CC4CARB: (free!) rationally designed compound libraries based on your ideas!

Dear All,

NIAID and RTI International have recently announced the initiation of CC4CARB Chemistry Center for Combating Antibiotic Resistance). In brief,

  • CC4CARB synthesizes compound libraries (free of charge!) based on scaffolds that you propose
  • The focus is on creating novel chemical matter that might have antibacterial activity (there appears to be a focus on Gram-negatives, but there is also mention of Gram-positives)
  • The library comes pre-formatted on 96-well plates (or as solids) and will be made available first to the proposal submitter but also to other requestors if approved by NIAID.  
  • Under a separate contract, MIC testing is performed with the library compounds on select drug-resistant and wild type Gram-negative and Gram-positive bacteria.
  • Here’s their brochure
  • The website is https://www.cc4carb-collection.org/

Wow! Per a presentation on the website, the ultimate goal is a curated, structurally diverse library of about 8k compounds that can be screened as desired. In effect, this addresses the challenges of the cost of library construction raised by Miethke et al. (2021 Nature Reviews Chemistry).

The issue of IP (intellectual property; a patent on any drug ultimately discovered based on the library) is not covered on the CC4CARB website, but one can guess that compounds in the library would be unlikely to be an actual drug candidate. On this point, I’ve learned that NIAID is currently considering a contract modification to allow the proposal submitter time to patent their idea(s) prior to the information being made public. They envision an embargo period of ~6 months after the last compound is made for the agreed Individual Library Production Plan (ILPP). Importantly, compounds may be sent in smaller bunches to make the compounds available to organization sooner than at the end of the ILPP. Since an ILPP will take ~9 to ~12 months to complete, the submitter will likely start receiving compounds ~3 months after the start of the ILPP. Also, CC4CARB is currently accepting scaffold ideas if they are covered under a patent to support analog production. 

All to the good as pooled community thinking is a valuable tool! On that theme, I also note that the Open Source Antibiotic project (go here for their Feb 2022 newsletter) is currently working on two compound series. 

While I am pleased to see these projects, the development curmudgeon in me has to note that finding a clinical candidate drug is only the start: the work of pre-IND GLP testing, GMP manufacturing, and clinical development will require further years of effort and incur several hundred million dollars in costs. The CC4CARB team says that NIAID and RTI will work with submitters to progress any critical discoveries as would (I am sure) CARB-X and Novo REPAIR.

And even if all of the work up to initial approval were free, there would still be a requirement for approximately $350m in running costs over the next 10 years just to keep the lights on and do required further R&D. These are real costs (9 Jan 2021 newsletter) that cannot be avoided if you want the drug to be available in the clinic — if there were a less expensive path, every small company would be on it.

And yet the recent GRAM report (“At Least 1.27m Deaths/Year Directly Attributable To AMR”) makes it clear that we desperately need new therapies … and for that we need pull incentives such as the PASTEUR Act.

OK … end of rant! Fingers crossed for progress on new mechanism compounds as well as pull incentives during 2022! 

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):

  • NIAID has released a four-pronged BAA (Broad Agency Announcement (HHS-NIH-NIAID-BAA2022-1) that covers therapeutics (antibacterial, antifungal, antiviral), vaccines (again, all 3 areas), and diagnostics. Lots of possibilities! The due date is 18 Mar 2022.
  • BARDA is seeking proposals under Project BioShield to support late stage development, regulatory approval and potential procurement of antibiotics against biothreat pathogens, Yersinia pestis, Francisella tularensis, and Burkholderia pseudomallei.  Small businesses can apply until April 6, 2022. Go here for the details.
  • JPIAMR’s 14th call is now open. Entitled “Disrupting drug resistance using innovative design”, the call seeks consortia that would seek to “improve the treatment of bacterial and fungal infections (including co-infection) and/or 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! Pre-proposals are due 8 Mar 2022; full proposals would be due 5 July 2022. Go here for details.
  • 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 contact@amractionfund.com.
  • 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!
  • 23 Feb 2022 (virtual, 8-9a EST): Pre-application webinar to provide more information and to answer questions. Register here.
  • 3 Mar 2022 (virtual, 2p GMT): The Longitude Prize (run by Nesta Challenges), CARB-X and FIND, have joined forces for a virtual event in March, AMR& Diagnostic Frontiers: Developing and increasing access to innovative diagnostics in and for low-and-middle-income countries (LMICs). Full agenda details and registration can be found here, including an invitation for diagnostic companies to pitch to a panel of global health representatives.
  • 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.
  • 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 AllianceCARB-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.

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