Source: Prothena
Bristol-Myers Squibb has taken an option on a tau protein-targeting antibody in early-stage clinical development from Prothena on July 12.
The deal is potentially worth around $2.2 billion with a $55 million upfront payment. The antibody, called PRX005, specifically targets the microtubule-binding region (MTBR) of tau, which is thought to be 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 program comes two years after BMS paid $80 million to take exclusive, worldwide opt-in rights to PRX005. This means that BMS will now be responsible for development, manufacturing, and commercialization activities.
PRX005 originally arose from a 2018 alliance between Prothena and Celgene, which was acquired by BMS in 2019. The drug has completed a Phase I 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. 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 centerpiece 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. This could give its antibody an edge over rivals.
“Earlier this year, as part of our collaboration with Bristol Myers Squibb, we announced topline data from the single ascending dose portion of the Phase 1 clinical trial showing that PRX005 across three dose cohorts was safe and well tolerated with expected pharmacokinetic properties, meeting the primary objectives of the study. We are proud of our pioneering role in targeting this key region within the MTBR of tau and excited that Bristol Myers Squibb have exercised their option for worldwide rights to PRX005. At Prothena, we will continue advancing our broad portfolio of product candidates for Alzheimer’s disease, including PRX012, our next-generation antibody targeting amyloid beta, a well-validated disease pathway, and PRX123 an amyloid beta/tau dual-targeting vaccine with the potential to prevent Alzheimer’s disease. We believe that our portfolio is well-positioned to revolutionize the care of patients suffering from this devastating disease.”
– Gene Kinney, PhD, President and Chief Executive Officer, Prothena
“PRX005, identified and developed by Prothena through our partnership, has the potential to provide a meaningful disease-modifying treatment option for the millions of people that suffer from Alzheimer’s disease. PRX005 becomes a key component of our commitment to the Alzheimer’s disease community and our neuroscience portfolio, and we look forward to continuing its development.”
– Richard Hargreaves, Senior Vice President and Head of Bristol Myers Squibb’s Neuroscience Thematic Research Center
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 II 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.
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.
