AC Immune is fighting Alzheimer’s disease on three fronts armed with monoclonal antibodies, vaccines, and small molecules. It is attacking amyloid beta (Abeta) oligomers and tau tangles, the key misfolded proteins involved in the pathological processes of Alzheimer’s.
Andrea Pfeifer, Ph.D., helped to co-found AC Immune in 2003 with Claude Nicolau, Ph.D., to advance a liposome technology invented in Dr. Nicolau’s laboratory at Tufts University. The method involves attaching peptides mimicking the pathological conformation of antigens to liposomes to specifically target conformational proteins like Abeta. These abnormal proteins are associated with about 20 human diseases including Alzheimer’s, Huntington’s, Parkinson’s, and Creutzfeldt-Jakob disease.
The body’s immune system does not recognize Abeta or tau as foreign proteins. AC Immune’s immunotherapies trigger the body to make antibodies against these misfolded proteins. “All the antibodies induced attack the pathologic conformation, but do not touch normal healthy proteins,” says Dr. Pfeifer, now CEO.
The company’s SupraAntigen™ technology generates conformation-sensitive antibodies that inactivate all forms of Abeta. Because a single liposome can carry up to 400 antigens on its surface, it has a big, or “supra” impact. The liposomes, made of cholesterol and fatty acids, do not cause inflammation or other immune reactions. Tests show absolutely no antibody response to the inert liposomes in mice or people. “Dosages can be high compared to other drugs,” says Dr. Pfeifer, because “we see hardly any side effects.”
SupraAntigens precisely discriminate against abnormal and normal forms of a protein, and a better safety profile results from this high affinity, says Dr. Pfeifer. The approach does not require T-cell activation, so no brain inflammation or toxicity occurs. “When working in the brain, you need an extremely safe treatment,” she emphasizes.
The SupraAntigen platform makes both mAbs and vaccines. Hundreds of mAbs are generated after injecting a mouse, and ones with the highest affinity and specificity for a target protein are selected for further testing.
The company’s chemical Morphomer™ platform produces small molecule drugs that block the aggregation of Abeta. The Morphomer program grew out of the SupraAntigen platform. “We learned exactly where our liposomes bind and the most effective sites to destroy in sick proteins. We designed small molecules to bind exactly to these sites,” says Dr. Pfeifer. This chemical route proved harder, and it took five years. The lead small molecule, ACI-91, helps to transport Abeta out of the brain and is in Phase II trials.