SHANGHAI, China I October 15, 2020 I Shanghai Henlius Biotech, Inc. (2696.HK) announced that the company entered into a co-development and exclusive license agreement with Essex Bio-Investment and Zhuhai Essex (collectively called Essex), two wholly-owned subsidiaries of Essex Bio-Technology Limited (Essex Bio-Technology, 1061.HK). Pursuant to the agreement, Henlius agreed to co-develop its bevacizumab HLX04 indicated for ophthalmic diseases such as wet age-related macular degeneration (wAMD) with Essex and to grant an exclusive license to Essex to develop, manufacture and commercialize HLX04 in the field of human ophthalmic therapies globally.

According to the agreement, Henlius will be mainly responsible for the pre-clinical and clinical development of HLX04, whereas, Essex is responsible for regulatory filings and commercialisation of HLX04 globally. Essex will be responsible for 80% of all costs and expenses in relation to the development of HLX04. After signing the agreement and upon reaching of certain milestones, Henlius is entitled to receive a signing payment and subsequent regulatory and commercial milestone payments of up to US$43 million. In addition, Henlius is also entitled to receive US$30 million for every US$1 billion above the first US$600 million of the cumulative net sales. Henlius will also be eligible to receive royalties of up to 10% of the product annual net sales. Essex has a right to grant a sublicense to third parties and Henlius is entitled to receive 20% of the related sublicensing revenue, and the relevant share ratio can be adjusted through bilateral negotiation. Through this collaboration, Henlius and Essex will share the risks and costs in the development of HLX04 for the treatment of ophthalmic diseases. This collaboration will fully utilize the advantages of Henlius in research and development and Essex in global commercialisation of ophthalmic drugs, to best strategize for the global development and commercialization of HLX04.

The incidence of ophthalmic diseases is increasing year by year in China, especially in the middle-aged and elderly patients. As of now, the number of patients with wAMD has exceeded 5 million in China and up to 30 million worldwide [1-2]. HLX04 (recombinant anti-VEGF humanized monoclonal antibody injection) is a bevacizumab biosimilar independently developed and manufactured by Henlius. Via specific binding with vascular endothelial growth factor (VEGF), HLX04 can block the interaction between VEGF and its receptors, thus inhibiting angiogenesis. Results from pre-clinical and clinical studies have demonstrated significant efficacy of VEGF inhibitors on ophthalmic diseases caused by fundus angiogenesis [3-4]. Since bevacizumab has not been approved for the treatment of ophthalmic diseases globally despite of its broad use, HLX04 has the potential to be one of the first bevacizumabs approved for these indications.

With the aim to benefit a broader patient population, Henlius is developing HLX04 for ophthalmic diseases, including wet age-related macular degeneration (wAMD) and diabetic retinopathy (DR). In January 2019, the investigational new drug application (IND) of HLX04 for indications of wAMD and DR has been approved by the NMPA. With this collaboration, Henlius and Essex plan to conduct global multi-centre clinical trials of HLX04 in China, Australia, the European Union and the United States, and apply marketing authorization in different countries and regions around the globe based on the research results. Meanwhile, Henlius has submitted a patent for a new formulation of HLX04 with potential better safety and stability, designed for ophthalmic use. 

In the future, Henlius will also actively collaborate with more partners to make progress by win-win cooperation and bring more high-quality and affordable biologics through consistently innovation to benefit patients around the world.

About oncology indications of HLX04

In addition to potential in the treatment of ophthalmic diseases, HLX04 is also essential for the inhibition of tumour angiogenesis, growth and metastases [5]. Recently, the phase 3 clinical trial of HLX04 in metastatic colorectal cancer has successfully met its primary and secondary endpoints and Henlius has submitted a New Drug Application (NDA) of HLX04 for the treatment of advanced, metastatic or recurrent non-small cell lung cancer and metastatic colorectal cancer to the National Medical Products Administration (NMPA) and has received the NDA acceptance notification from NMPA. At the same time, Henlius is also actively carrying out the clinical study of HLX04 in combination with HLX10 (an innovative anti-PD-1 mAb) of Henlius, and the indications cover multiple advanced solid tumours such as metastatic non-squamous non-small cell lung cancer (phase 3 clinical trial) and advanced hepatocellular carcinoma (phase 2 clinical trial).

About Essex Bio-Technology

Essex Bio-Technology is a bio-pharmaceutical company that develops, manufactures and commercialises genetically engineered therapeutic rb-bFGF (FGF-2), having six commercialised biologics marketed in China since 1998. The products of the Company are principally prescribed for the treatment of wounds healing and diseases in Ophthalmology & Dermatology, which are marketed and sold through approximately 8,880 hospitals and managed directly by its 43 regional sales offices in China. Leveraging on its in-house R&D platform in growth factor and antibody, the Company maintains a pipeline of projects in various clinical stages, covering a wide range of fields and indications.

Reference Notes

[1] 华医学会眼科学分会眼底病学组中国老年性黄斑变性临中国老年性黄斑变性临床诊断治疗路径[J]华眼底病杂志,2013,029(004):343-355.
[2] 邹海东,张皙,许迅等.上海市静安区曹家渡街道年龄相关性黄斑变性的患病率调查. 华眼科杂志2005, 41(1):15-19.
[3] Chen C Y, Wong T Y, Heriot W J. Intravitreal Bevacizumab (Avastin) for Neovascular Age-related Macular Degeneration: A Short-term Study [J]. American Journal of Ophthalmology, 2007, 143(3):510-512.
[4] Rich R M , Rosenfeld P J , Puliafito C A , et al. Short-term safety and efficacy of intravitreal bevacizumab (Avastin) for neovascular age-related macular degeneration.[J]. Retina, 2006, 26(5):495.
[5] Kazazi-Hyseni F, Beijnen JH, Schellens JH. Bevacizumab. Oncologist. 2010;15(8):819‐825.

SOURCE: Shanghai Henlius