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DOD TRANSFER AWARDS

COVID-19 ACTION. EXPANSION OF VIAL PRODUCTION TO CREATE INDUSTRIAL BASE CAPABILITIES FOR NATIONAL DEFENSE

DOMINICAN REPUBLIC AT-RISK YOUTH INITIATIVE

THE PURPOSE IS TO INTEGRATE OPPORTUNITY YOUTH WITH STRONG LEVELS OF VULNERABILITY FROM POOR AND MARGINALIZED NEIGHBORHOODS INTO THE OPPORTUNITIES PRODUCED BY ECONOMIC GROWTH AND ADDRESS CHALLENGES DESCRIBED ABOVE, THEREBY CONTRIBUTING TO PRODUCTIVE FUTURE LIVES AND ACTIVE CITIZENSHIP. THIS REQUIRES MITIGATING, REDUCING, AND ELIMINATING ALL FACTORS WHICH CONTRIBUTE TO A YOUNG PERSON NOT BEING ABLE TO ACCESS THESE OPPORTUNITIES WITHIN THEIR COMMUNITIES AND EVENTUALLY FALLING INTO LIFESTYLES THAT LEAD TO CRIME AND VIOLENCE. COMMUNITIES THAT STRENGTHEN THEIR RESILIENCE AND REDUCE RISK FACTORS WHICH FOSTER YOUTH CRIME AND VIOLENCE ARE CRITICAL IN REDUCING THE TRADITIONAL PATTERNS OF INTERGENERATIONAL POVERTY AND RESULTING BEHAVIORS (I.E, GENDER-BASED VIOLENCE, MACHISMO, SCHOOL DESERTION, EARLY AND FORCED UNIONS, BULLYING, ETC.).

DEVELOPMENT OF METHIONYL-TRNA SYNTHETASE INHIBITORS FOR GRAM POSITIVE BACTERIAL INFECTIONS

MICRONEEDLE DELIVERY OF ZANAMIVIR FOR TREATMENT OF INFLUENZA

THIS PROJECT WILL SCALE A NEW, HIGH-PERFORMANCE BACK-CONTACT SILICON MODULE TECHNOLOGY TO FULL-SIZE RESIDENTIAL PV MODULES AND DEVELOP THE PROCESSES AND SUPPLY CHAIN TO MANUFACTURE THEM AT HIGH VOLUME.

BROAD SPECTRUM ANTIVIRAL NUCLEOSIDE PHOSPHONATE ANALOGS

PRODRUGS OF NEURAMINIDASE INHIBITORS FOR INCREASED ORAL BIOAVAILABILITY

NOVEL, SELF-APPLIED MICROARRAY PATCH (MAP) OF ZANAMIVIR FOR TREATMENT OF THE FLU - ABSTRACT YEARLY INFLUENZA EPIDEMICS STRIKE MILLIONS OF PEOPLE, CAUSING UP TO 500,000 DEATHS. FATALITY CAUSED BY MOST SEASONAL INFLUENZA VIRUSES IS <0.03%, BUT WITH SIGNIFICANT MORTALITY IN THE YOUNG AND THE ELDERLY POPULATIONS. WHEN A NEW PATHOGENIC INFLUENZA STRAIN ENTERS THE POPULATION, A PANDEMIC COULD KILL TENS OF MILLIONS OF PEOPLE WITH A NEGATIVE ECONOMIC IMPACT ESTIMATED TO BE OVER 150 BILLION DOLLARS. DUE TO THE INCOMPLETE EFFICACY OF THE CURRENT VACCINES, EFFECTIVE DRUG TREATMENT IS NECESSARY. PRESENTLY, INFLUENZA TREATMENT IS ONLY SOMEWHAT EFFECTIVE, AND SOME INFLUENZA STRAINS ARE RESISTANT TO THE CURRENTLY MARKETED THERAPEUTICS, ADAMANTANES AND THE NEURAMINIDASE INHIBITOR TAMIFLU®. HOWEVER, WHILE ZANAMIVIR (ZAN, RELENZA®) REMAINS HIGHLY ACTIVE AGAINST OSELTAMIVIR-RESISTANT INFLUENZA STRAINS, ITS THERAPEUTIC IMPACT IS SEVERELY LIMITED BY ITS ROUTE OF ADMINISTRATION, VIA ORAL INHALATION, WHICH RENDERS IT UNSUITABLE FOR PATIENTS WITH A COMPROMISED RESPIRATORY SYSTEM. THEREFORE, DEVELOPMENT OF A NOVEL DELIVERY ALTERNATIVE FOR ZAN AS WE PROPOSE HERE, IS POISED TO ADDRESS A SIGNIFICANT UNMET MEDICAL NEED. TRANSDERMAL DRUG DELIVERY OFFERS A NUMBER OF IMPROVEMENTS OVER OTHER DELIVERY SYSTEMS. THE DRUG DIRECTLY ENTERS THE SYSTEMIC CIRCULATION, CIRCUMVENTING ABSORPTION AND FIRST-PASS BARRIERS TYPICAL FOR ORAL DELIVERY. IT AVOIDS SKIN PUNCTURE BY SYRINGE NEEDLES, ELIMINATING PAIN AND PATIENT VISITS TO A CLINICIAN. TRANSDERMAL DELIVERY OF ZAN COULD ALLOW LARGE NUMBERS OF PATIENTS TO BE REACHED DURING AN INFLUENZA OUTBREAK, WHICH WILL BE PARTICULARLY IMPORTANT IN LIGHT OF THE ADDED RISK DURING THE ONGOING COVID-19 PANDEMIC. WHILE ZAN ITSELF CANNOT CROSS THE HUMAN SKIN BARRIER AT THERAPEUTIC RATES, MICROARRAY PATCH (MAP) - ENHANCED TRANSDERMAL DELIVERY IS AN ELEGANT, EFFICIENT, AND PAINLESS METHOD FOR INCREASING THE SKIN PERMEATION OF MANY DRUGS, INCLUDING ZAN. OUR NOVEL DRUG-DEVICE COMBINATION PRODUCT, TSR-066, CONSISTS OF A SWELLABLE MICRONEEDLE ARRAY, WHICH WILL CONTINUOUSLY DELIVER ZAN FROM A SPECIALLY FORMULATED RESERVOIR OVER 5 DAYS. THIS FAST-TRACK SBIR PROPOSAL WILL SUPPORT OPTIMIZATION OF THE MAP WITH A FOCUS ON THE APPLICATOR COMPONENT AND SUBSEQUENT MANUFACTURING OF SUPPLIES FOR THE PHASE I CLINICAL STUDY. WE HAVE OBTAINED AGREEMENT WITH THE FDA ON THE PRECLINICAL STUDIES NEEDED IN ORDER TO OPEN THE IND, AS WELL AS ON THE PHASE I CLINICAL DEVELOPMENT PLANS AND THE 505(B)2 REGULATORY STRATEGY. IN ADDITION TO THE EXPERIMENTAL WORK PROPOSED HERE, WE ARE DEVELOPING A ROBUST IP EXPANSION STRATEGY FOR TSR-066, AS WELL AS FUTURE PRODUCT CANDIDATES THAT STAND TO BENEFIT FROM MAP-ENABLED DELIVERY. THE END RESULT OF THIS WORK WILL BE A NOVEL, TRANSDERMAL DELIVERY APPROACH FOR ZAN, WHICH WILL EXPAND ITS REACH INTO PATIENT GROUPS FOR WHICH RELENZA® IS CONTRAINDICATED AND ALLOW FOR SIMPLE ADMINISTRATION OF ZAN FOR BOTH TREATMENT AND PREVENTION OF THE FLU. WE HAVE ASSEMBLED A TEAM OF EXPERT ADVISORS AND COLLABORATORS TO ENSURE SUCCESSFUL COMPLETION OF THIS RESEARCH PLAN.

ORAL ANTIVIRAL PRODRUGS FOR BIODEFENSE INITIATIVE

IMPROVING ABSORPTION AND TARGETING OF ANTIVIRAL DRUGS

DEVELOPMENT OF SYNTHETIC HIGH-DENSITY LIPOPROTEINS FOR TREATMENT OF SEPSIS - ENTER THE TEXT HERE THAT IS THE NEW ABSTRACT INFORMATION FOR YOUR APPLICATION. THIS SECTION MUST BE NO LONGER THAN 30 LINES OF TEXT. SEPSIS REPRESENTS A MAJOR HEALTH ISSUE, WHICH CLAIMS OVER 270,000 LIVES EACH YEAR IN THE UNITED STATES ALONE, RESULTING IN MORE THAN $23 BILLION IN HEALTH CARE COSTS. WHILE SEPSIS IS CAUSED BY BACTERIAL INFECTIONS THAT ARE TREATED WITH INTRAVENOUS (IV) ANTIBIOTICS, THE OFTEN VERY RAPID PROGRESSION INTO SEPTIC SHOCK AND ULTIMATELY ORGAN FAILURE IS A CONSEQUENCE OF AN OVERREACTION OF THE IMMUNE AND COAGULATION SYSTEM. THE PROGNOSIS FOR SEPSIS REMAINS POOR, WITH MORTALITY RATES EXCEEDING 30%, DUE TO A LACK OF EFFECTIVE TREATMENT OPTIONS. THUS FAR, EFFORTS TO THERAPEUTICALLY BLOCK ANY SINGLE STEP IN THE INFLAMMATION OR COAGULATION PATHWAYS HAVE HAD LITTLE IMPACT ON PATIENT SURVIVAL. HIGH-DENSITY LIPOPROTEIN (HDL) IS A KEY COMPONENT OF CIRCULATING BLOOD AND PLAYS ESSENTIAL ROLES IN VASCULAR ENDOTHELIAL CELL (EC) HEALTH AND BALANCE OF THE IMMUNE SYSTEM RESPONSE. CLINICAL DATA DEMONSTRATE THAT HDL LEVELS DROP BY 40-70% IN SEPTIC PATIENTS, WHICH IS ASSOCIATED WITH POOR SURVIVAL PROGNOSIS. WE AND OTHERS HAVE SHOWN THAT INFUSIONS OF SYNTHETIC HDL (SHDL) RESULT IN IMPROVED SURVIVAL IN MOUSE MODELS OF SEPSIS. PROPHYLACTIC ADMINISTRATION OF A FIRST GENERATION SHDL PRODUCT IN HUMANS SUBSEQUENTLY CHALLENGED WITH AN ENDOTOXIN INFUSION WAS SHOWN TO SUPPRESS INFLAMMATION, INHIBIT HYPOTENSION AND MARKEDLY DECREASE THE SEVERITY OF CLINICAL SYMPTOMS. THESE PRECLINICAL AND CLINICAL STUDIES INDICATE THAT REPLENISHING CIRCULATING HDL IN SEPSIS PATIENTS MAY PROVIDE AN EFFECTIVE THERAPY APPROACH, AND HDL ITSELF MAY SERVE AS A PREDICTIVE MARKER FOR PATIENT OUTCOMES. PREVIOUS SHDL CANDIDATES HAVE BEEN TESTED CLINICALLY IN SEPSIS RELEVANT SETTINGS, BUT DEVELOPMENT WAS DISCONTINUED DUE TO SAFETY CONCERNS RELATED TO PRODUCT IMPURITIES. NEWER AND SAFER VERSIONS OF SHDL HAVE BEEN DEVELOPED WHICH HAVE BEEN SHOWN TO BE SAFE IN HUMANS. WE HAVE SINCE DEVELOPED SPS-701, WITH FURTHER OPTIMIZED COMPOSITION TO MAXIMIZE ANTI- INFLAMMATORY PROPERTIES AND UTILITY FOR SEPSIS. THE OBJECTIVE OF THIS GRANT IS THEREFORE TO PERFORM THE INITIAL PRECLINICAL STUDIES AND DEVELOP THE REGULATORY STRATEGY FOR FILING AN INVESTIGATIONAL NEW DRUG (IND) APPLICATION TO ADVANCE SPS-701 TOWARDS CLINICAL EVALUATION FOR THE TREATMENT OF SEPSIS.

MICRONEEDLE DELIVERY OF TROSPIUM CHLORIDE OPTIMIZED FOR IMPROVED TOLERANCE AND PATIENT OUTCOMES IN OVERACTIVE BLADDER DISEASE - ABSTRACT OVERACTIVE BLADDER (OB) IS A DISEASE THAT AFFLICTS BOTH MEN AND WOMEN AND IS DRIVEN BY THE AGING POPULATION WITH A PREVALENCE ESTIMATED AS HIGH AS 39% IN THE US AND 45% FOR ALL WOMEN OVER 65. OB IS ACCOMPANIED WITH A SIGNIFICANT LOSS OF QUALITY OF LIFE WITH DOCUMENTED INCREASES IN FALLS, ANXIETY, AND DEPRESSION. THE MUSCARINIC ANTAGONISTS (ANTICHOLINERGICS) ARE THE PRIMARY DRUGS FOR TREATMENT, BUT THESE AGENTS ARE ASSOCIATED WITH NUMEROUS SIDE EFFECTS AND DRUG-DRUG INTERACTIONS LEADING TO DISCONTINUATION OF THERAPY IN OVER 50% OF PATIENTS IN 6-12 MONTHS. FURTHERMORE, WITH AGE THERE IS A GROWING CONCERN FOR ANTICHOLINERGIC DRUG OVERLOAD (ESPECIALLY DUE TO DRUG-DRUG INTERACTIONS) LEADING TO ADDITIONAL EFFECTS SUCH AS COGNITION IMPAIRMENT AND OTHER CNS AFFECTS. STUDIES HAVE SHOWN THAT THE PHARMACODYNAMICS EFFICACY OF MUSCARINIC ANTAGONISTS IN OB THERAPY IS STRONGLY ASSOCIATED WITH AREA UNDER THE CONCENTRATION-TIME CURVE (AUC) AND THAT THE MANY SIDE EFFECTS ARE RELATED TO MAXIMUM PLASMA CONCENTRATIONS (CMAX). OXYBUTYNIN, ONE OF THE AGENTS WITH THE MOST SIDE EFFECTS, WAS FORMULATED AS AN ADHESIVE PATCH, WHICH GREATLY REDUCED CHOLINERGIC SIDE EFFECTS DUE TO A CONSTANT EFFECTIVE DRUG CONCENTRATION. UNFORTUNATELY, THE PATCH HAD ITS OWN SIGNIFICANT SIDE EFFECTS, MAINLY SERIOUS SKIN IRRITATIONS DUE TO THE PERMEATION ENHANCERS NEEDED FOR EFFECTIVE DELIVERY. GIVEN THE VERY LARGE POPULATION AFFLICTED WITH OB, AND THE MANY OB DRUGS AND FORMULATIONS WHICH FAIL TO ADEQUATELY TREAT THE DISEASE, THERE REMAINS A DESPERATE UNMET MEDICAL NEED FOR NEW THERAPY OPTIONS. MULTIPLE ADVANTAGES OF MICRONEEDLE TRANSDERMAL DELIVERY OVER OTHER TRANSDERMAL METHODS HAVE BEEN DOCUMENTED. MORE RECENTLY, SWELLABLE HYDROGEL MICRONEEDLES (HMN) HAVE BEEN SHOWN TO BE A HIGHLY EFFICIENT AND PAINLESS METHOD FOR INCREASING THE SKIN PERMEATION OF DRUGS WITHOUT ADDITIVES, SHARPS, OR POLYMERIC MONOMERS ENTERING THE CIRCULATION. WE HAVE SELECTED TROSPIUM CHLORIDE (TC), THE OB DRUG WITH THE BEST EFFICACY AND LEAST SIDE EFFECTS, YET PLAGUED BY POOR BIOAVAILABILITY AND HIGH PHARMACOKINETIC VARIABILITY FOR DELIVERY VIA HMN. THE PRODUCT WILL BE A DRUG-FREE HMN ARRAY WITH A TC DRUG RESERVOIR TO ENABLE A TIGHTLY CONTROLLED DELIVERY OF TC, PROVIDING EFFICACIOUS AUCS WITH CONSISTENT PLASMA CONCENTRATIONS. THIS SELF-ADMINISTERED PATCH IS DESIGNED TO DELIVER TC OVER THE COURSE OF A WEEK, AND WILL BE THE FIRST OB TREATMENT WITH BOTH EXCELLENT EFFICACY, AS WELL AS HIGH PATIENT COMPLIANCE AND SATISFACTION. THE END RESULT OF THIS WORK WILL BE A NOVEL, TRANSDERMAL DELIVERY APPROACH FOR TC WITH READILY TRANSLATABLE PK, EFFICACY AND INITIAL PRECLINICAL SAFETY DATA, READY TO COMPLETE PRECLINICAL DEVELOPMENT ACTIVITIES LEADING TO THE OPENING OF AN IND. WE HAVE ASSEMBLED A TEAM OF EXPERT ADVISORS AND COLLABORATORS TO ENSURE SUCCESSFUL COMPLETION OF THIS RESEARCH PLAN.

REAP RENEWABLE ENERGY SYSTEM (RES) GRANT UNRESTRICTED AMOUNT

IN-LINE PRE-LAMINATION INSPECTION VIA NON-CONTACT ELECTROLUMINESCENCE FOR MODULE MANUFACTURING OF ADVANCED INTERCONNECT TECHNOLOGIES

NUCLEOSIDE PHOSPHONATE ANALOGS FOR THE TREATMENT OF ADENOVIRAL INFECTION

BROAD SPECTRUM ANTIVIRAL NUCLEOSIDE PHOSPHONATE ANALOGS

NOVEL PRODRUGS FOR TREATMENT OF HUMAN CMV INFECTION

CELL-PENETRATING ANTIMICROBIAL THERAPEUTICS FOR TREATMENT OF COMPLICATED SKIN AND SOFT TISSUE INFECTIONS

MICRONEEDLE DELIVERY OF ZANAMIVIR FOR TREATMENT OF INFLUENZA INFECTIONS

A NOVEL COMBINATION THERAPY TO TREAT BIOFILM-BASED PNEUMONIA INFECTIONS

WISCONSIN SMP COALITION OF WISCONSIN AGING GROUPS SENIOR MEDICARE PATROL PROJECT

WISCONSIN SMP COALITION OF WISCONSIN AGING GROUPS SENIOR MEDICARE PATROL PROJECT

CLINICAL VALIDATION OF A MIRNA BLOOD TEST TO IDENTIFY HIGH-RISK INDIVIDUALS ELIGIBLE FOR LOW-DOSE COMPUTED TOMOGRAPHY SCREENING FOR LUNG CANCER EARLY

THIS PROJECT WILL PROVIDE LEGAL REPRESENTATION TO VICTIMS 55 YEARS OF AGE OR OLDER THAT HAVE BEEN THE VICTIM OF FINANCIAL EXPLOITATION, FIDUCIARY ABUSE, SCAMS, AND IDENTITY THEFT. THE ELDER FINANCIAL EMPOWERMENT LEGAL SERVICES PROJECT WILL PROVIDE REPRESENTATION FOR VICTIMS IN COURT PROCEEDINGS IN EFFORTS TO STABILIZE THEIR LIVES THROUGH REMITTANCE EFFORTS AND BY PROTECTING REMAINING ASSETS; LEGAL REPRESENTATION IN INDIVIDUAL AT RISK RESTRAINING ORDERS PROCEEDINGS, SMALL CLAIMS ACTIONS, CHAPTER 7 BANKRUPTCY PROCEEDINGS, AND PROCEEDINGS TO REVIEW/REVOKE/RESTORE/REIMBURSE ABUSIVE FIDUCIARIES; ADVOCACY FOR VICTIM COMPENSATION; AND COLLABORATION WITH ELDER SUPPORT OFFICES AND ORGANIZATIONS STATEWIDE TO COMPLEMENT THE SERVICES EACH PROVIDES TO ENSURE THAT VICTIMS RECEIVE THE EXPERTISE AND FULL RANGE OF SERVICES THEIR CASES REQUIRE.

SPANDRELS ARE THE COMPONENTS OF COMMERCIAL BUILDING WALLS THAT EXIST BETWEEN THE VISION GLASS (WINDOWS). THESE ARE COMMONLY CONSTRUCTED OF GLASS BUT HAVE NO TECHNICAL NEED TO TRANSMIT LIGHT. INTEGRATING STATE-OF-ART SILICON PV MODULE FABRICATION INTO THIS COMPONENT IS A PRIME CANDIDATE FOR TRULY BUILDING-INTEGRATED PV. HOWEVER, THIS UNION OF KNOWN SPANDREL FABRICATION AND PV MODULE PRODUCTION HAS MANY UNKNOWNS: TECHNICAL, FINANCIAL, AND MARKET ADOPTION. THIS PROJECT SEEKS TO DERISK THESE UNKNOWNS AND PROVIDE A STRONG BASE OF MODELLING, EXPERIMENTAL DATA, AND MARKET RESEARCH TO ENABLE PRACTICAL BUSINESS DECISION FOR DEVELOPING NOT JUST A NEW PRODUCT BUT AN ENTIRELY NEW MARKET SECTOR.

NOVEL, SAFE, EFFICACIOUS HEPARIN REVERSAL - ABSTRACT ANTICOAGULANTS AND THEIR REVERSAL AGENTS ARE KEY COMPONENTS OF STANDARD OF CARE FOR MANAGING THROMBOSIS. HEPARIN IN PARTICULAR IS USED FOR THROMBOSIS PREVENTION IN MULTIPLE CLINICAL INDICATIONS, INCLUDING PROCEDURES SUCH AS CARDIOPULMONARY BYPASS AND CATHETER ABLATION, AFTER WHICH HEPARIN’S ANTICOAGULANT ACTIVITY REQUIRES PROMPT NEUTRALIZATION. IN FACT, AROUND A MILLION CLINICAL CASES ANNUALLY REQUIRE HEPARIN REVERSAL IN THE US ALONE. PROTAMINE SULFATE, THE ONLY FDA-APPROVED REVERSAL AGENT FOR HEPARIN, IS A 60-YEAR-OLD DRUG WITH A BLACK BOX WARNING. ITS CLINICAL USE IS CONSTRAINED BY TWO MAJOR LIMITATIONS: (I) REQUIREMENT OF TITRATION BECAUSE OF ITS VERY NARROW THERAPEUTIC SAFETY WINDOW; AND (II) POTENTIALLY LIFE-THREATENING HYPERSENSITIVITY REACTIONS OR ANAPHYLAXIS. THUS, THERE IS AN UNMET MEDICAL NEED TO DISCOVER NOVEL HEPARIN-REVERSAL AGENTS WITH A WIDER THERAPEUTIC WINDOW AND BETTER SAFETY PROFILE. FURTHERMORE, ALTHOUGH PROTAMINE CAN REVERSE THE ACTION OF UNFRACTIONATED HEPARIN, IT IS INEFFECTIVE IN REVERSING THE ANTICOAGULANT ACTION OF LOW MOLECULAR WEIGHT (MW) HEPARINS. THEREFORE, A NOVEL, EFFECTIVE REVERSAL AGENT WITH A SUPERIOR SAFETY PROFILE COMPARED TO PROTAMINE WOULD NOT ONLY IMPROVE CURRENT TREATMENT PARADIGMS, BUT HAS ALSO THE VERY ATTRACTIVE COMMERCIAL POTENTIAL TO EXPAND THE CLINICAL USE OF LOW MW HEPARINS AS A SAFER ALTERNATIVE TO UNFRACTIONATED HEPARIN. WE AIM TO DEVELOP A SAFER AND MORE EFFICACIOUS HEPARIN-REVERSAL DRUG TO REPLACE PROTAMINE. OUR PROPRIETARY POLYANION MODULATING DENDRIMER (POMOD) CHEMISTRY PLATFORM IS IDEAL FOR CREATING DRUGS THAT SELECTIVELY BIND AND INHIBIT RELATIVELY UNSTRUCTURED POLYANIONIC SUBSTANCES SUCH AS HEPARINS. THE PROPOSED RESEARCH WILL PROVIDE PRECLINICAL PROOF-OF-CONCEPT THAT OUR LEAD CANDIDATE, POMOD-1.1, IS A SAFE AND EFFECTIVE HEPARIN REVERSAL THERAPEUTIC WITH PROPERTIES THAT WARRANT FULL PRECLINICAL PRODUCT DEVELOPMENT. WE WILL DEMONSTRATE EFFICACY WITH INTRAVENOUS ADMINISTRATION IN RAT MODEL, AND ESTABLISH THE PHARMACOKINETIC (PK) AND PHARMACODYNAMIC (PD) RELATIONSHIP. IN ADDITION, WE WILL ASSESS THE EXPLORATORY TOXICOLOGY PROFILE OF POMOD-1.1 IN RATS. THESE DATA WILL PROVIDE AN INITIAL ESTIMATE OF THE THERAPEUTIC WINDOW. FURTHERMORE, OUR LEARNINGS FROM THIS RESEARCH CAN BE APPLIED TO THE DESIGN AND TESTING OF OTHER POMODS WHICH BIND POLYPHOSPHATE OR OTHER POLY-ANIONS WHICH ARE IMPLICATED IN SEVERAL DISEASE STATES. THE END RESULT OF THIS WORK WILL BE A NOVEL, BEST-IN-CLASS SAFE AND EFFECTIVE HEPARIN-REVERSAL AGENT TO PROVIDE SUPERIOR TREATMENT OPTIONS TO PATIENTS. WE HAVE ASSEMBLED A TEAM OF EXPERT ADVISORS AND COLLABORATORS TO ENSURE SUCCESSFUL COMPLETION OF THIS RESEARCH PLAN.

THE PURPOSE OF THIS AGREEMENT IS TO GROW NEW AND BEGINNER FAMERS AND HEALTHY COMMUNITIES ACROSS MISSISSIPPI THROUGH OUTREACH AND TRAINING.

MICRONEEDLE DELIVERY OF TROSPIUM CHLORIDE OPTIMIZED FOR IMPROVED TOLERANCE AND PATIENT OUTCOMES IN OVERACTIVE BLADDER DISEASE - ABSTRACT OVERACTIVE BLADDER (OB) IS A DISEASE THAT AFFLICTS BOTH MEN AND WOMEN AND IS DRIVEN BY THE AGING POPULATION WITH A PREVALENCE ESTIMATED AS HIGH AS 39% IN THE US AND 45% FOR ALL WOMEN OVER 65. OB IS ACCOMPANIED WITH A SIGNIFICANT LOSS OF QUALITY OF LIFE WITH DOCUMENTED INCREASES IN FALLS, ANXIETY, AND DEPRESSION. THE MUSCARINIC ANTAGONISTS (ANTICHOLINERGICS) ARE THE PRIMARY DRUGS FOR TREATMENT, BUT THESE AGENTS ARE ASSOCIATED WITH NUMEROUS SIDE EFFECTS AND DRUG-DRUG INTERACTIONS LEADING TO DISCONTINUATION OF THERAPY IN OVER 50% OF PATIENTS IN 6-12 MONTHS. FURTHERMORE, WITH AGE THERE IS A GROWING CONCERN FOR ANTICHOLINERGIC DRUG OVERLOAD (ESPECIALLY DUE TO DRUG-DRUG INTERACTIONS) LEADING TO ADDITIONAL EFFECTS SUCH AS COGNITION IMPAIRMENT AND OTHER CNS AFFECTS. STUDIES HAVE SHOWN THAT THE PHARMACODYNAMICS EFFICACY OF MUSCARINIC ANTAGONISTS IN OB THERAPY IS STRONGLY ASSOCIATED WITH AREA UNDER THE CONCENTRATION-TIME CURVE (AUC) AND THAT THE MANY SIDE EFFECTS ARE RELATED TO MAXIMUM PLASMA CONCENTRATIONS (CMAX). OXYBUTYNIN, ONE OF THE AGENTS WITH THE MOST SIDE EFFECTS, WAS FORMULATED AS AN ADHESIVE PATCH, WHICH GREATLY REDUCED CHOLINERGIC SIDE EFFECTS DUE TO A CONSTANT EFFECTIVE DRUG CONCENTRATION. UNFORTUNATELY, THE PATCH HAD ITS OWN SIGNIFICANT SIDE EFFECTS, MAINLY SERIOUS SKIN IRRITATIONS DUE TO THE PERMEATION ENHANCERS NEEDED FOR EFFECTIVE DELIVERY. GIVEN THE VERY LARGE POPULATION AFFLICTED WITH OB, AND THE MANY OB DRUGS AND FORMULATIONS WHICH FAIL TO ADEQUATELY TREAT THE DISEASE, THERE REMAINS A DESPERATE UNMET MEDICAL NEED FOR NEW THERAPY OPTIONS. MULTIPLE ADVANTAGES OF MICRONEEDLE TRANSDERMAL DELIVERY OVER OTHER TRANSDERMAL METHODS HAVE BEEN DOCUMENTED. MORE RECENTLY, SWELLABLE HYDROGEL MICRONEEDLES (HMN) HAVE BEEN SHOWN TO BE A HIGHLY EFFICIENT AND PAINLESS METHOD FOR INCREASING THE SKIN PERMEATION OF DRUGS WITHOUT ADDITIVES, SHARPS, OR POLYMERIC MONOMERS ENTERING THE CIRCULATION. WE HAVE SELECTED TROSPIUM CHLORIDE (TC), THE OB DRUG WITH THE BEST EFFICACY AND LEAST SIDE EFFECTS, YET PLAGUED BY POOR BIOAVAILABILITY AND HIGH PHARMACOKINETIC VARIABILITY FOR DELIVERY VIA HMN. THE PRODUCT WILL BE A DRUG-FREE HMN ARRAY WITH A TC DRUG RESERVOIR TO ENABLE A TIGHTLY CONTROLLED DELIVERY OF TC, PROVIDING EFFICACIOUS AUCS WITH CONSISTENT PLASMA CONCENTRATIONS. THIS SELF-ADMINISTERED PATCH IS DESIGNED TO DELIVER TC OVER THE COURSE OF A WEEK, AND WILL BE THE FIRST OB TREATMENT WITH BOTH EXCELLENT EFFICACY, AS WELL AS HIGH PATIENT COMPLIANCE AND SATISFACTION. THE END RESULT OF THIS WORK WILL BE A NOVEL, TRANSDERMAL DELIVERY APPROACH FOR TC WITH READILY TRANSLATABLE PK, EFFICACY AND INITIAL PRECLINICAL SAFETY DATA, READY TO COMPLETE PRECLINICAL DEVELOPMENT ACTIVITIES LEADING TO THE OPENING OF AN IND. WE HAVE ASSEMBLED A TEAM OF EXPERT ADVISORS AND COLLABORATORS TO ENSURE SUCCESSFUL COMPLETION OF THIS RESEARCH PLAN.

PHASE 1 CLINICAL TRIAL TO ASSESS THE PHARMACOKINETICS, SAFETY AND TOLERANCE OF A ZANAMIVIR TRANSDERMAL SYSTEM IN HEALTHY SUBJECTS - ABSTRACT YEARLY INFLUENZA EPIDEMICS STRIKE MILLIONS OF PEOPLE, RESULTING IN UP TO 500,000 DEATHS. FATALITIES CAUSED BY MOST SEASONAL INFLUENZA VIRUSES IS <0.03%, WITH SIGNIFICANT MORTALITY IN THE YOUNG AND ELDERLY POPULATIONS. PRESENTLY, INFLUENZA TREATMENT IS ONLY PARTIALLY EFFECTIVE, AND SOME INFLUENZA STRAINS ARE RESISTANT TO THE CURRENTLY MARKETED THERAPEUTICS, ADAMANTANES AND THE NEURAMINIDASE INHIBITOR TAMIFLU®), AND EVEN THE RECENTLY APPROVED CAP- DEPENDENT ENDONUCLEASE INHIBITOR BALOXAVIR MARBOXIL (XOFLUZA®). ZANAMIVIR (ZAN, RELENZA®), REMAINS HIGHLY ACTIVE AGAINST OSELTAMIVIR-RESISTANT INFLUENZA STRAINS, HOWEVER, ITS THERAPEUTIC IMPACT IS SEVERELY LIMITED BY ITS ROUTE OF ADMINISTRATION, ORAL INHALATION, WHICH RENDERS IT UNSUITABLE FOR PATIENTS WITH COMPROMISED RESPIRATORY SYSTEMS. THEREFORE, THE DEVELOPMENT OF A NOVEL DELIVERY ALTERNATIVE FOR ZAN WILL ADDRESS A SIGNIFICANT UNMET MEDICAL NEED. TRANSDERMAL DRUG DELIVERY OFFERS SEVERAL IMPROVEMENTS OVER OTHER DELIVERY SYSTEMS. THE DRUG DIRECTLY ENTERS THE SYSTEMIC CIRCULATION, AVOIDING SYRINGE NEEDLES, AND COULD ALLOW LARGE NUMBERS OF PATIENTS TO BE REACHED DURING AN INFLUENZA PANDEMIC OUTBREAK. ZAN ITSELF CANNOT CROSS THE HUMAN SKIN BARRIER AT THERAPEUTIC RATES, HOWEVER, MICROARRAY-ENABLED TRANSDERMAL DELIVERY IS AN ELEGANT, EFFICIENT, AND PAINLESS METHOD FOR INCREASING THE SKIN PERMEATION OF MANY DRUGS, INCLUDING ZAN. OUR NOVEL DRUG-DEVICE COMBINATION PRODUCT, TSR- 066, CONSISTS OF A SWELLABLE MICROARRAY PATCH (MAP), WHICH CONTINUOUSLY DELIVERS ZAN OVER 5 DAYS. THIS DELIVERY APPROACH FOR ZAN WILL EXPAND ITS REACH INTO PATIENT GROUPS FOR WHICH RELENZA® IS CONTRAINDICATED. BASED ON THE WELL-ESTABLISHED PRECLINICAL AND CLINICAL SAFETY OF ZAN, TSRL HAS ACHIEVED AN AGREEMENT WITH THE FDA THAT TSR-066 CAN BE DEVELOPED USING A 505(B)2 REGULATORY STRATEGY. UPON COLLECTION OF SUFFICIENT DATA TO SUPPORT THE CHANGE IN THE ROUTE OF ADMINISTRATION UNDER OUR ONGOING SBIR GRANTS, TSRL PLANS TO SUBMIT AN INVESTIGATIONAL NEW APPLICATION (IND) IN 2024. THIS FAST-TRACK SBIR WILL ALLOW FOR THE PLANNING AND CONDUCT OF A PHASE 1 CLINICAL TRIAL TO ASSESS THE PHARMACOKINETICS, SAFETY AND TOLERANCE OF TSR-066 IN HEALTHY SUBJECTS. DURING THE PHASE I PORTION OF THE GRANT, WE WILL ASSEMEBLE THE CLINICAL DEVELOPMENT TEAM, DEVELOP THE CLINICAL PROTOCOL, INVESTIGATOR BROCHURE, CONSENT FORM, CASE REPORT FORM, BUDGET, AND MANUAL OF OPERATIONS. THESE DOCUMENTS WILL BE PREPARED THROUGH COLLABORATION WITH BIA CLINICAL GROUP, LLC AND REVIEWED BY OUR SCIENTIFIC COLLABORATORS, THE CLINICAL RESEARCH UNIT UTILIZED FOR THE STUDY, AND PARTICIPATING CLINICAL RESEARCH ORGANIZATIONS. THE PHASE II PORTION OF THE GRANT WILL BE THE ACTUAL CONDUCT OF THE TRIAL. WE HAVE FORMED A COLLABORATIVE NETWORK OF RESEARCHERS AND DRUG DEVELOPMENT SPECIALISTS THAT WILL ALLOW US TO SUCCESSFULLY COMPLETE THE PROPOSED RESEARCH PLAN.

WISCONSIN SMP (SENIOR MEDICARE PATROL)

DEVELOPMENT OF ORALLY DELIVERED, NON-ABSORBABLE AT1 RECEPTOR ANTAGONISTS FOR INFL

BILE ACID CONJUGATES FOR IMPROVING THE ORAL BIOAVAILABILITY OF BISPHOSPHONATES

BASEBALL CARES

TO BRING AWARENESS AND CONNECTS MISSISSIPPI YOUTH AND YOUNG ADULT TO AGRICULTURE SECTORS, TRAINING THEM TO FARM AND DEVELOP AGRIBUSINESS USING URBAN, SUSTAINABLE AND CLIMATE SMART PRACTICES.

WISCONSIN SMP COALITION OF WISCONSIN AGING GROUPS SENIOR MEDICARE PATROL PROJECT

WATCH US GROW - OUTREACH <(>&<)> TRAINING

NEW PRODRUG STRATEGIES FOR CIDOFOVIR DESIGNED FOR MITIGATING FIRST-PASS METABOLISM

THE PURPOSE OF THIS AWARD IS TO SUPPORT THE PROJECT JURNAL TV ? MEDIA DEVELOPMENT PROGRAM

DEVELOPMENT OF THE ORALLY DELIVERED NON-ABSORBABLE ACE INHIBITOR ENALAPRILAT FOR

PRODRUGS OF NEURAMINIDASE INHIBITORS FOR INCREASED ORAL BIOAVAILABILITY

EDUCATION AND ENFORCEMENT AGAINST ELDER FINANCIAL EXPLOITATION

THE PURPOSE OF THIS AWARD IS TO SUPPORT THE PROJECT JURNAL TV DIGITAL INNOVATION: MAXIMIZING REACH AND REVENUE.

REAP UNDERUTILIZED TECHNOLOGY 24/31

WISCONSIN SMP COALITION OF WISCONSIN AGING GROUPS SENIOR MEDICARE PATROL PROJECT

WISCONSIN SMP COALITION OF WISCONSIN AGING GROUPS SENIOR MEDICARE PATROL PROJECT

WEED AND SEED

WISCONSIN SMP COALITION OF WISCONSIN AGING GROUPS SENIOR MEDICARE PATROL PROJECT

THE PURPOSE OF THIS GRANT IS TO SUPPORT THE PROJECT LOCAL TELEVISION AT THE SERVICE OF THE CITIZENS

REAP UNDERUTILIZED TECHNOLOGY 24/31

RBCS REAP IRA TECH ASSIST GRANTS

RBCS REAP IRA TECH ASSIST GRANTS

ASSISTANCE TO FIREFIGHTERS GRANT

THE PURPOSE OF THIS AWARD IS TO SUPPORT THE PROJECT YOUTH FORWARD MOLDOVA

SWPTSA AND USDA SOIL HEALTH COLLABORATIVE PROJECT. 12-NCE DUE TO COVID 19. AMEND 3 TO CHANGE END DATE FOR CLOSEOUT

THE PURPOSE OF THIS GRANT IS TO SUPPORT THE PROJECT "EUROPA, I AM WAITING YOU!"

THE PROPOSAL SUPPORTS ASYLUM SEEKERS, REFUGEES, AND STATELESS PERSONS, IN PARTICULAR INTERNATIONAL STUDENTS AT RISK OF MARGINALIZATION.

THE PURPOSE OF THIS GRANT IS TO SUPPORT THE PROJECT "MODERNIZATION OF TECHNICAL EQUIPMENT AND COMPUTERS FOR 2016-2021."

SUPPORTS THE DEVELOPMENT AND IMPLEMENTATION OF AN INTERNATIONAL COMMUNITY BASED PARTICIPATORY RESEARCH, CBPR, TRAINING PROGRAM FOR MEDICAL STUDENTS, RESEARCHERS AND COMMUNITY LEADERS IN UNDERSERVED AREAS OF THE DOMINICAN REPUBLIC

THE PURPOSE OF THIS AWARD IS TO SUPPORT THE PROJECT VISIT OF MARGUERITE MARIAMA

SMALL, RURAL SCHOOL ACHIEVEMENT PROGRAM

SMALL, RURAL SCHOOL ACHIEVEMENT PROGRAM

SMALL, RURAL SCHOOL ACHIEVEMENT PROGRAM

PROJECT WOULD CONNECT URBAN FARMERS AND COMMUNITY GARDENS IN ATLANTIC COUNTY WITH THE ORGANIZATIONS, RESOURCES, AND KNOWLEDGE NEEDED TO MAKE

SMALL, RURAL SCHOOL ACHIEVEMENT PROGRAM

SMALL, RURAL SCHOOL ACHIEVEMENT PROGRAM

SMALL, RURAL SCHOOL ACHIEVEMENT PROGRAM

SMALL, RURAL SCHOOL ACHIEVEMENT PROGRAM

PROPOSE AND DOCUMENT A PARTICIPATORY COMMUNITY BASED COVID19 RESPONSE MODEL IN THE UNDERSERVED COMMUNITY OF GUACHUPITA, SANTO DOMINGO

SMALL, RURAL SCHOOL ACHIEVEMENT PROGRAM

SMALL, RURAL SCHOOL ACHIEVEMENT PROGRAM

SMALL, RURAL SCHOOL ACHIEVEMENT PROGRAM

APPLICATION FOR SMALL, RURAL SCHOOL ACHIEVEMENT PROGRAM

APPLICATION FOR SMALL, RURAL SCHOOL ACHIEVEMENT PROGRAM

APPLICATION FOR SMALL, RURAL SCHOOL ACHIEVEMENT PROGRAM

APPLICATION FOR SMALL, RURAL SCHOOL ACHIEVEMENT PROGRAM

SRSA APPLICATION

SMALL, RURAL SCHOOL ACHIEVEMENT PROGRAM

SRSA APPLICATION 2018

THE OFFICE FOR CULTURAL POLICIES OF ROME LOCAL GOVERNMENT IN COLLABORATION WITH CASA DELLE LETTERATURE IS ORGANIZING THE NINTH EDITION OF THE INTERNA

OCEANS'15 MTS/IEEE GENOVA

THIS GRANT SUPPORTS THE COSTS INCURRED TO IMPLEMENT MEASURES TO RESPOND TO THE NOVEL CORONAVIRUS 2019 (COVID-19), WHICH MAY INCLUDE WORKPLACE SAFETY, MARKET PIVOTS, RETROFITTING FACILITIES, TRANSPORTATION, WORKER HOUSING, AND MEDICAL EXPENSES. IT PROVIDES NEEDED RELIEF TO THE FOOD PROCESSORS, DISTRIBUTORS, FARMERS MARKETS, AND PRODUCERS FOR THEIR COSTS INCURRED BETWEEN JANUARY 27, 2020, THE DATE UPON WHICH THE PUBLIC HEALTH EMERGENCY WAS DECLARED BY THE U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICE (HHS) UNDER SECTION 319 OF THE PUBLIC HEALTH SERVICE ACT, AND DECEMBER 31, 2021. BENEFICIARIES INCLUDE THE EMPLOYEES OF THE FOOD PROCESSORS, DISTRIBUTORS, FARMERS MARKETS, AND PRODUCERS.

SRSA APPLICATION

DEVELOPMENT AND APPLICATION OF A POINT-OF CARE ASSAY FOR PLASMA BILIRUBIN

APPLICATION FOR SMALL, RURAL SCHOOL ACHIEVEMENT PROGRAM