Novartis Discontinues Phase III Development of TIM-3 Antibody Sabatolimab After STIMULUS MDS2 Trial Fails to Meet Primary Endpoint

On January 31, Novartis updated its pipeline progress in the 2023 financial report. The Phase III STIMULUS MDS2 study of its TIM-3 monoclonal antibody sabatolimab (MBG453) in combination therapy for intermediate, high, or very high-risk myelodysplastic syndromes (MDS) or chronic myelomonocytic leukemia-2 (CMML-2) did not meet the primary endpoint of overall survival (OS). Based on this, Novartis has removed it from its pipeline. Additionally, Novartis has decided to discontinue the development of BTK inhibitor remibrutinib for Sjögren's syndrome.

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TIM-3 is a receptor protein in the TIM family, expressed on the surface of T cells, Treg cells, and innate immune cells (dendritic cells, natural killer cells, monocytes). Previously, Novartis believed that sabatolimab could inhibit the function of the TIM-3 receptor, thereby simultaneously targeting myeloid leukemia cells and immune cells. This not only can kill cancer cells but may also enhance the activity of immune cells.

As the frontrunner in the TIM-3 race, the failure of sabatolimab's Phase III study has undoubtedly dealt a heavy blow to the entire field. In fact, even before Novartis exited the competition, several pharmaceutical giants had already abandoned their respective TIM-3 projects. Roche cut its PD-1/TIM-3 bispecific antibody RG7769 from its portfolio in its Q1 2022 financial report; Eli Lilly faced setbacks twice on the TIM-3 target, with both its PD-L1/TIM-3 bispecific antibody LY3415244 and TIM-3 monoclonal antibody LY3321367 failing during Phase I clinical trials.

According to the PharmCube database, there are a total of 49 projects (including terminated ones) developed around TIM-3, with the majority in preclinical stages.

Currently, the most advanced TIM-3 pipeline is cobolimab under GSK, which is undergoing Phase II/III studies in non-small cell lung cancer patients. This pipeline was acquired by GSK for $5.1 billion through the acquisition of Tesaro.

In China, both TQB2618 from Zhengda Tianqing and surzebiclimab from BeiGene, two TIM-3 monoclonal antibodies, have advanced to Phase II clinical trials, while Hengrui's SHR-1702 remains in Phase I.

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