Innovent Announces Phase III ORIENT-16 Trial of TYVYT® (Sintilimab Injection) Plus Chemotherapy Meets Primary Endpoint in First-Line Treatment of Advanced Gastric or Gastroesophageal Junction Adenocarcinoma

SAN FRANCISCO and SUZHOU, China, Aug. 16, 2021 /PRNewswire/ -- Innovent Biologics (HKEX: 01801), a biopharmaceutical company dedicated to the research, development, manufacturing, and commercialization of innovative drugs for the treatment of major diseases including cancer, metabolic diseases, and autoimmune diseases, today announced that the innovative PD-1 inhibitor sintilimab (Tyvyt®), jointly developed by Innovent and Eli Lilly^®(Sintilimab Injection) in combination with chemotherapy (oxaliplatin + capecitabine) as first-line treatment for unresectable locally advanced, recurrent, or metastatic gastric or gastroesophageal junction adenocarcinoma: the interim analysis of the randomized, double-blind, multicenter Phase III clinical study (Study Code: ORIENT-16) met the primary endpoint.

Based on the interim analysis conducted by the independent data monitoring committee (iDMC), sintilimab in combination with chemotherapy significantly prolonged overall survival (OS) compared with placebo plus chemotherapy in both the intent-to-treat (ITT) population and the PD-L1-positive population, meeting the pre-specified superiority criteria. The safety profile was consistent with previously reported clinical studies of sintilimab, with no new safety signals identified. Relevant study results will be presented at upcoming international academic conferences.

Based on the recommendation of the Independent Data Monitoring Committee, Innovent Bio plans to submit Tyvyt®^®Communicated with the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) regarding the marketing authorization application for the new indication of (Sintilimab Injection) in combination with oxaliplatin and capecitabine as first-line treatment for advanced gastric cancer.

Director Xu Jianming, Principal Investigator of the ORIENT-16 study and Director of the Department of Gastrointestinal Oncology at the Fifth Medical Center of the Chinese PLA General Hospital, stated: “The ORIENT-16 study is China’s first randomized controlled Phase III clinical trial to demonstrate that first-line treatment with a PD-1 monoclonal antibody combined with chemotherapy can significantly extend overall survival in patients with advanced gastric cancer. Gastric cancer is one of the most common malignancies worldwide, with nearly half of all cases occurring in China. Patients with unresectable advanced or metastatic gastric cancer have a poor prognosis and currently rely primarily on traditional chemotherapeutic agents as the mainstay of treatment. Moreover, targeted therapies benefit only a limited patient population, underscoring an urgent need for more effective treatment options. The success of the ORIENT-16 study is poised to change this clinical landscape.”，bringing new and more effective treatment options to a broad population of patients with gastric cancer."

Dr. Zhou Hui, Senior Vice President of Innovent Bio, stated: "Although immunotherapy has transformed the treatment paradigm for many malignant tumors, breakthroughs in advanced gastric cancer have been rare. Treatment options for advanced gastric cancer remain extremely limited, reflecting a significant unmet clinical need. The ORIENT-16 study was conducted as a clinical trial focused on patient needs and guided by clinical value. Through the tireless efforts of all investigators, we are pleased with these encouraging results, which demonstrate the clinical value of sintilimab in combination with chemotherapy as a first-line treatment for advanced gastric cancer. We look forward to Tyvyt^®(Sintilimab Injection) will be able to benefit more patients with gastric cancer at the earliest opportunity. We also sincerely thank every participant who took part in this study for collaborating with us to complete this landmark clinical trial.The success of this study also makes Tyvythas become one of the few PD-1 inhibitors globally to demonstrate clinical efficacy in first-line treatment across five major cancer indications, including first-line non-squamous non-small cell lung cancer, first-line squamous non-small cell lung cancer, first-line liver cancer, first-line esophageal cancer, and first-line gastric cancer.”

AboutORIENT-16 Study

The ORIENT-16 study is a randomized, double-blind, multicenter, phase III trial comparing the efficacy and safety of sintilimab versus placebo, in combination with chemotherapy (oxaliplatin plus capecitabine), as first-line treatment for unresectable locally advanced, recurrent, or metastatic gastric and gastroesophageal junction adenocarcinoma (ClinicalTrials.gov, NCT03745170). The primary endpoint is overall survival in the overall population and the PD-L1-positive population.

# About Gastric Cancer

Gastric cancer is one of the most common malignant tumors worldwide. According to data from the World Health Organization's GLOBOCAN database, there were over 1 million new cases of gastric cancer globally in 2020 (accounting for approximately 5.6% of all new cancer cases), making it the fifth most common malignancy worldwide. Half of these cases occur in East Asia, primarily in China. Gastric cancer is the third leading cause of cancer-related deaths globally, with approximately 769,000 patients dying from the disease annually. Currently in China, first-line treatment for advanced or metastatic gastric cancer primarily consists of platinum-based doublet or triplet chemotherapy. The 5-year survival rate is approximately 5% to 20%, with a median overall survival of only about one year.

About Sintilimab

Sintilimab, Chinese brand name: Daboshu^®(Sintilimab Injection) is an innovative PD-1 inhibitor drug of international quality, jointly developed by Innovent Biologics and Eli Lilly and Company. Sintilimab is a human immunoglobulin G4 (IgG4) monoclonal antibody that specifically binds to the PD-1 molecule on the surface of T cells, thereby blocking the PD-1/Programmed Death-Ligand 1 (PD-L1) pathway responsible for tumor immune tolerance. This reactivates the anti-tumor activity of lymphocytes, ultimately achieving the therapeutic goal against tumors. Currently, over twenty clinical studies (including more than 10 registrational clinical trials) are underway to evaluate the anti-tumor efficacy of sintilimab in various solid tumors and hematological malignancies. Innovent Biologics is also conducting global clinical research on sintilimab injection.

Sintilimab has been approved in China for four indications, including:

Additionally, the marketing authorization application for sintilimab monotherapy as a second-line treatment for squamous NSCLC has been accepted for review by the National Medical Products Administration (NMPA) of China.

Sintilimab has also met the study endpoints in three additional clinical trials, including:

In May 2021, the U.S. FDA officially accepted for review the marketing application for sintilimab in combination with pemetrexed and platinum-based chemotherapy as a first-line treatment for non-squamous NSCLC.

Sintilimab was successfully included in China's National Reimbursement Drug List in November 2019, becoming the first and only PD-1 inhibitor to enter the national medical insurance list in China that year.

Disclaimer:

1. This indication is an investigational use of the drug and has not yet been approved in China;

2. Innovent Bio does not recommend the use of any unapproved drugs/indications;

3. For healthcare professionals only.

# About Innovent Bio

“Rooted in Trust, Realized in Action,” developing high-quality biologics that are affordable to the public is the vision and goal of Innovent Biologics. Established in 2011, Innovent Biologics is dedicated to the development, manufacturing, and commercialization of innovative medicines for the treatment of major diseases, including cancers, autoimmune disorders, and metabolic conditions. On October 31, 2018, Innovent Biologics was listed on the Main Board of The Stock Exchange of Hong Kong Limited under the stock code: 01801.

Since its establishment, the company has distinguished itself among numerous biopharmaceutical companies through its innovative achievements and internationalized operational model. It has established a product pipeline comprising 25 new drug candidates, covering multiple therapeutic areas including oncology, metabolic diseases, and autoimmune disorders, six of which have been selected for the National "Major New Drug Creation" Program. The company currently has five products (sintilimab injection, trade name: Tyvyt^®, English Trademark: TYVYT^®；Bevacizumab biosimilar, trade name: Byvasda^®, English Trademark: BYVASDA^®; Adalimumab biosimilar, brand name: Sulinxin^®, English Trademark: SULINNO^®; Rituximab biosimilar, Brand name: Dabohua^®, English Trademark: HALPRYZA^®; pemigatinib oral inhibitor, trade name: Pemazyre^®, English trademark: PEMAZYRE^®) received marketing approval, one marketing application was accepted by the NMPA, the U.S. marketing application for sintilimab was accepted by the FDA, five products entered Phase III or pivotal clinical studies, and an additional 14 products have entered clinical trials. Sintilimab was successfully included in the National Reimbursement Drug List in November 2019, becoming the first and only PD-1 inhibitor in China to be included in the NRDL that year.

Innovent Bio has assembled a high-caliber team specializing in biologic drug development and commercialization at an internationally advanced level, including numerous overseas-educated experts. The company has established strategic partnerships with international collaborators such as Eli Lilly and Company (USA), Adimab, Incyte, MD Anderson Cancer Center, and Hanmi (South Korea). Innovent Bio is committed to working alongside all stakeholders to advance the development of China's biopharmaceutical industry, thereby improving public access to medicines and fulfilling the people's pursuit of health and well-being. For more details, please visit the company website:www.innoventbio.com。

Forward-Looking Statements

Information contained in this press release may include certain forward-looking statements. Such statements are inherently subject to significant risks and uncertainties. The use of words such as "anticipate," "believe," "predict," "expect," "intend," and other similar terms in connection with the Company is intended to identify forward-looking statements. The Company undertakes no obligation to continuously update these forward-looking statements.

These forward-looking statements are based on the current views, assumptions, expectations, estimates, projections, and understanding of our management regarding future matters at the time such statements are made. These statements are not guarantees of future developments and are subject to risks, uncertainties, and other factors, some of which are beyond the Company's control and difficult to predict. Therefore, actual results may differ materially from the information contained in the forward-looking statements due to future changes and developments in our business, competitive environment, and political, economic, legal, and social conditions.