Shanghai, China, 26 July 2023 - Shanghai Henlius Biotech, Inc. (2696.HK) announced a phase 1/2 clinical trial of HLX04-O, a recombinant anti-VEGF humanised monoclonal antibody injection jointly developed by the company and Essex, has been completed in patients with wet age-related macular degeneration (wAMD). The results of this study demonstrated the good safety and tolerability of HLX04-O.

This single-arm, open-label, multicentre, phase 1/2 study aimed to evaluate the safety and preliminary efficacy of HLX04-O via intravitreal injection (IVT) in patients with active wet age-related macular degeneration (wAMD). The study consisted of two parts. Part 1 was a safety run-in stage which enrolled 6 patients. Part 2 was a single-arm, open-label, multicentre, phase 2 study and 20 patients (including 6 patients from part 1) were enrolled in this part. All patients received HLX04-O IVT (1.25 mg/0.05 mL) every four weeks until death, withdrawal of informed consent, loss to follow-up, study termination by sponsor, or completion of one-year treatment. For part 1, the primary endpoint was safety event related to HLX04-O that occurred within four weeks after the first dose of HLX04-O; secondary endpoints were the systemic pharmacokinetic characteristics of HLX04-O after the first and fourth IVT administration. For part 2, the primary endpoint was the mean change of letters from baseline in best corrected visual acuity (BCVA) at week 12; secondary endpoints included other efficacy measures, safety, immunogenicity, and systemic pharmacokinetic characteristics. The results showed that HLX04-O was safe and well tolerated in wAMD patients, and preliminary efficacy was observed.

HLX04-O is a recombinant anti-VEGF humanized monoclonal antibody injection constructed using genetic engineering technology independently developed by Henlius. 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 signalling pathway, inhibit endothelial cell proliferation and reduce angiogenesis, thereby treating eye diseases associated with angiogenesis. According to the requirements of ophthalmic drugs, the Company has developed HLX04-O which optimizes the prescription, specifications, and production processes of HANBEITAI, assuming that the active ingredients remain unchanged. Through a series of comparability analysis, it is proved that the changes in the production process and prescription of the preparation have no adverse impact on the quality, safety and efficacy of the preparation.

As of now, the clinical trial applications of HLX04-O had been approved in Singapore and other countries and regions. Moreover, the first patients in the United States (US), China, the European Union (EU) and Australia were dosed in phase 3 clinical trials of HLX04-O for wAMD. Through the cooperation with Essex, Henlius will speed up the clinical trials of HLX04-O around the globe and apply marketing authorization in China, Australia, the EU, and the US based on the research results. HLX04-O has the potential to be one of the first bevacizumab approved for ophthalmic diseases, benefiting more patients with eye diseases worldwide. Looking forward, Henlius will always place a high value on clinical data and will continue to diversify innovation by strengthening internal innovation capabilities and external collaboration, extending new drug forms, and processing more clinical trials to generate more effective treatments.

About wAMD

Age-related macular degeneration 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 become blind due to AMD each year ^[2]. Wet age-related macular degeneration (wAMD) is characterized by the formation of subretinal choroidal neovascularization (CNV) and is responsible for approximately 90% of cases of AMD-related blindness. Due to an aging population, 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^-6.

About Henlius

Henlius (2696.HK) is a global biopharmaceutical company with the vision to offer high-quality, affordable, and innovative biologic medicines for patients worldwide with a focus on oncology, autoimmune diseases, and ophthalmic diseases. Up to date, 5 products have been launched in China, 1 has been approved for marketing in overseas markets, 18 indications are approved worldwide, and 3 marketing applications have been accepted for review in China, the U.S., and the EU, respectively. Since its inception in 2010, Henlius has built an integrated biopharmaceutical platform with core capabilities of high-efficiency and innovation embedded throughout the whole product life cycle including R&D, manufacturing and commercialization. It has established global innovation centers and Shanghai-based manufacturing facilities in line with global Good Manufacturing Practice (GMP), including Xuhui Plant certificated by China and the EU GMP and Songjiang First Plant certificated by China GMP.

Henlius has pro-actively built a diversified and high-quality product pipeline covering over 20 innovative monoclonal antibodies (mAbs) and has continued to explore immuno-oncology combination therapies with proprietary HANSIZHUANG (anti-PD-1 mAb) as backbone. Apart from the launched products HANLIKANG (rituximab), the first China-developed biosimilar, HANQUYOU (trastuzumab for injection, trade name in Europe: Zercepac^®; trade names in Australia: Tuzucip^® and Trastucip^®, the first China-developed mAb biosimilar approved both in China and Europe, HANDAYUAN (adalimumab) and HANBEITAI (bevacizumab), the innovative product HANSIZHUANG has been approved by the NMPA for the treatment of MSI-H solid tumors, squamous non-small cell lung cancer (sqNSCLC) and extensive-stage small cell lung cancer (ES-SCLC), making it the world’s first anti-PD-1 mAb for the first-line treatment of SCLC. Its NDA for the treatment of esophageal squamous cell carcinoma (ESCC) is under review. What's more, Henlius has conducted over 30 clinical studies for 16 products, expanding its presence in major markets as well as emerging markets.

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