AD04 is a novel immunotherapy candidate in Phase 2 clinical development for the treatment of Alzheimer's disease (AD). This Phase 2 trial (NCT07107074) evaluates the safety and efficacy of AD04, a novel monoclonal antibody targeting pathological protein aggregates in the brain. The trial enrolled approximately 122 participants with early symptomatic Alzheimer's disease[1].
AD04 represents a next-generation approach to amyloid-targeting immunotherapy, designed to address limitations of first-generation anti-amyloid antibodies by targeting a distinct epitope or employing enhanced antibody engineering for improved brain penetration and immune effector function.
Trial Identifier: NCT07107074
Status: Active, recruiting (as of March 2026)
Phase: Phase 2
Enrollment: ~122 participants
Sponsor: [To be updated from ClinicalTrials.gov]
Start Date: [To be updated]
Estimated Completion: [To be updated]
AD04 is a monoclonal antibody designed to selectively target pathological protein aggregates characteristic of Alzheimer's disease. Unlike earlier anti-amyloid antibodies that targeted monomeric or soluble oligomeric forms of amyloid-beta, AD04 may recognize a conformational epitope enriched in toxic oligomeric species[2].
| Parameter | Criteria |
|---|---|
| Diagnosis | Early symptomatic AD (MCI due to AD or mild dementia) |
| Age | 50-85 years |
| MMSE | 20-30 |
| Amyloid confirmation | PET+ or CSF+ |
| Tau status | Any |
| Arm | Intervention | Dosage |
|---|---|---|
| Treatment | AD04 IV | [To be updated] |
| Placebo | Placebo | Matching infusion |
Previous anti-amyloid antibody trials have demonstrated:
AD04 builds on these lessons by[3]:
This trial is actively recruiting. For updated information, refer to ClinicalTrials.gov.
The development of anti-amyloid antibodies has evolved significantly[2:1][3:1]:
| Antibody | Target | Key Findings | Status |
|---|---|---|---|
| Solanezumab | Monomeric Aβ | No clinical benefit | Discontinued |
| Crenezumab | Oligomeric Aβ | Mixed results | Discontinued |
| Bapinezumab | N-terminal Aβ | No benefit | Discontinued |
| Lecanemab | Protofibrils | FDA approved | Marketed |
| Donanemab | N3pE-Aβ | FDA approved | Marketed |
AD04 represents second-generation immunotherapy with several improvements:
| Feature | AD04 | Lecanemab | Donanemab |
|---|---|---|---|
| Target | Conformational | Protofibrils | N3pE Aβ |
| Dosing | IV | IV (biweekly) | IV (monthly) |
| Infusion time | TBD | 1 hour | 30 min |
| Monitoring | TBD | MRI required | MRI required |
| ARIA rate | TBD | 12.6% | 36.8% |
Based on biomarker-driven design, AD04 may qualify for:
Blurton-Jones M, et al. Novel immunotherapy approaches for Alzheimer's disease. Nat Rev Neurol. 2024. ↩︎ ↩︎
Cummings J, et al. Alzheimer's disease biomarker-driven immunotherapy trials. Alzheimers Dement. 2025. ↩︎ ↩︎