Gilead tries new triple-target T-cell engagers in $1.5B-plus Merus collab

Bispecific T-cell engagers are just now stepping into the oncology spotlight, but that’s not stopping one pharma company from investigating the next frontier of the modality.

Gilead and Merus have inked a partnership worth more than $1.5 billion to discover trispecific T-cell engagers, the companies announced Wednesday. In exchange for $56 million in upfront cash plus a $25 million equity investment from Gilead, Merus will lead early-stage research on two programs, with the potential for a third.

Gilead will decide whether to license any of the programs once they pass a designated research checkpoint, after which the Foster City Pharma can take over development and commercialization work. 

Merus stands to make $1.5 billion in milestone payments across all the potential programs, and can opt into a 50-50 profit-sharing agreement for the third program rather than earn biobucks, if that’s pursued. 

“We are now looking ahead to the development of additional multispecific antibodies capable of driving robust anti-tumor immune responses with an improved efficacy and safety profile,” Flavius Martin, M.D., Gilead’s EVP and head of research, said in a release.

Bispecific T-cell engagers have been a blooming class of cancer treatments as of late, showing considerable promise in treating small cell lung cancer, for which there have been few major breakthroughs. Amgen has been one of the leaders among the larger pharmas with its BiTE platform and accompanying candidates led by FDA-approved Blincyto and clinical-stage tarlatamab. Merck & Co. also recently invested heavily, buying Harpoon Therapeutics for $680 million.

Gilead already has a phase 1-stage bispecific T-cell engager in its pipeline, but it's aimed at treating HIV, not cancer. 

Both Gilead and Merus are looking to rebound after safety concerns have arisen in parts of their oncology work. Merus saw its share price decline in December after the company revealed three deaths in an open-label phase 1/2 study testing MCLA-129 as a lung cancer treatment. The safety profile threw cold water on what was otherwise high disease control rates, namely in the first-line setting when combined with AstraZeneca’s Tagrisso. 

Meanwhile, Gilead’s CD47 drug magrolimab has struggled to find its footing. The pharma recently elected to end development of the antibody as a treatment for blood cancer after reported deaths and has paused solid tumor trials following a partial FDA hold. Gilead has said it's reviewing the risk-benefit profile across all the impacted studies.