Roche and clinical stage biotechnology company, Prothena Corporation 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 is currently in preclinical development and is expected to enter phase I clinical trials in patients with Parkinson's disease 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 disease, 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."
"We are excited to be working with Roche to develop PRX002 as a disease modifying treatment for Parkinson's disease and potentially other synucleinopathies. Roche is a global leader in drug development with significant experience in developing drugs to treat neurological diseases," said Dale Schenk, PhD, president and chief executive officer of Prothena. "By combining Roche's expertise with our own, this collaboration will greatly enhance our development efforts with PRX002 and allow us to move forward in a more comprehensive manner. This collaboration also represents an important milestone in our growth as we continue to execute on our corporate strategy to be a leading fully-integrated biotechnology company."
Roche and Prothena will collaborate on the development of PRX002 for Parkinson's disease and potentially other synucleinopathies. Prothena also has an option to co-promote PRX002 in the US. In the US, the companies will share all development and commercialization costs, as well as profits, on a 70/30 basis (70 per cent Roche and 30 per cent Prothena). Outside the US, Roche will have sole responsibility for developing and commercializing PRX002 and will pay Prothena up to double-digit royalties on net sales.
Under the terms of the agreement, Prothena will receive an upfront payment and near-term clinical milestone totaling $45 million. Prothena is also eligible to receive additional payments of up to $380 million upon the achievement of development, regulatory and first commercial sales milestones plus up to an additional $175 million in ex-US commercial milestone payments. The total worldwide upfront and milestone payments may amount up to $600 million.
Also as part of the agreement, 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.
The transaction is subject to customary regulatory clearances including expiration of the applicable Hart- Scott-Rodino waiting period. Prothena's legal and financial advisers on the transaction were Latham & Watkins LLP and BioAsset Advisors, respectively.
PRX002, a monoclonal antibody targeting alpha-synuclein, has been tested in various cellular and animal models of synuclein-related disease and has shown in multiple transgenic mouse models of Parkinson's disease, that 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.
Prothena Corporation plc is focused on the discovery, development and commercialization of novel antibodies for the potential treatment of a broad range of diseases that involve protein misfolding and cell adhesion, particularly on the discovery, development and commercialization of potential therapeutic monoclonal antibodies directed specifically to disease-causing proteins.
Roche is working on new molecular entities in neuroscience that could become the next generation of medicines for a range of diseases including schizophrenia, multiple sclerosis, depression, neurodevelopmental disorders, Parkinson's disease and Alzheimer's disease.
Roche is a leader in research-focused healthcare with combined strengths in pharmaceuticals and diagnostics.