Testing of small molecule compounds for optimization of biochemical, physiochemical and pharmacokinetic properties
(i) This is a combined synopsis/solicitation for commercial items prepared in accordance with the format in Subpart 12.6 as supplemented with additional information included in this notice. This announcement constitutes the only solicitation; proposals are being requested and a written solicitation will not be issued. (ii) The solicitation number is 75N95019Q00148 and the solicitation is issued as a Request for Quotation (RFQ) on a Full and Open competitive basis. This acquisition is for a commercial item or service and is conducted under the authority of the Federal Acquisition Regulation (FAR) Part 13-Simplified Acquisition Procedures; FAR Subpart 13.5-Test Program for Certain Commercial Items; and FAR Part 12-Acquisition of Commercial Items. This acquisition is NOT expected to exceed the simplified acquisition teshold of $250,000.00. A Fixed-Price type of contract is contemplated for any resulting contract entered into as a result of this solicitation. (iii) The solicitation document and incorporated provisions and clauses are those in effect tough Federal Acquisition Regulation (FAR) Federal Acquisition Circular (FAC) Number/Effective Date: 2019-01 / 01-22-2019. (iv) The North American Industry Classification System (NAICS) code for this procurement is 541380-Testing Laboratories with associated small business size standard of 15 Million USD. This requirement is released with no set-aside restriction. (v) This requirement is for the National Center for Advancing Translational Sciences (NCATS) at the National Institutes of Health (NIH). The NCATS Chemical Genomics Center (NCGC) is tasked with identifying and developing novel small molecule leads against a wide spectrum of human disease targets, which it accomplishes by screening thousands of small molecules in collaboration with both intra-and extramural researchers. In pursuit of this goal, the Center has a strong internal transdisciplinary team of scientists who continually discover novel small molecules for application against a wide range of human diseases. 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). They must also display a non-negligible free fraction (the percent of total drug that is not bound to plasma protein) in order to efficaciously engage their targets in vivo. When drugs are dosed in preclinical species (mouse, rat, dog or monkey) or in humans, they enter into systemic blood circulation. There, blood plasma proteins such as albumin are often effective at binding to drugs, and in many cases, a significant percentage of the drug that is in circulation is plama protein-bound. Importantly, the portion of drug that is bound to plasma protein is not available to act at its desired target. Only the unbound portion is free to act at the target to produce the desired effect. Because drugs have widely varying propensities for binding to plasma protein, the percentage that binds to such protein (and the corresponding free fraction) must be determined experimentally. In order for doses to be properly calculated, it is essential to know the unbound fraction of a drug, as a drug given at a certain dose (for example, 100 mg) would yield only a low level of unbound drug (the active species) if plasma protein binding is high (for example, 99%), but a much higher level of unbound drug if plasma protein binding is moderate (for example, 20%). For a given compound, binding to plasma protein may vary across species. That is, binding to mouse, rat, dog, monkey or human plasma proteins may vary. For that reason, preclinical drug discovery programs that test in a variety of preclinical species, and that ultimately want to advance compounds into human clinical trials, will ultimately need to be able to test for plasma protein binding against mouse, rat, dog, monkey and human plasma proteins. Testing of a set of 20 small molecule compounds for binding to mouse and human plasma protein will allow a determination of the compounds' free (unbound) fraction in the presence of such proteins, and will provide essential information that will aid in dosing calculations for preclinical and clinical studies. (vi) The purpose of this requirement is to obtain results for the following types of testing on four studies: 1. Testing of twenty (20) small molecule compounds for binding to mouse and human plasma protein. 2. Testing of thirty (30) small molecule compounds for activation of the PXR and AhR nuclear receptors. 3. Testing of ten (10) small molecule compounds for inhibition of the CYP enzymes CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6 and CYP3A4. 4. Testing of sixty (60) small molecule compounds for inhibition of the CYP enzymes CYP2C9, CYP2D6 and CYP3A4. Statement of Work: The contractor will perform pharmacokinetic assessment of desired compounds within CD-1 male mice, with an emphasis being placed on the plasma exposure of the desired compounds over a given time frame. These studies will commence within 5 business days of receipt of the compounds by the contractor. These studies will be completed within 10 business days of receipt of the compounds. 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. Specifically, the Contractor will perform the tasks on the following NCATS studies: 1. Plasma Protein Binding Study - (NCATS_PPB_03082019) Contractor will: a. Test each of 20 small molecule compounds for binding to mouse and human plasma protein. b. Provide a comprehensive report with the results of the experiments of each of the 20 compounds tested for binding to mouse and human plasma protein. 2. PXR and AhR Study - (NCATS_PXR_03082019) Contractor will: a. Test each of 30 small molecule compounds for activation of the PXR and AhR nuclear receptors. b. Provide a comprehensive report with the results of testing the 30 compounds for activation of PXR and AhR. 3. CYP Inhibition Study - (NCATS_CYP10_03082019) Contractor will: a. Test each of 10 small molecule compounds for inhibition of CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6 and CYP3A4. Each compound must be tested in singlicate (n = 1) at seven different concentrations that cover a range of 0.1 uM to 100 uM. b. Provide a comprehensive report with the results of the experiments of each of the 10 compounds tested for inhibition of CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6 and CYP3A4. The report must include an IC50 determination for each of the above experiments. 4. CYP Inhibition Study - (NCATS_CYP60_03082019) Contractor will: a. Test each of 60 small molecule compounds for inhibition of CYP2C9, CYP2D6 and CYP3A4. Each compound must be tested in singlicate (n = 1) at seven different concentrations that cover a range of 0.1 uM to 100 uM. b. Provide a comprehensive report with the results of the experiments of each of the 60 compounds tested for inhibition of CYP2C9, CYP2D6 and CYP3A4. The report must include an IC50 determination for each of the above experiments. 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. Section 508-Electronic and Information Technology Standards: Contractor will not be involved in EIT Standards. Publications and Publicity: Contractor will not publish results of the work. Confidentiality of Information: Contractor will keep the results of the acquisition confidential. (vii) The Government anticipates award of a firm fixed-price purchase order for this acquisition, The Government anticipates that 2 months of contractor services will be required to successfully perform this requirement after receipt of material to be analyzed provided by the Government. Delivery will be FOB destination. The place of delivery and acceptance will be 9800 Medical Center Drive, Rockville, MD 20850. (viii) The provision at FAR 52.252-1, Solicitation Provisions Incorporated by Reference (Feb 1998), applies to this acquisition. This solicitation incorporates one or more solicitation provisions by reference, with the same force and effect as if they were given in full text. Upon request, the Contracting Officer will make their full text available. The offeror is cautioned that the listed provisions may include blocks that must be completed by the offeror and submitted with its quotation or offer. In lieu of submitting the full text of those provisions, the offeror may identify the provision by paragraph identifier and provide the appropriate information with its quotation or offer. Also, the full text of a solicitation provision may be accessed electronically at these addresses: https://www.acquisition.gov/browse/index/far https://www.hhs.gov/grants/contracts/contract-policies-regulations/hhsar/index.html (End of provision) The following provisions apply to this acquisition and are incorporated by reference: FAR 52.204-7, System for Award Management (Oct 2018) FAR 52.204-16, Commercial and Government Entity Code Reporting (Jul 2016) FAR 52.212-1, Instructions to Offerors-Commercial Items (Oct 2018) FAR 52.212-3, Offeror Representations and Certifications-Commercial Items (Oct 2018) FAR 52.222-52, Exemption from Application of the Service Contract Labor Standards to Contracts for Certain Services-Certification (May 2014) HHSAR 352.239-73, Electronic and Information Technology Accessibility Notice (December 18, 2015) The clause at FAR 52.252-2, Clauses Incorporated by Reference (Feb 1998), applies to this acquisition. This contract incorporates one or more clauses by reference, with the same force and effect as if they were given in full text. Upon request, the Contracting Officer will make their full text available. Also, the full text of a clause may be accessed electronically at these addresses: https://www.acquisition.gov/browse/index/far https://www.hhs.gov/grants/contracts/contract-policies-regulations/hhsar/index.html (End of clause) The following clauses apply to this acquisition and are incorporated by reference: FAR 52.204-13, System for Award Management Maintenance (Oct 2018) FAR 52.204-18, Commercial and Government Entity Code Maintenance (Jul 2016) FAR 52.212-4, Contract Terms and Conditions--Commercial Items (Oct 2018). The provisions of FAR clause at 52.212-5, Contract Terms and Conditions Required to Implement Statutes or Executive Orders-Commercial Items (OCT 2018) 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) 52.222-51 Exemption from Application of the Service Contract Labor Standards to Contracts for Maintenance, Calibration, or Repair of Certain Equipment-Requirements (May 2014) The following provisions and clauses apply to this acquisition and are incorporated as an attachment: NIH Invoice and Payment Provisions (2/2014) (ix) The provision at FAR clause 52.212-2, Evaluation - Commercial Items, applies to this acquisition. The following is an addendum to 52.212-2: Responses received to this RFQ will be evaluated on a Trade-Off basis. The award will be made on a competitive best value basis, using "tradeoff" among price-cost and non-price-cost factors. The Government may elect to award to other than the lowest priced offeror, or other than the offeror with the highest rated non-price-cost proposal. In either case, a tradeoff will be conducted. The government reserves such right of flexibility in conducting the evaluation as necessary to assure an award with the contractor providing the best value to the government. Although technical factors are of paramount consideration in the award, cost or price is also important to the overall award decision. All evaluation factors other than cost or price, when combined, are significantly more important than cost or price. However, cost or price may become a critical factor in source selection in the event two or more offerors are determined to be essentially equal following the evaluation of all factors other than cost or price. Each quotation will be evaluated in strict conformity with the evaluation factors, utilizing written critiques. The evaluation will be based upon the demonstrated capabilities of the prospective contractor in relation to the needs of the project as set forth in the RFQ and will use an adjectival evaluation rating scheme based on the following responses: Excellent (Risk level: Very low); Good (Risk level: Low); Acceptable (Risk Level: Neutral); Marginal (Risk level: High); Unacceptable (Risk level: Very high). The following factors shall be used to evaluate offers, listed in order of relative importance: Professional Expertise; Technical Approach; Organizational Experience. 1.) Professional Expertise: The offeror must demonstrate their knowledge, qualifications and professional experience as it correlates to the experience outlined in this requirement; Proposal clearly detail offerors' relevant experience and knowledge of the requirement as described in this requirement. 2.) Technical Approach: The offeror must demonstrate an understanding of the work, including creativity and thoroughness shown in understanding the objectives of the work and specific tasks, planned execution of the project, ability to address anticipated potential problem areas, and creativity and feasibility of solutions to problems and future integration of new processes. 3.) Organizational Experience: The offeror shall submit with their proposal a detailed list of the last two (2) contracts completed during the past tee (3) years and / or contracts awarded currently in process that are similar in nature to the work scope. Contracts listed may include those entered into by the Federal Government, agencies of state and local governments and commercial concerns. Newly formed entities without prior contracts should list contracts and subcontracts as required above for such key personnel Offeror's submitting a response must provide a completed Price Quote to be evaluated and considered for award. Price quotes must indicate fixed unit pricing and total cost, including shipping cost and estimated time of delivery after receipt of order if applicable. Prices shall be quoted on an itemized basis with fixed-price pricing structure included for all work to be performed in accomplishing this requirement. (x) The Offerors to include a completed copy of the provision at FAR clause 52.212-3, Offeror Representations and Certifications-Commercial Items, with its offer. (xi) The clause at FAR 52.212-4, Contract Terms and Conditions-Commercial Items, applies to this acquisition. (xii) The clause at FAR 52.212-5, Contract Terms and Conditions Required to Implement Statutes or Executive Orders-Commercial Items, applies to this acquisition and is incorporated in full text. (xiii) The following additional contract requirement(s) or terms and conditions as determined by the contracting officer are necessary for this acquisition and consistent with customary commercial practices. There are no additional contract requirement(s) or terms and conditions applicable to this acquisition. (xiv) The Defense Priorities and Allocations System (DPAS) are not applicable to this requirement. (xv) Responses to this solicitation must include sufficient information to establish the interested parties' bona-fide capabilities of providing the product or service. The price quote shall include: 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. The Dun & Bradstreet Number (DUNS), the Taxpayer Identification Number (TIN), and the certification of business size must be included in the response. All offerors must have an active registration in the System for Award Management (SAM) www.sam.gov. (xvi) All responses must be received no later than the date specified in this announcement. Late responses will not be accepted. All responses must reference the subject solicitation number. Responses must be submitted electronically to hunter.tjugum@nih.gov. Facsimile responses will not be accepted. For information regarding this solicitation, contact Hunter Tjugum by email at hunter.tjugum@nih.gov or by phone at 301-827-5304.. 75N95019Q00148 Department of Health and Human Services National Institutes of Health
6/3/19, 5:54 PM Testing of small molecule compounds for optimization of biochemical, physiochemical and pharmacokinetic properties
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 chemical material as a probe to investigate the mechanisms of diseases and to potentially assist in the development of new methods of treating such diseases. 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). They must also display a non-negligible free fraction (the percent of total drug that is not bound to plasma protein) in order to efficaciously engage their targets in vivo. When drugs are dosed in preclinical species (mouse, rat, dog or monkey) or in humans, they enter into systemic blood circulation. There, blood plasma proteins such as albumin are often effective at binding to drugs, and in many cases, a significant percentage of the drug that is in circulation is plama protein-bound. Importantly, the portion of drug that is bound to plasma protein is not available to act at its desired target. Only the unbound portion is free to act at the target to produce the desired effect. Because drugs have widely varying propensities for binding to plasma protein, the percentage that binds to such protein (and the corresponding free fraction) must be determined experimentally. In order for doses to be properly calculated, it is essential to know the unbound fraction of a drug, as a drug given at a certain dose (for example, 100 mg) would yield only a low level of unbound drug (the active species) if plasma protein binding is high (for example, 99%), but a much higher level of unbound drug if plasma protein binding is moderate (for example, 20%). For a given compound, binding to plasma protein may vary across species. That is, binding to mouse, rat, dog, monkey or human plasma proteins may vary. For that reason, preclinical drug discovery programs that test in a variety of preclinical species, and that ultimately want to advance compounds into human clinical trials, will ultimately need to be able to test for plasma protein binding against mouse, rat, dog, monkey and human plasma proteins. Testing of a set of 20 small molecule compounds for binding to mouse and human plasma protein will allow a determination of the compounds' free (unbound) fraction in the presence of such proteins, and will provide essential information that will aid in dosing calculations for preclinical and clinical studies. 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 on four studies: 1. Testing of twenty (20) small molecule compounds for binding to mouse and human plasma protein. 2. Testing of thirty (30) small molecule compounds for activation of the PXR and AhR nuclear receptors. 3. Testing of ten (10) small molecule compounds for inhibition of the CYP enzymes CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6 and CYP3A4. 4. Testing of sixty (60) small molecule compounds for inhibition of the CYP enzymes CYP2C9, CYP2D6 and CYP3A4. 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. Plasma Protein Binding Study - (NCATS_PPB_03082019) Contractor will: a.) Test each of 20 small molecule compounds for binding to mouse and human plasma protein. b.) Provide a comprehensive report with the results of the experiments of each of the 20 compounds tested for binding to mouse and human plasma protein. 2. PXR and AhR Study - (NCATS_PXR_03082019) Contractor will: a.) Test each of 30 small molecule compounds for activation of the PXR and AhR nuclear receptors. b.) Provide a comprehensive report with the results of testing the 30 compounds for activation of PXR and AhR. 3. CYP Inhibition Study - (NCATS_CYP10_03082019) Contractor will: a.) Test each of 10 small molecule compounds for inhibition of CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6 and CYP3A4. Each compound must be tested in singlicate (n = 1) at seven different concentrations that cover a range of 0.1 uM to 100 uM. b.) Provide a comprehensive report with the results of the experiments of each of the 10 compounds tested for inhibition of CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6 and CYP3A4. The report must include an IC50 determination for each of the above experiments. 4. CYP Inhibition Study - (NCATS_CYP60_03082019) Contractor will: a.) Test each of 60 small molecule compounds for inhibition of CYP2C9, CYP2D6 and CYP3A4. Each compound must be tested in singlicate (n = 1) at seven different concentrations that cover a range of 0.1 uM to 100 uM. b.) Provide a comprehensive report with the results of the experiments of each of the 60 compounds tested for inhibition of CYP2C9, CYP2D6 and CYP3A4. The report must include an IC50 determination for each of the above experiments. 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 of work within two (2) 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 Teshold is anticipated for any contract resulting from this requirement. The anticipated award date is June 1, 2019. 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 a capability statement with 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 shall be clearly delineated in any response provided. Technical experience may include, but is not limited to: Experience (> 5 years) in the testing of small molecule compounds as described in this announcement; evidence of published manuscripts in peer-reviewed journals of this or a related field; Access to all critical instrumentation necessary for this statement of work; Testing the aforementioned compounds in all the assays described above in. 75N95019Q00148 Department of Health and Human Services National Institutes of Health
4/26/19, 5:17 PM