Innovate Biopharmaceuticals Announces Collaboration with Institut Gustave Roussy to Study Regulation of Intestinal Permeability and the Gut Microbiota using Larazotide in Immuno-oncology Checkpoint Inhibitor Failure Pre-Clinical Models
Professor Zitvogel’s work focuses on intestinal microbiome dysbiosis and its effects on responses to chemotherapy and checkpoint inhibitors suggesting a nexus between the gut and immune surveillance of cancers.1,2 Her team and others have found that primary resistance to immune checkpoint inhibitors, such as CTLA-4 and PD-1 based immunotherapies, can be attributed to abnormal gut microbial composition.3
Intestinal permeability is compromised in numerous diseases where a disruption of the epithelial barrier that separates the lumen from the host’s immune system may contribute to uncontrolled inflammation. Larazotide is a gut-restricted peptide which has been shown to re-normalize intestinal permeability in various inflammatory and metabolic preclinical models. Through this collaboration, Innovate and Pr. Zitvogel seek to understand how the therapeutic effect of immune checkpoint inhibitors such as antibodies to CTLA-4 and PD-1, is modulated by blocking translocation of bacterial antigens and toxins and certain metabolites from interacting with the host immune system in pre-clinical oncology models.
This emerging area of groundbreaking research looking at uncovering the role of the gut microbiome in the induction of cancer and response to immune checkpoint and chemotherapy, will be one of only four afternoon educational sessions to be held on Friday afternoon,
Sandeep Laumas, M.D., CEO of Innovate, stated, “We are pleased to work with Professor Zitvogel to understand how larazotide’s re-normalization of intestinal permeability could affect the immune checkpoint therapeutic response in tumor models as well further help elucidate the complex interaction of the gut microbiome with the immune system in cancer.”
Pr. Zitvogel, MD, PhD, Scientific Director of the Gustave Roussy Immuno-Oncology Program, said, "We need to deconvolute the delicate interactions between the intestinal epithelial cells, the microbiome and the immune system in the gut and their consequences on tumor immunosurveillance. I am excited to study how larazotide could normalize these interactions in advanced cancer patients to optimize their therapies."
About larazotide acetate for celiac disease
In celiac disease, larazotide is the only drug which has successfully met its primary endpoint with statistical significance in a Phase 2b efficacy clinical trial (342 patients). Innovate completed the End of Phase 2 Meeting with the FDA and is preparing to launch the Phase 3 registration clinical trials for celiac disease in the second quarter of 2019. Nearly 600 subjects have been exposed to larazotide in clinical trials, and a safety profile comparable to placebo has been demonstrated. Larazotide has received Fast Track designation from the FDA for celiac disease.
Innovate is a clinical stage biotechnology company focused on developing novel therapeutics for autoimmune and inflammatory diseases. Innovate’s lead drug candidate, larazotide acetate, has a mechanism of action that renormalizes the dysfunctional intestinal barrier by decreasing intestinal permeability and reducing antigen trafficking, such as gliadin fragments in celiac disease, and bacterial toxins and immunogenic antigens in nonalcoholic steatohepatitis (
Institut Gustave Roussy, leader in the fight against cancer in
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1Vétizou, M., Pitt, J.M., Daillère, R., Lepage, P., Waldschmitt, N., Flament, C., Rusakiewicz, S., Routy, B., Roberti, M.P., Duong, C.P. and Poirier-Colame, V., 2015. Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota. Science, 350(6264), pp.1079-1084. 10.1126/science.aad1329.
3Gopalakrishnan, V., Spencer, C.N., Nezi, L., Reuben, A.,
Source: Innovate Biopharmaceuticals, Inc