Biogen has made another big investment play in Alzheimer’s disease, penning a $350m upfront agreement with gene-editing specialist Sangamo for rights to tau-targeting drug ST-501 as part of a broader R&D alliance.
The tie-up also covers a second drug called ST-502 – in development for Parkinson’s disease and other neurodegenerative diseases characterised by the abnormal clumping of alpha-synuclein protein (synucleinopathies) – as well as a third unnamed candidate for a neuromuscular disease. Biogen also claims exclusive rights to nine additional undisclosed neurological targets.
The deal is sizeable considering both ST-501 and ST-502 are still in preclinical development, with the upfront payment – split between $125m in cash and $225m in new Sangamo stock – backed up by $2.37bn in milestones tied to development, regulatory, and commercial targets.
Tau is emerging as a target for drug development in Alzheimer’s as well as other disorders like frontotemporal dementia.
The licensing deal comes as Biogen prepares to file its amyloid-targeting Alzheimer’s therapy aducanumab, which had been written off last year after disappointing clinical trial results but was resurrected after it appeared to show a benefit on longer-term follow-up.
Sangamo’s specialises in the development of gene-editing drugs based on its zinc finger nuclease (ZFN) technology, which can be used to regulate the expression of genes but had disappointing results in a mucopolysaccharidosis type II trial last year.
Biogen’s deal is an endorsement of the technology platform at a time when rival gene-editing technologies like CRISPR/Cas9 seem to be gathering momentum, with encouraging preliminary results from trial of Vertex and CRISPR Therapeutics’ CTX001 in blood disorders last November.
“As a pioneer in neuroscience, Biogen will collaborate with Sangamo on a new gene regulation therapy approach, working at the DNA level, with the potential to treat challenging neurological diseases of global significance,” said Al Sandrock, Biogen’s head of R&D.
Sangamo’s zinc finger protein transcription factor (ZFP-TF) approach involves introducing double-stranded DNA breaks engineered to target specific sequences in a cell.
The cell tries to fix the break using another copy of the sequence as a backup, such as the other unbroken chromosome in the pair but – by supplying a new template using an adeno-associated virus (AAV) vector – the system can be forced to insert a desired sequence instead.
“Highly specific, potent, and tunable repression of tau and alpha synuclein has been demonstrated in preclinical studies using AAV vectors to deliver tau-targeted (ST-501) and alpha synuclein-targeted (ST-502) ZFP-TFs,” according to the partners.
Sangamo also has a gene therapy platform, with a first candidate for haemophilia A heading for late-stage development at partner Pfizer later this year.