Anti-infectives

 

Discovery of new antibacterials, antivirals, antifungals, and antiparasitics

Evotec provides bespoke anti-infective drug discovery and development services from target identification to investigational new drug (“IND”) and has an established and proven track record of contributing to the discovery and development of multiple anti-infective agents from pre-clinical candidates through to marketed drugs.

Evotec has established a leading-edge platform enabling the discovery and development of new therapies and vaccines to treat and prevent serious and life-threatening infections arising from Gram-positive and Gram-negative bacteria including multi-drug resistant (“MDR”) organisms, fungal pathogens, viruses and parasites. Evotec’s expertise also reaches beyond conventional antimicrobial agents into multiple alternative platforms such as targeting virulence attributes, specific pathogen antibodies, ‘resistance breakers’, combination therapies, and phage technologies.

Our anti-infective discovery team of >160 FTEs has a breadth of experience with multiple compound classes: small molecules, natural products, biologics, peptides, antibodies, combinations, biocides and vaccines. We carefully evaluate and adopt the most efficient and optimal drug discovery approaches from phenotypic screening to target-based discovery. Evotec has extensive experience in multiple target classes including folate, non-mevalonate, aromatic biosynthesis, protein synthesis, ribosome, virulence attributes and resistance pathways as well as determining the mechanism of action (“MOA”) of new antimicrobials discovered from phenotypic screening.

Key capabilities of Evotec’s anti-infective discovery platform

EvostrAIn™

  • Comprehensive collection of strains and clinical isolates used to establish the activity profile of lead compounds and candidates, both in vitro and in vivo
  • Highly characterised strains with in many cases defined mechanism of resistance
  • Extensive range of geographically diverse human bacterial and fungal pathogens that cover isolates susceptible and resistant to current antimicrobial drugs
  • Many strains and isolates validated in in vivo models of infection allowing rapid progress to in vivo models of disease

Microbiology, virology, mycology, parasitology

  • Industry-standard methods adopted including CLSI and EUCAST to test compounds for antimicrobial activity against organisms from our extensive collection, EvostrAIn™, or strains provided by our collaborators
  • HTS (whole-cell) and medium-throughput screening for hit identification of antimicrobial activity on a BSL 2 contained platform
  • MIC, MBC/MFC, time-kill, PAE and intracellular killing studies using single or combination agents
  • Virology: plaque assays (cytopathic effect), ELISA, neutralisation assay, ViroToxGlo™
  • Frequency of resistance determination and detailed characterisation of resistant mutants
  • Early assessment of cytotoxicity potential against multiple mammalian cell lines
  • Hollow fibre PK/PD or bioreactor human cell systems for detailed profiling of novel anti-infective agents
  • Compound/drug combination studies for assessment of synergistic, antagonistic and additive effects
  • Bespoke methods for susceptibility profiling developed for testing novel agents where standardised methods are not appropriate
  • Mechanism of action determination and in vitro target validation studies

In vivo models of infection

  • Evotec specialises in assessing the efficacy of lead and candidate compounds in highly relevant and validated disease models across all important pathogens including ESKAPE organisms, fungi, viruses, and parasites
  • Extensive range of established models that are well-suited to the development of multiple classes of agent including small molecules, natural products, peptides, antibodies, other biologics and vaccines
  • Multiple endpoints from pathogen to host, including biomarkers
  • Bespoke service and customised studies to meet the exact requirements based on programme needs and parameters/endpoints of interest
  • Compound efficacy assessment against bacterial, fungal, viral, and parasitic infections addressing different sites of infection (localised and systemic):
    • Gram-positive bacteria (including Staphylococcus aureus, Streptococcus pneumoniae)
    • Gram-negative bacteria (including Pseudomonas aeruginosa, Escherichia coli, Acinetobacter baumanii)
    • Anaerobes (including Clostridium difficile)
    • Fungal pathogens (including Candida spp., Aspergillus spp., Mucorales, Malassezia spp.)
    • Viruses (including Respiratory Syncytial Virus (RSV), Human Rhinovirus (HRV))
    • Parasites (including Toxoplasma gondii)

ADMET & PK/PD profiling

  • Translation of PK data into efficacy models to optimise outcomes and ‘humanisation’ of PK/dosing
    • Correlation of exposure with efficacy and drug response
    • Magnitude of effect
    • Defining PD drivers and which parameters are important to achieve efficacy
    • Understanding of post-antibiotic effect (PAE)
    • Mathematical modelling of data
  • ADME/PK profiling specific to the development of anti-infectives
  • Bioassay/bioactivity drug quantification
  • Development of bespoke PK models and assays with drug quantification in multiple tissues/sites
  • Tolerability assessment of new compounds utilising multiple endpoints

Evotec’s highly accomplished drug discovery platform including high-throughput screening, structure-based drug design, medicinal chemistry, bioinformatics research, proteomic, biomarker and reagent production platforms can also be accessed to support and accelerate anti-infective drug discovery programmes.

Summary

  • EvostrAIn™ – An extensive range of geographically diverse human pathogenic bacteria and fungi pathogens covering isolates susceptible and resistant to current antimicrobial drugs
  • Range of in vitro offerings for screening, compound profiling and MOA determination
  • Comprehensive range of established in vivo models encompassing bacterial, fungal, viral, and parasitic infections. Development of customised and bespoke models
  • Expertise with multiple classes of anti-infective agent including small molecules, natural products, peptides, antibodies, other biologics and vaccines

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