NIAID RFA: Centers for Accelerating Phage Therapy (CAPT-CEP)

Dear All,

I was delighted to learn today that NIAID has released RFA-AI-24-069, a notice of funding opportunity (NOFO) soliciting applications to establish Centers for Accelerating Phage Therapy to Combat ESKAPE Pathogens (CAPT-CEP). The CAPT-CEPs will focus on developing preclinical assays, tools, and models for robust phage therapy R&D and advancing phage clinical research. Applications are due by 28 Jan 2025; letters of intent must be received 30 days prior to the due date. 

This RFA expects CAPT-CEPs to “develop novel, high-throughput, and cutting-edge assays, tools, and models for phage therapy that can be applied to other phage R&D studies; and to perform essential studies to understand PK/PD and to evaluate optimal delivery systems and dosages of phages, which can be used in designing future clinical trials to combat ESKAPE pathogens.” If ESKAPE pathogens are not familiar, you can see my summary of priority pathogen lists — created in 2008 by Lou Rice’s “No ESKAPE” paper, ESKAPE is the grandfather/grandmother of all the priority pathogen lists.

Quoting further from the RFA, we can see the goal is the creation of enabling tools:

• “Applications must focus on the preclinical development of phage therapies that target at least one of the ESKAPE pathogens listed above.
• “Projects should focus on developing necessary assays, tools, and models and conducting essential studies for robust phage therapeutics R&D for treating infections due to ESKAPE pathogens. 
• “Applications from academic institutions are encouraged to include a substantive investment and participation in the project by an industry participant to facilitate appropriate and validated product development activities.”

Wow! Wow! Good for NIAID to encourage industry collaborations — and as is typical, applications can come from anywhere in the world. It’s also quite clear that NIAID envisions a collaborative network of multiple CAPT-CEPs … very nice to see! I’ve put a few more details from the RFA webpage below my signature if you want to get a feel for the types of projects envisioned by NIAID.

I have long wanted to see phage therapies gain some R&D traction … the ability to selectively kill bacteria is so very obvious under the microscope. But, developing standardized phage products has proven very hard. Phage are non-traditional agents that will generally be used as add-on agents (rather than standalone), thus creating a need to find settings in which superiority designs are feasible. The selectivity of phage is a challenge as narrowly targeted agents are surprisingly difficult to develop — see the newsletters from 1 Mar 2017 (FDA workshop), 13 Apr 2017 (FDA Ad Comm), and 5 May 2017 (IDSA white paper). You might also be interested in WHO’s 3-part phage-focused webinar series from earlier this year as well as EMA’s 28 Jan 2024 concept paper on phage manufacturing. And don’t forget about WHO’s dedicated Bacteriophage group on the AMR Community Exchange Platform. If you’re not already a member of the exchange platform, you can register here. 

Anyway, time to get busy! Apply for and establish a CAPT-CEP! Go solve those problems! With thanks and 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.

A bit more detail quoted verbatim from the RFA webpage: NIAID anticipates considerable variety among the proposed CAPT-CEP themes and objectives.

Overarching themes could include, but are not limited to:

• Developing assays, tools, and models, including in silico, in vitro, and in vivo, to help standardize phage therapy R&D
• Generating suitable in vitro and in vivo models for phage research against ESKAPE pathogens
• Understanding PK/PD relationships for phages
• Determining (poly)valency, delivery routes, and dosages of different phage products

CAPT-CEP multidisciplinary research projects contributing to a unifying theme could include, but are not limited to:

• Development of user-friendly and reproducible high-throughput assays, including phage in vitro and in vivo susceptibility tests, and in vivo phage transduction assays.
• Approaches to develop tools, including in silico models, to identify/isolate the most appropriate potential phage therapeutic candidates, including polyvalent phages, to treat ESKAPE bacterial infections.
• Strategies to develop ready-to-use (synthetic or bioengineered) phage therapeutics with broad host ranges.
• Development of in vitro organoids and in vivo animal models to study phage therapy. This includes chronic infection and inflammation models.
• Systems pharmacological studies to advance robust PK/PD models for phages, including applying Artificial Intelligence (AI) and machine learning technologies.
• Tools to evaluate and optimize (poly)valency, routes, and dosages of phage products.
• Approaches to minimize phage neutralization by the host immune response and to enhance stabilization of phage therapeutics.
• Novel methods to optimize phage cocktails to increase bacterial coverage and to prevent the selection of phage-resistant mutants without generating undesired cross-activity.
• Test-of-concept studies using developed assays and tools in appropriate in vivo models. These studies may include  efficacy studies in small animals, assessment of safety and toxicity, immunogenicity, resistance development, and evaluation of proper delivery routes, doses, and formulations.