Despite the availability of a number of new targeted therapies, many cancers, particularly, solid tumors, remain refractory to treatment or cure. Tumor growth and malignant progression frequently involve the expression of genes coding for secreted proteins and extracellular receptors that result in significantly altered and abnormal cell growth as well as perturbations in multiple regulatory pathways. FivePrime’s oncology discovery efforts are focused on the identification of the key secreted proteins and extracellular receptors that drive tumor growth, angiogenesis, metastasis, and resistance to chemotherapy. 

FivePrime’s approach entails a combination of in vivo and cell-based screens that utilize the company’s proprietary cancer models. These models include tumor xenografts that are derived directly from human primary tumors and which, because they are maintained in animals rather than on plastic dishes, maintain the complex histological characteristics of human cancers. Our cell-based models include cancer stem cell lines that have been isolated by FivePrime’s scientists and validated to be highly tumorigenic. 

FivePrime’s lead product in oncology is FP-1039, a first in class ligand trap that inhibits most members of the FGF (Fibroblast Growth Factor) family.  FGF proteins are growth factors that, along with VEGF (Vascular Endothelial Growth Factor) and EGF (Epidermal Growth Factor), play important roles in the growth and maintenance of many solid tumors.

FP-1039 is a soluble fusion protein consisting of the extracellular portion of Fibroblast Growth Factor Receptor 1 (FGFR1) that is attached to the base of a human antibody. The drug is designed to neutralize the activity of the several different FGF ligands and inhibit their signaling through all of the different FGF receptors. Data indicate that FP-1039 is a very effective inhibitor of the complex and crucial FGF signaling pathway. Moreover, FP-1039 is expected to exert a dual effect on cancer cells both as a result of direct inhibition of tumor cell growth as well as by the inhibition of tumor-associated angiogenesis—both of which are FGF mediated processes.    

Work by academic groups has established that: 

•  Over-expression of FGF ligands and/or receptors correlates with poor prognosis in a variety of tumor types

•  Genomic amplification of the FGFR1 gene has been detected in several types of cancer, including breast cancer where this amplification correlates with poor survival and increased metastases

•  Stimulation of the FGF pathway increases cell proliferation in multiple cancer cell lines

•  Inhibitors of the FGF pathway can suppress angiogenesis in tumors that have escaped VEGF blockade in vivo

•  The FGF pathway may be necessary for maintaining the tumorigenicity of cancer stem cells 

In preclinical studies at FivePrime, FP-1039:

•  Demonstrated direct anti-tumor activity in a variety of in vivo and in vitro models, including in patient derived xenografts

•  Strongly inhibited both FGF and VEGF induced angiogenesis in vivo 

FP-1039 is currently being studied in a Phase I dose escalation trial in patients with advanced solid tumors at two leading oncology centers. Patients receive weekly doses of FP-1039 by intravenous administration to characterize its safety and tolerability.  Additionally, the pharmacokinetics and preliminary anti-tumor activity of FP-1039 are being assessed.  For more information on FP-1039 Phase I Clinical Trial please visit:  http://www.clinicaltrials.gov/ct2/show/NCT00687505?term=five+prime&rank=1 .