Roche and Prothena will co-develop and co-commercialize antibodies that target alpha-synuclein – including PRX002, Prothena’s preclinical monoclonal antibody for Parkinson’s disease – in a deal that could yield Prothena up to $600 million.

Prothena will receive an up-front payment and near-term clinical milestone payment totaling $45 million. The company is also eligible for an additional $380 million tied to development, regulatory and first commercial sales milestones – plus up to an additional $175 million in payments tied to ex-U.S. commercial milestones.

Alpha-synuclein, found extensively in neurons, is a major component of pathological inclusions that characterize Parkinson’s and other synucleinopathies, such as dementia with Lewy bodies, neurodegeneration with brain iron accumulation type 1, and multiple system atrophy. By targeting one of Parkinson’s key molecular determinants, the companies reason that PRX002 has the potential to slow down or reduce the disease’s progression.

“This approach is consistent with our strategy in other neurodegenerative diseases, such as Alzheimer’s, Huntington, multiple sclerosis, or spinal muscular atrophy, where we target the molecular pathophysiology and intervene early with the objective to slowdown or halt the progression of disease,” Luca Santarelli, head of neuroscience and small molecules research at Roche, said in a statement.

PRX002 is set to enter Phase I trials in 2014. In multiple transgenic mouse models of Parkinson’s disease, passive immunization with 9E4 (the murine version of PRX002) reduced the appearance of synuclein pathology, protected synaptic connections, and improved performance by the mice in behavioral testing. PRX002 may slow or reduce the neurodegeneration associated with synuclein misfolding and/or cell-to-cell transmission of pathogenic forms of synuclein, the companies said.

Prothena has an option to co-promote PRX002 in the U.S., where the partners will share all development and commercialization costs, as well as profits, on a 70/30 basis (70% Roche and 30% Prothena). Outside the U.S., Roche will have sole responsibility for developing and commercializing PRX002, and will pay Prothena up to double-digit royalties on net sales.

As part of their agreement, Roche and Prothena will also launch a research collaboration focused on optimizing early-stage antibodies targeting alpha-synuclein including incorporation of Roche’s proprietary Brain Shuttle™ technology, designed to increase delivery of therapeutic antibodies to the brain.

Prothena is a drug discoverer spun out last year from Elan, now being acquired by Perrigo in an $8.6 billion deal set to close by year’s end.

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