Isabelle LE MERCIER

Leading a research and discovery team to develop allogenic cell therapies : - Established in vivo pharmacology workflows from the ground up, both at external and internal Animal Care Facility (ACF). - Developed and implemented hematology and solid tumor models to evaluate adaptable and allogeneic CAR-T cell therapies. - Developed pharmacology assays to assess dose-efficacy relationships of targeting modules for adaptable CAR-T cells. - Established and validated high-quality ex vivo analytical platforms, including quantitative flow cytometry and ELISA/MSD-based assays. - Directed IND-enabling nonclinical pharmacology studies, including planning and execution of pivotal efficacy and toxicity assessments to support regulatory filings. - Oversee team operation, ACF setup and operation, and compliance with institutional and regulatory standards.

Program Team Lead for an AI driven immuno-oncology small molecule drug discovery program leveraging scRNAseq data : - Led multi-disciplinary program team including biologists, computational scientists, computational chemists and chemists. - Defined targetable cell behaviors of interest using scRNAseq data to predict interventions to change them. In particular, implemented an integrated analysis approach combining patients’ data, in vitro data and preclinical in vivo data to strengthen the quality and diversity of predictions. - Developed and validated immune cell-based screening phenotypic assays accurately reflecting the targeted cell behaviors. - Established screening cascade for hit identification to lead selection, including orthogonal assays to identify/eliminate hits with undesired MOAs. - Managed all in vitro and in vivo pharmacology studies for the program, overseeing both internal efforts and collaborations with CROs.

Led the Immuno-Oncology Target Identification and Validation platform : - Conducted in vivo genome-wide and combination CRISPR/Cas9 screens in primary T cells to identify novel targets and target combinations with high relevance for immuno-oncology therapies. - Identified and validated the 2 specific targets currently being pursued for TIL (Tumor-Infiltrating Lymphocyte) edits in KSQ-001 and KSQ-004 programs. - Identified over 20 novel targets, leading to the initiation of multiple immuno-oncology small molecule drug discovery both internal and in collaboration with partners Immunology lead for several internal small molecule drug discovery programs : - Developed genetic validation assays and immune cell-based assays for preclinical target validation, mechanism of action identification and cross species translatability evaluation. - Initiated and managed collaborative partnerships with CROs, leading to the development of two proprietary transgenic mouse strains. - Managed a team of direct reports ranging from Associate Scientists to Senior Scientists.

VISTA agonists preclinical development for the treatment of autoimmune and inflammatory diseases enabling Pharma partnership: - Developed multiple in-vivo autoimmune models (chronic and acute allo-GvHD, xeno-GvHD, Colitis etc.) for target validation, lead candidate selection and MOA studies. - Contributed to the filing of multiple patent applications.

Prof. Randolph Noelle lab, Geisel Medical School at Dartmouth College, Lebanon, NH Characterized VISTA as negative checkpoint regulator and therapeutic target for immuno-oncology and autoimmune diseases Developed in-vivo models in immuno-oncology, transplantation, tolerance and autoimmunity

Dr. Jacqueline Marvel lab “Apoptosis and CD8 T cells memory” (INSERM U851, Lyon France) Developed flow cytometry panels to provide high confidence ex-vivo biology data to validate modeling approaches for pathogen-specific immune responses

Dr. Christophe Caux lab “Cytokines and Cancer” (INSERM U590, Lyon, France). Thesis title: Characterization of tumor associated alterations of myeloid and plasmacytoid dendritic cells in mouse mammary tumors Developed and characterized multiples syngeneic tumor models to recapitulate human pathology Identified a new mechanism of tumor evasion Validated a novel therapeutic strategy using intra-tumoral TLR ligand delivery