Technology

HoloMoA

Digital Holographic Microscopy and Artificial Intelligence for the rapid detection of the Mechanism of Action of antimicrobials, including novelty detection.

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Objectif/Description technologique

HoloMoA is a decision support tool to facilitate the classification of the possible Mechanisms of Action (MoA) of antimicrobial compounds in preclinical development.

BIOASTER has developed a phenotypic approach to predict the novelty of new antimicrobial MoA or classify antimicrobial MoA based on time-lapse Digital Inline Holographic Microscopy coupled to an artificial intelligence and deeplearning pipeline. It relies on the building of image databases representing the phase maps of bacteria cells and integrating the mode of action of reference antimicrobials.
HoloMoA is a cost-effective, rapid and label-free technology based on the assessment of phenotypic changes to multiple examples of single cells in a sample that have been treated with antimicrobials. The system can take single time-point measurements (2 h) or monitor activity over a time course of several hours. Multiple antimicrobials can be examined in combination and the system is suitable for use with different microorganisms.

Technology Holoama

Background

Any company working on the design and development of novel antimicrobials must determine the MoA early in the development process. Currently, identification of the MoA of an antimicrobial is complex, involving combinations of different technologies, time-consuming and expensive. There is a clear need for alternative more economical and faster technology, to perform phenotypic screening of molecules, and to be able to understand complex therapeutic solutions and we believe that HoloMoA provides this.

While not yet a regulatory requirement, the understanding of an antimicrobials MoA is highly desirable as it can de-risk future development plans for a number of reasons:

Toxicity: Predictive toxicity can save money by assessing potential cross-reactivity with human targets

Resistance: Identification of the mechanism of action can allow prediction of the likelihood of resistance development

Optimization: Further optimization of a molecule can be facilitated by a detailed understanding of the MoA

Novelty: Antimicrobials with novel targets &/or MoA are highly desirable when considering the current global AMR crisis

Added Value: All of the above can undoubtedly add value to the antimicrobial assets of any company working in antimicrobial R & D when looking to out-license assets

Advantage

  • Simple technology requiring no specialist knowledge once databases completed
  • Label-free technology based on digital inline holographic microscopy • Live bacteria, so time-course of measurements possible
  • Time-frame for measurement: 0 to >24 h, typically 2 h
  • Medium-throughput, semi-automated platform
  • Simpler, faster, less expensive than classical methods
  • Provide the potential MoA during preclinical development with good accuracy • Detect the novelty of the MoA of new antimicrobials in development

Potential Applications

HoloMoA has the potential to facilitate & accelerate new antimicrobial preclinical drug development from discovery to lead up optimization by:

  • Providing a decision tool to allow selection of a series of molecules to go into lead optimization
  • Potentially characterize the novelty of the mechanism of action of candidate antimicrobials
  • Potential to expand the database to many other target pathogens, including fungi and other eukaryotic pathogens
  • Potential to expand studies to phenotypic changes to mammalian cells to facilitate toxicity analysis and antiviral screening
  • Potential to combine technology with other phenotypic screening technologies in development at Bioaster – potentially on the same cells, not just the same sample

Outlook

BIOASTER is seeking partners aiming to work together on the future development of the HoloMoA project:

  • Test more compounds with different MoA, compound combinations and compounds with novel MoA, to expand the database, improve the algorithm/s and enhance statistical significance of the data
  • Expand the scope to other target pathogens, including Gram positive bacteria, ESKAPE pathogens, parasites and fungi
  • Extend the technology to assess phenotypic changes to mammalian cells, allowing the potential for toxicity screening, antiviral studies and studies involving intracellular pathogens
  • Create stand-alone units with potential diagnostic or laboratory equipment manufacturers
  • Combine the technology with other phenotypic screening technologies develop by partners or existing within BIOASTER