Merck & Co’s earlier efforts to find new therapies for Alzheimer’s disease resulted in failure, but the company is returning to the field via an R&D alliance with UK biotech Cerevance that will seek out new drug targets.
Merck is paying $25 million upfront to tap into Cerevance’s NETSseq transcriptomics technology, used to discover proteins that are either over- or under-expressed in disease states, and is also licensing one unidentified programme at the drug discovery stage.
The partnership could be worth more than $1.1 billion to the UK biotech, which specialises in neurological diseases and has taken a Parkinson’s disease candidate into phase 2 proof-of-concept testing.
Merck was among a clutch of companies that tried to bring a now-defunct category amyloid-targeting therapies for Alzheimer’s – the BACE inhibitors – through clinical development.
Its most advanced drug candidate, verubecestat, was abandoned in 2018 after an interim look at data from the phase 3 APEC S study concluded the drug was unlikely to show a benefit.
Not long after, other BACE inhibitors from Biogen/Eisai, Eli Lilly and AstraZeneca also fell by the wayside, and a litany of failures for other amyloid-targeting therapies – plus the abject failure of the one drug to gain regulatory approval – has undermined the amyloid hypothesis of Alzheimer’s.
After decades of research and drug development, it seems we are no closer to answering the question: does amyloid cause Alzheimer’s, or does Alzheimer’s result in amyloid?
Taking a new tack
There’s no word yet on the drug targets that will be explored in the Cerevance partnership, but Merck head of neuroscience discovery, Jason Uslaner, said that the collaboration will focus on “new targets” for therapeutic intervention – suggesting that it will look beyond amyloid and other well-trodden Alzheimer’s pathways like tau protein.
Merck has an active tau programme licensed from Teijin Pharma in 2017, which still appears to be active as Teijin booked a milestone payment from Merck for the project in December 2021 related to the start of clinical trials of the antibody drug.
“Progress in our understanding of the biology of neurodegenerative diseases continues to reveal compelling new mechanisms for potential therapeutic intervention,” added Uslaner.
The only mention of Alzheimer’s in Cerevance’s pipeline is an undisclosed target expressed on brain microglial cells involved in neuroinflammation that regulates the NLRP3 inflammasome.
Cambridge-based Cerevance said its NETSseq technology has been used to sift through protein expression in thousands of post-mortem, healthy and diseased human brain tissue samples across a range of ages and brain regions.
The analyses can “expose biological pathways underlying neurodegenerative and psychiatric diseases that would be difficult to see in animal models or differentiated human stem cells,” according to the biotech.
It could be many years before the alliance bears fruit – if it does at all – but any attempt to broaden the scope of Alzheimer’s research is to be welcomed.
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