4500005266S
PNEUMONIA IS A COMMON CLINICAL DIAGNOSIS THAT OFTEN LACKS A MICROBIOLOGICAL DIAGNOSIS BECAUSE NO PATHOGEN IS IDENTIFIED. WITHOUT A MICROBIOLOGICAL DIAGNOSIS, ANTIBIOTICS TARGETING A BROAD RANGE OF PATHOGENS ARE USED, INCREASING THE RISKS FOR RESISTANCE ALONG WITH POOR OUTCOMES IF INAPPROPRIATE ANTIBIOTICS ARE CHOSEN. THIS RESEARCH PROGRAM PROPOSES TO DIAGNOSE LOWER RESPIRATORY TRACT BACTERIAL INFECTIONS AND THEIR ASSOCIATED ANTIMICROBIAL RESISTANCE IN FOUR HOURS, MUCH FASTER THAN CURRENT CULTURE TECHNIQUES. THE LONG-TERM GOAL OF THIS RESEARCH PROGRAM IS TO DEVELOP RAPID DIAGNOSTIC TESTS THAT WILL BE INDICATED IN ALL PATIENTS WITH A CLINICAL SUSPICION FOR PNEUMONIA. THE SHORT-TERM OBJECTIVE WILL FOCUS ON PNEUMONIAS CAUSED BY STAPHYLOCOCCUS AUREUS, PSEUDOMONAS AERUGINOSA, AND HAEMOPHILUS INFLUENZAE, WITH THE GOAL OF HAVING RESULTS AVAILABLE IN 4 HOURS. THE STRATEGY USED IN THIS DIAGNOSTIC TEST DISTINGUISHES IT FROM COMPETITORS AND ALTERNATIVES. THIS DIAGNOSTIC IS BASED ON DETECTING RNA SEQUENCE(S) SPECIFIC FOR THE PATHOGEN CAUSING PNEUMONIA IN A HUMAN PATIENT. TESTING WILL BE DONE ON BLOOD DRAWN DIRECTLY FROM THE PATIENT, MAKING IT LESS INVASIVE THAN OTHER METHODS THAT OBTAIN SAMPLES FROM THE AIRWAYS, SUCH AS BRONCHOSCOPY OR DEEP SUCTIONING. THIS TEST WILL NOT REQUIRE THE SPECIMEN TO BE CULTURED, ALLOWING FOR FASTER RESULTS THAN TRADITIONAL MICROBIOLOGICAL METHODS. THE RNA TARGETED BY THE TEST IS IDENTIFIED VIA RNA SEQUENCING OF BLOOD FROM PATIENTS WITH THE INFECTION. RNA SEQUENCING DATA SHOWS RNA SPECIFIC TO THE PATHOGEN OF INTEREST (S. AUREUS., P. AERUGINOSA, AND H. INFLUENZAE) THAT IS ALSO SPECIFIC FOR AN ACTIVE INFECTION. TARGETING RNA ALSO ENSURES THAT THE INFECTION IS CURRENT SINCE RNA IS LESS STABLE THAN DNA, LASTING MINUTES TO HOURS WHEN FROM A BACTERIUM. THE METHOD, HOWEVER, IMMEDIATELY STABILIZES THE RNA FOR TESTING. RNA ALSO IDENTIFIES BACTERIA THAT ARE ACTIVELY MAKING RESISTANCE PROTEINS, RATHER THAN BACTERIA WITH THE POTENTIAL FOR RESISTANCE BASED ONLY ON GENOMIC DNA. AT THE END OF THIS PROJECT, PCR BASED TESTS WILL BE CREATED THAT ARE INFORMED BY RNA SEQUENCING DATA. THESE WILL DIAGNOSE PNEUMONIA DUE TO S. AUREUS., P. AERUGINOSA, AND H. INFLUENZAE, ALONG WITH RELEVANT ANTIBIOTIC RESISTANCE, USING BLOOD FROM THE PATIENT. THIS PCR TESTING PLATFORM USES FDA-APPROVED INSTRUMENTATION TO FACILITATE TRANSITIONING FROM A RESEARCH LABORATORY TO A CLINICAL MICROBIOLOGY LABORATORY.
Rhode Island Hospital
Definitive Contract 75A50122C00028
$449.7k 2/28/25 4500005270S
OUR PROJECT AIMS TO DEVELOP A NEW DRUG EFFECTIVE AGAINST MULTIDRUG-RESISTANT (MDR) GRAM-NEGATIVE BACTERIA. OUR EARLY LEAD COMPOUNDS ARE DERIVED FROM A NATURAL PRODUCT AND REPRESENT A NOVEL CLASS OF COMPOUNDS FEATURING A NOVEL MODE OF ACTION. THE AGENTS ARREST THE FUNCTION OF BAMA, AN ESSENTIAL COMPONENT FOR BACTERIAL SURVIVAL, WHICH NO CURRENT DRUGS TARGET. BAMA, IS AN ESSENTIAL COMPONENT OF THE Ã -BARREL ASSEMBLY MACHINERY (BAM), LOCATED IN THE OUTER MEMBRANE (OM) OF GRAM-NEGATIVE BACTERIA; THE TARGET IS NOT PRESENT IN HUMANS (SPECIFIC). BAMA FOLDS AND INTEGRATES OM-PROTEINS INTO THE OM; INHIBITION LEADS TO OM BLEBBING AND ULTIMATELY CELL LYSIS (ESSENTIAL). SINCE BAMA HAS NOT BEEN TARGETED BY ANY EXISTING DRUGS, BACTERIA HAVE NOT DEVELOPED TARGET-BASED RESISTANCE. HENCE, OUR PROGRAM CAN BE REGARDED AS THE FOUNDATION FOR THE DEVELOPMENT OF A FIRST IN CLASS BAMA INHIBITOR. WE WILL FOCUS ON TREATING HOSPITAL-ACQUIRED INFECTIONS SUCH AS PNEUMONIA CAUSED BY MDR BACTERIA. THESE INFECTIONS ARE CLASSIFIED AS A Â CRITICAL PRIORITYÂ BY THE WORLD HEALTH ORGANIZATION (WHO) DUE TO THEIR SEVERITY AND LIMITED TREATMENT OPTIONS.
Justus-Liebig-Universitaet Giessen
Definitive Contract 75A50122C00028
$274.6k 2/28/25 4500004904S
THE MYERS LABORATORY EXTENSIVELY REDESIGNS NATURAL ANTIBIOTIC SCA¿OLDS THEN PREPARES THEM BY CHEMICAL SYNTHESIS TO ACCESS NEW ANTIBIOTICS E¿ECTIVE AGAINST MULTIDRUG-RESISTANT BACTERIAL PATHOGENS. THE STRATEGY PERMITS SCA¿OLD MODI¿CATIONS THAT CANNOT BE ACHIEVED BY SEMI- SYNTHESIS AND PROVIDES A MEANS TO OVERCOME EXISTING CLASS-BASED RESISTANCE MECHANISMS AS WELL AS BROADEN THE SPECTRUM OF ACTIVITY. RECENTLY, EXPLORATIONS TO EXPAND AND REDE¿NE THE LINCOSAMIDE CLASS HAVE DELIVERED A SET OF PARTICULARLY PROMISING LEAD MOLECULES, COLLECTIVELY TERMED THE OXEPANOPROLINAMIDES (OPPS). OPPS OVERCOME RESISTANCE MECHANISMS THAT RENDER >10 OTHER CLASSES OF RIBOSOME-TARGETING ANTIBIOTICS INACTIVE (INCLUDING LINCOSAMIDES, MACROLIDES, AND OXAZOLIDINONES) AND ARE IMPERVIOUS TO RESISTANCE MECHANISMS THAT DISABLE ANTIBIOTICS WITH DI¿ERENT TARGETS (E.G., CELL-WALL BIOSYNTHESIS INHIBITORS, AND GYRASE AND TOPOISOMERASE INHIBITORS). THE LEAD OPPS ARE POTENT, BROAD-SPECTRUM AGENTS, AND DEMONSTRATE IN VIVO E¿CACY AGAINST MULTIDRUG-RESISTANT (MDR) GRAM-POSITIVE AND GRAM-NEGATIVE ORGANISMS. OPPS SHOW EXQUISITE POTENCY IN VITRO AGAINST STAPHYLOCOCCUS, STREPTOCOCCUS, AND ENTEROCOCCUS SPP., INCLUDING STRAINS CONSTITUTIVELY EXPRESSING LINCOSAMIDE RESISTANCE DETERMINANTS. OPPS ALSO POTENTLY INHIBIT MANY HIGH-PRIORITY, MDR GRAM-NEGATIVE PATHOGENS IN VITRO INCLUDING NEISSERIA GONORRHOEAE AND ESCHERICHIA COLI. IN VITRO SAFETY PRO¿LING EXPERIMENTS REVEAL THAT OPPS SELECTIVELY INHIBIT BACTERIAL CELL GROWTH AND SUGGEST THAT THEY MAY O¿ER A LARGE THERAPEUTIC WINDOW. WITH THE SUPPORT OF CARB-X, THIS PROGRAM SEEKS TO PRO¿LE FOUR HIGHLY PROMISING LEAD MOLECULES TO ASSESS THEIR POTENTIAL AS LEAD CANDIDATES FOR THE TREATMENT OF COMMUNITY-ACQUIRED BACTERIAL PNEUMONIA (CABP). THIS PROGRAM WILL EVALUATE THE LEAD OPPS IN A WELL-DE¿NED SET OF ASSAYS TO FURTHER CHARACTERIZE THEIR SAFETY, E¿CACY, AND PHARMACOKINETIC PROPERTIES. THESE CHARACTERIZATIONS WILL ENABLE OUR GROUP TO EITHER PROGRESS ONE OR MORE OPPS CLOSER TO NOMINATION AS A PRE-CLINICAL CANDIDATE OR INFORM FUTURE ANALOG DEVELOPMENT TO ADDRESS ANY LIABILITIES EXHIBITED BY THIS CLASS OF ANTIBACTERIAL AGENTS.
President And Fellows Of Harvard College
Definitive Contract 75A50122C00028
$483.5k 2/28/25 4500004892S
THE CONCURRENT RISE OF ANTIMICROBIAL RESISTANCE AND INCIDENCE OF SEXUALLY TRANSMITTED INFECTIONS IS A WORRYING COMBINATION. IN THE PAST DECADE, CASES OF GONORRHOEA HAVE MORE THAN DOUBLED IN MANY COUNTRIES Â IN THE US THERE WERE MORE THAN 1.6 MILLION NEW INFECTIONS LAST YEAR, HALF OF WHICH WERE ANTIBIOTIC RESISTANT. OVER THE PAST 80 YEARS, NEISSERIA GONORRHOEAE, THE CAUSATIVE AGENT OF GONORRHEA, HAS STEADILY DEVELOPED RESISTANCE TO ALL ANTIMICROBIAL TREATMENTS. ALREADY TODAY, ONLY ONE RECOMMENDED TREATMENT OPTION REMAINS, AND FAILURES HAVE BEEN OBSERVED IN MULTIPLE COUNTRIES. GONORRHEA WILL CONTINUE TO DEVELOP RESISTANCE TO ANY NEW ANTIMICROBIALS, AND IN JUST A FEW YEARS UNTREATABLE DISEASE COULD BE WIDESPREAD. AN ALTERNATIVE SOLUTION IS URGENTLY NEEDED Â A VACCINE. THERE ARE NO KNOWN EXAMPLES OF A PATHOGEN DEVELOPING RESISTANCE TO A VACCINE. BY PREVENTING INFECTIONS AND ILLNESS, ANTIBIOTIC PRESCRIPTIONS ARE REDUCED, AND SO IS DEVELOPMENT OF RESISTANCE. WIDESPREAD USE OF STREPTOCOCCAL VACCINES HAS EVEN BEEN SHOWN TO SIGNIFICANTLY REDUCE CIRCULATING LEVELS OF RESISTANT BACTERIA. FURTHERMORE, AS VACCINES ARE ENTIRELY PATHOGEN SPECIFIC, THEY DO NOT HARM THE NATURAL MICROBIOME. LIMMATECH BIOLOGICS AG IS DEVELOPING A VACCINE IS BASED ON A COMBINATION OF NOVEL ANTIGENS DELIVERED IN A NOVEL PRODUCTION PLATFORM. IMMUNE EVASION BY N. GONORRHOEAE MEANS THAT NATURAL INFECTION WITH THE PATHOGEN DOES NOT RESULT IN PROTECTIVE IMMUNITY, AND MANY GONOCOCCAL SURFACE ANTIGENS ARE HIGHLY VARIABLE IN STRUCTURE OR EXPRESSION, MAKING THEM POOR TARGETS FOR VACCINATION. OUR VACCINE IS DESIGNED TO OVERCOME THESE MECHANISMS BY AVOIDING PHASE VARIABLE STRUCTURES AND IMMUNOGENIC SURFACE DECOY ANTIGENS. ALL OUR ANTIGENS ARE HIGHLY CONSERVED BETWEEN STRAINS, INCLUDING RESISTANT CLINICAL ISOLATES, AND THIS, TOGETHER WITH THE MULTIVALENT DESIGN OF THE VACCINE MEANS COVERAGE IS EXPECTED TO BE 100%. ALL OUR ANTIGENS ARE HIGHLY IMMUNOGENIC IN PRECLINICAL STUDIES. THEY HAVE BEEN EXTENSIVELY VALIDATED USING A SET OF COMPLEMENTARY IN VITRO ASSAYS THAT DEMONSTRATE ANTIBODY FUNCTIONALITY AND PROTECTIVE MECHANISMS OF ACTION. THESE ASSAYS HAVE ALSO BEEN USED TO CONFIRM ANTIBODY FUNCTIONALITY AGAINST MULTIPLE STRAINS INCLUDING AMR CLINICAL ISOLATES. WE ARE CURRENTLY IN THE PROCESS OF SELECTING OUR FINAL LEAD VACCINE CANDIDATE AND PLAN TO START THE FIRST CLINICAL STUDY ON THIS VACCINE IN 2026.
Limmatech Biologics AG
Definitive Contract 75A50122C00028
$749.8k 2/28/25 4500005279S
THE PROPOSAL IS TO PERFORM TARGETED FEASIBILITY STUDIES SUPPORTING EFFORTS TO DEVELOP AND BRING TO MARKET A ROBUST, LOW-COST INSTRUMENT FOR NEONATAL SEPSIS DIAGNOSIS THAT PERFORMS PATHOGEN DETECTION, PATHOGEN IDENTIFICATION (ID), AND PHENOTYPIC ANTIMICROBIAL SUSCEPTIBILITY TESTING (AST) DIRECTLY FROM WHOLE BLOOD IN 3-8 HOURS FROM BLOOD DRAW TO RESULT, WITH =5 MINUTESÂ HANDLING TIME, IN A SINGLE INSTRUMENT. COMPETITIVE ADVANTAGES INCLUDE DIAGNOSTIC SPECIMEN, CAPABILITY, AST MODALITY, SPEED, EASE OF USE, AND AFFORDABILITY.
Astradx Inc.
Definitive Contract 75A50122C00028
$1.3m 2/28/25