BMS takes option on Prothena Alzheimer’s drug in $2.2bn deal


Bristol-Myers Squibb has upgraded a long-running alliance with Prothena in Alzheimer’s disease, taking an option on a tau protein-targeting antibody in early-stage clinical development.

The deal – potentially worth around $2.2 billion with a $55 million upfront payment – covers PRX005, an antibody that specifically targets the microtubule-binding region (MTBR) of tau, which Prothena thinks is most closely associated with the pathogenic spread of the protein in the brains of Alzheimer’s patients.

The decision to go all-in on the programme comes two years after BMS paid $80 million to take exclusive, worldwide opt-in rights to PRX005, and means that the big pharma will now be responsible for development, manufacturing, and commercialisation activities.

PRX005 originally arose from a 2018 alliance between Prothena and Celgene, which was acquired by BMS in 2019, and also covers two other proteins thought to be involved in Alzheimer’s pathology.

The anti-MTBR-tau drug has completed a phase 1 single ascending dose (SAD) study, with topline data reported in January showing that it was safe and well-tolerated and crossed into the central nervous system effectively, meeting its main objectives. Meanwhile, an ongoing multiple ascending dose (MAD) study is due to report results before the end of the year.

The latest opt-in makes PRX005 the centrepiece of BMS’ small neuroscience pipeline, which currently consists of only a handful of early-stage drug candidates. The company’s head of neuroscience research, Richard Hargreaves, said the drug “has the potential to provide a meaningful disease-modifying treatment option for the millions of people that suffer from Alzheimer’s disease.”

According to Dublin, Ireland-based Prothena, the presence of MTBR fragments in cerebrospinal fluid correlates with dementia stages in Alzheimer’s more closely than fragments of other regions of the tau protein, which could give its antibody an edge over rivals.

To date, however, tau-targeting therapies for Alzheimer’s haven’t had a great track record. Biogen abandoned the development of its antibody candidate gosuranemab in 2021, and Roche/AC Immune’s semorinemab missed the mark in the phase 2 TAURIEL trial in early-stage Alzheimer’s in 2020.

TauRx’ tau aggregation inhibitor HMTM (formerly LMTX) wasn’t able to improve on placebo in a 2016 study, but remains in development and is being prepared for regulatory filings, despite questions about the design of its phase 3 LUCIDITY trial reported last year.

One big hope for tau is that it could boost the modest clinical effectiveness of amyloid-targeting therapies – spearheaded by Eisai and Biogen’s recently-approved Leqembi (lecanemab) – if they can be used in combination.

Tau tangles are one of the characteristic hallmarks of Alzheimer’s visible in the brain, along with amyloid plaques.