All in on cancer immunotherapy

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Founded in 2011, iTeos Therapeutics began its activities at the end of 2012. Active in the field of cancer immunotherapy, the company develops innovative drugs by focusing on the tumor microenvironment. At the time of its launch, iTeos benefited from the results of BioWin’s Cantol project, the objective of which was to discover and validate immunomodulatory candidate medicines designed to inhibit IDO1, thereby bolstering the immune system’s response to cancerous cells. 

You created iTeos in parallel with the Cantol project, which was a good catalyst.

Michel Detheux, CEO at iTeos: “Indeed, we integrated IDO1 targets that were studied during the Cantol project. The results we got during the project strengthened the interest in that target and for a new drug discovery program. This program was a real success, and consequently we signed a deal with Pfizer, allowing us to start a phase I clinical trial in August 2016. Furthermore, the Cantol project allowed us to benefit from substantial support from the Walloon Region. In four years’ time, we received 10 million euros in grants, partially granted by BioWin.”

What was the aim of the Cantol project?

Detheux: “To understand this, you have to begin with the fundamentals and explain how a tumor can develop and escape from the immune system thanks to a mechanism called immunosuppression. To put it simply, T-lymphocytes recognize foreign antigens, expressed by cancer or any other pathogen agents. T-lymphocytes need tryptophan, an essential amino acid, to function properly. To defend itself, the tumor expresses two enzymes, IDO1 and TDO2, that break down the tryptophan into kynurenine. This is the same mechanism that a pregnant woman uses to tolerate her fetus, which is a foreign body due to the expression of paternal antigens. The tumor has hijacked this mechanism to become invisible, just like the fetus throughout the pregnancy. In the tumor microenvironment, we observe a reduction in the concentration of tryptophan and an increase in the concentration of kynurenine, which inhibits T-lymphocytes. If you block these enzymes, which was the original aim of the Cantol project, you will restore the tryptophan concentration, reduce the concentration of kynurenine and thereby restore the capacity of the T-lymphocytes to attack the tumor. In only two years’ time, iTeos developed inhibitors against these enzymes as candidate drugs.”

Since 2011, the pharmaceutical industry and its clinicians have obtained extraordinary results — between 10% and 40% of patients, according to their degree of sickness and treatment, are in complete remission.

Cancer immunotherapy is not new; why the rush to develop this therapy that we are seeing today? 

Detheux: “It is true that the concept of cancer immunotherapy has existed for decades, but results have only been demonstrated since 2011 with Yervoy, an antibody that blocks an inhibitory mechanism of the immune system. It provoked a change of paradigm and a genuine revolution in this field by significantly increasing the percentage of patients who were totally cured. Since 2011, the pharmaceutical industry and its clinicians have obtained extraordinary results — between 10% and 40% of patients, according to their degree of sickness and treatment, are in complete remission.

Upon the discovery of the IDO1 inhibitors, you signed a deal with Pfizer.

Detheux: “In 2014, we sought financing opportunities to develop the iTeos activities. I was in contact with 42 investment funds and 28 pharmaceutical companies. Finally, we concluded an agreement with Pfizer worth 24 million euros upfront; on top of this, we will receive milestone payments and royalties.”

Is iTeos aiming to become a leading player in immunotherapy? 

Detheux: “iTeos Therapeutics has the ambition to become an international player in its domain. We started with just 4 people when we launched our activities in 2012. Between January 2015 and April 2016, the company expanded to 40 employees. The team includes 14 different nationalities and attracts people from all over the world. Our Chief Scientific Officer and Chief Medical Officer have  20 years of experience working in the US. What is important for me is to integrate all this expertise, enabling us to move from target discovery to clinical trials. We are planning more phase I trials with our own programs, one at the end of 2017 and hopefully two in 2018. As a biotechnology company, reaching the clinical trial stage is extremely important for us, not only because it is a real milestone in creating value, but also in terms of the continuity of activities to arrive at that point. My ambition is to be a company that lasts, one with long-term activities of world-class quality.

You mention “another partner.” Are you collaborating with companies other than Pfizer?

Detheux: “We also concluded an agreement with Adimab, which has a technology to express human antibodies on the surface of yeast. We are using this strategy to expand our drug discovery programs with antibodies. Not just with small molecules — as illustrated by the IDO1 program — but also with antibodies, elements that are very important in immuno-oncology. Adimab is very efficient when it comes to quickly identifying candidate drugs. We are speaking in terms of a few months, whereas conventional technologies take several years.”

We try to reproduce the mechanisms that the tumor uses to develop immunosuppression. This enables us to either discover new targets or reposition existing drugs.

What are your current projects and programs?

Detheux: “For our cancer immunotherapy, we have a very effective partnership with the Biopark in Gosselies to test the molecules in vivo. We also develop translational medicine strategies to select the patients and biomarkers we’ll target during the clinical phase and design the molecules accordingly. Other activities such as medicinal chemistry, pharmacology, toxicity and production of clinical batches are subcontracted to key international players.

At present, we have five proprietary programs running in addition to the two partnered ‘small molecules’ programs of which I spoke earlier: IDO1 and TDO2.

Our first program is based on a strategy called the ‘best in class’: These are existing molecules that we improve to make them more effective for applications in immuno-oncology. This program is beginning to deliver and will enable us to arrive at a clinical stage by the end of 2017.  Another ‘small molecules’ program targets an important mechanism to activate T-lymphocytes.

Finally, we have three antibody programs that are targeting the T-lymphocytes. These targets were selected thanks to our knowledge in tumor immunology. Our ambition is to bring one to three programs to the clinical stage by the end of 2018.
And we do not plan to stop there!”

What else do you have in the pipeline?

Detheux: “The strategical partnership with Pfizer gave us the opportunity to start our first projects. In addition to the five proprietary programs I just mentioned, we validated a target discovery platform. We identify new targets and thereby develop an original portfolio in the medium term, based on unknown tumor mechanisms in addition to those that we have known about for years. We try to reproduce the mechanisms that the tumor uses to develop immunosuppression. This enables us to either discover new targets or reposition existing drugs.

This platform is the result of our cooperation with Pfizer, but we can develop it independently. It is an important asset for iTeos to further develop its activities. In the long term, this will allow us to create our own combinations to go to the market, and hopefully it will make us the partner of choice for other world-level pharmaceutical companies.”

In collaboration with Amélie Moyaerts, BioWin