AC Immune ACI-24 shows dose-response in Phase 1b/2 Alzheimer's trial
AC Immune has released interim 12-month data from the first three cohorts of its Phase 1b/2 ABATE trial, reporting that its anti-amyloid beta (Abeta) active immunotherapy ACI-24 was generally safe and well tolerated across 74 patients with prodromal Alzheimer's disease. Anti-Abeta antibody responses were detected at every dose level tested, with a clear dose-response relationship observed.
Crucially, no cases of amyloid-related imaging abnormalities with oedema (ARIA-E) were identified across cohorts AD1 to AD3, a safety concern that has dogged passive anti-amyloid therapies such as lecanemab and donanemab. The absence of ARIA-E to date will be seen as an encouraging differentiator, though the trial remains at an early phase and the cohorts are small.
Immunogenicity and the AD4 cohort
Despite the broadly positive safety picture, AC Immune acknowledged that the magnitude of the antibody response may not be sufficient for effective amyloid plaque removal. The company said it evaluated the addition of a supplementary adjuvant to boost immunogenicity while ABATE was already under way, and a fourth cohort, AD4, has since been initiated to test this enhanced formulation.
Martin Zügel, interim chief executive and chair of the board, said: "The nature of the antibody response observed in ABATE suggests that we should further enhance immunogenicity for more effective plaque removal."
This pivot to a higher-immunogenicity design mid-trial reflects a recurring challenge for active immunotherapy approaches in Alzheimer's disease, a field that suffered a significant setback with the AN1792 vaccine more than two decades ago due to T-cell-mediated meningoencephalitis. More recent active vaccine candidates, including those from Janssen and others, have struggled to induce robust and consistent antibody titres. AC Immune's decision to introduce an adjuvant in AD4 is a rational response, though it means the programme's most clinically informative data remains some way off.
Takeda partnership and commercial context
ACI-24 is partnered with Takeda under an exclusive worldwide option and licence agreement. AC Immune received a $100 million upfront payment and a $12 million milestone on first dosing in cohort AD4. If Takeda exercises its option, it would assume responsibility for all further clinical development, global regulatory activities, and commercialisation. AC Immune remains eligible for an option exercise fee plus development, commercial, and sales-based milestones totalling up to approximately $2.1 billion, alongside tiered double-digit royalties on net sales.
The Takeda agreement provides AC Immune with substantial non-dilutive funding during a period when the broader Alzheimer's therapeutics market is being reshaped. The approvals of lecanemab (Eisai and Biogen) and donanemab (Eli Lilly) have validated the amyloid hypothesis but also raised the bar for any new entrant. An active vaccine, if it can match the efficacy of monoclonal antibodies without the ARIA risk, could offer a more convenient and scalable dosing profile. That remains the strategic thesis, though ABATE is still some distance from generating the plaque-removal and cognitive data needed to test it.
Regulatory and development path
AC Immune is responsible for conducting the ABATE trial. The release did not provide a timeline for reporting full cohort data or for Takeda's option exercise window. Investors will be focused on when AD4 dose data become available and whether the adjuvanted formulation materially improves antibody titres. The programme also includes a Down syndrome arm, where recruitment into the third sub-cohort has concluded, though no DS data were reported in this interim release.
The Lausanne-based company trades on NASDAQ under the ticker ACIU.