WHO antibacterial preclinical pipeline review
Published: June 2022
WHO’s 2021 update of the global review of antibacterial therapeutic products in preclinical development captures 217 antibacterial products that are in the preclinical stage as of September 2021.
Candidate products are reported by country of development, type and size of developer, preclinical stage, infection stage being targeted, route of administration, treatment modality and mode of action. Some characteristics of the products are also reported such as whether the product is new or repurposed, is a new chemical class or if it has a new mechanism of action. Details of pathogen-specific products and activity against drug-resistant phenotypes are also reported.
See also:
Health products in the pipeline from discovery to market launch for all diseases
What you see | Scope and limitations | Data sources | Previous versions
What you see
The data visualization shows the numbers of antibacterial products by:- geographical distribution and developer’s characteristics (charts A). (hover over the circles in chart A for details on the country and number of products)
- preclinical stage (chart B)
- infection stage targeted (chart C)
- route of administration (chart D)
- new agent or repurposed (chart E)
- single agent or combination (chart F)
- whether or not agent has non-traditional modality (chart G)
- whether or not agent is new chemical class (chart H)
- whether or not agent is new or repurposed (chart I)
- treatment modality (chart J)
- mode of action (chart K)
- whether or not the product is pathogen-specific (chart L) and the pathogens targeted by the products (chart M).
- whether or not the product is active against resistant phenotypes (chart N) and drug-resistant phenotypes targeted by the products (chart O)
- list of products with further information on each product (chart P) (hover on the stage to open a popup window for additional information, including product developer).
Points to note:
- As of September 2021, a total of 217 antibacterial therapeutics are in preclinical development (click on each product type at the top left and view chart A.1).
- Around 52% of the products (113) are being developed in Europe, followed by the Americas region (35%; 76) (chart A.1); with 92% (199) of the products being developed by high income countries (chart A.2).
- Most products are developed by private institutions (64%; 140 products), followed by public institutions (20%; 44 products) (chart A.3).
- 37% of the products (81) are developed by micro sized entities (<10 employees), followed by small and large to medium sized entities (33% and 31% of products, respectively) (chart A.4).
- Almost 88% of the products (232) target the diseases at their symptomatic stage (chart C).
- 92% (199) of the products are new agents (chart E) and more than two-thirds (70%; 152) are single agents (i.e., direct-acting small molecules) (chart F).
- 90 products (41%) are direct acting antimicrobial peptides (chart J).
- The top mode of action is 'direct membrane effect' (56 products) (chart K).
- 95 products (44%) are pathogen-specific, with the top three pathogens targeted being Pseudomonas aeruginosa, M. tuberculosis and Staphylococcus aureus (with 21, 20 and 19 products respectively) (select “yes” in chart L and view chart M).
- 59% (128) of products are active against resistant phenotypes (chart N).
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, analysis and limitations of the data
Scope
- The review focuses on candidate antibacterial products that target WHO priority pathogens, Mycobacterium tuberculosis and Clostridioides 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;
--topical decolonising agents;
--non-specific inorganic substances;
--biodefence agents;
--agents not developed for systemic use (injectable or oral formulations) or inhalation but only for topical application (e.g., creams or eye drops);
--new formulations of existing treatments;
--authorised antibacterials that are being repurposed.
Analysis
- The analysis was conducted by the WHO Advisory Group on the R&D of Antibacterial Treatments comprised of clinicians, microbiologists, and leading experts in antibiotic R&D, pharmacokinetics/pharmacodynamics (PK/PD) and antibiotic resistance.
- Products under development (at or in the three years prior to the review) were assessed against the available evidence of activity against the priority pathogens. Assessment for use against OPPs was done for products not active against critical priority pathogens.
- Products developed against M. tuberculosis and C. difficile were assessed in terms of these pathogens respectively. Their activity was not assessed against the priority pathogens.
- Antibacterial products are evaluated against the four WHO Innovation criteria: new chemical class, new target, new mode of action and absence of known cross-resistance.
Limitations of the data
- The report relies on data available in the public domain and input from the WHO Technical Advisory Group on R&D.
- Particularly, the analysis and assessment of the preclinical pipeline relies largely on data submitted by the respective developers through the open WHO data call. When available other sources were used for additional information, or the developer was contacted for clarification.
- The WHO Secretariat welcomes any additional information and/or feedback on the data presented in this document, which should be sent to: antibacterialpipeline@who.int for incorporation in subsequent reviews.