iTeos Therapeutics wasted no time in making an announcement today that it will completely wind down its operations and double down on its promise to enact strategic alternatives to maximize shareholder value. I claim it is doubling down because it first signified its intention to garner such a move when it reported topline results from its phase 2 GALAXIES Lung-201 Study. This particular trial was being done in collaboration with its partner GlaxoSmithKline to evaluate the use of its anti-TIGIT monoclonal antibody belrestotug with the PD-1 inhibitor drug dostarlimab (marketed as JEMPERLI) for the treatment of patients with previously untreated, unresectable, locally advanced, or metastatic PD-L1 high non-small cell lung cancer (NSCLC).
The data released isn’t actually entirely bad because, in terms of objective response rate (ORR), there was a win with respect to it. However, what truly fell short of expectations of achieving a meaningfully clinical outcome was the failure of progression-free survival (PFS). The doublet of belrestotug as an anti-TIGIT antibody together with dostarlimab wasn’t strong enough to beat dostarlimab alone as a monotherapy with respect to this efficacy endpoint. Things would have actually been okay if belrestotug proved itself useful in at least one other cancer indication. Unfortunately, at the same time the PFS failure was announced in the targeting of patients with PD-1 high NSCLC, there was also the mention of a failure of the drug to perform well in the phase 2 GALAXIES H&N-202 trial targeting patients with PD-L1 positive head and neck squamous cell carcinoma (HNSCC).
In this case, the doublet of belrestotug and dostarlimab failed to beat dostarlimab alone as a monotherapy in targeting these specific HNSCC patients. However, this time around, the ORR was the endpoint where a clinically meaningful threshold was not reached. At this time, this was the first when iTeos noted that it would evaluate options to maximize shareholder value. Typically, in this situation, a biotech would take several months to look for such strategic alternatives. This may still be the case, but today it doubled down on its promise to wind down further development of other drugs that were being advanced in its pipeline. What was also announced with the two trial failures was that its partner GlaxoSmithKline and iTeos both agreed to terminate the collaboration agreement made between the two for the development of belrestotug.
All is not lost for the company because it is possible that it could still maximize shareholder value for investors. The reason why is because despite belrestotug being put in the back burner, the company was still in the process of developing two other oncology drugs as part of its pipeline advancement. These two drugs in question are ENT1 inhibitor EOS-984 and TREM2 antagonist EOS-215, targeting patients with advanced solid tumors. Speaking of which, the company noted in its Q1 of 2052 earnings release that it was anticipating the release of data from its phase 1 trial of EOS-984 in the 2nd half of 2025. This would be the use of this drug either alone as monotherapy or in combination with the PD-L1 drug KEYTRUDA (pembrolizumab) for the targeting of advanced solid tumors.
The biotech even boasts a preclinical program of ENT1 targeting to be used to treat obesity patients. The end game goal is to sell off these assets and establish shareholder value. Besides the selling of assets to help shareholders, it is also wanting to leverage its cash balance of $624.3 million as of March 31st of 2025 to establish its intended strategic alternatives. Whether or not the company is successful in its endeavors of achieving these goals remains to be seen, but there is some potential with the other oncology candidates from its pipeline. Thus, it is possible that some interest could be garnered for them. The concept of anti-TIGIT development as a science was there, but the execution wasn’t delivered.
Belrestototug, as an anti-TIGIT monoclonal antibody, was deployed to block the TIGIT protein inhibitory action of ligands CD112 and CD155 on tumor cells. By blocking this inhibitory process, this allows CD8+ T-cells and natural killer (NK) cells to engage with both of these ligands through the CD226 receptor and generate a substantial anti-tumor immune response. In addition, another mechanism of action deployed for belrestotug was to have an antibody-dependent cellular cytotoxicity (ADCC) effect and deplete T-regulatory cells (T-regs) from the tumor microenvironment (TME). T-regs are crucial for regulating the immune response, and tumors use these to shield themselves from the immune system. Unfortunately, this didn’t pan out as well as iTeos thought it would, and thus it is left with attempting to maximize shareholder value with the selling of assets and other strategic actions.