Testing of compounds for inhibition of 50 and 374 wild-type kinase enzymes

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. The National Center for Advancing Translational Sciences (NCATS) is a translational science center whose 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. 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. NCATS is currently synthesizing structurally novel analogs of NCGC00371481 that may show improved properties relative to previous analogs. In order to assess these analogs' selectivity, we need to test them against structurally-related kinase enzymes. The full - kinome' is known to contain >400 wild-type kinase enzymes, and these are all closely related in terms of protein structure and function. As such, compounds that inhibit our intended targets (IRAK1, IRAK4 and FLT3) will likely also inhibit many other closely related kinase enzymes as unintended off-targets. Such activity - termed - off-target inhibition' - can cause undesired safety-related side-effects when compounds are dosed in preclinical species, or in the clinic. In order to minimize the chances of unwanted side-effects, we need to minimize the inhibition of kinase off-targets. NCATS has recently devised kinome mini-panels, which are representative sets of kinases that are meant to predict inhibitory activity against the full kinome. NCATS believes that a testing against a representative set of 50 kinase enzymes can be predictive of the inhibitory activity that a compound will display against the full kinome of >400 kinases. Testing against a representative set of 50 is more efficient than testing against a full set of >400, and thus may be used in early rounds of research as a method of estimating kinase selectivity. Testing of 10 small molecule compounds for inhibition of a representative set of 50 wild-type kinase enzymes will allow a determination of their - off-target' activity. That data will facilitate the further prioritization and optimization of compounds in this series for therapeutic use against a variety of cancers, including MDS and AML. Testing of 5 small molecule compounds for inhibition of the full kinome panel of 374 wild-type kinase enzymes will allow a determination of their - off-target' activity. That data will facilitate the further prioritization and optimization of compounds in this series 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. The current potential requirement must also be tested using Kinase HotSpot assay technology, or its equal, to ensure consistency of data. 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: 1. Testing results of 10 novel small molecule compounds for inhibition of a set of 50 wild-type kinase enzymes. 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 as potential treatments for cancers such as AML and MDS. 2. Testing results of 5 novel small molecule compounds for inhibition of a set of 374 wild-type kinase enzymes. 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 as potential treatments for cancers such as AML and MDS. 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: 1. Perform experiments using the Kinase HotSpot assay platform, or its equal, testing each of 10 small molecule compounds for inhibitory activity against at least 50 wild-type kinase enzymes. 2. Provide a comprehensive report with the results of the 10-dose IC50 singlet titrations of each of the 10 compounds against the 50 wild-type kinases. 3. Perform experiments using the Kinase HotSpot assay platform, or its equal, testing each of 5 small molecule compounds for inhibitory activity against at least 374 wild-type kinase enzymes. 4. Provide a comprehensive report with the results of the 10-dose IC50 singlet titrations of each of the 5 compounds against the 374 wild-type kinases. 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 period of performance will be effective for 6 months from the Effective Date of Contract. Delivery/Warranty Offerors should 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; Testing using the Kinase HotSpot assay platform against at least 374 wild-type kinase enzymes, so that a variety of representative panels can be constructed, and so that, in the event that initial testing against the representative panel of 50 shows activity, follow-up testing against the full panel of 374 can be performed using the same Kinase HotSpot assay technology; Testing using the Kinase HotSpot assay platform against at least 50 mutant forms of kinase enzymes, in the event that inhibitory activity against a wild-type enzyme suggests follow-up testing against mutant forms; Access to all critical instrumentation necessary for this statement of work; Testing the aforementioned compounds in all the assays described above in <6 months' time. Respondents must provide clear and convincing documentation of their capability in providing analytical quality control and any other requirements and services specified in this notice. Respondents must provide a general overview of the respondents' opinions about the difficulty and /or feasibility of the potential requirement, and any information regarding innovative ideas or concepts. The Respondent must also provide information in sufficient detail of the respondents' (a) staff expertise, including their availability, experience, and formal and other training; (b) current in-house capability and capacity to perform the work; (c) prior completed projects of similar nature; (d) corporate experience and management capability; and (e) examples of prior completed Government contracts, references, or other related information. The respondent must also provide their DUNS number, organization name, address, point of contact, and size and type of business (e.g., 8(a), HubZone, etc.) pursuant to the applicable NAICS code and any other information that may be helpful in developing or finalizing the acquisition requirements. One (1) copy of the response is required and must be in Microsoft Word or Adobe PDF format using 11-point or 12-point font, 8-1/2" x 11" paper size, with 1" top, bottom, left and right margins, and with single or double spacing. The response is limited to ten (10) pages. The 10-page limit does not include the cover page, executive summary, CV's or references, if requested. The information submitted must be must be in and outline format that addresses each of the elements of the product requirement. A cover page and an executive summary may be included but is not required. The response must include the respondents' technical and administrative points of contact, including names, titles, addresses, telephone and fax numbers, and e-mail addresses. All responses to this notice must be submitted electronically to the Contract Specialist and Contracting Officer. Facsimile responses are NOT accepted. Respondents must reference the announcement number on all correspondence related to this Small Business Sources Sought notice. The response must be submitted to Hunter Tjugum electronically, at contact@example.gov, and be received prior to the closing date specified in this announcement. CONCLUDING STATEMENTS Disclaimer and Important Notes. This notice does not obligate the Government to award a contract or otherwise pay for the information provided in response. The Government reserves the right to use information provided by respondents for any purpose deemed necessary and legally appropriate. Any organization responding to this notice should ensure that its response is complete and sufficiently detailed to allow the Government to determine the organization's qualifications to perform the work. Respondents are advised that the Government is under no obligation to acknowledge receipt of the information received or provide feedback to respondents with respect to any information submitted. After a review of the responses received, a pre-solicitation synopsis and solicitation may be published in Federal Business Opportunities. However, responses to this notice will not be considered adequate responses to a solicitation. Confidentiality. No proprietary, classified, confidential, or sensitive information should be included in your response. The Government reserves the right to use any non-proprietary technical information in any resultant solicitation(s).