An immunotherapy company founded nearly four years ago in Lausanne, Switzerland, secured its largest deal to date by signing an agreement with Genentech Inc. worth more than $300 million.

AC Immune Ltd. entered the exclusive global license agreement and research collaboration to develop its anti-beta-amyloid antibodies as potential treatments for Alzheimer's and other diseases. The company, founded in February 2003, has developed conformation-specific antibodies against beta-amyloid, a protein generated by its SupraAntigen technology and one recognized as an important target in the disease modification of Alzheimer's.

"We were offered partnerships by many companies," said Andrea Pfeifer, the company's CEO and a co-founder, who described AC Immune's position as a "paradise" for a small biotech company. "We selected Genentech very carefully. We thought for the antibody development, they were the best partner."

South San Francisco-based Genentech's top marketed products include the anti-VEGF antibody Avastin, approved to treat colon and non-small-cell lung cancers; the anti-HER2 antibody Herceptin, for breast cancer; and the anti-CD20 antibody Rituxan, for non-Hodgkin's lymphoma. The drugs had U.S. sales in the third quarter of $435 million, $302 million and $509 million, respectively.

Under the agreement with AC Immune, Genentech will make an undisclosed up-front payment to the company, and could pay more than $300 million in clinical and regulatory milestone payments, as well as royalties. The milestones cover the development of AC Immune's technology for Alzheimer's disease and other applications. Genentech will commercialize any products that reach the market. In the meantime, the company will provide funding for a multiyear collaborative research program, covering all development and clinical costs of the lead antibody and those that follow.

AC Immune's chief financial officer, Armin Mader, said the terms of the deal will provide his company with enough money for the next three years "to develop other programs at full speed."

Pfeifer declined to give a timeline as to when the lead antibody might move from preclinical trials to the clinic. The company has a vaccine for Alzheimer's disease, separate from this agreement, that is slated to enter clinical trials next year, she said. AC Immune also is working on small molecules.

The company uses its immunology platform, called the SupraAntigen technology, to develop active and passive immunotherapies, such as vaccines and monoclonal antibodies, against Alzheimer's disease. The technology is able to generate conformation-sensitive antibodies.

In Alzheimer's disease, the normal beta-amyloid protein "makes a transformation and becomes a bad protein," Pfeifer told BioWorld Today. That results in the formation of plaques in the brain that "basically kill the nerves," she said.

A challenge of the disease is that the problem proteins come from within the human body and do not elicit an immune reaction, and the difference between the good and bad proteins is expressed only by a conformational change in the protein structure.

AC Immune's lead product has a "high affinity for the bad protein, and this is what makes it quite interesting," Pfeifer said.

The product is highly active in animal disease models of Alzheimer's disease, and it has induced the transition from an insoluble to the soluble form of the plaque forming beta-amyloid protein, which has directly correlated with memory improvement.

It is unknown how much current therapies attack the good protein in the body, Pfeifer said, and there are no therapies available today that modify Alzheimer's disease. Current treatments only slow the progression.

"The market potential of a disease-modifying Alzheimer's treatment is anything between $2 billion and $4 billion," Pfeifer said.

Beyond Alzheimer's disease, AC Immune's antibodies could be used to treat a variety of other diseases related to the central nervous system. The company also is developing therapies against the multidrug resistance of cancers.

Aside from its SupraAntigen platform, AC Immune has a platform focused on the chemistry of small molecules, Morphomers, which are noncovalent complexes of small molecules with particular sequences of the target proteins.