Roche's TIGIT Monoclonal Antibody Collapses Again, And A Large Number of Domestic Biopharmaceutical Companies are Deployed

On May 11, 2022, Genentech, a subsidiary of Roche, announced the Phase III of its TIGIT monoclonal antibody tiragolumab combined with PD-L1 monoclonal antibody atezolizumab (Tecentriq®) in the first-line treatment of locally advanced or metastatic NSCLC with high PD-L1 expression Clinical SKYSCRAPER-01 Interim Analysis Results.

The results showed that the combination therapy did not meet its co-primary endpoint of progression-free survival (PFS). But overall survival (OS), another primary endpoint, is immature, and Roche said it will continue the clinical study until the next planned data analysis.

In fact, as early as March 30, 2022, Roche issued a press release, pointing out that the phase III pivotal SKYSCRAPER-02 trial of its immunotherapy drug tiragolumab, with Roche FDA-approved PD-L1 inhibitor Tecentriq (atezolizumab), carboplatin In combination with etoposide chemotherapy, its co-primary endpoints of overall survival (OS) and progression-free survival (PFS) have not been met in 490 patients with extensively advanced small cell lung cancer (ES-SCLC).

Nonetheless, Roche will continue to study tiragolumab in non-small cell carcinoma (NSCLC) in the Phase III pivotal trials SKYSCRAPER-01 and SKYSCRAPER-03.

Potential target for tumor therapy: TIGIT

In the field of tumor, the emergence of immunotherapy is a major progress in tumor treatment in recent years. It has become an indispensable part of tumor treatment, and is even known as a magic drug with broad-spectrum anti-tumor effects. However, the overall effective rate of PD-1 treatment is currently only 10-30%. Therefore, finding new targets for new drugs without corresponding antibodies is becoming the goal of many domestic and foreign pharmaceutical companies.

Among them, TIGIT is considered to be one of the most promising and potential targets.

TIGIT (also known as WUCAM, Vstm3, VSIG9) is a receptor of the Ig superfamily that plays a key role in limiting adaptive and innate immunity. TIGIT is expressed in lymphocytes, especially effector and regulatory CD4+ T cells, follicular helper CD4+ T cells, effector CD8+ T cells and natural killer (NK) cells.

Binding of TIGIT to its cognate ligand PVR directly inhibits lymphocyte activation. TIGIT and PVR are widely expressed in different types of solid tumors, indicating that the TIGIT-PVR signaling pathway may be a major tumor immune escape mechanism and a novel immune checkpoint after PD-1/PD-L1.

Although the efficacy of TIGIT antibody alone is limited, it can produce a synergistic effect with PD-1 drugs, and it can exert a 1+1>2 effect in combination.

In 2018, Professor Tian Zhigang and Professor Sun Rui from the University of Science and Technology of China published a paper on the potential anti-tumor value of TIGIT in "Nature Immunology". They found that if TIGIT exists during tumor development, immune cells are often in a state of exhaustion. In this case, even if immunotherapy is used to improve the anti-tumor ability of immune cells, the effect is still limited. Anti-TIGIT mAb can reverse the state of immune cell exhaustion, thereby improving the anti-tumor ability of the patient's immune system, and may be effective against a variety of tumors.

Many biotechs in China are deployed in TIGIT, who can become famous in one battle?

Today, TIGIT targets have become popular targets, and there are many domestic and foreign companies deploying TIGIT-targeted drugs, including Roche, Merck, BMS, Arcus Biosciences, OncoMed, etc. At present, Roche is in a leading position, and two clinical indications of tiragulumab have entered the phase III clinical stage.

There are also many innovative pharmaceutical companies in China that have deployed TIGIT targeted drugs, including BeiGene, Innovent Bio, Henlius, Junshi Bio, Kangfang Bio, Tianjing Bio, and Pumis.

BeiGene

At present, the fastest research and development of TIGIT in China is ociperlimab of BeiGene, and 7 clinical trials of combined use are in progress. Last year, BeiGene launched an international multi-center Phase 3 clinical trial of TIGIT monoclonal antibody combined with PD-1 tislelizumab in the treatment of locally advanced, unresectable or metastatic non-small cell lung cancer (NSCLC), head-to-head Merck K drug.

On December 20, 2021, BeiGene and Novartis reached a cooperation agreement, and Novartis will obtain the rights and interests of BeiGene's TIGIT antibody in the United States, Canada, many European countries and Japan. To this end, Novartis will make an upfront payment of $300 million, additional payments of $600 million or $700 million, milestones of $1.895 billion, and a 20-25 percent share of sales.

BeiGene's TIGIT monoclonal antibody is currently the second in the world in research and development progress. Now that Roche's tiragolumab has failed, ociperlimab is expected to become the world's first in-class product from fast follow, but it may also mean that the role of TIGIT targets in non-small cell lung cancer is limited. The ultimate success still needs clinical testing.

Innovent Bio

IBI939 is the first TIGIT antibody in China developed by Innovent, which can bind to TIGIT and block its interaction with CD155 to enhance immune activation. The drug is currently in Phase I clinical stage.

Innovent Bio also has a PD-1/TIGIT dual antibody drug candidate, IBI321, which has also entered the clinical research stage.

Henlius

Shanghai Henlius currently has two TIGIT antibody drugs under development. The first HLX53 is a nano-monoclonal antibody targeting TIGIT, and its main indication is solid tumors. Another HLX-301 is a nano-dual-antibody drug that can block both PD-L1 and TIGIT targets at the same time, and is currently in Phase 2 clinical trials.

Epilogue

As a new immunotherapy target, TIGIT plays an important role in the immune regulation of the body and plays a very important role in regulating the anti-tumor functions of T cells and NK cells.

Although the interim results of Roche's TIGIT drug tiragolumab Phase III clinical trial did not meet expectations, the industry still believes that TIGIT antibody may become a new generation of immunotherapy drugs after PD-1/PD-L1 immunotherapy. We will wait and see who will be the first to win the TIGIT antibody in the future.