Shanghai, China, 16th June, 2020 ? Shanghai Henlius Biotech, Inc. (2696.HK) today announced that the HLX04-mCRC03 study has successfully met the predefined primary endpoint. HLX04-mCRC03 is a randomized, double-blind, parallel-controlled, multi-centre phase 3 clinical trial comparing the efficacy, safety and immunogenicity of HLX04 (bevacizumab biosimilar) or bevacizumab (Avastin?) in combination with oxaliplatin and fluoropyrimidine-based chemotherapy (XELOX or mFOLFOX6) as first-line treatment in patients with metastatic colorectal cancer (mCRC). Professor Shukui Qin of No.81 Hospital of People's Liberation Army and Professor Jin Li of Shanghai East Hospital affiliated to Shanghai Tongji University are co-leading principle investigators (co-PIs) of this study.

Colorectal cancer is the third most common malignancy in China. There are? 388,000 newly diagnosed colorectal cancer cases in 2015 in China^[1]?and the incidence increases with age. About 290,000 patients die of colorectal cancer? per year, making it a big threat to human lives and health. Metastasis happens frequently in colorectal cancers and the majority of patients with colorectal cancer are diagnosed at advanced stages^[2]. The most common sites for metastasis are liver, lung and abdominal cavity, among which liver metastasis is most frequently seen. There are about 50% of all mCRC patients suffer from liver metastasis^[3]. Currently, surgery and chemotherapy remain the mainstay of mCRC treatment. Clinical studies suggest that combining bevacizumab with chemotherapy can significantly slow the disease progression and prolong survival for mCRC patients; therefore, this combination therapy is the current standard of care for first-line mCRC treatment.

HLX04 is a bevacizumab biosimilar independently developed by Henlius in accordance with the Chinese biosimilar guideline. The target indications of HLX04 include mCRC and non-squamous non-small-cell lung cancer. Bevacizumab can specifically bind with vascular endothelial growth factor (VEGF) to inhibit tumour angiogenesis^[4]. VEGF acts to promote the growth of blood vessels, which is important for wound healing and the maintenance of normal functions. However, VEGF can also activate tumour angiogenesis and thus promote tumour growth. Via blocking the binding of VEGF and its receptor, HLX04 can inhibit tumour angiogenesis and prevent tumour growing or metastasis.

HLX04 is shown to be highly similar to the reference product in product quality, pharmacology, pharmacokinetics, pharmacodynamics, toxicology and immunogenicity in analytical studies, preclinical studies and phase 1 clinical study. During the 2018 annual meeting of Chinese Society of Clinical Oncology (CSCO), Henlius has presented the data from the multi-centre, randomized, double-blinded, four-arm parallel Phase 1 clinical pharmacology equivalent study of HLX04. Results from this study showed that HLX04 is bioequivalent to the reference products (Avastin? of United States licensed, European Union approved and China approved) in pharmacokinetics and the incidence of adverse events is also similar to the reference products. These results established a solid foundation for the following Phase 3 study.

Bevacizumab originator has been approved in China for the treatment of mCRC and advanced, metastatic or relapsed non-small-cell lung cancer. Bevacizumab has also been included in the National Reimbursement Drug List in 2017. According to estimated data from IQVIA CHAP?, the sales of bevacizumab in China has reached RMB 2.878 billion in 2019.

In addition, Henlius innovatively explores the regimen of HLX04 combined with Henlius own anti-PD-1 monoclonal antibody (mAb) HLX10, leading the immune-oncology mAb combination therapy in China. HLX10 combined with HLX04 for the treatment of advanced solid tumour is the first domestic mAb combination therapy approved for clinical trials in China. Henlius has successfully initiated the pivotal Phase 3 clinical trial (HLX10-002-NSCLC301; NCT03952403) of this combination therapy as first-line treatment in non-squamous non-small cell lung cancer. It is a three-arm, randomized, double-blind, multi-centre Phase 3 trial, aiming to compare the efficacy and safety of HLX10 in combination with chemotherapy, HLX10 + HLX04 in combination with chemotherapy and chemotherapy alone. At the same time, the clinical trial of the combination of HLX10 and HLX04 as second-line treatment of hepatocellular carcinoma has also been initiated. It is a single-arm, open labelled, multi-centre Phase 2 clinical trial, aiming to assess the efficacy, safety and tolerability of HLX10 combined with HLX04 for patients with advanced hepatocellular carcinoma who have progressed after standard treatment or are intolerable to standard treatment. There are few studies exploring the effect of immune checkpoint inhibitors combined with anti-angiogenesis mAbs in this indication in China and Henlius is currently leading in progressions in clinical studies in this area.