Innovent Biologics and Lilly Announce NMPA Approval of TYVYT® (Sintilimab Injection) in Combination with Pemetrexed and Platinum Chemotherapy for First-Line Treatment of Non-Squamous Non-Small Cell Lung Cancer

San Francisco, USA and Suzhou, China, February 3, 2021 /PRNewswire/ -- Innovent Biologics (Hong Kong Stock Exchange stock code: 01801), a biopharmaceutical company dedicated to the research, development, production, and sales of innovative drugs for treating major diseases such as cancer, metabolic disorders, and autoimmune conditions, today jointly announced with Eli Lilly and Company (NYSE: LLY) that the PD-1 inhibitor Tyvyt, an innovative drug co-developed by both parties,^®(Sintilimab Injection) has officially received approval from the National Medical Products Administration (NMPA) for use in combination with pemetrexed and platinum-based chemotherapy as first-line treatment for non-squamous non-small cell lung cancer (nsqNSCLC). This is Tyvyt.^®(Sintilimab Injection) The second approved indication, following its initial approval by the NMPA in December 2018 for the treatment of relapsed or refractory classical Hodgkin lymphoma in patients who have undergone at least two lines of systemic chemotherapy.

The approval of this indication is based on a randomized, double-blind, Phase III controlled clinical study (ORIENT-11) -- Tyvyt^®(Sintilimab Injection) or placebo in combination with Alimta^®(Pemetrexed Disodium for Injection) and platinum-based agents are used as first-line treatment for advanced or recurrent non-squamous NSCLC without EGFR sensitizing mutations or ALK gene rearrangements. This study randomly enrolled 397 subjects, who were randomized in a 2:1 ratio into the experimental group (n=266) and the control group (n=131). The ORIENT-11 study confirmed that Tyvyt^®(Sintilimab Injection) Combined with Alimta^®(Pemetrexed Disodium for Injection) and Platinum versus Placebo Combined with Alimta^®(Pemetrexed Disodium for Injection) and platinum-based chemotherapy significantly prolonged progression-free survival (PFS). The median PFS assessed by an independent radiology review committee was 8.9 months in the experimental group and 5.0 months in the control group, with a hazard ratio (HR) of 0.482 (95% CI: 0.362–0.643; P < 0.00001). Overall survival (OS) data were not yet mature at the interim analysis. The safety profile was consistent with previously reported findings for Tyvyt^®(Sintilimab Injection) The study results were consistent, with no new safety signals identified.

With extended follow-up, the median OS in the experimental group remained unreached in the updated analysis, while the median OS in the control group was 16.0 months. Sintilimab combined with chemotherapy significantly prolonged OS, with a HR (95% CI) of 0.606 (0.437, 0.841), P=0.00250.^[1]. Detailed OS update data are scheduled to be published in the near future.

Professor Zhang Li from the Department of Medical Oncology at Sun Yat-sen University Cancer Center stated, “Approximately 60% of NSCLC cases in China are non-squamous NSCLC, and nearly 50% of these patients lack driver gene mutations. This subset of patients with advanced lung cancer is not eligible for targeted therapy, has limited treatment options, and represents a significant unmet medical need. In recent years, research on activating the human immune system to attack tumor cells by inhibiting immune checkpoints has progressed rapidly. The use of immune checkpoint inhibitors (such as anti-PD-1/PD-L1 antibodies) has provided new therapeutic options for the first-line treatment of recurrent or metastatic advanced NSCLC, including Tyvyt^®(Approval of new indications for Sintilimab Injection will benefit more patients.)”

Dr. Liu Yongjun, President of Innovent Bio, stated, “As an achievement of the National Major New Drug Creation Special Project, Tyvyt^®(Sintilimab Injection) is a PD-1 inhibitor of international quality. The approval of this new indication marks Tyvyt^®(Sintilimab Injection) Significant Development Progress in the Field of Non-Small Cell Lung Cancer. We sincerely look forward to Tyvyt^®“(Sintilimab Injection) enables an increasing number of patients to benefit. Innovent Bio will continue its efforts, staying true to its original mission of developing high-quality biologics that are affordable for the general public, thereby bringing hope for life to more patients.”

Dr. Zhou Hui, Vice President of Medical Science and Strategic Oncology at Innovent Bio, stated, “In China, lung cancer ranks first among all cancers in both incidence and mortality. Despite advances in treatment technologies, there remains a substantial unmet clinical need for effective lung cancer therapies. This time, Tyvyt^®“The approval of the new indication for Sintilimab Injection provides more treatment options for patients with first-line non-squamous non-small cell lung cancer. We hope that through our unremitting efforts, more Chinese patients with advanced lung cancer will benefit, thereby reducing the burden on society and patient families.”

Julio Gay-ger, President and General Manager of Eli Lilly China, stated, “Oncology is one of Eli Lilly’s key strategic therapeutic areas globally, and we have long been deeply committed to the field of lung cancer. This time, Tyvyt^®(The approval of the lung cancer indication for sintilimab injection) marks another significant milestone in the strategic alliance between Eli Lilly and Innovent Bio, and will also help Eli Lilly China further enhance its influence in the field of lung cancer. Eli Lilly has always been committed to promoting the development of anti-tumor treatments in China and will continue to do its utmost to contribute to the early realization of the “Healthy China 2030” goal.

Dr. Li Wang, Senior Vice President of Eli Lilly China and Head of the Drug Development and Medical Affairs Center, stated：“In recent years, the successive emergence of tumor immunotherapy drugs has changed the landscape of tumor treatment and also provided new ideas for lung cancer treatment. Clinical research results indicate that the combination therapy of tumor immunotherapy and chemotherapy has a definite efficacy and has gradually become one of the feasible options for lung cancer treatment. We are now discussing Tyvyt (sintilimab injection)…”^®“We are thrilled about the approval of the new indication for sintilimab injection. In the future, we will continue to strengthen our collaboration with Innovent Bio to further explore its clinical potential in the field of tumor immunotherapy, aiming to bring new treatment options to more cancer patients in China.”

# Regarding Non-Squamous Non-Small Cell Lung Cancer

Cancer has long been one of the leading causes of death worldwide, representing a major category of diseases that severely threaten human life and health and constrain socioeconomic development, with its incidence and mortality rates continuing to rise rapidly. Lung cancer is currently the most prevalent malignant tumor in China, ranking first in both incidence and mortality. Among all lung cancers, non-small cell lung cancer (NSCLC) accounts for approximately 80% to 85%. About 70% of NSCLC patients are diagnosed with locally advanced or metastatic disease that is not amenable to curative surgery. Furthermore, a significant proportion of early-stage NSCLC patients who undergo surgical treatment experience recurrence or distant metastasis, ultimately leading to death due to disease progression. Approximately 60% of NSCLC patients in China have non-squamous NSCLC. Among these, nearly 50% lack EGFR sensitizing mutations or ALK gene rearrangements. These patients with advanced lung cancer are not eligible for targeted therapy, have limited treatment options, and represent a substantial unmet medical need.

About Tyvyt® (Sintilimab Injection)

Tyvyt®^®(Sintilimab Injection) is an innovative PD-1 inhibitor of international quality, jointly developed by Innovent Biologics and Eli Lilly in China. In December 2018, Tyvyt^®(Sintilimab Injection) was first approved by the NMPA for the treatment of relapsed or refractory classical Hodgkin lymphoma in patients who have undergone at least two lines of systemic chemotherapy. In February 2021, Tyvyt^®(Sintilimab Injection) was approved by the NMPA in combination with pemetrexed and platinum-based chemotherapy for the first-line treatment of non-squamous non-small cell lung cancer (nsqNSCLC). Tyvyt^®(Sintilimab Injection) was successfully included in the National Reimbursement Drug List (NRDL) in November 2019, becoming the first and only PD-1 inhibitor to enter the NRDL that year.

Currently, Tyvyt^®(Sintilimab Injection) Three additional supplemental New Drug Applications (sNDAs) for new indications have been accepted for review by the NMPA. In August 2020, the NMPA formally accepted Tyvyt^®(Sintilimab Injection) Combined with Gemzar^®(Gemcitabine for Injection) and platinum-based chemotherapy as first-line treatment for squamous non-small cell lung cancer: application for a new indication. In January 2021, the NMPA officially accepted the application for Tyvyt^®(Sintilimab Injection) Combined with Byvasda^®(New Indication Application for Bevacizumab Injection in the First-Line Treatment of Liver Cancer Patients and Tyvyt)^®(Sintilimab Injection) New Indication Application for Second-line Treatment of Squamous Non-small Cell Lung Cancer. In addition, in May 2020, Tyvyt^®The ORIENT-2 study of sintilimab injection as monotherapy for second-line treatment of advanced/metastatic esophageal squamous cell carcinoma also met its 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, reactivating the anti-tumor activity of lymphocytes, and thus achieving the purpose of treating tumors. Currently, more than twenty clinical studies (including over ten registrational clinical trials) are underway to evaluate the anti-tumor effects of sintilimab in various solid tumors and hematologic malignancies. Innovent Bio is also conducting global clinical research on Sintilimab Injection.

About Innovent Bio

“Rooted in Trust, Realized through Action.” Innovent Bio’s vision and goal is to develop high-quality biologics that are affordable to the general public. Founded 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 innovative achievements and an internationalized operating model. It has built a product pipeline comprising 23 new drug candidates, covering multiple disease areas including oncology, metabolic diseases, and autoimmune disorders. Among these, six candidates were selected for the National “Major New Drug Development” Special Project, and four products (Sintilimab Injection, brand name: Tyvyt^®, English trademark: TYVYT^®; Bevacizumab biosimilar, brand name: Byvasda^®, English trademark: BYVASDA^®; Adalimumab biosimilar, brand name: Sulixin^®, English Trademark: SULINNO^®; Rituximab biosimilar, brand name: Dabohua^®, English trademark: HALPRYZA^®) received NMPA approval for market launch; four candidates have entered Phase III or pivotal clinical studies, and an additional 15 products have entered clinical development. Sintilimab was successfully included in the National Reimbursement Drug List (NRDL) in November 2019, becoming the first and only PD-1 inhibitor to be included in the NRDL that year.

Innovent Bio has assembled a high-caliber team for the development and industrialization of biologics, featuring international advanced expertise and numerous overseas-returning experts. The company has established strategic collaborations with international partners including Eli Lilly and Company, Adimab, Incyte, MD Anderson Cancer Center, and Hanmi Pharmaceutical. Innovent Bio is committed to working collaboratively to advance the development of China’s biopharmaceutical industry, thereby improving drug accessibility for the public and fulfilling people’s aspirations for better health and well-being. For more details, please visit the company’s 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 over a century ago, our founder was committed to producing high-quality medicines to meet genuine 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 truly need them. 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

In March 2015, Innovent Bio and Eli Lilly and Company entered into a biologic drug development collaboration, 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 and Company will jointly develop and commercialize 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 a Chinese innovative pharmaceutical enterprise and a global pharmaceutical giant, covering new drug research and development, clinical studies, manufacturing quality, and marketing and sales. In August 2020, Innovent Bio and Eli Lilly and Company announced the expansion of Tyvyt^®(Strategic cooperation on sintilimab injection) Innovent Bio will grant Eli Lilly an exclusive license for sintilimab in regions outside of China, and Eli Lilly will be committed to promoting sintilimab in North America, Europe, and other regions.

[1] Data sourced from the Package Insert of Sintilimab Injection.