LONDON – Immuno-oncology specialist Iteos Therapeutics SA has bounced back from Pfizer Inc.'s rebuff of its lead program, sealing a $75 million series B round that will enable the company to take forward two other compounds that aim to tweak the tumor microenvironment.
The funding provides the means to advance EOS-100850, an adenosine A2A antagonist, into clinical development later this year and toward phase II proof of concept, while a second product, EOS-884448, an anti-TIGIT antibody, will enter the clinic in 2019.
Gosselies, Belgium-based Iteos will use some of the money to set up a new U.S. base in Cambridge, Mass., and to progress other compounds it has designed to modulate the tumor microenvironment to activate an antitumor immune response.
However, Michel Detheux, CEO of Iteos, told BioWorld that EOS-200271, an indoleamine 2,3-dioxgenase inhibitor, is "on hold for the moment," after Pfizer cut short a phase I study in glioblastoma and handed back the rights at the start of the year. (See BioWorld, Jan. 5, 2018.)
Iteos has trumpeted IDO1 inhibitors as among the most promising immuno-oncology drugs currently in development, and EOS-200271 as the only one of five such products to have brain penetration confirmed in patients. The company previously had said it would resume phase I development in 2018.
The oversubscribed series B was led by new investor MPM Capital, with other new investors HBM Partners, Curative Partners and 6 Dimensions Capital. Existing investors followed on.
The new lead program, EOS-100850, builds on the fact that high levels of adenosine and adenosine-producing enzymes are found in various tumor types, while the A2A receptor is expressed on immune cells, including T cells, NK cells and dendritic cells. Binding of adenosine to the A2A receptor on immune cells blocks the activation and effector functions of antitumor immune cells, promoting immune suppression.
There are several A2A receptor antagonists in clinical development in oncology. However, Detheux noted, those compounds initially were designed for treating Parkinson's disease and are not optimized for use in immuno-oncology.
In addition to questions about efficacy, A2A receptor antagonists designed for treating Parkinson's are likely to have neurological side effects when used to treat cancer. Iteos has discovered and patented selective A2A antagonists which do not cross the blood-brain barrier.
The compounds inhibit adenosine-mediated suppression of T-cell activation and cytotoxic activity in mouse models, driving an antitumor effect.
Following dose escalation in the phase I study starting in the last quarter of 2018, Detheux said there will be "many shots on goal" in terms of developing EOS-100850 in combination with marketed checkpoint inhibitors and other cancer therapies.
"We are reviewing what to go for with an expert panel [brought together] by MPM. There are many different tumor types we could address," said Detheux.
Iteos has selected a lead antibody against TIGIT (T-cell immune-receptor with Ig and ITIM domains), a co-inhibitory receptor found on all T-cell subtypes and NK cells, expression of which is greatly increased in the tumor microenvironment. Binding of TIGIT ligands triggers a negative signal in T cells and NK cells, preventing their activation.
The inhibitory role of TIGIT on immune cells also is mediated in part by competition for binding of the same ligands to the T-cell and NK-cell co-stimulatory molecule, CD226.
Many tumor types express TIGIT ligands and the ratio of expression for TIGIT/CD226 on T cells is modified in tumor microenvironments and shifts toward TIGIT. Iteos said its anti-TIGIT antibody has been effective in several mouse models, as a monotherapy and in combination with checkpoint inhibitors.
Further back in discovery Iteos is working on reactivating interferon production within tumor cells, in its Sting program (stimulator of interferon genes). Stimulation of the Sting pathway is a means of generating a de novo immune response, prompting tumor cell death, generation of antigens, and activation of the innate and adaptive immune system. The company has begun rational design of small-molecule agonists.
Despite EOS-200271 falling from favor at Pfizer, Ansbert Gadicke, co-founder and managing director of MPM, said Iteos has discovered oncology drugs that could have significant advantages over competitor products.
"We think about Iteos as having a fantastic scientific team. They are moving several top immuno-oncology compounds towards the clinic and building in a category where they have the best compounds out there" Gadicke told BioWorld.
It may be somewhat crowded, but immuno-oncology remains an attractive area to invest, Gadicke said. Oncology is the largest field within pharmaceuticals. "Within oncology, most of the key advances are in immuno-oncology: unless you don't want to be competitive in the largest area, you want to be in immuno-oncology," he said.
The fact that there are so many different approaches, targets and modalities being used in attempts to elicit an immune response to cancers is "an opportunity and a strength," said Gadicke.