TIGIT (T cell immunoreceptor with Ig and ITIM domains) – The red hot corner of immune-oncology market drawing huge Interest

Interest in TIGIT has increased since last 2-3 years and several key players are now active in this field including BeiGene’s Ociperlimab, which is in Phase III stage of development for NSCLC; early and mid-stage active players include Innovent Biologics, BMS/Compugen, Astrazeneca, iTeos Therapeutics/GSK. Recently, in AACR, iTeos Therapeutics presented the data of its Anti-TIGIT Antibody, EOS-448/GSK4428859A, which is being developed in collaboration with GSK for the treatment of cancer. In clinical studies, the treatment with EOS-448 reduces TIGIT-positive cells in tumor biopsies, which is the first evidence of a treatment impact on the tumors of patients who have been treated with an anti-TIGIT antibody. Moreover, in preclinical studies the treatment with EOS-448 reduced suppressive and fatigued immune cell populations in preclinical experiments and blood samples from patients with advanced malignancies, demonstrating engagement of FcR, an important component in many immune system effector activities. iTeos Therapeutics is being evaluated in a Phase I/II trial in combination with Merck’s Blockbuster, Keytruda  or with Inupadenant in patients with lung cancer, head and neck cancer, melanoma and other Advanced solid tumors (NCT05060432). Additionally, the company has also registered another Phase I/II trialof its ant-TIGIT antibody in collaboration with GSK and BMS in patients with Relapsed/Refractory Multiple Melanoma (RRMM), which is expected to initiate patient recruitment in May 2022. (NCT05289492).

As per the early trial data presented for the potent anti-TIGIT antibody, EOS-448, we believe that it has a higher potency in cell-based assays than other anti-TIGIT monoclonal antibodies under clinical development, which may lead to its selection as a treatment candidate. However, we cannot overlook the recent failure of Roche’s anti-TIGIT drug in a Phase III trial for lung cancer, and therefore should give more time to the drug to generate data from other combination trials along with Merck and BMS in the future.

Other pharma companies, which presented the preclinical data of their TIGIT blockers include NeoImmuneTech and Akeso.

Quick Update on other TIGIT Immunotherapies

  • Roche disappointed with Tiragolumab’s failure. Caveats to work upon for other TIGIT players?

Last month in March 2022, came one of the latest disappointment for Roche’s TIGIT-blocking drug, Tiragolumab, which failed in a Phase III trial (SKYSCRAPER-02) of extensive stage-small cell lung cancer patients. Roche’s TIGIT-blocker. Tiragolumab, when added to chemotherapy and Tecentriq, wasn’t superior on measures of survival when compared with chemo and Tecentriq alone. However, the company looks forward to other Phase III trials in more common and less aggressive types of lung cancer.

  • Novartis entering  TIGIT space

In December 2021, Novartis entered into a blockbuster deal with BeiGene for its TIGIT inhibitor ociperlimab, which is being tested in two Phase III trials for NSCLC in combination with BeiGene’s already approved Tislelizumab (in China) an anti-PD-1 antibody. This is Novartis’ first anti-TIGIT drug in the pipeline.

  • Gilead Sciences acquires Domvanalimab and AB308.

In November 2021, Gilead Sciences acquired Arcus Biosciences’ anti-TIGIT molecules, domvanalimab and AB308. Domvanalimab is an Fc-silent anti-TIGIT antibody in Phase II and III trials for NSCLC, whereas AB308 is an Fc-enabled anti-TIGIT antibody under Phase I evaluation.

  • BMS agreement with Agenus

In May 2021, BMS and Agenus entered into a definitive agreement, where BMS was granted a global exclusive license to Agenus’ proprietary bispecific antibody program, AGEN1777 that blocks TIGIT and a second undisclosed target. The product has shown potential in preclinical studies and is now set for human clinical trials.