Novartis Submits IND Application for TIM-3 Monoclonal Antibody MBG453 in China

Today, the latest public announcement from the Center for Drug Evaluation (CDE) of China’s National Medical Products Administration revealed that Novartis has submitted an investigational new drug application for MBG453 in China, which has been accepted. MBG453 is an investigational monoclonal antibody targeting the TIM-3 receptor developed by Novartis. This marks the first time the drug has been submitted for clinical trial approval in China. TIM-3 is an emerging target in the field of immunotherapy research; no anti-TIM-3 monoclonal antibodies have been approved globally to date, and Novartis’ MBG453 is one of the most advanced candidates in its class.

Image source: Screenshot from the CDE official website

Currently, Novartis is developing MBG453 for the treatment of acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). According to reports, the TIM-3 receptor is an inhibitory receptor expressed on the surface of immune cells and myeloid leukemia cells, and its expression level correlates with the severity of acute myeloid leukemia and myelodysplastic syndromes. As a TIM-3 monoclonal antibody, MBG453 can inhibit the function of the TIM-3 receptor, thereby simultaneously targeting myeloid leukemia cells and immune cells. This not only kills cancer cells but also enhances the activity of immune cells.

According to information on the ClinicalTrials.gov website, Novartis has registered nine clinical studies involving MBG453, covering indications such as acute myeloid leukemia, myelodysplastic syndromes, and advanced malignancies. Among these is a multicenter, randomized, double-blind, placebo-controlled Phase 3 clinical study designed to evaluate the efficacy of MBG453 in combination with azacitidine for the treatment of myelodysplastic syndromes or chronic myelomonocytic leukemia-2 (CMML-2).

According to data previously released by Novartis, MBG453 has already demonstrated favorable safety and anti-cancer activity in the treatment of patients with myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) during Phase I clinical trials. Novartis has high hopes for this innovative therapy, believing it could become a cornerstone in the treatment of various myeloid diseases.

TIM-3 (T cell immunoglobulin domain and mucin domain-3) is an inhibitory molecule expressed on the surface of T cells. It contributes to T cell exhaustion during cancer progression and chronic viral infections, playing a critical role in the killing of tumor cells. TIM-3 has emerged as a novel target in immunotherapy research, following CTLA-4 and PD-1. Furthermore, studies have indicated that anti-TIM-3 monoclonal antibodies may exert synergistic effects with antibodies targeting PD-1/PD-L1, offering a potential therapeutic strategy for patients who have developed resistance to PD-1/PD-L1 inhibitors.

Since the publication of the article “Immunotherapy: Goodbye PD-1, Hello TIM-3” in a Nature subsidiary journal in 2016, the target TIM-3 has garnered increasing attention. Currently, no TIM-3 antibody drugs have been approved for marketing worldwide. However, according to incomplete statistics, there are approximately 20 investigational TIM-3 antibody projects underway globally, with Novartis’ MBG453 being one of the most advanced candidates in its class.

In addition to Novartis’ MBG453, numerous TIM-3 antibodies developed by other companies have also entered clinical development, including GlaxoSmithKline’s (GSK) TSR-022, Eli Lilly’s LY3321367, and Roche’s RO7121661 (a TIM-3/PD-1 bispecific antibody), among others. In China, several companies have begun to pursue this target, including Jiangsu Hengrui Medicine, Kelun Pharmaceutical, ZhiKang Hongyi Biopharma, and BeiGene.

References:

[1] Center for Drug Evaluation, National Medical Products Administration of China. Retrieved April 26, 2020, from http://www.cde.org.cn/news.do?method=changePage&pageName=service&frameStr=3