Initiation of fruquintinib Phase III registration study in colorectal cancer

Shanghai – Monday, December 15, 2014: HMP today announces that it has initiated FRESCO, a Phase III registration study in colorectal cancer (“CRC”) patients in China, for fruquintinib (HMPL-013), its investigational small molecule which selectively inhibits vascular endothelial growth factor receptors (“VEGFR”).  Preparations and site selection began in the middle of this year, with the first patient dosed on December 12, 2014.

This randomized, double-blind, placebo-controlled, multicenter, Phase III registration study is targeted at treating patients with locally advanced or metastatic CRC, who have failed at least two prior systemic antineoplastic therapies, including fluoropyrimidine, oxaliplatin and irinotecan.  Patients will be randomized at a 2:1 ratio to receive either: 5 milligrams of fruquintinib orally once per day, on a three-weeks-on / one-week-off cycle, plus best supportive care (“BSC”); or placebo plus BSC.  The primary endpoint is overall survival, with secondary endpoints including progression free survival, objective response rate, disease control rate and duration of response.  More than 400 patients will be enrolled in about 25 centers, with top-line results expected in 2016.

Fruquintinib is designed to selectively inhibit VEGF receptors, namely VEGFR1, VEGFR2, and VEGFR3.  In the first-in-human Phase I clinical trial 40 patients were treated with fruquintinib. Detailed results of the Phase I clinical trial are available at http://chi-med.com/eng/irinfo/presentations.htm, and were presented at the annual meeting of the American Association for Cancer Research in April 2013.  Based on the Phase I data in CRC, a Phase Ib study was initiated which treated a further 62 CRC patients.  Detailed results of the Phase Ib clinical trial were presented at the annual meeting of the American Society of Clinical Oncology in May 2014, and also can be found at http://chi-med.com/eng/irinfo/presentations.htm.  Clinical trials for solid tumors including CRC, non-small cell lung cancer and gastric cancer are ongoing at various stages in China as either single-agent therapy or combined with chemotherapy.

In October 2013, HMP entered into a licensing, co-development and commercialisation agreement in China with Eli Lilly and Company for fruquintinib.

About vascular endothelial growth factor (“VEGF”) and colorectal cancer in China

At an advanced stage, tumors secrete large amounts of VEGF, a protein ligand, to stimulate formation of excessive vasculature (angiogenesis) around the tumor in order to provide greater blood flow, oxygen, and nutrients to the tumor. VEGF and VEGF receptors (“VEGFRs”) play a pivotal role in tumor -related angiogenesis, and inhibition of the VEGF/VEGFR pathway. This represents an exciting therapeutic strategy in blocking the development of new blood vessels essential for tumors to grow and invade.

In 2012, there were an estimated 390,000 cases of colorectal cancer diagnosed in China, 10.2% of the total China cancer incidence, making colorectal cancer the third most commonly diagnosed cancer in China.  It was the fifth most common cause of cancer death in China after lung, liver, stomach and esophagus cancer.

To date, several anti-VEGF/VEGFR agents have shown clinical efficacy against a number of tumor types. Given the scale and growth in the China oncology market, the market for VEGF/VEGFR inhibitors in China is expected to develop quickly in the next few years.

The Phase III Trial Evaluating Fruquintinib Efficacy and Safety in 3+ Line Colorectal Cancer Patients (“FRESCO”) can be found under ClinicalTrials.gov identifier NCT02314819.