Food allergy (FA) has rapidly increased over 2 decades affecting 32 million Americans, with annual costs of $25 billion. FA anaphylaxis, a potentially life-threatening condition, increased 200-400% in children from toddlers to teens.10 Peanut/ tree nut and sesame allergy often co-exist, last a lifetime, cause severe reactions, and there is currently no cure. Common treatments, either prophylactic i.e., food avoidance, or therapeutic i.e., food allergen oral immunotherapy are limited and impractical. Safe, effective, and non-food restricted therapeutics are needed. FA is primarily mediated by food protein specific immunoglobulin E. Persistent IgE caused by long-lived plasma cells (IgE+LPC) is a significant barrier to FA mitigation. General Nutraceutical Technology LLC (GNT), a NY-based biotechnology startup, is building on groundbreaking research for FA started at Icahn School of Medicine at Mount Sinai. Our oral product "NIT-X" contains the small molecule compound berberine captured by nanoparticles. It significantly increased bioavailability, showed excellent preclinical safety and nearly 100% reduction of PN-IgE and protection against anaphylaxis in animal model of peanut and tree nut allergies, associated with suppressing IgE+ plasma cells/B cells, reducing IL-4, increasing IFN-γ, inducing a distinct B cell transcriptomic profile. We hypothesize that by restoring balanced immunity. NIT-X will be a potentially novel non-food restricted therapeutic for severe and multiple FAs. The goals of this SBIR Phase II are generating robust NIT-X Chemistry, Manufacturing and Control (CMC), along further preclinical pharmacokinetic (PK), toxicology and pharmacology data, and file the phase Ia clinical study. We will conduct 4 Specific Aims: #1 Generating NIT-X CMC data, characterization of product and preclinical PK profile; #2. Further generation of data on NIT-X preclinical toxicology; #3. Investigate dose efficacy of NIT-X in murine models. #4. File phase Ia clinical trial as a sub-program to an ongoing parent botanical IND. Solid SBIR phase I feasibility data and strong team and design for phase II study enable GNT to generate rigorous date for CMC, preclinical PK, safety, and efficacy for obtaining approval of IND for a subproject to the current IND for clinical trials with NIT-X, towards commercialization for treating FA.
Public Health Relevance Statement: NARRATIVE Food Allergy is a serious and potentially life-threatening condition, affecting approximately 32 million people in the US, for which there is currently no cure. We developed an innovative berberine nanomedicine called NIT-X that showed excellent preclinical bioavailability, safety and nearly complete suppression of IgE and protection from peanut and tree nut anaphylaxis. NIT-X is not specific for any food and represents a novel food allergy treatment, even for those who suffer from multi-food allergies or have very high risk of reactions.
Project Terms: absorption; Accidents; 21+ years old; Adult Human; adulthood; Adult; Affect; ages; Age; Anaphylactic Reaction; Anaphylactic Shock; Anaphylaxis; Antibodies; B-Lymphocytes; B blood cells; B cell; B cells; B-Cells; B-cell; Berberine; Umbellatine; Biochemistry; Biological Chemistry; Biological Availability; Bioavailability; Physiologic Availability; Biotechnology; Biotech; Chemistry; Child; 0-11 years old; Child Youth; Children (0-21); kids; youngster; Clinical Research; Clinical Study; Clinical Trials; Double-Blind Method; Double-Blind Study; Double-Blinded; Double-Masked Method; Double-Masked Study; Pharmaceutical Preparations; Drugs; Medication; Pharmaceutic Preparations; drug/agent; Investigational Drugs; Investigational New Drugs; Epithelial Cells; Food; Food Hypersensitivity; Allergic to food; Allergy to food; Food Allergy; Goals; Hematology; Histamine; Histology; Hypersensitivity; Allergy; Immunoglobulin A; IgA; IgE; Immunoglobulin E; Immunoglobulin G; 7S Gamma Globulin; IgG; Immunity; Immunosuppression; Immunosuppression Effect; Immunosuppressive Effect; immune suppression; immune suppressive activity; immune suppressive function; immunosuppressive activity; immunosuppressive function; immunosuppressive response; Industry; Inflammation; Interferon Type II; IFN-Gamma; IFN-g; IFN-γ; IFNG; IFNγ; Immune Interferon; Interferon Gamma; lFN-Gamma; Interleukin-4; B cell growth factor; B-Cell Differentiation Factor-1; B-Cell Growth Factor-1; B-Cell Growth Factor-I; B-Cell Proliferating Factor; B-Cell Stimulating Factor; B-Cell Stimulating Factor-1; B-Cell Stimulation Factor-1; B-Cell Stimulatory Factor-1; BCDF-1; BCGF; BCGF-1; BCSF 1; BSF-1; BSF1; Binetrakin; IL-4; IL4 Protein; Interleukin-4 Precursor; Lymphocyte Stimulatory Factor 1; MCGF-2; Mast Cell Growth Factor-2; T-Cell Growth Factor 2; Laboratories; Marketing; mast cell; Marrow Mast Cell; Tissue Basophils; mastocyte; Morbidity - disease rate; Morbidity; mortality; Mus; Mice; Mice Mammals; Murine; Persons; Nuts; Parents; parent; Pesticides; Drug Kinetics; Pharmacokinetics; Pharmacology; Placebos; Sham Treatment; sham therapy; Plasma; Blood Plasma; Plasma Serum; Reticuloendothelial System, Serum, Plasma; Plasma Cells; Blood Plasma Cell; Plasmacytes; plasmocyte; Production; Proteins; Research; Risk; Safety; medical schools; medical college; school of medicine; Technology; Testing; Time; Toxicology; Trees; Work; anti-IgE; anti-IgEid; Generations; CSIF; CSIF-10; Cytokine Synthesis Inhibitory Factor; IL-10; IL10; IL10A; Interleukin 10 Precursor; Interleukin-10; Mediating; Acute; Chronic; Solid; Clinical; Encapsulated; Residual; Residual state; Phase; intestinal epithelium; Individual; Therapeutic; Heavy Metals; Life; Area Under Curve; programs; Oral; Reaction; prophylactic; Body Surface; meetings; meeting; Nut Hypersensitivity; Nut Allergy; Tree Nut Allergy; Tree Nut Hypersensitivity; allergic to nuts; allergy to nuts; American; Animal Model; Animal Models and Related Studies; model of animal; microbial; Pharmacology and Toxicology; novel; Amendment; Toddler; Categories; drug development; immunoreaction; Immune reaction; Annual Reports; omalizumab; Sesame; Sesame - dietary; food allergen; nanomedicine; nano medicinal; nano medicine; nanomedicinal; small molecule; Dose; Botanicals; Data; Nutraceutical; Small Business Innovation Research Grant; SBIR; Small Business Innovation Research; Preparation; preparations; Teenagers; Teen; teen years; teenage; nano; Placebo Control; placebo controlled; pre-clinical; preclinical; cost; nano particle; nano-sized particle; nanosized particle; nanoparticle; Outcome; protective effect; innovate; innovative; innovation; transcriptomics; new drug treatments; new drugs; new pharmacological therapeutic; new therapeutics; new therapy; next generation therapeutics; novel drug treatments; novel drugs; novel pharmaco-therapeutic; novel pharmacological therapeutic; novel therapy; novel therapeutics; murine model; mouse model; commercialization; high risk; FDA approved; common treatment; pre-clinical safety; preclinical safety; phase II study; phase 2 study; oral immunotherapy; phase 1 trial; phase I trial; phase II designs; phase 2 designs; phase I designs; phase 1 designs; food avoidance; Phase 1a Clinical Trial; Phase Ia Clinical Trial; manufacture
