IBC-Ab002
Alzheimer's disease
DiscoveryPreclinicalPhase 1Phase 2Phase 3
Alzheimer's
disease
Completed Phase 1b of IBC-Ab002 in patients with Early AD. Phase 2b in early Alzheimer's disease is planned for H1 2027.
Increasing evidence indicates that disease progression is influenced not only by processes within the central nervous system, but also by age-related dysfunction of the peripheral immune system. Under normal conditions, peripheral immune cells contribute to immune surveillance, tissue repair and the resolution of inflammation. In AD, this protective systemic response may become insufficient to effectively counterbalance ongoing pathological processes in the brain.
Preclinical studies have shown that transient blockade of the PD-1/PD-L1 immune checkpoint can activate a coordinated peripheral immune response, including the recruitment of immune-regulatory and monocyte-derived cells to the brain. This response is associated with reduced neuroinflammation and attenuation of disease pathology in models of amyloidosis and tauopathy.
Senescent microgliaclearance
Reducedinflammation
Synapsesrescue
Reducedtau-pathology
Slow-down cognitivedeterioration
- Wild type mice
- 5xFAD, untreated
- 5xFAD, IgG control
- 5xFAD, Anti-PD-L1
Phase 1b study
Study Design
Randomized, dose-ascending, double-blind, placebo-controlled Phase 1b
40 participants with early AD
5 cohorts: 6 active, 2 placebo each
Placebo IBC-Ab002
Duration: 48-week treatment 4 IV infusions (Q12W)
11 centers in the United Kingdom, Netherlands and Israel
Primary endpoints: Dose-related safety and tolerability
Exploratory endpoints: Peripheral immunophenotyping and disease-specific cerebrospinal fluid (CSF) biomarker analysis
Safety
IBC-Ab002 was found to have a favorable safety profile and was well tolerated in patients with Early AD
0
ARIA events at any dose (Amyloid-Related Imaging Abnormalities)
0
Treatment-related serious adverse events
0
Chronic immune-related adverse event, managed with medication
Exploratory biomarkers
Markers of synaptic damage
Neurogranin
Involved in synaptic plasticity, learning, and memory.
Median difference vs placebo
0.0%
VAMP-2
Associated with episodic and semantic memory and global cognition.
Median difference vs placebo
0.0%
AD-related tau pathology
pTau217
Sensitive marker of amyloid-associated tau pathology.
Median difference vs placebo
0.0%
pTau181
Reflects tau phosphorylation and neuronal pathology.
Median difference vs placebo
0.0%
Total-Tau
CSF marker of neuronal injury.
Median difference vs placebo
0.0%
The preliminary CSF findings are consistent with preclinical evidence that anti-PD-L1 treatment may reduce neuroinflammation and support neuronal and synaptic integrity.
Cognitive assessments showed no signs of unexpected deterioration in any active treatment group; however, the short follow-up and the small sample size limit any conclusions regarding clinical efficacy. An adequately powered evaluation of cognitive endpoints is planned for an upcoming phase 2 study.
Selected publications from IBC-Ab002 studies
Clinical - Phase 1bNature MedicineImmunotherapy with a short-lived anti-PD-L1 antibody in Alzheimer's disease: a phase 1b, randomized, double-blind trial2026Full paper PreclinicalNature MedicinePD-1 immune checkpoint blockade reduces pathology and improves memory in mouse models of Alzheimer's disease2016Full paper PreclinicalNature CommunicationsPD-1/PD-L1 checkpoint blockade harnesses monocyte-derived macrophages to combat cognitive impairment in a tauopathy mouse model2019Full paper PreclinicalAlzheimer's & Dementia · AAICIBC-Ab002, an anti-PD-L1 monoclonal antibody tailored for treating Alzheimer's disease2020Full paper PreclinicalAlzheimer's & Dementia · AAICPD-L1 blockade therapeutic effect in Tau P301S (line PS19) mouse model of tauopathy2020Full paper PreclinicalNature AgingAlzheimer's disease modification mediated by bone marrow-derived macrophages via a TREM2-independent pathway in mouse model of amyloidosis2021Full paper
Publications Sources
- Croese et al. - Immunotherapy with a short-lived anti-PD-L1 antibody in Alzheimer's disease: a phase 1b, randomized, double-blind trial. Nature Medicine (2026).
- IBC-Ab002 studies - ClinicalTrials.gov
- Scheltens P. et al. Alzheimer's disease. Lancet 397, 1577–1590 (2021).
- Sun P.-Y. et al. Rejuvenation of peripheral immune cells attenuates Alzheimer's disease-like pathologies and behavioral deficits in a mouse model. Sci. Adv. 10, eadl1123 (2024).
- Pasinetti G. M. Anti-inflammatory drugs fall short in Alzheimer's disease. Nat. Med. 14, 916 (2008).
- Begemann M. et al. Drugs with anti-inflammatory effects to improve outcome of traumatic brain injury: a meta-analysis. Sci. Rep. 10, 16179 (2020).
- Salminen A. Activation of immunosuppressive network in the aging process. Ageing Res. Rev. 57, 100998 (2020).
- Rickenbach C. et al. Altered T-cell reactivity in the early stages of Alzheimer's disease. Brain 148, 3364–3378 (2025).
- Baruch K. et al. PD-1 immune checkpoint blockade reduces pathology and improves memory in mouse models of Alzheimer's disease. Nat. Med. 22, 135–137 (2016).
- Ben-Yehuda H. et al. Key role of the CCR2–CCL2 axis in disease modification in a mouse model of tauopathy. Mol. Neurodegener. 16, 39 (2021).
- Baruch K. & Yoles E. Commentary: chronic PD-1 checkpoint blockade does not affect cognition or promote tau clearance in a tauopathy mouse model. Front. Aging Neurosci. 12, 135 (2020).