Given the nascent and nuanced field of SBE R&D, we sought to use the broadest possible inclusion criteria and incorporated various types of molecules or biologics tested for or used with direct action against snake venom toxins with product development in mind. Products and candidates could be applicable for use in any context, including high-income countries and low- and middle-income countries.

For inclusion in the dataset, products and candidates needed to:

• Be synthetic or natural small molecules (drugs) or immunoglobulin (animal plasma/serum-derived or recombinant) or non-immunoglobulin- (animal, natural or recombinant) based biological therapies (biologics), with no restrictions: entries could be entirely new chemical or biological entities (NCEs) or existing/repurposed/label extensions
• Have a direct inhibitory action on snake venom toxins, neutralising venom components to have a therapeutic effect on snakebite envenoming
• Have evidence of research and development (candidates) towards product development, or use (products) at any point since 2015
• Be either investigated for potential clinical use and/or used currently in clinical treatment of snakebite envenoming from WHO medically important category 1 or 2 snakes (or both) only

Specific exclusions were:

• Adjunct and supportive therapies which only modify responses to action of and symptoms caused by snake venom toxins
• Devices, diagnostics and other non-medicine-related biomedical products with an indication for SBE
• Basic and fundamental research which was not geared towards product development

We undertook a series of partially sequential, partly overlapping, but mutually reinforcing steps to develop a database of product and candidate profiles. These were:

1. Identify and validate products and candidates through multiple sources that are or were in use or in development since 2015;
2. Collect information on the products’ and candidates’ preclinical and/or clinical development, and associated data;
3. Research additional context around the products and candidates (e.g., immunisation/production strategy, paraspecificity, region of use and/or registration etc.,) to build out multi-field entry profiles;
4. Validate and sense check candidate profiles through independent, external reviews by clinical research and subject matter experts in the field.

For a more detailed description of the methodology, see here.

We found a total of 127 products marketed and/or available for use, along with 196 candidate medicines (drugs and biologics) actively investigated since 2015.

Available SBE products, while many, are:

• uniform (they are entirely animal plasma-derived antibody-based antivenoms);
• highly species specific and immunoreactive;
• expensive to produce;
• and require only limited safety and effectiveness evidence to enter the market: just under half of products have neither preclinical nor clinical evidence available.

Novel SBE therapeutics under investigation are many and diverse, including new plasma-derived antivenoms, recombinant (some humanised) antibodies and fragments, whole proteins or peptides, DNA aptamers, synthetic small molecules and botanical extract isolates and compounds.

Nearly all candidates are in discovery or preclinical stages of development, with just eight in clinical development: two synthetic drugs and six animal plasma-derived immunoglobulin (traditional type antivenom) biologics.

Notably, the two drug candidates in clinical development – methyl-varespladib and DMPS (unithiol) – have only appeared recently in the SBE R&D space. Both of these are repurposed drugs, offering insight into the pace of progress that might be expected going forward, especially given over a third of all candidates are repurposed.