D 75N95021Q00075_SOW.pdf

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

STATEMENT OF WORK

75N95021Q00075

TITLE: In-vivo Efficacy Study of a Niclosamide Prodrug in a Golden Syrian Hamster Model of

SARS-CoV-2 (COVID-19)

BACKGROUND AND OBJECTIVE

The COVID-19 pandemic poses the most significant health crisis of our lifetimes. While the race for several vital vaccines is underway, antiviral small molecule therapy will play an extremely important role in reducing the morbidity and mortality associated with COVID-19. Several studies have led to the discovery of existing compounds, such as remdesivir, which have been authorized for emergency use to combat the ongoing pandemic.

Niclosamide is an old anthelminthic drug. Its potential as an anti-cancer and anti-viral agent has been demonstrated in numerous recent publications and clinical trials aiming to utilize its potential beyond its historic use of treating tapeworm infections in the gut. These studies have continually faced challenges in terms of oral absorption due to niclosamide’s poor solubility and permeability.

NCATS has discovered niclosamide analogs with better solubility, permeability and microsomal stability, indicative of better in vivo exposures, but with similar potency in their ability to rescue the cytopathic effect of SARS-CoV-2 infection in cell-based studies. NCATS also invested efforts in discovering niclosamide prodrugs that have better solubility and permeability and are effectively metabolized to the active drug. One of these promising prodrugs will now be tested in an animal model of SARS-CoV-2 infection.

The objective of this acquisition is to test NCATS’ prodrug in the Golden Syrian Hamster model, which has been identified as the species of choice for live virus SARS-CoV-2 efficacy studies.

These experiments must be conducted under biosafety level 3 (BSL-3) containment conditions by experts well versed in performing live virus studies in the hamster model.

PERIOD OF PERFORMANCE

The Government anticipates a period of performance of four (4) weeks from receipt of test article compounds from NCATS or finalization of the study plan, whichever is later, but will be based on the schedule and timeline of the awardee. NCATS anticipates, but does not guarantee, sending the test article compounds within two (2) weeks after the date of award.

This requirement supports the development of therapeutics to combat COVID-19. Timeliness is a critical factor in meeting the Government’s needs and the contractor must be able to begin work as quickly as possible after the date of award.

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 requirements listed below.

CLIN 01: In-vivo Efficacy Study of a Niclosamide Prodrug in a Golden Syrian Hamster Model of SARS-CoV-2

This requirement includes:

A. Study Plan. The contractor will submit a draft study plan to the Government. The contractor and Government will work together to finalize the study plan. The study plan must be finalized before the efficacy study begins.

B. Efficacy Study. The contractor will perform an in-vivo efficacy study of a Niclosamide Prodrug in a Golden Syrian Hamster Model of SARS-CoV-2. This efficacy study will include:

1) 36 Golden Syrian Hamsters between the age of 6-8 weeks.

2) All male hamsters are to be used. Administration of test articles or vehicle will be by mouth (per os; PO) for all groups involved in the study.

3) Animals to be divided into six groups, with six hamsters per group.

4) Six groups will consist of:

a. Group 1- Vehicle control (for EIDD-2801 group), Study Day-1 (SD-1)

b. Group 2- Positive control dosing of EIDD-2801, 250mpk, BID, SD-1

c. Group 3- Vehicle control (for subsequent prodrug groups), SD-1

d. Group 4- Prodrug, 30mpk, BID, SD-1

e. Group 5- Prodrug, 60mpk, BID, SD-1

f. Group 6- Prodrug, 60mpk, SD, SD-1

5) Nasal inoculation of SARS-CoV-2 to be performed on Day 0.

6) Oral swabs to be collected on Days 2 and 4. Oral swabs to be analysed by polymerase chain reaction (PCR) to measure the viral loads.

7) Clinical observations and weights to be recorded throughout the study.

8) Cardiac punctures to be conducted on Day 4. Lung samples to be divided and frozen.

9) Immunohistochemistry and histopathology to be performed on lung samples.

10) Infectious virus titers to be determined from lung samples. 50% tissue culture infectious dose (TCID50) to be reported.

C. Deliverable. The contractor will provide a final report that details the results of the study.

The report will be submitted electronically to the NCATS point of contact designated on the purchase order.

GOVERNMENT RESPONSIBILITIES

The Government will provide the test article compounds to the contractor and will work with the contractor to finalize the study plan.

OTHER CONSIDERATIONS

Travel: This requirement does not involve travel.

Data Rights: The clause at FAR 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: The clause at HHSAR 352.224-71, Confidential Information (December 18, 2015) is included in the solicitation and resultant award. This clause includes:

(c)(2)(i) The publication or dissemination of the following types of information are restricted under this contract: information about niclosamide prodrug.

(c)(2)(ii) The reason for restricting the types of information identified in subparagraph (i) is: This compound is the proprietary intellectual property of the Government.