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First Patient Dosed in Phase 1 Study of Henlius Innovative Anti-c-MET Monoclonal Antibody HLX55 for the Treatment of Advanced Solid Tumours

2020-03-04
Shanghai, China, March 3, 2020 – Shanghai Henlius Biotech, Inc. (2696.HK) announced that the first patient was dosed in Taiwan China, in a Phase 1 study (HLX55-001) of HLX55, an innovative anti-c-MET humanised monoclonal antibody developed by Henlius, for the treatment of advanced solid tumours refractory to standard therapy.
 
c-MET aberrant activation: closely associated with many tumours
 
c-MET-targeted therapies, of late years, have been tested in preclinical and patients to seek potential benefits for cancer treatment. c-MET is a tyrosine kinase receptor which regulates cellular pathways involved in cell proliferation, motility, invasion, and apoptosis1. Aberrant activation of c-MET can be detected in many malignant tumors such as non-small cell lung cancer (NSCLC), gastric cancer, brain cancer, breast cancer, colorectal cancer, head and neck cancer, and liver cancer2.
 
Besides, aberrant activation of c-MET was found to be associated with the resistance development in targeted therapies. Signal transduction between the c-MET and EGFR pathways was confirmed to be closely linked in many cancer types3,4. For majority of NSCLC patients, the expression and activation of c-MET were associated with initial resistance and acquired resistance to EGFR inhibitors5,6.
 
Therefore, c-MET-targeted therapy may provide more effective and personalised treatment options with great potential for combinations, not only for patients with tumours driven by c-MET aberrant activation, but also for patients with acquired resistance caused by aberrant activation of c-MET. Although there is a huge unmet medical need for the treatment of this patient population, no drugs specifically targeting c-MET have been approved for marketing currently.
 
HLX55: inhibiting c-MET activation via dual mechanisms
 
HLX55 can specifically bind to the human c-MET Sema/PSI domain. It inhibits c-MET activation by blocking the HGF ligand binding and promotes the degradation of c-MET, with a dual mechanism of action. The antitumor effect and safety of HLX55 have been proved in preclinical studies. These data provide a scientific basis for subsequent clinical trials. Henlius has been focusing on promoting the clinical development of HLX55, and obtained approval for HLX55 clinical trials in Taiwan China and Mainland China.
 
Great potential of HLX55 for combination with other candidate products
 
Henlius actively implements the product development strategy. On top of biosimilar, Henlius has built an extensive pipeline in bio-innovative and combination therapy. While quickly driving clinical studies of novel products in different countries and areas, Henlius is also actively diversifying versatile in-house combination therapy portfolio with a focus on anti-PD-1/PD-L1 mAbs to capture future immuno-oncology opportunities. The development of HLX55 will help Henlius advance forward in the areas of lung, gastric and colon cancer, and offer meaningful insights into its potential combinations with other candidate products including HLX10 (anti-PD-1 mAb) and HLX07 (anti-EGFR mAb), enabling more personalised treatment options for patients with aberrant activation of c-MET.
 

Looking forward, Henlius will continue to advance the development of bio-innovative by virtue of its established and integrated innovation platform, underscoring its long-term commitment to providing affordable and effective therapies for patients worldwide.


About HLX55-001


The study was an open labelled, multi-centre, dose finding/expansion global Phase 1 clinical trial, primarily aiming to evaluate the safety, identify Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) of HLX55 in patients with advanced or metastatic solid tumours refractory to standard therapy in the first stage, and further investigating the efficacy and safety of HLX55 in the second stage in patients with advanced or metastatic tumours with histologically confirmed c-MET mutations or amplifications or overexpression and refractory to standard therapy. The secondary objectives included characterizing the pharmacokinetics (PK) at different dose levels, evaluating changes in serum concentration of Hepatocyte Growth Factor (HGF) as a surrogate pharmacodynamics (PD) biomarker and immunogenicity of HLX55. Exploratory objectives included identifying biomarkers predicating efficacy of HLX55 related to c-MET.


About Henlius



Henlius (2696.HK) is a leading biopharmaceutical company in China with the vision to offer high-quality, affordable and innovative biologics for patients worldwide with a focus on oncology and autoimmune diseases. Since its inception in 2010, Henlius has built an integrated and efficient global R&D platform with key facilities in Shanghai, Taipei and California. The three R&D centers closely collaborate with each other to ensure a highly productive and cost-efficient R&D process. Starting from biosimilar, Henlius presses forward with novel mAb products and immuno-oncology combination therapies with proprietary anti-PD-1 and PD-L1 mAbs as backbone. Henlius establishes a diversified product pipeline of biosimilars, bio-innovative drugs and combination therapies, and builds an integrated platform covering the whole product lifecycle including R&D, commercial-scale production and commercialization. On September 25, 2019, Henlius was listed on the Main Board of the Stock Exchange of Hong Kong Limited with the stock code: 2696.HK.

Until now, in addition to one product launched commercially, two products under New Drug Application (NDA) review and one product under Marketing Authorization Application (MAA) review, Henlius has conducted over 20 clinical studies for 15 products and 7 combination therapies worldwide. HLX01 (汉利康®, rituximab injection), the first product of Henlius, has been granted approval by the NMPA as the first approved biosimilar in China. HLX03 (adalimumab injection) and HLX02 (trastuzumab for injection) have their NDA under priority review by the NMPA. HLX02 is also the first China-manufactured biosimilar developed in a global setting. In June 2019, the MAA for HLX02 was accepted for review by EMA. Moreover, Henlius advances immuno-oncology combination therapies with proprietary mAbs including HLX10 (anti-PD-1 mAb) as backbone in combination with chemotherapy and other mAbs including HLX04 (bevacizumab biosimilar) and HLX07 (anti-EGFR mAb). The global multi-center clinical trials are ongoing in various countries and regions worldwide.


Reference

1.Han Z, Wu Y, Wang K, et al. Analysis of progress and challenges for various patterns of c-MET-targeted molecular imaging: a systematic review. EJNMMI Res. 2017;7(1):41.
2.Bean J, Brennan C, Shih JY, et al. MET amplification occurs with or without T790M mutations in EGFR mutant lung tumors with acquired resistance to gefitinib or erlotinib. Proc Natl Acad Sci U S A. 2007;104(52):20932-20937.
3.Agarwal S, Zerillo C, Kolmakova J, et al. Association of constitutively activated hepatocyte growth factor receptor (Met) with resistance to a dual EGFR/Her2 inhibitor in non-small-cell lung cancer cells. Br J Cancer. 2009;100(6):941-949.     
4.Breindel JL, Haskins JW, Cowell EP, Zhao M, Nguyen DX, Stern DF. EGF receptor activates MET through MAPK to enhance non-small cell lung carcinoma invasion and brain metastasis. Cancer Res. 2013;73(16):5053-5065.  
5.Zhang Y, Xia M, Jin K, et al. Function of the c-Met receptor tyrosine kinase in carcinogenesis and associated therapeutic opportunities. Mol Cancer. 2018;17(1):45. 
6.Wang W, Li Q, Takeuchi S, et al. Met kinase inhibitor E7050 reverses three different mechanisms of hepatocyte growth factor-induced tyrosine kinase inhibitor resistance in EGFR mutant lung cancer. Clin Cancer Res. 2012;18(6):1663-1671.