Cabiralizumab (FPA008)

Cabiralizumab (FPA008) is an antibody that inhibits colony stimulating factor-1 receptor (CSF1R) that emerged from Five Prime’s discovery platform.  Five Prime set out to discover the most potent modulators of macrophage survival by screening its comprehensive library of extracellular proteins.  Using our discovery platform, we identified a novel protein target called interleukin 34 (IL-34) that activates 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 targets tumor-associated macrophages (TAMs), which are elevated in many tumors and thought to be involved in suppressing the immune response against tumors.  Cabiralizumab also targets the macrophages that form the tumor mass in pigmented villonodular synovitis (PVNS), which is also known as tenosynovial giant cell tumor (TGCT).

fpa008mechanism

Cabiralizumab (FPA008) Status

We are currently studying cabiralizumab (FPA008) in a Phase 1a/1b clinical trial (NCT02526017) evaluating it in combination with OPDIVO® (nivolumab), Bristol-Myers Squibb's (BMS) 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.

In January 2018, our partner, BMS, initiated a multi-arm Phase 2 clinical trial (NCT03336216), evaluating cabiralizumab and Opdivo® (nivolumab) with and without chemotherapy in patients with advanced pancreatic cancer that has progressed following first-line chemotherapy. Effective treatment for patients with microsatellite stable (MSS) pancreatic cancer remains a significant unmet need and is a cancer for which existing immunotherapies have not demonstrated success to date, as the vast majority of pancreatic cancers are of the MSS type.

Five Prime is also evaluating cabiralizumab monotherapy in a Phase 2 study (NCT02471716) in the orphan indication, PVNS. 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 a 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.