How did you go from the lab bench to the creation of Innate Pharma?
On the NK side, antitumor activity was demonstrated in vitro in humans and in vivo in mice, and it was unclear what could be done clinically or in which indications.
In 1995, I was a researcher in a lab working on T cells but already specialized in NK cells since my post doc at Harvard Medical School in Boston. So I proposed setting up a new team, the first at the time in Marseille, focused on innate immunity, at the Marseille-Luminy Immunology Center (CIML) to work on NK cells, how they function at a molecular level, and their antitumor potential.
At this time, we discovered the mode of action of inhibitory receptors expressed by NK cells and proposed a structural and functional definition of the family of ITIM inhibitory receptors (Immunoreceptor Tyrosine-based Inhibition Motif). It was at this point that I spoke to Hervé Brailly, during one of the exchanges that we had as part of his activity at Immunotech.
Everything started from there: the desire to study how we could transform scientific discoveries into therapies to treat patients. I wanted to create bridges between the two worlds of basic and applied research, academia and industry. Hervé had the same desire and the entrepreneurial spirit. We met in Paris at the University Institute of France, with Marc Bonneville and Jean Jacques Fournié to develop our project and choose our targets. I had met Alessandro Moretta during my post doc at Harvard at a congress in Stockholm in 1991, in 1992 and finally in 1995 at the assembly of my team at the CIML, and our meetings were always very exciting. He took part in the Innate project as early as 1998.
And what did we know about the role and activation of immune cells?
Much happened in the early 2000s proving the ability of the immune system to kill cancer cells in vivo. One of the trigger papers was that of the American immunologist Robert Schreiber in Nature who proposed a new diagram to explain the evolution of cancers. Subsequently, the "3E" scenario emerged. This scenario is based on experiments conducted in mice and describes three key stages of interaction between cancer cells and the immune system: Elimination, Balance and Exhaustion. In the first instance, cancer cells are recognized and eliminated. Secondly, the cancer restarts, even develops, but is still under control. Finally, the balance breaks down and the cancer escapes the immune cells and progresses.
Another article, important for Innate, was published in 2002 by Andrea Velardi. It concerns the non-recognition of the "self" by NK cells, this time in humans, in the case of a marrow transplant (thus of immune cells of a donor) practiced to treat a certain type of leukemia. This non-recognition allowed the cancer cells of the patient to be destroyed by the donor's immune cells.
Later, the shape of the survival curves of the patients treated in the first immunotherapy trials with antibodies blocking the inhibitory receptors changed our understanding of the situation: when it works, immunotherapy targeting immune control helps control the disease in the long run.
What about Innate today?
We remain known for our expertise in innate immunity and NK cells in particular, although obviously our portfolio now extends beyond this. Beyond the targeting of immune checkpoints, we are developing programs in the field of tumor antigens and the tumor microenvironment. Our strength is that we have continued to put a premium on scientific excellence, as evidenced by our recent publications. We have four programs in clinical development today, and more than 30 molecules in our portfolio.
I find myself completely in the dynamics of Innate. As I do, it aims to keep very strong links between both basic research and industry, and to build bridges between these two worlds.