Development of an antimicrobial therapeutic demands a structured, evidence-based approach that integrates early strategic planning with rigorous preclinical characterisation to maximise the likelihood of clinical translation. The foundation rests on three pillars: establishing target product profiles (TPPs) to guide progression decisions and align with clinical need; comprehensively evaluating efficacy, spectrum of activity and early toxicity; and, from hit-to-lead onwards, using structure–activity relationship optimisation to develop leads, maintain efficacy while balancing toxicity and drug-like properties. Systematic evaluation of resistance mechanisms—extending beyond serial passage to examine mutational pathways and target modification—coupled with early susceptibility testing, enables clinical breakpoint definition and resistance prediction. When non-traditional modalities such as phage therapeutics or anti-virulence agents are under investigation, additional considerations include the need for pathogen-specific preclinical efficacy models and strategies to establish clinical proof-of-concept. This section synthesises practical frameworks, decision-making criteria, and assay methodologies from the global AMR community to support robust antimicrobial development.
Resources
21 resourcesIntroduces the stages of the process from discovery to clinical trials and pharmaceutical development.
The challenges of progressing antibacterial drug discovery projects for small and medium-sized enterprises (SMEs) and the potential solutions.
The full antimicrobial development journey from discovery to Phase 1 clinical trial, detailing strategies for hit-to-lead and preclinical candidate selection and outlining non-clinical, regulatory, and CMC requirements for first-in-human studies.
Examines Go/No-Go decision-making in antibacterial drug discovery from both industry and academic perspectives, emphasising the role of TPPs and TCPs in guiding preclinical progression. It also highlights how structured support helps translate academic findings into viable drug candidates.
Showcases expert-led success stories and scientific advances in novel antibiotics, including breakthroughs against multidrug-resistant Gram-negative bacteria and the development of endolysins through to human trials.
Provides practical guidance on identifying high-quality hits and leads and developing effective Target Product Profiles (TPP) to support antibiotic drug development, featuring expert insights from CARB-X, GARDP, ESCMID, and ASM collaborators.
The speakers discuss the breadth of new approaches to antibiotic discovery, with a focus on synthetic biology as well as the need for interdisciplinary collaboration in drug discovery.
Highlights the growing trend of non-traditional antibacterial therapies—such as anti-virulence agents, bacteriophages, and microbiome-modifying treatments—emphasising the need for novel preclinical models and the significant challenge of demonstrating clinical efficacy.
Explores the role of efflux pumps in antibiotic resistance and highlights recent advances in efflux pump inhibitor research, including mechanistic insights, novel inhibitor scaffolds, and strategies targeting the hydrophobic trap in RND-type pumps to combat multidrug-resistant Gram-negative bacteria.
Explores key techniques for assessing the risk of resistance selection by novel antibacterials, including methods to investigate resistance origins and strategies to manage the translation of resistance risk from in vitro studies to clinical settings.
Discusses strategies to assess and improve predictions of antimicrobial resistance emergence during drug discovery, focusing on testing approaches and addressing risk prediction enhancements.
Explores innovative approaches to resistance testing beyond traditional serial passage methods, addressing the reality of mutational resistance and evaluating testing strategies for both single- and multi-target antimicrobial agents.
Highlights the development of novel antibiotics through under-explored targets and new chemical scaffolds, including a case study on zosurabalpin, a promising agent targeting lipopolysaccharide transport with a distinct mode of action.
Showcases approaches to enhance drug discovery, including structure–activity relationship optimisation through case studies and the validation of MAIP, an open-access tool that significantly improves hit rates in identifying novel, drug-like antimalarial compounds.
Explores innovative targeted drug delivery systems for infectious diseases, including phage-based antibacterial delivery, DNA nanostructures functionalised for bacterial targeting, and nanocarriers designed to overcome biological barriers and enhance intra-bacterial and biofilm penetration.
Discusses strategies for successful drug development project management, highlighting team performance, goal setting, risk mitigation. It also addresses the unique challenges of antimicrobial R&D through personal insights and practical approaches.
Highlights the central role of small companies and academic labs in antibiotic R&D, the challenges they face, lessons from industry and funders, and strategies to avoid common grant proposal pitfalls.
The role of physicochemical properties and emerging AI approaches in antibiotic drug discovery, with expert talks and a roundtable discussion led by GARDP and CARB-X at the ESCMID/ASM 2018 conference.
Explores the Investigational New Drug (IND) preparation process explains de-risking activities that save time and cost while promoting faster advancement of your product into the clinic.
This encyclopaedia has short definitions of key terms in the Research and Development of Antimicrobials.
Provides resources and checklists to support product development activities, including TPP creation.
*PACE Delivery Partner Network Member: links to members with drug discovery and microbiology expertise
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