Innovent and Lilly Jointly Announce the Approval of TYVYT® (sintilimab injection) by China NMPA in Combination with Pemetrexed and Platinum Chemotherapy as First-Line Therapy for Nonsquamous Non-Small

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, and Eli Lilly and Company, today jointly announced that the National Medical Products Administration (NMPA) of China has approved the supplemental New Drug Application (sNDA) of TYVYT® (sintilimab injection) in combination with pemetrexed and platinum chemotherapy as first-line therapy for people with nonsquamous non-small cell lung cancer (nsqNSCLC). This is the second approved indication of TYVYT® (sintilimab injection) in China, following the first approved indication by the NMPA in December 2018 for the treatment of relapsed or refractory classical Hodgkin's lymphoma after at least two lines of systemic chemotherapy.

The approval was based on a randomized, double-blind, Phase 3 clinical trial (ORIENT-11), which evaluated TYVYT® (sintilimab injection) or placebo in combination with ALIMTA® (pemetrexed injection) and platinum chemotherapy as first-line therapy for people with advanced or recurrent nsqNSCLC without sensitizing EGFR mutations or ALK rearrangements. A total of 397 participants were enrolled and were randomized in a 2:1 ratio (266 participants in the sintilimab combination arm, 131 participants in the placebo combination arm). ORIENT-11 demonstrated a statistically significant improvement in progression-free survival (PFS) of TYVYT® (sintilimab injection) in combination with ALIMTA® and platinum chemotherapy compared with placebo in combination with ALIMTA® and platinum chemotherapy. The median PFS of sintilimab combination arm and placebo combination arm assessed by Independent Radiographic Review Committee was 8.9 months and 5.0 months respectively, HR (95%CI) = 0.482 (0.362,0.643), P < 0.00001. Overall survival (OS) was not mature at interim analysis. The safety profile is consistent with previously reported TYVYT® (sintilimab injection) studies, and no new safety signals were identified.

At updated analysis after extended follow up, median OS of sintilimab combination arm was still not reached, while median OS of placebo combination arm was 16.0 months. Sintilimab combination significantly improved overall survival, HR (95%CI) = 0.606 (0.437,0.841), P=0.00250[1]. Details of the updated OS result will be published in near future.

Professor Li Zhang, head of the department of Oncology from Sun Yat-sen University Cancer Center, stated: "In China, about 60 percent of NSCLC cases are nonsquamous NSCLC, of which nearly 50 percent patients are gene-driven negative. There are large unmet medical needs for such patients with advanced lung cancer where targeted therapy is not suitable and treatment options are limited. In recent years, research on activating the human body's immune system by suppressing immune checkpoints to make it play a role in attacking tumor cells have progressed rapidly. Using immune checkpoint inhibitors (such as anti-PD-1/PD-L1 antibodies) have provided new clinical approaches in the first-line treatment of recurrent or metastatic advanced NSCLC. We hope the new indication approval of TYVYT® (sintilimab injection) can benefit more patients."

Dr. Yongjun Liu, President of Innovent, stated: "The efficacy and safety profile of TYVYT® (sintilimab injection) as a high-quality PD-1 inhibitor is further proven in the ORIENT-11 trial. We are excited about the approval of TYVYT® in this new indication which marks a milestone for TYVYT® (sintilimab injection) in the treatment of NSCLC. We look forward to bringing this treatment option to nonsquamous non-small cell lung cancer patients."

Dr. Hui ZHOU, Vice President of Medical Science and Strategy Oncology of Innovent, stated: "In China, lung cancer has the highest incidence and mortality rate among all tumor types. Although treatment technology is advancing, there is still a large number of lung cancer patients lack of effective treatments. The new indication of TYVYT® (sintilimab injection) has provided more treatment option for patients with first-line nonsquamous NSCLC. We sincerely hope that TYVYT® (sintilimab injection) will help more patients with advanced lung cancer and their families."

Julio Gay-ger, Lilly China President and GM, stated: "Oncology is one of the most important strategic therapeutic areas for Lilly. In particular, we have been deeply rooted in lung cancer treatment for many years. The approval of the new indication for TYVYT® (sintilimab injection) marks another major milestone under the Lilly-Innovent strategic collaboration and will also help to strengthen Lilly China's footprint in lung cancer. We will keep supporting the development of cancer therapies in China and devote ourselves to achieving the Healthy China 2030 goal."

Dr. Li WANG, Senior VP of Lilly China and Head of Lilly China Drug Development and Medical Affairs Center, stated: "In recent years, the development of immuno-oncology therapies have progressed and changed the overall landscape of cancer treatment for many tumor types. Results of multiple clinical studies show that immuno-oncology therapy has become one of the standard treatment options for lung cancer due to its proven clinical benefit. We're very excited about the approval and will keep working with Innovent to further explore TYVYT's clinical potential in the field of immuno-oncology therapy with the hopes of helping more patients in China." 

About Nonsquamous Non-Small Cell Lung Cancer

Cancer has been one of the leading causes of death in the world, with rapidly rising morbidities and mortalities. Among all cancers, lung cancer is a malignancy with the highest morbidity and mortality in China. NSCLC accounts for about 80 percent to 85 percent of lung cancer. Approximately 70 percent of NSCLC are locally advanced or metastatic at initial diagnosis, rendering the 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 60 percent of people with NSCLC in China have the nonsquamous subtype, and 50 percent of people with nsqNSCLC are without sensitizing EGFR mutations or ALK rearrangements. These patients do not respond well to targeted therapy and there are limited treatment options available to them, and therefore this is a huge unmet medical need.

About TYVYT® (Sintilimab Injection)

TYVYT® (sintilimab injection) is an innovative PD-1 inhibitor with global quality standards jointly developed by Innovent and Eli Lilly and Company. In December 2018, TYVYT® (sintilimab injection) was first approved by the China NMPA for the treatment of relapsed or refractory classic Hodgkin's lymphoma after two lines or later of systemic chemotherapy. In February 2021, TYVYT® (sintilimab injection) was approved by the China NMPA in combination with pemetrexed and platinum chemotherapy as first-line therapy for the treatment of nonsquamous non-small cell lung cancer. TYVYT® (sintilimab injection) was included in the National Reimbursement Drug List (NRDL) in 2019 as the first PD-1 inhibitor and the only PD-1 included in the list in that year.

Currently TYVYT® (sintilimab injection) has three supplemental New Drug Applications ("sNDA") under review by the NMPA. In August 2020, the NMPA accepted sNDA for TYVYT® (sintilimab injection) in combination with GEMZAR® (gemcitabine for injection) and platinum chemotherapy as first-line therapy in squamous NSCLC. In January 2021, the NMPA accepted the sNDA for TYVYT® (sintilimab injection) in combination with BYVASDA® (bevacizumab injection) as first-line therapy in Hepatocellular Carcinoma (HCC) and the sNDA for TYVYT® (sintilimab injection) as second-line therapy in squamous NSCLC. Besides, 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.

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® 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.

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.

Note:

[1] The OS data comes from label of TYVYT® (sintilimab injection).

TYVYT® (sintilimab injection) is not an approved product in the United States.

BYVASDA® (bevacizumab biosimilar injection) is not an approved product in the United States.

SULINNO® (adalimumab biosimilar injection) is not an approved product in the United States.

HALPRYZA® (rituximab biosimilar injection) is not an approved product in the United States.

TYVYT® (sintilimab injection, Innovent)

BYVASDA® (bevacizumab biosimilar injection, Innovent)

SULINNO® (adalimumab biosimilar injection, Innovent)

HALPRYZA® (rituximab biosimilar injection, Innovent)

ALIMTA® and GEMZAR® are trademarks owned by or licensed to Eli Lilly and Company, its subsidiaries, or affiliates.