2019-05-15T16:33:00-05:00 2018-12-31 942682998 OUM & CO LLP 601 CALIFORNIA STREET SUITE 1800 SAN FRANCISCO CA 94108 990 2018-01-01 465727883 GRACE SCIENCE FOUNDATION GRAC 4152557666 235 KANSAS STREET SUITE 200 SAN FRANCISCO CA 94103 MATTHEW R WILSEY PRESIDENT 4152557666 2019-05-15 1 BRADFORD WEISERT P00044664 4154343744 38.122.223.90 2019-05-15 13:42:10 PD P DA39A3EE5E6B4B0D3255BFEF95601890AFD80709 B2956A4CF5B6977AD3DAA1C1E57949EE5A3782BF 2018 2019-02-21 02:37:17Z MATTHEW R WILSEY 235 KANSAS STREET SUITE 200 SAN FRANCISCO CA 94103 1204078 0 X WWW.GRACESCIENCE.ORG X 2014 CA 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. 7 7 0 10 0 0 1651481 1187802 0 0 0 12186 25626 0 1677107 1199988 696567 898851 0 0 0 0 0 0 0 223947 175213 920514 1074064 756593 125924 2109224 2196374 16500 0 2092724 2196374 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 RESEARCH FACILITIES WHICH ARE CONDUCTING MEDICAL RESEARCH IN VARIOUS FIELDS RELATING TO THE SEARCH FOR UNDERSTANDING AND TREATMENT OF THIS CONDITION, AND FOSTERING COLLABORATION BETWEEN ACADEMIA, RESEARCH INSTITUTIONS, HOSPITALS, PRIVATE COMPANIES, AND GOVERNMENTAL AGENCIES. 0 0 255345 250000 STANFORD UNIVERSITY (BERTOZZI LAB) - TEAM BEGAN INVESTIGATING A POSSIBLE ROLE FOR FERROPTOSIS AND OXIDATIVE STRESS IN THE PATHOLOGIES ASSOCIATED WITH NGLY1 DEFICIENCY. THESE FINDINGS TOUCH ON KNOWN PATHWAYS AND COULD THEREFORE INFORM POTENTIAL THERAPEUTIC STRATEGIES. ADDITIONALLY, THE TEAM MADE SIGNIFICANT PROGRESS ON A FLUOROGENIC PROBE TO DETECT NGLY1 ACTIVITY IN LIVE CELLS THAT DOES NOT REQUIRE THE CELLS TO BE GENETICALLY ENGINEERED. THE TEAM ALSO DEVELOPED A FIRST VERSION OF NGLY1-TURBOID, A SYSTEM DESIGNED TO IDENTIFY NGLY1 INTERACTORS AND POTENTIAL SUBSTRATES. THIS IS CRITICAL TO UNCOVERING PROTEINS INVOLVED IN NGLY1 FUNCTION AS WELL AS ADDITIONAL PROTEINS, LIKE NFE2L1, THAT NGLY1 MAY REGULATE THROUGH DEGLYCOSYLATION. SUCH PROTEINS COULD SERVE AS POTENTIAL TARGETS FOR A SMALL COMPOUND THERAPEUTIC AND COULD PROVIDE ESSENTIAL INSIGHT INTO NGLY1 BIOLOGY. 170966 165621 SALK INSTITUTE FOR BIOLOICAL SCIENCES (GAGE LAB) - TEAM GENERATED NEURONS FROM THE INDUCED PLURIPOTENT STEM CELLS (IPSCS) OF NGLY1 DEFICIENT PATIENTS TO CHARACTERIZE THEIR FUNCTIONAL CHANGES COMPARED WITH CONTROL SAMPLES. THEY DISCOVERED NEURITIC BEADING IN PATIENT NEURONS, A HALLMARK OF NEURONAL TOXICITY IN SEVERAL PATHOGENIC CONDITIONS. THEY ALSO OBSERVED THE PRESENCE OF PROTEIN AGGREGATES AND REDUCED SYNAPTIC ACTIVITY IN PATIENT CELLS COMPARED WITH CONTROLS. IN ADDITION TO NEURONS, THE TEAM ALSO DERIVED GLIAL PROGENITOR CELLS (GPCS) FROM IPSCS AND DID NOT OBSERVE THE FUNCTIONAL DEFECTS IN PRIMARY ASTROCYTES AS FOUND IN NEURONS. THESE DISCOVERIES IDENTIFIED PHENOTYPES THAT CAN BE LEVERAGED FOR HIGH-THROUGHPUT DRUG SCREENS AND PROVIDE INSIGHT AS TO THE CELL TYPES AFFECTED BY THE DISEASE IN PATIENTS. 128395 123050 MASSACHUSETTS GENERAL HOSPITAL (RUVKUN LAB) - TEAM CONTINUED THEIR ANALYSIS OF THE GENETIC MODIFIERS OF PROTEASOME DYSFUNCTION THEY PREVIOUSLY IDENTIFIED IN PNG-1 / NGLY1 DEFICIENT C. ELEGANS. THIS LED TO THE IDENTIFICATION OF A SPECIFIC PATHWAY WHOSE DISRUPTION APPEARS BENEFICIAL TO PROTEASOME DYSFUNCTION IN NGLY1 DEFICIENT ANIMALS, A FINDING THAT COULD TRANSLATE INTO A POTENTIAL THERAPY FOR THE DISEASE IN HUMANS. THEY ALSO DEMONSTRATED NGLY1 UNIQUELY ALLOWS EDITING OF THE UNDERLYING CODING SEQUENCE OF A GENE AT THE POST-TRANSLATIONAL LEVEL TO INFLUENCE THE ACTIVITY OF ONE OF ITS SUBSTRATES, THE KEY TRANSCRIPTIONAL REGULATOR SKN-1A / NFE2L1. ADDITIONALLY, THE TEAM DEMONSTRATED THAT SKN-1A/NFE2L1 IS ACTIVATED BY MISFOLDED PROTEINS, A FINDING WITH POTENTIAL RELEVANCE TO NEURODEGENERATIVE DISEASES. COLLECTIVELY, THESE RESULTS WERE SUBMITTED TO TWO SEPARATE, INFLUENTIAL JOURNALS. 113085 107740 UNIVERSITY OF TEXAS SOUTHWESTERN (YAN LAB) - TEAM TESTED SEVERAL COMPOUNDS THAT ARE KNOWN TO ACTIVATE A SPECIFIC PROTEIN INVOLVED IN THE RESPONSE TO OXIDATIVE STRESS FOR RESCUE OF DEFECTS IN NGLY1 DEFICIENT CELLS. THEY FOUND SULFORAPHANE (SFN) COULD SUBSTANTIALLY RESCUE INNATE IMMUNE SIGNALING AND MITOPHAGY DEFECTS AND IMPROVE MITOCHONDRIAL MORPHOLOGY AND HOMEOSTASIS. SFN TREATMENT OF PREGNANT NGLY1 -/- MICE ALSO SHOWED PARTIAL RESCUE OF EMBRYONIC LETHALITY, PROVIDING A PRECLINICAL STUDY OF THE DRUG IN MICE. THROUGH A GENETIC APPROACH, THE TEAM GENERATED EVIDENCE THAT NGLY1 DEFICIENCY TRIGGERS THE STING-DEPENDENT INNATE IMMUNE SENSING PATHWAY IN MOUSE EMBRYONIC STEM CELLS. THE TEAM ALSO GENERATED A TAMOXIFEN INDUCIBLE NGLY1 KO MOUSE MODEL THAT CAN BE USED FOR A VARIETY OF PURPOSE, FOR INSTANCE THE STUDY OF DISEASE PHENOTYPES, BIOMARKER EVALUATION, AND GENE THERAPY PROOF OF CONCEPT EXPERIMENTS. 65345 60000 UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL (GAO LAB) - TEAM CONSTRUCTED THREE DIFFERENT RAAV VECTORS CONTAINING THE HUMAN NGLY1 (HNGLY1) TRANSGENE FOR CHARACTERIZATION OF THEIR DELIVERY AND EXPRESSION IN MICE TO UNDERSTAND THE EFFECTS OF OVEREXPRESSING HNGLY1 AND EVALUATE THE SAFETY OF DELIVERING HNGLY1 USING RAAV. THEY QUANTIFIED THE PRESENCE OF THE RAAV VECTOR GENOME AND HNGLY1 IN THE VARIOUS MOUSE TISSUES (INCLUDING LIVER, HIPPOCAMPUS, CORTEX, AND CEREBELLUM) AND DID NOT OBSERVE ANY DELETERIOUS EFFECTS ON THE MICE. THESE EXPERIMENTS ARE IMPORTANT PROOF OF CONCEPT EXPERIMENTS FOR AN NGLY1 GENE THERAPY APPROACH AS THEY DEMONSTRATED SUCCESSFULLY DELIVERY OF HNGLY1 USING DIFFERENT CONFIGURATIONS OF A RAAV VECTOR AND A LACK OF TOXICITY TO THE ANIMAL. 55345 50000 THE JACKSON LABORATORY (CAT LUTZ) - THE TEAM GENERATED A TRANSGENIC MOUSE EXPRESSING HUMAN NGLY1 IN A CONDITIONAL CRE-DEPENDENT MANNER, SHOWING IT COULD RESCUE THE MOUSE EMBRYONIC LETHALITY PHENOTYPE OF AN NGLY1 DEFICIENT MOUSE MODEL. THEY ALSO DEMONSTRATED A DOUBLE NGLY -/- / ENGASE -/- KNOCKOUT IS PARTIALLY VIABLE FOR A CERTAIN ALLELE OF NGLY1 AND BEGAN DEEP PHENOTYPIC ANALYSIS OF THESE MICE TO DETERMINE WHETHER THEY EXHIBIT ANY PATHOLOGIES. IF SO, THESE MICE COULD BE A USEFUL MODEL FOR TESTING POTENTIAL THERAPIES THAT COULD REVERSE PATHOLOGIES ASSOCIATED WITH NGLY1 DEFICIENCY (SINCE THE SINGLE KNOCKOUT MOUSE IS EMBRYONIC LETHAL). LASTLY, THE TEAM GENERATED SEVERAL TISSUE-SPECIFIC CONDITIONAL KNOCK-IN CLINICAL ALLELES OF NGLY1 TO HELP UNDERSTAND WHICH TISSUES ARE IMPORTANT IN THE DISEASE PATHOLOGY. 147783 142440 OTHER PROGRAM SERVICES ARE RELATED TO RESEARCH AND DEVELOPMENT TO UNDERSTAND AND CURE CARE DISEASES BEGINNING WITH NGLY1 DEFICIENCY. 381558 360180 936264 1 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 1 5 0 0 0 0 0 0 0 0 0 0 0 0 X 7 7 1 0 0 0 0 1 0 0 0 0 0 0 1 0 0 0 0 0 0 0 CA X X GRACE SCIENCE FOUNDATION 4152557666 235 KANSAS STREET SUITE 200 SAN FRANCISCO CA 94103 X MATTHEW WILSEY PRESIDENT 20.00 X X 0 0 0 EGON DURBAN CHIEF FINANCIAL OFFICER 1.00 X X 0 0 0 KEN DRAZAN SECRETARY 1.00 X X 0 0 0 PETE BRIGER DIRECTOR 1.00 X 0 0 0 CHELSEA CLINTON DIRECTOR 1.00 X 0 0 0 J TAYLOR CRANDALL DIRECTOR 1.00 X 0 0 0 ELLE STEPHENS DIRECTOR 1.00 X 0 0 0 0 0 0 0 0 0 0 0 1187802 30437 1187802 5825 5825 10451 4090 6361 6361 6361 1199988 0 0 12186 861351 861351 37500 37500 12413 12413 4275 4275 81250 81250 8760 8760 12086 861 11225 41991 36552 5439 955 955 BRANDING/LOGO/VIDEO/WEB 13150 13150 OTHER FEES (BANK, CREDI 173 173 FILING FEES 160 160 1074064 936264 137800 0 2109224 2192300 4074 2109224 2196374 16500 0 16500 0 X 0 0 0 0 2092724 2196374 2092724 2196374 2109224 2196374 125924 -22274 0 X 0 0 0 X 664490 1560381 600124 1677107 1157365 5659467 664490 1560381 600124 1677107 1157365 5659467 1760433 3899034 5659467 X PART II AND LINE 13 GRACE SCIENCE FOUNDATION WAS FORMED ON MAY 19, 2014. 2018 IS THE FOUNDATION'S FIFTH YEAR OF EXISTENCE. 0 0 0 0 0 0 0 0 0 CANADA NGYL1 WORK IN MOFFAT'S LABS AT UNIVERSITY OF TORONTO 37500 CHECK 1 0 0 0 0 0 0 1 PERLARA PBC 6000 SHORELINE CT SUITE 204 S SAN FRANCISCO CA 94080 100000 ASSAY DEVELOPMENT & COMPOUND SCREENING STANFORD UNIVERSITY 3145 PORTER DRIVE PALO ALTO CA 94304 941156365 501(C)(3) 268187 NGLY1 WORK IN BERTOZZI/SNYDER/STEINMETZ LABS & NATURAL HISTORY PROTOCOL DEVELOPMENT BROAD INSTITUTE 415 MAIN STREET CAMBRIDGE MA 02142 263428781 501(C)(3) 39050 CMAP STUDY & GENETIC SEQUENCING BAYLOR COLLEGE OF MEDICINE 1102 BATES AVENUE SUITE 48002 HOUSTON TX 77030 741613878 501(C)(3) 178158 NGLY1 WORK IN JAFAR-NEJAD LAB SALK INSTITUTE FOR BIOLOGICAL STUDIES 10010 N TORREY PINES ROAD LA JOLLA CA 92037 952160097 501(C)(3) 124215 NGLY1 WORK IN GAGE LAB THE JACKSON LABORATORY 600 MAIN STREET BAR HARBOR ME 04609 010211513 501(C)(3) 50000 NGLY1 WORK WITH CAT LUTZ UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL 55 LAKE AVENUE NORTH WORCESTER MA 01655 043167352 501(C)(6) 30000 NGLY1 WORK IN GAO LAB UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER 5323 HARRY HINES BLVD DALLAS TX 75390 756002868 501(C)(6) 71741 NGLY1 WORK IN YAN LAB 7 1 PART I, LINE 2: * 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. X 3 30437 FAIR MARKET VALUE 0 0 0 FORM 990, PART VI, SECTION A, LINE 2 THE PRESIDENT OF THE FOUNDATION HAS IMMATERIAL OWNERSHIP INTEREST, IN THE INVESTMENTS OF FORTRESS AND SILVER LAKE, 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 FROM 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.