Another Giant Entering, the TIGIT Antibody Market is Highly Competitive

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 combination immunotherapy, launching a registered phase III clinical trial to evaluate Domvanalimab (AB154) in combination with Imfinzi®(durvalumab), a PD-L1 inhibitor. The efficacy in the treatment of unresectable stage III NSCLC was studied. 

Ociperlimab (BGB-A1217) is a novel humanized lgG1 monoclonal antibody, which binds to TIGIT and blocks the interaction between TIGIT and tumor cell surface ligand. It has high affinity, specificity, and complete function of Fc effect. Its Phase Ⅲ trial, Advantig-302, in its combination with tislelizumab versus PEM-BRO-LI-ZU-MAB for the treatment of untreated, locally advanced or metastatic NSCLC with high PD-L1 expression is ongoing. 

As shown by the table above, pharmaceutical giants such as Roche, MSD and BMS have all laid out their positions in the market of TIGTI monoclonal antibody. With the entry of GSK, the competition in this field will be more intense in the future. The indications for TIGIT expanded from NSCLC to melanoma. Chinese bio pharmaceuticals companies have also begun to take places in the TIGIT market. TopAlliance, Henlius and other enterprises have independently developed anti-TIGIT monoclonal antibodies, but the current progress is slow. 

In addition, it is worth mentioning that through the continuous efforts of enterprises, there have been enterprises developed TIGIT targeted bispecific antibodies, such as BMS/Agenus Agen1777 and Innovent/Eli Lilly IBI321. 

TIGIT products are trading frequently 

With the rising of TIGIT targets, the number of trading on the product has increased in recent years. The collaboration between enterprises will in turn accelerate the development of this field. 

In December 2018, Astellas acquired Potenza Therapeutics for $400 million, acquiring the company's TIGIT, NRP1 and GITR antibodies, but the TIGIT program disappeared from Astellas's developing line last year. 

In April 2019, Mereo Biopharma acquired Oncomed Phaemaceuticals, acquiring four projects of the later, including the TIGIT antibody Etigilimab (now MPH-313). 

In May 2020, Gilead begun a 10-year partnership with Arcus Biosciences to develop and commercialize drug candidates in the Arcus developing line, including novel PD-1 inhibitors and TIGIT inhibitors. 

In October 2020, Arcus Biosciences entered a partnership with AstraZeneca to initiate a registered phase III clinical trial to evaluate the ongoing development of an anti-TIGIT antibody, domvanalimab (AB154), in combination with Imfinzi®(durvalumab), a PD-L1 inhibitor in the field of efficacy in the treatment of unresectable stage III NSCLC. 

In May 2021, BMS announced a $1.56 billion licensing agreement with Agenus to acquire the exclusive worldwide licensing rights for Agen1777, Agenus' proprietary bispecific antibody project.

In June 2021, GSK collaborates with iTEOS Therapeutics to develop and commercialize EOS-448 jointly.