Tyvyt® (Sintilimab Injection) Achieves Primary Endpoint in Phase II ORIENT-2 Trial for Second-Line Treatment of Advanced Esophageal Squamous Cell Carcinoma

SUZHOU, China, May 14, 2020 /PRNewswire/ -- Innovent Biologics (HKEX stock code: 01801), a biopharmaceutical company dedicated to the research, development, manufacturing, and commercialization of innovative drugs for the treatment of major diseases such as cancer, autoimmune disorders, and metabolic diseases, today jointly announced with Eli Lilly and Company (NYSE ticker symbol: LLY) that Tyvyt, an innovative PD-1 inhibitor co-developed by the two parties^®Sintilimab Injection (hereinafter referred to as Sintilimab) met the prespecified primary endpoint in a randomized, controlled Phase II clinical trial (ORIENT-2) evaluating its use as second-line treatment for advanced esophageal squamous cell carcinoma. Compared with chemotherapy monotherapy, Sintilimab monotherapy significantly prolonged overall survival (OS) and reduced the risk of death. The safety profile was consistent with previously reported findings for Sintilimab, with no new safety signals identified. Detailed study results will be presented in a poster discussion (Abstract No. 4511) at this year’s ASCO Annual Meeting.

Innovent Bio and Eli Lilly plan to communicate with the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) regarding the results of this study.

Professor Xu Jianming from the Fifth Medical Center of the Chinese PLA General Hospital, the principal investigator of the ORIENT-2 study, stated, “The incidence of esophageal squamous cell carcinoma (ESCC) in Asian countries is significantly higher than in Western countries. Current treatment modalities still primarily rely on conventional chemotherapy and radiotherapy, with traditional chemotherapeutic agents showing very limited efficacy in second-line treatment for patients with advanced ESCC. Over the past decade, immunotherapy has made remarkable progress across multiple tumor types; however, its development in ESCC has been slow, leaving a substantial unmet clinical need. The ORIENT-2 study confirmed that sintilimab monotherapy can prolong overall survival in this patient population. We have observed that sintilimab demonstrates superior clinical efficacy compared to conventional chemotherapy in ESCC, holding promise to provide patients with a more effective new treatment option.”

Dr. Zhou Hui, Vice President of Medical Science and Strategic Oncology at Innovent Bio, stated: “Tyvyt^®(Sintilimab Injection) was approved by the NMPA in 2018 for the treatment of relapsed or refractory classical Hodgkin lymphoma in patients who have received at least two lines of systemic chemotherapy. To evaluate the efficacy of sintilimab in treating other types of tumors, we currently have more than 20 clinical studies underway. The results of the ORIENT-2 study demonstrated the potential clinical value of sintilimab in treating patients with advanced esophageal cancer, bringing new hope to this patient population. We are also concurrently conducting a randomized, double-blind, multicenter, Phase III study (ORIENT-15) to assess the efficacy and safety of sintilimab or placebo in combination with paclitaxel and cisplatin as first-line treatment for unresectable, locally advanced recurrent or metastatic esophageal squamous cell carcinoma. Through these clinical studies, we aim to provide patients with more effective cancer treatment options. We anticipate that sintilimab will benefit a broader population of patients with esophageal squamous cell carcinoma.

“From Hodgkin lymphoma to lung cancer, and now to esophageal cancer, we are pleased to see the clinical efficacy of sintilimab validated in an increasing number of tumor types,” said Dr. Li Wang, Senior Vice President of Eli Lilly China and Head of the Drug Development and Medical Affairs Center. “The achievement of the primary endpoint in the ORIENT-2 study would not have been possible without all the participating patients, investigators, clinical trial centers, and our colleagues at Innovent Bio. We extend our respect and gratitude to them, and look forward to bringing this novel treatment regimen to Chinese patients with esophageal cancer as soon as possible.”

AboutORIENT-2 Study

The ORIENT-2 study is a comparison of Tyvyt^®A Randomized, Open-Label, Multicenter, Phase II Controlled Clinical Study on the Efficacy and Safety of Sintilimab Injection Combined with Paclitaxel or Irinotecan in Patients with Advanced/Metastatic Esophageal Squamous Cell Carcinoma Who Failed First-Line Therapy (ClinicalTrials.gov, NCT03116152). The Primary Endpoint Was Overall Survival (OS).

A total of 190 subjects were enrolled in this study and randomized in a 1:1 ratio to receive Tyvyt, respectively.^®(sintilimab injection) or a treatment drug selected by the investigator from paclitaxel or irinotecan, until disease progression, intolerable toxicity, withdrawal of informed consent, death, or other circumstances specified in the protocol that require discontinuation of treatment occur, whichever comes first.

On Advanced or Metastatic Esophageal Squamous Cell Carcinoma (ESCC）

In China, the incidence and mortality rates of esophageal cancer rank third and fourth, respectively, with squamous cell carcinoma (SCC) accounting for approximately 90% of all esophageal cancer cases. A significant proportion of patients with early-stage esophageal SCC who undergo surgical treatment still experience recurrence or distant metastasis. Currently, the standard treatment for esophageal SCC remains conventional chemotherapy and radiotherapy. There are no targeted therapies approved for esophageal SCC in China, resulting in limited treatment options and a substantial unmet clinical need.

About Tyvyt® (Sintilimab Injection)

Tyvyt^®(Sintilimab Injection) is an innovative, international-quality biologic drug jointly developed by Innovent Biologics and Eli Lilly in China. Its first approved indication was relapsed/refractory classical Hodgkin lymphoma, and it was included in the 2019 edition of the Chinese Society of Clinical Oncology (CSCO) Guidelines for Diagnosis and Treatment of Lymphoma. During the 2019 National Reimbursement Drug List negotiations, Tyvyt^®(Sintilimab Injection) is the only PD-1 inhibitor included in the National Reimbursement Drug List. In April 2020, the NMPA officially accepted the application for Tyvyt.^®(Sintilimab Injection) in combination withAlimta^®(Pemetrexed Disodium for Injection) and platinum-based chemotherapy as first-line treatment for non-squamous non-small cell lung cancer: application for new indication. In May 2020, Tyvyt^®(Sintilimab Injection) in Combination with Gemzar^®(Gemcitabine for Injection) and Platinum-Based Chemotherapy as First-Line Treatment for Squamous Non-Small Cell Lung Cancer: Phase III Study Meets Primary Endpoint

Tyvyt®^®(Sintilimab Injection) 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 that leads to tumor immune tolerance. This reactivates the anti-tumor activity of lymphocytes, achieving the goal of cancer treatment. Currently, more than 20 clinical studies (including over 10 registration-enabling trials) are underway to evaluate the anti-tumor efficacy of sintilimab in various solid tumors and hematologic malignancies. Innovent Bio is also conducting global clinical research on Sintilimab Injection.

Statement:

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

About Innovent Bio

“Rooted in Trust, Realized through Action.” Innovent Bio’s vision and goal is to develop high-quality biologics that are affordable for the general public. Established in 2011, Innovent Bio is dedicated to the development, manufacturing, and commercialization of innovative medicines for the treatment of major diseases, including cancer, autoimmune disorders, and metabolic diseases. On October 31, 2018, Innovent Biologics (Suzhou) Co., Ltd. was listed on the Main Board of The Stock Exchange of Hong Kong Limited, with stock code: 01801.

Since its establishment, the company has stood out among numerous biopharmaceutical companies with its innovative achievements and internationalized operation model. It has established a product pipeline comprising 23 new drug candidates, covering multiple therapeutic areas including oncology, autoimmune diseases, and metabolic disorders. Among these, six candidates were selected for the National "Major New Drug Creation" Special Project, 16 have entered clinical studies, five have reached Phase III or pivotal clinical trials, and marketing applications for four monoclonal antibody products have been accepted by the NMPA, three of which were included in the priority review program. One product (Sintilimab Injection, brand name: Tyvyt^®, English Trademark: TYVYT^®) received NMPA approval for market launch, with the first approved indication being relapsed/refractory classical Hodgkin lymphoma, and in November 2019, it became the only PD-1 inhibitor included in the updated National Reimbursement Drug List.

Innovent Bio has assembled a world-class team of experts in the development and industrialization of high-end biologics, including numerous overseas-returning specialists, and has established strategic collaborations with international pharmaceutical companies such as Eli Lilly and Company, Adimab, Incyte, and Hanmi Pharmaceutical. Innovent Bio is committed to working together with all stakeholders to elevate the development of China’s biopharmaceutical industry, thereby enhancing drug accessibility for the public and fulfilling people’s aspirations for better health and well-being. For more details, please visit the company website:www.innoventbio.com。

About Eli Lilly and Company

Eli Lilly and Company is a global leader in the pharmaceutical industry, dedicated to improving human health through innovation. Founded more than a century ago, the company was established with a commitment to producing high-quality medicines that meet real medical needs. Today, we remain steadfast in this mission and guide our work by it. Worldwide, our employees strive to discover and develop life-changing medicines and deliver them to patients who need them most. Furthermore, we are committed to enhancing public understanding of diseases and improving disease management, while giving back to society through philanthropy and volunteerism. For more information about Eli Lilly and Company, please visit:www.lilly.com。

On the Strategic Cooperation Between Innovent Bio and Eli Lilly

Innovent Bio and Eli Lilly reached a biologic drug development collaboration in March 2015, which remains one of the largest partnerships to date between a Chinese biopharmaceutical company and a multinational pharmaceutical corporation. Under the terms of the agreement, Innovent Bio and Eli Lilly will jointly develop and commercialize products in China, including Tyvyt^®Oncology drugs, including sintilimab injection. In October 2015, the two parties announced a further expansion of their established drug development collaboration by adding three novel oncology therapeutic antibodies. In August 2019, the collaboration was extended to the field of diabetes, with Innovent Bio licensed to develop and commercialize in China a potential global best-in-class novel clinical-stage diabetes drug from Eli Lilly. These three collaborations with Eli Lilly and Company mark that Innovent Bio has established a comprehensive strategic partnership between an innovative Chinese pharmaceutical company and a global pharmaceutical giant, covering new drug research and development, clinical studies, manufacturing quality, and marketing and sales.