This Project Grant award from the National Institute of Allergy and Infectious Diseases (NIAID), under the Allergy and Infectious Diseases Research program (CFDA 93.855), aims to develop new antimicrobial agents and combination therapies to combat the growing threat of Gram-negative bacterial pathogens, specifically carbapenem-resistant Acinetobacter baumannii (CRAB) and Klebsiella pneumoniae (CRKP). The $2,308,174 award, with a performance period from August 2024 to May 2029, will fund three...
This federal Project Grant award from the National Institute of Allergy and Infectious Diseases (NIAID) under the Allergy and Infectious Diseases Research program (CFDA 93.855) provides $802,798 to The Research Foundation For The State University Of New York to develop a novel class of antibiotics called Biamyxins (BMX) to target multidrug-resistant Gram-negative bacterial infections. The key products and services to be delivered include: Optimization of the lead BMX compound, HCC-0010, to...
The National Institute of Allergy and Infectious Diseases (NIAID) awarded a $288,360 Project Grant under CFDA 93.855 (Allergy and Infectious Diseases Research) to Biological Mimetics, Inc. to develop a novel vaccine candidate that stimulates immune protection against multi-drug resistant Acinetobacter baumannii (MDR-AB). The Phase I project aims to (1) identify and characterize key immunogenic components of MDR-AB that lead to protective immunity, (2) develop a prototype vaccine formulation, and...
This Project Grant award from the National Institute of Allergy and Infectious Diseases (NIAID) under the Allergy and Infectious Diseases Research program (CFDA 93.855) provides $741,917 to West Virginia University Research Corporation to develop therapeutic antibodies for the treatment of multidrug-resistant Pseudomonas aeruginosa infections, with a focus on sepsis. The key objectives are to characterize the mechanism of action of a lead antibody candidate, formulate it into a multivalent...
The National Institute of Allergy and Infectious Diseases (NIAID) awarded a $240,878 Project Grant under the Allergy and Infectious Diseases Research program (CFDA 93.855) to The Medical University of South Carolina (MUSC) for a clinical trial planning project titled "Novel Strategies for Treatment of Mycobacterium Abscessus Pulmonary Disease". The key goals are to: 1) Develop a detailed trial protocol and required documentation to initiate a future randomized, blinded,...
This National Science Foundation (NSF) Small Business Innovation Research (SBIR) Phase I award to Bactria Pharmaceuticals LLC is providing $274,937 to develop therapeutic drugs that restore antibiotic sensitivity in bacteria that cause severe healthcare-associated infections. The goal is to combat antimicrobial resistance in gram-negative pathogens through the use of small molecule efflux pump inhibitors (EPIs). The project involves three key activities: cryo-electron microscopy to understand...
This Project Grant award, valued at $299,163, was provided by the National Institute of Allergy and Infectious Diseases (NIAID) under the Allergy and Infectious Diseases Research program (CFDA 93.855). The project aims to develop a novel antimicrobial approach that combines endolysin proteins from the awardee's metagenomic database with self-replicating mRNA (repRNA) delivery using lipid nanoparticles. The key objectives are to evaluate whether repRNA can successfully express a lysin targeting...
This Project Grant award from the National Institute of Allergy and Infectious Diseases (CFDA 93.855 - Allergy and Infectious Diseases Research) provides $895,538 to HMH Hospitals Corporation, doing business as Hackensack University Medical Center, for a research project titled "Shorter and More Effective Oral Regimens for M. abscessus Pulmonary Disease". The primary objectives are to discover all-oral drug regimens, either using FDA-approved agents or novel preclinical/clinical...
This Project Grant award from the National Institute of Allergy and Infectious Diseases (NIAID), under the Allergy and Infectious Diseases Research program (CFDA 93.855), provides $155,227 to The Johns Hopkins University to generate proof-of-concept data on a novel strategy to treat Mycobacterium abscessus (MAB) chronic lung disease. The project aims to investigate whether a monoclonal antibody (CMTX-101) can effectively disrupt MAB biofilms in the lungs, which could enhance the efficacy of...
This $361,237 Project Grant awarded by the National Institute of Allergy and Infectious Diseases (NIAID) under the Allergy and Infectious Diseases Research program (CFDA 93.855) aims to develop a new class of species-specific antimicrobial peptides called PNA-STAMPS to target Streptococcus pneumoniae (Spn), a major human pathogen. The project builds on preliminary data showing that fusing a broad-spectrum antimicrobial peptide (AMP) to an Spn-specific secreted peptide can selectively eliminate...
DEVELOPMENT OF A MECHANISTICALLY NOVEL SYNERGISTIC ADJUVANT TO PARTNER WITH POLYMYXIN ANTIBIOTICS - ACINETOBACTER BAUMANNII (AB) AND RELATED SPP. CAUSE SEVERE NOSOCOMIAL PNEUMONIA, WOUND, BLOOD, AND URINARY TRACT INFECTIONS, WITH MORTALITY RATES RANGING FROM 25-75%. THE EMERGENCE OF MULTIDRUG-RESISTANT (MDR) AB ISOLATES HAS MADE IT DIFFICULT TO TREAT WITH MOST STANDARD-OF-CARE ANTIBIOTICS. CARBAPENEMS HAVE SERVED AS THE PREFERRED THERAPY TO TREAT AB INFECTIONS, HOWEVER, OVER 50% OF INFECTIONS ARE NOW CARBAPENEM-RESISTANT AB (CRAB). CONSEQUENTLY, THE WHO AND CDC HAVE CLASSIFIED CRAB AS A PRIORITY-1 CRITICAL AND URGENT THREAT PATHOGEN. POLYMYXIN B (PMB) AND COLISTIN HAVE BECOME THE ANTIBIOTICS OF LAST RESORT TO TREAT CRAB DESPITE THEIR LOW THERAPEUTIC INDEX DUE TO POTENTIAL NEPHROTOXICITY. TO ADDRESS THIS UNMET MEDICAL NEED, WE AIM TO DEVELOP AN EFFECTIVE COMBINATION AGENT COMPRISING A POLYMYXIN POTENTIATOR AND AN EFFICACIOUS, MECHANISTICALLY NOVEL ANTIBIOTIC, MEDINAMYCIN (MEDM). MEDM IS UNAFFECTED BY CLINICALLY RELEVANT MODES OF ANTIBIOTIC RESISTANCE, EXHIBITS LOW FOR AND PROVIDES ROBUST SYNERGISTIC BACTERICIDAL ACTIVITY AGAINST AB, INCLUDING COLISTIN-RESISTANT, MDR, AND CRAB ISOLATES, AND IS PREDICTED TO BE A SAFE AND EFFECTIVE ANTIBIOTIC TO PERMIT LOWER EFFECTIVE DOSES OF PMB, THEREBY REDUCING ADVERSE EFFECTS. AIM 1 (PHASE 1) VALIDATE THE FEASIBILITY OF DEVELOPING SEMISYNTHETIC MEDM ANALOGS EFFECTIVE IN COMBINATION WITH PMB AND/OR SPR741 AGAINST POLYMYXINR AB. IMPROVE MEDM BIOPROCESS TO DELIVER >1 G FOR AIM 1 STUDIES. DEMONSTRATE CHEMICAL TRACTABILITY. DEVELOP THE STRUCTURE ACTIVITY RELATIONSHIP (SAR) OF NEW ANALOGS USING MOA, FOR, MICROBIOLOGICAL ACTIVITY, AND CYTOTOXICITY ASSAYS. DEMONSTRATE IN VIVO EFFICACY OF A MEDM ANALOG + PMB AGAINST A PMBR AB ISOLATE IN MURINE BACTEREMIA INFECTION MODEL. AIM 2 (PHASE 2) COMPLETE BIOPROCESS OPTIMIZATION AND CONDUCT A SEMISYNTHETIC LEAD OPTIMIZATION WITH THE GOAL OF IDENTIFYING MEDM ANALOGS WITH IMPROVED POTENCY AND/OR DRUG LIKE PROPERTIES. INCREASE RELIABLE PRODUCTION LEVELS OF MEDM TO >250 MG/L USING 20L BIOREACTORS, EVENTUALLY PRODUCING 30 G OF MEDM. USING THIS MATERIAL, PREPARE UP TO 150 SEMISYNTHETIC ANALOGS IN AN ITERATIVE FASHION ACCORDING TO EMERGING SAR. MEASURE AB MIC FOR ALL COMPOUNDS, AND FOR SELECT COMPOUNDS EVALUATE SYNERGISTIC INHIBITORY CONCENTRATION WITH POTENTIAL POLYMYXIN PARTNERS, IN VITRO TOX AND ADME, FOR, KILL CURVES, PK AND MIC90 TO SELECT POLYMYXIN PARTNER AND ANALOGS TO ADVANCE TO IN VIVO TESTING IN AIM 3. AIM 3 (PHASE 2) IN VIVO CHARACTERIZATION OF MEDM ANALOGS IN COMBINATION WITH SELECTED POTENTIATOR IN RELEVANT MOUSE MODELS OF AB INFECTION TO IDENTIFY LEAD SERIES OF COMBINATION PRODUCT. TEST EFFICACY OF SUPERIOR MEDM ANALOGS + POLYMYXIN POTENTIATOR AGAINST A PMBR AB CLINICAL ISOLATE IN A MOUSE PERITONITIS INFECTION MODEL, FOLLOWED BY A DEEP THIGH AND NEUTROPENIC MOUSE LUNG INFECTION MODEL. IN EACH STUDY, DEMONSTRATE THAT A MEDM ANALOG PROVIDES STATISTICALLY SIGNIFICANT EFFICACY (P < 0.05) IF COMBINED WITH POLYMYXIN AT A SUB-EFFICACIOUS DOSE TO IDENTIFY LEAD MEDM SERIES FOR COMBINATION PRODUCT. DOSE FRACTIONATION STUDIES WILL ALSO BE PERFORMED.