ZXH951 project

　　ZXH951 is a Class I new drug (new chemical entity, NCE) currently under joint development by Shanghai Zhongxi Pharmaceutical Co., Ltd, Zhejiang Xianju Pharmaceutical Co., Ltd. and SiniWest Holdings, Inc. (USA) with self-owned intellectual property and product manufacturing rights. This NCE is a novel progesterone receptor (PR) antagonist and relevant patents have been filed in China, U.S.A., U.K. and internationally (PCT).

　　Based on the pharmacological property of ZXH951, it can be used for the treatment of hormone-dependent breast cancer, early pregnancy termination and emergency contraception. According to the investigational new drug (IND) application guidelines set forth by the SDA, systemic studies have been carried out by the joint product development group including chemistry, manufacturing, control (CMC), pharmacology and toxicology.

　　Pharmaceutical research confirmed the chemical structure of ZXH951, developed synthetic routes and production processes, and established quality control (QA/QC) methods. As shown by pharmacological studies, ZXH951 has significant inhibitory effects on proliferation of breast cancer cells which possess both progesterone and estrogen receptors; suppresses the growth of hormone-dependent breast cancer in animal models; has both preventive therapeutic properties; can significantly inhibit growth of multiple drug-resistant tumor cell lines and reverse the resistance; demonstrates negative effects on tumor cell adhesion, mobilization and invasion; inhibit new blood vessel formation, and blocks tumor metastasis in vivo. Meanwhile, early pregnancy termination and anti-implantation (including mechanisms of action) studies were performed in animals which indicate that ZXH951 has a better efficacy than the control drug (RU486). Acute and chronic toxicology experiments suggest that ZXH951 is safe and has no teratogenic and mutagenic effects. General pharmacology tests show ZXH951 to have no adverse effects on animal respiratory, CNS and cardiovascular systems. Therefore, preclinical studies on ZXH951 carried out in recent years have achieved the targeted goals.

Clinical indications

Newly diagnosed hormone-dependent breast cancer patients and breast cancer patients who developed drug-resistant during chemotherapy.

　　Breast cancer ranks number one in all female tumors. There are over 1.2 million new cases of breast cancer and 0.5 million deaths recorded each year worldwide according to the WHO statistics. Around 8.2 million breast cancer patients currently live in the world. Estimated conservatively, annual sales of anti-breast cancer drugs amount at over US$12 billion. Assuming that ZXH951 can occupy 7% of international breast cancer drug market, sales are expected to be US$84 million (around RMB￥700 million).

　　In China, it is estimated that between 50,000 and 90,000 new cases of breast cancer were diagnosed with 30,000 to 40,000 deaths recorded each year. In the coastal big cities such as Shanghai, breast cancer has become number one in all-female tumors. There are about 120,000 to 150,000 breast cancer patients who require treatment or clinical monitoring each year. About two thirds of breast cancer patients use hormone therapy and major drugs include tamoxifen, medroxy progesterone acetate (MPA) and megesterol acetate("Megace"), etc. The mechanisms of action are to block estrogen supply, but clinical efficacies are not ideal (effective rate is 30%-50%). The newly launched new drug, Femara, has a good effect on tamoxifen-resistant patient. Sales reached US$500 million in the first quarter of this year. The pharmacological mechanism of ZXH951 is novel and is complementary to tamoxifen. Therefore, it is possible that using the two drugs jointly may achieve additive effect and ZXH951's market prospect is rather promising.

Early pregnancy termination and emergency contraception.

　　According to the WHO statistics, there are around 50 million cases of unwanted pregnancy termination each year in the world, including at least 20 million cases in China. As estimated, the world market size for this indication is around US$200 million (RMB￥1.65 billion) and the domestic market share would be around RMB￥430 million (based on RMB￥25 per treatment). Projected conservatively, with a market share of 30% and the revenue from ZXH951 sales will be RMB￥130 million when the market matures.

　　Furthermore, according to analysis on artificial abortion figures at present, demand for emergency contraception will be 3-5 times higher. Therefore, the worldwide cases for emergency contraception would be between 150 and 250 million, including 51-85 million cases in China. If the ex-manufacturing price is RMB￥9 per use, the domestic market size would be between RMB￥460 and 770 million. Projected conservatively, with a market share of 30%, ZXH951's sales revenue will be RMB￥140 to 230 million and the medium figure is RMB￥190 million. Domestic sales for these two indications are expected to be RMB￥320 million.