D1 SOW 052021.pdf

STATEMENT OF WORK (SOW)

General Information

Title of Project:

Synthesis of metarrestin analogs

Statement of Need and Purpose:

The National Center for Advancing Translational Sciences (NCATS) Division of Preclinical

Innovation (DPI) worked on the identification of compounds selectively targeting the metastatic state. NCATS uses the perinucleolar compartment (PNC), a complex nuclear structure associated with metastatic behaviors of cancer cells, as a phenotypic marker for a high-content screen of over 140,000 structurally diverse compounds.

Reduction of PNC prevalence was used as a phenotypic marker to screen for compounds that interfere with cellular mechanisms essential for the metastatic capability of cancer cells. This led to the discovery of a compound that was further optimized in a medicinal chemistry campaign to produce metarrestin.

Metarrestin shows anti-oncogenic properties in vitro, including inhibition of migration and invasion. It demonstrates desirable pharmacokinetic properties and bioavailability, and in an animal model of pancreatic metastasis, it significantly reduced metastatic burden in the lung and liver and extended survival.

Thus, NCATS would like to synthesize analogs of metarrestin as a backup candidate.

Background Information and Objective:

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 part of the National

Institutes of Health (NIH), which mission it 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.

The Division of Preclinical Innovation (DPI) plans, conducts and uses both internal and contract resources to advance collaborative research projects across the preclinical phases of the translational science spectrum. Specifically, this division:

• Plans, conducts and collaborates on research to develop new methods and technologies to enhance preclinical processes.

• Plans, conducts and collaborates on research to evaluate existing and developing approaches, technologies, and processes in the preclinical spectrum.

• Supports training programs relevant to preclinical phases of translational science.

• Allocates DPI resources to preclinical extramural and intramural investigators.

• Collaborates with other NIH Institutes and Centers and the scientists they support.

• Consults with stakeholders, including patients, industry and regulators.

Metarrestin is a small molecule perinucleolar compartment (PNC) disassembler that is progressing to human clinical trials at NCI as an anti-metastasis agent for pancreatic cancer.

The preclinical development was supported by NCATS. NCATS has a requirement to synthesize analogs of metarrestin with alternate properties as a backup candidate. The

Contractor shall engage in the iterative synthesis of around 60 analogs designed at NCATS.

The goal is to maintain activity while increasing polarity.

Period of Performance:

The anticipated period of performance is 12 months from date of award.

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:

Specific Requirements:

NCATS will digitally provide sixty (60) compound structures of metarrestin analogs, such as the chemical structure demonstrated below (the chemical name is 4-(7-benzyl-4-imino-5,6-diphenyl-

4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-3-yl)cyclohexan-1-ol) in batches of compound structures to the Contractor.

After the analysis of each batch of compound structures provided by NCATS, NCATS and the

Contractor will coordinate and agree on the compounds to be synthetized based on the chemical process.

The Contractor shall perform the synthesis of at least thirty-five (35) compound analogs in 10-

30mg of compounds in iterative rounds of medicinal chemistry, with at least 95% purity as characterized by LCMS. 1H NMR of key intermediates and analogs.

The analogs shall be shipped to NCATS during the Period of Performance.

Government Responsibilities:

The Government anticipates, but does not guarantee, sending compound structures of metarrestin analogs in 3 (three) to 6 (six) batches, with the first batch being sent shortly after contract award and each subsequent batch being sent after the other, during the performance of the purchase order with reasonable time for the contractor to perform the services.

Delivery or Deliverables:

The contractor shall deliver to NCATS at least thirty-five (35) compound analogs in 10-30mg of compounds in iterative rounds of medicinal chemistry, with at least 95% purity as characterized by LCMS. 1H NMR of key intermediates and analogs.

The delivery shall be made to NCATS, at the following location:

NCATS/NIH

9800 Medical Center Dr

Rockville, MD 20850

Reporting Requirements:

The Contractor shall provide updates every three (3) weeks on the progress of the project, or more often as appropriate. Updates shall be provided electronically to Samarjit Patnaik at patnaiks@mail.nih.gov.

Data Rights:

FAR Clause 52.227-14, Rights in Data-General (May 2014) is included in the solicitation and resultant award. Under 52.227-14(c)(1), the contractor must obtain approval from the contracting officer to assert copyright in any data first produced in performance of this contract and published in academic, technical or professional journals, symposia proceedings, or similar works. Under 52.227-14(d)(2), the contractor must obtain approval from the contracting officer to use, release to others, reproduce, distribute, or publish any data first produced or specifically used by the contractor in the performance of this contract.

In addition, the Contractor shall keep the results of this requirement confidential.

mailto:patnaiks@mail.nih.gov