Technical cooperation sought by a French research team with an industrial partner (pharma/biotech) for the development of a new innovative therapy drug to treat aggressive leukemia

A French research team has developed a new innovative biotherapy drug: a third generation CAR T cell targeting CD123 (CAR123) to treat BPDCN (Blastic plasmacytoid dendritic cell neoplasm) with very encouraging preclinical results. This CAR123 has been selected against 6 different CAR123, for its high activity against BPDCN and low cytotoxicity against CD123+Low normal hematopoietic progenitors, monocytes and endothelial cells (Low "on target off tumor effect"). BPDCN is an aggresive leukemia derived from plasmacytoid dendritic cells, for which the French center has developed clinical and biological expertise, positioning it as a national reference center in France (ministerial declaration 2021) allowing access to patients to realise a clinical trial. BPDCN is an orphan disease (approximately 30 new patients in France per year/ 1400 in Europe and USA). Till now, there is no consensus on the treatment of BPDCN except the interest of allogeneic stem cell transplantation (ASCT) in first remission after polychemotherapy or tagraxofusp. However, ASCT is not available to all patients, and about 40 % of patients relapse after ASCT. It is estimated that about 60 % of patients do not receive curative therapy so improved treatments are clearly needed for this chemotherapy-refractory leukemia. A CAR-T cell is a T lymphocyte that has been genetically modified to express a receptor that recognises a molecule expressed by leukemic cells. CAR123 recognises the CD123 protein, which is highly expressed by 100 % of BPDCN cells and importantly, in 100 % cases. The team developed a third generation CAR-T cell that specifically bind to and destroy CD123+ leukemia cells (BPDCN), allowing eradication of the leukemia cells and potentially curing the patients. After the preclinical validation of CAR123 and its publication in 2020, the further development of this innovative drug requires its evaluation in a human clinical trial. This project has been partially funded by the French government in 2021. At this step, the French laboratory is seeking a private partner to take part in the project, under technical cooperation. Co-development or technology transfer are two possible ways of cooperation. The trial to be conducted in BPDCN will benefit from the existing French network to rapidly include BPDCN patients in order to demonstrate the absence of toxicity of the selected CAR123 and its efficacy in a very aggressive disease. After the study, obtainment of an orphan drug status will allow fast access to early commercial program in first line treatment in BPDCN as an alternative to allograft or as a bridge to allograft. Finally this work will allows (1) to evolve on the BPDCN market in Europe and worldwide (first-line positioning is targeted) and (2) to be clinically evaluated in others CD123+ leukemias offering a more important commercial development. Indeed acute myeloid leukemias (AML) express CD123 in 90 to 100% of cases as well as acute lymphoid leukemias (ALL) in 70% of cases and should be sensitive to CAR123. These leukemias have a higher incidence (respectively 3500 and 900 new cases/year in France) and there is always an unmet need especially in AML and in some situations in ALL. Working with the French laboratory can provide a strong position to the partner to have a third generation CAR 123 in its pipeline. Till now, only two competitive programs with third generation CAR CD123 are running in China without any communicated results. CAR CD 123 under trial evaluation in USA and Europe (phase I or I/II) are second generation of CAR T cells.