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Henlius Plans to File the NDA of Novel anti-PD-1 mAb HLX10 for the Treatment of MSI-H Solid Tumours, the Phase 2 Clinical Trial has Met the Primary Endpoint

Shanghai, China, March 28th, 2021 – Shanghai Henlius Biotech, Inc. (2696.HK) announced that the Phase 2 study of its innovative PD-1 inhibitor HLX10 in patients with unresectable or metastatic microsatellite instability-high or mismatch repair-deficient (MSI-H/dMMR) solid tumors that fail to respond to the standard therapy has met the primary endpoint. Henlius plans to file a New Drug Application (NDA) to the National Drug Products Administration (NMPA) for the treatment of MSI-H solid tumours based on the results from the Phase 2 trial of HLX10, which will be presented at upcoming medical conferences. Professor Shukui Qin of No.81 Hospital of People's Liberation Army and Professor Jin Li of Shanghai East Hospital affiliated to Shanghai Tongji University are co-leading principal investigators of this study.

In accordance with precision medicine, MSI-H solid tumors cover a wide range of cancer types

The defect of mismatch repair (MMR) that can lead to base mismatch or insert in microsatellites during DNA replication, and the accumulation of incorrect bases usually causes microsatellite instability (MSI)[1]. MSI-H often occurs in several cancer types, such as endometrial cancer, colorectal cancer, gastric cancer, renal cell carcinoma, ovarian cancer, etc[2]. Studies have revealed that the prevalence of MSI-H across all tumor types is 14%[3]. Patients who suffer from this disease usually have higher response rates for immune checkpoint inhibitors[4-5]. Thus, MSI-H is becoming a more and more important biomarker for the immunotherapy predictions of patients with solid tumors. If the patient is MSI-H positive and meets the treatment criteria, the corresponding immunotherapy can be carried out without screening tumor sites and pathological classification, which aligns with the advanced concept of precision medicine and is applicable to a wide range of cancer types.

Currently, the U.S. Food and Drug Administration (US FDA) has approved PD-1 target mAb for the treatment of second-line MSI-H/dMMR advanced solid tumors and first/second-line MSI-H/dMMR colorectal cancers. While there are still no anti-PD-1 mAb approved for MSI-H/dMMR advanced solid tumors in China, the treatment needs are far from being met.

Excellent clinical study results lay the foundation for subimtting HLX10 NDA

HLX10, a novel recombinant humanised anti-programmed cell death protein 1 (PD-1) mAb independently developed by Henlius, has the potential to treat a variety of solid tumours. HLX10 has exhibited better pharmacokinetics, pharmacodynamics properties, favourable safety, tolerability profile and anti-tumor activity in preclinical and early clinical research studies. This study is a single-arm, open-label, multi-centre, Phase 2 study, aimed to evaluate the efficacy, safety and tolerability of HLX10 in patients with unresectable or metastatic MSI-H/dMMR solid tumuors that fail to respond to the standard therapy. The primary efficacy endpoint was objective response rate (ORR) assessed by independent radiological review committee (IRRC) per RECIST v1.1. Secondary endpoints included ORR assessed by investigators, duration of response (DoR), progression-free survival (PFS), overall survival (OS), safety and tolerability. The results of this clinical study demonstrated the good efficacy and safety of HLX10 in this class of indications.

Multiple major cancer types clinical trials on fast track with forward-looking global layout

Henlius has adopted a differentiated "Combo+Global" strategy on HLX10, pioneering the combination immunotherapy. Currently, HLX10 has been approved for clinical trials in China, the United States, the European Union and other countries and regions. A total of 10 immuo-oncology therapies clinical trials of HLX10 are ongoing to evaluate its safety and efficacy in a wide variety of solid tumors that cover MSI-H solid tumours, lung cancer (LC), hepatocellular carcinoma (HCC), esophageal carcinoma (EC), head and neck squamous cell carcinoma (HNSCC) and gastric cancer (GC) etc., including three Phase 3 global multi-centre clinical trials in squamous non-small cell lung cancer (sqNSCLC), extensive-stage small cell lung cancer (ES-SCLC) and neo-/adjuvant treatment for GC. It is worth mentioning that, the NDA filing of HLX10 in combination with chemotherapy for the first-line treatment of sqNSCLC in China will also be expected in the second half of 2021.

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.

Reference Notes

[1] Yang G, Zheng RY, Jin ZS. Correlations between microsatellite instability and the biological behaviour of tumours. J Cancer Res Clin Oncol. 2019 Dec;145(12):2891-2899.

[2] Hause, R., Pritchard, C., Shendure, J. et al. Classification and characterization of microsatellite instability across 18 cancer types. Nat Med 22, 1342–1350 (2016).

[3] Lorenzi M, Amonkar M, Zhang J, et al. Epidemiology of Microsatellite Instability High (MSI-H) and Deficient Mismatch Repair (dMMR) in Solid Tumors: A Structured Literature Review[J]. Journal of Oncology, 2020, 2020.

[4] Michael J Overman, Ray McDermott, Joseph L Leach, et al. Nivolumab in patients with metastatic DNA mismatch repair deficient/microsatellite instability-high colorectal cancer (CheckMate 142): results of an open-label, multicenter, phase 2 study[J]. Lancet Oncology, 2017,18(9):1182-1191.

[5] Aurelien Marabelle, Dung T Le, Paolo A Asciert, et al. Efficacy of Pembrolizumab in Patients With Noncolorectal High Microsatellite Instability/Mismatch Repair-Deficient Cancer: Results From the Phase II KEYNOTE-158 Study[J]. J Clin Oncol, 2020, 38(1): 1-10.