Discovering a Target

PebRx began with a question: why does APOE4, a gene variant carried by up to 25% of the U.S. population, make the brain so much more vulnerable to Alzheimer's disease? In pursuing that question, our scientists traced APOE4's effects to brain inflammation and to an enzyme at its center, cPLA2. In APOE4 carriers, cPLA2 is hyperactivated, driving a lipid inflammation pathway that can progress for years before symptoms appear and before irreversible damage occurs.

That finding defined our mission: to intercept the disease at its molecular root, rather than respond after memory loss begins. PebRx is developing novel therapeutics and diagnostics to detect and treat APOE4-driven brain inflammation. Our lead program, the BRI-Series of brain-penetrant cPLA2 inhibitors, targets this pathway directly. Paired with companion PET imaging to identify and monitor patients, BRI-Series is the first step in a pipeline built to bring precision, disease-modifying therapies to the largest untreated genetic risk group in Alzheimer's disease.