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IDO 1: a promising new target for immunotherapy

Written by DS on in the category Insights with the tags , .


iTeos Therapeutics started in 2012 as a spin-off from the Ludwig Institute for Cancer Research (LICR), one of the top three cancer institutes in the world, and the UCL. In 2014, they licensed rights to pre-clinical compounds targeting IDO1 and TDO2 to Pfizer, providing the company with the necessary resources to expand from 7 to 40 people and develop a pipeline of 5 proprietary programs, for hot (inflamed) and cold (not inflamed) tumors. Since then, Pfizer and iTeos have moved one IDO1 program into the clinic. They expect to get additional programs into the clinic in 2018.

A first clinical trial with IDO1

The Indoleamine 2,3-dioxygenase (IDO1) mechanism was initially discovered by LICR in Brussels. It is one of the main mechanisms used by cancer cells to escape an immune response. IDO1 is an enzyme that degrades tryptophan into kynurenine, resulting in inactivation of T-cells. It is the same mechanism that is used by a pregnant woman to allow the baby to develop, without an immune reaction by  the mother’s immune system. “If you manage to inhibit this mechanism,” says Michel Detheux, CEO of iTeos, “the tumor becomes visible again for the immune system and can be attacked. IDO1 is a cornerstone in the strategy to develop novel immunotherapies.”

We are a spinoff of one of the most successful and well known cancer research institutes in the world, and only two years after the startup, we signed a licensing agreement  with one of the top 3 pharma companies in the world.
 

In September 2016, iTeos and Pfizer started a clinical trial with IDO1 inhibitors.  “The drug candidate is able to pass through the blood-brain barrier. Hence, it is being tested in patients with glioblastoma. The first results are to be expected in 2017,” explains Detheux.

A2A receptor antagonists: even more promising?

Next to IDO1 inhibitors, iTeos is focusing on a number  of other programs, including adenosine A2A receptor antagonists. Many different types of tumors produce high levels of adenosine within the tumor microenvironment. Adenosine modulates the immune response in such a way that tumor cells are no longer attacked. Detheux adds: “I believe that these A2A antagonists are even more promising than the IDO1 inhibitors. We are developing this program independently and plan a first clinical trial early in 2018.”

Other companies such as Heptares (UK), Palobiofarma (Spain), Juno Therapeutics (Seattle, US), Corvus Pharmaceuticals (CA, US) and Arcus Bioscienes (CA, US) also focus on A2A receptors as a possible route to fight cancer. Detheux comments: “Indeed, but we believe we have the best-in-class approach designing a compound for application in immune-oncology, which is superior to that of our competitors.”
iTeos also has 3 other proprietary programs underway, i.e.:

  • TIGIT inhibitory antibodies (candidate selection  2017)
  • Galectin-3 inhibitory antibodies (lead identification  2017) and
  • STING agonists for cold tumors (Proof of Concept for Targeted Delivery in late  2017)

I want to stress that cancer immunotherapy is revolutionary and that more than half of the trials in oncology are currently dedicated to immunotherapy.”
 

Collaborations leading to an IPO

ITeos has received a number of public grants for  for early- stage discovery, including 1.6 million euros through a BioWin project called IT-Targets, shared with  ChemCom S.A., ImmunXperts S.A., the de Duve Institute and IRIBHM.  This project will focus on G protein-coupled receptors (GPCRs), which will be selected by profiling the most important immune cell types purified from clinical samples. Detheux comments: “GPCRs have been underexploited in oncology. We want to identify and validate novel GPCR-targets for cancer immunotherapy treatment.”

We are building a unique mix of expertise in tumor immunology and translational medicine to develop new immuno-oncology drugs.
 

iTeos recently also announced a collaboration with Cristal Therapeutics, a Dutch expert in nanotechnology, to develop a program targeting cold tumors. They also have a collaboration  with Adimab, an expert in antibody development. “They are the perfect partner to fully develop our antibody programs,” comments Detheux.

“The strategy of iTeos,” continues Detheux, “is to identify partners that could be investors but also pharmaceutical partners, and who  will support the development of iTeos as a sustainable company in cancer immunotherapy. We want to be able to fund best-in-class as well as first-in-class programs in the long term, with the goal  of achieving  clinical proof of concept.”

We manage our resources very carefully.   We invested only 4.4 million euros to get one program in the clinic and to develop  a pipeline with 5 proprietary programs only  4 years after we were founded.


“We are currently working on a series C fundraising to move our other programs into the clinic  and if everything goes as expected, we should be ready for an IPO in 2019 or 2020. This will be in Europe or the US, depending on the progress of our programs, and the location of our investors,” concludes Detheux.

This article appears in the BioVox White Paper on Immunotherapy, May 2017. Download the complete work here for free.

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Cancer immunotherapy: the ultimate ally in the tumor war

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