Cabiralizumab (FPA008)

Cabiralizumab (FPA008) is an antibody that inhibits colony stimulating factor-1 receptor (CSF1R). Cabiralizumab (FPA008) is currently in a Phase 1a/1b clinical trial evaluating it in combination with OPDIVO® (nivolumab), Bristol-Myers Squibb's PD-1 immune checkpoint inhibitor, in multiple tumor types.Cabiralizumab (FPA008) targets macrophages and monocytes, immune cells that are activated or elevated in multiple disease settings.

Tumor-associated macrophages (TAMs) are elevated in many tumors and are thought to be involved in suppressing the immune response against tumors.  These cells also secrete a variety of proteins, including tumor necrosis factor alpha, or TNFa, interleukin-6, or IL-6, and interleukin-1 beta, or IL-1ß, that attract and activate inflammatory cells. Derivatives of these inflammatory cells directly destroy bone tissue in joints.

Cabiralizumab (FPA008) emerged from Five Prime’s discovery of a novel protein target called interleukin 34 (IL-34) during a screen of our protein library for novel proteins that activate monocytes and macrophages. We were then able to use our protein library and our receptor-ligand matching technology to identify IL-34’s receptor, CSF1R, which is known to be expressed on the surface of monocytes and macrophages. Before our discovery of IL-34, CSF1R was thought to have only one ligand called CSF1. Both CSF1 and IL-34 bind to and activate CSF1R and therefore promote the survival and activity of monocytes and macrophages. Cabiralizumab (FPA008) blocks the binding of both CSF1 and IL-34 to CSF1R, thereby inhibiting the activity and survival of these cells.


Cabiralizumab (FPA008) Status

In September 2016, Five Prime announced it initiated the Phase 1b portion of the clinical trial evaluating the immunotherapy combination of cabiralizumab (FPA008) with OPDIVO® (nivolumab), Bristol-Myers Squibb's PD-1 immune checkpoint inhibitor, in multiple tumor types. These tumor types include: non-small cell lung cancer, squamous cell carcinoma of the head and neck, pancreatic cancer, glioblastoma, renal cell carcinoma and ovarian cancer.

Cabiralizumab (FPA008) was designed and developed at Five Prime through the initiation of clinical trials in multiple macrophage-dependent diseases. In October 2015, Five Prime announced an exclusive worldwide license and collaboration agreement with BMS, a recognized leader in the field of immuno-oncology, for the development and commercialization of Five Prime's CSF1R antibody program, including cabiralizumab (FPA008). Terms of the agreement include $350 million upfront and $1.4 billion in potential development and regulatory milestone payments per CSF1R antibody product to Five Prime, plus royalty percentages ranging from the high teens to low twenties on net sales.

Five Prime will continue running the trial through to completion and BMS is responsible for funding the study except for Five Prime internal costs. BMS will drive future development in immuno-oncology, including combinations with OPDIVOand potentially other BMS products and pipeline candidates. BMS is also responsible for manufacturing and commercialization of cabiralizumab (FPA008), although Five Prime retains the right to co-promote cabiralizumab (FPA008) in the U.S. Five Prime has the right under the agreement to explore combinations of cabiralizumab (FPA008) with its own oncology pipeline candidates and development of cabiralizumab (FPA008) in pigmented villonodular synovitis (PVNS) and non-oncology indications. 

Five Prime is continuing to evaluate cabiralizumab (FPA008) in a Phase 2 study in the orphan indication, PVNS, as part of its independent development. 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.