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First Patient Dosed in Phase 1 Clinical Trial of Henlius Bevacizumab HLX04-O

Shanghai, China, July, 19th, 2021 - Shanghai Henlius Biotech, Inc. (2696.HK) announced that the first patient was dosed in a Phase 1 clinical trial in China for HLX04-O, a recombinant anti-VEGF humanized monoclonal antibody injection jointly developed by the Company and Essex, for the treatment of wet age-related macular degeneration (wAMD).

This is a single-arm Phase 1 clinical study conducted in patients with wAMD. As a safety run-in stage, six to twelve patients were planned to be enrolled in this study. The primary objective is to evaluate the safety and tolerability of HLX04-O in the study eye of wAMD patients. The secondary objective is to evaluate the systemic pharmacokinetic profiles of HLX04-O after intravitreal injection. Previously, a series of studies including non-clinical pharmacodynamics, safety pharmacology, repeat-dose toxicity, pharmacokinetics, toxicokinetics, immunotoxicity, immunogenicity, and local irritation of HLX04-O vitreous injection in the treatment of wAMD have been carried out, providing clinical evidence on effectiveness and safety of HLX04-O.

Age-related macular degeneration (AMD) is one of the leading causes of visual impairment and blindness in the elderly worldwide[1]. According to the World Health Organization (WHO), about 30 million people have suffered from AMD globally, and about half a million people go blind due to AMD each year[2]. wAMD is characterized by the formation of subretinal choroidal neovascularization (CNV) and accounts for approximately 90% of all AMD-related blindness. Due to population aging, wAMD has become a serious social medical problem and indicated a huge burden of unmet need[3]. With the development of treatment for fundus diseases, anti-VEGF drugs are becoming the first-line therapy for the management of wAMD[4], and the efficacy and safety of vitreous injection of bevacizumab for wAMD have been verified in multiple clinical studies[5-11].

In October 2020, Henlius entered into a co-development and exclusive license agreement with Essex. With this collaboration, Henlius and Essex plan to conduct global multi-centre clinical trials of HLX04-O in China, Australia, the European Union(EU) and the United States(US), and apply marketing authorization in different countries and regions around the globe based on the research results. As of now, HLX04-O has received clinical approvals in China, Australia, the US, Singapore and EU countries including Latvia, Hungary and Spain with global multi-centre clinical trials gathering pace.

It is believed that through the collaboration of Henlius and Essex, HLX04-O has the potential to be one of the first bevacizumabs approved for ophthalmic diseases, benefiting more patients with eye diseases worldwide. Looking forward, Henlius will continue advancing the development of innovative biologics by the virtue of its established and integrated innovation platform, underscoring its long-term commitment to providing affordable and effective therapies for patients worldwide.

About HLX04-O

HLX04-O is a new ophthalmic preparation product developed based on HLX04, a bevacizumab biosimilar independently developed by the Company, through optimizing the prescription, specifications and production processes of HLX04 according to the requirements of ophthalmic drugs, without changing the active ingredients, and is intended to be used for the treatment of wAMD. By means of comparability studies, it shows that changes in production processes and prescriptions of the preparation have no adverse impact on the quality, safety and efficacy of the pharmaceutical preparation. HLX04-O can inhibit VEGF’s binding to its receptor Flt-1(VEGFR-1) and KDR(VEGFR-2) on endothelial cells to inhibit the activation of its tyrosine kinase signaling pathway, inhibit endothelial cell proliferation and reduce angiogenesis, thereby treating eye diseases associated with angiogenesis.

Reference Notes:
[1] 欧阳灵艺, 邢怡桥. 抗VEGF药物在湿性年龄相关性黄斑变性中的应用进展[J]. 国际眼科杂志, 2020(1).
[2] Resnikoff S, Pascolini D, Etya'ale D, Kocur I, Pararajasegaram R, Pokharel GP, Mariotti SP. Global data on visual impairment in the year 2002. Bull World Health Organ. 2004 Nov;82(11):844-51.
[3] Wong WL, Su X, Li X, et al. Global prevalence of age-related macular degeneration and disease burden projection for 2020 and 2040: a systematic review and meta-analysis. Lancet Glob Health. 2014;2(2):e106-116.
[4] Li X R , Liu J P . Recognition of anti-VEGF therapy base on the mechanism of VEGF in wet age-related macular degeneration[J]. Zhonghua Shiyan Yanke Zazhi/Chinese Journal of Experimental Ophthalmology, 2012, 30(4):289-292.
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[6] Martin DF, Maguire MG, Ying GS, Grunwald JE, Fine SL, Jaffe GJ. Ranibizumab and bevacizumab for neovascular age-related macular degeneration. N Engl J Med. 2011 May 19;364(20):1897-908.
[7] Chakravarthy U, Harding SP, Rogers CA, Downes SM, Lotery AJ, Wordsworth S, Reeves BC. Ranibizumab versus bevacizumab to treat neovascular age-related macular degeneration: one-year findings from the IVAN randomized trial. Ophthalmology. 2012 Jul;119(7):1399-411.
[8] Kodjikian L, Souied EH, Mimoun G, Mauget-Faÿsse M, Behar -Cohen F, Decullier E, Huot L, Aulagner G; GEFAL Study Group. Ranibizumab versus Bevacizumab for Neovascular Agerelated Macular Degeneration: Results from the GEFAL Noninferiority Randomized Trial. Ophthalmology. 2013 Nov;120(11):2300-9.
[9] Krebs I, Schmetterer L, Boltz A, Told R, Vécsei-Marlovits V, Egger S, Schönherr U, Haas A, Ansari-Shahrezaei S, Binder S; MANTA Research Group. A randomized double-masked trial comparing the visual outcome after treatment with ranibizumab or bevacizumab in patients with neovascular age-related macular degeneration. Br J Ophthalmol. 2013 Mar;97(3):266-71.
[10] Berg K, Pedersen TR, Sandvik L, Bragadóttir R. Comparison of ranibizumab and bevacizumab for neovascular age-related macular degeneration according to LUCAS treat-and-extend protocol. Ophthalmology. 2015 Jan;122(1):146-52.
[11] Schauwvlieghe AM, Dijkman G, Hooymans JM, Verbraak FD, Hoyng CB, Dijkgraaf MG,Peto T, Vingerling JR, Schlingemann RO. Comparing the Effectiveness of Bevacizumab to Ranibizumab in Patients with Exudative Age-Related Macular Degeneration. The BRAMD Study. PLoS One. 2016 May 20;11(5):e0153052.