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Targeting Therapeutics Development to Relieve Bottlenecks

Solicitation Number: BAA-NIAID-DMID-NIH-AI-2014007
Agency: Department of Health and Human Services
Office: National Institutes of Health
Location: National Institute of Allergy and Infectious Diseases
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BAA-NIAID-DMID-NIH-AI-2014007
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Combined Synopsis/Solicitation
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Added: Jun 13, 2014 11:50 am

Background

Research supported and conducted by NIAID, National Institutes of Health (NIH), Department of Health and Human Services (DHHS), strives to understand, treat and ultimately prevent the myriad of infectious, immunologic, and allergic diseases that threaten millions of human lives. The NIAID Division of Microbiology and Infectious Diseases (DMID) supports extramural research to control and prevent diseases caused by virtually all infectious agents, with the exception of the human immunodeficiency virus (HIV). This includes basic and applied research to develop and evaluate therapeutics, vaccines, and diagnostics, which are funded through a variety of research grants and contracts. The NIAID also has a mission to advance the development of new medical countermeasures (MCM) against the biological agents that are most likely to be used in a terror attack on civilian populations.


The current NIAID Strategic Plan for Biodefense Research(http://www.niaid.nih.gov/topics/BiodefenseRelated/Biodefense/Documents/biosp2007.pdf)establishes a strategy for developing new and improved medical countermeasures against a broad array of emerging and re-emerging infectious diseases (http://www.niaid.nih.gov/topics/emerging/Pages/list.aspx), which includes NIAID Category A-C Priority Pathogens. The NIAID's plan reflects the Institute's partnerships with the HHS Public Health Emergency Medical Countermeasures Enterprise (PHEMCE) and Department of Homeland Security.

The HHS PHEMCE coordinates interagency efforts aiming to optimize our preparedness for public health emergencies with respect to the creation, stockpiling, and use of medical countermeasures. Led by the Assistant Secretary for Preparedness Response (ASPR), HHS, PHEMCE consists of the NIH, Food and Drug Administration (FDA), and Centers for Disease Control and Prevention (CDC), along with ex officio participation from other federal agencies. The PHEMCE Implementation Plan for Threats Chemical, Biological, Radiological, and Nuclear (CBRN) (http://www.phe.gov/Preparedness/mcm/phemce/Pages/strategy.aspx) sets the current priorities for medical countermeasure development against advanced, enhanced, and emerging threats and advanced agents.


In August 2012 the NIAID held a workshop entitled "Bridging the Gap: Overcoming Bottlenecks in the Development of Therapeutics for Infectious Diseases" This workshop brought together product development experts from industry, government, academia and the non-profit sector to identify and clarify challenges in the development of therapeutics for infectious diseases. One of the areas highlighted by participants was the importance of medicinal chemistry in early drug development, and the need to integrate chemistry and biology as well as computational and structural biology in early drug development. This solicitation is intended to help address this need. The full report from the workshop can be found at:


http://www.niaid.nih.gov/about/organization/dmid/bottlenecks/Pages/summary.aspx



Technical Objectives



The primary objective of this BAA is to support the advancement of promising lead therapeutics to the clinical drug candidate stage for the treatment of emerging infectious and biodefense diseases as listed in NIAID Category A, B and C Priority Pathogens(http://www.niaid.nih.gov/topics/BiodefenseRelated/Biodefense/research/pages/cata.aspx). 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 broadspectrum anti-virals, 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. The lead compound should have a demonstrated path in the synthesis of derivatives at multiple sites on its core molecular scaffold. 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. This evaluation may include determination of the activity, selectivity, ADMET properties as well as chemical synthesis of derivatives in order to develop a structure-activity relationship. A lead compound is selected among the lead candidates and their derivatives, and a lead compound typically exhibits the best panel of activity, selectivity, ADMET properties and chemical feasibility. Further in vitro and in vivo testing of a lead compound may be performed in order to verify its selection.



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




Contracts awarded under this BAA will not support:

�� Screening of compound libraries or compound series for hit identification



�� Development of devices, prophylactic products or diagnostics


�� Development of biopharmaceutical products


�� Development of animal infectious and/or efficacy models


�� Compounds intended to be administered solely as aerosols


�� Manufacturing, characterization and release of cGMP material


�� Conduct of Investigational New Drug (IND)-enabling non-clinical studies


�� Development, submission, and sponsorship of an Investigational New Drug (IND)


�� Clinical studies in humans


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. Additionally, strategies to overcome bacterial and viral drug resistance could extend the clinical utility of existing broad spectrum anti-infectives and have immediate benefits. Moreover, broad spectrum treatments directed towards host targets, host receptors, and cellular processes can directly prevent or treat diseases. These approaches could provide clinical utility when used alone or in combination with conventional antiinfectives.


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.


Organizations responding to this BAA must have documented expertise in drug discovery and development, including demonstrated knowledge of regulatory guidelines and submission processes for candidate products directed against biological threats identified as NIAID Category A, B and C Priority Pathogens


(http://www.niaid.nih.gov/topics/BiodefenseRelated/Biodefense/research/pages/cata.aspx)


or 2012 HHS PHEMCE Strategy and Implementation Plan


(http://www.phe.gov/Preparedness/mcm/phemce/Pages/strategy.aspx) and shall complete and submit the Summary of Related Activities form from the following website


(http://oamp.od.nih.gov/sites/default/files/DGS/contracting-forms/summary-relatedactivities.pdf)


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(Draft)

Posted Date:
June 13, 2014
Description: BAA-NIAID-DMID-NIH-AI-2014007
:
Office of Acquisitions
6700 B Rockledge Room 3214 MSC7612
Bethesda, Maryland 20892-7612
:
Mr. Sevag Kasparian,
Contracting Officer
Phone: 3014960992
:
Mr. Charles Jackson,
Contracting Officer
Phone: 301-451-3686