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CAMBRIDGE, Mass.—Proteostasis Therapeutics Inc., a company developing novel therapeutics to address diseases caused by defects in protein folding, trafficking and clearance, and Tokyo-based Astellas Pharma Inc. have entered into a worldwide collaboration to research and develop therapeutic candidates that modulate the unfolded protein response (UPR) through the use of Proteostasis Therapeutics’ proprietary Disease Relevant Translation (DRT) and Proteostasis Network (PN) platform.
Proteostasis Therapeutics will receive an initial upfront payment from Astellas, along with a securities investment. Proteostasis Therapeutics is also eligible for research funding support, future development and commercial milestones that could result in total payments of over $400 million, as well as tiered royalties. Further, Astellas has the right to begin two additional projects under the same terms, which, if fully exercised, would bring the total potential value of the collaboration to $1.2 billion.
“We are very pleased to be collaborating with Astellas, a worldwide leader in the development of innovative therapeutics,” said Meenu Chhabra, president and CEO at Proteostasis Therapeutics. “Our novel approach to drug discovery, coupled with Astellas’ track record in drug development, will enable rapid discovery and development of therapies for important unmet medical needs.”
The PN consists of more than 2,000 proteins organized into pathways that can be regulated. The PN ensures that every protein within a cell will reach its final destination correctly folded with appropriate function or be degraded and cleared to prevent damage. Disease, genetic mutations, environmental factors and aging can cause the PN to become imbalanced, which can lead to a decrease in protein quality control and contribute to diseases categorized as loss-of-function or gain-of-toxic-function disorders. Loss-of- function diseases, such as cystic fibrosis, are often caused by inherited mutations resulting in inefficient folding and excessive degradation. Gain-of- toxic-function disorders, which include Alzheimer’s, Huntington’s and Parkinson’s diseases, appear to arise from aggregation-associated toxicity.
Proteostasis Therapeutics is developing novel therapeutics designed to pharmacologically control or rebalance the PN, either by restoring its normal state or enhancing the capacity of the compromised PN to create a therapeutic state sufficient to control or delay progression of disease.
The collaboration will focus on one genetic disease and further explore additional indications that can be affected through modulation of the UPR pathway. Stress induced by accumulation of unfolded proteins in the endoplasmic reticulum is observed in many diseases which are now recognized as protein conformational diseases, including genetic diseases, neurodegenerative diseases and retinal degenerative diseases. Selective modulation of the UPR pathway in nonclinical investigations improved the stress response and restored function, suggesting that it can be beneficial as potential novel disease-modifying therapies for multiple diseases with high unmet medical needs.
“Proteostasis Therapeutics has a novel platform that offers a differentiated approach to discovering drugs for unmet medical needs,” commented Dr. Kenji Yasukawa, senior vice president and chief strategy officer at Astellas. “It complements our existing internal and externalized R&D initiatives, and we continue to invest in innovative technologies that can provide new therapeutic options to patients. We look forward to working closely with Proteostasis Therapeutics to identify lead candidates for clinical development and potential commercialization.”
As part of the agreement, the companies will conduct discovery, screening and preclinical research to identify lead compounds for clinical development. Upon candidate selection, Proteostasis Therapeutics will have the rights to opt in for global co-development and United States co- promotion.
This collaboration is being led by Astellas Innovation Management (AIM).
The impact of this collaboration has been accounted in revised Astellas’ forecasts for fiscal year ending March 2015, which was announced on Oct. 31. AIM’s goal is to enhance and accelerate the process of screening and realizing external opportunities to strengthen innovation at the preclinical development stage. The unit oversees strategic alliance activities with external partners and is responsible for a series of activities at acquiring external innovation opportunities in the preclinical development stage, such as strategy planning, screening, scientific assessment and alliance negotiations, so that strategic external business alliances can be strategically and systematically performed.
Proteostasis Therapeutics’ DRT platform combines a proprietary screening approach with state-of-the-art medicinal chemistry to generate highly selective drug candidates and is advancing a pipeline inclusive of a lead program in cystic fibrosis and a partnership with Biogen Idec for neurodegenerative diseases.
The company’s DRT platform utilizes functionally pertinent assays and disease relevant models to identify highly translatable therapies associated with the modulation of protein homeostasis pathways within the cell. These pathways are part of cellular “quality control” machinery, known as the protein homeostasis network as well as by the PN moniker. By modifying the function and capacity of the PN, the company’s therapeutic product candidates correct for imbalances in the PN resulting from the cumulative effects of disease, genetic mutations, environmental factors and aging.
Astellas Pharma has approximately 18,000 employees worldwide. The organization is committed to becoming a global category leader in urology, immunology (including transplantation) and infectious diseases, oncology, neuroscience and diabetes mellitus complications and kidney diseases.