围绕“Combo+Global”（联合治疗+国际化）差异化开发战略，斯鲁利单抗已获得中国、美国、欧盟等国家及地区的临床试验许可，目前共开展10项肿瘤免疫疗法临床试验，适应症广泛覆盖肺癌、肝细胞癌、食管癌、头颈癌和胃癌等高发大癌种，全球范围内累计入组约2300名受试者，也印证了国际市场对斯鲁利单抗质量的信心与认可。目前，斯鲁利单抗“泛癌种”治疗高度微卫星不稳定型（MSI-H）实体瘤适应症的上市注册申请也已于2021年4月获国家药监局（NMPA）受理并被纳入优先审评审批程序，有望于2022年上半年获批上市。

以斯鲁利单抗为基础，公司依据全球及中国癌症发病人群特点，重点聚焦肺癌和消化道肿瘤领域。复宏汉霖现已实现肺癌一线的全面临床布局，在鳞状非小细胞肺癌（sqNSCLC）、非鳞状非小细胞肺癌（nsNSCLC）和SCLC均就斯鲁利单抗开展试验，覆盖了超过90%的肺癌患者。基于其中一项在既往未接受治疗的局部晚期或转移性sqNSCLC患者中开展的随机、双盲、国际多中心III期临床试验，斯鲁利单抗一线治疗局部晚期或转移性sqNSCLC的上市注册申请已获得NMPA受理。未来，凭借丰富的国际临床研究数据，复宏汉霖将不断拓展斯鲁利单抗的国际布局，惠及全球更多患者。

Henlius’ Phase 3 clinical study of novel PD-1 inhibitor serplulimab for the treatment of first-line extensive-stage small cell lung cancer (ES-SCLC) meets primary study endpoint

Shanghai, China, December 7th, 2021 – Shanghai Henlius Biotech, Inc. (2696.HK) announced that the first interim analysis met the primary study endpoint of the overall survival (OS) of the Phase 3 clinical study (NCT04063163) of its innovative PD-1 inhibitor serplulimab in combination with chemotherapy in previously untreated patients with extensive-stage small cell lung cancer (ES-SCLC). There is no anti-PD-1 mAb approved for the treatment of extensive-stage small cell lung cancer worldwide.

The study's main purpose is to explore the efficacy and safety of serplulimab in combination with chemotherapy in previously untreated patients with ES-SCLC. Based on the results of a pre-defined interim analysis conducted by the Independent Data Monitoring Committee (IDMC), serplulimab in combination with chemotherapy showed a significant improvement in OS against chemotherapy, which met the pre-defined efficacy criteria, with good safety and no detection of a new safety signal. IDMC suggested that the company can hence communicate with healthy authority.

Professor Ying Cheng, the principal investigator of NCT04063163, Director of Jilin Department of Medical Oncology Cancer Center, Jilin Province Lung Cancer Diagnosis and Treatment Center, and Jilin Cancer Hospital Malignant Tumor Clinical Research Integrated Diagnosis and Treatment Center, said, "I’m very excited to see that the Phase 3 study of serplulimab in ES-SCLC has met its primary endpoint OS, and its efficacy and safety have been fully validated. This study is the first and largest ES-SCLC international multi-center clinical study led by Chinese researchers for anti-PD-1 mAb. The favorable clinical results show China's ability to innovate with a high clinical trial level. We are looking forward to serplulimab launching as soon as possible, which brings a drug with Chinese independent intellectual property to patients with small cell lung cancer all over the world."

IDMC Chairman of NCT04063163, and Cancer Hospital Chinese Academy of Medical Sciences, Professor Jie Wang, said, "SCLC is a type of lung cancer with strong invasion and poor prognosis, among which ES-SCLC cancer cells are prone to metastasis. At present, ES-SCLC is still mainly treated with chemotherapy or chemotherapy combined with PD-L1 inhibitors. It is easy to progress after chemotherapy, and the 5-year survival rate is generally less than 5%. The prognosis has not been improved for a long time. The results of the Phase 3 trial of serplulimab bring a new option for anti-PD-1 mAb as a first-line ES-SCLC therapy."

Professor Giorgio Scagliotti from the Medical Oncology, University of Turin in Italy, one of IDMC members, said, "There are limited choices for SCLC clinical treatment, especially in anti-PD-1 mAb. Currently, the first-line treatment is chemotherapy or anti-PD-L1 mAb combined with chemotherapy according to the NCCN guidelines. This international multi-center Phase 3 clinical study on ES-SCLC has been carried out in many countries in Asia and Europe, with more than 580 subjects worldwide. It is believed that by means of international multi-center clinical data, serplulimab will enter the international market and benefit more patients worldwide."

Mr. Jason Zhu, President of Henlius, said, "Serplulimab is an innovative mAb independently developed by Henlius, and the company has carried out a comprehensive first-line treatment layout for lung cancer. Based on the large number of unmet clinical needs, the company has invested in SCLC. The excellent results of this Phase 3 study are expected to contribute serplulimab in becoming the first anti-PD-1 mAb for the first-line treatment of SCLC, which will significantly improve the overall prognosis. Henlius focuses on high-incidence cancers both globally and in China. In the future, we will proactively promote the combination immunotherapy of serplulimab and international clinical research, benefiting more patients around the world."

SCLC is highly malignant, and the available treatment is limited

According to GLOBOCAN data, lung cancer (LC) is the second commonly diagnosed cancer globally and accounts for 11.4% of the global cancer incidence in 2020^[1]. It is estimated that there are 810,000 new cases with LC in China in 2020, and LC is the leading cause of cancer incidence and mortality^[2]. SCLC accounts for 15%-20% among LC^[3], and is the most aggressive subtype of LC, which is divided into limited stage small cell lung cancer (LS-SCLC) and ES-SCLC. Most patients are already in extensive stage when diagnosed^[4]. Patients with ES-SCLC always have rapid tumour growth and poor prognosis. Some of them have shorter survival due to extensive tumor metastasis and poor physical status only with supportive care.

Over 20 years, etoposide plus carboplatin/cisplatin is still the standard of care for ES-SCLC, but 80% of patients with limited stage disease and almost all patients with extensive stage disease relapse within one year, with a median survival of only 4 to 5 months after relapse. The emergence of immune checkpoint inhibitors provides a new option. At present, anti-PD-L1 mAb combined with chemotherapy has been recommended by the latest NCCN guidelines and CSCO guidelines as the first-line treatment for ES-SCLC. However, the application of immunotherapy in ES-SCLC still faces challenges. In recent years, a number of PD-1 mAbs have failed in the area. Therefore, more effective first-line treatment of PD-1 inhibitors is urgently needed.

Centering on the unmet needs of patients, covering the first-line treatment of all types of lung cancer

Henlius has adopted a differentiated "Combo+Global" strategy on serplulimab. Currently, serplulimab 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 serplulimab are ongoing to evaluate its safety and efficacy in a wide variety of solid tumors that cover LC, hepatocellular carcinoma, esophageal carcinoma, head and neck squamous cell carcinoma  and gastric cancer etc. Up to date, about 2300 patients have been enrolled worldwide, proving that the quality of serplulimab has built trust in foreign markets. In April, the New Drug Application (NDA) of serplulimab for the treatment of MSI-H solid tumours was accepted by the National Medical Products Administration (NMPA) and granted priority review, which is expected to be approved in the first half of 2022.

According to the characteristics of cancer patients both globally and in China, the company focus on lung cancer and gastrointestinal cancer with serplulimab as the backbone. Henlius has achieved a comprehensive first-line clinical layout of LC, and has carried out trials on serplulimab in sqNSCLC, non-squamous non-small cell lung cancer and SCLC, covering more than 90% of lung cancer patients. Based on a randomized, double-blind, international multi-center Phase 3 clinical trials conducted in previously untreated patients with locally advanced or metastatic sqNSCLC, the NDA of serplulimab for first-line treatment of locally advanced or metastatic sqNSCLC has been accepted by the NMPA. In the future, with abundant international clinical research data, Henlius will continue expanding the international distribution of serplulimab and benefit more patients around the world.