Innovent and Lilly Jointly Announce the Approval of TYVYT® (sintilimab injection) by China NMPA in Combination with Chemotherapy as First-line Treatment of Advanced or Metastatic Gastric or Gastro...

SAN FRANCISCO and SUZHOU, China, June 26, 2022 /PRNewswire/ -- Innovent Biologics, Inc. ("Innovent") (HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures and commercializes high-quality medicines for the treatment of cancer, autoimmune, metabolic, ophthalmology and other major diseases, and Eli Lilly and Company ("Lilly", NYSE: LLY), 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 fluorouracil and platinum-based chemotherapy for the first-line treatment of unresectable, locally advanced, recurrent or metastatic gastric or gastroesophageal junction adenocarcinoma.

This is the sixth NMPA-approved indication of TYVYT®. TYVYT® is the first domestic PD-1 inhibitor approved for the first-line treatment of gastric cancer and is currently approved for the first-line treatment in five major types of cancers. In China, TYVYT® was approved for the treatment of relapsed or refractory classical Hodgkin's lymphoma in December 2018, first-line treatment of nonsquamous non-small cell lung cancer (NSCLC) in February 2021, first-line treatment of squamous NSCLC, and the first-line treatment of hepatocellular carcinoma in June 2021; and the first-line treatment of esophageal squamous cell carcinoma in June 2022.

The approval in China was based on the results of a randomized, double-blind, multicenter Phase III clinical trial (ORIENT-16, NCT03745170) evaluating sintilimab in combination with chemotherapy (oxaliplatin and capecitabine), compared to placebo in combination with chemotherapy, for the first-line treatment of unresectable, locally advanced, recurrent or metastatic gastric or gastroesophageal junction adenocarcinoma. Based on the interim analysis by Independent Data Monitoring Committee (iDMC), sintilimab in combination with chemotherapy demonstrated superior overall survival (OS), compared to placebo plus chemotherapy, with a 34.0% reduction in the risk of death (HR 0.660，95%CI 0.505-0.864，p=0.0023) and a 5.5-month improvement in median OS (mOS 18.4 months vs. 12.9 months) in patients with combined positive score (CPS) ≥5, and 23.4% reduction in the risk of death (HR 0.766, 95%CI 0.626-0.936，p=0.0090）and a 2.9-month improvement in mOS (15.2 months vs. 12.3 months) in all patients regardless of PD-L1 expression. The safety profile of sintilimab in this study was consistent with that observed in previously reported studies of sintilimab, and no additional safety signals were identified for the combination of sintilimab and chemotherapy. The results of ORIENT-16 study were presented at the European Society for Medical Oncology (ESMO) Congress 2021^[1].

Prof. Jianming Xu, The Fifth Medical Center of People's Liberation Army General Hospital stated: "Gastric cancer ranks fifth for global cancer incidence and is the third leading cause of cancer mortality worldwide^[2]. Nearly half of global gastric cancer incidence cases and mortality cases occur in China annually^[2]. The ORIENT-16 study demonstrated that sintilimab in combination with chemotherapy significantly prolonged overall survival of patients with gastric cancer^[1]. We are encouraged by the approval of sintilimab, the first domestic anti-PD-1 monoclonal antibody approved for the treatment of gastric cancer, bringing a new and effective treatment option to be provided to patients with gastric cancer in China."

Dr. Yongjun Liu, President of Innovent, stated: "We are grateful for the recognition received from the Chinese regulatory authorities for TYVYT® (sintilimab injection). This is the second sNDA approval this year, following the first one of ESCC, and enabling TYVYT® (sintilimab injection) to be the domestically first innovative PD-1 inhibitor for the first-line treatment of five major type of cancers. We look forward to bringing TYVYT® (sintilimab injection) as a new standard first-line treatment option for patients with advanced gastric cancer, and opening a new chapter of immunotherapy for gastric cancer. Innovent will uphold our mission of 'to develop, manufacture and commercialize high-quality biopharmaceutical products that are affordable to ordinary people' and make continuous contributions to the 'Healthy China 2030' implementation."

Dr. Hui Zhou, Senior Vice President of Innovent, stated, "The approval of TYVYT® by the NMPA for the treatment of gastric cancer represents an important step forward for Innovent to further expand market coverage and is an important milestone for product development and commercial strategy. Data from the ORIENT-16 study demonstrated significant improvement in overall survival in patients with advanced gastric cancer and safety profile was consistent with that observed in previously reported studies of sintilimab. Survival benefit and reduction in the risk of death were observed, regardless of PD-L1 expression^[1]. Gastric cancer is one of the most common malignancies in China and has different disease characteristics when compared with Western population. Innovent will continue to focus on these unmet medical needs and conduct additional clinical trials to untap the potential of our innovative molecules. We hope to bring more safe and efficacious treatment options to cancer patients both in China and worldwide."

Mr. Julio Gay-Ger, President and General Manager of Lilly China, stated, "China is well-known for gastrointestinal cancers^[2]. The approval of TYVYT® (sintilimab injection) as first-line treatment for gastric cancer marks another milestone. So far, TYVYT® has covered major cancer types including lymphoma, lung cancer, liver cancer, esophageal cancer and gastric cancer, benefiting millions of Chinese patients. With our commitment to oncology, Lilly strives for bringing high-quality and affordable innovative drugs to Chinese cancer patients through both independent R&D and local partnerships. We look forward to continually working with our partner Innovent in bringing more innovative anti-tumor drugs to Chinese patients."

Dr. Li Wang, Senior Vice President of Lilly China and Head of Lilly China Drug Development and Medical Affairs Center, stated, "The ORIENT-16 study, led by Chinese investigators, is the first randomized, double-blind Phase III clinical study in China to demonstrate the significant benefit of immunotherapy combined with chemotherapy for the first-line treatment of advanced gastric cancer^[1]. It provided strong evidence for the treatment of advanced gastric cancer in China. The approval of TYVYT® (sintilimab injection) as first-line treatment for gastric cancer has provided a new option and fresh perspective for existing treatment, and will further benefit more and more Chinese gastric patients"

About the ORIENT-16 Study

ORIENT-16 is a randomized, double-blind, multi-center Phase 3 clinical study evaluating sintilimab or placebo, in combination with chemotherapy (oxaliplatin and capecitabine), for the first-line treatment of unresectable, locally advanced, recurrent or metastatic gastric or gastroesophageal junction (G/GEJ) adenocarcinoma (ClinicalTrials.gov, NCT03745170). The primary endpoint was overall survival, in PD-L1 positive (CPS>5) and all randomized patients^[1].

As of the cutoff date for the interim analysis, a total of 650 patients were enrolled and randomly assigned with a 1:1 ratio to receive sintilimab or placebo in combination with chemotherapy until disease progression, unacceptable toxicity, withdrawal of consent, or death, whichever occurs first. The study met both primary endpoints and the safety profile of sintilimab in this study was consistent with that observed in previously reported studies of sintilimab, and no additional safety signals were identified for the combination of sintilimab and chemotherapy. The results were published at the ESMO Congress 2021.

About Gastric Cancer

Gastric cancer is one of the most common malignant tumor types worldwide. According to GLOBOCAN estimates, there were approximately one million new cases in 2020 and 769,000 new deaths of gastric cancer each year, making it the fifth most common cancer and third leading cause of cancer death globally^[2],[3]. About half of all gastric cancer cases occurred in East Asia, mainly in China^[2]. The first-line treatment of advanced gastric cancer is still limited. Currently, the 5-year survival rate of advanced or metastatic gastric cancer ranges from 5 to 20 percent. The median survival was about 1 year for patients who received chemotherapy only^[4],[5].

About Sintilimab

Sintilimab, marketed as TYVYT® (sintilimab injection) in China, is a PD-1 immunoglobulin G4 monoclonal antibody jointly developed by Innovent and Eli Lilly and Company. 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^[6]. 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 six indications as below, with the first four included in the National Reimbursement Drug List (NRDL), 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 non-squamous non-small cell lung cancer lacking EGFR or ALK driver mutations;
• In combination with gemcitabine and platinum chemotherapy, for the first-line treatment of squamous non-small cell lung cancer;
• In combination with BYVASDA® (bevacizumab biosimilar injection) for the first-line treatment of unresectable or advanced hepatocellular carcinoma;
• In combination with cisplatin plus paclitaxel or cisplatin plus 5-fluorouracil for the first-line treatment of esophageal squamous cell carcinoma;
• In combination with fluorouracil and platinum-based chemotherapy for the first-line treatment of unresectable, locally advanced, recurrent or metastatic gastric or gastroesophageal junction adenocarcinoma.

Innovent currently has the regulatory submission for sintilimab in combination with bevacizumab biosimilar and chemotherapy for EGFR-mutated non-squamous NSCLC following EGFR-TKI treatment under review in the China's NMPA.

Additionally, two clinical studies of sintilimab have met their primary endpoints:

• Phase 2 study as second-line treatment of esophageal squamous cell carcinoma;
• Phase 3 study as second-line treatment for squamous NSCLC with disease progression following platinum-based chemotherapy.

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, ophthalmology and other major diseases. On October 31, 2018, Innovent was listed on the Main Board of the Stock Exchange of Hong Kong 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 32 valuable assets in the fields of cancer, metabolic, autoimmune disease and other major therapeutic areas, with 7 products approved for marketing in China – TYVYT® (sintilimab injection), BYVASDA® (bevacizumab biosimilar injection), SULINNO® (adalimumab biosimilar injection), HALPRYZA® (rituximab biosimilar injection) , Pemazyre® (pemigatinib oral inhibitor) and olverembatinib (BCR-ABL TKI) and Cyramza® (ramucirumab), 3 assets under NMPA NDA review, 3 assets in Phase 3 or pivotal clinical trials, and an additional 19 molecules in clinical studies.

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. For more information, please visit: www.innoventbio.com. and www.linkedin.com/company/innovent-biologics/.

Note:

Sintilimab is not an approved product in the United States.

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

TYVYT® (sintilimab injection, Innovent)

BYVASDA® (bevacizumab biosimilar injection, Innovent)

HALPRYZA® (rituximab biosimilar injection, Innovent)

SULINNO® (adalimumab biosimilar injection, Innovent)

Pemazyre® (pemigatinib oral inhibitor, Incyte Corporation). Pemazyre® was discovered by Incyte Corporation and licensed to Innovent for development and commercialization in Mainland China, Hong Kong, Macau and Taiwan.

CYRAMZA® (ramucirumab, Eli Lilly). Cyramza® was discovered by Eli Lilly and licensed to Innovent for commercialization in Mainland China.

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. To learn more about Lilly, please visit us at www.lilly.com and https://newsroom.lilly.com/social-channels.

About Eli Lilly and Company's strategic cooperation with Innovent Biologics

Lilly entered into a strategic collaboration with Innovent focused on biological medicine in March 2015 – a groundbreaking partnership between a Chinese pharmaceutical company and a multinational pharmaceutical company. Under the agreement, Lilly and Innovent will co-develop and commercialize 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 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 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. In March 2022, Lilly and Innovent deepened the strategic partnership in oncology.

Innovent Biologics, Inc. Forward-Looking Statements

This news release may contain certain forward-looking statements that are, by their nature, subject to significant risks and uncertainties. The words "anticipate", "believe", "estimate", "expect", "intend" and similar expressions, as they relate to Innovent Biologics, Inc. ("Innovent" or "Company"), are intended to identify certain of such forward-looking statements. The Company does not intend to update these forward-looking statements regularly.

These forward-looking statements are based on the existing beliefs, assumptions, expectations, estimates, projections and understandings of the management of the Company with respect to future events at the time these statements are made. These statements are not a guarantee of future developments and are subject to risks, uncertainties and other factors, some of which are beyond the Company's control and are difficult to predict. Consequently, actual results may differ materially from information contained in the forward-looking statements as a result of future changes or developments in our business, the Company's competitive environment and political, economic, legal and social conditions.

The Company, the Directors and the employees of the Company assume (a) no obligation to correct or update the forward-looking statements contained in this site; and (b) no liability in the event that any of the forward-looking statements does not materialise or turn out to be incorrect.

Eli Lilly and Company Forward-Looking Statement

This press release contains forward-looking statements (as that term is defined in the Private Securities Litigation Reform Act of 1995) about sintilimab and reflects Lilly's current beliefs and expectations. However, as with any pharmaceutical product, there are substantial risks and uncertainties in the process of drug research, development, and commercialization. Among other things, there can be no guarantee that future study results will be consistent with study results to date, or that sintilimab will receive additional regulatory approvals or be commercially successful. For further discussion of these and other risks and uncertainties, see Lilly's most recent Form 10-K and Form 10-Q filings with the United States Securities and Exchange Commission. Except as required by law, Lilly undertakes no duty to update forward-looking statements to reflect events after the date of this release.

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