GlaxoSmithKline (GSK) and iteos Therapeutics have announced a collaboration to jointly develop and commercialize EOS-448. EOS-448 is an anti-TIGIT monoclonal antibody, which is in the phase I development.
According to the agreement, both companies will share responsibility and costs for the worldwide development of EOS-448, as well as its commercialization in the United States, while GSK is solely responsible for the commercialization of EOS-448 besides US. iTeos will receive an advance payment of $625 million, an additional $1.45 billion in development and commercialization milestone payments and franchise.
What is TIGIT?
TIGIT, the T-cell immunoglobulin and ITIM domains, belongs to the immunoglobulin superfamily and is an immune checkpoint protein that is primarily expressed on the surface of activated or "depleted" T cells and NK cells. PVR (CD155) is a high-affinity ligand for TIGIT, while CD155 is usually overexpressed in human malignancies and is almost not expressed or weakly expressed in normal human tissues.
Research findings: TIGIT interacts with PVR receptors that are highly expressed on tumor cells to mediate the inhibitory signal of immune response to directly inhibit the killing effect of NK cells and T cells on tumor cells, which is similar to the inhibitory effect of PD-1 on T cells.
Several preclinical trials have shown that TIGIT and PD1/L1 monoclonal antibodies have synergistic anti-tumor effects. The combination of these two drugs is expected to increase response of patients to immunotherapy and expand the beneficial population.
Currently, no TIGIT monoclonal antibody is approved for use. Several of them were developing.
As an emerging target in the era of immunotherapy in recent years, no anti-TIGIT monoclonal antibody has been approved so far.
According to public information, several TIGIT monoclonal antibodies are currently under development, among which Roche's tiragolumab, Merck's Vibostolimab (MK-7684), BeiGene's BGB-A1217 and Argus Biosciences' AB154 have made rapid progress.
Tiragolumab, a TIGIT-targeted, humanized monoclonal antibody, was awarded breakthrough drug designation by the FDA in January this year for combination with atezolizumab as the first-line treatment of metastatic NSCLC with high PD-L1 expression, EGFR and ALK negative. The phase II research results of its combination with Tecentriq in the treatment of PD-L1 positive, locally advanced unresectable or metastatic NSCLC showing: Comparing with Tecentriq monotherapy, the combination of tiragolumab+Tecentriq achieved both primary endpoints: The overall response rate (ORR) was significantly higher (37% vs 21%) and the risk of disease progression or death was significantly lower by 42% (median PFS: 5.6 vs 3.9 months). Also, an exploratory analysis of patients with high PD-L1 expression (TPS≥50%) showed: Comparing with Tecentriq monotherapy, the combination of tiragolumab+Tecentriq significantly increased ORR (66% vs 24%) and significantly reduced the risk of disease progression or death by 70% (median PFS: not achieved vs 4.11 months).
Vibostolimab, an anti-TIGIT monoclonal antibody, was evaluated in combination with PEM-BRO-LI-ZU-MAB in a phase 1 clinical study in patients with advanced/metastatic solid tumors who had not received anti-PD-1/PD-1 treatment. The result shows: Overall tolerability was acceptable, with median ORR and PFS of 29% and 5.4 months for all patients and 46% and 8.4 months for 13 patients with TPS≥1%, respectively. Clinical trials of vibostolimab are ongoing in combination with other drugs to treat melanoma.
Domvanalimab, a monoclonal antibody targeting TIGIT that blocks TIGIT activity at the nanomolar level, thereby inhibits immunosuppression and enhancing immune activity, and has shown good safety in clinical trials. In 2020, AstraZeneca and Arcus Biosciences started a collaboration on the co...
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