D1 SOW 071321.pdf

Version 11-30-2016-1 FAR Part 11—Describing Agency Needs

STATEMENT OF WORK (SERVICES)

(SOW)

General Information

Title of Project:

In vitro transporter assessment for GS-441524. This is a COVID-19 related activity.

Statement of Need and Purpose:

The purpose of this requisition is to conduct in vitro transporter assessment for GS-441524 with a contract research organization (CRO). The project centers around assessing if GS-441524 is a substrate for reported nucleoside analogs.

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 part of the National

Institutes of Health (NIH), which mission it is to catalyze the generation of innovative methods and technologies that will enhance the development, testing and implementation of diagnostics and therapeutics across a wide range of human diseases and conditions.

COVID-19 is caused by a beta coronavirus called Severe Acute Respiratory Syndrome

Coronavirus 2 (SARS-CoV-2). Remdesivir is a broad-spectrum antiviral medication developed by Gilead Sciences and approved by the FDA for the treatment of COVID-19. It must be administered intravenously which limits its utility, especially in the outpatient population. Other issues that prevent its widespread use as a treatment for COVID-19 include: 1) difficulty on the synthesis, limiting large scale production; 2) efficient metabolism by the liver, which prevents systemic exposure after oral dosing; 3) it is a pro-drug, and the cells that metabolize it into an active drug (e.g., hepatocytes, macrophages) may not be the same as the cell types most susceptible to infection and tied to COVID-19 progression (e.g., pneumocytes).

GS-441524, the parent nucleoside of remdesivir, has similar efficacy to remdesivir in vitro. GS-

441524 is one of major circulating metabolites of remdesivir, and its plasma levels in human after dosing remdesivir are at or above the efficacious levels determined in vitro. The bioavailability of orally administered GS-441524 across species was determined by Therapeutic

Development Branch (TDB), supporting its further development as a potential oral drug.

GS-441524 is a stable crystalline compound with good physical properties for formulation. In addition, the 3-step synthesis of GS-441524 makes it suitable for large scale production.

Because of these advantages, and to support the drug development for this compound, information on whether GS-441524 is a substrate for reported nucleoside analog transporters needs to be assessed. Results obtained from this study will help to understand the elimination mechanism for GS-441524. This activity is related to the NIH response to the current COVID-19 pandemic.

Period of Performance:

The period of performance is three (3) months from the date of contract award including the receipt of the compound for the services

Scope of Work

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:

The contractor shall conduct in vitro transporter study for GS-441524 in order to assess whether

GS-441524 is a substrate for concentrative nucleoside transporters (CNT) CNT1, CNT2, CNT3 and equilibrative nucleoside transporter (ENT) ENT1, ENT2, and ENT4.

Specific Requirements:

The experiment conditions shall meet the Federal Drug Administration (FDA) guidance for transporter substrate assessment on studies with CNT1, CNT2, CNT3 ,ENT1, ENT2, ENT4 and positive/negative controls.

Government Responsibilities:

The Government will not furnish property, facilities, workspace, computers, or other equipment.

The contractor will not use federal facilities. The Government will provide ~ 10 mg GS-441524 in powder form in order for the contractor to accomplish the requirements described above, which the Government anticipates shipping to the Contractor immediately after contract award. The

Government will have the responsibility to review and approve the comprehensive reports

Delivery or Deliverables:

1. Provide study protocol prior to the study;

2. Experiment data for the transporter substrate assessment; and

3. Study report.

The contractor shall provide the protocol, experiment data and report for the contents of this

Statement of Work electronically to Xin Xu at xin.xu3@nih.gov

Reporting Requirements:

The contractor shall provide a summary report on:

1. Study date and site;

2. Source of cells and other materials used in the experiment;

3. Bioanalytical method;

4. Transporter experiment design;

mailto:xin.xu3@nih.gov

5. Calculation and data analysis on transporter substrate assessment for the test compound and positive/negative controls; and

6. Conclusion of the findings.

Other Considerations:

Information System Security Plan:

Standard CRO lab Information System Security Plan.

Data Rights:

FAR Clause 52.227-14, Rights in Data-General (May 2014) is included in the solicitation and resultant award. Under 52.227-14(c)(1), the contractor must obtain approval from the contracting officer to assert copyright in any data first produced in performance of this contract and published in academic, technical or professional journals, symposia proceedings, or similar works. Under 52.227-14(d)(2), the contractor must obtain approval from the contracting officer to use, release to others, reproduce, distribute, or publish any data first produced or specifically used by the contractor in the performance of this contract.

Confidentiality of Information:

HHSAR Clause 352.224-71, Confidential Information (Dec 2015) is included in the solicitation and resultant award.

Evaluating Factors:

Notwithstanding the evaluating factors provided in the solicitation, the following relevant experience shall be addressed by the contractor on its quote:

- Contractor shall perform in vitro transporter studies with CNT1, CNT2, CNT3, ENT1, ENT2, and ENT4 using scientists that have significant experience (≥ 5 years); and

- Contractor shall have significant experience in in conducting in vitro transporter assessment (≥ 5 years).