FPA008 fires things up for Five Prime

NEW YORK & SOUTH SAN FRANCISCO, Calif.—Five Prime Therapeutics Inc. is capping off 2015 on a high note with the announcement of an exclusive worldwide license and collaboration agreement with Bristol-Myers Squibb Co.—an agreement that includes the development and commercialization of Five Prime’s colony stimulating factor 1 receptor (CSF1R) antibody program, including FPA008, which is in Phase 1 development for immunology and oncology indications. This deal takes the place of an existing clinical collaboration agreement to evaluate the safety, tolerability and preliminary efficacy of combining Bristol-Myers Squibb’s Opdivo (nivolumab), a programmed-death (PD-1) immune checkpoint inhibitor, with FPA008 in six tumor types.

The agreement stipulates that Five Prime will receive an upfront payment of $350 million, with the potential for up to $1.05 billion in development and regulatory milestone payments per anti-CSF1R product for oncology indications and up to $340 million in development and regulatory payments per anti-CSF1R product for non-oncology indications. Five Prime will also be eligible to receive double-digit royalties, which could be enhanced in the United States if the company chooses to exercise its co-promotion option.

“We believe this transformational collaboration with Bristol-Myers Squibb for our CSF1R antibody program represents the best of both worlds in terms of maximizing the potential of FPA008,” Dr. Lewis T. “Rusty” Williams, president and CEO of Five Prime Therapeutics, remarked in a press release. “Bristol-Myers Squibb has undisputed leadership in the immuno-oncology landscape, deep clinical development and regulatory expertise and an established commercial infrastructure to deliver important new therapies to patients. Bristol-Myers Squibb also has a rich pipeline of clinical candidates and approved products, a number of which may have therapeutic synergy when coupled with FPA008, given the potential of CSF1R inhibition to suppress the activity and survival of tumor-associated macrophages. At the same time, Five Prime will continue to conduct trials in pigmented villonodular synovitis (PVNS) and immuno-oncology with FPA008, which is a product of our proprietary protein platform and our discovery of IL-34, one of the two ligands for CSF1R that FPA008 blocks.”

For its part, Bristol-Myers Squibb will be responsible for developing and manufacturing FPA008 for all indications, subject to Five Prime’s option to conduct certain future studies at its own cost, including registration studies to support approval of FPA008 in PVNS and in combination with Five Prime’s internal immuno-oncology pipeline assets. Five Prime will continue with the ongoing Phase 1a/1b trial currently evaluating Opdivo in combination with FPA008 in six tumor settings through to completion, which is part of Five Prime and Bristol-Myers Squibb’s initial clinical collaboration announced in November 2014. Bristol-Myers Squibb will be responsible for global commercialization, and Five Prime will retain rights to a co-promotion option in the United States.

“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, executive vice president and chief scientific officer of Bristol-Myers Squibb. “This agreement, which builds upon our existing relationship with Five Prime in immuno-oncology, is another important example of our commitment to expanding our presence in this space and to researching novel combination regimens.”

As described on Five Prime’s website, “FPA008 is an antibody that inhibits colony stimulating factor-1 receptor (CSF1R), targets macrophages and monocytes, immune cells that are activated or elevated in multiple disease settings.” The compound is also being explored in a Phase 1 trial in rheumatoid arthritis, and Five Prime continues to evaluate FPA008 in a Phase 1/2 study for PVNS as well. The company notes that PVNS is “a locally aggressive tumor of the synovium where over-expression of CSF1 recruits macrophages to form the tumor mass in the joints. PVNS patients experience a high level of joint morbidity and have no approved treatment options.”

News of the deal has been well received. Zacks noted on Oct. 15 that Five Prime’s shares were up $10.45, or 61.8 percent, in the wake of the news, with Bristol-Myers Squibb’s stock also posting a slight gain of $1.13, or 1.82 percent. George Budwell of Motley Fool noted that “an extended research agreement with a Big Pharma like Bristol is noteworthy in and of itself for a tiny biotech” like Five Prime, adding that the company “could be looking at a huge upswing in revenue during the next few years if this partnership goes according to plan.”