Genentech and AC Immune announced a second deal on treatments for Alzheimer’s disease Monday. The two companies, which collaborated on crenezumab, which targets beta amyloid proteins, are now taking on Tau proteins, which are thought to contribute to the degenerative brain disease. Both approaches employ antibodies to combat the disease.

“What this deal now allows us is to go after Alzheimer’s disease from two very different but equally important directions” Genentech Partnering’s head of neuroscience, Alexander Schuth, told MM&M.

The new agreement includes an undisclosed upfront payment to AC Immune and up to about $418 million in additional milestone payments as well as royalties based on net sales. AC Immune will handle pre-clinical development.

In a healthy brain, Tau proteins ensure cell structure. In Alzheimer’s patients, however, these proteins are abnormal and create tangles. Schuth said that these tangles are of particular note because they have been shown to have a one-to-one relationship with the disease’s progression: for example, memory loss is often the first symptom of the disease and it is where the tangles first appear. The next stage is personality decline, at which point there are tangles in the frontal temporal lobe. The disease finally affects activities like speaking and swallowing, at which point tangles have surfaced in the motor cortex.

Genentech is currently testing its beta amyloid protein treatment, crenezumab, in two settings: a treatment setting in which patients have already shown symptoms of the disease, and in a preventive setting. The latter was approved in May for use among a group of healthy patients with strong genetic links to the disease.

Schuth said it is too early to tell if the anti-Tau approach will be considered as a preventative treatment. He noted that Tau may have an edge over the beta amyloid approach among symptomatic patients.

Alzheimer’s is the sixth-leading cause of death in the United States. The Obama Administration set a 2025 goal for a cure, or at least a treatment. The Alzheimer’s Association estimates 6.7 million adults ages 65 or older will have Alzheimer’s by then—a 30% increase from the current 5.2 million. Unless a treatment can slow or cure the disease, the association expects this number to hit 11 million to 16 million by 2050.

Elsewhere in large pharma partnerships, Merck announced it is investing $15 million in Ambrx’s targeted biotechnology treatments. The collaboration also includes an additional $288 million in milestone payments if the biotechnology for successfully discovering, developing and commercializing products based on pre-determined targets, according to a company statement.

The collaboration centers on developing what was described as “rationally optimized biologic drug conjugates based on Ambrx’s site-specific protein medicinal chemistry.” [Update: An Ambrx spokesman told MM&M the new treatments will be in oncology and non-cancer fields. The spokesperson added that Ambrx is undertaking completely new research that is not part of its current pipeline.] Ambrx could also stand to gain royalties on next sales. Neither Ambrx nor Merck representatives were available for comment about the deal.

Ambrx’s pipeline is a combination of independent research that includes diabetes, obesity and cancer treatments, as well as collaborations with Pfizer, Eli Lilly and EMD Serono for unspecified conditions.

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Deborah Weinstein