GSK
Pharmaceutical R&D Manufacturer
Recently,GSKGSK Releases 2025 Q2 Financial Report: TIM3 Antibody Cobolimab Combined with PD-1 Antibody Dostarlimab Fails to Meet Primary Endpoint of Overall Survival in Phase III Clinical Trial; Cobolimab + Dostarlimab + Docetaxel Shows No Improvement in Overall Survival for Non-Small Cell Lung Cancer (NSCLC) Patients Compared to Control Group
Cobolimab, acquired by GSK in 2019 through the acquisition of Tesaro, is a humanized IgG4 antibody targeting TIM-3.Although it failed in NSCLC, GSK has not abandoned the development of cobolimab. Currently, the Phase II clinical trial of this drug for hepatocellular carcinoma is still ongoing.
TIM-3, fully known as T cell immunoglobulin and mucin domain-containing protein 3, was first discovered in 2002. In 2016, an article titled "PD-1 says goodbye, TIM-3 says hello" published in Nature drew industry attention to this emerging target.
From the perspective of the mechanism of action, TIM3 is a negative regulatory immune checkpoint. The signaling pathway it mediates plays an important role in regulating T-cell activity and quantity. It can participate in tumor immune suppression and its progression by mediating cell apoptosis. In cancer cells, high expression of TIM3 can activate the β-catenin/interleukin-1β (IL-1β) signaling pathway, remodel the immune microenvironment, promote cancer cell metastasis, and is closely related to poor patient prognosis.
In addition, the study also found that patients who do not respond to PD-1 monoclonal antibody treatment are often associated with high expression of TIM-3. Therefore, TIM-3 antibodies are expected to synergize with anti-PD-1/PD-L1 antibodies, for the treatment of patients resistant to PD-1/PD-L1.
The above advantages make TIM-3 an attractive target for cancer immunotherapy, with numerous MNCs entering the field.
Despite a deep understanding of the mechanism of action of TIM-3, the drug development process has been extremely challenging. CurrentlyCountless MNCs have stumbled at the TIM-3 target.
In 2019, Eli Lilly terminated the PD-L1/TIM-3 bispecific antibody LY3415244 and TIM-3 monoclonal antibody LY3321367 projects due to clinical trial results that did not meet expectations.
In 2020, Roche's TIM-3/PD-1 bispecific antibody RO-7121661 presented preclinical data at the AACR: it demonstrated better inhibition of MC38 tumor cell growth in huPD-1/huTIM-3 transgenic C57/BL6 mice compared to PD-1 monoclonal antibody. However, in Roche’s later disclosed R&D pipeline, RO-7121661 is no longer listed.
In 2024, the final analysis of Novartis' anti-TIM-3 monoclonal antibody Sabatolimab in a Phase Ib trial combined with hypomethylating agents showed that Sabatolimab demonstrated some clinical activity in patients with high-risk and very high-risk myelodysplastic syndromes. However, the addition of Sabatolimab to hypomethylating agents did not result in significant improvements in complete response rate (CR) or progression-free survival (PFS).
In 2025, AstraZeneca and BMS successively announced the discontinuation of the development of their TIM-3 antibodies.
Against the backdrop of MNCs retreating, Chinese pharmaceutical companies have become the main force in TIM-3 research and development. Companies such as Zhengda Tianqing, Jianxin Bio, BeiGene, Logicure Bio, Kelun-Biotech, and Genova Bio are all involved in its development.
TQB2618, developed by Zhongshan Tianqing, is a humanized monoclonal antibody targeting TIM-3. For this product, Zhongshan Tianqing has conducted multiple clinical studies, including: clinical trials in combination with demethylating agents in subjects with relapsed/refractory acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS); a Phase Ib/II clinical trial in combination with bemarituzumab for patients with extensive-stage small cell lung cancer (ES-SCLC) who have failed first-line standard treatment; a Phase 1b clinical study for fourth-line and later-line treatment of advanced colorectal cancer, among others.
LB1410, developed by Jianxin Biotech, is a self-developed recombinant humanized anti-PD-1/TIM-3 bispecific antibody based on the sequence upgrade of pembrolizumab (Keytruda). It is intended for use in advanced malignant tumors such as renal cell carcinoma and cervical cancer that have developed resistance after immunotherapy, radiotherapy, chemotherapy, or targeted therapy. In Phase I clinical trials, LB1410 monotherapy achieved a disease control rate of 63.3% in immunotherapy-resistant solid tumors, with significant tumor shrinkage observed in multiple patients with immune-resistant cervical cancer and renal cell carcinoma, reaching partial response (PR).
Currently, the research and development of TIM-3 related projects are still in the early stages, and whether they can succeed in the future remains uncertain. In contrast, MNCs are scaling back their pipelines, aiming to concentrate more resources on potential projects with greater certainty.
GSKExceptIn addition to terminating the TIM3 antibody cobolimab, the decision to halt the development of the anti-TIGIT antibody belrestotug was also disclosed in the semi-annual financial report, along with the termination of a malaria adjuvant recombinant protein vaccine (GSK3437949).
AstraZeneca Reveals in Its Half-Year Report: Development of Three Cell Therapy Products Terminated—CAR-T Products AZD5851 and AZD6422, and TCR-T Therapy NT-125. Among them, NT-125, a multispecific TCR-T therapy, was once a key pipeline for AstraZeneca. It could integrate up to five different neoantigen-specific TCRs in a single cell product, reducing the likelihood of tumor antigen escape. However, NT-125 failed to meet the primary endpoint in a Phase I clinical trial targeting multiple solid tumors.
In March this year, BMS announced the abandonment of the previously acquired KRAS G12D inhibitor MRTX1133 project, which was in Phase I clinical stage.
In January this year, Astellas announced the termination of an early-stage CAR-T therapy, ASP2802, an autologous cell therapy targeting CD20-positive B-cell lymphoma, which is currently in Phase I clinical trials.
Under the new changing landscape, MNCs have embarked on a journey of "streamlining and focusing." Amid this major trend, targets that have not been clinically proven to be valuable find themselves in a rather awkward position. Although setbacks faced by multiple pharmaceutical companies have caused the TIM-3 track to cool down rapidly, it is not yet the final moment—TIM-3’s future remains full of possibilities. Hopefully, Chinese pharmaceutical companies will bring about breakthrough results.
Main references:
1、https://www.gsk.com/media/zhfdbsly/q2-2025-results-announcement.pdf.
2、Rozalén C, Sangrador I, Avalle S, et al. TIM3+ breast cancer cells license immune evasion during micrometastasis outbreak [J]. Cancer Cell, 2025.
3、Phase I/Ib clinical trial of Sabatolimab, an Anti-TIM-3 Antibody,Alone and in Combination With Spartalizumab, an Anti-PD-1 Antibody, in AdvancedSolid Tumors”.
4、Zeidan AM, Ando K, Rauzy O, et al. Sabatolimab plus hypomethylating agents in previously untreated patients with higher-risk myelodysplastic syndromes (STIMULUS-MDS1): a randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Haematol. Published online December 5, 2023. doi:10.1016/S2352-3026(23)00333-2.
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