NIH-NCATS-RFQ-21-006466

Post Date/ Solicitation Issue Date

September 7, 2021 12:00 pm

Closing Response Date

September 24, 2021 12:00 pm

Proposed Award Date

September 20, 2021 12:00 pm

Project Title

Testing of compounds in mouse pharmacokinetic studies

Contracting Office

National Institute on Drug Abuse (NIDA)

Small Business Size Standard

$16.5 million

FPDS Classification Code

B529-Special Studies/Analysis- Scientific Data

Estimated Period of Performance

12 months after contract award and receipt of first batch of material

Competition Status

Competitive

Single-Sole Source Determination

N/A

Background/Description of Requirement

1. Statement of Need and Purpose:

This order provides for testing of 4 small molecule compounds in mouse pharmacokinetic studies.  These compounds are drug molecules being evaluated for a kinase inhibitor program.  Testing of the compounds for their pharmacokinetic properties in mouse will provide critical information on compound clearance, exposure, and bioavailability.

2. Background Information and Objective:

The National Institutes of Health (NIH) is the nation’s leading medical research agency and the primary Federal agency whose mission is to seek fundamental knowledge about the nature and behavior of living systems and the application of that knowledge to enhance health, lengthen life, and reduce illness and disability, conducting, supporting and making medical discoveries that improve people’s health and save lives.  The National Center for Advancing Translational Sciences (NCATS) is a translational science center that prides itself on its productive pipeline and is innovative in a number of ways. NCATS brings together a diverse range of scientists, including medicinal chemists, biologists, toxicologists, and engineers, in order to ultimately translate basic science into real products and services that help improve people’s lives. Included in this process is the development of unique small molecules as potential anticancer agents.

Prior work at NCATS has produced a series of small molecule inhibitors, including NCGC00371481 and its structural analogs.  Compounds such as ‘1481 have shown promising results in cellular and mouse models of myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML).  Further optimization of the biochemical, physiochemical and pharmacokinetic properties of these compounds is required, and may eventually produce a clinical candidate that could be used to treat cancers such as MDS and / or AML.

In order for a candidate compound to advance into clinical trials, it must display a wide range of acceptable properties.  For this program, a potential clinical candidate must display potent inhibition of the desired targets.  It must also display suitable pharmacokinetic (PK) properties in a range of preclinical species, including at least one rodent species (mouse or rat), as well as at least one higher preclinical species (dog or monkey).  Good PK profiles in these species are required 1) in order to build models that predict good pharmacokinetic properties in humans, and 2) so that compounds can be given at high doses and high plasma exposure levels in preclinical safety studies.

 In order to characterize and optimize the pharmacokinetic properties of our compounds in mouse, we need to run a series of mouse pharmacokinetic studies.  Testing a set of 4 small molecule compounds in mouse PK studies will provide critical data that identify the strengths and weaknesses of our current compounds’ PK profiles, and will help us optimize those profiles so that we can identify a suitable candidate for clinical trials.

3. General Requirements:

Independently and not as an agent of the Government, the Contractor shall furnish all the necessary services, qualified personnel, material, equipment, and facilities, not otherwise provided by the Government as needed to perform the Statement of Work below.

4. Specific Requirements:
   1. Test each of 4 small molecule compounds in mouse pharmacokinetic studies comprised of two dosing arms (IP or IV dosing in each arm, n = 3 mice per arm).  Test compounds will be administered as single doses (IP or IV dosing), and in each study arm, 8 serial blood draws will be taken at 8 different time points covering a range of at least 8 hours, and up to 24 hours, post-dose.  Plasma samples will be analyzed by LCMS to determine the concentration of test compound at each time point.
   2. Provide a comprehensive report for each of the 4 compounds (one report per compound) detailing results from the pharmacokinetic study.  The report must contain the following:
      • A graphical plot of plasma concentration of test compound vs. time
      • A table of raw data showing the plasma concentration of test compound at each time point in each mouse, as well as the average or mean concentration across all 3 mice, and the standard deviation or standard error for each mean value.
      • Calculated oral bioavailability (F%), clearance rate (Clp), half-life (t1/2), area under the curve (AUC), maximal concentration (Cmax), and volume of distribution (Vd) for the compound.  
   3. Contractor will run the assays using scientists that have significant experience (>3 years) in the testing of small molecule compounds in mouse pharmacokinetic experiments.
   4. Contractor will have significant experience (>3 years) in running mouse pharmacokinetic experiments.
5. Reporting Requirements: The contractor will provide monthly updates on the progress of the project, or more often as appropriate.
6. Travel: N/A
7. Data Rights: FAR 52.227-17, Rights in Data – Special Works
8. Government Responsibilities: Government will not furnish property, facilities, workspace, computers, or other equipment. Contractor will not use federal facilities. Government will have the responsibility to review and approve the final report. Government will have the responsibility to provide sufficient quantities of the lead compound in order to contractor to accomplish the necessary work.