Shanghai, China, March, 31, 2020 - Shanghai Henlius Biotech, Inc. (2696.HK) announced that HLX07, a recombinant anti-epidermal growth factor receptor (EGFR) humanised monoclonal antibody (mAb) injection, demonstrated favorable safety and tolerability profile in a prospective, open-label, dose-escalation Phase 1 clinical study (HLX07FIH, NCT02648490) for the treatment of advanced solid tumours. Tumour response was observed in this study and preliminary efficacy of HLX07 was established, which effectively supported for further research. Currently, a Phase 1b/2 clinical study of HLX07 has been initiated in Mainland China.
Low immunogenicity and high affinity endowing HLX07 a broad clinical prospect
HLX07 is the first bio-better independently developed by Henlius. As a humanised anti-EGFR mAb, HLX07 has a well-validated target and its mechanism of action is relatively clear. The originator of HLX07 is cetuximab, which is a chimeric human mouse anti-EGFR mAb. Based on Henlius’ advanced antibody engineering platform, a series of optimisation processes, e.g. humanisation, affinity maturation and stable cell line construction, have been conducted for HLX07 to reduce the immunogenicity and increase the affinity of the product. Pre-clinical studies in different tumour models demonstrated an equivalent or even stronger tumour inhibition and lower toxicity of HLX07, compared to cetuximab at same dose levels.
EGFR belongs to the receptor tyrosine kinases family and plays an important role in maintaining normal cell functions such as cell proliferation, differentiation and migration. Mutation or overexpression of EGFR is considered to be closely associated with the occurrence of various solid tumours including non-small cell lung cancer, colorectal cancer, head and neck cancer, breast cancer, cervical cancer, bladder cancer, thyroid cancer, and gastric cancer [1]. The original drug of HLX07, cetuximab, is one of the most commonly used biologics in the treatment of colorectal cancer, and can also be used in the treatment of head and neck squamous cell cancer and non-small cell lung cancer. According to estimation of IQVIA CHPA, the sales of commercialized monoclonal antibody drugs targeting EGFR amounted to approximately RMB 1.385 billion in Mainland China in 2019, suggesting a big market for anti-EGFR drugs.
Positive results from early phase clinical study and smooth development of following Phase 1b/2 clinical study
As of now, Henlius has applied for patents of HLX07 in several jurisdictions including Mainland China, Taiwan China, the United States, the European Union, and Australia. Moreover, Henlius has received clinical trial approvals for HLX07 in the treatment of solid tumors in Mainland China, the United States, and Taiwan China. The latest findings of Phase 1 clinical trial of HLX07 was reported at the 22nd annual meeting of Chinese Society of Clinical Oncology (CSCO) and the 2019 European Society for Medical Oncology Asia congress (ESMO Asia) and was granted as one of the “Best Posters” at the 2019 ESMO Asia Congress.
Professor Ye Guo, Shanghai East Hospital, the investigator of Phase 1b/2 clinical study of HLX07, said “The results of Phase 1 clinical study of HLX07 indicated no major safety signals and good tolerability. Much to our delight, the study also suggested the potential of HLX07 to be used in both monotherapy and combination therapy in the treatment of advanced solid tumours. Currently, the Phase 1b/2 clinical study of HLX07 in combination with chemotherapy is ongoing. We expect this combo therapy to demonstrate better efficacy and safety than chemotherapy alone and can benefit more patients with advanced tumours, such as gastrointestinal cancer and head and neck cancer, in the future.”
Combination therapy and bispecific antibody opportunities of HLX07
In the future, HLX07 is to be developed as monotherapy and in combination therapies with chemotherapy drugs as well as other mAbs from Henlius’ extensive portfolio. Based on the company’s differentiated strategy of “Global +Combo”, Henlius is now evaluating the combination therapy of HLX07 with its bio-innovative product HLX10 (anti-PD-1 mAb) for the treatment of solid tumours related to EGFR such as head and neck squamous cell cancer. Clinical trial applications for this combination therapy have been approved by the National Medical Products Administration (NMPA).
Leveraging the company’s antibody R&D experience and achievements in various antibody assets covering immune-oncology targets, anti-angiogenesis targets and tumour-specific targets, along with the established comprehensive bispecific antibody R&D and engineering platform, Henlius will further explore the feasibility of combining EGFR and other targets for the development of bispecific antibodies.
“We are glad that Phase 1 clinical study of HLX07 demonstrated favorable safety and tolerability results. Looking forward, Henlius will continue bringing more innovative products into clinical phase and exploring combination therapies with improved efficacy to provide patients with quality and affordable biologics,” said Dr. Scott Liu, co-founder and chief executive officer of Henlius.
About Phase 1 clinical study of HLX07
The study is a prospective, open-labelled, dose-escalation Phase 1 clinical trial designed to assess HLX07 in the treatment for metastatic or recurrent solid tumours refractory to standard therapy. The study is designed as a Phase 1 trial for innovative drugs, with the primary objectives to assess the safety and tolerability of HLX07, establish the dose-limiting toxicity (DLT) and further determine the recommended Phase 2 dose (RP2D) based on the pharmacokinetics (PK) and pharmacodynamics (PD) data. The secondary objectives include potential efficacy of HLX07 in the treatment for metastatic or recurrent solid tumours, the HLX07 related pharmacokinetics files and immunogenicity. The exploratory objectives include discovering biomarkers of HLX07 for predicting efficacy and safety.
The safety profile of HLX07 was concluded with no major safety signals and well-tolerated up to 800mg for 28 days with no DLTs and MTD. Pharmacokinetic profiles showed exposure was dose dependent with single and multiple infusions of HLX07, and accumulation was observed in high dose levels. Tumour response was observed in patients with advanced solid tumours. This study established the safety and preliminary efficacy of HLX07 to treat solid tumours as antibody targeting Epidermal growth factor receptor (EGFR).
参考文献：
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Tebbutt, N., Pedersen, M. W., and Johns, T. G. (2013). Targeting the ERBB family in cancer: couples therapy. Nat. Rev. Cancer 13, 663–673. doi: 10.1038/nrc3559