PROPOSAL PORTAL WILL OPEN 22 JUNE 2026 AT 11:59PM ET.
Download the full program announcement here.
Fighting Infections. Sparing the Rest.
Antibiotics are the foundation of modern medicine. Every year, one in three people worldwide rely on them to treat common conditions like urinary tract infections (UTIs), ear infections, and pneumonia.1,2 Beyond outpatient care, they are essential for the hundreds of millions of individuals who undergo surgery, receive chemotherapy, or need a solid organ transplant each year.3,4
However, this foundation is under global threat. Bacteria are developing resistance faster than we can innovate. Today, 1 in 6 infections are resistant to standard first-line treatments.5 The consequences of this crack in the foundation are severe. In 2021, resistant infections were linked to 1.14 million deaths, exceeding the death toll of HIV/AIDS or malaria. If left unaddressed, resistant infections are projected to kill more than 8 million people every year by 2050.6
What are the limits of current practice?
Bacterial resistance primarily arises due to selective pressure exerted by human use of antibiotics.7,8,9 While 85-90% of bacterial infections are local—contained to sites like the bladder, middle ear, skin, or lungs—nearly 100% of antibiotics are administered systemically via oral tablets or injections.10 This mismatch exposes the entire body, including the microbiomes (communities of trillions of generally non-harmful bacteria) to the antibiotic, creating selection pressure. The off-target impact on the gut microbiome in particular creates a “resistance factory” where antibiotics lead to resistant pathogen expansion.11,12,13,14 Gut colonization with a resistant pathogen makes individuals 20-times more likely to develop a future resistant infection.15,16,17
We need a novel approach. What if we could reformulate existing antibiotics to be focused – so that they treat the infection and spare the rest of our bacteria to avoid driving resistance?
Why now: Growing resistance meets new technologies
Our scientific understanding of and ability to document the microbiome has evolved, leading to a better understanding of how microbiome alterations contribute to resistant infections.18 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. These advances in microbiome science and therapeutic innovations provide the opportunity to focus antibiotics at the site of infection and avoid impact on the gut microbiome.19,20,21
What is the path forward?
Focused antibiotics can leverage these innovative technologies to avoid off-target effects on the trillions of bacteria normally residing in our microbiomes. Early research indicates that successful formulation of existing antibiotics using such technologies can drastically reduce selection of resistant pathogens in our gut microbiome while maintaining treatment efficacy. Three approaches, in particular are of interest:
- Approach 1: Release or activation of the antibiotic at the site of infection alone.22
- Approach 2: Minimize gut exposure to the active antibiotic by altering the pharmacokinetics of the molecule.23
- Approach 3: Direct delivery of the antibiotic to the site of infection.24
Program Goal
The goal of the Focused Antibiotics program is to reformulate existing antibiotics to spare the gut microbiome without loss of treatment efficacy.
Scaling these formulations as first-line therapeutics for the most common outpatient bacterial infections, Focused Antibiotics could reduce the global annual occurrence of antibiotic-driven resistant infections by as much as 40% — potentially avoiding over 100 million resistant infections even within a decade of real-world use.
Thrust 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 1 aims to design and develop focused antibiotics to treat urinary tract infections (UTI), lower respiratory tract infections (LRTI) and/or acute otitis media (AOM) that do not impact the gut microbiome while maintaining efficacy. We are interested in work that uses one of the three approaches listed above. Work is divided into two sub-thrusts:1A focusing on carrier discovery and optimization, and 1B focusing on pre-clinical development of investigational products.
Applicants can apply to both Thrust 1A and Thrust 1B or to Thrust 1A or 1B alone. Performers in Thrusts 1A and 1B are expected to maintain frequent, extensive collaboration. Technical developments must be shared every 3 to 6 months to facilitate the seamless transition of carriers from discovery (1A) into pre-clinical development (1B) and 1B performance data to directly inform 1A optimization. The objective is to achieve an overall portfolio success rate of at least 3 of 4 investigational candidates designed and selected in 1A completing successful demonstration in 1B.
Thrust 1A: Create new carrier options, such as nanoparticles or peptides, that can be formulated with existing antibiotics to enable the development of focused antibiotics.
Despite promising preclinical data, significant gaps remain in developing carriers for targeted antibiotic delivery systems. Thrust 1A seeks discovery and design efforts to establish well-characterized carrier options that enable focused delivery of antibiotics to the site of infection and eliminate impact on the gut microbiome.
Carriers that work across a range of different syndromes (especially urinary tract infection (UTI), lower respiratory tract infection (LRTI), and/or acute otitis media (AOM)) and can be compatible with first-line antibiotics will be prioritized.25,26,27,28,29,30 We are interested in approaches compatible with oral administration. Carriers may utilize passive, active, or stimuli-responsive targeting mechanisms, or combination approaches. Carriers may also be used to change an antibiotic’s pharmacokinetics such that it avoids impact on the gut microbiome. Carriers should demonstrate < 5% exposure of active antibiotic in the gut and retention of antimicrobial activity.
Thrust 1B: Through pre-clinical development, including IND-enabling development, demonstrate that focused antibiotics do not cause gut microbiome changes (as compared to placebo) and have the same efficacy in an animal model as standard first-line treatment for the relevant infection.
Thrust 1B is focused on the pre-clinical development of carrier technologies (e.g., nano-carriers or peptide-drug conjugates) or direct delivery technologies paired with existing antibiotics to address UTI, AOM, and/or LRTI. Use of first-line antibiotics for the indications proposed (e.g., amoxicillin) is strongly preferred. A non-first-line antibiotic may be used so long as there is a justification for using it. Preservation of the gut microbiome (no change in microbiome measures versus placebo), efficacy in in vitro and animal models versus first-line antibiotics for the targeted indication(s), safety, and prevention of resistance development should be demonstrated.
Thrust 2: Identify specific antibiotic-induced human gut microbiome changes that predict the development of subsequent resistant bacterial infection with >80% accuracy.
While it is well-established that antibiotic-induced alterations to the gut microbiome facilitate the development of resistant infections, a significant knowledge gap persists regarding the specific microbial changes that drive this risk. Without identifying these precise predictive factors, it remains challenging to refine focused antibiotic approaches or demonstrate the clinical value of microbiome-sparing therapies. Thrust 2 will bridge this gap by identifying specific antibiotic-induced gut microbiome changes that predict subsequent resistant bacterial infections with an accuracy >80%. Thrust 2 will also seek to identify microbiome factors that protect against antibiotic-induced microbiome changes, and quantify the population attributable fraction (PAF) for individual-level antibiotic use in the development of resistant bacterial infections.
Download the full program announcement here.
Program Director.
Call for abstracts and proposals.
We are soliciting abstracts and proposals for work over three (3) years in one or more of the following thrust areas (see Thrust areas in full program announcement). Proposers should clearly relate work in these thrust areas to one or more of the program goals.
It is not necessary to form a large consortium or teams to address all facets of the program. The strength of this approach will manifest through program-level integration of efforts from individuals and small agile teams with deep (and sometimes narrow) expertise. Across all projects, Wellcome Leap will facilitate iterative and collaborative integration of findings to refine models and improve and validate predictive measures and adapt approaches as teams make progress towards shared goals.
Process and timeline
30 DAYS FOR PREPARATION AND SUBMISSION OF ABSTRACT
15-Day Abstract review round
30 DAYS FOR PREPARATION OF FULL PROPOSALS AFTER ABSTRACT FEEDBACK
30-Day Full proposal review round
25-page full proposals including technical approach, milestones, costs, and key personnel submitted. Proposals should specifically address abstract feedback.
All submissions will receive a ‘selected for funding’ or ‘not selected for funding’ decision. Those selected will proceed to contract signature as the final gate with work expected to commence within approximately 30 days.
Who is eligible?
Performers from universities and research institutions; small, medium, and large companies (including venture-backed); and government or non-profit research organizations are invited to propose.
Wellcome Leap accepts project proposals from any legal entity, based in any legal jurisdiction, including academic, non-profit, for-profit, and regulatory/professional organizations. Applicants are encouraged to contact Wellcome Leap about joining its Health Breakthrough Network by executing its MARFA (or CORFA for commercial entities) agreement. Full execution of the Wellcome Leap MARFA is not required for application submission but is required for any award.
I understand that the information being disclosed will be reviewed and evaluated independently on behalf of Leap. I am submitting information with the intention that it imposes no confidentiality obligations on Leap. Furthermore, my submission does not breach any confidentiality obligations that I owe to others; there is no legal reason why I cannot submit information; and I am not underage or otherwise legally incompetent. By submitting, I am not granting, other than for the purpose of evaluation, any rights in relation to any patent, copyright, or design. I am not relying upon Leap in any way for legal advice, including (but not limited to) whether the contents of my submission can be protected under IP law. I recognize that Leap may already be aware of or funding the same or related efforts as described by my submission. I agree that no contractual obligation or working relationship is being created between myself and Leap by submitting this information. If the submission is deemed of interest, I may be required to sign a further Agreement with Leap so that any confidential information, that is subsequently shared, is protected.
I acknowledge and consent to the use of AI systems operated by third parties to process such data. These systems may generate summaries, insights or other recommendations based on the content of the application. You waive any claims against Wellcome Leap related to the use of AI for summarization, provided that complies with applicable laws and internal policies.
Full proposal application steps.
- Download guidelines
- Download full proposal template (and cost and schedule template)
- We’ll remind you when the application portal opens on 22 June 2026 at 11:59pm ET.
- Upload your full proposal and submit your application before 29 June 2026 at 11:59pm ET.
More details will be provided for the proposal round of submissions.
If you have questions, please review our FAQ section here – current version, updated 10 April 2026.
Send inquiries to focusedantibiotics@wellcomeleap.org