Shanghai, China, July 29, 2020-Shanghai Henlius Biotech, Inc. (2696.HK) announced that the first patient was dosed in Chinese mainland in a Phase 2 clinical trial of HLX10, a recombinant humanised anti-programmed cell death protein 1 (PD-1) monoclonal antibody (mAb) injection, in combination with HLX07, a recombinant anti-epidermal growth factor receptor (EGFR) humanised monoclonal antibody injection, for the treatment of recurrent or metastatic squamous cell carcinoma of head and neck (SCCHN). This is the second mAb combination therapy of Henlius which received clinical trial approval from the National Medical Products Administration (NMPA) and also the first mAb combination therapy developed for the treatment of SCCHN that has entered into clinical trial stage.

Challenge dilemmas in the treatment of SCCHN and lead its innovative combination therapy development

Head and neck cancer is the 5th most prevalent cancer worldwide，with more than 500,000 newly diagnosed cases each year. Moreover, the incidence of this health problem is higher in China than other countries and regions, and an increasing population of patients has being diagnosed. There are varied origins for Head and neck cancer. Except of eyes, brain, ears, thyroid and esophagus, tumors originating from other head and neck tissues or organs are all considered as head and neck cancer. Accounting for nearly 90% patients, SCCHN is the most common type of head and neck cancer and the majorities of SCCHN patients show EGFR over-expression.

Before the emergence of immunotherapy, the anti-EGFR receptor antibodies and chemotherapies were used as major effective therapeutic modalities in SCCHN while their clinical benefits proved to be limited and problems of resistance of EGFR targeting have been found. In recent years, though more and more clinical evidence has suggested that significant benefits were observed in some advanced SCCHN patients with monotherapy of immune checkpoints inhibitor, there is still a large proportion of the patients who response poorly to this therapy. Innovative therapies are strongly needed to further improve the survival benefits of advanced SCCHN patients. As immune-regulatory mechanism of EGFR antibody gradually been discovered, novel combination therapies of anti-EGFR monoclonal antibody and immune checkpoint inhibitor may provide a breakthrough to solve the treatment dilemmas of SCCHN.

HLX10 is a novel anti-PD-1 monoclonal antibody independently developed by Henlius and has exhibited better pharmacokinetics, pharmacodynamics properties, favourable safety, tolerability profile and anti-tumor activity in preclinical and early clinical research. HLX07 is the first bio-better independently developed by Henlius. On the basis of cetuximab, 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. In preclinical animal model tests, HLX07 exhibited better anti-tumor activities than cetuximab in variety of xenograft models including human head and neck cancer xenograft. In December 2019, the investigational new drug (IND) applications for the combination therapy of HLX10 and HLX07 has been approved by the National Medical Products Administration(NMPA), for the treatment of recurrent or metastatic head and neck squamous cell carcinoma.

The clinical trial which just dosed the first patient is an open-label, Phase 2 clinical study to evaluate the clinical efficacy and safety in HLX10 combined with HLX07 in patients with advanced recurrent or metastatic head and neck squamous cell carcinoma. The study primarily aims to assess objective response rate (ORR) at week 16 and the safety profile of HLX10 in combination with HLX07. Secondary objectives include evaluating other efficacy endpoints, immunogenicity and pharmacokinetics file. Exploratory objective includes identifying biomarkers for therapeutic response and/or drug resistance. Were the clinical trial of this combination therapy for SCCHN went well, it will hopefully break through the limitations of established therapeutic modalities and lead to a new and more effective treatment options for patients with SCCHN.

Comprehensive international layout and quickly implementation of combination therapies focusing on HLX10

To maximize the clinical potential of HLX10, a differentiated strategy of "Combo plus Global" is adopted by Henlius in the development of HLX10. Currently, more than 10 clinical trials has been conducted to explore the efficacy of HLX10, in which several of them are phase 2/3 pivotal trials that can be potentially used to submit New Drug Application of HLX10. In addition to SCCHN, Henlius has actively explored the efficacy of HLX10 in a variety of solid tumours covering lung, gastric and uterine cancer and hepatocellular and esophageal carcinoma etc. It is worth mentioning that HLX10 in combination with HLX04, a bevacizumab biosimilar developed by Henlius independently has been approved for the treatment of advanced solid tumors in September 2018, making it the first domestic mAbs combination therapy that has received IND approval in China.

The manufacturing and development of HLX10 is strictly in accordance with international standards and its manufacturing facility based in Shanghai has passed on-site inspections and/or audits conducted by EU QP. The position of HLX10 to be a global product and to benefit patients around the world will become a major differentiation advantage of HLX10. Besides Chinese mainland, HLX10 has been approved for clinical trials in the United States and Taiwan China successively, with multiple international clinical trials accounting for a high proportion in all of the clinical trials being conducted of HLX10. With the initiation of multiple international clinical trials and the enrollment of patients in overseas trial sites, the pace of HLX10 to enter international market will be accelerated.

Apart from conducting international trials of HLX10, Henlius also actively seeks for international cooperation opportunities with the aim to benefit more patients in the world, especially patients in emerging markets. Henlius has reached a collaboration agreement with PT Kalbe Genexine Biologics (KG Bio), upon which KG Bio is granted exclusive rights to develop and commercialize HLX10 in relation to its first monotherapy and two combination therapies in 10 Southeast Asian countries.

Self-developed extensive portfolio forwards affordable diversified immune-oncology combination therapies

The combination of in-house innovative mAbs has significant advantages in the development of combination immunotherapy, which can greatly reduce time and cost in the development process. Fully leveraging innovative in-house capabilities, Henlius has built an extensive pipeline across different categories of targets including tumour-specific target, angiogenesis target, immunotherapeutic target, etc. to make affordable and extensive combination therapies possible. Meawhile, the relevant data and insights on PD-(L)1 and EGFR pathway and on structure-activity relationship of anti-PD-1 and anti-EGFR antibodies that can be accumulated during the development of combination therapy of HLX10 and HLX07 will lay the foundation for Henlius' future endeavours in the development of bispecific antibodies with PD-1 and EGFR target.

【参考文献】

[1] Fitzmaurice C, Allen C, Barber R M, et al. Global, regional, and national cancer incidence, mortality, years of life lost, years lived with disability, and disability-adjusted life-years for 32 cancer groups, 1990 to 2015: a systematic analysis for the global burden of disease study[J]. JAMA oncology, 2017, 3(4): 524-548.

[2] Chen W , Zheng R , Baade P D , et al. Cancer statistics in China, 2015[J]. CA: A Cancer Journal for Clinicians, 2016, 66(2):115-132.

[3] Sanderson RJ, Ironside JA. Squamous cell carcinomas of the head and neck. BMJ. 2002;325(7368):822‐827.

[4] Ang KK, Andratschke NH, and M. L, Epidermal growth factor receptor and response of head-andneck carcinoma to therapy. Int J Radiat Oncol Biol Phys., 2004 3 1;58(3):959–65.

[5] Concha-Benavente F and Ferris RL, Oncogenic growth factor signaling mediating tumor escape from cellular immunity. Curr Opin Immunol, 2017 45: p. 52–59.

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 and autoimmune diseases. 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 commercialisation. It has three R&D facilities in Shanghai, Taipei and California and a Shanghai-based manufacturing facility certificated by China and the European Union (EU) Good Manufacturing Practice (GMP).

Henlius has pro-actively built a diversified and high-quality product pipeline covering over 20 innovative monocolonal antibodies (mAb) and has continued to explore immuno-oncology combination therapies with proprietary HLX10 (anti-PD-1 mAb) as backbone. After 汉利康® (HLX01, rituximab) was launched commercially, HLX02 (Zercepac® in the EU, trastuzumab) is approved in the EU as the first Chinese mAb biosimilar entering the EU market. Meanwhile, HLX02 will also potentially be lauched within 2020 in China, becoming the first Chinese trastuzumab biosimialr. Up to date, in addition to 2 products launched successfully and 1 product (HLX03 adalimumab) to be potentially launched within 2020, Henlius has conducted over 20 clinical studies for 10 products and 8 combination therapies worldwide. Products have been licensed out to nearly 100 countries and regions.