Wellcome Leap Program: Focused Antibiotics

Funding to redesign current antibiotics so they protect the gut microbiome while maintaining their effectiveness in treating infections.

The Wellcome Leap Program, established by Wellcome, aims to deliver breakthroughs in human health by providing funding at scale and within short timeframes. Wellcome Leap’s fifteenth funding initiative is Focused Antibiotics, which aims to reformulate existing antibiotics to spare the gut microbiome without loss of treatment efficacy.

Antibiotics play a crucial role in modern healthcare, with about a third of the global population depending on them each year to treat common infections such as ear infections and pneumonia. They are also vital for many medical procedures, including surgeries, chemotherapy and organ transplants. However, their effectiveness is increasingly at risk as bacteria evolve resistance more quickly than new treatments are developed. Currently, a significant portion of infections no longer respond to standard antibiotics, leading to serious consequences. Resistant infections already cause over a million deaths annually and, without action, could result in more than 8 million deaths per year by 2050.

Bacterial resistance largely develops because widespread antibiotic use puts pressure on microbes to adapt. Although most infections are confined to specific areas like the bladder, ear, skin or lungs, antibiotics are usually delivered throughout the whole body. This broad exposure affects not only the targeted bacteria but also beneficial microbial communities, especially in the gut, encouraging the growth of resistant strains. As a result, people carrying these resistant bacteria are far more likely to develop difficult-to-treat infections in the future.

A novel approach is needed to avoid resistance by reformulating existing antibiotics so they focus on treating the site of infection and avoid impact on the gut microbiome. There is now a better understanding of how microbiome alterations contribute to resistant infections. Therapeutic innovations have shown that targeted treatment using nano-carriers or peptide carriers can reduce off-target effects on human cells and improve treatment success. Three approaches in particular are of interest:

• Approach 1: Release or activation of the antibiotic at the site of infection alone.
• Approach 2: Minimise gut exposure to the active antibiotic by altering the pharmacokinetics of the molecule.
• Approach 3: Direct delivery of the antibiotic to the site of infection.

Proposals are required for work in one or more of the following Thrust Areas:

• Thrust Area 1: Demonstrate investigational focused formulations of existing antibiotics that do not impact the gut microbiome while maintaining or improving efficacy relative to standard-of-care antibiotics in pre-clinical in vitro and animal models.
• Thrust Area 2: Identify specific antibiotic-induced human gut microbiome changes that predict the development of subsequent resistant bacterial infection with >80% accuracy.
  

Proposers should clearly relate work in these Thrust Areas to one or more of the programme goals. The programme seeks to demonstrate the success of the approach for three of the most common human infections: ear infections, respiratory infections and urinary tract infections. Together, these infections account for more than half of all outpatient antibiotic prescriptions.