Allergic diseases including atopic dermatitis, food allergy, and allergic asthma represent a global health problem that disproportionately impacts children. Surprisingly, there are no approved approaches to prevent the development of these diseases in at-risk individuals, resulting in chronic morbidity and economic burden. The management of asthma, for example, carries a steep cost burden of billions of dollars per year in the US alone, of which nearly 20 billion is spent on standard of care treatments with variable efficacy. Food allergy management is generally limited to allergen avoidance and rescue from severe acute anaphylaxis. There is a crucial need to develop innovative strategies to prevent the onset of these Type 1 allergic diseases rather than treating their symptoms. A preventative approach targeting at-risk individuals could significantly reduce the morbidity and healthcare burden associated with these increasingly common conditions. Studies confirm the link between gut microbiota development, immunological training, and allergic disease onset in childhood, and it is now clear that allergic disease risk is associated with aberrant microbial exposures over the first year of life. Longitudinal gut microbiota profiling studies in infants and children show that a loss of specific immunomodulatory commensal bacteria, and their metabolic networks, precedes allergic disease development. Using infant gut microbiota data sets and in vivo allergic disease models, Siolta Therapeutics has designed a live biotherapeutic product (LBP), STMC-103H, to stimulate tolerant immunological development and prevent allergic disease onset in at-risk individuals. STMC-103H contains three distinct active ingredient bacteria isolated from healthy human stool. Siolta has performed extensive cGMP manufacturing development, including formulation, process, and analytical method development, to support Phase 1 and Phase 2 clinical trials of STMC-103H under an IND with the FDA. In this project, we will build on our previous STMC-103H drug product development to improve the stability, potency, and characterization approaches for late-stage clinical trials and subsequent commercialization. Success of this project will directly support the regulatory and commercial development of STMC-103H. Indirectly, this work will improve the manufacturing and clinical development of diverse candidate LBPs containing sensitive live bacteria with high therapeutic potential. Siolta will also seek to license novel manufacturing approaches to other LBP developers.
Public Health Relevance Statement: NARRATIVE The human gut microbiota is a crucial environmental factor that influences the development of immune tolerance in childhood, thus making early-life live microbial interventions an attractive approach for allergic disease prevention. To this end, Siolta Therapeutics has developed a novel live biotherapeutic product, STMC-103H, for the prevention of allergic disease. Siolta aims to continue the innovative manufacturing development of the novel live biotherapeutic STMC-103H to support late-stage clinical and commercial development.
Project Terms: Allergens; Anaphylaxis; Anaphylactic Reaction; Anaphylactic Shock; Antioxidants; anti-oxidant; Asthma; Bronchial Asthma; Bacteria; Anaerobic Bacteria; anaerobe; Biological Response Modifier Therapy; Biological Therapy; biological therapeutic; biological treatment; biologically based therapeutics; biotherapeutics; biotherapy; capsule; Capsules; Cells; Cell Body; Child; 0-11 years old; Child Youth; Children (0-21); youngster; Clinical Research; Clinical Study; Clinical Trials; Atopic Dermatitis; Atopic Eczema; Atopic Neurodermatitis; Disseminated Neurodermatitis; allergic dermatitis; allergic eczema; Desiccation; Dessication; Disease; Disorder; Pharmaceutical Preparations; Drugs; Medication; Pharmaceutic Preparations; drug/agent; Eosinophilia; Excipients; Feces; stool; Flow Cytometry; Flow Cytofluorometries; Flow Cytofluorometry; Flow Microfluorimetry; Flow Microfluorometry; flow cytophotometry; Food Hypersensitivity; Allergic to food; Allergy to food; Food Allergy; Freeze Drying; Freeze Dryings; Lyophilization; Freezing; Goals; Cyclic GMP; Guanosine Cyclic Monophosphate; cGMP; Human; Modern Man; Hypersensitivity; Allergy; Immediate hypersensitivity; Atopic Hypersensitivity; IgE-Mediated Hypersensitivity; Type I Hypersensitivity; humoral hypersensitivity; IgE; Immunoglobulin E; Immune Tolerance; Immunologic Tolerance; immune system tolerance; immune unresponsiveness; immunological paralysis; Infant; Allergic inflammation; 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; Lactobacillus; Lung; Lung Respiratory System; pulmonary; Lymph; lymphatic fluid; Methods; Morbidity - disease rate; Morbidity; Powders; Powder dose form; Primary Prevention; Production; Public Health; QOL; Quality of life; Risk; Treg; regulatory T-cells; Regulatory T-Lymphocyte; Temperature; Testing; United States Food and Drug Administration; Food and Drug Administration; USFDA; Work; Healthcare; health care; Mediating; Data Set; Dataset; Extrinsic asthma; Allergic asthma; atopic asthma; extrinsic allergic asthma; analytical method; base; method development; improved; Acute; Chronic; Clinical; Phase; Link; Evaluation; Training; pediatric; Childhood; Individual; Recovery; Licensing; Th-2 Cell; Type 2 Helper Cell; Th2 Cells; Metabolic Networks; Biochemical Pathway; disease onset; disorder onset; Onset of illness; Phase 2 Clinical Trials; phase II protocol; Phase II Clinical Trials; Therapeutic; Infiltration; microbioreactor; Bioreactors; Life; programs; Immunes; Immune; Oral; Reaction; System; Probiotics; success; microbial; Immunomodulation; immune modulation; immune regulation; immunologic reactivity control; immunomodulatory; immunoregulatory; immunoregulation; novel; disease prevention; disorder prevention; Secondary Prevention; member; disease risk; disorder risk; disorder model; Disease model; Environmental Factor; environmental risk; Environmental Risk Factor; Prevention; Reporting; Allergic; Intervention Strategies; interventional strategy; Intervention; Phase I Clinical Trials; Early-Stage Clinical Trials; Phase 1 Clinical Trials; phase I protocol; Pharmaceutical Agent; Pharmaceuticals; Pharmacological Substance; Pharmacologic Substance; preventing; prevent; global health; Symptoms; Economic Burden; Supplementation; in vivo; Update; Validation; Immunologics; Immunochemical Immunologic; Immunologic; Immunological; Immunologically; Molecular; Process; Development; developmental; pre-clinical; preclinical; cost; design; designing; allergic airway inflammation; allergic airway epithelium inflammation; clinical efficacy; novel strategies; new approaches; novel approaches; novel strategy; innovation; innovate; innovative; Impairment; Microbe; Metagenomics; Functional Metagenomics; mouse model; murine model; commercialization; standard of care; Biological Markers; bio-markers; biologic marker; biomarker; product development; clinical material; process optimization; liquid formulation; potency testing; gut microbiota; GI microbiota; Gastrointestinal microbiota; enteric microbial community; enteric microbiota; gastrointestinal microbial flora; gut commensal; gut community; gut flora; gut microbe community; gut microbial community; gut microbial composition; gut microbial consortia; gut microbiotic; gut microflora; intestinal flora; intestinal microbes; intestinal microbiota; intestinal microflora; intestinal tract microflora; Allergic Disease; Formulation; clinical development; therapeutic candidate; commensal bacteria; commensal bacterial species
