{"id":270370359,"generated_unique_award_id":"ASST_NON_R44AG097355_075","fain":"R44AG097355","uri":"R44AG097355-3714970453","category":"grant","type":"04","type_description":"PROJECT GRANT (B)","description":"HUMAN IPSC NEURAL SPHEROIDS TO SCREEN FOR COMPOUNDS THAT BLOCK TAU PROPAGATION - RESEARCH & RELATED OTHER PROJECT INFORMATION NOVORON BIOSCIENCE, INC. 7. PROJECT SUMMARY APPROXIMATELY 6.9 MILLION PEOPLE AGED 65 AND OLDER IN THE UNITED STATES HAVE ALZHEIMER’S DEMENTIA (AD).1,2 AD AND OTHER DEMENTIAS ARE A MAJOR ECONOMIC BURDEN EXPECTED TO COST $360 B IN 2024, OF WHICH $231 B WILL BE FUNDED THROUGH MEDICARE AND MEDICAID.3 THERE IS AN URGENT NEED TO IDENTIFY AND DEVELOP DISEASE-MODIFYING THERAPEUTICS AS CURRENT THERAPIES ONLY ADD 0.65 QUALITY-ADJUSTED LIFE YEARS AND COST $130,000 PER YEAR.4,5 TAUOPATHIES, INCLUDING AD, EXHIBIT PRION-LIKE NEURON-TO-NEURON TRANSSYNAPTIC PROPAGATION OF TAU.6 HERE, WE PROPOSE A PLATFORM-BASED STRATEGY TO EVALUATE NOVEL THERAPIES DESIGNED TO INHIBIT THE PROPAGATION AND AGGREGATION OF PATHOLOGICAL TAU. AS PART OF THIS PLATFORM, WE WILL USE LRP1 (AN ESTABLISHED MODEL KNOWN TO INFLUENCE TAU PROPAGATION) WT AND KO HUMAN INDUCED PLURIPOTENT STEM CELL (HIPSCS) DERIVED NEURAL ORGANOIDS TO CONFIRM THAT OUR SYSTEM ACCURATELY DETECTS CHANGES IN TAU PROPAGATION. THIS ROBUST, MULTI-FACETED PLATFORM WILL ENABLE THE IDENTIFICATION AND VALIDATION OF CANDIDATES THAT DISRUPT TAU PATHOLOGY, PROVIDING A PATH TOWARD NEW TREATMENTS FOR AD AND OTHER TAUOPATHIES. OUR TEAM AND OTHERS HAVE SHOWN THAT ORGANOIDS GENERATED FROM HIPSCS SERVE AS A SCALED-DOWN AND THREE- DIMENSIONAL MODEL OF THE HUMAN BRAIN, MIMICKING VARIOUS DEVELOPMENTAL FEATURES AT THE CELLULAR AND MOLECULAR LEVELS. UNLIKE ANIMAL MODELS, WHICH DO NOT ALWAYS TRANSLATE TO HUMAN UTILITY, OR OTHER IN VITRO MODELS, WHICH CANNOT CAPTURE THE COMPLEXITY OF HUMAN TISSUES, ORGANOIDS RECAPITULATE ASPECTS OF IN VIVO BRAIN DEVELOPMENT AND FUNCTION IN A DISH. ORGANOIDS ARE RECOGNIZED FOR THEIR USEFULNESS AS A TRANSLATIONALLY VALID ORGAN-LEVEL PLATFORM IN THE DRUG DISCOVERY SPACE FOR COLON CANCER, CYSTIC FIBROSIS, AND PRECISION THERAPY. CORTICAL ORGANOIDS HAVE FURTHER PROVEN TO BE INFORMATIVE MODELS OF HUMAN BRAIN DEVELOPMENT, TISSUE ORGANIZATION AND CELL-CELL INTERACTIONS, AND MATURATION, SUGGESTING A LIKELY UTILITY IN THERAPEUTIC ADVANCEMENT. CORTICAL ORGANOIDS RETAIN PROPERTIES OF A NEURAL ORGAN TO A LARGE DEGREE, INCLUDING INTEGRATION OF SUPPORTING CELLS, CYTOSKELETAL STRUCTURING, CELLULAR ORGANIZATION INTO PARTICULAR REGIONS, AND IN SOME CASES, IN VIVO-LIKE SPONTANEOUS NETWORK ACTIVITY. OUR TEAM RECENTLY USED RETT SYNDROME ORGANOIDS TO IDENTIFY DONEPEZIL (APPROVED FOR AD AS ARICEPT) THAT IS NOW ENTERING A DOD-FUNDED PHASE II CLINICAL TRIAL. WE WILL CREATE LRP1 WT AND KO ORGANOIDS TO OPTIMIZE AND VALIDATE THE UTILITY OF THE ORGANOIDS IN SCREENING WITH CONTROL COMPOUNDS AND THE ABILITY OF THE EXPERIMENTAL SMALL MOLECULES TO MODULATE TAU PROPAGATION. THIS PROJECT BRINGS TOGETHER THE EXPERTISE OF NOVORON BIOSCIENCE, BRAINSTORM THERAPEUTICS, AND DEFINED BIOSCIENCE TO DEVELOP HUMAN-RELEVANT BRAIN MODELS FOR DRUG DISCOVERY. BY EMPLOYING ADVANCED HIPSC-DERIVED CORTICAL BRAIN ORGANOID TECHNOLOGIES, WE AIM TO ESTABLISH A SCALABLE, HIGH-THROUGHPUT SCREENING PLATFORM TO IDENTIFY SMALL MOLECULES THAT DISRUPT TAU-LRP1 INTERACTIONS. THE PROJECT ADDRESSES CRITICAL UNMET NEEDS IN ALZHEIMER’S DRUG DEVELOPMENT AND WILL GENERATE NEW INSIGHTS INTO TAU PATHOLOGY MECHANISMS.","subaward_count":0,"total_subaward_amount":null,"total_subsidy_cost":0.0,"total_loan_value":0.0,"total_obligation":2502765.0,"date_signed":"2025-09-16","base_and_all_options":null,"base_exercised_options":null,"non_federal_funding":0.0,"total_funding":2502765.0,"total_account_outlay":1074694.0,"total_account_obligation":2502765.0,"account_outlays_by_defc":[{"code":"Q","amount":1074694.0}],"account_obligations_by_defc":[{"code":"Q","amount":2502765.0}],"record_type":2,"cfda_info":[{"applicant_eligibility":"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 for-profit and nonprofit), and individuals. National Research Service Award: Individual NRSAs may be made for postdoctoral training to applicants who hold 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) or for predoctoral training to applicants registered for doctoral research training.  Institutional NRSAs may be made for both predoctoral and postdoctoral research training. Predoctoral awardees must have a baccalaureate degree. Applicants must be citizens of the United States or admitted for permanent residency. Individual NRSA awardees must be nominated and sponsored by a public or private nonprofit institution having staff and facilities suitable to the proposed research training.  Nonprofit domestic organizations may apply for the Institutional NRSA.  SBIR grants can be awarded only to domestic small businesses (entities that are independently owned and operated for profit, are not dominant in the field in which research is proposed, and have no more than 500 employees). Primary employment (more than one-half time) of the principal investigator must be with the small business at the time of award and during the conduct of the proposed project.  In both Phase I and Phase II, the research must be performed in the U.S. or its possessions.  STTR grants can be awarded only to domestic small business concerns (entities that are independently owned and operated for profit, are not dominant in the field in which research is proposed and have no more than 500 employees) 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 other than a fellowship must be assessed for scientific merit by a scientific review group and receive approval from a national advisory council. Individual funding opportunity announcements published in the NIH Guide provide more detail on eligibility. ","beneficiary_eligibility":"Beneficiary eligibility is the same as applicant eligibility.\nAny nonprofit or for-profit organization, company, or institution engaged in biomedical research. Students pursuing doctoral research training.","cfda_federal_agency":"NATIONAL INSTITUTES OF HEALTH, HEALTH AND HUMAN SERVICES, DEPARTMENT OF","cfda_number":"93.866","cfda_objectives":"To encourage biomedical, social, and behavioral research and research training directed toward greater understanding of the aging process and the diseases, special problems, and needs of people as they age. The National Institute on Aging has established programs to pursue these goals.  The Division of Aging Biology emphasizes understanding the basic biological processes of aging.  The Division of Geriatrics and Clinical Gerontology supports research to improve the abilities of health care practitioners to respond to the diseases and other clinical problems of older people.  The Division of Behavioral and Social Research supports research that will lead to greater understanding of the social, cultural, economic and psychological factors that affect both the process of growing old and the place of older people in society. The Division of Neuroscience fosters research concerned with the age-related changes in the nervous system as well as the related sensory, perceptual, and cognitive processes associated with aging and has a special emphasis on Alzheimer's disease. Small Business Innovation Research (SBIR) program: To expand and improve the SBIR program; to increase private sector commercialization of innovations derived from Federal research and development; to increase 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.  Small Business Technology Transfer (STTR) program: To stimulate and foster scientific and technological innovation through cooperative research 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$3,692,324,814.00; FY 25$3,731,553,875.00; FY 26 est $260,983,928.00; - Amounts shown are actual/estimated amounts available for research grants including SBIR/STTR, centers, research career awards, research project grants, and cooperative agreements. Data obligations shown are Actual Obligations for FY 2023, FY 2024 and Estimated Obligations for FY 2025.(Other Financial Assistance) FY 24$54,561,917.00; FY 25$45,910,769.00; FY 26 est $830,543.00; - Data obligations shown are Actual Obligations for FY 2023, FY 2024 and Estimated Obligations for FY 2025.","cfda_popular_name":"(Aging)","cfda_title":"Aging Research","cfda_website":"http://www.nia.nih.gov/","federal_action_obligation_amount":2502765.0,"non_federal_funding_amount":0.0,"sam_website":"https://sam.gov/fal/571e780222b243c5a70e0d375d364007/view","total_funding_amount":2502765.0}],"transaction_obligated_amount":2502765.0,"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 Insitute on Aging"},"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 Insitute on Aging"},"period_of_performance":{"start_date":"2025-09-16","end_date":"2027-05-31","last_modified_date":"2026-06-05"},"recipient":{"recipient_hash":"1cf13b02-5150-b5df-f227-2988efc33bec-R","recipient_name":"NOVORON BIOSCIENCE INC","recipient_uei":"K4L2JH8P6EE5","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":"SAN DIEGO","county_code":"073","county_name":"SAN DIEGO","address_line1":"1155 ISLAND AVE STE 100","address_line2":null,"address_line3":null,"congressional_code":"50","zip4":"7230","zip5":"92101","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":"073","county_name":"SAN DIEGO","city_name":"SAN DIEGO","state_code":"CA","state_name":"CALIFORNIA","congressional_code":"50","zip4":"7230","zip5":"92101","address_line1":null,"address_line2":null,"address_line3":null,"foreign_province":null,"foreign_postal_code":null},"total_outlay":1074694.0,"funding_opportunity":{"number":"PA-24-245","goals":"NOT APPLICABLE"}}