Roche and Prothena have entered into a worldwide collaboration to develop and commercialize antibodies that target alpha-synuclein including PRX002, Prothena's monoclonal antibody for the treatment of Parkinson's disease, which currently is in preclinical development and is expected to enter phase I clinical trials in patients with Parkinson's in 2014.
Synuclein proteins are a family of charged proteins found throughout the body. One protein from this family, alpha-synuclein, is found extensively in neurons and is a major component of pathological inclusions that characterize several neurodegenerative disorders, including Parkinson's, dementia with Lewy bodies, neurodegeneration with brain iron accumulation type 1 and multiple system atrophy, which collectively are termed synucleinopathies.
"Parkinson's is a severely debilitating and progressive neurodegenerative disease that leads to both a gradual worsening of motor function and cognitive and behavioral alterations," said Luca Santarelli, head of neuroscience and small molecules research at Roche. "Currently, there is no treatment that modifies its course, and by targeting one of Parkinson's key molecular determinants, PRX002 has the potential to slowdown or reduce its 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."
Roche and Prothena will collaborate on the development of PRX002 for Parkinson's and potentially other synucleinopathies. Prothena also has an option to co-promote PRX002 in the U.S. In the U.S., the companies will share all development and commercialization costs, as well as profits, on a 70/30 basis (70% Roche, 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.
Prothena will receive an upfront payment and near-term clinical milestone totaling $45 million. Prothena also is eligible to receive additional payments of up to $380 million in milestones plus up to an additional $175 million in ex-U.S. commercial milestones. The total worldwide upfront and milestone payments could total up to $600 million.
Roche and Prothena will initiate a research collaboration focused on optimizing early stage antibodies targeting alpha-synuclein, including incorporation of Roche's proprietary Brain Shuttle technology to increase delivery of therapeutic antibodies to the brain.