Innovent and Lilly Jointly Announce the China NMPA Approval of TYVYT® (sintilimab injection) in Combination with Gemcitabine and Platinum Chemotherapy as First-Line Therapy for People with Squamous No

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 jointly announced that the National Medical Products Administration (NMPA) of China has approved the supplemental New Drug Application (sNDA) for TYVYT® (sintilimab injection) in combination with gemcitabine and platinum chemotherapy as first-line therapy for people with unresectable locally advanced or metastatic squamous non-small cell lung cancer (sqNSCLC).

This is the third NMPA-approved indication of TYVYT® (sintilimab injection), following the approval in December 2018 for the treatment of relapsed or refractory classical Hodgkin's lymphoma, and the approval in February 2021 for the first-line treatment of nonsquamous non-small cell lung cancer (nsqNSCLC). This is also the first regulatory approval of a PD-1/PD-L1 immunotherapy in combination with gemcitabine and platinum chemotherapy for the first-line treatment for people with sqNSCLC.

This new approval was based on a randomized, double-blind, Phase 3 clinical trial (ORIENT-12) which evaluated TYVYT® (sintilimab injection) or placebo in combination with GEMZAR® (gemcitabine) and platinum chemotherapy as first-line therapy for people with unresectable locally advanced or metastatic sqNSCLC.

Professor Caicun Zhou, head of the Oncology Department at Shanghai Pulmonary Hospital, stated: "Lung cancer is the leading cause (nearly 25%) of all cancer deaths, of which non-small cell lung cancer accounts for about 80 to 85 percent. Approximately 70 percent of patients with non-small cell lung cancer have unresectable tumors at the time of diagnosis, and 30 to 60 percent of patients with Stage I-III non-small cell lung cancer who undergo radical surgery subsequently have recurrence or distant metastasis. Over the past two decades, drug development for non-small cell lung cancer has been mainly focused on nonsquamous non-small cell lung cancer, while drug development for squamous non-small cell lung cancer has been relatively slow due to its unique epidemiology, histopathology and molecular biology. The ORIENT-12 study showed that, in the first-line treatment of patients with squamous non-small cell lung cancer, TYVYT® (sintilimab injection) in combination with gemcitabine and platinum chemotherapy demonstrated a statistically significant improvement in progression-free survival compared to placebo and gemcitabine and platinum chemotherapy. Meanwhile, although the median overall survival data was not yet mature, the TYVYT® (sintilimab injection) combination arm showed a potential overall survival benefit over chemotherapy alone. The approval of TYVYT® (sintilimab injection) provides a new clinical approach in China for the first-line treatment of advanced or metastatic squamous non-small cell lung cancer. We look forward to offering this new indication of TYVYT® (sintilimab injection) and helping to treat people with squamous non-small cell lung cancer in China."

Dr. Yongjun Liu, President of Innovent, stated: "As one of the most life-threatening diseases, cancer has always been a key focus for the pharmaceutical companies, researchers and clinicians that help develop oncology treatments. Innovent is committed to discovering and developing innovative medicines for diseases with unmet medical needs. This approval of TVYYT® (sintilimab injection) in a third indication represents another remarkable achievement for our novel, high quality PD-1 inhibitor in cancer treatment. We are very excited about this approval, and we look forward to now offering this as a first-line treatment option for people with squamous non-small cell lung cancer."

Dr. Hui ZHOU, Senior Vice President of Clinical Development of Innovent, stated: "In China, lung cancer has the highest incidence and mortality rate among all tumor types. Although treatment development has been advancing in recent years, there is still a large number of people with lung cancer that lack effective treatment options – particularly those with the squamous type. This new indication of TYVYT® (sintilimab injection) provides an additional first-line treatment option for people with squamous non-small cell lung cancer. We are hopeful that TYVYT® (sintilimab injection) will help many people with this type of cancer."

Julio Gay-ger, Lilly China President and General Manager, 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. We're excited to see two new indications for TYVYT® (sintilimab injection) in combination with two Lilly classic anti-tumor drugs – pemetrexed and gemcitabine, respectively – and platinum chemotherapy as first-line therapy for people with non-small cell lung cancer, both approved this year by the NMPA within a few months of each other. We are committed to the development and commercialization of effective cancer therapies and devote ourselves to helping patients with more innovative products through independent R&D and strategic collaborations."

Dr. Li WANG, Senior Vice President of Lilly China and Head of Lilly China Drug Development and Medical Affairs Center, stated: "Results of multiple clinical studies show that immuno-oncology therapy has become one of the standard global treatment options for lung cancer due to its proven clinical efficacy and safety. The approval of this new indication has further demonstrated its potential to treat people with lung cancer. Lilly will continue to work closely with Innovent to further explore TYVYT's clinical potential in other tumor types with the hopes of helping more cancer patients." 

About Squamous Non-Small Cell Lung Cancer

Lung cancer is a malignancy with the highest morbidity and mortality in China. Non-small cell lung cancer (NSCLC) accounts for about 80 to 85 percent of lung cancer. Approximately 70 percent of people with NSCLC have locally advanced or metastatic disease 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 in China with NSCLC have tumors of the squamous subtype and there are limited approved second-line therapies for these patients. Therefore, this remains a huge unmet medical need in China.

About ORIENT-12

ORIENT-12 （ClinicalTrials.gov, NCT03629925）is a randomized, double-blind, Phase 3 clinical trial evaluating TYVYT® (sintilimab injection) or placebo in combination with GEMZAR® (gemcitabine) and platinum chemotherapy (carboplatin or cisplatin) as a first-line treatment for advanced or metastatic squamous non-small cell lung cancer (sqNSCLC). A total of 357 participants were enrolled and randomized in a 1:1 ratio (179 participants in the TYVYT® (sintilimab injection) combination arm, 178 participants in the placebo combination arm).

ORIENT-12 demonstrated a statistically significant improvement in progression-free survival (PFS), the study's primary endpoint, of TYVYT® (sintilimab injection) in combination with GEMZAR® and platinum chemotherapy compared with placebo in combination with GEMZAR® and platinum chemotherapy. The median PFS of the TYVYT® (sintilimab injection) combination arm was 5.5 months compared to 4.9 months on the placebo combination arm (HR=0.536, 95% CI: 0.422-0.681, P< 0.00001) as assessed by Independent Radiographic Review Committee (IRRC), and 6.7 months compared to 4.9 months respectively (HR=0.532, 95% CI: 0.419-0.674, P< 0.00001), as assessed by the study's investigators. Overall survival (OS), a secondary endpoint, of the TYVYT® (sintilimab injection) combination arm showed a positive trend when compared to the placebo combination arm (HR=0.567, 95%CI: 0.353-0.909, P=0.01701), though the data were not yet mature at an interim analysis. The safety profile is consistent with previously reported TYVYT® (sintilimab injection) studies, and no new safety signals were identified.

About Sintilimab

Sintilimab, marketed as TYVYT® (sintilimab injection) in China, is an innovative PD-1 inhibitor with global quality standards jointly developed by Innovent and Lilly. Sintilimab is a type of immunoglobulin G4 monoclonal antibody, which binds to PD-1 molecules on the surface of T-cells, blocks the PD-1 / PD-Ligand 1 (PD-L1) pathway, and reactivates T-cells to kill cancer cells. Innovent is currently conducting more than 20 clinical studies of sintilimab to evaluate its safety and efficacy in a wide variety of cancer indications, including more than 10 registrational or pivotal clinical trials.

In China, sintilimab has been approved for three indications, including:

The treatment of relapsed or refractory classic Hodgkin's lymphoma after two lines or later of systemic chemotherapy

In combination with pemetrexed and platinum chemotherapy, for the first-line treatment of nonsquamous non-small cell lung cancer

In combination with gemcitabine and platinum chemotherapy, for the first-line treatment of squamous non-small cell lung cancer

Additionally, Innovent currently has regulatory submissions under review in China for sintilimab:

In combination with BYVASDA® (bevacizumab injection) for the first-line treatment of hepatocellular carcinoma

The second-line treatment of squamous non-small cell lung cancer

In May 2021, the U.S. FDA accepted for review the Biologics License Application (BLA) for sintilimab in combination with pemetrexed and platinum chemotherapy for the first-line treatment of nonsquamous non-small cell lung cancer.

Sintilimab was included in China's 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.

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 24 valuable assets in the fields of cancer, metabolic, autoimmune disease 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, sintilimab's Biologics License Application (BLA) acceptance in the U.S. , 6 assets in Phase 3 or pivotal clinical trials, and an additional 14 molecules in clinical trials. In 2019, TYVYT® was the first PD-1 inhibitor included in the National Reimbursement Drug List (NRDL) and the only PD-1 inhibitor included in the NRDL in that year.

Innovent has built an international team with advanced talent in high-end biological drug development and commercialization, including many global 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 many collaborators to help advance China's biopharmaceutical industry, improve drug availability 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 into a licensing agreement with Lilly to develop and commercialize a potentially global best-in-class diabetes medicine in China. Its collaboration with Lilly is an example of how 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 sintilimab, whereby Lilly obtained an exclusive license for sintilimab for geographies outside of China and plans to pursue registration of sintilimab in the U.S. and other geographies outside of China.

Note:

[1] The PFS and OS data in China approved indication label for TYVYT® (sintilimab injection).

TYVYT® (sintilimab injection; Innovent), BYVASDA® (bevacizumab biosimilar injection; Innovent), SULINNO® (adalimumab biosimilar injection; Innovent), and HALPRYZA® (rituximab biosimilar injection; Innovent) are not approved products in the United States.