First up, we have an update to WHO’s review of the clinical antibacterial pipeline. The review by Butler et al. in AAC (and for transparency, know that I am a co-author) covers both traditional and non-traditional products. It found that as of 30 June 2021:
- There were 76 antibacterial agents in clinical development (45 traditional and 31 non-traditional) with 28 in Phase 1, 32 in Phase 2, 12 in Phase 3, and four under regulatory evaluation.
- Forty-one out of 76 (54%) targeted WHO priority pathogens, 16 (21%) against mycobacteria, 15 (20%) against C. difficile, and 4 (5%) are non-traditional agents with broad-spectrum effects.
- Nineteen of the 76 antibacterial agents have new pharmacophores and four of these have new modes of actions not previously exploited by marketed antibacterial drugs.
- Despite there being 76 antibacterial clinical candidates, this analysis indicated that there were still relatively few clinically differentiated antibacterial agents in late-stage clinical development, especially against critical Priority Pathogens.
The antibacterial pipeline is so VERY thin! Per the report’s Tables 2 and 3, there are only 7 late-stage or recently approved products covering a WHO Critical pathogen (carbapenem-resistant Acinetobacter, Pseudomonas, or Enterobacteriales; go here to review the various priority pathogen lists). Five of these were approved in the window July 2017 to June 2021 and 2 are currently in Phase 3. By comparison, one estimate found that there were ~1300 drugs in development for cancer in 2020.
OK, so that’s the bad news. But, I will remind you that the current P3 pipeline is the result of decisions made 10+ years ago … it takes years for things to reach this stage (for more on this, see Dheman 2020 CID and the accompanying Rex-Outterson editorial). Encouragingly, however, the current funding environment is starting to show real signs of preclinical innovation. As discussed in this 17 Mar 2021 newsletter, a recent preclinical pipeline review noted 135 direct-acting small molecule projects that represented potential new classes, new targets, or new mechanisms of action. It just takes time … and lots of it (for more insight, see this 17 Jan 2020 newsletter for a time-to-best-in-class graphic)
On that note, JPIAMR’s 14th call is now open and seeks to address this very problem! Entitled “Disrupting drug resistance using innovative design”, the call seeks consortia that would seek to (formatting added for clarity):
- “improve the treatment of bacterial and fungal infections (including co-infection)
- “the prevention of the emergence/spread of resistance in humans, animals or plants
- “through the improvement of the efficacy, specificity, delivery, combinations and/or repurposing of drugs and plant protection agents.”
Bacteria, fungi, human health, animal health, and plant health are all in scope for this intriguing call. Repurposing is tricky but as Sir James Black (1988 Nobel in Medicine for work leading to the discovery of propranolol and cimetidine) is famously quoted as saying, “The most fruitful basis for the discovery of a new drug is to start with an old drug.” So, I’ll cross my fingers for success from this project!
Could this be you? Pre-proposals are due 8 Mar 2022; full proposals would be due 5 July 2022. Go here for details!
All best wishes, –jr
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.
Current funding opportunities (most current list is here):
- The AMR Action Fund is now open 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 firstname.lastname@example.org.
- INCATE (Incubator for Antibacterial Therapies in Europe) is a newly launched early-stage funding vehicle. Details are still coming into focus, but per comments on 25 Aug 2021 at the BIOCOM conference, their goal is to support ~4 companies per year with about $250k/company. Contact details are on their website (https://www.incate.net/).
- CARB-X recently announced that their existing resources will be reserved to fund their existing portfolio (more than 80 total awards, and counting, as they include contracting from prior rounds). New rounds from CARB-X will occur only after new funding is obtained in 2021.
- It’s not a funder, but AiCuris’ AiCubator offers incubator support to very early stage projects. Read more about it here.
- 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.
- 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).
Upcoming meetings of interest to the AMR community (most current list is here):
- [If you missed it, you can now watch the video] 8 Dec: “The New Winds Pushing and Pulling Antibacterial Development.” This was a GREAT program that featured talks from the UK team behind the NHS “Netflix” pilot, Kevin Outterson’s recently released report documenting the need for global Pull incentives to have a value of $2.2 – 4.8b, and speakers covering PASTEUR and work in the EU on pull incentives. The video is here — please make time to listen to this program!
- [NEW] 19 Jan 2022 (virtual): REVIVE (GARDP) Webinar: Target candidate profiles and target product profiles for new antimicrobials. Moderated by Sumati Nambiar, the program will cover perspectives on new agents both from WHO and Industry. Go here to register.
- [NEW] 26 Jan 2022 (virtual, 2-3.30p CET): REVIVE (GARDP) Webinar: New technologies and strategies to overcome the challenges of sexually transmitted infections. Moderated by Amir Schroufi and Remco Peters, the program will covers strategies for managing STDs with a particular focus on the developing world. Go here to register.
- 2-3 Feb 2022 (virtual): 10th Advances Against Aspergillosis and Mucormycocosis. Registration closes on 30 Jan 2022. Go here for details.
- 2-3 Feb 2022 (virtual): Antimicrobial Chemotherapy Virtual Conference jointly organised by GARDP with the British Society for Antimicrobial Chemotherapy (BSAC), Center for Disease Dynamics, Economics & Policy (CDDEP) and the Indian Council of Medical Research (ICMR). Click here for details.
- 3-6 Mar 2022 (Albuquerque, New Mexico): Biannual meeting of the MSGERC (Mycoses Study Group Education and Research Consortium). Details are here.
- 6-11 Mar 2022 (Il Ciocco, Tuscany): Gordon Research Conference entitled “New Antibacterial Discovery and Development”. Go here for details, go here for the linked 5-6 Mar Gordon Research Seminar that precedes it.
- [NEW] 9 Mar 2022 (virtual, and in-person): BioInfect Conference, Alderley Park, UK (near Manchester). This long-running Bionow-sponsored annual conference draws a very strong audience. Go here for details.
- 7-8 Apr 2022 (Basel and in person, we hope): The 6th edition of the annual AMR conference sponsored by the BEAM Alliance, CARB-X, the Novo REPAIR Impact Fund, the IMI Accelerator, and the European Biotechnology Network. Go here for the hold-the-date page and a way to be kept informed about the meeting.
- 9-13 May 2022 (Athens and online): 40th Annual Meeting of the European Society for Paediatric Infectious Diseases, Go here for details.
- 20-24 Sep 2022 (New Delhi): 21st Congress of the International Society for Human and Animal Mycology (ISHAM). Go here for details.
- 25-28 Oct 2022 (Stellenbosch, South Africa): The University of Cape Town’s H3D Research Centre will celebrate its 10th anniversary with a symposium covering the Centre’s research on Malaria, TB, Neglected Tropical Diseases, and AMR. Go here to register.