The VacSYn Phase 2 trial (NCT06015841) is testing ACI-7104 in adults with early-stage Parkinson's disease. Part 1 enrolled 34 participants (mean age 62.1 years, 65% men). They were randomized to receive ACI-7104 (25 people) or placebo (9 people) as intramuscular injections given at prespecified intervals over 74 weeks. Data were reported through roughly week 100.

• Safety and tolerability: All primary safety and tolerability endpoints were met. Most adverse events were mild and resolved without prolonged consequences. The most common effects were injection-site reactions (55.9%), followed by fatigue, headache, and symptoms described as common cold.
• Immunogenicity: ACI-7104 produced a strong, boostable antibody response. By week 100, 100% of vaccine recipients had developed antibodies against the vaccine's alpha-synuclein target. Antibodies were detectable in blood and showed measurable penetration into cerebrospinal fluid, consistent with central target engagement.
• Target engagement signals: The trial observed signals consistent with reduced levels of alpha-synuclein oligomers in cerebrospinal fluid in earlier studies of the precursor vaccine. Part 1 reported significant antibody production and CSF penetration, supporting the intended mechanism of binding aggregated alpha-synuclein.

# Why these findings matter

The approach aims to reduce toxic aggregated alpha-synuclein, particularly oligomers thought to drive nerve damage and inflammation in Parkinson's. Demonstrating safety and a reproducible antibody response that reaches the central nervous system is a necessary early step before testing whether that immune activity translates into slower symptom progression or biomarker changes.

# What comes next

AC Immune plans to advance VacSYn into Part 2. The company will submit the finalized Part 2 design to the U.S. Food and Drug Administration and intends regulatory meetings in early 2027. Part 2 will focus on generating clinical proof-of-concept data and will monitor progression of Parkinson's signs and symptoms alongside digital, imaging, and fluid biomarkers. The stated aim is to design an expanded Phase 2 trial to provide evidence of clinical activity that could support entry into Phase 3.

# Practical takeaways for patients and clinicians

• ACI-7104 showed a favorable short-term safety profile in a small early cohort and consistently induced antibodies targeted at aggregated alpha-synuclein.
• These are preliminary results focused on immune response and safety, not on definitive clinical benefit. Part 2 will test clinical and biomarker effects.
• Patients interested in immunotherapy trials for Parkinson's should watch for Part 2 site openings and FDA feedback on the trial design.

# Bottom line

Part 1 of the VacSYn Phase 2 trial achieved its primary goals: ACI-7104 was generally safe and generated a robust antibody response that reached the cerebrospinal fluid. The program is moving to Part 2 to test whether those immune responses translate into measurable clinical or biomarker benefits.