D1 SOW Statement of Work.pdf

STATEMENT OF WORK (SERVICES)

(SOW)

GENERAL INFORMATION

Title of Project:

NCATS Antiviral Program for Pandemics (APP) Antiviral Library. This is a COVID-19 action

Statement of Need and Purpose:

The National Center for Advancing Translational Sciences (NCATS), Division of Preclinical

Innovation (DPI), Compound Management (CM) seeks obtain the professional services to design and produce a large-scale APP Antiviral Library composed of individual small molecules to support the NCATS DPI CM and the APP with the capability for large scale development of anti-viral biological assays based on screening against small molecule of the library.

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.

NCATS is one of 27 Institutes and Centers at the NIH and its mission 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.

Experts in NCATS DPI develop system approaches that improve the efficiency and effectiveness of the translation process. Examples include advancing new technologies to make preclinical research more predictive and efficient or de-risking potential drug targets or research projects to make them more attractive for commercial investment. Using state-of-the-art resources to enable the ongoing operation of all NCATS translational research activities within

Automation, Compound Management (CM), Analytical Chemistry, and Informatics.

The NCATS DPI CM staff operate in partnership with the automation team. Using numerous types of sophisticated and automated sample management and liquid-handling instrumentation, these experts provide follow-up and dose-response library-plating services for NCATS screening activities.

NCATS has become a key partner in the Antiviral Program for Pandemics (APP), a multi-agency initiative that includes National Institute of Allergy and Infectious Diseases (NIAID) and

Biomedical Advanced Research and Development Authority (BARDA), to accelerate antiviral development through early discovery and preclinical development of safe and effective oral antivirals. The initial priority for the APP is to develop treatments for SARS-CoV-2 and other coronaviruses, with the program expanding to address other virus families with pandemic potential. NCATS will apply its proficiency in drug discovery and development and its cutting-edge technologies to fill critical needs of the APP, such as (i) target validation, (ii) high-throughput screening (HTS) for drug starting points, (iii) medicinal chemistry for lead optimization, and (iv) preclinical, investigational new drug (IND)-enabling development.

NCATS DPI CM has the capacity for large scale development of anti-viral biological assays and screening them against the APP Antiviral Library of small molecule, with the aim of identifying compounds that can serve as starting points for medicinal chemistry optimization and preclinical to IND drug candidate development.

Thus, this Statement of Work seeks to obtain the professional services to design and produce a large-scale APP Antiviral Library. The services shall include designing the library and obtaining the small molecules for delivery to NCATS.

Period of Performance:

The anticipated period of performance is September 23, 2022 through September 22, 2023 (12-months) or 12-months from date of award.

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:

Specific Requirements:

The contractor shall design and produce a large-scale APP Antiviral Library composed of individual small molecules in two (2) phases, as follows:

Phase 1. LIBRARY DESIGN

1.1. The Contractor shall undertake all activities related to the design of the library by identifying and selecting compounds with the following criteria:

1.1.1. Compounds must have rationale in design towards targeting anti-viral activity

1.1.2. Library must be chemically diverse in structure

1.1.3. A large number of novel scaffolds (chemotypes) must be highly represented

1.1.4. Library must have suitable chemical property distributions for drug discovery

(molecular weight, lipophilicity, solubility, number of h-bond donors & acceptors, polar surface area, etc.) to enable high quality leads for medicinal chemistry

1.1.5. Library must conform to structural filters to exclude compounds that would not be suitable leads; however, targeted covalent modification (such as towards viral proteases) is acceptable

1.1.6. Library must aim to target, at a minimum, the virus family listed below in the

Viral Families section

1.1.7. Library must cover, at a minimum, a list of diverse mechanisms that are described below in the Mechanisms section

1.1.8. Compounds must be readily available and provided in sufficient quantities.

Their structures cannot be blinded from submission in public databases

1.1.9. Compounds must be at least 90% pure

1.1.10. Compounds must be formatted and delivered in accordance with NCATS

Compound Management requirements. All labware and consumables shall be provided by the Contractor.

1.1.11. Contractor may consult at any time with NCATS in designing the library and selecting compounds.

1.2. Viral Families – The design of the APP Ativiral Library must target the following viral families:

1.2.1. Coronaviridae

1.2.2. Filoviridae

1.2.3. Flaviviridae

1.2.4. Paramyxoviridae

1.2.5. Bunyavirales

1.2.6. Togaviridae

1.2.7. Picornaviridae

1.2.8. Other pandemic or epidemic causing viruses such as influenza

1.3. Mechanisms - the APP Antiviral Library must target a diversity of mechanisms that affect the virus itself or host-virus interactions. Described below are categories and specific targets as examples at a minimum, though more mechanisms may be proposed.

1.3.1. Library must focus on various phases of a virus life cycle such as:

1.3.1.1. Viral attachment to a host (mammalian) cell

1.3.1.2. Viral genes and proteins released into the host cell

1.3.1.3. Viral replication within the host cell

1.3.1.4. Viral assembly within the host cell

1.3.1.5. Release of new viruses to infect other host cells

1.3.2. Targeted mechanisms must include compounds that may target proteins such as TMPRSS2, SARS ACE2-RBD interaction, 3CLpro, PLpro & other viral proteases, integrases, viral NSPs, RNA helicases, DNA polymerases, reverse transcriptases, neuraminidase, viral envelope proteins, RNA targeting compounds, eEF1A transcription factor interactions, modulators of post translational modulators (epigenetic targets), host-viral interactions

1.3.3. Small portion of the library should contain novel mimetics of nucleotides or nucleosides

1.3.4. Library may include compounds that target the supplemental list of mechanisms, as provided in the Appendix A – APP ANTIVIRAL LIBRARY

SUPPLEMENTAL LIST OF MECHANISMS.

1.4. Contractor shall provide a library design report addressing all elements identified in this Library Design Phase as well as any additional findings or recommendations.

Upon acceptance by NCATS of this report, NCATS will provide notice to proceed to the Compound Acquisition, Phase 2.

Phase 2. COMPOUND ACQUISITION

2.1. Contractor shall provide the list of compounds to NCATS for review in a format agreed upon including, but not limited to the following information:

2.1.1. Chemical Structure

2.1.2. SMILES representation

2.1.3. InChi

2.1.4. Structure ID

2.1.5. Sample ID

2.1.6. PubChem SID

2.1.7. Other NIH-specified identifiers, as needed

2.1.8. Molecular Formula

2.1.9. Molecular Weight

2.1.10. Sample Supplier

2.1.11. Supplier ID (structure and sample)

2.1.12. Sample purity

2.1.13. Storage tube barcode

2.1.14. Solvent used

2.1.15. Concentration

2.1.16. Volume

2.1.17. Known Hazards

2.1.18. Controlled substance designation (if applicable)

2.1.19. Price or cost

2.1.20. Expected Delivery Time

2.2. NCATS will review the list of proposed compounds. NCATS and Contractor may engage in a dialog to refine the list.

2.3. The compound acquisition may be separated into interim deliveries based on compound availability, lead time, delivery schedule, and other factors at NCATS discretion. NCATS and Contractor may engage in a dialog for the interim deliveries. NCATS shall be able to select compounds à la carte.

2.4. Prior to acquiring compounds, Contractor shall obtain NCATS approval by submitting interim reports including the list of compounds to be acquided, with at least the information requested on Phase 2, 2.1.

2.5. Contractor shall procure the approved compounds upon receipt of the approved list provided by NCATS.

2.5.1. Non-severable requirement. This statement of work requires delivery of the entire library according to the Library Design, approved on Phase 1. Although

NCATS will determine the identity and volumes of individual compounds to be delivered, delivery of any specific compound is not severable.

2.5.2. Delivery of the entire library will be summarized in a final report to be submitted within 15 days after completion of the library.

2.5.3. Substantial transformation. The Government has determined that the contractor’s selection, identification, and presentation of compounds according to the criteria listed in Phase 2, 2.1. constitutes a substantial transformation by the contractor of raw materials into a product capable of meeting the Government’s specifications for inclusion in an automated compound store.

LEVEL OF EFFORT:

The Government anticipates award of a mixed Firm-Fixed Price (FFP) and Time & Material

(T&M) type of contract. For the LIBRARY DESIGN, Phase 1, the anticipated contract type is

FFP. Thus level of effort does not apply.

For COMPOUND ACQUISITION, phase 2, the anticipated contract type is Time & Material

(T&M), whereas the following mix of Labor Categories (LCAT) and Level of Effort (LOE) is suggested:

LCATS – Job Title LOE - Hours

Program Manager 940

Sr. Scientist 940

Analyst 940

Quoter shall propose the LCAT and estimated LOE based on their suggested technical approach to achieving the objectives of this SOW.

For planning purposes, quoter should assume a materials budget of $2,000,000 for the

COMPOUND ACQUISITION, phase 2.

A description of all corresponding commercial job titles, experience, functional responsibility and education for those types of employees who will perform services shall be provided.

At minimum, the educational requirements and years of experience for the LCATS provided in this SOW are as follows:

LCAT Education Years of Experience

Program Manager Bachelor's 8

Sr Scientist Ph.D. 10+

Analyst Bachelor's 2

GOVERNMENT RESPONSIBILITIES

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

Performance of the services shall be at the Contractor facility. The Government will have the responsibility to review and approve the reports in order for the contractor to perform the services described herein the SOW.

DELIVERABLES AND REPORTS

All written deliverable reports shall be submitted in electronic draft format for the COR’s review and comment. Final copies shall be delivered to the COR five (5) working days after receipt of the Government’s comments.

The delivery schedule of products is outlined in a delivery schedule table below:

Deliverable Deliverable Due Date

Library Design Report addressing all elements identified in the Library Design, Phase 1, as well as any additional findings or recommendations

Three (3)Months after award

Interim Reports including the list of compounds to be acquired, with at least the information requested on Phase 2, 2.1

As determined by the

COR

Final Report encompassing the full description of the APP Antiviral Library including the description of all phases of the specific requirements of this Statement of Work.

15 days of the last delivery based on the last Interim Report

Moreover, the Contractor shall provide monthly updates on the progress of the project, or more often as appropriate. Updates shall be provided electronically to the COR.

The timely submission of deliverables is essential to successful completing this requirement.

Once the Interim Reports are approved by NCATS, the Contractor shall proceed with the compounds acquisition with interim delivery to the below address, FOB Destination:

National Center for Advancing Translational Sciences (NCATS)

9800 Medical Center Drive [Building and Room for to be provided at award.]

Rockville, MD 20850

OTHER CONSIDERATIONS

Travel:

Travel is not required in the performance of this Statement of Work

Key Personnel:

Key personnel proposed must include at a minimum a Program Manager and a Sr. Scientist.

For each proposed key person, a resume is required.

A resume shall be provided for each person proposed for the project. All staff for which resumes are submitted will be considered key staff and dedicated to this project if a contract is awarded.

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.

Non-Personal Services and Inherently Governmental Functions:

Pursuant to FAR 37.1, no personal services will be performed under this task order. All work requirements will flow only from the COR to the contractor's project manager. No contractor employee will be directly supervised by the government. All individual employee assignments, and daily work direction, will be given by the applicable employee supervisor. If the contractor believes any government action or communication has been given that would create a personal services relationship between the government and any contractor employee, the contractor shall promptly notify the contracting officer of this communication or action.

Pursuant to FAR 7.5, the contractor shall not perform any inherently governmental actions under this task order. No contractor employee will hold him or herself out to be a government employee, agent or representative. No contractor employee will state orally or in writing at any time that he or she is acting on behalf of the government. In all communications with third parties in connection with this contract, contractor employees will identify themselves as contractor employees and specify the name of the company for which they work. In all communications with other government contractors in connection with this task order, the contractor employee will state that they have no authority to in any way change the task order and that if the other contractor believes this communication to be a direction to change their contract, they should notify the contracting officer for that contract and not carry out the direction until a clarification has been issued by the contracting officer.

The contractor will ensure that all of its employees working on this task order are informed of the substance of this article. Nothing in this article will limit the government's rights in any way under the other provisions of the task order, including those related to the government's right to inspect and accept the services to be performed under this task order. The substance of this article will be included in all subcontracts at any tier.