Cabiralizumab (FPA008)

Cabiralizumab also targets the macrophages that form the tumor mass in pigmented villonodular synovitis. 

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) targets tumor-associated macrophages (TAMs) are elevated in many tumors and are thought to be involved in suppressing the immune response against tumors. 

fpa008mechanism

Cabiralizumab (FPA008) Status

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. 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.

Five Prime is also evaluating cabiralizumab (FPA008) in a Phase 2 study in the orphan indication, PVNS, as part of its independent development. PVNS is a rare, locally aggressive tumor of the synovium. It is characterized by local over-expression of CSF-1, which recruits macrophages into the joints, forming the non-malignant tumor mass. It is associated with high morbidity, and there are no approved therapies for the condition. 

Collaboration Agreement

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 also has an option to co-promote cabiralizumab in the United States.