Antibacterial R&D is very hard! Two great pipeline reviews + an Industry-level view

So, if you want a new antibacterial, you should have started 15-25 years ago: 9-10 years from the start of Phase 1, plus the 5-15 years before Phase 1.  

Ugh. Makes one think first of the lessons of the 9 Apr 2024 newsletter entitled “48,015 → 0: Antibacterial discovery is hard. Really, really hard” (the title is the message) and then of FDA’s 40-year review of timelines (Dheman et al., 30 June 2020 newsletter) which concluded that the development times from IND to approval would rise to above 9 years and that success rates were steadily falling. In addition, a related paper by Darrow et al. (30 June 2020 newsletter again) noted that antibacterial agents fell behind all other antimicrobials in their ability to use the expedited designations that facilitate development: Orphan Drug, Priority Review, Fast Track, Accelerated Approval, and Breakthrough Therapy Designation.

Inhale, exhale — but then get back to the research bench! The lesson from the papers by Theuretzbacher et al. and Paterson is that continuous innovation is going to be needed to keep us ahead of the pace of emergence of resistance: #AMRSOS! GRAM report: “at least 1.27m deaths/year directly attributable to AMR.”

And yet it is frustratingly hard to bring innovative products to market. There is a deep challenge here that revolves around our lack of a good way to develop antimicrobials for rare infections. We have tools for rare diseases (e.g., genetic diseases) but not for rare infections. Hmm! Hmm!

Meditatively yours, John and Stephan

John H. Rex, MD | Chief Medical Officer, F2G Ltd. | Operating Partner, Advent Life Sciences. Follow me on Twitter: @JohnRex_NewAbx. See past newsletters and subscribe for the future: https://amr.solutions/blog/. All opinions are my own.

Stephan Harbarth, MD, MS | Hôpitaux Universitaires de Genève | stephan.harbarth@hug.ch | All opinions are my own.

Current funding opportunities

• The Trinity Challenge on Community Access to Effective Antibiotics is a £1 million innovation competition that seeks applications to answer the question: “How can data and technology improve stock control and/or reduce the use of substandard and falsified oral antibiotics for community use in low- and middle-income countries?” Applications are open at this website until 24 April 2025.
• HERA posted a call on 24 Mar 2025 entitled “Development of a Rapid Point-of-care Antimicrobial Susceptibility Testing Diagnostic Medical Device (HADEA/2025/CPN/0006).” In it, they call for tenders under which they will provide up to 13m EUR for development of a point-of-care diagnostic medical device that can provide antimicrobial susceptibility results on the bacteria or fungi causing an infection in humans, within one hour or less from subject sample collection, and ideally, to also allow for pathogen identification. To apply, you must submit a request to participate by 12 May 2025; selected candidates who met the eligibility criteria will be able to submit a full technical tender. Go to the EU Funding and Tenders Portal to apply; see also the 19 Feb 2025 newsletter for details.
• ENABLE-2 has continuously open calls for both its Hit-to-Lead program as well as its Hit Identification/Validation incubator. Applicants must be academics and non-profits in Europe due to restrictions from the funders. Applications are evaluated in cycles … see the website for details on current timing for reviews. 
• CARB-X will have two during 2025 that span two areas: (i) Small molecules for Gram-negatives (the focus is on Pseudomonas aeruginosa) and (ii) Diagnostics for typhoid (the focus is diagnosis of acute infections in 60 minutes or less). See this 26 Feb 2025 newsletter for a discussion of the call and go here for the CARB-X webpage on the call. The first cycle will accept expressions of interest during the window 16-30 April 2025; the 2nd round will be open 1-12 Dec 2025.
• BARDA’s long-running BAA (Broad Agency Announcement) for medical countermeasures (MCMs) for chemical, biological, radiological, and nuclear (CBRN) threats, pandemic influenza, and emerging infectious diseases is now BAA-23-100-SOL-00004 and offers support for both antibacterial and antifungal agents (as well as antivirals, antitoxins, diagnostics, and more). Note especially these Areas of Interest: Area 3.1 (MDR Bacteria and Biothreat Pathogens), Area 3.2 (MDR Fungal Infections), and Area 7.2 (Antibiotic Resistance Diagnostics for Priority Bacterial Pathogens). Although prior BAAs used a rolling cycle of 4 deadlines/year, the updated BAA released 26 Sep 2023 has a 5-year application period that ends 25 Sep 2028 and is open to applicants regardless of location: BARDA seeks the best science from anywhere in the world! See also this newsletter for further comments on the BAA and its areas of interest.
• HERA Invest was launched August 2023 with €100 million to support innovative EU-based SMEs in the early and late phases of clinical trials. Part of the InvestEU program supporting sustainable investment, innovation, and job creation in Europe, HERA Invest is open for application to companies developing medical countermeasures that address one of the following cross-border health threats: (i) Pathogens with pandemic or epidemic potential, (ii) Chemical, biological, radiological and nuclear (CBRN) threats originating from accidental or deliberate release, and (iii) Antimicrobial resistance (AMR). Non-dilutive venture loans covering up to 50% of investment costs are available. A closing date is not posted insofar as I can see — applications are accepted on a rolling basis; go here for more details.
• The AMR Action Fund is open on an ongoing basis to proposals for funding of Phase 2 / Phase 3 antibacterial therapeutics. Per its charter, the fund prioritizes investment in treatments that address a pathogen prioritized by the WHO, the CDC and/or other public health entities that: (i) are novel (e.g., absence of known cross-resistance, novel targets, new chemical classes, or new mechanisms of action); and/or (ii) have significant differentiated clinical utility (e.g., differentiated innovation that provides clinical value versus standard of care to prescribers and patients, such as safety/tolerability, oral formulation, different spectrum of activity); and (iii) reduce patient mortality. It is also expected that such agents would have the potential to strongly address the likely requirements for delinked Pull incentives such as the UK (NHS England) subscription pilot and the PASTEUR Act in the US. Submit queries to contact@amractionfund.com.
• INCATE (Incubator for Antibacterial Therapies in Europe) is an early-stage funding vehicle supporting innovation vs. drug-resistant bacterial infections. The fund provides advice, community, and non-dilutive funding (€10k in Stage I and up to €250k in Stage II) to support early-stage ventures in creating the evidence and building the team needed to get next-level funding. Details and contacts on their website (https://www.incate.net/).
• These things aren’t sources of funds but would help you develop funding applications
  • The Global AMR R&D Hub’s dynamic dashboard (link) summarizes the global clinical development pipeline, incentives for AMR R&D, and investors/investments in AMR R&D.
  • Diagnostic developers would find valuable guidance in this 6-part series on in vitro diagnostic (IVD) development. Sponsored by CARB-X, C-CAMP, and FIND, it pulls together real-life insights into a succinct set of tutorials.
• In addition to the lists provided by the Global AMR R&D Hub, you might also be interested in my most current lists of R&D incentives (link) and priority pathogens (link).