Testing of compounds for kinase inhibition

INTRODUCTION
This is a Small Business Sources Sought (SBSS) notice. This is NOT a solicitation for proposals, proposal abstracts, or quotations. The purpose of this notice is to obtain information regarding: (1) the availability and capability of qualified small business sources; (2) whether they are small businesses; HUBZone small businesses; service-disabled, veteran-owned small businesses; 8(a) small businesses; veteran-owned small businesses; woman-owned small businesses; or small disadvantaged businesses; and (3) their size classification relative to the North American Industry Classification System (NAICS) code for the proposed acquisition. Your responses to the information requested will assist the Government in determining the appropriate acquisition method, including whether a set-aside is possible. An organization that is not considered a small business under the applicable NAICS code should not submit a response to this notice.

This notice is issued to help determine the availability and type of qualified Small Business companies technically capable of meeting this potential 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. The notice is strictly for research and information purposes only.

The information requested will assist the Government in determining the appropriate acquisition method including small business socio-economic set-aside possibilities and to determine the availability of qualified Small Business companies technically capable of meeting the Government's potential requirement. All Small Business companies with the capability and availability to perform the requirement under the applicable NAICS code are invited to submit a response to this notice.

NORTH AMERICAN CLASSIFICATION SYSTEM (NAICS) CODE
The NAICS code applicable to this requirement is 541380-Testing Laboratories with associated small business size standard of 15 Million USD.
BACKGROUND
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 anti-cancer 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.

NCATS is currently synthesizing structurally novel analogs of NCGC00371481 that may show improved properties relative to previous analogs. To assess these analogs' abilities to inhibit their desired targets, NCATS needs to test them for inhibitory activity against the kinase enzymes IRAK1, IRAK4 and FLT3. Once that 'on-target' activity is assessed, a subset of the most promising analogs will be selected and tested for additional activity against clinically relevant mutant forms of FLT3, as well as against related 'off-target' kinase enzymes that compounds such as NCGC00371481 are known to inhibit.

The testing of 100 small molecule compounds against the kinase enzymes IRAK1, IRAK4, FLT3 and two related kinases will allow a determination of their activity. Results from this data will facilitate the further optimization of these compounds for therapeutic use against a variety of cancers, including MDS and AML.

Prior analogs in this series were tested against IRAK1, IRAK4, FLT3, and other relevant kinase enzymes using Kinase HotSpot assay technology. To ensure consistency in the data and to make a direct comparison, there is no other known technology for the current set of compounds to be tested other than using Kinase HotSpot assay technology.

Purpose and Objectives
This Small Business Sources Sought notice seeks to determine eligible sources capable of achieving the essential features of this potential requirement. The purpose of this potential requirement is to obtain results for the following types of testing:

1. Initial testing of 100 novel small molecule compounds for inhibition of the kinase enzymes IRAK1, IRAK4, FLT3, and related kinases. This testing will inform on kinase inhibitory activity in our compound series and will facilitate further optimization and development of these IRAK4 / FLT3 inhibitor compounds.

Project Requirements
This Small Business Sources Sought notice seeks responses from qualified sources that are capable of providing the following salient service requirements of this potential government requirement deemed as the essential features needing to be achieved. Specifically, Offerors to this Small Business Sources Sought notice shall possess the capability to provide the following types of testing as essential requirements:

1. Perform experiments using the Kinase HotSpot assay platform testing each of 100 small molecule compounds for inhibitory activity against IRAK1, IRAK4, FLT3, and two additional kinases, to be selected from the following: FLT3 (D835Y), FLT3 (F594_R595insR), FLT3 (F594_R595insREY), FLT3 (ITD), FLT3 (ITD)-NPOS, FLT3 (ITD)-W51, FLT3 (R595_E596insEY), FLT3 (Y591_V592insVDFREYEYD), BLK, LCK, and RET.

Offerors submitting a response to this Small Business Sources Sought notice shall possess the ability to achieve the salient government essential features identified in this notice and provide documented evidence to be able to fully achieve the characteristicis of the subject requirement described herein.

Period of Performance
The contractor is expected to deliver results within six (6) months of the effective date of contract award and batch of material to analyze. The Government will send the contractor the material to synthesize after the effective date of contract award.

A Fixed-Price type of Purchase Order award not exceeding the Simplified Acquisition Threshold is anticipated for any contract resulting from this requirement. The anticipated award date is August 1, 2019.

Delivery/Warranty
A comprehensive report with the results of the 10-dose IC50 titrations of each of the 100 compounds against IRAK1, IRAK4, FLT3, and two additional kinases will be required. Offerors must indicate an estimated delivery time in full after receipt of an order and any other training or warranty considerations applicable. Inspection and acceptance will be performed at NCATS located at 9800 Medical Center Drive, Rockville, MD 20852.

CAPABILITY STATEMENTS/INFORMATION SOUGHT
Interested parties are expected to review this notice to familiarize itself with the requirements of this project. Failure to do so will be at your firm's own risk.

Respondents must provide clear and convincing evidence of possessing the knowedge, skills, abilities and experience to successfully perform the requirements described in this announcement. Detailed prior experience in implementing similar requirements to the requirement described in this announcement must be clearly delineated in any response provided. Technical experience can include, but is not limited to: Experience (> 5 years) in the testing of small molecule compounds for kinase inhibitory activity using the Kinase HotSpot assay platform; Access to all critical instrumentation necessary for this statement of work; Testing the aforementioned compounds in all the assays described above in.