Pfizer drops iTeos IDO1 cancer drug due to lack of efficacy

Pfizer has returned the rights to the IDO1 inhibitor it licensed from iTeos Therapeutics. The Big Pharma dumped the drug after failing to find signs of efficacy in a phase 1 brain cancer trial, but iTeos thinks it has a future and is preparing to raise money to power ahead solo.

Pfizer paid €24 million ($29 million) upfront to secure the rights to the then-preclinical IDO1 program in 2014. The drug, EOS200271, moved into a phase 1 monotherapy trial in patients with malignant gliomas in 2016. But interim data on the 17 patients enrolled in the study fell short of Pfizer’s expectations, prompting it to return the rights to iTeos.

ITeos is more upbeat about the drug. While acknowledging the lack of efficacy that soured Pfizer’s view, iTeos CEO Michel Detheux, Ph.D., thinks other parts of the data are equally important. The trial suggested EOS200271 crosses the blood-brain barrier, a characteristic that sets it apart from IDO1 drugs in development at companies including Bristol-Myers Squibb and Incyte.

An effective IDO1 inhibitor that penetrates the brain would be a valuable weapon against cancer. As it stands, checkpoint inhibitors such as Keytruda and Opdivo can control primary tumors in some patients, particularly when paired with IDO1 inhibitors, but then be undone by unmanageable brain metastases. This creates an opportunity for a brain-penetrating IDO1 inhibitor. 

“If you have an IDO1 inhibitor which is able to control the immunosuppression of brain metastases you will increase long-term survival,” Detheux said.

ITeos came out of the Pfizer-sponsored trial with evidence EOS200271 gets into the brain. What it lacks is evidence the drug can control tumors after entering the organ. That was enough to prompt Pfizer to walk away. But given the study never hit its maximum tolerated dose, it isn’t necessarily a death knell for the candidate.

When paired with the antitumor activity EOS200271 has shown in preclinical, that was enough to encourage iTeos that the lack of clinical efficacy is due to the wrong regimen, not an ineffective drug. 

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ITeos is reviewing the full dataset and talking to KOLs before deciding on the exact path forward. But it already sees a future for the drug, both as a monotherapy and in combination with other therapies. The next step is to file an IND to get the program back on track, something iTeos expects to do around the middle of the year. 

EOS200271 is advancing toward its second crack at the clinic in parallel to an adenosine A2A receptor antagonist. ITeos expects to get the A2A program into humans in the fourth quarter of 2018, at which point it will join a short list of companies with drugs aimed at the receptor and IDO1, two of the key mechanisms of immunosuppression.

ITeos’ evolution into a clinical-stage biotech will dial up its cash requirements. The Belgian biotech began life with a small series A, after which it turned to local grants and the proceeds of the Pfizer deal to fund its advance. 

This year, with two drugs heading toward the clinic, iTeos is planning to raise money.