2023-11-16T23:02:16-06:00 2022-12-31 WITHUMSMITHBROWNPC 601 CALIFORNIA STREET SUITE 1800 SAN FRANCISCO CA 94108 990 2022-01-01 465727883 Grace Science Foundation % GRACE SCIENCE FOUNDATION GRAC 6507464591 873 SANTA CRUZ AVENUE SUITE 200 MENLO PARK CA 94025 MATTHEW R WILSEY PRESIDENT 6507464591 2023-11-16 true MATTHEW R WILSEY XXX-XX-XXXX Rebecca Stidham P01406582 4154343744 2 2022 2023-04-26 12:10:37Z X MATTHEW R WILSEY 873 SANTA CRUZ AVENUE SUITE 200 MENLO PARK CA 94025 1236228 false X www.gracescience.org X 2014 CA SEE PART III LINE 1 7 7 0 0 0 0 1325647 1206450 0 0 1466 29778 0 0 1327113 1236228 885550 967948 0 0 0 0 0 0 0 227582 250534 1113132 1218482 213981 17746 3128030 3183591 29929 51224 3098101 3132367 X THE MISSION OF THE FOUNDATION IS TO SUPPORT AND FUND THE DEVELOPMENT OF LIFE-SAVING TREATMENT FOR PATIENTS THAT ARE DEFICIENT IN THE N-GLYCANESE ENZYME AND THOSE SUFFERING FROM RELATED GENETIC DISEASES. THE ACTIVITIES OF THE FOUNDATION WILL INVOLVE PROVIDING GRANT FUNDING TO HOSPITALS AND MEDICAL RESESARCH FACILITIES WHICH ARE CONDUCTING MEDICAL RESEARCH IN VARIOUS FIELDS RELATING TO THE SEARCH FOR UNDERSTNADING AND TREATMENT OF THIS CONDITION, FOSTERING COLLABORATION BETWEEN ACADEMIA, RESEARCH INSTITUTIONS, HOSPITALS, PRIVATE COMPANIES, AND GOVERNMENTAL AGENCIES. false false 298348 298348 THE Charles River Laboratories Team has imported and is maintaining a colony of Ngly1 knockout rats for use in evaluating therapies to treat NGLY1 Deficiency. This knockout model has been a key foundation to test adeno-associated virus (AAV)-mediated gene delivery for rescue of disease-associated phenotypes and has supported an investigational new drug (IND) application to the FDA for an NGLY1 Deficiency gene therapy clinical study. Team has also conducted a study to monitor clinical phenotypes and collect biological samples in homozygous mutant and heterozygous (carrier) NGLY1 knockout rats across the lifespan from birth to eighteen months of age. 133374 133374 The Scripps Research Institute (Bollong Lab) Team is testing the ability of small molecule modulators of the transcriptional regulators NRF1 (NFE2L1) and NRF2 (NFE2L2) for the rescue of phenotypic changes associated with NGLY1 Deficiency. The team has identified NRF1 modulating compounds that protect NGLY1 knockout cells from proteasomal stress and has been characterizing their activity. In addition, a potent and selective brain penetrant NRF2 modulating compound has been identified and is being characterized and formulated for in vivo testing. These compounds establish a proof of concept for NGLY1 Deficiency therapy development based on NRF1/2 modulation. 132178 132178 The T. David Gladstone Institute (Finbeiner Lab) Team has imported and is analyzing cellular phenotypes in a neuronal model of NGLY1 Deficiency to define disease mechanisms for the design and testing of candidate therapies. The team has been using robotic microscopy to investigate phenotypic differences in an NGLY1 mutant human neural cell line following differentiation from neural precursor cells to mature neurons. The team is using genetically encoded biosensors to monitor cell viability, mitochondrial shape and dynamics, proteasomal activity, autophagy flux, protein aggregation and NRF1-dependent transcriptional activity. The goal is to identify cellular changes that can be used to assess or screen for candidate drugs that can correct cellular changes caused by NGLY1 Deficiency. 114390 114390 The University of Texas SW Medical Center (Yan Lab 55000 55000 The New York Stem Cell Foundation 49110 49110 Boston's Children's Hospital (Yu Lab) 48500 48500 Albert Einstein's College of Medicine-Kaushik Lab 37934 37934 Hilltop Lab Animals, Inc. 25367 25367 Baylor College of Medicine (Jafar-Nejad Lab) 23872 23872 Purdue University 16998 16998 University of Houston 12500 12500 The Regents of the University of California 8552 8552 Qiagen, LLC 5098 5098 Transnetyx 2300 2300 Genetic Alliance 1978 1978 BPS Bioscience 1360 1360 Reveal Bioscience 1000 1000 The Jackson Laboratory 89 89 Luna PBC, Inc. 404048 404048 967948 true true false false false false false false false false false false false false false false false false false false false false false false false false false true false false false false false false false false false false false false false false false false false false true 4 0 true 0 false false false false false false false false false false false false X 7 7 true false false false false true false false false false false true false false false false false false false CA X X GRACE SCIENCE FOUNDATION 6507464591 873 SANTA CRUZ AVENUE SUITE 200 MENLO PARK CA 94025 X X Matthew Wilsey President 0.0 0.0 X X 0 0 0 Egon Durban Chief Financial Officer 0.0 0.0 X X 0 0 0 KEN DRAZAN Secretary 0.0 0.0 X X 0 0 0 Pete Briger Director 0.0 0.0 X 0 0 0 Chelsea Clinton Director 0.0 0.0 X 0 0 0 J Taylor Crandall Director 0.0 0.0 X 0 0 0 Elle Stephens Director 0.0 0.0 X 0 0 0 0 0 0 0 false false false KEVIN LEE 415 CENTRAL PARK WEST 7D NEW YORK NY 10025 CONSULTING 101332 1 1206450 1206450 0 29778 29778 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1236228 29778 967948 967948 0 0 0 0 0 0 0 0 0 0 11298 11298 12600 12600 0 0 0 139219 139219 8041 8041 2395 2395 1597 1597 0 0 61828 61828 0 791 791 0 0 0 970 970 SHIPPING FEES 6891 6891 REIMBURSABLE EXPENSES 4904 4904 1218482 967948 250534 0 381790 186218 2745587 2996735 0 0 0 0 0 0 0 0 0 0 0 0 653 638 0 0 0 0 0 0 0 0 0 0 0 0 3128030 3183591 29929 51224 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 29929 51224 X 0 0 0 0 0 0 3098101 3132367 3128030 3183591 17746 16520 X false false false X 1157365 1522789 1447474 1325647 1206450 6659725 0 0 1157365 1522789 1447474 1325647 1206450 6659725 2407154 4252571 20581 6706 1466 29778 58531 0 0 6718256 0.63299 0.64835 X RESTRICTED RESTRICTED RESTRICTED RESTRICTED RESTRICTED RESTRICTED RESTRICTED RESTRICTED CHARLES RIVER LABORATORIES 251 BALLARDVALE STREET WILMINGTON MA 01887 298348 NGLY1 CALIBR 11119 N TORREY PINES LA JOLLA CA 92037 133374 NGLY1 (BOLLONG LAB) THE T DAVID GLADSTONE INSTITUTE 1650 OWENS STREET SAN FRANCISCO CA 94158 132178 NGLY1 (FINKBEINER LAB) THE UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTE 5323 HARRY HINES BLVD DALLAS TX 75390 114390 NGLY1 (YAN LAB) NEW YORK STEM CELL FOUNDATION INC 619 W 54TH ST NEW YORK NY 10019 202905531 55000 NGLY1 BOSTON CHILDREN'S HOSPITAL 300 LONGWOOD AVENUE BOSTON MA 02115 49110 NGLY1 (YU LAB) ALBERT EINSTEIN COLLEGE OF MEDICINE 1300 MORRIS PARK AVENUE BRONX NY 10461 48500 NGLY1 (KAUSHIK LAB) HILLTOP LAB ANIMALS INC 131 HILLTOP DR SCOTTDALE PA 15683 37934 NGLY1 BAYLOR COLLEGE OF MEDICINE ONE BAYLOR PLAZA BCM 200 HOUSTON TX 77030 741613278 25367 NGLY1 (JAFAR-NEJAD LAB) PURDUE UNIVERSITY 610 PURDUE MALL WEST LAFAYETTE IN 47907 23872 NGLY1 UNIVERSITY OF HOUSTON 4800 CALHOUN ROAD HOUSTON TX 77204 16998 NGLY1 THE REGENTS OF THE UNIVERSITY OF CALIFORNIA 1111 FRANKLIN ST OAKLAND CA 94607 12500 NGLY1 QIAGEN LLC 19300 GERMANTOWN ROAD GERMANTOWN MD 20874 8552 NGLY1 TRANSNETYX 8110 Cordova Rd Ste 119 CORDOVA TN 38016 5098 NGLY1 Part I Description of Procedure for Monitoring Use of Funds * BEFORE FUNDING A PRINCIPAL INVESTIGATOR, THE FOUNDATION REQUIRES A DETAILED PROPOSAL WITH OBJECTIVES AND MILESTONES. * THE PROPOSALS ARE REVIEWED BY THE FOUNDATION AND SCIENTIFIC ADVISORY BOARD. * THE PROPOSALS ARE OFTEN REVISED SEVERAL TIMES TO GET THE CORRECT FIT. * Once funded, each principal investigator submits a written summary every quarter. * This update is two to three pages in length. * The reports discuss progress, highlight roadblocks and identify where they need help. *THE FOUNDATION STEPS-IN WHERE APPROPRIATE TO MAKE SURE OBJECTIVES AND MILESTONES ARE MET. * IN ADDITION TO QUARTERLY REPORTS, THE FOUNDATION HOLDS A MONTHLY CONFERENCE CALL WHERE TWO TO THREE PRINCIPAL INVESTIGATORS PRESENT THEIR LATEST WORK. * BEYOND THE ABOVE TWO INITIATIVES, THE FOUNDATION HOLDS ONE TO TWO IN-PERSON MEETINGS PER YEAR. * DR. KEVIN LEE (CHIEF SCIENTIFIC OFFICER), DR. SELINA DWIGHT (PROGRAM MANAGER), AND MATT WILSEY(PRESIDENT) CONTACT RESEARCHERS AND PRINCIPAL INVESTIGATORS ON A REGULAR BASIS VIA EMAIL, PHONE, OR ONE ON ONE MEETINGS. THE PRESIDENT ENSURES THAT EVERY DOLLAR IS USED TO SUPPORT THE GRACE SCIENCE FOUNDATION'S MISSION. PART II: THE FOUNDATION REQUESTS AND OBTAINS TO THE BEST OF THEIR ABILITY THE FEIN'S FROM ORGANIZATIONS IT PROVIDES GRANT FUNDING. FORM 990, PART III, LINE 4D, OTHER PROGRAM SERVICES THE UNIVERISTY OF TEXAS SOUTHWESTERN MEDICAL CENTER (YAN LAB) Team continues work generating and characterizing several mouse models of NGLY1 Deficiency, including models in which the gene is inactivated in certain tissues and conditionally after birth. These mouse models have allowed them to characterize neurological phenotypes including neuronal loss, neuropathological changes, inflammation, sensory and motor defects, and disease associated biomarkers, all of which are also observed in NGLY1 Deficiency patients These animal models provide a foundation for testing candidate therapies, including gene therapies and small molecule drugs. The team has also found that NGLY1 Deficiency in mice triggers a specific innate immune pathway mediated by the cGAS/STING pathway. Using genetic and pharmacological approaches, the team has uncovered three different targets that can be modulated to reduce disease associated phenotypes and improve survival. suggest potential targets for candidate therapy development. EXPENSES $114,390. INCLUDING GRANTS OF $114,390. REVENUE $0. FORM 990, PART III, LINE 4D, OTHER PROGRAM SERVICES THE NEW YORK STEM CELL FOUNDATION Team has developed and validated four additional patient-derived induced pluripotent stem cell (iPSC) lines to complement and expand human cell models of NGLY1 Deficiency. CRISPR-mediated genome editing was used to produce isogenic control lines to establish disease-specific characteristics. Team has further used these iPSC lines to generate human neuronal models of NGLY1 Deficiency and has characterized NGLY1-dependent neuronal phenotypes including changes in cellular architecture, mitochondrial function, intracellular aggregates, neuronal activity, and patterns of gene expression. Team has tested whether these pathologies can be reversed by restoring NGLY1 function or blocking oxidative stress-induced cell death. EXPENSES $55,000. INCLUDING GRANTS OF $55,000. REVENUE $0. FORM 990, PART III, LINE 4D, OTHER PROGRAM SERVICES THE BOSTON CHILDREN'S HOSPITAL (YU LAB) Team is developing tools and resources to determine whether knockdown of the gene FBXO6 (F-box gene 6) can rescue phenotypic consequences associated with NGLY1 Deficiency. The team established a cellular assay system to test the ability of anti-sense oligonucleotides (ASOs) to knockdown FBXO6 and designed and tested a series of candidate ASOs. The team identified a series of ASOs that inhibit FBXO6 by >75% and initiated studies to assess their activity to block FBXO6 function in cells. These studies set the stage for subsequent research to test rescue of NGLY1-associated phenotypes in cellular and in vivo systems. EXPENSES $49,110. INCLUDING GRANTS OF $49,110. REVENUE $0. FORM 990, PART III, LINE 4D, OTHER PROGRAM SERVICES THE ALBERT EINSTEIN COLLEGE OF MEDICINE (KAUSHIK LAB) Team is testing the hypothesis that defects in NGLY1 function leads to the impairment of cellular proteostasis pathways that recognize and clear misfolded and aggregated proteins and defective organelles. Using NGLY1 knockout rat and mouse tissues, NGLY1 mutant cell lines, and NGLY1 Deficiency patient fibroblasts, the team has observed significant impairment in macro- and chaperone mediated-autophagy and defects in lysosomal biogenesis. These results highlight the potential of drugs that target the autophagy-lysosome pathway to reverse cellular defects associated with NGLY1 Deficiency. The team has begun evaluating drug-like chemical modulators of the autophagy-lysosomal system for their ability to reduce cellular proteotoxicity in NGLY1 deficiency models. EXPENSES $48,500. INCLUDING GRANTS OF $48,500. REVENUE $0. FORM 990, PART III, LINE 4D, OTHER PROGRAM SERVICES THE HILLTOP LAB ANIMALS, INC. Team has imported and established a colony of Ngly1 knockout mice for use in testing therapies to treat NGLY1 Deficiency. A breeding colony has been established, and mutant phenotypes have been characterized. This model system has been used to test drug candidates for their ability to rescue NGLY1 Deficiency-associated neurological symptoms and for genetic studies to test whether blocking other pathways (including FBXO6) has potential to treat NGLY1 Deficiency. EXPENSES $37,934. INCLUDING GRANTS OF $37,934. REVENUE $0. FORM 990, PART III, LINE 4D, OTHER PROGRAM SERVICES THE BAYLOR COLLEGE OF MEDICINE (JAFAR-NEJAD LAB) Team continues genetic and pharmacological studies to gain insights into pathways regulated by NGLY1 and potential targets for therapy development. This research has uncovered a link between NGLY1 and AMP-regulated kinase (AMPK) a critical cellular energy sensor. AMPK activity is reduced in animal models of NGLY1 Deficiency and in patient cell lines. Restoring AMPK levels or activity by genetic or pharmacological tools restores energy homeostasis in NGLY1 deficient cells and organisms. Team is researching the mechanisms and cellular contexts of AMPK regulation by NGLY1 and testing potential therapies to reverse AMPK-associated pathologies in NGLY1 Deficiency. EXPENSES $25,367. INCLUDING GRANTS OF $25,367. REVENUE $0. FORM 990, PART VI, SECTION A, LINE 2: THE PRESIDENT OF THE FOUNDATION HAS IMMATERIAL OWNERSHIP INTEREST, IN THE IVNESTMENTS OF FORTRESS AND SILVERLAKE, WHICH ARE MANAGED BY TWO OF THE DIRECTORS. FORM 990, PART VI, SECTION A, LINE 7A: THE PRESIDENT OF THE FOUNDATION HAS AUTHORITY TO ELECT ONE OR MORE MEMBERS OF THE GOVERNING BODY. FORM 990, PART VI, SECTION A, LINE 8A: THE GOVERNING BODY OF THE FOUNDATION DID NOT MEET DURING THE YEAR. FORM 990, PART VI, SECTION A, LINE 8B: THE FOUNDATION DOES NOT HAVE ANY COMMITTEES. FORM 990, PART VI, SECTION B, LINE 11B: PRIOR TO FILING FORM 990, THE FOUNDATION'S PRESIDENT WILL REVIEW THE FORM. FORM 990, PART VI, SECTION C, LINE 18: AVAILABLE UPON REQUEST. FORM 990, PART VI, SECTION C, LINE 19: AVAILABLE UPON REQUEST. FORM 990 PART IX LINE 11G DESCRIPTION:CONSULTING TOTAL FEES:139219