Innovent Announces NMPA Acceptance of a Supplemental New Drug Application for Sintilimab as Second-Line Therapy for Squamous Non-Small Cell Lung Cancer

Innovent Biologics, Inc., a world-class biopharmaceutical company that develops, manufactures and commercializes high-quality medicines for the treatment of cancer, metabolic, autoimmune and other major diseases, today announced with Eli Lilly and Company that the National Medical Products Administration (NMPA) of China has accepted the supplemental New Drug Application (sNDA) for TYVYT® (sintilimab injection) as second-line therapy for squamous non-small cell lung cancer (sqNSCLC). The application is the third sNDA for TYVYT® (sintilimab injection) in NSCLC.

This sNDA was based on a randomized, open-label, Phase 3 clinical trial (ORIENT-3)—evaluating TYVYT® (sintilimab injection) as second-line therapy for patients with advanced or recurrent sqNSCLC whose cancer had progressed on first-line platinum-based chemotherapy. Based on the final analysis in the pre-specified full analysis set, TYVYT® demonstrated a statistically significant improvement in overall survival (OS) compared with docetaxel, which met the pre-specified superiority criteria. The progression-free survival (PFS) and objective response rate (ORR) were also significantly improved. The safety profile is consistent with previously reported sintilimab studies, and no new safety signals were identified. Detailed data will be released in an upcoming international academic conference or journal.

The principal investigator of ORIENT-3, Professor Yuankai Shi, Associate Dean of Cancer Hospital, Chinese Academy of Medical Sciences, stated: "Lung cancer is the leading cause of cancer death globally, of which NSCLC accounts for 80% to 85%. In the past few decades, drug development of NSCLC has mainly focused on nonsquamous NSCLC, while drug development of squamous NSCLC has been slower due to its unique epidemiological, histopathological and molecular characteristics. In China, the options for second-line immunotherapy are even more limited. The ORIENT-3 study confirmed that the anti-PD-1 monoclonal antibody sintilimab significantly improved OS for the second-line treatment of squamous NSCLC patients, which is of great clinical value. We hope that the positive results of ORIENT-3 can potentially help more squamous NSCLC patients."

"TYVYT® (sintilimab injection) is the first anti-PD-1 monoclonal antibody included in the New Catalogue of the National Reimbursement Drug List," said Dr. Hui Zhou, Vice President of Medical Science and Strategy Oncology of Innovent. "In August 2020, the NMPA accepted a new indication application for TYVYT® (sintilimab injection) in combination with chemotherapy for first-line treatment of squamous NSCLC. In ORIENT-3 study, sintilimab as second-line monotherapy demonstrated a significantly improved survival benefit for patients with advanced squamous NSCLC, and we look forward to the approval of this indication, to potentially help more patients with this type of lung cancer."

"We are excited about these results, showing TYVYT® (sintilimab injection) significantly improved overall survival in this patient population. This study underscores the joint commitment from Lilly and Innovent to provide innovative treatment options to patients with lung cancer," said Dr. Wang Li, Senior Vice President of Lilly China and Head of Lilly China Drug Development and Medical Affairs. "We would like to thank the patients, the investigators, the clinical trial centers and our colleagues from Innovent that are involved in the study. We look forward to working together to potentially bring this new treatment option to patients in China with squamous NSCLC."

About ORIENT-3 Trial

ORIENT-3 is a randomized, open-label, multi-center, Phase 3 clinical trial in China to evaluate the efficacy and safety of TYVYT® (sintilimab injection) as second-line therapy for advanced or metastatic sqNSCLC (ClinicalTrials.gov, NCT 03150875). The primary endpoint is overall survival (OS). The secondary endpoints include progression-free survival (PFS) assessed by investigators based on RECIST v1.1, objective response rate (ORR) and safety profile.

A total of 290 patients were enrolled in ORIENT-3 and randomized in a 1:1 ratio to receive either TYVYT® (sintilimab injection) 200mg or docetaxel every three weeks. The patients received treatment until radiographic disease progression, unacceptable toxicity or any other conditions that require treatment discontinuation.

About Squamous NSCLC

Lung cancer is a malignancy with the highest morbidity and mortality in China. NSCLC accounts for about 80 to 85 percent of lung cancer. Approximately 70 percent of people with NSCLC have locally advanced or metastatic NSCLC at initial diagnosis, rendering many of those patients with no chance of radical resection. Meanwhile, even after radical surgery, patients still have a high chance of recurrence and eventually die from disease progression. About 30 percent of people with NSCLC in China have tumors of the squamous subtype and there are limited second-line immunotherapies for these patients. In China, there remains a huge unmet medical need.

About TYVYT® (Sintilimab Injection)

TYVYT® (sintilimab injection), an innovative drug with global quality standards jointly developed in China by Innovent and Eli Lilly and Company, has been granted marketing approval by the NMPA for the treatment of relapsed or refractory classic Hodgkin's lymphoma after two lines or later of systemic chemotherapy, and is included in the 2019 Guidelines of Chinese Society of Clinical Oncology for Lymphoid Malignancies. TYVYT® was included in the National Reimbursement Drug List (NRDL) in 2019 as the historically first PD-1 inhibitor entering in NRDL and the only PD-1 included in the list in that year.

In April 2020, the NMPA accepted the sNDA for TYVYT® (sintilimab injection) in combination with ALIMTA® (pemetrexed) and platinum chemotherapy as first-line therapy for the treatment of patients with non-squamous non-small cell lung cancer (NSCLC). In May 2020, TYVYT® (sintilimab injection) monotherapy met the primary endpoint of overall survival in the Phase 2 ORIENT-2 study as second-line therapy in patients with advanced or metastatic esophageal squamous cell carcinoma. In August 2020, the NMPA accepted the sNDA for TYVYT® in combination with GEMZAR® (gemcitabine for injection) and platinum chemotherapy as first-line therapy in squamous NSCLC. In September 2020, TYVYT® (sintilimab injection) in combination with BYVASDA® (bevacizumab biosimilar injection) as a first-line treatment in advanced hepatocellular carcinoma met the predefined primary endpoints of overall survival and progression-free survival in an interim analysis of the Phase 3 ORIENT-32 study. In January 2021, the NMPA accepted the sNDA for TYVYT® as second-line therapy for sqNSCLC.

TYVYT® (sintilimab injection), is a type of immunoglobulin G4 monoclonal antibody, which binds to PD-1 molecules on the surface of T-cells, block the PD-1 / PD-Ligand 1 (PD-L1) pathway and reactivate T-cells to kill cancer cells. Innovent is currently conducting more than 20 clinical studies with TYVYT® (sintilimab injection) to evaluate its safety and efficacy in a wide variety of cancer indications, including more than 10 registrational or pivotal clinical trials. Meanwhile, Innovent is conducting clinical research studies on TYVYT® (sintilimab injection) worldwide.

About Innovent

Inspired by the spirit of "Start with Integrity, Succeed through Action," Innovent's mission is to develop, manufacture and commercialize high-quality biopharmaceutical products that are affordable to ordinary people. Established in 2011, Innovent is committed to developing, manufacturing and commercializing high quality innovative medicines for the treatment of cancer, autoimmune, metabolic and other major diseases. On October 31, 2018, Innovent was listed on the Main Board of the Stock Exchange of Hong Kong, S.A.R., China Limited with the stock code: 01801.HK.

Since its inception, Innovent has developed a fully integrated multi-functional platform which includes R&D, CMC (Chemistry, Manufacturing, and Controls), clinical development and commercialization capabilities. Leveraging the platform, the company has built a robust pipeline of 23 valuable assets in the fields of cancer, metabolic, autoimmune diseases and other major therapeutic areas, with 4 products - TYVYT® (sintilimab injection), BYVASDA® (bevacizumab biosimilar injection) , SULINNO® (adalimumab biosimilar injection) and HALPRYZA® (rituximab biosimilar injection) - officially approved for marketing in China, four assets in Phase 3 or pivotal clinical trials, and additional 15 molecules in clinical trials. TYVYT® (sintilimab injection) is the first PD-1 inhibitor included in the NRDL.

Innovent has built an international team of advanced talents in high-end biological drug development and commercialization, including many overseas experts. The company has also entered into strategic collaborations with Eli Lilly and Company, Adimab, Incyte, MD Anderson Cancer Center, Hanmi and other international partners. Innovent strives to work with all relevant parties to help advance China's biopharmaceutical industry, improve drug availability to ordinary people and enhance the quality of the patients' lives.

About Eli Lilly and Company

Lilly is a global healthcare leader that unites caring with discovery to create medicines to make life better for people around the world. We were founded more than a century ago by a man committed to creating high-quality medicines that meet real needs, and today we remain true to that mission in all our work. Across the globe, Lilly employees work to discover and bring life-changing medicines to those who need them, improve the understanding and management of disease, and give back to communities through philanthropy and volunteerism.

About Innovent Biologics' strategic collaboration with Eli Lilly and Company

Innovent entered into a strategic collaboration with Lilly focused on biological medicine in March 2015 – a groundbreaking partnership between a Chinese pharmaceutical company and a multinational pharmaceutical company. Under the agreement, Innovent and Lilly are co-developing and commercializing oncology medicines, including TYVYT® (sintilimab injection) in China. In October 2015, the two companies announced the extension of their existing collaboration to include co-development of three additional oncology antibodies targeting oncology indications. In August 2019, Innovent further entered a licensing agreement with Lilly to develop and commercialize a potentially global best-in-class diabetes medicine in China. Its collaboration with Lilly indicates that Innovent has established a comprehensive level of cooperation between China's innovative pharmaceuticals sector and the international pharmaceuticals sector in fields such as R&D, CMC, clinical development and commercialization. In August 2020，Lilly and Innovent announced a global expansion of their strategic alliance for TYVYT® (sintilimab injection), whereby Lilly obtained an exclusive license for TYVYT® (sintilimab injection) for geographies outside of China and plans to pursue registration of TYVYT® (sintilimab injection) in the U.S. and other markets.