Bristol-Myers Squibb and Five Prime Therapeutics have entered into an exclusive worldwide license and collaboration agreement for the development and commercialization of Five Prime’s colony stimulating factor 1 receptor (CSF1R) antibody program, including FPA008, which is in phase I development for immunology and oncology indications. The agreement replaces the companies’ existing clinical collaboration agreement to evaluate the safety, tolerability and preliminary efficacy of combining Opdivo (nivolumab), Bristol-Myers Squibb’s programmed-death 1 (PD-1) immune checkpoint inhibitor, with FPA008 in six tumor types.

“By blocking a key mediator of immunosuppression in the tumor microenvironment, CSF1R inhibition with FPA008 represents a potentially important complementary immuno-oncology mechanism of action to the T-cell directed antibodies and co-stimulatory molecules in our pipeline,” said Francis Cuss, MB BChir, FRCP, executive vice president and chief scientific officer of Bristol-Myers Squibb.

Bristol-Myers Squibb will make an upfront payment of $350 million to Five Prime. Bristol-Myers Squibb will be responsible for the development and manufacturing of FPA008 for all indications, subject to Five Prime’s option to conduct, at its own cost, certain future studies including registrational studies to support approval of FPA008 in PVNS and FPA008 in combination with Five Prime’s internal pipeline assets in immuno-oncology.

Five Prime will continue to conduct the current phase Ia/Ib trial evaluating the combination of Opdivo and FPA008 in six tumor settings, which was announced as part of the companies’ initial clinical collaboration in November 2014, through to completion. Bristol-Myers Squibb will be responsible for global commercialization, and Five Prime will retain rights to a U.S. co-promotion option.

In addition to the upfront payment, Five Prime will be eligible to receive up to $1.05 billion in development and regulatory milestone payments per anti-CSF1R product for oncology indications (including combinations with Opdivo and any other agent), and up to $340 million in development and regulatory milestone payments per anti-CSF1R product for non-oncology indications, as well as double digit royalties, such royalties to be enhanced in the U.S. in the event that Five Prime exercises its co-promotion option.