Iteos draws a neat line under IDO

Last year Pfizer pulled out of a deal covering Iteos’s lead asset, an IDO inhibitor. The subsequent implosion of Incyte’s IDO project epacadostat made that move look like a masterstroke.

But Iteos pushed on undeterred, switching its focus to an A2a inhibitor and building a neat case around this oncology asset to differentiate it from Corvus’s similarly acting compound, which flunked in the clinic a year ago. Today it was rewarded with a $75m investment – the largest funding round ever for a private Belgian biotech group, according to EvaluatePharma.

Remarkably, Iteos has yet to take either the A2a inhibitor, EOS100850, or its second asset, the anti-Tigit MAb EOS884448, into the clinic, and until today had raised just €4.4m ($5.1m). Yet the $75m round beats the $64m raised by Movetis, a Belgian group bought by Shire, and a $50m round hauled in by Ablynx – acquired by Sanofi.

Pharma companies have already been sniffing around Iteos. “At the time that we received the term sheets from MPM [Capital, which led today’s raise] we also received term sheets from pharma,” Michel Detheux, Iteos’s chief executive, revealed to EP Vantage.

The funds will allow the group to start clinical trials with EOS100850 this year and with EOS884448 in 2019. They will also pay for Iteos’s expansion into US offices, a move that hints at a possible future on the US public markets.

Parkinson’s to cancer

Adenosine A2a receptor inhibition is far better known as being associated with treating Parkinson’s disease, but the rationale behind using it in oncology is that adenosine is a key suppressor of immune cells in the tumour microenvironment.

However, the approach was dealt a serious blow when Corvus’s CPI-444 disappointed at last year’s AACR meeting (AACR – Parkinson’s approach to cancer needs more work, April 5, 2017). This is where Iteos comes in: rather than repurposing anti-Parkinson’s agents the Belgian group “tailored” its A2a antagonist for the tumour microenvironment, where adenosine levels can be over 20 times higher than in the brain, said Mr Detheux.

While the Parkinson’s compounds are competitive antagonists EOS100850 is not, meaning that it is unaffected by these high adenosine concentrations. A final differentiating characteristic – EOS100850’s lack of brain penetration – means that the Iteos compound does not cause caffeine-like side effects.

The only other A2a antagonist designed not to be brain-permeable is owned by Arcus Biosciences, a company with which Mr Detheux said Iteos has been in direct competition for the past four years.

Arcus was founded by the management team that sold an IDO-focused company, Flexus, to Bristol-Myers Squibb for $800m (Taiho shows Arcus trying to repeat the Flexus trick, September 21, 2017). At this year's AACR Arcus’s A2a antagonist, AB928, generated data in healthy volunteers; Iteos’s plan is to test multiple ascending doses of EOS100850 immediately in cancer patients.

Arcus, which raised around $200m before completing a $120m IPO in March, also boasts an anti-Tigit project, AB154 – a direct competitor with Iteos’s EOS884448. “We have a better Tigit programme,” said Mr Detheux, adding that this was a crowded space, including Roche’s tiragolumab and Bristol-Myers Squibb’s BMS-986207.

IDO no go

As for IDO, the chief exec was unambiguous, stating: “Today our IDO programme is inactive; it cannot be a target on which we build the future of our company. The field has been blasted by the Incyte data.”

Before Incyte’s IDO failure Iteos was blaming Pfizer’s discontinuation on the wrong oncology indication being targeted, and was still hoping to start a phase I monotherapy trial with its molecule, EOS200271, this year.

Another way in which Iteos has changed is that it now wants to retain its projects until proof of concept rather than licensing them out at the preclinical stage at which the Pfizer deal was done.

Perhaps Pfizer’s involvement, though it ultimately came to nothing, validated Iteos as a start-up capable of striking big pharma deals. The company is certainly capable of raising cash.

To contact the writer of this story email Jacob Plieth in London at [email protected] or follow @JacobPlieth on Twitter

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