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Harnessing Enzymatic Activity for Lifesaving Remedies (HEALR)
Microbial infections are a problem of particular concern to the DoD. The DoD has long recognized the warfighter’s outsized risk of exposure to infectious disease, including the rise of antimicrobial resistant (AMR) and multidrug resistant (MDR) pathogens that have challenged military wound care in Iraq and Afghanistan. Furthermore, the responsibility of the DoD to protect the homeland encompasses biological threat agents, including many bacterial threat agents and their associated toxins, for which there are few effective countermeasures or narrow time windows for countermeasure delivery.
The development of new therapeutics for addressing microbial infections is not only a military health challenge but also a growing public health issue. Reports show that antibiotic resistance is on the rise and is an imminent global health threat. In 2019, the United States (U.S.) Military Infectious Diseases Threat Prioritization Panel ranked MDR organisms as a Tier 1 threat to the U.S. military from among > 60 global diseases. Despite this looming crisis, there has been a notable exodus of pharmaceutical companies from the antibiotic space, as well as several high profile failures of biotechnology companies focused on antibiotic development.
Common chemo- and bio-therapeutic strategies for treating microbial infections include small molecules, biologics, and vaccines. HEALR seeks to establish an orthogonal approach to treating microbial infections by harnessing advancements in recruiting native cellular host machinery to recognize and eliminate disease-related targets. Specifically, HEALR will develop new medical countermeasures (MCMs) that result in host-driven degradation or deactivation of bacterial targets. By harnessing innate cellular processes, approaches such as proteolysis targeting chimeras (PROTACs) and similar methods can achieve superior outcomes over existing therapies.
HEALR aims to develop: (1) tools to target microbial pathogens via protein degradation (i.e., target-binding ligand development); (2) innovative modalities to enable new pathways to protein degradation or deactivation; and (3) a platform that leverages these advances to permit flexible and rapid response to emerging threats.
o Proposal Abstract Due Date and Time: August 11, 2020, 4:00 PM ET
o Full Proposal Due Date and Time: September 17, 2020, 4:00 PM E
Areas of Interest
The HEALR program includes three technical areas (TAs) that will run concurrently for the duration of the program. Proposals that do not address all TAs as characterized within this section will be deemed non-conforming and may not be considered for review.
The three technical areas are:
1. Technical Area 1 (TA1): Microbial Targeting. Develop and demonstrate innovative methods to screen and identify new threat-binding ligands against microbial targets.
2. Technical Area 2 (TA2): Host Machinery Engagement. Develop and demonstrate new strategies to engage cellular processes to degrade or deactivate targets.
3. Technical Area 3 (TA3): Platform Integration. Develop the tools to integrate threatand host-binding ligands to rapidly construct, optimize, and deliver safe and effective countermeasures against new microbial threats.