Testing of compounds for block of cardiac ion channels

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 in 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 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 NCGC00371481 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.   

In order for a candidate compound to advance into clinical trials, it must display a wide range of acceptable properties.  For this program, the compounds must display potent inhibition of the desired targets (IRAK4 and FLT3).  Candidate compounds also need to be free of various types of cardiotoxicity, for instance any undesired effects on heart rate (bradycardia or tachycardia or abnormally slow or fast heart rate), blood pressure (too high or too low), or the potentially-lethal condition known as ‘torsades de pointes’ (translated as "twisting of peaks") that results from prolongation of the cardiac QT interval.  These undesired cardiotoxicities can often be traced directly to a block of a key ion channel:  hERG for QT prolongation, hNav1.5 for effects on heart rate, or hCav1.2 for effects on blood pressure.  Preclinical testing of candidate drug compounds for block of these important ion channels is a widely-used strategy for the early identification of potential sources of cardiotoxicity.  Optimization of compounds within a series so that key compounds do not block these channels is typically a prerequisite for identifying a drug candidate that can advance into human clinical trials.

A variety of different biological assay formats are available to test ion channel block.  These include binding assays, functional assays, and a specific type of functional assay known as patch-clamp.  Of these, patch-clamp assays are widely regarded as the ‘gold standard’ and are the ones that give the most reliable data.  Thus, NCATS prefers the testing of these compounds to be conducted in patch-clamp assays, or in other highly reliable functional assays such as FLIPR assays, as opposed to binding assays, which tend to be less informative.

Testing of 60 small molecule compounds for block of hERG, hNav1.5 and hCav1.2 in patch-clamp or FLIPR assays will allow a determination of the compounds’ activity against these targets and will help to identify any unwanted properties that would need to be removed in subsequent, further testing of compounds.

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 contractor services to perform testing of 60 small molecule compounds for blocking potential of the important cardiac-related ion channels: hERG, hCav1.2 and hNav1.5. These drug molecules are the compounds that are being evaluated for the dual IRAK4-FLT3 kinase program. Testing of the compounds for their capacity to block hERG, hCav1.2 and hNav1.5 will help to identify potential sources of cardiotoxicity, and to provide insight into any potential issues that would need to be solved in order for drug candidates to advance into human clinical testing.

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.

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. Contractor shall:

1. Perform IC50-determining experiments, testing each of 60 small molecule compounds at 5 dose concentrations in duplicate, in patch-clamp assays for block of hERG and hNav1.5, and in FLIPR assays for block of hCav1.2.

1. Provide a comprehensive report with the results of the experiments of each of the 60 compounds against hERG, hNav1.5 and hCav1.2, allowing for a giga-ohm seal around the channel.

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, including possessing the capability to work with radioactive compounds and biological tissue.

Period of Performance/Level of Effort                               

The period of performance will be effective for 12 months from the Effective Date of Contract or receipt of material to analyze. The Government anticipates the vendor will be required to provide 1 PhD level-Manager and 1 Ph.D. level scientist to work for a total 1-2 months of time to fully achieve this requirement.

Deliverables/Reporting Requirements

Deliverables will include one (1) report on the study performed, including the data analysis and report of the results of the contents of the scope of work. Contractor will provide monthly updates on the progress of the project, or more often as appropriate. Contractor will be expected to stay in e-mail or phone contact with the government representative as needed. Delivery, inspection and acceptance of any items delivered 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:

1) Experience (> 5 years) in running experments in the same or similar field;

2) Access to all critical instrumentation necessary for this statement of work;

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 hunter.tjugum@nih.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).