Pfizer and Sangamo Therapeutics are linking arms to develop a potential gene therapy to treat amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD).
Both ALS and FTLD are neurodegenerative disorders caused by mutations in the C9ORF72 gene that involve hundreds of additional repetitions of a six base pair sequence of DNA. This ultimately leads to the deterioration of motor neurons, in the case of ALS, or neurons in the frontal and temporal lobes, in the case of FTLD.
As yet there are no cures available that halt or turn back the progression of either disease.
The companies are hoping to address this by developing a gene therapy using Sangamo’s zinc finger protein transcription factors (ZFP-TFs) technology. This engineers ZFP designed to identify and bind to a precise sequence of DNA, and an attached transcriptional repressor domain that suppress expression of the gene.
Sangamo and Pfizer intend to explore allele-specific ZFP-TFs with the potential to differentiate the mutant C9ORF72 allele from the wild type allele and to specifically down-regulate expression of the mutant form of the gene.
The deal is structured so that Sangamo is responsible for development of ZFP-TF candidates, and Pfizer for subsequent research, development, manufacturing and commercialisation for the C9ORF72 ZFP-TF programme and any resulting products.
Sangamo receives a $12 million upfront payment from Pfizer, and is also eligible to receive potential development and commercial milestone payments of up to $150 million, as well as tiered royalties on net sales.
This not the firms first joint foray into co-developing gene-based treatments, having signed a deal in May last year to develop and commercialise potential gene therapy products for Hemophilia A.
"The precision and flexibility of zinc finger proteins enables targeting of virtually any genetic mutation. Collaboration with the right partner for a given therapeutic application is a key component of our corporate strategy and enables us to pursue the vast opportunity set of our platform,” noted Sandy Macrae, Sangamo’s chief executive.