WHO antibacterial preclinical pipeline review

Published: November 2019

WHO’s first global review of antibacterial products in preclinical development captures 252 antibacterial products that are being developed in 145 institutions around the world. These products target WHO priority pathogens, Mycobacterium tuberculosis and Clostridium difficile. This is the first comprehensive overview of the preclinical antibacterial pipeline to date that is based on publicly available data. This overview will be updated on a regular basis.

Candidate products are reported by country of development, preclinical stage, treatment modality, infection stage being targeted, product type, mode of action, and pathogen category for pathogen-specific products. Details of bacterial spectrum target, route of administration and developers are also reported. 

See also:

Antibacterial products in clinical development for priority pathogens

Health products in the pipeline from discovery to market launch for all diseases

What you see | Scope and limitations | Data sources | Current version

What you see

The data visualization shows the numbers of antibacterial products by geographical distribution (charts A), preclinical stage (chart B), treatment modality (chart C), infection stage targeted (chart D), and product type (chart E). Popups in chart A give details of country and number of products (hover over the circles). Chart F shows the bacterial spectrum targeted and chart G the route of administration. The pathogens targeted by, and the mode of action of the products are shown in chart H and chart I respectively. Chart J lists the products by preclinical stage together with further information on each product (hover on the stage to open a popup window for additional information, including product developer, mode of action).

Points to note:

  • A total of 252 antibacterial products targeting the WHO priority pathogens, Mycobacterium tuberculosis and Clostridium difficile are in preclinical development (chart B).
  • The majority of products (51%) are being developed in Europe, followed by the Americas region (34%) (chart A).
  • 108 products are single agents (i.e. direct-acting small molecules) followed by 28 that are phage/phage products and 27 that are antimicrobial peptides (chart C).
  • More than three quarters (76%; 242) of all the products target the diseases at their symptomatic stage (chart D); over 80% of all the products are curative treatments (chart E).
  • 100 products (40%) target a single pathogen, with 43 of those targeting Mycobacterium tuberculosis (select “targeted pathogen specific” in chart F and view chart H).
  • Almost one third (29%; 75) of the products target cell wall synthesis or directly act on the membrane (hold the ‘Ctrl’ key to select both “Cell wall synthesis” and “Direct membrane effect” in chart I and view the numbers).

To explore the data further

  • Select a stage of development, product type, spectrum, pathogen, or another element (e.g. by clicking on a bar in a chart or a cell in a table) – or a combination of elements– to display the corresponding data in the other charts.
  • Hover the cursor on a bar, a slice in a pie chart or a cell in a table to see more information in a popup window.
  • Hold the ‘Ctrl’ key on your keyboard to select more than one option.
  • Undo a selection by clicking ‘undo’ or ‘reset’ near the bottom of the page or by clicking the same element again.

Scope and limitations of the data

Scope
  • The review focuses on candidate antibacterial products that target WHO priority pathogens, Mycobacterium tuberculosis and Clostridium difficile that are in lead-optimization (post hit expansion), preclinical candidate, to formal Investigational New Drug Application (IND). IND is also termed as a Clinical Trial Application (CTA), or for regulatory authorities that do not use IND/CTA, this is indicative of the commencement of human testing.
  • The review includes both traditional and non-traditional products:
    -- direct- and indirect-acting antibacterials;
    -- small and large molecules;
    -- antivirulence agents;
    -- biofilm disruptors;
    -- potentiators;
    -- microbiome modifying agents;
    -- immunomodulators;
    -- re-purposed non-antibiotics and antibiotics from animal to human use;
    -- de-colonisation agents;
    -- combination therapies.
  • The review does not include:
    -- vaccines;
    -- diagnostics;
    -- antifungals;
    -- antivirals;
    -- antiparasitics;
    -- wound care agents;
    -- unspecific supportive treatments;
    -- medical devices;
    -- products for industrial or animal use.

 

 Limitations of the data

 

  • The preclinical pipeline review relies largely on data submitted by the respective developers through an open WHO data call.
  • A thorough data cleaning was undertaken and, where available, other sources were used for additional information. Alternatively, the developer was contacted to clarify or fill gaps in the submission.
  • In the absence of clinical data as well as detailed data on the different molecules in development, no independent assessment was undertaken with respect to the bacterial targets or innovativeness of the individual projects.
  • The WHO Secretariat welcomes any additional information and/or feedback on the data presented in this document, which should be sent to paulins@who.int. WHO will hold another open WHO data call for the next antibacterial preclinical pipeline review at a future date; it encourages wide participation.