Fruquintinib

Key Features and Advantages

  • Currently in Phase II & III clinical trial in patients with solid tumors, including colorectal, lung and gastric cancer
  • MOA: inhibits all three forms of VEGF receptors (VEGFR-1,2,3)
  • Demonstrated highly potent efficacy and safety profile in vitro and in vivo

Fruquintinib (HMPL-013) is a novel small molecule compound that selectively inhibits vascular endothelial growth factor receptors (VEGFRs). In low oral doses, fruquintinib has potent inhibitory effects on multiple human tumor xenografts, including some refractory tumors such as pancreatic cancer and melanoma. The unique kinase selectivity and potent profile provides a promising compound opportunity and strong differentiation against existing products on the market such as Sutent™ and Nexavar™ as well as other compounds currently in the clinical development for cancer.

In vitro, fruquintinib demonstrated a highly potent and selective kinase profile against VEGF receptors 1,2 and 3. In vivo, fruquintinib demonstrated broad spectrum anti-tumor activity via oral dosing in multiple tumor xerografts such as BGC-823, BXPC-3 and A375.

Non-clinical safety studies carried out by Hutchison MediPharma indicated that fruquintinib is generally well tolerated in animals. Fruquintinib is neither mutagenic nor teratogenic. GLP-toxicity studies in rats and dogs indicated fruquintinib has a better safety window.

About the Vascular Endothelial Growth Factor in Cancer Tumors
Angiogenesis, the process of developing new blood vessels, is critical for tumor cell growth, survival, invasion and metastasis. The vascular endothelial growth factor (VEGF) and VEGF receptors (VEGFRs) play a pivotal role in tumor-related angiogenesis, and the VEGF/VEGFR pathway is an important target for anti-angiogenic drug development and tumor therapy. Inhibition of VEGF signaling in tumor vasculature therefore represents an exciting therapeutic strategy, with the potential to arrest the development of new blood vessels essential for tumor growth and metastasis. Several anti-VEGF agents have shown efficacy in a range of tumor types.