HMPL-013
Fruquintinib (HMPL-013) is a novel small molecule compound that selectively inhibits vascularendothelial growth factor receptor (VEGFR). In quite low dose, Fruquintinib has potent inhibitory effects on multiple human tumor xenografts, including some refractory tumors such as pancreatic cancer and melanoma. The unique kinase profile provides a promising compound opportunity and strong differentiation against existing products on the market such as Sutent and Nexavar as well as compounds currently in the clinical development for cancer. Hutchison MediPharma has global rights to Fruquintinib.
Key Features
- IND filed with the SFDA in Aug, 2009
- MOA: potent inhibitor targeting tumor angiogenic blood vessels formation
- Demonstrated efficacy and safety profile in vitro and in vivo
- Strong IP protection in chemical compounds and medical use
Mechanism of Action (MOA)
Inhibit all three forms of VEGF receptors (VEGFR-1,2,3)
Competitive Advantages
Competitive Advantages
- Highly potent efficacy and excellent kinase selectivity
- Large safety margin based on preliminary assessment
- Broad spectrum anti-tumor activity
- Low costs of goods. Imported drugs of targeted therapies such as Sutent and Nevavar are very expensive. Fruquintinib is planned to be marketed in China for cancer patients.
- Fruquintinib differentiates from other VEGFR inhibitors in clinical development in China, by inhibiting all three forms of VEGFRs
- Strong IP position and protection
Preclinical Studies
a) Efficacy
- In Vitro: Fruquintinib demonstrated highly potent kinase selectivity profile
- In Vivo: Fruquintinib demonstrated broad spectrum anti-tumor activity via oral dosing in multiple tumor xerografts such as BGC-823、BXPC-3 and A375
b) Safety
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.
Clinical Plans
- Conduct Phase I clinical trial in patients with solid tumors in China estimated at 2Q2010
- Conduct Phase II (POC) clinical trial in patients with multiple types of solid tumors (liver carcinoma, renal carcinoma, colon carcinoma, melanoma, pancreatic carcinoma and NSCLC) in China
Manufacturing
Kilogram quantities of API and drug product have been manufactured under cGMP for the human clinical studies.
Intellectual Property
Hutchison MediPharma filed patent applications both in US and China in 2007 and PCT application in 2008. The applications claimed the chemical compounds and their medical use.
Potential Market of VEGFR Inhibitors
Vascular Endothelial Growth Factor (VEGF) is an important signaling protein involved in both vasculogenesis and angiogenesis. Vascular Endothelial Growth Factor Receptor (VEGFR) tyrosine kinase inhibitor is being developed for the treatment of cancer and acts as an angiogenesis inhibitor.
Vascular Endothelial Growth Factor (VEGF) is an important signaling protein involved in both vasculogenesis and angiogenesis. Vascular Endothelial Growth Factor Receptor (VEGFR) tyrosine kinase inhibitor is being developed for the treatment of cancer and acts as an angiogenesis inhibitor.
Two small molecule VEGFR inhibitors have been launched and indication expansion caused their substantial sales growth in seven major markets from $206 million in 2006 to $685 million in 2008. Datamonitor forecasts the small molecule VEGFR inhibitors will reach to $5.4 billion in 2016.
The current marketed VEGFR inhibitors are quite expensive and have unfavorable side effect profiles. There is a strong market need for a safe oral drug which is effective and convenient. Fruquintinib is currently a promising oral drug candidate in clinical development. Once approved in US and other major markets, Fruquintinib could make the annual sales of $500-$800 million dollars.
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