Biogen Idec will use Proteostasis Therapeutics’ scientific platform and preclinical work on protein degradation as part of a collaboration by the companies to research and develop therapeutic candidates for neurodegenerative diseases based on inhibition of Usp14.
In a deal that could net Proteostasis more than $200 million, the companies agreed to conduct preclinical research to identify lead compounds for clinical development. At specified points in development, Proteostasis will have the option to receive potential milestones or opt in for global co-development and U.S. co-commercialization rights to identified compounds.
The companies are looking to build on preclinical research that has shown that inhibiting Usp14, a deubiquitinating enzyme, modulates proteasome activity and increases the degradation rate of aggregation-prone proteins, including α-synuclein in Parkinson's disease and tau in Alzheimer's disease. Usp14 technology was originally developed at Harvard Medical School by professors Daniel Finley, Ph.D., and Randall King, Ph.D., M.D., both members of the Proteostasis Scientific Advisory Board, and funded in part by the Blavatnik Biomedical Accelerator program. It is being advanced under license from Harvard University.
The collaboration is intended to develop Usp14 inhibitors as disease-modifying approaches for disorders involving toxic protein aggregation using Proteostasis’ platform, which revolves around modulating protein homeostasis pathways within the cell. These pathways are part of the cellular "quality control" machinery called the protein homeostasis network or proteostasis network (PN) that regulates protein folding, trafficking, and clearance. By modifying the PN’s function and capacity, the company’s product candidates are designed to correct for imbalances in the PN resulting from cumulative effects of disease, genetic mutations, environmental factors, and aging.
The company credits its platform with identifying proteostasis regulators that modulate protein homeostasis pathways to correct the folding, trafficking, and functional activity of the DF508 cystic fibrosis transmembrane conductance regulator (CFTR). That research is in preclinical phases.
“We look forward to advancing our disease-modifying approach to develop therapeutic candidates that can address several protein aggregation disorders, including Parkinson’s disease and Alzheimer’s disease,” Markus Haeberlein, Ph.D., Proteostasis’ svp and head of research, said in a statement.
Proteostasis will receive an undisclosed initial up-front payment from Biogen Idec, along with an undisclosed equity investment, and is eligible for research funding support and future development and commercial milestones that Proteostasis said could result in total payments of up to $200 million, as well as tiered royalties.