Spero

ADVANCED HUMAN ON A CHIP SYSTEMS FOR DRUG DISCOVERY

DEVELOPMENT OF SPR206, A DIRECT ACTING POLYMYXIN ANTIBIOTIC WITH REDUCED NEPHROTOXICITY, TO TREAT MULTIDRUG-RESISTANT GRAM-NEGATIVE BACTERIAL PATHOGENS

MODULATORY ROLE OF BLOOD-BRAIN-BARRIER AND ENZYMATIC ACTIVITY IN AN INNOVATIVE HUMAN MODEL OF CHOLINERGIC DRUG INDUCED DEMENTIA - PROJECT SUMMARY/ABSTRACT THE BURDEN ASSOCIATED WITH POLYPHARMACY AND INAPPROPRIATE DRUG USE IS THE THIRD LEADING CAUSE OF DEATH IN THE USA. WITH ADVANCED AGE, PROVIDING MEDICAL CARE CAN PRESENT CHALLENGES AS THESE PATIENTS ARE AT RISK FOR COMORBIDITIES AND HAVE THE LARGEST BURDEN OF ILLNESS. THERE IS THE UNMET NEED OF HAVING PROPER APPROACHES AND INNOVATIVE TOOLS TO IDENTIFY NOT ONLY DRUGS BUT ALSO DRUG REGIMENS ASSOCIATED WITH THE HIGHEST RISK OF DRUG-RELATED ADVERSE EVENTS (ADES). MEDICATIONS WITH ANTICHOLINERGIC PROPERTIES HAVE FREQUENTLY BEEN CITED IN THE LITERATURE AS A MAJOR CAUSE FOR AN INCREASE IN ADES. THE RESULTING PRESCRIPTION CASCADE INCREASES THE RISK OF MULTI-DRUG INTERACTIONS ON ENZYMATIC SYSTEMS (SUCH AS THE CYTOCHROME P450 SUPERFAMILY) USED TO METABOLIZE MANY DRUGS WITH ANTICHOLINERGIC PROPERTIES. HENCE, INNOVATIVE APPROACHES AND TOOLS DEVELOPED TO ADDRESS THESE SITUATIONS SHOULD CONSIDER NOT ONLY INDIVIDUAL DRUG PHARMACOLOGICAL PROPERTIES BUT ACCOUNT FOR CONDITIONS ASSOCIATED WITH THE IMPACT OF MULTI-DRUG INTAKE AND INTERACTIONS. WE SEEK TO USE HESPEROS’ PATENTED MULTI-ORGAN FUNCTIONAL SYSTEMS TO INVESTIGATE DRUG-INDUCED DEMENTIA AND ALZHEIMER’S DISEASE (AD) IN TERMS OF DEFICITS IN BASIC INFORMATION PROCESSING IN THE PRESENCE OF ANTICHOLINERGIC DRUGS IN COLLABORATION WITH TABULA RASA HEALTHCARE (TRHC) AND OUR AD CONSULTANT, DR. DAVE MORGAN AT MSU. TRHC HAS CREATED BASIC AND CLINICAL ALGORITHMS THAT HELP QUANTITATIVELY SCORE THE RISK OF ADES, INCLUDING AN ASSESSMENT OF DRUG ANTICHOLINERGIC PROPERTIES AND MULTI- DRUG INTERACTIONS, WITH A SPECIAL LOOK AT COMPETITIVE INHIBITION. INCREASED KNOWLEDGE ON THESE FACTORS THROUGH THE CONDUCT OF PROPOSED STUDIES WITH HESPEROS’S EXPERIMENTAL SYSTEMS SHALL IMPROVE THE PREDICTIVITY OF RISK STRATIFICATION POSSIBILITIES, HELP DECREASE THE RISK OF ADES IN ELDERLY PATIENTS, DECREASE HOSPITALIZATIONS, AND REDUCE OVERALL MEDICAL COSTS. THE VALUE OF TRHC’S CDSS AND RISK STRATIFICATION STRATEGY HAS BEEN DEMONSTRATED BY PUBLICATIONS IN PEER-REVIEW JOURNALS AND FILING OF THREE PATENTS. THERE ARE FEW IN VITRO MODELS THAT EXAMINE ANTICHOLINERGIC DRUG PROPERTIES IN THE CNS WHILE ASSESSING THEIR ASSOCIATION BETWEEN ANTICHOLINERGIC BURDEN AND RISK OF DEMENTIA, INCLUDING AD. THUS, A PRECLINICAL SCREENING MODEL BASED ON FUNCTIONAL ASSAYS COMPOSED OF NORMAL AND AD MUTANT HUMAN CELLS TO EVALUATE THE EFFECTS OF ANTICHOLINERGIC DRUGS IN CONDITIONS MIMICKING ASPECTS OF AD ENABLES A PLATFORM FOR UNDERSTANDING MULTIPLICATIVE EFFECTS AND TO INFORM TRHC’S PHARMACOKINETIC/PHARMACODYNAMIC CLINICAL MODELS. NO OTHER MODELS ASSESSING THE ANTI-CHOLINERGIC BURDEN OF DRUGS TAKE INTO ACCOUNT THEIR DOSE, DURATION OF TREATMENT AND CONCOMITANT DRUG ADMINISTRATION LEADING TO A CHANGE IN THEIR DISPOSITION. CHANGES IN LONG-TERM POTENTIATION WILL BE USED AS THE COGNITIVE READOUT AS IT IS A FUNCTIONAL MEASUREMENT KNOWN TO CORRELATE WITH CHANGES IN MEMORY AND LEARNING. THE INTEGRATION OF THIS NEURONAL MODULE WITH A SYSTEM THAT INCLUDES A BLOOD-BRAIN-BARRIER AND A LIVER WITH FUNCTIONAL ENZYMATIC SYSTEMS WOULD ALLOW TESTING OF COMBINATIONAL THERAPEUTICS AND VARIABILITY IN THEIR METABOLIC DISPOSITION DUE TO EXPECTED MULTI-DRUG INTERACTIONS IMPACTING DRUG METABOLISM SYSTEMS AS OBSERVED IN PATIENTS WITH POLYPHARMACY.

HUMAN ON A CHIP SYSTEMS TO INVESTIGATE DISEASE COMORBIDITIES COMMON IN THE AGED POPULATION

FUNCTIONAL INTEGRATED HUMAN-ON-A-CHIP SYSTEMS FOR ALZHEIMER'S RESEARCH

BALLOON OVERTUBE ACCESS DEVICE FOR IMPROVED INTERVENTIONAL ENDOSCOPY IN THE UPPER GI - PROJECT SUMMARY – ASPERO MEDICAL IS DEVELOPING AN INNOVATIVE, HIGHLY FLEXIBLE BALLOON OVERTUBE ACCESS DEVICE (BOAD) TO INCREASE THE ADOPTION AND SAFETY OF ENDOSCOPIC SUBMUCOSAL DISSECTION (ESD) AND IMPROVE ENDOSCOPIC MUCOSAL RESECTION (EMR) IN THE UPPER GASTROINTESTINAL (GI) TRACT. CLINICALLY, ESD IS A RAPIDLY EMERGING APPROACH THAT IS PREFERRED OVER EMR FOR THE REMOVAL OF CANCEROUS AND PRECANCEROUS LESIONS IN THE UPPER GI (I.E., ESOPHAGUS AND STOMACH) BECAUSE IT OFFERS A HIGHER EN BLOC RESECTION RATE (91.7% VS. 46.7%), A HIGHER R0 RESECTION RATE (80.3% VS. 42.3%), AND A MUCH LOWER RECURRENCE RATE (0.9% VS. 12.2%). DESPITE THESE ADVANTAGES, LONGER PROCEDURE TIME, HIGHER RISK OF PERFORATION, AND TECHNICAL CHALLENGES OF USING THE REQUIRED TOOLS LEADS MANY INTERVENTIONAL ENDOSCOPISTS TO CHOOSE THE EASIER EMR TECHNIQUE OVER THE SUPERIOR ESD TECHNIQUE. THIS DISCONNECT BETWEEN CLINICAL BENEFIT AND CLINICAL PRACTICE PRESENTS AN OPPORTUNITY TO DRAMATICALLY IMPROVE PATIENT CARE BY INCREASING THE ADOPTION OF A WELL-ESTABLISHED, EVIDENCE-BASED TECHNIQUE THROUGH A NEW ENABLING DEVICE. IN THIS DIRECT-TO-PHASE II SBIR, ASPERO PROPOSES TO DESIGN AND TEST THE BOAD TO INCREASE THE ADOPTION OF ESD, COMPLETING DEVELOPMENT THROUGH PRECLINICAL TESTING AND DESIGN FREEZE, IN PREPARATION FOR VERIFICATION AND VALIDATION AND ULTIMATELY SUBMISSION OF A 510(K) APPLICATION FOR FDA CLEARANCE. THIS PROJECT BUILDS ON ASPERO’S PRIOR WORK, WHICH DEMONSTRATED AN INNOVATIVE PILLAR TEXTURED BALLOON OVERTUBE REDUCES SLIPPAGE DURING ENDOSCOPY PROCEDURES IN THE SMALL BOWEL, INCREASING ENDOSCOPE STABILITY. THE PROJECT ALSO BUILDS ON ASPERO’S INNOVATIVE C-TUBE DEVICE, WHICH IS THE FIRST COLONOSCOPY TOOL TO INCORPORATE AN ADDITIONAL WORKING CHANNEL WITH ROTATIONAL AND POSITIONAL CONTROL FOR THE USE OF A SECOND TOOL. ADAPTING THESE INNOVATIONS FOR USE IN THE UPPER GI AND COMBINING THEM WITH INTEGRATED HANDLE CONTROLS IS EXPECTED TO DELIVER A DEVICE THAT MITIGATES THE DISADVANTAGES OF ESD AND INCREASES ADOPTION OF THE PROCEDURE TO IMPROVE PATIENT OUTCOMES. AIM 1. PRODUCE AN INTEGRATED BALLOON AND OVERTUBE SHAFT DESIGN WITH INDEPENDENT WORKING CHANNEL AND USER-DEFINED HANDLE CONTROLS FOR UPPER GI USE. MILESTONE: DELIVER A DEVICE WITH INTEGRATED HANDLE CONTROLS THAT ACCOMMODATES MULTIPLE ENDOSCOPE SIZES, STABILIZES THE SURGICAL FIELD, INCORPORATES A SECOND WORKING CHANNEL FOR CONCURRENT TOOL USE, ALLOWS FOR INDEPENDENT ROTATION OF THE OVERTUBE AND ENDOSCOPE, AND INCORPORATES MICRO-POSITIONAL CONTROLS FOR A TOOL IN THE SECOND WORKING CHANNEL. AIM 2. ADVANCE BOAD TO DESIGN FREEZE IN PREPARATION FOR VERIFICATION, VALIDATION, AND FDA SUBMISSION. MILESTONES: CONFIRM USER ACCEPTANCE AND CLINICAL UTILITY OF THE DEVICE IN AN IN VIVO SIMULATED USE ANALYSIS. IMPACT—AT COMPLETION OF THIS PROJECT, ASPERO WILL BE POSITIONED TO THEN COMPLETE VERIFICATION AND VALIDATION TESTING OF THE BOAD THROUGH PHASE IIB AND/OR EXTERNAL SUPPORT, WHICH WILL FACILITATE 510(K) SUBMISSION. REAL-WORLD USE IS EXPECTED TO REDUCE ESD PROCEDURE TIME, REDUCE THE RISK OF PERFORATIONS, AND INCREASE ADOPTION BY INTERVENTIONAL ENDOSCOPISTS. INCREASED ADOPTION OF ESD IS EXPECTED TO REDUCE THE RECURRENCE RATE FOR LESIONS IN THE UPPER GI, RESULTING IN INCREASED OVERALL AND PROGRESSION-FREE SURVIVAL.

HUMAN NEUROMUSCULARJUNCTION PLATFORM TO EVALUATE BOTULINUM TOXIN POTENCY

MICRO-TEXTURED BALLOONS WITH IMPROVED TRACTION FOR BETTER CONTROL IN ENDOSCOPY - PROJECT SUMMARY ASPERO MEDICAL HAS DEVELOPED A MICRO-TEXTURED BALLOON WITH REDUCED SLIPPAGE FOR USE WITH ALL STANDARD ENDOSCOPES FOR GASTROINTESTINAL ENDOSCOPY. THE CURRENTLY USED SMOOTH BALLOONS ARE PRONE TO SLIPPAGE THAT REDUCES THE SUCCESS RATE OF ENDOSCOPIC PROCEDURES, WHICH INCREASES THE NUMBER OF PROCEDURES AND CONTRIBUTES AN ESTIMATED $100–300 MILLION IN EXCESS COSTS FOR PATIENTS AND INSURERS EACH YEAR. IN A PHASE I SBIR (1R43DK126504), ASPERO OPTIMIZED THE BALLOON DESIGN FOR PERFORMANCE AND SCALABILITY. THE COMPANY SUBSEQUENTLY FINALIZED MANUFACTURING CONTROLS, COMPLETED AN FDA 510(K) PRE-SUBMISSION MEETING, AND PREPARED A 510(K) APPLICATION FOR FDA REVIEW. IN CONSULTATION WITH CLINICAL ADVISORS, OTHER CLINICIANS, AND KEY OPINION LEADERS IN THE FIELD, ASPERO DETERMINED THAT SUCCESSFUL ADOPTION OF THE DEVICE (ASPERO ANCORA)—AND THE RESULTING BENEFICIAL IMPACT ON PROCEDURE SUCCESS RATE AND PATIENT COSTS—WILL REQUIRE CLINICAL EVIDENCE OF SUPERIORITY COMPARED TO WELL-KNOWN, ESTABLISHED DEVICES THAT ARE ALREADY ON THE MARKET. THEREFORE, IN THIS PHASE II APPLICATION, ASPERO PROPOSES A MULTI-SITE, RANDOMIZED, DOUBLE-MASKED CLINICAL STUDY TO ESTABLISH THE SUPERIORITY OF ASPERO ANCORA VS. THE OLYMPUS ST-SB1. THE STUDY WILL COMPARE PROCEDURE SUCCESS RATES IN THE MIDDLE THIRD OF THE SMALL BOWEL. SUCCESS RATES IN THIS PORTION OF THE BOWEL WITH CURRENT DEVICES, INCLUDING THE OLYMPUS OVERTUBE, ARE ESTIMATED TO BE ABOUT 50%. MARKET RESEARCH INDICATES CLINICIANS WOULD CONSIDER AN INCREASE FROM 50% TO 60% TO BE CLINICALLY VALUABLE AND SUFFICIENT GROUNDS FOR SWITCHING TO A NEW DEVICE. HOWEVER, BASED ON THE PERFORMANCE OF ANCORA IN ANIMAL STUDIES, ASPERO ANTICIPATES A SUCCESS RATE OF AT LEAST 75%, AND THE PROPOSED STUDY IS POWERED BASED ON THIS EXPECTATION. NOTABLY, THE PROPOSED STUDY WOULD BE THE FIRST COMPARATIVE BALLOON STUDY IN WHICH THE CLINICIAN IS MASKED TO THE IDENTITY OF THE DEVICE. AIM. DEMONSTRATE SUPERIORITY OF THE ASPERO ANCORA BALLOON OVERTUBE COMPARED TO THE OLYMPUS ST-SB1 BALLOON OVERTUBE. THE STUDY WILL INCLUDE 110 CONSENTING PATIENTS WITH LESIONS IN THE MIDDLE THIRD OF THE SMALL BOWEL (PREVIOUSLY CONFIRMED BY VIDEO CAPSULE ENDOSCOPY). THESE INDIVIDUALS WILL BE RANDOMIZED TO RECEIVE ENTEROSCOPY WITH THE ANCORA OR ST-SB1 BALLOON OVERTUBE, WHICH WILL BE ORALLY INSERTED AND REMOVED BY A STUDY ASSISTANT TO MASK THE SURGEON TO THE DEVICE IDENTITY. THE PRIMARY OUTCOME OF INTEREST IS SUCCESS IN IDENTIFYING THE LESION, WHICH INDICATES SUFFICIENT BALLOON CONTROL TO REACH AND VISUALIZE THE SITE. SUPERIORITY OF THE ANCORA BALLOON OVERTUBE WILL BE DEMONSTRATED IF IT ACHIEVES A SUCCESS RATE OF 75% COMPARED TO A SUCCESS RATE OF 50% WITH THE OLYMPUS ST-SB1 BALLOON OVERTUBE. IMPACT—DEMONSTRATION OF SUPERIORITY OF ASPERO ANCORA IS NECESSARY FOR ADOPTION BY CLINICIANS. BROAD ADOPTION IS EXPECTED TO IMPROVE PROCEDURE SUCCESS RATES, REDUCE TIME TO DIAGNOSIS OR TREATMENT (THEREBY, IMPROVING PATIENT OUTCOMES), AND REDUCE THE BURDEN AND COSTS OF CARE FOR PATIENTS, PROVIDERS, AND INSURERS.

RECYCLABLE THERMOSET POLYMERS FROM LIGNIN DERIVED PHENOLS

BIODISTRIBUTION AND PK MODELING OF RAT VS. HUMAN SYSTEMS

DEVELOPMENT OF AN INTEGRATED 4-ORGAN ANIMAL MODEL

HLS-DEVELOPMENT OF A CARDIAC ISCHEMIA MODEL IN AN ORGAN-ON-A-CHIP PLATFORM - PROJECT SUMMARY OUR OVERALL STRATEGY FOR HESPEROS IS TO UTILIZE MICROPHYSIOLOGICAL SYSTEMS IN COMBINATION WITH FUNCTIONAL READOUTS TO ESTABLISH PLATFORMS CAPABLE OF SOPHISTICATED ANALYSIS OF CHEMICALS AND DRUG CANDIDATES FOR TOXICITY AND EFFICACY DURING PRE-CLINICAL TESTING, WITH INITIAL EMPHASIS ON PREDICTIVE TOXICITY. THIS IS A SERVICE BASED COMPANY AND IS DEVELOPING LOW-COST IN VITRO SYSTEMS UTILIZING A NOVEL “PUMPLESS” MICROPHYSIOLOGICAL PLATFORM DESCRIBED IN US PATENT 8,748,180B2. THE COMMERCIALIZATION POTENTIAL OF OUR SYSTEM HAS BEEN VALIDATED BY THE AWARD OF A PHASE IIB SBIR TO APPLY ADVANCED MANUFACTURING TECHNIQUES TO INCREASE OUTPUT AND LOWER COST OF PRODUCTION. THE PUMPLESS INTEGRATED SYSTEM, USING A ROCKING MOTION TO PUMP THE SERUM-FREE CELLULAR MEDIUM, REDUCES THE COMPLEXITY AND COST OF THE FLUIDIC CIRCUIT DESIGN AND SIMPLIFIES SET-UP AND OPERATION OF THE DEVICE. HICKMAN HAS DEVELOPED MICROELECTRODE ARRAYS AND CANTILEVER SYSTEMS THAT ARE INTEGRATED ON CHIP FOR NONINVASIVE ELECTRONIC AND MECHANICAL READOUTS. WE HAVE DETAILED AN IN VITRO CARDIAC SYSTEM WHERE THE TWO MAIN COMPONENTS OF FUNCTION, ELECTRICAL CONDUCTION AND MUSCLE FORCE, HAVE BEEN REPRODUCED IN VITRO. THE INDEPENDENT MEASUREMENT OF THESE TWO KEY VARIABLES ALLOWS A DETAILED DESCRIPTION OF A COMPOUND’S EFFECT ON OVERALL CARDIAC FUNCTION AND IS CURRENTLY BEING USED UNDER CONTRACT BY MULTIPLE COMPANIES. BECAUSE WE CAN MEASURE THESE FUNCTIONAL OUTPUTS INDEPENDENTLY, WE CAN ALSO USE THESE READOUTS TO GIVE IDEAS ON MECHANISM OF ACTION OF A COMPOUND. WE HAVE ADAPTED THIS CHIP BASED SYSTEM INTO A PLATFORM FOR TESTING CARDIAC ISCHEMIA AND REPERFUSION AS PUBLISHED IN APL BIOENGINEERING THAT DEMONSTRATED AN INVESTIGATIONAL COMPOUND EFFECTIVELY REDUCED ISCHEMIA/REPERFUSION DAMAGE IN VITRO. THE HUMAN IPSC CARDIAC CELLS USED IN THIS DEVICE WERE SHOWN TO REACH SOME ASPECTS OF FUNCTIONAL MATURATION AS PRIMARILY EVIDENCED BY PATCH CLAMP ELECTROPHYSIOLOGICAL MEASUREMENTS INDICATING RESTING MEMBRANE POTENTIALS OF -85 MV OR BETTER. WE WILL EXPAND THIS SYSTEM BY INTEGRATING A HEMODYNAMIC MODULE OF VASCULAR SMOOTH MUSCLE CELLS AND MICROVASCULAR ENDOTHELIAL CELLS WITH THE MICROFLUIDIC SYSTEM AND DEVELOP CONTINUOUS MONITORING INSTRUMENTATION. THIS CARDIAC ORGAN-ON-A-CHIP PLATFORM WILL BE VALIDATED BY SCREENING COMPOUNDS THAT ACT EITHER DIRECTLY ON THE CARDIAC CELLS OR AFFECT HEMODYNAMICS, AND WILL BE USED TO SCREEN INVESTIGATIONAL COMPOUNDS FROM OUR PHARMA PARTNERS. A MICROPHYSIOLOGICAL SYSTEM WILL BE DEVELOPED WITH CONTINUOUS READOUTS FOR SMOOTH MUSCLE CELL CONTRACTION, CARDIAC ELECTRICAL AND MECHANICAL FUNCTION, FITTED WITH ENVIRONMENTAL SENSORS, AND INTEGRATED WITH AN ENVIRONMENTAL CHAMBER FOR INDUCING ISCHEMIA. WE WILL FIRST OPTIMIZE AND VALIDATE ENVIRONMENTAL CONDITIONS AND PROTOCOLS FOR INDUCING AND MEASURING CARDIAC ISCHEMIC DAMAGE, FOLLOWED BY VALIDATION WITH ISCHEMIA DRUGS WITH PUBLISHED IN VIVO AND IN VITRO RESULTS. THE UNIQUENESS WILL BE THE COMBINATION OF HICKMAN’S FUNCTIONAL MODULES WITH SHULER’S “PUMPLESS” SYSTEM, AS WELL AS CONTINUOUS MEASUREMENT OF BOTH CARDIAC AND HEMODYNAMIC EFFECTS. OUR TEAM CONTAINS ALL OF THE SKILL SETS REQUIRED TO CONSTRUCT, EVALUATE AND COMMERCIALIZE THE INTEGRATED SYSTEM AND ASSOCIATED COMPONENTS TO ACHIEVE THE GOALS.

DEVELOPMENT OF COMPOUNDS THAT EXPAND THE SPECTRUM OF ANTIBACTERIAL AGENTS AGAINST KEY MULTIDRUG RESISTANT GRAM-NEGATIVE PATHOGENS

SBIR PHASE II: ADVANCED BALLOON ENDOSCOPY OVERTUBE

SPERLU SELECTIVE PROCESS FOR EFFICIENT REMOVAL OF LIGNIN AND UPGRADING

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SELECTIVE CATALYSIS FOR ONE-STEP LIGNOCELLULOSE DELIGNIFICATION AND LIGNIN VALORIZATION TO HIGH VALUE METHOXYPHENOLS

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A NOVEL GYRASE INHIBITOR FOR THE TREATMENT OF DRUG-SUSCEPTIBLE AND MULTIDRUG-RESISTANT MYCOBACTERIUM TUBERCULOSIS INFECTIONS

SEE NOTICE OF AWARD, ATTACHMENT 1 - TERMS AND CONDITIONS, ATTACHMENT D - STATEMENT OF WORK, ABSTRACT

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PURPOSE: TO PROMOTE ECONOMIC REVITALIZATION AND COMMUNITY DEVELOPMENT THROUGH INVESTMENT IN AND FINANCIAL ASSISTANCE TO COMMUNITY DEVELOPMENT FINANCIAL INSTITUTIONS (CDFIS). PLANNED ACTIVITIES: FINANCIAL ASSISTANCE MUST BE USED FOR FINANCIAL PRODUCTS, FINANCIAL SERVICES (REGULATED INSTITUTIONS ONLY), DEVELOPMENT SERVICES, LOAN LOSS RESERVES, AND CAPITAL RESERVES (REGULATED INSTITUTIONS ONLY), IN AN ELIGIBLE MARKET OR THE RECIPIENT’S APPROVED TARGET MARKET. END GOALS: THE GOAL OF THE FINANCIAL ASSISTANCE IS FOR CDFIS TO BUILD THEIR FINANCIAL CAPACITY TO LEND TO ELIGIBLE MARKETS AND/OR THEIR TARGET MARKETS, IN ORDER TO SERVE RURAL AND URBAN LOW INCOME PEOPLE, AND COMMUNITIES ACROSS THE NATION THAT LACK ADEQUATE ACCESS TO AFFORDABLE FINANCIAL PRODUCTS AND FINANCIAL SERVICES. BENEFICIARIES: PROFIT ORGANIZATION, PRIVATE NONPROFIT INSTITUTION/ORGANIZATION, OTHER PRIVATE INSTITUTION/ORGANIZATION INVESTMENT AREAS AND TARGETED POPULATIONS, AS DEFINED IN 12 C.F.R. 1805. SUBRECIPIENTS: THERE ARE NO SUBRECIPIENTS FOR THIS PROGRAM. BROADBAND: SPECIFIC ACTIVITIES RELATING TO BROADBAND USAGE ARE NOT KNOWN AT THE TIME OF AWARD. REASON/PURPOSE OF MODIFICATION: THE RIEGLE ACT (P.L. 103 325), THE STATUTE WHICH AUTHORIZES THE CDFI PROGRAM, REQUIRES THAT FINANCIAL ASSISTANCE AWARDS, INCLUDING BASE FINANCIAL ASSISTANCE (BASE FA), DISABILITY FUNDS FINANCIAL ASSISTANCE (DF FA), AND PERSISTENT POVERTY COUNTIES FINANCIAL ASSISTANCE (PPC FA), BE MATCHED WITH FUNDS FROM NON FEDERAL GOVERNMENT SOURCES AND COMPARABLE IN FORM AND VALUE TO THE FA AWARD. MODIFICATIONS WOULD BE REQUIRED IF THERE IS A CHANGE IN THE FORM AND/OR AMOUNT ORIGINALLY OBLIGATED FOR THE AWARD, BASED ON APPROVED MATCHING FUNDS. NOTE: MATCHING FUNDS ARE REQUIRED ONLY FOR ORGANIZATIONS APPLYING AS CATEGORY II/CORE FA APPLICANTS UNDER THE CDFI PROGRAM. MATCHING FUNDS ARE NOT REQUIRED FOR ANY NATIVE CDFI APPLICANTS OR HOUSING PRODUCTION FINANCIAL ASSISTANCE AWARDS (HP FA). ADDITIONALLY, MATCHING FUNDS ARE NOT REQUIRED FOR SMALL AND EMERGING CDFI ASSISTANCE (SECA) FA APPLICANTS AND HEALTHY FOOD FINANCING INITIATIVES (HFFI) FA APPLICANTS, PENDING FINAL FY 2025 APPROPRIATIONS LANGUAGE.

HUMAN ON A CHIP SYSTEM TO INVESTIGATE GENETIC RISK FACTORS IN ALZHEIMER'S DISEASE

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MICRO-TEXTURED BALLOONS WITH IMPROVED TRACTION FOR BETTER CONTROL IN ENDOSCOPY

INTEGRATION OF A KIDNEY MODULE INTO A 4-ORGAN HUMAN-ON-A-CHIP SYSTEM.

SBIR PHASE I: MANUFACTURING OF NATURAL ISOEUGENOL AND FERULATE FROM NON-FOOD BIOMASS AS A PRECURSOR TO BIOBASED VANILLIN.

HLS-DEVELOPMENT OF A CARDIAC ISCHEMIA MODEL IN AN ORGAN-ON-A-CHIP PLATFORM

SBIR PHASE I: ADVANCED BALLOON ENDOSCOPY OVERTUBE

SBIR PHASE I: SELECTIVE CATALYTIC HYDRODEOXYGENATION (HDO) OF WOOD BIOMASS TO MARKET DRIVEN HIGH VALUE PHENOLIC CHEMICALS

HIGH-PERFORMING BIORENEWABLE MICRONUTRIENTS FOR AGRICULTURAL APPLICATIONS