Drug Research and Development Business

Hutchison MediPharma's development activities are focused on two target therapeutic areas: auto-immune/inflammatory disorders and oncology. Excluding HMPL-004, Hutchison MediPharma's anti-inflammatory drug candidate in phase II clinical trials in North America and Europe, the Company has a pipeline of early stage candidates at or nearing Investigational New Drug (IND) application submission. The discovery portfolio consists of botanical candidates, semi-synthetic natural product drugs, and synthetic single chemical entity projects, including HMPL-011, HMPL-012, HMPL-013, HMPL-813 and HMPL-309.

During 2009, HMPL concluded discovery work on three small molecule drug candidates HMPL-011 for auto-immune disease, and HMPL-012 and HMPL-013, which are both high quality kinase candidates for use in the treatment of cancer. Three IND applications were made during 2009. HMPL-011 was submitted and subsequently approved for Phase I trials in Australia. HMPL-012 and HMPL-013 have been submitted to the SFDA for fast-track IND approval and are currently under review.

HMPL-012 (Sulfatinib) is a novel VEGFR/FGFR compound that inhibits multiple kinases, crucial for tumour growth, apoptosis and invasion/metastasis. Sulfatinib demonstrated broad-spectrum anti-tumor activity via oral dosing against a variety of human tumors in xenograft models. Its unique kinase profile provides a promising opportunity and potential therapeutic differentiation agains existing products on the market. HMPL-012 was submitted to the SFDA in June 2009 for fast-track IND review. It is envisaged that HMPL-012 could be used as a single agent or in combination with chemotherapies for the inhibition of tumour growth as well as invasion/metastasis. HMPL-012 is expected to initiate clinical trials in China in the second quarter of 2010.

HMPL-011 is a novel cytokine modulator that controls the production of pro-inflammatory cytokines. It was advanced into a first-in-human Phase I clinical trial in Australia in October 2009. HMPL-011 is a potential first-in-class new chemical entity with a novel mechanism of action being developed as an oral therapy for auto-immune disease. In pre-clinical studies, the drug candidate has shown efficacy in animal models of rheumatoid arthritis, multiple sclerosis, and other auto-immune diseases. It has demonstrated an acceptable safety margin in animal toxicological evaluations. The Phase I clinical trial is a randomized, placebo-controlled, double-blind, single ascending dose trial in healthy male volunteers. The trial’s primary objective is to evaluate the safety, tolerability, and pharmacokinetics of HMPL-011. The study is expected to report results in the first half of year 2010.

HMPL-013 is another novel chemical entity and the second drug candidate discovered internally for tumour-growth inhibition via blocking the VEGFR (vascular endothelial growth receptor) target. It was submitted to the SFDA in August 2009 for fast-track IND review. It is differentiated from HMPL-012 and other marketed drugs in this class by its kinase selectivity in vitro and superior potency in vivo against a variety of human xenografts. In 2009 the IND-enabling evaluations were completed and an IND application is being prepared.

HMPL progressed two further novel EGFR (epidermal growth factor receptor) inhibitors, HMPL-813 and HMPL-309, into preclinical testing. These two novel chemical entities are highly potent and selective EGFR inhibitors with excellent pharmacokinetic properties and exhibit potent in vivo anti-tumour activity.