WHO antibacterial preclinical pipeline review
Published: August 2024
WHO’s 2023 update of the global review of antibacterial therapeutic products in preclinical development captures 244 antibacterial products that are in the preclinical stage as of 31 December 2023.
Candidate products are reported by country of development, type and size of developer, preclinical stage, infection stage being targeted, spectrum of action, 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.
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 (Panel A), by WHO region (chart A.1), income group (chart A.2), developer type (chart A.3), and size of developer institution (chart A.4) (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); where each agent may have more than one
- 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 of a new chemical class (chart H)
- whether or not agent has a new mechanism of action (chart I)
- treatment modality (chart J)
- mode of action (chart K)
- whether or not the agent is pathogen-specific (chart L) and the pathogens targeted (chart M); where each agent may have more than one
- whether or not the product is active against drug resistant phenotypes (chart N) and activity against drug-resistant phenotypes (chart O); where each agent may have more than one.
- 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 31 December 2023, a total of 244 antibacterial therapeutics are in preclinical development (click on each product type at the top left and view chart A.1).
- Around 55% of the products (134) are being developed in Europe, followed by the Region of the Americas (35%; 85) (chart A.1); with 95% (232) of the products being developed by high-income countries (chart A.2).
- Most products are developed by private institutions (65%; 160 products), followed by academic institutions (17%; 41 products) and public institutions (14%; 34 products), non-profit organizations (4%; 9 products). (chart A.3).
- Of the 244 products, 38.9% (95) are developed by micro-sized entities (<10 employees); small-sized entities with 11-50 employees account for 28.3% (69), followed by large (22.1%; 54) and medium-sized entities (10.7%;26). (chart A.4).
- 91% of the products (221) target the diseases at their symptomatic stage (chart C).
- 93% (227) of the products are new agents (chart E) and more than two-thirds (80%; 196) are single agents (i.e., direct-acting small molecules) (chart F).
- 148 products (61%) are direct-acting of which 115 are small molecules and 33 are antibacterial peptides (chart J).
- The top mode of action is ‘direct membrane effect’ (68 products) (chart K).
- 91 products (37%) are pathogen-specific, with the top three pathogens targeted being M. tuberculosis, Pseudomonas aeruginosa, and Staphylococcus aureus (with 26, 20 and 12 products, respectively) (select “yes” in chart L and view chart M).
- 48% (117) 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
- This antibacterial preclinical pipeline analysis focuses on products developed to address drug-resistant infections caused priority pathogen according to the WHO 2024 bacterial priority pathogen list 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 IRC Team. The WHO Advisory Group on the R&D of Antibacterial Treatments was also consulted and 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 WHO 2024 bacterial priority pathogens list. Assessment for use against OPPs was done for products not active against critical priority pathogens.
- Products developed against C. difficile were assessed in terms of these pathogens respectively. Their activity was not assessed against the priority pathogens.
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.