SOW_SOW.pdf

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

STATEMENT OF WORK (SERVICES)

(SOW)

GENERAL INFORMATION

Title of Project:

Testing of compounds for inhibition of 3 kinases in HotSpot assays

Statement of Need and Purpose:

NCATS requires the testing of novel small molecule compounds using the Kinase HotSpot Assay Platform. This testing is for:

1. The testing of thirty-five (35) novel small molecule compounds for inhibition of a set of 3 wild-type kinase enzymes. This testing will inform on potency in our compound series, and will facilitate further optimization and development of these IRAK4 / FLT3 inhibitor compounds as potential treatments for cancers such as AML and MDS.

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 translational science center that prides itself on its tremendously 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 IRAK4 / FLT3 kinase dual 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.

We are currently synthesizing structurally novel analogs of NCGC00371481 that may show improved properties relative to previous analogs. In order to assess these analogs’ on-target potency against targets like IRAK4 and FLT3, we need to test them for activity vs. a panel of 3 wild-type kinases. Testing a set of 35 small molecule compounds vs. 3 wild-type kinases will allow optimization of on-target potency in this compound series.

Period of Performance:

The period of performance is 12 months from the date of contract 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:

1. Test thirty-five (35) novel small molecule compounds for inhibition of a set of 3 wild-type kinase enzymes.

The contractor will:

a. Test each of the 35 small molecule compounds for inhibitory activity against a set of 3 wild-type kinase enzymes, using the Kinase HotSpot assay platform.

i. Compounds will be tested in 10 different doses, which will be determined by the Government at the time the compounds are submitted.

ii. The 10 different doses will be used to generate an IC50 curve.

iii. The Government anticipates sending the 35 compounds in one batch of 35 compounds

b. Provide one comprehensive report providing results of testing each of the 35 compounds against the 3 wild-type kinases.

LEVEL OF EFFORT:

Estimated personnel: 1 PhD level-Manager. 1 Ph.D. level scientist. 1 - 2 months total.

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 sufficient quantities of the lead compounds in order for the contractor to accomplish the requirements described above. The Government will have the responsibility to review and approve the comprehensive reports.

DELIVERY OR DELIVERABLES

As noted in the Requirements section above, the contractor will provide the data analysis and report for the contents of this statement of work. The data analysis and report shall be submitted within 60 business days after receipt of the compounds, and shall be submitted electronically to Scott Hoyt at scott.hoyt@nih.gov. Timely delivery of the report is essential to the successful completion of this work.

REPORTING REQUIREMENTS

The contractor will provide monthly updates on the progress of the project, or more often as appropriate. A single copy of the update shall be provided electronically to Scott Hoyt at scott.hoyt@nih.gov.

mailto:scott.hoyt@nih.gov

OTHER CONSIDERATIONS

Travel:

No travel is required.

Key Personnel:

None specified.

Information System Security Plan:

Not applicable.

Data Rights:

FAR 52.227-17, Rights in Data – Special Works

Section 508—Electronic and Information Technology Standards:

The contractor will not be involved in EIT standards.

Publications and Publicity:

The contractor will not publish results of the work.

Confidentiality of Information:

The contractor will keep the results of the acquisition confidential.