Founded in 1999 in Marseille, Innate Pharma is currently developing a large portfolio of innovative therapeutic antibodies capable of improving the treatments of cancers by exploiting the immune system.
Its most advanced molecule, monalizumab, is a blocking antibody that prevents the inhibition of CD8+ T lymphocytes and NK (Natural Killer) cells by tumor cells expressing HLA-E. By acting simultaneously on innate and adaptive immunity, monalizumab may re-establish a broad anti-tumor response, notably in the case of resistant cancers. “The challenge of immunotherapy is, on the one hand, to mobilize the immune system and ensure that lymphocyte cells reach the tumor bed and, on the other hand, to lift tumor immunosuppression to trigger an effective immune response,” said Mondher Mahjoubi, CEO and Chairman of the Executive Board of Innate Pharma.
As early as 2015, AstraZeneca was attracted by the potential of this innovation. The group acquired part, then all, of the rights of monalizumab. Never before had a French biotech company signed such a large deal, for a potential total amount of $1.275 billion.
At the end of April 2022, the start of PACIFIC-9, a very large Phase 3 clinical trial that could enroll 1,000 patients, has resulted in the payment of $50 million, bringing to $450 million the milestone payments already received by Innate for this molecule. The purpose of this trial is to analyze the efficacy of AstraZeneca’s molecule durvalumab in combination with either monalizumab or oleclumab (another AstraZeneca antibody) in patients with non-operable non-small cell lung cancer who have not made any progress after chemoradiotherapy.
Monalizumab is also being tested in phase 3 in a study on ENT cancers (head and neck).
“Innate Pharma has demonstrated recognized know-how. As is evidenced by a number of partnerships, not only with manufacturers but also with the academic world. It is a source of pride and a sign of respect for the scientific excellence of our research laboratories,” Mondher Mahjoubi, CEO and Chairman of the Executive Board of Innate Pharma.
A portfolio that is revolutionizing immuno-oncology
The Innate Pharma portfolio contains a number of molecules, in addition to monalizumab, which result from the same approach aimed at boosting the immune system against tumor cells.
Another promising molecule, lacutamab is currently being evaluated in a phase 2 clinical trial called TELLOMAK, in cutaneous T-cell lymphoma (CTCL), an orphan disease. “Preliminary results are very encouraging,” the CEO was pleased to point out. The European Medicines Agency (EMA) and the Food and Drug Administration (FDA) in the U.S. could grant it accelerated marketing authorization based on the results of this trial.
Another line of development aims to overcome immunosuppression mechanisms in the tumor microenvironment to restore the immune response. Two molecules in development in Innate’s portfolio target the adenosine pathway, known for its key role in tumor immunosuppression: In early June 2022, IPH5201, also co-developed in partnership with AstraZeneca, entered Phase 2 for an indication in lung cancer, and for which a milestone payment of €5 million has been made to Innate; and also IPH5301, this time developed by Innate on its own. A phase 1 is currently taking place at the Paoli-Calmettes Institute, the anti-cancer center in Marseille.
The biotech company has also developed a versatile technology platform called ANKETTM (Antibody-based NK cell Engager Therapeutics). This new generation of sophisticated antibodies aims to bring together cancer cells and NK cells, the killer cells, but “(they) do more than stimulate NK cells – they are equipped with homing heads to direct NK cells to tumor cells,” Mondher Mahjoubi added.
It allows the development of an antibody which is predetermined based on the target and can be used for several types of cancers. Among other projects a first drug candidate from this platform, for various forms of blood cancers, has been in clinical development since 2021 with the Sanofi laboratory.