Testing of Compounds in Rat Pharmacokinetic Studies

This is a Sources Sought notice. This is NOT a solicitation for proposals, proposal abstracts, or quotations. The purpose of this notice is to obtain information regarding the availability and capability of all qualified sources to perform a potential requirement. For equipment/supply requirements, responses must include: (1) the place of manufacturing (i.e. address if supply/equipment is a domestic end product and include country of manufacture), as well as (2) the size status of the manufacturer under the applicable NAICS code (i.e. address Non-Manufacturer Rule). This notice is issued to help determine the availability of qualified companies technically capable of meeting the Government requirement and to determine the method of acquisition. It is not to be construed as a commitment by the Government to issue a solicitation or ultimately award a contract. Responses will not be considered as proposals or quotes. No award will be made as a result of this notice. The Government will NOT be responsible for any costs incurred by the respondents to this notice. This notice is strictly for research and information purposes only. Background: 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 in order to 1) 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 compounds in rats, NCATS is seeking to run a series of rat pharmacokinetic experiments. Testing a set of 20 small molecule compounds in rat PK studies will provide critical data that identify the strengths and weaknesses of current compounds PK profiles, and will help optimize those profiles so that NCATS can identify a suitable candidate for clinical trials. Purpose and Objectives: The purpose of this acquisition is to acquire testing services of 20 small molecule compounds in rat pharmacokinetic studies. Specific Requirements: The Contractor shall: 1. Test each of 20 small molecule compounds in rat pharmacokinetic studies comprised of two dosing arms (one oral, one IV, n = 3 rats per arm). Test compounds will be administered as a single doses (either oral or IV, depending on the study arm), 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 20 compounds detailing results from the pharmacokinetic experiment. The report must contain the following: a. A graphical plot of plasma concentration of test compound vs. time b. A table of raw data showing the plasma concentration of test compound at each time point in each rat, as well as the average or mean concentration across all 3 rats, and the standard deviation or standard error for each mean value. c. 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 shall run the assays with scientists that have significant experience (>3 years) in the testing of small molecule compounds in rat pharmacokinetic experiments. 4. Contractor shall have significant experience (>3 years) in running rat pharmacokinetic experiments. Period of Performance: 12 months from contract award Capability statement /information sought: Respondents must provide clear and convincing documentation of their capability of providing the equipment specified in this notice. The respondent must also provide their DUNS number, organization name, address, point of contact, and size and type of business (e.g., 8(a), HubZone, etc., pursuant to the applicable NAICS code and any other information that may be helpful in developing or finalizing the acquisition requirements. One (1) copy of the response is required and must be in Microsoft Word or Adobe PDF format using 11-point or 12-point font, 8-1/2 x 11 paper size, with 1 top, bottom, left and right margins, and with single or double spacing. The information submitted must be in an outline format that addresses each of the elements of the service requirement and in the capability statement /information sought paragraphs stated herein. The response must include the respondents technical and administrative points of contact, including names, titles, addresses, telephone numbers, and e-mail addresses. All responses to this notice must be submitted electronically to the Contract Specialist. Facsimile responses are NOT accepted. The response must be submitted to Sarah Adan, at e-mail address contact@example.gov with the subject line NCATS-22-002754SS. The response must be received on or before March 21, 2022, 12:00 pm, Eastern Time. Disclaimer and Important Notes: This notice does not obligate the Government to award a contract or otherwise pay for the information provided in response. The Government reserves the right to use information provided by respondents for any purpose deemed necessary and legally appropriate. Any organization responding to this notice should ensure that its response is complete and sufficiently detailed to allow the Government to determine the organization's qualifications to perform the work. Respondents are advised that the Government is under no obligation to acknowledge receipt of the information received or provide feedback to respondents with respect to any information submitted. After a review of the responses received, a pre-solicitation synopsis and solicitation may be published in SAM.gov. However, responses to this notice will not be considered adequate responses to a solicitation. Confidentiality: No proprietary, classified, confidential, or sensitive information should be included in your response. The Government reserves the right to use any non-proprietary technical information in any resultant solicitation(s).