Roche Submits Fourth IND Application in China for TIGIT Inhibitor Tiragolumab This Month

According to the latest public announcement on the website of the Center for Drug Evaluation (CDE) under China’s National Medical Products Administration, Roche has once again submitted a clinical trial application for its investigational TIGIT inhibitor tiragolumab, which has been accepted by the CDE. To date, this marks the fourth clinical trial application filed in China this month for this investigational new drug. Notably, TIGIT is an emerging immune checkpoint target following CTLA-4 and PD-1. No drugs targeting this pathway have yet been approved for marketing globally, and Roche’s tiragolumab is the most advanced TIGIT antibody in global development. In China, IBI939, developed by Innovent Biologics, was the first TIGIT antibody to receive clinical trial approval, with the first patient dosed in its Phase 1 clinical study not long ago.

TIGIT (T cell immunoreceptor with Ig and ITIM domains), fully known as T-cell immunoglobulin and ITIM domain protein, is an immune checkpoint inhibitor primarily expressed on the surface of T cells and NK cells. TIGIT competes with the co-stimulatory molecule CD226 (DNAM-1) for binding to the ligands CD155 and CD112.

Studies have found that NK cells in most tumors express TIGIT. The role of TIGIT in tumor immune suppression is similar to that of PD-1/PD-L1, and TIGIT inhibitors can exert synergistic anti-tumor effects with PD-1/PD-L1 inhibitors. Currently, TIGIT has become one of the hot targets for pharmaceutical companies in the field of immune checkpoint inhibitors, following CTLA-4 and PD-1/L1.

Currently, multiple multinational pharmaceutical companies have pipeline layouts in this target area. Information from the ClinicalTrials.gov website indicates that several registered clinical trials are evaluating the efficacy of TIGIT antibodies as monotherapy or in combination with other drugs for various cancers. The TIGIT antibodies involved include BMS-986207 from Bristol Myers Squibb (BMS), OMP-313M32 from OncoMed Pharmaceuticals, MTIG7192A from Genentech, MK-7684 from Merck & Co. (MSD), and AB154 from Arcus Biosciences, among others.

Among these, Roche’s tiragolumab is currently the TIGIT inhibitor with the most advanced global development progress. Not long ago, Roche presented Phase II clinical data on the combination of tiragolumab and the PD-L1 antibody Tecentriq for the treatment of non-small cell lung cancer (NSCLC) at the ASCO meeting. Preliminary analysis results showed that the tiragolumab and Tecentriq combination therapy met both primary co-endpoints: the objective response rate (ORR) reached 31.3%, compared to 16.2% in the control group; the progression-free survival (PFS) for patients in the combination therapy group was 5.4 months, higher than the 3.6 months observed in the control group; furthermore, the combination therapy reduced the risk of disease progression or death by 43%. In addition, exploratory analysis conducted in the patient subgroup with high PD-L1 expression revealed that the combination therapy increased the ORR to 55.2%, significantly higher than the 17.2% in the control group, and also reduced the risk of disease progression or death by 67%.

In China, multiple companies have invested in the research and development of TIGIT antibodies. According to company websites and public information:

Innovent Biologics' TIGIT Antibody IBI939:

It is the first TIGIT inhibitor approved for clinical trials in China. According to a press release from Innovent Biologics, it directly binds to TIGIT, relieving the inhibition and exhaustion of T cells and NK cells, thereby promoting T cell- and NK cell-mediated antitumor effects. Meanwhile, it is expected to synergistically enhance the antitumor activity of PD-1/PD-L1 antibody drugs and delay the development of drug resistance. Last month, Innovent Biologics announced that the first patient had been dosed in the Phase I clinical study of IBI939. This Phase Ia/Ib clinical study, conducted in China, evaluates IBI939 in subjects with advanced malignant tumors, aiming to assess the safety, tolerability, and antitumor activity of IBI939 as monotherapy or in combination with Tyvyt (sintilimab injection) in subjects with advanced tumors.

BeiGene’s Investigational TIGIT Monoclonal Antibody BGB-A1217:

Currently, BeiGene has initiated a Phase 1a/1b clinical trial in China and Australia to evaluate BGB-A1217 in combination with tislelizumab for the treatment of patients with advanced solid tumors, aiming to assess the safety, tolerability, pharmacokinetics, and preliminary anti-tumor activity of the combination therapy. The investigational drug is currently in the Phase 1b stage.

Meanwhile, three investigational TIGIT antibodies—Henlius’s HLX53, Junshi Biosciences’ JS006, and Stabivie Biotech’s mAb-7—are in the preclinical stage and are intended for the treatment of solid tumors. In addition, some other companies are also developing TIGIT antibodies but have not yet disclosed detailed information.

Currently, no TIGIT antibodies have been approved for marketing worldwide. We are pleased to see so many companies investing in the research and development of this novel immunotherapy. We hope that these investigational products will progress smoothly and yield favorable results, thereby providing patients with more treatment options at an earlier date.

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