GlaxoSmithKline is boosting its cancer drug pipeline through a partnership with iTeos Therapeutics, a deal that gives the pharmaceutical giant a chance to catch up to its peers in the pursuit of a hot cancer target seen as a promising way to expand the reach of cancer immunotherapy.

The heart of the deal is EOS-448, a monoclonal antibody that Belgium-based iTeos designed to target the TIGIT protein. GSK agreed to pay $625 million up front to join in the development of the drug. According to the deal terms announced Monday, GSK could pay iTeos up to $1.45 billion more tied to the achievement of development and commercialization milestones.

TIGIT is a so-called checkpoint protein. Found on the surface of a number of immune cells, it blocks the immune response. In cancer, this mechanism promotes tumor growth by stopping the activation and proliferation of immune cells that would fight the disease. Blocking checkpoint proteins enables immune cells to recognize and fight cancer cells. The current slate of checkpoint inhibitors block PD-1 or PD-L1, but not all people respond to such treatments. TIGIT-blocking drugs could potentially bring checkpoint inhibition to more cancer patients.

So far, iTeos has advanced its TIGIT-targeting drug to early-stage clinical testing in patients with advanced solid tumors. The company presented preliminary Phase 1/2a results for its drug during the annual meeting of the American Association for Cancer Research in April. As of the Dec. 31, 2020, data cutoff, 22 patients were enrolled. The company reported that EOS-448 was well tolerated by patients with no dose-limiting toxicities observed. There was limited data about the drug’s potential efficacy. In one patient whose melanoma was resistant to treatment with pembrolizumab, the checkpoint inhibitor that Merck markets as Keytruda, the company reported a confirmed partial response to treatment. In nine others, the iTeos drug led to stability of the disease.

With those early results, iTeos has advanced EOS-448 into tests in combination Keytruda. But iTeos’s partnership with GSK lays the groundwork for studies of the antibody in combination with GSK cancer drugs, as well including a test with dostarlimab (Jemperli), a PD-1 blocking checkpoint inhibitor that the FDA recently approved as a treatment for endometrial cancer. GSK and iTeos said that this combination study is expected to begin next year. Furthermore, the companies plan to test various combinations of as many as three different drugs together in order to potentially address many types of cancer.

GSK’s partnership with iTeos comes less than one month after Bristol Myers Squibb agreed to pay $200 million up front for rights to an Agenus anti-TIGIT drug currently in preclinical development. The Agenus drug is a bispecific antibody. Other companies developing TIGIT-targeting antibodies include Merck, Mereo Biopharma, Roche, Astellas Pharma, BeiGene, and Seagen.

GSK and iTeos will share in the work and the expenses for global development of EOS-448, according to the agreement. They’ll also share in commercializing the drug—if it’s approved. U.S. profits will be split equally. Outside of the U.S., GSK now has an exclusive license to commercialize the drug; Iteos will receive royalty payments from its sales.

In the nearer term, the deal infuses iTeos with cash to support additional cancer drug R&D. The company’s other clinical-stage candidate, inupadenant, targets the adenosine A2a receptor to address cancer immunosuppression. That iTeos small molecule is currently in an open-label, dose-escalation Phase 1/2a study enrolling adults with solid tumors. At the recent annual meeting of the American Society of Clinical Oncology, the company reported updated results from a dataset of 43 patients. In five of them, the drug showed durable responses and stable disease for six months or longer.

Photo by GlaxoSmithKline