Center for accelerated development of drug candidates targeting high threat bacterial infections

SUMMARY The global rise in antimicrobial resistance (AMR) poses a grave public health threat, limiting treatment options and causing substantial morbidity and mortality. Particularly concerning is the rise of AMR among both Gram- negative (GN) and Gram-positive (GP) bacterial pathogens in hospital and community settings. Addressing this urgent medical need demands the development of effective new antibiotics targeting high-threat AMR pathogens, yet the current pipeline's capacity to meet this demand is insufficient. With antibiotic development now predominantly driven by biotech, academia plays an increasingly pivotal role in collaborating with industry to foster the development of clinically viable drug candidates. Our Center of Excellence in Translational Research (CETR) drug accelerator was established to leverage the expertise of five seasoned drug developers from academic (CDI, Rutgers) and pharmaceutical/biopharmaceutical (Merck, Prokaryotics, BioVersys) sectors. This collaborative effort aims to advance mature antibacterial small molecule inhibitor programs through preclinical development, resulting in multiple IND submissions for clinical assessment. Our focus is on combating clinically significant, high-threat, drug-resistant bacterial pathogens including GP: nontuberculous mycobacteria (NTM) Mycobacterium abscessus and Mycobacterium avium; methicillin resistant Staphylococcus aureus, and Enterococci; fastidious GN: Neisseria gonorrhea, Haemophilus influenzae, Moraxella catarrhalis, Legionella pneumophila, Chlamydia pneumoniae, and Mycoplasma pneumoniae, and non-fastidious GN pathogens: Acinetobacter baumannii and Burkholderia spp by prioritizing development of both narrow- and broad-spectrum small molecule inhibitors targeting key enzymes and prominent pharmacological targets. All of our Projects are advanced with mature compounds representing new chemical classes that can overcome existing mechanisms of resistance and are poised to be developed as preclinical development candidates. The CETR includes an integrated network of science cores staffed by experienced directors, facilitating efficient compound identification and optimization. Clear criteria for compound progression with ‘go, no-go’ metrics have been established to ensure streamlined development processes. The CETR fosters synergy among Projects, developing distinct drug candidates targeting overlapping threat agents. By bringing together highly accomplished Project leaders and partners from academia and industry, supported by experienced Core leaders, world-class Scientific Advisory Board members, and regulatory specialists, we will effectively navigate preclinical development stages, swiftly advancing optimized leads through rigorous milestones as preclinical development candidates for IND-enabling and de-risking studies. The goal of our efforts is to develop multiple preclinical development candidates suitable for IND submission. Strong industry collaboration facilitates downstream clinical development for select Projects, while others are poised for licensing or partnership with biopharmaceutical companies. Through our concerted endeavors, we strive to address the critical need for new antibiotics to combat the growing threat of antimicrobial resistance. Project Number: 1U19AI189168-01 | Fiscal Year: 2025 | NIH Institute/Center: National Institute of Allergy and Infectious Diseases (NIAID) | Principal Investigator: David Perlin | Institution: HACKENSACK UNIVERSITY MEDICAL CENTER, HACKENSACK, NJ | Award Amount: $7,562,521 | Activity Code: U19 | Study Section: Special Emphasis Panel[ZAI1 CAB-M (J1)] View on NIH RePORTER: https://reporter.nih.gov/project-details/1U19AI18916801