Innovent and Lilly Jointly Announce the Approval of TYVYT® (sintilimab injection) by China NMPA in Combination with Chemotherapy as First-Line Treatment for Esophageal Squamous Cell Carcinoma

SAN FRANCISCO, INDIANAPOLIS and SUZHOU, China, June 20, 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) today announced that the Center for Drug Evaluation (CDE) of China's National Medical Products Administration (NMPA) has approved the supplemental New Drug Application (sNDA) for TYVYT® (sintilimab injection) in combination with cisplatin plus paclitaxel or cisplatin plus 5-fluorouracil chemotherapy for the first-line treatment of unresectable, locally advanced, recurrent or metastatic esophageal squamous cell carcinoma (ESCC).

This is the fifth NMPA-approved indication of TYVYT®. In China, TYVYT® was approved for: the treatment of relapsed or refractory classical Hodgkin's lymphoma in December 2018; the first-line treatment of non-squamous non-small cell lung cancer (NSCLC) in February 2021; and the first-line treatment of squamous NSCLC as well as the first-line treatment of hepatocellular carcinoma in June 2021.

The new approval was based on the interim analysis of ORIENT-15, a global randomized, double-blind, multi-center Phase 3 clinical trial – which evaluated sintilimab in combination with chemotherapy compared to placebo in combination with chemotherapy as first-line therapy for ESCC. Based on the interim analysis conducted by the Independent Data Monitoring Committee (IDMC), sintilimab in combination with chemotherapy demonstrated a statistically significant improvement in the primary endpoint of overall survival (OS) compared to placebo in combination with chemotherapy regardless of PD-L1 expression status, meeting the pre-defined superior efficacy criteria. Safety profile was consistent with that observed in previously reported studies of sintilimab without new or unexpected safety signals. The results of ORIENT-15 were published in British Medical Journal on April 19, 2022^[1].

Prof. Shen Lin, Principal Investigator of ORIENT-15 Study, Peking University Cancer Hospital and Institute, stated," Esophageal cancer is one of the most common cancers in China ranking fifth in cancer prevalence and the fourth in mortality cases, with squamous cell carcinoma as most predominant histologic type^[2]. In the past, median OS was approximately 10 months for chemotherapy as the first-line standard of care^[3]. The results of ORIENT-15 demonstrated that sintilimab plus chemotherapy as the first-line treatment for ESCC significantly improved overall survival (OS) and progression-free survival (PFS) compared to placebo plus chemotherapy, with median OS of 16.7 months（vs. 12.5 months, HR=0.63） and median PFS of 7.2 months（vs. 5.7months,HR=0.56） for sintilimab plus chemotherapy. In addition, the results showed the general applicability of sintilimab with two different chemotherapy regimens^[1]. The approval of sintilimab in combination with chemotherapy as a first-line treatment for ESCC is exciting news and will provide an effective and affordable treatment option for patients living with ESCC in China."

Dr. Yongjun Liu, President of Innovent, stated," TYVYT® (sintilimab injection) is the only innovative PD-1 inhibitor with positive Phase 3 studies results as a first-line treatment for five major types of cancer, including the squamous/non-squamous non-small cell lung cancer, liver cancer, gastric cancer and now esophageal cancer. We are encouraged by the results of the ORIENT-15 study, a global multi-center phase 3 trial demonstrating sintilimab as a high quality treatment option with great clinical value for people living with esophageal cancer. Innovent is committed to our mission of developing high-quality biopharmaceuticals that are affordable and contribute to the 'Healthy China 2030' Plan for cancer prevention and treatment."

Dr. Hui Zhou, Senior Vice President of Innovent, stated, "There is a huge unmet clinical need for the first-line treatment of advanced or metastatic ESCC. The results of ORIENT-15 demonstrated that sintilimab can bring significant clinical benefit to the treatment of ESCC. Today, the NMPA of China approval marks another important milestone for sintilimab, and we believe the positive study results will soon translate into superior clinical benefits for ESCC patients. We believe the approval of this new indication will further strengthen the leadership position of TYVYT® (sintilimab injection) and bring hopes to more Chinese cancer patients in broader market."

Mr. Julio Gay-Ger, President and General Manager of Lilly China, stated, "From Hodgkin's lymphoma, lung cancer, liver cancer, and now to esophageal squamous cell carcinoma (ESCC), we are excited to see another indication of TYVYT® (sintilimab injection) approved in China in a short of time, bringing new options to Chinese esophageal cancer patients. With our commitment to oncology, Lilly strives to bring high-quality and affordable innovative drugs to Chinese cancer patients through both independent R&D and local partnerships. TYVYT® (sintilimab injection) sets a great example for our partnership with Innovent, and the new approval will further benefit more Chinese cancer patients."

Dr. Li Wang, Senior Vice President of Lilly China and Head of Lilly China Drug Development and Medical Affairs Center, stated, "The approval of TYVYT® (sintilimab injection) for the first-line indication of esophageal squamous cell carcinoma (ESCC) demonstrated the clinical value of combined immunotherapy in this field. The number of new cases and deaths of esophageal cancer in China accounts for more than half of the world's total^[2]. The ORIENT-15 study, starting from the Chinese ESCC population while having a global perspective, achieved promising results of benefiting the entire population, bringing new options and new hope for the treatment of ESCC patients^[1]."

About the ORIENT-15 Study

ORIENT-15 is a global randomized, double-blind, multicenter Phase 3 clinical study evaluating sintilimab in combination with chemotherapy (cisplatin plus paclitaxel or 5-fluorouracil [5-FU]), compared to placebo in combination with chemotherapy, for the first-line treatment of unresectable locally advanced, recurrent or metastatic esophageal squamous cell carcinoma (ClinicalTrials.gov, NCT03748134). At the time of interim analysis, a total of 659 eligible patients (of the planned 676 estimated participants) were enrolled and randomly assigned into the experimental group or control group in a 1:1 ratio. The primary endpoints were overall survival (OS) in all randomized patients and OS in PD-L1 positive (defined as CPS ≥10) patients^[1].

Based on the interim analysis conducted by the Independent Data Monitoring Committee (IDMC), sintilimab in combination with chemotherapy demonstrated a statistically significant improvement in the primary endpoint of overall survival (OS) compared to placebo in combination with chemotherapy, regardless of PD-L1 expression status, meeting the pre-defined superior efficacy criteria. Safety analyses revealed no new safety signals. The results of ORIENT-15 were published in British Medical Journal on April 19, 2022^[1].

About Esophageal Squamous Cell Carcinoma (ESCC)

Esophageal cancer (EC) is one of the most common malignant tumors worldwide that begins in the inner layer (mucosa) of the esophagus, which connects the throat to the stomach. Based on GLOBOCAN 2020 estimates, approximately 600,000 new cases of esophageal cancer are diagnosed and approximately 540,000 deaths result from the disease worldwide each year^[4]. Esophageal cancer is the seventh most commonly diagnosed cancer and the sixth leading cause of death from cancer worldwide^[4]. More than half of new and fatal cases of esophageal cancer in the world occur in China^[2]. In China, it is estimated there were approximately 320,000 new cases of esophageal cancer diagnosed and approximately 300,000 deaths resulting from the disease in 2020^[2]. Esophageal cancer is the fifth most commonly diagnosed cancer and the fourth leading cause of death from cancer in China, where it has a five-year survival rate of only 30%^[2].

The two main types of esophageal cancer are squamous cell carcinoma (SCC) and adenocarcinoma. In China, SCC is the predominant histologic type, accounting for more than 90% of all esophageal cancer^[5]. In the past, first-line standard systemic therapy was chemotherapy based on platinum drugs for unresectable locally advanced, recurrent or metastatic ESCC, which calls for more effective first-line treatment options. Several PD-1 inhibitors have been approved as first-line treatment in combination with chemotherapy^[6],[7] .

About Sintilimab

Sintilimab, marketed as TYVYT® (sintilimab injection) in China, is a PD-1 immunoglobulin G4 monoclonal antibodyjointly 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^[8]. 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 and included in the National Reimbursement Drug List (NRDL) for four indications, and recently approved for one additional indication 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.

Additionally, Innovent currently has two regulatory submissions under review in the China's NMPA for sintilimab:

• In combination with chemotherapy for the first-line treatment of unresectable, locally advanced, recurrent or metastatic gastric or gastroesophageal junction adenocarcinoma;
• In combination with bevacizumab biosimilar and chemotherapy for EGFR-mutated non-squamous NSCLC following EGFR-TKI treatment.

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 http://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, 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.

SOURCE Innovent Biologics