Shanghai, China, September 9th, 2020 ?Shanghai Henlius Biotech, Inc. (2696.HK) announced that the New Drug Application (NDA) of its bevacizumab biosimilar HLX04 has been accepted by the National Medical Products Administration (NMPA). HLX04, which becomes the fourth product of Henlius that has received NDA acceptance notification from NMPA, can be potentially used for the treatment of advanced, metastatic or recurrent non-small cell lung cancer and metastatic colorectal cancer. Henlius has previously submitted NDAs for its rituximab biosimilar????^?, trastuzumab biosimilar????^?(HLX02, EU brand name: Zercepac^?)and adalimumab HLX03. The NDAs of ???^??and ???^??have been approved successively.

HLX04 was developed with the bevacizumab originator as reference product and the development process is in line with China?s biosimilar guidelines. Via specific binding with vascular endothelial growth factor (VEGF), HLX04 can block the interaction between VEGF and its receptors. This will inhibit tumour angiogenesis, which is essential for the growth and metastases of tumour.

The NDA of HLX04 is mainly supported by a series of study data, including comparative pharmaceutical quality studies, comparative non-clinical studies, comparative clinical studies. Different from currently approved bevacizumab biosimilars in China, the phase 3 study of HLX04 was conducted among Chinese patients with metastatic colorectal cancer, which helps to accumulate more clinical evidence and experience of bevacizumab in this patient population. Recently, this study has reached its primary and secondary endpoints. This is a randomized, double-blind, parallel-controlled, multicenter phase 3 clinical trial aimed to compare the efficacy, safety and immunogenicity of HLX04 or the reference bevacizumab in combination with oxaliplatin and fluoropyrimidine-based chemotherapy (XELOX or mFOLFOX6) as first-line treatment in patients with metastatic colorectal cancer. The primary endpoint of this comparative study, progression-free survival rate at week 36 (PFSR36w), was met after the database lock (DBL) as assessed by committee. Study results show that HLX04 is similar to the reference product in terms of efficacy, safety and immunogenicity. Detailed data of this phase 3 study will be presented on 19th September by Professor Li Jin, the leading principle investigator of this study, during the 23rd annual conference of Chinese Society of Clinical Oncology (CSCO).

Among all malignant tumours, lung cancer has the highest incidence both in China and around the globe and is the leading cause of cancer death. According to GLOBOCAN data, there is estimated to be 774,000 new cases of lung cancer and around 690,000 patients die of lung cancer in 2018. Non-small cell lung cancer take up to 80%-85% of all lung cancer cases, making it the most common type of lung cancers. The incidence of colorectal cancer ranks second among all malignant tumours in China, with 522,000 new cases in 2018. Clinical study showed that adding bevacizumab to traditional chemotherapies can significantly delay disease progression and prolong survival for patients with metastatic colorectal cancer. However, due to reasons like drug accessibility, there still exists unmet medical needs of bevacizumab in China. According to Frost & Sullivan, sales of bevacizumab has reached RMB 320 million in 2018. With the launching of bevacizumab biosimilars and with more bevacizumab combos being approved, sales of bevacizumab has the potential to reach RMB 1.77 billion in 2030.

Leveraging Henlius? broad pipeline, the company is actively developing combo therapies of HLX04 and its anti-PD-1 monoclonal antibody (mAb) HLX10 for the treatment of various solid tumours. Of note is that HLX04 plus HLX10 is the first domestic dual mAb combo therapy that has received IND approval. Clinical development of this combo in first-line non-squamous non-small cell lung cancer patients has entered pivotal phase 3 stage. The design of this study has taken into consideration advantages of other similar trials and has its own innovations as well. It is a three-arm study to compare the efficacy and safety of the combination of HLX10 and chemotherapy, the combination of HLX10, HLX04 and chemotherapy and chemotherapy alone. Clinical development of HLX10 and HLX04 combination among second-line liver cancer patients has entered phase 2. Currently, there are few studies exploring combinations of immune checkpoint inhibitors and anti-angiogenesis drugs in this patient population in China and this phase 2 study is in a leading position in this area. In addition, Henlius is also developing HLX04 for ophthalmic diseases, including wet age-related macular degeneration and diabetic retinopathy, with the aim to benefit a broader patient population.