{"id":270355267,"generated_unique_award_id":"ASST_NON_R41DK142395_075","fain":"R41DK142395","uri":"R41DK142395-2205484177","category":"grant","type":"04","type_description":"PROJECT GRANT (B)","description":"DEVELOPMENT OF AN IMMUNE EVASIVE STEM CELL LINE FOR TYPE 1 DIABETES REGENERATIVE THERAPY - PROJECT SUMMARY TYPE 1 DIABETES MELLITUS (T1DM) IS AN AUTOIMMUNE DISEASE CHARACTERIZED BY THE DESTRUCTION OF INSULIN-PRODUCING Β-CELLS WITHIN PANCREATIC ISLETS, CULMINATING IN DYSREGULATED BLOOD GLUCOSE LEVELS, AFFECTING 2 MILLION AMERICANS. THE STANDARD OF CARE FOR T1DM IS CONTINUOUS GLUCOSE MONITORING AND EXOGENOUS INSULIN THERAPY. DESPITE SIGNIFICANT ADVANCEMENTS IN INSULIN DELIVERY METHODS, ONLY 17% OF CHILDREN AND 21% OF ADULTS ACHIEVE THE RECOMMENDED HBA1C LEVELS OF <7.5 AND 7%, RESPECTIVELY. CLINICAL ISLET TRANSPLANTATION (CIT), DURING WHICH ALLOGENEIC DONOR ISLETS ARE INJECTED INTO THE PORTAL VEIN, HAS SUCCESSFULLY OBTAINED 78% INSULIN INDEPENDENCE; HOWEVER, CIT IS CHALLENGED BY ALLOGENEIC HUMAN CADAVERIC ISLET SUPPLY, GRAFT FAILURE, AND THE NEED FOR CHRONIC IMMUNOSUPPRESSION. IMPLANTATION OF CADAVER ISLETS OR STEM CELL-DERIVED ISLETS (SC-ISLETS) EITHER UNENCAPSULATED OR SURROUNDED BY A SEMIPERMEABLE ENCAPSULATING MEMBRANE DESIGNED TO BE IMMUNE-PROTECTIVE IS ALSO BEING EXPLORED BUT REQUIRES IMMUNOSUPPRESSION OR PRESENTS THE RISK OF FIBROSIS, RESPECTIVELY. NONE OF THE CURRENT TREATMENTS HAVE REPLICATED NATIVE Β-CELL FUNCTION; THEREFORE, THERE IS A CRITICAL UNMET NEED FOR MORE EFFICACIOUS T1DM TREATMENTS. THUS, ALEUTIAN THERAPEUTICS (ALEUTIAN) IS DEVELOPING A NOVEL CELL THERAPY THAT ADDRESSES THE LIMITATIONS OF AVAILABLE TREATMENT OPTIONS FOR T1DM. ALEUTIAN’S INNOVATIVE NOVEL TECHNOLOGY INVOLVES THE GENERATION OF ALLOGENEIC ISLET-LIKE ORGANOIDS FROM PLURIPOTENT STEM CELLS AND GENE MODIFICATION TO ENABLE IMMUNE EVASION UPON TRANSPLANTATION. TOGETHER, THESE INNOVATIONS WILL ALLEVIATE THE CELL SUPPLY LIMITATION AND THE REQUIREMENT FOR IMMUNE SUPPRESSION TREATMENT OF CURRENT CELL THERAPIES. ALEUTIAN’S ACADEMIC COLLABORATOR HAS PREVIOUSLY CONDUCTED ANIMAL STUDIES DEMONSTRATING: 1) THE SUCCESSFUL DIFFERENTIATION OF STEM CELLS INTO ISLET-LIKE ORGANOIDS AND GLYCEMIC CONTROL UPON TRANSPLANTATION; AND 2) THE EXTENSION OF CELL SURVIVAL FOLLOWING THE INTRODUCTION OF PROGRAMMED CELL DEATH LIGAND 1, A KNOWN REGULATOR OF IMMUNE TOLERANCE, IN AN IMMUNE-COMPETENT XENO MOUSE MODEL. HOWEVER, THESE CELLS DO NOT SURVIVE IN THE MICE LONG-TERM DUE TO XENO AND ALLO IMMUNE REJECTION. ALEUTIAN THEREFORE PLANS TO DEVELOP A PANEL OF EDITS TARGETING BROAD INNATE AND ADAPTIVE IMMUNE COMPARTMENTS. THE GOAL OF THIS PHASE I STUDY WILL BE TO SHOW IN VITRO PROOF-OF-CONCEPT OF IMMUNE EVASION WITH THESE EDITS AND THE ABILITY TO DIFFERENTIATE INTO ALLOGENEIC ISLET-LIKE ORGANOIDS. WE AIM TO PRODUCE AND BANK THE GENE-EDITED CELL LINES AND SUBSEQUENTLY EVALUATE THEM FOR SC-ISLET DIFFERENTIATION, IN VITRO FUNCTION, AND IMMUNE EVASION IN VITRO. SUCCESSFUL COMPLETION OF THE PROPOSED PHASE I STUDY WILL SHOW THAT ENGINEERED STEM CELL-DERIVED ISLET-LIKE ORGANOIDS ARE CAPABLE OF GLUCOSE-STIMULATED INSULIN SECRETION WHILE EVADING IMMUNE REACTIVITY IN VITRO, WHICH WILL INFORM PHASE II IN VIVO EFFICACY STUDIES.","subaward_count":0,"total_subaward_amount":null,"total_subsidy_cost":0.0,"total_loan_value":0.0,"total_obligation":372067.0,"date_signed":"2025-09-06","base_and_all_options":null,"base_exercised_options":null,"non_federal_funding":0.0,"total_funding":372067.0,"total_account_outlay":176862.72,"total_account_obligation":372067.0,"account_outlays_by_defc":[{"code":"Q","amount":176862.72}],"account_obligations_by_defc":[{"code":"Q","amount":372067.0}],"record_type":2,"cfda_info":[{"applicant_eligibility":"Project Grants: Universities, colleges, medical, dental and nursing schools, schools of public health, laboratories, hospitals, State and local health departments, other public or private institutions, both non-profit and for-profit, and individuals who propose to establish, expand, and improve research activities in health sciences and related fields. NRSAs: Support is provided for academic and research training only, in health and health-related areas that are periodically specified by the National Institutes of Health.  To be eligible, predoctoral awardees must have completed the baccalaureate degree and postdoctoral awardees must have a professional or scientific degree (M.D., Ph.D., D.D.S., D.O., D.V.M., Sc.D., D.Eng., or equivalent domestic or foreign degree). Individuals must be nominated and sponsored by a public or nonprofit private institution having staff and facilities appropriate to the proposed research training program. All awardees must be citizens or have been admitted to the United States for permanent residence.   Nonprofit domestic organizations may apply for the Institutional NRSA. SBIR and STTR grants can be awarded only to domestic small businesses that meet the following criteria: 1) Is independently owned and operated, is not dominant in the field of operation in which it is proposing, has a place of business in the United States and operates primarily within the United States or makes a significant contribution to the US economy, and is organized for profit; 2) Is (a) at least 51% owned and controlled by one or more individuals who are citizens of, or permanent resident aliens in, the United States, or (b) for SBIR only, it must be a for-profit business concern that is at least 51% owned and controlled by another for-profit business concern that is at least 51% owned and controlled by one or more individuals who are citizens of, or permanent resident aliens in, the United States. 3) Has, including its affiliates, an average number of employees for the preceding 12 months not exceeding 500, and meets the other regulatory requirements found in 13 C.F.R. Part 121. Business concerns are generally considered to be affiliates of one another when either directly or indirectly, (a) one concern controls or has the power to control the other; or (b) a third-party/parties controls or has the power to control both. STTR grants which \"partner\" with a research institution in cooperative research and development. At least 40 percent of the project is to be performed by the small business concern and at least 30 percent by the research institution. In both Phase I and Phase II, the research must be performed in the U.S. and its possessions. To be eligible for funding, a grant application must be approved for scientific merit and program relevance by a scientific review group and a national advisory council.","beneficiary_eligibility":"Health professionals, graduate students, health professional students, scientists, and researchers, any nonprofit or for-profit organization, company, or institution engaged in biomedical research.  Project Grants: Although no degree of education is either specified or required, nearly all successful applicants have doctoral degrees in one of the sciences or professions. NRSAs: Predoctoral awardees must have completed the baccalaureate degree and postdoctoral awardees must have a professional or scientific degree.","cfda_federal_agency":"NATIONAL INSTITUTES OF HEALTH, HEALTH AND HUMAN SERVICES, DEPARTMENT OF","cfda_number":"93.847","cfda_objectives":"(1) To promote extramural basic and clinical biomedical research that improves the understanding of the mechanisms underlying disease and leads to improved preventions, diagnosis, and treatment of diabetes, digestive, and kidney diseases.  Programmatic areas within the National Institute of Diabetes and Digestive and Kidney Diseases include diabetes, digestive, endocrine, hematologic, liver, metabolic, nephrologic, nutrition, obesity, and urologic diseases.  Specific programs areas of interest include the following: (a)  For diabetes, endocrine, and metabolic diseases areas:  Fundamental and clinical studies including the etiology, pathogenesis, prevention, diagnosis, treatment and cure of diabetes mellitus and its complications; Normal and abnormal function of the pituitary, thyroid, parathyroid, adrenal, and other hormone secreting glands; Hormonal regulation of bone, adipose tissue, and liver; on fundamental aspects of signal transduction, including the action of hormones, coregulators, and chromatin remodeling proteins; Hormone biosynthesis, secretion, metabolism, and binding; and on hormonal regulation of gene expression and the role(s) of selective receptor modulators as partial agonists or antagonists of hormone action; and Fundamental studies relevant to metabolic disorders including membrane structure, function, and transport phenomena and enzyme biosynthesis; and basic and clinical studies on the etiology, pathogenesis, prevention, and treatment of inherited metabolic disorders (such as cystic fibrosis).  (b)  For digestive disease and nutrition areas:  Genetics and genomics of the GI tract and its diseases; Genetics and genomics of liver/pancreas and diseases; Genetics and genomics of nutrition; genetics and genomics of obesity; Bariatric surgery; Clinical nutrition research; Clinical obesity research; Complications of chronic liver disease; Fatty liver disease; Genetic liver disease; HIV and liver; Cell injury, repair, fibrosis and inflammation in the liver; Liver cancer; Liver transplantation; Pediatric liver disease; Viral hepatitis and infectious diseases; Gastrointestinal and nutrition effects of AIDS; Gastrointestinal mucosal and immunology; Gastrointestinal motility; Basic neurogastroenterology; Gastrointestinal development; Gastrointestinal epithelial biology; Gastrointestinal inflammation; Digestive diseases epidemiology and data systems;  Nutritional epidemiology and data systems; Autoimmune liver disease; Bile, Bilirubin and cholestasis; Bioengineering and biotechnology related to digestive diseases, liver, nutrition and obesity; Cell and molecular biology of the liver; Developmental biology and regeneration; Drug-induced liver disease; Gallbladder disease and biliary diseases; Exocrine pancreas biology and diseases; Gastrointestinal neuroendocrinology; Gastrointestinal transport and absorption; Nutrient metabolism; Pediatric clinical obesity; Clinical trials in digestive diseases; Liver clinical trials; Obesity prevention and treatment; and Obesity and eating disorders.   (c)  For kidney, urologic and hematologic diseases areas:  Studies of the development, physiology, and cell biology of the kidney; Pathophysiology of the kidney; Genetics of kidney disorders; Immune mechanisms of kidney disease; Kidney disease as a complication of diabetes; Effects of drugs, nephrotoxins and environmental toxins on the kidney; Mechanisms of kidney injury repair; Improved diagnosis, prevention and treatment of chronic kidney disease and end-stage renal disease; Improved approaches to maintenance dialysis therapies; Basic studies of lower urinary tract cell biology, development, physiology, and pathophysiology; Clinical studies of bladder dysfunction, incontinence, pyelonephritis, interstitial cystitis, benign prostatic hyperplasia, urolithiasis, and vesicoureteral reflux; Development of novel diagnostic tools and improved therapies, including tissue engineering strategies, for urologic  disorders;Research on hematopoietic cell differentiation; metabolism of iron overload and deficiency; Structure, biosynthesis and genetic regulation of hemoglobin; as well as Research on the etiology, pathogenesis, and therapeutic modalities for the anemia of inflammation and chronic diseases. \r\n(2)  To encourage basic and clinical research training and career development of scientists during the early stages of their careers.  The Ruth L. Kirschstein National Research Service Award (NRSA) funds basic and clinical research training, support for career development, and the transition from postdoctoral biomedical research training to independent research related to diabetes, digestive, endocrine, hematologic, liver, metabolic, nephrologic, nutrition, obesity, and urologic diseases. (3)  To expand and improve the Small Business Innovation Research (SBIR) program.  The SBIR Program aims to increase and facilitate private sector commercialization of innovations derived from Federal research and development; to enhance small business participation in Federal research and development; and to foster and encourage participation of socially and economically disadvantaged small business concerns and women-owned small business concerns in technological innovation. (4)  To utilize the Small Business Technology Transfer (STTR) program.  The STTR Program intends to stimulate and foster scientific and technological innovation through cooperative research and development carried out between small business concerns and research institutions; to foster technology transfer between small business concerns and research institutions; to increase private sector commercialization of innovations derived from Federal research and development; and to foster and encourage participation of socially and economically disadvantaged small business concerns and women-owned small business concerns in technological innovation.","cfda_obligations":"(Grant) FY 24$1,673,951,000.00; FY 25$1,704,164,000.00; FY 26 est $111,289,000.00; - The amounts above are the total Project Grants, NRSA and SBIR/STTR awards. The Project Grants and NRSA awards include Type 1 Diabetes funds and exclude TAPS.  The SBIR/STTR awards include Type 1 Diabetes funds.(Cooperative Agreement) FY 24$297,521,000.00; FY 25$339,002,000.00; FY 26 est $0.00; - ","cfda_popular_name":"","cfda_title":"Diabetes, Digestive, and Kidney Diseases Extramural Research","cfda_website":"http://www2.niddk.nih.gov","federal_action_obligation_amount":372067.0,"non_federal_funding_amount":0.0,"sam_website":"https://sam.gov/fal/ed40658522e6457eb7e4239eaa67ff76/view","total_funding_amount":372067.0}],"transaction_obligated_amount":372067.0,"funding_agency":{"id":830,"has_agency_page":true,"toptier_agency":{"name":"Department of Health and Human Services","code":"075","abbreviation":"HHS","slug":"department-of-health-and-human-services"},"subtier_agency":{"name":"National Institutes of Health","code":"7529","abbreviation":"NIH"},"office_agency_name":"NIH National Institute of Diabetes and Digestive and Kidney Diseases"},"awarding_agency":{"id":830,"has_agency_page":true,"toptier_agency":{"name":"Department of Health and Human Services","code":"075","abbreviation":"HHS","slug":"department-of-health-and-human-services"},"subtier_agency":{"name":"National Institutes of Health","code":"7529","abbreviation":"NIH"},"office_agency_name":"NIH National Institute of Diabetes and Digestive and Kidney Diseases"},"period_of_performance":{"start_date":"2025-09-07","end_date":"2027-03-31","last_modified_date":"2026-09-04"},"recipient":{"recipient_hash":"1ea4dd83-c77b-a514-8ad3-ce40fe97fb01-R","recipient_name":"ALEUTIAN THERAPEUTICS, INC.","recipient_uei":"E797SLBJB9F1","recipient_unique_id":null,"parent_recipient_hash":null,"parent_recipient_name":null,"parent_recipient_uei":null,"parent_recipient_unique_id":null,"business_categories":["Category Business","Small Business"],"location":{"location_country_code":"USA","country_name":"UNITED STATES","state_code":"CA","state_name":"CALIFORNIA","city_name":"LOS ANGELES","county_code":"037","county_name":"LOS ANGELES","address_line1":"1730 SAWTELLE BLVD PH 9","address_line2":null,"address_line3":null,"congressional_code":"36","zip4":"6177","zip5":"90025","foreign_postal_code":null,"foreign_province":null}},"executive_details":{"officers":[{"name":null,"amount":null},{"name":null,"amount":null},{"name":null,"amount":null},{"name":null,"amount":null},{"name":null,"amount":null}]},"place_of_performance":{"location_country_code":"USA","country_name":"UNITED STATES","county_code":null,"county_name":null,"city_name":null,"state_code":"CA","state_name":"CALIFORNIA","congressional_code":null,"zip4":null,"zip5":null,"address_line1":null,"address_line2":null,"address_line3":null,"foreign_province":null,"foreign_postal_code":null},"total_outlay":176862.72,"funding_opportunity":{"number":"PA-23-232","goals":"NOT APPLICABLE"}}