Gilead Explores Triple-Target T-Cell Engagers in over $1.5B Merus Partnership

Bispecific T-cell engagers are gaining prominence in oncology, yet this hasn’t deterred a pharmaceutical collaboration from exploring the next phase of this treatment approach. Gilead and Merus have joined forces in a partnership exceeding $1.5 billion to investigate trispecific T-cell engagers, as recently announced. Under this agreement, Merus will lead early-stage research on two programs, with the potential for a third, in exchange for an initial payment of $56 million and a $25 million equity investment from Gilead.

Gilead will assess the possibility of licensing any of these programs upon reaching specified research milestones. Following this, Gilead will take over responsibility for further development and commercialization. Merus stands to receive up to $1.5 billion in milestone payments across all potential programs and has the option to opt for a 50-50 profit-sharing arrangement for the third program instead of milestone payments.

Dr. Flavius Martin, Gilead’s EVP and head of research, expressed excitement for the development of additional multispecific antibodies capable of eliciting robust anti-tumor immune responses with improved efficacy and safety profiles.

Bispecific T-cell engagers have emerged as promising cancer therapies, particularly in addressing small cell lung cancer, where breakthroughs have been limited. Among larger pharmaceutical companies, Amgen has been at the forefront with its BiTE platform and associated candidates such as the FDA-approved Blincyto and tarlatamab in clinical stages. Merck & Co. has also made significant investments, acquiring Harpoon Therapeutics for $680 million.

While Gilead currently has a phase 1-stage bispecific T-cell engager in its pipeline, intended for HIV treatment rather than cancer, the company is now broadening its focus.

Both Gilead and Merus are seeking to overcome recent safety concerns in their oncology endeavors. Merus faced a share price decline in December following the disclosure of three deaths in an open-label phase 1/2 study of MCLA-129 for lung cancer treatment. Despite promising disease control rates, particularly in combination with AstraZeneca’s Tagrisso in first-line settings, safety issues emerged.

Meanwhile, Gilead’s CD47 drug magrolimab has encountered challenges. The company recently discontinued its development as a blood cancer treatment due to reported deaths and has paused solid tumor trials following a partial FDA hold. Gilead is currently reassessing the risk-benefit profile across all affected studies.