75N95023Q00620

Post Date/ Solicitation Issue Date

August 10, 2023 12:00 pm

Closing Response Date

August 15, 2023 3:00 pm

Proposed Award Date

August 28, 2023 12:00 pm

Project Title

Testing of Compounds in CYP Inhibition Assays

Contracting Office

National Center for Advancing Translational Sciences (NCATS)

Small Business Size Standard

$19 million

FPDS Classification Code

Q301 - Medical- Laboratory Testing

Estimated Period of Performance

6 months after award

Competition Status

Non-Competitive

Single-Sole Source Determination

The essential characteristics of the testing of compounds in CYP inhibition assays that limit the availability to a sole source are that the contractor must have significant experience (>5 years) in the testing of compounds in CYP inhibition assays using Cyprotex’s CYP inhibition assay platform. Only this suggested source can furnish the requirements, to the exclusion of other sources, NCATS needs to employ the same assay platform using Cyprotex's existing assays for CYP inhibition that was previously used to generate prior data on the program in order to maintain continuity of service and allow a direct, apples-to-apples comparison of newly generated and previously generated data. Therefore, the essential characteristics described herein for the testing services required limit the availability to a sole source.

Background/Description of Requirement

The National Center for Advancing Translational Sciences (NCATS) requires the testing of novel small molecule compounds in CYP inhibition assays:

The testing of twenty-seven (27) novel small molecule compounds in three CYP enzyme inhibition assays:  CYP3A4 (midazolam substrate), CYP2C9, and CYP2D6.  This testing will inform on CYP inhibitory activity in the NCATS compound series, and will facilitate further optimization and development of these IRAK4 / FLT3 inhibitor compounds as potential treatments for cancers such as acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS).

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 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 MDS and 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.

The NCATS is currently synthesizing structurally novel analogs of NCGC00371481 that may show improved properties relative to previous analogs. In order to assess these analogs’ ADME (absorption, distribution, metabolism and excretion) properties, we need to test them in assays that measure inhibition of CYP enzymes.

In order for a compound to advance into clinical trials, it must display a wide range of acceptable properties.  For instance, compounds must not potently inhibit major CYP enzymes such as CYP2C9, CYP2D6 and CYP3A4.  These enzymes are responsible for oxidizing and metabolizing a majority of the toxins the body is exposed to, as well as for metabolizing many of the drug medications a patient may be taking.  If a compound causes unwanted inhibition of these CYP enzymes, it could interfere with the metabolism and elimination of toxins from the body.  The compound could also disrupt the metabolism of other drug medications a patient is taking, causing an undesired and potentially dangerous buildup of the unmetabolized drug in the body.  This situation is referred to as a drug-drug interaction.  Therefore, the NCATS needs to test our novel small molecule compounds in CYP inhibition assays, to ensure that they will not cause unwanted drug-drug interactions, or interfere with the elimination of toxins from the body.

Scope of Work:

Test twenty-seven (27) novel small molecule compounds in three CYP inhibition assays.  The contractor shall:

a. Test each of the 27 small molecule compounds for inhibition of CYP3A4 (midazolam substrate), CYP2C9 (tolbutamide substrate), and CYP2D6 (dextromethorpan substrate).

i. Compounds shall be tested in 7 different doses (n = 1).  Doses will be determined by the Government at the time each batch is submitted.

ii. The 7 different doses will be used to generate an IC50 curve.

iii. The Government anticipates sending the 27 compounds in one batch of 27 compounds.

b. Provide one comprehensive report with the results of testing each of the 27 compounds in three CYP inhibition assays; one report for each of the four batches of compounds.

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 shall 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 shall 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.

Data Rights:

FAR 52.227-14, Rights in Data-General is applicable to this requirement.  All data provided by the Government or produced in the performance of this contract is confidential. Pursuant to 52.227-14(d), the contractor may not use, release to others, reproduce, distribute, or publish any data first produced in the performance of this contract.

Publications and Publicity:

The contractor shall not publish results of the work.

Confidentiality of Information:

The contractor shall keep the results of the acquisition confidential.

Quoter Terms and Conditions (To be completed by the Offeror):

1. Period of Performance OR Delivery Date After Receipt of Order:
2. Shipping Point (F.O.B. OR Destination):
3. Payment Discount Terms:
4. NIH BPA Number
5. DUNS No:
6. Name of Company:
7. Street Address, City, State, Zip code:
8. Name of Person Authorized to Provide Quote:
9. 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 28, 2023.

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/

1. 1. 1. 1. The provisions of FAR Clause 52.212-1 Instructions to Offerors—Commercial Items (Mar 2023) is applicable to this solicitation.
         2. The provisions of FAR Clause 52.212.2 Evaluation—Commercial Items (Nov 2021) 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:
            1. 1. 1. 1. Technical capability of the service offered to meet the Government requirement;
                     2. Price; and
                     3. Past performance [see FAR 13.106-2(b)(3)].
         3. The provisions of FAR Clause 52.212-3, Offeror Representations and Certifications—Commercial Items (Dec 2022), is applicable to this solicitation.
         4. The provisions of FAR Clause 52.212-4, Contract Terms and Conditions—Commercial Items (Dec 2022) with Addenda: Stop Work Order, FAR Clause 52.242-15 (Aug 1989) is applicable to this solicitation.
         5. The provisions of FAR clause at 52.212-5, Contract Terms and Conditions Required to Implement Statutes or Executive Orders—Commercial Items (Jun 2023) is applicable to this solicitation:

52.204-27 Prohibition on a ByteDance Covered Application (Jun 2023)

52.219-28 Post Award Small Business Program Rerepresentation (Mar 2023)

52.222-3 Convict Labor (Jun 2003)

52.222-19 Child Labor-Cooperation With Authorities and Remedies (Dec 2022)

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 (Jun 2020)

52.222-50 Combating Trafficking in Persons (Nov 2021)

52.223-18 Encouraging Contractor Policies to Ban Text Messaging While Driving (Jun 2020)

52.225-13 Restrictions on Certain Foreign Purchases (Feb 2021)

52.232-33 Payment by Electronic Funds Transfer-- System for Award Management (Oct 2018)

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 (Aug 2020),

52.204-18 Commercial and Government Entity Code Maintenance (Aug 2020).

The clause at HHSAR 352.222-70, Contractor Cooperation in Equal Employment Opportunity Investigations (Dec 2015) is applicable.

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 52.204-26 and submit completed copies as a separate document with their quotation.

1. FAR 52.204-24, Representation Regarding Certain Telecommunications and Video Surveillance Services or Equipment (Nov 2021)
2. FAR 52.204-25, Prohibition on Contracting for Certain Telecommunications and Video Surveillance Services or Equipment (Nov 2021)
3. FAR 52.204-26, Covered Telecommunications Equipment or Services-Representation (Oct 2020)
4. NIH Invoice and Payment Provisions (3/20/2023)

Period of Performance/Delivery Date:  6 months after contract award. Inspection and acceptance will be performed at NCATS located at 9800 Medical Center Drive, Rockville, MD 20852.  A firm fixed price type order is anticipated to be awarded as a result of this RFQ.

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.