Contact Points
Title of Project:
Testing of compounds for block of cardiac ion channels
Project Purpose or Objectives:
This order provides for testing of 19 small molecule compounds for block of the important cardiac-related ion channels hERG, hCav1.2 and hNav1.5. These compounds are drug molecules 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 alert us to any such issues that would need to be solved in order for drug candidates to advance into human clinical testing.
Background Information:
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.
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, abnormally slow or fast heart rate), blood pressure (too high or too low), or the potentially lethal condition known as ‘torsades de pointes’, which results from prolongation of the cardiac QT interval. These undesired cardiotoxicities can often be traced directly to 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’, the ones that give the most reliable data. We thus prefer that 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 are less informative.
Testing of 19 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, more advanced compounds.
Period of Performance:
Period of performance is within 12 months from the contract award and receipt of first batch of material. Estimated to be through 12/31/2021.
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:
Contractor will:
- Perform IC50-determining experiments, testing each of 19 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.
- Provide a comprehensive report with the results of the experiments of each of the 19 compounds against hERG, hNav1.5 and hCav1.2.
Specific Requirements
- Contractor will run the assays using scientists that have significant experience (>5 years) in the testing of small molecule compounds in patch-clamp assays for block of hERG, hNav1.5 and hCav1.2.
- Contractor must utilize equipment that allows for a gigaohm seal around the channel to ensure the generation of high-quality data.
- Contractor will have access to all critical instrumentation necessary for this statement of work.
- Contractor will be capable of testing the aforementioned 19 compounds in all the assays described above in <12 months’ time after receipt of compounds.
Level of Effort:
Estimated personnel: 1 PhD level-Manager. 1 Ph.D. level scientist. 1-2 months total.
Government Responsibilities:
Government will not furnish property, facilities, workspace, computers, or other equipment. Contractor will not use federal facilities. Government will have the responsibility to review and approve the final report. Government will have the responsibility to provide sufficient quantities of the lead compound in order to contractor to accomplish the necessary work
Delivery or Deliverables:
Contractor will provide the data analysis and report for the contents of this statement of work.
Reporting Requirements:
Contractor will provide monthly updates on the progress of the project, or more often as appropriate.
Data Rights:
Any data generated as a result of this contract will be the property of NCATS.
Publications and Publicity:
Contractor will not publish the results of the work.
Confidentiality of Information:
Contractor will keep the results of the acquisition confidential.
Quoter Terms and Conditions (To be completed by the Offeror):
- Period of Performance OR Delivery Date After Receipt of Order:
- Shipping Point (F.O.B. OR Destination):
- Payment Discount Terms:
- NIH BPA Number
- DUNS No:
- Name of Company:
- Street Address, City, State, Zip code:
- Name of Person Authorized to Provide Quote:
- Telephone Number and Email Address of Person Authorized to Provide Quote:
Contract Type:
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 17, 2020.
ADDITIONAL TERMS AND CONDITIONS, PROVISIONS, AND REPRESENTATIONS
The FAR Clauses are incorporated by reference and are provided in full text at https://www.acquisition.gov/
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- The provisions of FAR Clause 52.212-1 Instructions to Offerors—Commercial Items (OCT 2018) is applicable to this solicitation.
- The provisions of FAR Clause 52.212.2 Evaluation—Commercial Items (Oct 2014) is applicable to this solicitation. The Government will evaluate quotations or offers in accordance with FAR 13.106-2 and award a purchase order from this solicitation to the responsible offeror whose quote conforming to the solicitation will be most advantageous to the Government, price and other factors considered. The following factors shall be used to evaluate quotes.
- Technical capability of the item offered to meet the Government requirement;
- Price; and
- Past performance [see FAR 13.106-2(b)(3)].
- The provisions of FAR Clause 52.212-3, Offeror Representations and Certifications—Commercial Items (Dec 2019), is applicable to this solicitation.
- The provisions of FAR Clause 52.212-4, Contract Terms and Conditions—Commercial Items (OCT 2018) with Addenda: Stop Work Order, FAR Clause 52.242-15 (August 1989) is applicable to this solicitation.
- The provisions of FAR clause at 52.212-5, Contract Terms and Conditions Required to Implement Statutes or Executive Orders—Commercial Items (OCT 2019) is applicable to this solicitation:
52.222-3 Convict Labor (June 2003)
52.222-19 Child Labor-Cooperation With Authorities and Remedies (Jan 2018)
52.222-21 Prohibition of Segregated Facilities (Apr 2015)
52.222-26 Equal Opportunity (Sep 2016)
52.222-36 Equal Opportunity for Workers With Disabilities (Jul 2014)
52.222-50 Combating Trafficking in Persons (Mar 2015)
52.223-18 Encouraging Contractor Policies to Ban Text Messaging While Driving (Aug 2011)
52.232-33 Payment by Electronic Funds Transfer-- System for Award Management (Jul. 2013)
In addition, the following FAR provisions are applicable to this solicitation and incorporated by reference: 52.204-7 System for Award Management (Oct 2018),
52.204-13 System for Award Management Maintenance (Oct 2018),
52.204-16 Commercial and Government Entity Code Reporting (Jul 2016),
52.204-18 Commercial and Government Entity Code Maintenance (Jul 2016).
The following provisions and clauses apply to this acquisition and are incorporated as an attachment. Offerors MUST complete the provision at 52.204-24 and submit a completed copy as a separate document with their quotation.
- FAR 52.204-24, Representation Regarding Certain Telecommunications and Video Surveillance Services or Equipment (Dec 2019)
- FAR 52.204-25, Prohibition on Contracting for Certain Telecommunications and Video Surveillance Services or Equipment (Aug 2019)
- FAR 52.204-26, Covered Telecommunications Equipment or Services-Representation (Dec 2019)
- NIH Invoice and Payment Provisions (2/2014)
Summary Statement:
Responses to this notice must include sufficient information to establish the interested parties’ bona-fide capabilities of providing the product or service. The response shall include: the unit price, list price, shipping and handling costs, delivery days after contract award, delivery terms, prompt payment discount terms, F.O.B. Point (Destination or Origin), product or catalog number(s); product description; and any other information or factors that may be considered in the award decision. Such factors may include: past performance; special features required for effective program performance; trade-in considerations; probable life of the item selected as compared with that of a comparable item; warranty considerations; maintenance availability; and environmental and energy efficiency considerations.
Interested parties may identify in writing their interest and capability in response to this requirement. Responses to this notice shall contain sufficient information to establish the interested parties’ bona-fide capabilities for fulfilling the requirement and include: unit price, list price, shipping and handling costs, the delivery period after contract award, the prompt payment discount terms, the F.O.B. Point (Destination or Origin), the Dun & Bradstreet Number (DUNS), the Taxpayer Identification Number (TIN), and the certification of business size. All offerors must have an active registration in the System for Award Management (SAM) www.sam.gov.
All responses must be received by closing date and must reference the announcement. Responses may be submitted electronically to the attention of the contract specialist. Fax responses will not be accepted.
All responsible sources may submit a bid, proposal, or quotation which shall be considered by the agency.