BioWorld International Correspondent

AC Immune SA raised CHF21 million (US$17.2 million) in a Series B round from an undisclosed group of investors to advance its immunotherapy-based programs in what it calls "conformational diseases" and cancer.

The Lausanne, Switzerland-based company, which was established in 2003, is commercializing intellectual property from research conducted by its co-founder and chief scientific officer, Claude Nicolau, who also is visiting professor of medicine at Tufts University in Boston, and Jean-Marie Lehn, of Collège de France in Paris and Université Louis Pasteur, Strasbourg, who shared the 1987 Nobel prize in chemistry for his work on developing small organic molecules that mimic biologically active macromolecules.

Nicolau's work underlies AC Immune's proprietary antigen presentation platform, which can induce the production of antibodies that react with proteins in specific conformations. The Supramolecular Antigen Technology comprises a liposome plus lipid A structure, linked by two spacer regions to a pair of lysine residues to which an epitope of interest is tethered.

"The presentation method triggers the immune system to form antibodies that are selective for one or the other conformation," AC Immune Chief Financial Officer Armin M der told BioWorld International. The precise epitopes deployed are associated with protein aggregation processes, leading in the case of beta amyloid to the formation of the insoluble plaques that are characteristic of Alzheimer's.

The approach offers a potential method for breaking the immune tolerance associated with "self" proteins that cause disease when they undergo a switch to an abnormal conformation but that go unrecognized by the immune system. The company is developing both a vaccine, for active immunization, and monoclonal antibodies, for passive immunotherapy, against Alzheimer's disease. It already has demonstrated proof of concept in a transgenic mouse model. "We can either stop plaques from forming or we can dissolve aggregated material in vivo," M der said.

It also is developing a vaccine against P-170, a glycoprotein that is the cause of multidrug resistance in many cancers. Previous attempts to develop small-molecule drugs against that target have not been successful, M der said, as they were typically metabolized like cancer drugs and therefore imposed an additional liver toxicity burden, necessitating a reduction in dosage.

"The immune-based approach is a very neat one in the sense that you're attacking it via a completely different mechanism," he said.

The company's second platform, deriving from Lehn's work, is based around a class of therapeutics called "Morphomers," which are non-covalent complexes of small molecules that also show differing affinities for proteins, depending on their conformational states. The technology also is being applied to the development of an Alzheimer's therapy although the program is at an earlier stage.

AC Immune, which has raised CHF24 million since inception, has funding to take at least one of its programs through a Phase I trial by the end of 2007.

The company's founders include CEO Andrea Pfeifer, former head of global research at Nestlé SA; Roscoe Brady, head of the developmental and metabolic neurology branch of the National Institute of Neurological Disorders and Stroke in Bethesda, Md.; Wolfgang Stoiber, of Munich, Germany-based JSB Partners; Fred van Leuven, of the Catholic University of Louvain, Belgium; and Ruth Greferath, co-inventor of conformationally sensitive therapeutic antibodies and AC Immune's director of biology.