The NIAID Division of Microbiology and Infectious Diseases (DMID) has issued a new Broad Agency Announcement (BAA) to support the advancement of promising lead therapeutics to the clinical drug candidate stage for the treatment of emerging infectious and biodefense diseases.
Only candidate products against NIAID Category A, B and C Priority Pathogens are eligible under this solicitation.
Activities supported under this BAA include medicinal chemistry and preclinical in vitro and in vivo testing of a lead compound series in order to produce profiles of their efficacy, synthetic feasibility, stability, and toxicity, which will be used to identify a novel small molecule drug candidate for future clinical development. Of particular interest are broad-spectrum antivirals, and broad-spectrum anti-bacterials.
For the purposes of this BAA, the ideal lead compound for development is defined as a small molecule with demonstrated activity in appropriate in vitro assays or in vivo models against one or more selected bacterial or viral pathogens. A lead compound is more advanced in development than hit compounds and lead candidates. Hit compounds are potent modulators that are identified via in vitro or in vivo screening. Lead candidates are selected among the hit compounds for further evaluation.
Contracts awarded under this BAA will support:
- Chemical synthesis of analogs to develop structure-activity relationship profiles
- Chemical optimization of core molecular scaffolds to improve physiochemical properties to produce more drug-like molecules
- Synthetic route-scouting towards process development
- Formulation studies to optimize dosing, pharmacodynamics, product stability and other drug properties
- In vitro and non-GLP in vivo testing for toxicity, activity, ADME (absorption, distribution, metabolism, and excretion) properties
- Preclinical non-GLP efficacy testing for biodefense and emerging infectious diseases
Screening of compound libraries or compound series for hit identification; development of animal models; and development of devices, prophylactic products or diagnostics will not be considered under this funding opportunity.
Lead compounds with broad spectrum activity are encouraged. Broad spectrum activity is defined as a characteristic that enables a particular product to mitigate biological threats across a range or class of agents. There are a number of traditional threats for which effective treatments are either non-existent, of limited usefulness, or vulnerable to both naturally emerging and intentionally engineered antibacterial and antiviral resistance.
A limited number of anti-infectives with broad spectrum activity directed at common, invariable, and essential components of different classes of microbes could potentially be effective against both traditional and non-traditional threats. This approach would allow a small number of drugs to replace dozens of pathogen-specific drugs for use in a biothreat emergency.
Broad spectrum therapeutics supported under this BAA are specified as the following:
Broad spectrum anti-bacterial: Therapeutic with activity against more than one of the NIAID Category A, B and C bacterial threat agent AND including activity against at least one of the following bacterial pathogens: Bacillus anthracis, Francisella tularensis, Yersinia pestis, Burkholderia pseudomallei, B. mallei, and Rickettsia prowazeki.
Broad spectrum anti-viral: Therapeutic with activity against more than one of the NIAID Category A, B and C viral threat agent AND including activity against at least one of the following viral pathogens: Ebola virus, Marburg virus, Variola major, Dengue virus, Chikungunya virus and human influenza virus.
Host-directed broad spectrum therapeutic: Therapeutic directed at a host response thereby reducing morbidity and mortality from exposure/infection and is effective against more than one of the NIAID Category A, B and C bacterial or viral threat AND including at least one of the following bacterial and viral pathogens: Bacillus, Ebola virus, Marburg virus, Variola major, Dengue virus, anthracis, Francisella tularensis, Yersinia pestis, Burkholderia pseudomallei, B. mallei, Rickettsia prowazeki, Chikungunya virus and human influenza virus.
Further details are available under Solicitation Number: BAA-NIAID-DMID-NIH-AI-2014007.
