Testing of compounds in mouse pharmacokinetic experiments

NON-COMPETITIVE
COMBINED SYNOPSIS / SOLICITATION

Title: Testing of compounds in mouse pharmacokinetic experiments

(i) This is a combined synopsis/solicitation for commercial items prepared in accordance with the format in Subpart 12.6 as supplemented with additional information included in this notice. This announcement constitutes the only solicitation; proposals are being requested and a written solicitation will not be issued.

(ii) The solicitation number is 75N95019Q00323 and the solicitation is issued as a request for quotation (RFQ).

This acquisition is for a commercial item or service and is conducted under the authority of the Federal Acquisition Regulation (FAR) Part 13-Simplified Acquisition Procedures and FAR Part 12-Acquisition of Commercial Items, and is not expected to exceed the simplified acquisition threshold.

THIS IS A NON-COMPETITIVE (NOTICE OF INTENT) COMBINED SYNOPSIS SOLICITATION TO AWARD A CONTRACT OR PURCHASE ORDER WITHOUT PROVIDING FOR FULL OR OPEN COMPETITION (INCLUDING BRAND-NAME).

The National Institute on Drug Abuse (NIDA), NIDA Office of Acquisitions - NCATS Section, on behalf of the National Center for Advancing Translational Sciences (NCATS), intends to negotiate and award a purchase order without providing for full and open competition (including brand-name) to Charles River Laboratories, Inc., 251 Ballardvale St., Wilmington, MA 01887 for testing of compounds in mouse pharmacokinetic experiments.

Pursuant to FAR Subpart 13.501(a)(1)(iv) the rationale for the brand name justification is that Charles River Laboratories, Inc. has conducted several previous studies for NCATS. The studies must continue to be performed by the same lab to allow for continuity of science and to allow for an apples-to-apples comparison of the data generated from this service with data previously generated.

(iii) The solicitation document and incorporated provisions and clauses are those in effect through Federal Acquisition Circular 2019-05 dated August 13, 2019.

(iv) The associated NAICS code is 541380 and the small business size standard is $15,000,000.00 No set-aside restriction is applicable.

(v) 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 several ways. NCATS brings together a diverse range of scientists, including medicinal chemists, biologists, toxicologists, and engineers, 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.

(vi) 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) 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.
To characterize and optimize the pharmacokinetic properties of our compounds in mice, we need to run a series of mouse pharmacokinetic experiments. Testing a set of 11 small molecule compounds in mouse PK experiments 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.
For a given compound, pharmacokinetic properties may vary considerably across species. That is, properties in mouse, rat, dog, monkey or humans may vary. Preclinical drug discovery programs that want to advance compounds into human clinical trials ultimately need to test pharmacokinetics in mouse, rat, dog, and monkey prior to human testing. To maintain consistency, we prefer to run our mouse pharmacokinetic experiments using a vendor who can also provide future pharmacokinetic testing in rat, dog, and monkey.

Project requirements:
1. Test each of 11 small molecule compounds in mouse pharmacokinetic studies comprised of two dosing arms (one oral, one IV, n = 3 mice per arm).
2. Provide a comprehensive report for each of the 11 compounds detailing results from the pharmacokinetic experiment as described below in the Specific Requirements section.

Specific Requirements
1. Contractor will run the assays using scientists that have significant experience (>5 years) in the testing of small molecule compounds in mouse pharmacokinetic experiments.
2. Contractor will have significant experience (>5 years) in running mouse pharmacokinetic experiments.
3. Contractor must offer the option of follow-up pharmacokinetic testing in rat, dog, and monkey. This will allow continuity of service, and an 'apples-to-apples' comparison of pharmacokinetic data across all species.
4. Contractor will test compounds in mouse pharmacokinetic studies comprised of two dosing arms (one oral, one IV, n = 3 mice per arm). Test compounds will be administered as a single dose (either oral or IV, depending on the study arm), and in each study arm, 7 serial blood draws will be taken at 7 different time points covering a range of at least 8 hours post-dose. Plasma samples will be analyzed by LCMS to determine the concentration of test compound at each time point. That data will be used to construct a plot of test compound concentration in plasma vs. time for each dosing arm. A final report will be issued that contains these plots, as well as the 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. The report should list the formulation used for dosing and should include 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.
5. Contractor will have access to all critical instrumentation necessary for this statement of work.
6. Contractor will be capable of testing the aforementioned 11 compounds in all the assays described above in.