Sanofi Inks $213M Deal for Chinese Biotech I-Mab's CD73 Antibody Uliledlimab in Greater China

On September 25, Tianjing Biotechnology (Shanghai) Co., Ltd. ("Tianjing" or the "Company"), a fully integrated biotech company focused on the development, manufacturing, and collaborative commercialization of innovative biologics in the fields of autoimmune diseases and oncology, announced that it has entered into a strategic collaboration with Sanofi for the development, manufacturing, and commercialization of uliledlimab, Tianjing’s globally innovative self-developed CD73 antibody, in Greater China.

According to the terms of the agreement, Sanofi will pay Tianjing Biotechnology (Shanghai) Co., Ltd. an upfront payment and near-term milestone payments totaling approximately 32 million euros (about 250 million RMB); the potential total amount will not exceed approximately 213 million euros (about 1.7 billion RMB). Tianjing Biotechnology will also receive tiered royalties based on sales, as well as additional milestone payments for new indications.

At the same time, Sanofi will obtain the exclusive license rights for the development, production, and commercialization of Urelumab in mainland China, Hong Kong, Macao, and Taiwan.

Uliledlimab (also known as TJD5) is a highly differentiated CD73 humanized monoclonal antibody independently developed by Tianjing Biotechnology (Shanghai) Co., Ltd., which enhances the body's immune response to cancer cells by modulating the tumor microenvironment. Currently, this drug is undergoing pivotal research in China for the treatment of advanced non-small cell lung cancer (NSCLC) in combination with toripalimab.

At the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting, Tianjing Biotechnology (Shanghai) Co., Ltd. presented positive data from the Phase 1b/2 clinical trials conducted in the United States and China. In a group of 67 evaluable patients, this combination therapy achieved an objective response rate (ORR) of 31.3%. Notably, among PD-L1 positive patients, the ORR reached 63% in 16 patients with high CD73 expression, while the ORR was 20% in 25 patients with low CD73 expression. After an average follow-up of 10.4 months, the median duration of response (DOR) has not yet been reached, suggesting that the responses may be durable.

Data show that the combination of ulrelumab and toripalimab has demonstrated favorable safety and efficacy in treating NSCLC patients with high CD73 expression. Furthermore, the study revealed a close correlation between high tumor CD73 expression and treatment response, highlighting the value of CD73 expression as a predictive biomarker.

The main highlights of this cooperation include:

1) Tianjing Biotechnology will lead the clinical development of uliledlimab for specific cancer indications, and be responsible for clinical drug supply and long-term commercial production. Sanofi will share part of the clinical development costs and lead the commercialization of the product in the Greater China region.

2) Sanofi will pay Tianjing Biotechnology (Shanghai) Co., Ltd. an upfront payment and near-term milestone payments of approximately 32 million euros (about 250 million RMB), as well as specific registration and sales milestone payments; the potential total consideration does not exceed 213 million euros (about 1.7 billion RMB).

3) After the commercialization of the product, I-Mab Biopharma will be entitled to receive tiered royalties based on the net sales of uliledlimab in the Greater China region, with a maximum rate reaching double-digit percentages.

4) In addition to the aforementioned financial terms, Tianjing Biotechnology (Shanghai) Co., Ltd. will also receive additional milestone payments upon the regulatory approval of each new indication for Urelumab.

Dr. Zang Jingwu, founder and chairman of Tianjing Biotechnology (Shanghai) Co., Ltd., stated: "This strategic cooperation is an important milestone for Tianjing Biotechnology to maximize the value of its mature R&D pipeline based on the company's closed-loop industrial chain advantage after completing its strategic restructuring. Combined with the China market submission plans for two other products this year, we will comprehensively accelerate the commercialization process of our pipeline and build a diversified and sustainable revenue model for Tianjing. Sanofi’s leadership in the global and Chinese innovative drug fields makes it an ideal partner for Tianjing, and a wide range of cancer patients will benefit from the accelerated development and commercialization of ulerelimumab. This collaboration not only demonstrates Tianjing Biotechnology’s innovation capabilities but also highlights our core competitiveness in continuously building high-value strategic partnerships with industry leaders."

This strategic cooperation fully combines the innovative R&D strength of Tianjing Biotechnology (Shanghai) Co., Ltd. with Sanofi's mature commercialization network and channel advantages in the Chinese market, aiming to bring more breakthrough treatment options to cancer patients and meet the currently unmet clinical needs.

The immunosuppressive environment of the tumor microenvironment is one of the important reasons for the low efficacy of tumor immunotherapy, and the CD39-CD73-adenosine pathway is a key participant in the immunosuppressive environment.

CD73 is a multifunctional transmembrane glycoprotein widely expressed on the surface of various tissue cells. It interacts with CD39 to further hydrolyze AMP, produced by CD39 hydrolysis, into adenosine. Adenosine binds to receptors on immune cells, generating an immunosuppressive effect. In this pathway, CD73 acts as the rate-limiting enzyme, and inhibiting CD73 can effectively alleviate the immunosuppressive nature of the tumor microenvironment.

CD73 is highly expressed in a variety of cancers, such as breast cancer, pancreatic cancer, prostate cancer, etc., and its high expression is highly correlated with poor prognosis, easy metastasis, and chemotherapy resistance. Based on this, targeted therapy against CD73 has become a goal pursued by researchers. Currently, multiple antibody drugs targeting CD73 are in clinical trials.

Currently, globally, AstraZeneca's Oleclumab is the most advanced CD73 monoclonal antibody for cancer treatment. This candidate drug has entered phase III clinical trials. AstraZeneca's CD73 antibody Oleclumab is being tested in combination with a PD-L1 antibody for the treatment of stage III non-small cell lung cancer, while also exploring indications such as pancreatic cancer.

Tianjing Biotechnology's uliledlimab is the second-ranked CD73 antibody in global clinical progress, slightly behind AstraZeneca's, but its highly differentiated design and CD73 high-expression restricted clinical development strategy are expected to achieve better clinical efficacy.

Tianjing Biotechnology's uliledlimab effectively binds to CD73 in a non-substrate competitive manner, thereby reducing adenosine levels and enhancing the activity of anti-tumor immune cells. Preclinical studies show that uliledlimab effectively inhibits CD73 activity by binding to a unique C-terminal epitope through a single-molecule monovalent interaction with the CD73 intradimer. Its combination with immune checkpoint drugs such as PD-1 or PD-L1 antibodies is expected to enhance synergistic efficacy in cancer treatment.

In addition, the expression of CD73 is also related to immune cell infiltration and PD-L1 protein expression in the tumor microenvironment, indicating that CD73 may play a significant role in the response to tumor immunotherapy. Therefore, CD73 not only acts as a key rate-limiting enzyme regulating adenosine concentration in the tumor microenvironment but also participates in tumor cell metastasis through non-enzymatic functions, making it an important target that cannot be ignored in combination therapy.

Preclinical studies have shown that CD73 has a good synergistic effect with PD-(L)1. From the current global clinical development of CD73 monoclonal antibodies, the explored treatment regimens are mostly combinations of CD73 with PD-1 or other drugs. In the future, CD73 is expected to become a good partner for PD-1 class drugs, further improving the response rate of cancer immunotherapy.