GSK Raises Eyebrows in Checkpoint Inhibitor Megadeal with iTeos

gsk checkpoint inhibitor iteos

Analysts are abuzz over GSK’s co-development deal with immuno-oncology specialist iTeos Therapeutics earlier this month, wondering if it overpaid for the Belgian company’s next-generation checkpoint inhibitor. 

GSK’s oncology deal with iTeos earlier this month centered on an antibody drug that blocks an immune checkpoint called TIGIT. The candidate is currently in phase I testing for advanced solid tumors. The megadeal was worth €524M ($625M) upfront, as well as more than €1.2M ($1.4B) if developmental milestones are met. 

The hefty price tag reflects a recent spike in interest in TIGIT as an immune checkpoint target for cancer immunotherapies. Last month, US-based Agenus signed a similar deal with Bristol Myers Squibb for $200M (€168M) upfront.

TIGIT remains a speculative target today,” said Bertrand Delsuc, CEO and founder of the business intelligence firm Biotech Radar. “[I]t is likely GSK somewhat overpaid here.” 

However, Delsuc also observed that big cash is needed to secure deals in this increasingly competitive field.

The deal size […] is more than impressive when considering the maturity of the asset and its generated data,” said Lenny Van Steenhuyse, life sciences equity expert at the Belgian investment bank KBC Securities.

In a tweet earlier this month, Van Steenhuyse saw the deal as transformational for iTeos. He likened the impact to landmark deals between argenx and Johnson & Johnson in 2018 and between Galapagos and Gilead in 2019. 

Beyond the price tag, the deal is also noteworthy because of the terms. iTeos retained the rights to co-commercialize the candidate drug in the US, and receive royalties from GSK in the rest of the world. This hints to a strong ambition by the smaller partner to develop itself further as a biopharmaceutical company. 

[It] speaks of the deal-making capabilities of the iTeos team,” Van Steenhuyse said, noting that the company previously partnered an IDO1 inhibitor program with Pfizer.

Immune checkpoints such as TIGIT can be hijacked by cancer cells to let them hide from the immune system. The first generation of approved checkpoint inhibitors are antibodies that target PD-1, PD-L1 or CTLA-4, taking the brakes off the immune system and rejuvenating its capability to attack cancer.

While the first such drugs have resulted in strong responses for a subset of patients, to date they only have an effect in up to 30% of cases. They often cause significant unwanted inflammation as a side effect—a reflection of the complexity of our immune system. Early studies suggest that combination therapies including inhibitors against checkpoints like TIGIT have a chance of treating cancers that until now have proved hard to crack. 

Both our team and our colleagues at GSK believe this next wave of [immunotherapy] combinations, many featuring a TIGIT antagonist, will be the most competitive and dynamic areas of drug development over the coming years,” said an iTeos spokesperson. 

There is a critical need here, and there are so many possible combinations that need to be explored. The breadth and depth of GSK’s portfolio and expertise were very attractive as we thought about what an ideal partner would bring.

For a long time, GSK has aimed to treat cancer by targeting the CD226 axis, which is a range of receptors on the surface of immune cells. In this axis, certain tumor cell proteins can either activate CD226, which alerts immune cells, or the checkpoints TIGIT, CD96, and PVRIG, which tend to prevent immune cells from attacking the tumor. GSK plans to block the three checkpoints with drug combinations, so that more tumor cell proteins will activate the CD226 ‘alert system’. 

Several competitors in the niche of TIGIT inhibitors are focusing on lung cancer. This includes Roche, whose candidate tiragolumab was designated a Breakthrough Therapy for non-small cell lung cancer (NSCLC) by the US FDA last year, as well as Merck, which recently started a phase III trial of vibostolimab for the same indication. Last week, California-based Arcus Biosciences announced positive phase II data in NSCLC for its anti-TIGIT antibody, with more specific data expected later in the year.

Major caveats remain in research on TIGIT, says Delsuc. For iTeos’ candidate in particular, phase Ib data showed early signs of the drug removing obstacles to the immune response in peripheral blood, but it is unclear how effective it is in the tumor microenvironment.

There is also speculation over whether or not anti-TIGIT antibodies should also activate a cell target receptor called Fc: roughly half of over a dozen such prospective therapies seek to bind to the receptor, while the others do not. The debate reflects the amount of research required before TIGIT checkpoint inhibitors can enter the cancer immunotherapy arsenal.

This article was updated on 01/07/2021 to correct the description of GSK’s plans with the CD226 axis.

Cover image by Anastasiia Slynko

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