Strategy and Expansion
PebRx is especially interested in cytosolic phospholipase A2 (cPLA2), an enzyme whose pathway plays a central role in inflammatory lipid signaling in the brain. Our work has identified increased activation of this pathway in APOE4-associated Alzheimer's disease and has provided a basis for testing it as a useful therapeutic and diagnostic target.
We are developing and evaluating brain-penetrant cPLA2 inhibitors, including the BRI-Series, together with PET imaging approaches designed to measure related lipid pathways in the brain. Our preclinical studies examine how cPLA2 inhibition affects inflammatory signaling, synaptic function, cognition, cerebral amyloid angiopathy (CAA), and neurovascular injury, establishing whether the biology is sufficiently robust and reproducible to support further translational development.
| Program | Target | Indication(s) | Pre-IND | Phase 1 | Phase 2 |
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| BRI-Series | Small molecule inhibitor of cPLA2 | Brain bleeds in anti-Aβ therapy in APOE3/4 Alzheimer's Disease |
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| Familial and Sporadic CAA |
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| Alzheimer's Disease, Traumatic Brain Injury (TBI), Stroke |
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| 18F-FDHA | Fatty acid metabolism | Brain lipid metabolic alterations in neurodysfunction | |||
| 18F-AA | Neuroinflammation | Neuroinflammation in neurodysfunction |
BRI-50460: Brain-Penetrant cPLA2 Inhibitor
Proprietary, potent, BBB-penetrant, and selective small molecule inhibitor of cPLA2. PebRx's lead therapeutic is initially focused on reducing ARIA in the anti-amyloid treatment era, with expansion into CAA and broader neurovascular indications.
- A disease-modifying therapy for APOE4-associated Alzheimer's disease
- A vascular safety adjunct in the anti-amyloid treatment era
- A precision therapeutic for CAA and ARIA-associated neurovascular injury
Clinical Development Strategy
PebRx plans to pursue a development path initially focused on ARIA, followed by CAA in sporadic and Down syndrome AD, expanding to larger markets where brain inflammation drives pathology.