Lessons in Discovery from Lynn Silver + Pro-con on alternatives to antibiotics

Dear All:

“Good decisions come from experience, and experience comes from bad decisions … and paying attention.”

You’ve probably heard the first part of that before, but the “… and paying attention” is my addition and reflection upon reading Lynn Silver’s most recent commentary in the Springer Series Topics in Medicinal Chemistry, edited by Jed Fisher, Marvin Miller and Shahriar Mobashery. Entitled “The Antibiotic Future,” it is a discussion of the hurdles of antibiotic discovery and a summary of Lynn’s far-ranging & pithy insights. It’s not open access so you’ll have to download yourself, but here’s the link and the abstract:

  • Cite: Silver LL. The Antibiotic Future. In: Fisher J, Miller M, Mobashery S, editors. Topics in Medicinal Chemistry. Berlin, Heidelberg: Springer Berlin Heidelberg; 2017. p. 1-37.
  • Link: https://link.springer.com/chapter/10.1007/7355_2017_24
  • Abstract: Will the future of antibacterial therapy rely on an ongoing pipeline of new small molecule, direct-acting antibacterial agents that inhibit or kill bacterial pathogens, referred to here as antibiotics? What role will these small-molecule antibiotics have in the control of the bacterial infections of the future? Although there is today increased activity in the field of new antibiotic discovery, the history of this field over the past 30 years is a history of low output. This low output of new antibiotics does not encourage confidence that they can be central to the future control of bacterial infection. This low productivity is often blamed upon financial disincentives in the pharmaceutical industry, and on regulatory difficulties. But I believe that a critical underlying reason for the dearth of novel products is the fundamental difficulty of the science, coupled with a failure to directly grapple with the key scientific challenges that prevent forward motion. The future fate of antibiotic discovery will depend upon the degree to which the rate limiting steps of discovery are fully recognized, and the discovery technology turns to overcoming these blockades.

In the paper, Lynn covers everything from alternatives to antibiotics (see also below), natural products, the problem of frequency of resistance, combinations, the question of new vs. old targets, and more. This paper is great tour of the entire area and you’ll learn something from it whether you are new to the field or an old hand.

Lynn is truly a master of this field and she has over the years written many instructive papers. Just below, I provide a list of some of my favorites from her published works. If you’re doing drug discovery and haven’t explored her writings, I strongly encourage you to take an afternoon to study them in detail. I especially recommend the 2011 paper in CMR:

Finally, and if you’re interested in non-antibiotic alternative approaches, Lynn’s comments on this area may make you want to dig further. A good place to start would be with the 3 papers below — collectively, they provide a good set of pro-con comments on the challenges of this strategy. The alternatives that seek to work in combination or as enhancers are going to be very tricky to develop and it’s important to understand the issues:

In short, knowing what has come before is the only way that I know to avoid repeating past mistakes. If you’re going to make a mistake, please make a new one … it’s much more productive! Many thanks to Lynn for sharing her insights via these publications.

Best wishes,

–jr

John H. Rex, MD | Chief Medical Officer, F2G Ltd. | Chief Strategy Officer, CARB-X | Expert-in-Residence, Wellcome Trust. Follow me on Twitter: @JohnRex_NewAbx. See past newsletters and subscribe for the future: http://amr.solutions/blog.html

Upcoming meetings of interest to the AMR community:

Dear All,
 
The IDWeek 2024 program committee is again seeking programs on novel antimicrobial agents and novel diagnostics for presentation in pipeline sessions! Here’s what is sought:

  • “Industry partners are invited to submit antimicrobials that are in preclinical stages of development (Phase II and III preferred) or recently approved after January 2024.
  • “The pipeline sessions will include antibacterials, antifungals, and antivirals (excluding COVID-19 and HIV).
  • “The committee also invites companies developing novel diagnostic technologies with a minimum of some preliminary proof of concept data to submit.” 

This is a great opportunity to tell the story of your development project! The deadline to submit is Wednesday, June 26 via the application portal. Any questions should be directed to program@idsociety.org. Please share this email with anyone you think might be interested in applying!
 
In addition, I’ll also note that those with a more general story to tell should look at the BugHub Stage (and the Global BugHub stage). Both BugHub variants seek “presentations that touch on your experience of working in infectious diseases and presentations that ultimately lead to a greater understanding of our diverse field” via a TED Talk-esque speech about your work. The deadline for applications is 26 June, the same as for the pipeline sessions.

I look forward to seeing you there! 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.

John’s Top Recurring Meetings

Virtual meetings are easy to attend, but regular attendance at annual in-person events is the key to building your network and gaining deeper insight. My personal favorites for such in-person meetings are below. Of particular value for developers are the AMR Conference and the ASM-ESCMID conference. Hope to see you there!

  • 27-30 April 2024 (Barcelona, Spain): 34th ECCMID, the annual meeting of the European Society for Clinical Microbiology and Infectious Diseases. Go here for details. 
  • 17-20 Sep 2024 (Porto, Portugal): ASM/ESCMID Joint Conference on Drug Development to Meet the Challenge of Antimicrobial Resistance. Go here for the meeting’s general website. You can’t register (yet) for the 2024 event, but save the date!
  • 16-20 Oct 2024 (Los Angeles, USA): IDWeek 2024, the annual meeting of the Infectious Diseases Society of America. Save the date! More details to come!
  • 25-26 February 2025 (Basel, Switzerland): The 9th AMR Conference 2025. Go here to register

Upcoming meetings of interest to the AMR community:

  • [NEW]  9 Apr 2024 (virtual, 830a-10a ET): GARDP’s next REVIVE webinar entitled “Progressing a discovery project – Criteria and challenges.” Register here.
  • [NEW] 9 Apr 2024 (virtual, 10a-1130a ET): CDC webinar “Impacts of Antimicrobial Resistance on Cancer Care.” Click here for details and to register.
  • 10-11 Apr 2024 (virtual): Sepsis Alliance AMR Conference, a 2-day conference focused on “Practical technologies to manage sepsis and counteract the expanding challenge of antimicrobial resistance.” Go here for details and to register.
  • 26 Apr 2024 (Barcelona, Spain): ESCMID workshop entitled “Using Data Science and Machine Learning for Infection Science: A Hands-on Introduction.” Click here to register or here for more details. 
  • 27-30 April 2024 (Barcelona, Spain): 34th ECCMID, the annual meeting of the European Society for Clinical Microbiology and Infectious Diseases. See Recurring Meetings list, above.
  • 26-31 May 2024 (Montreal, Canada): EDAR7, the McGill AMR Centre’s 7th edition of their Environmental Dimension of Antimicrobial Resistance conference. Go here for details; final abstract deadline is 21 Dec 2023.
  • 28-29 May 2024 (in person, Uppsala, Sweden): Uppsala Antibiotic Days, a broad-ranging 2-day program hosted by the Uppsala Antibiotic Center. Go here for details and to register.
  • [NEW] 30-31 May 2024 (face-to-face in Rockville, Maryland as well as online, 8.30-5.30p ET on 30 May, 9-2.40p on 31 May): NIAID-sponsored workshop entitled “Towards realizing the promise of adjunctive immune therapy for invasive fungal infections”. The agenda covers host immunity to invasive fungal infections, immune modulators in the context of fungal infections; and strategies for testing immune modulators as adjunctive therapy. Go here for more details and to register.
  • 9-13 June 2024 (in person, Ascona, Switzerland): “New Approaches to Combat Antibiotic-Resistant Bacteria, 2nd Edition” is a Sunday-Thursday residential workshop focused on the deep biology of AMR. Sponsored by NCCR AntiResist (a Swiss National Science Foundation consortium), the scientific program has the feel of a Gordon Conference. Space is limited, so you are encouraged to apply promptly — go here for details.
  • 13-17 June 2024 (Atlanta, Georgia): ASM Microbe, the annual meeting of the American Society for Microbiology. You can’t register yet, but you can go here for general details.
  • 17-20 Sep 2024 (Porto, Portugal): ASM/ESCMID Joint Conference on Drug Development to Meet the Challenge of Antimicrobial Resistance. See Recurring Meetings list, above.
  • 16-20 Oct 2024 (Los Angeles, USA): IDWeek 2024, the annual meeting of the Infectious Diseases Society of America. See Recurring Meetings list, above. 
  • 19-27 Oct 2024 (Annecy, France, residential in-person program): ICARe (Interdisciplinary Course on Antibiotics and Resistance). Now in its 8th year, Patrice Courvalin directs the program with the support of an all-star scientific committee and faculty. The resulting soup-to-nuts training covers all aspects of antimicrobials, is very intense, and routinely gets rave reviews! Seating is limited, so mark your calendars now if you are interested. Applications open in March 2024 — go here for more details.
  • 4-5 Dec 2024 (in person, Washington, DC): “Fungal Dx 2024: Fungal Diagnostics in Clinical Practice” is a 2-day in-person workshop organized by ISHAM‘s Fungal Diagnostics Working Group. The program and registration links are available at https://fungaldx.com/; the agenda is comprehensive and features an all-star global list of speakers.

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