1-Statement-of-Work-Services_7.31.24.pdf

Version 11-30-2016-1 FAR Part 11—Describing Agency Needs

STATEMENT OF WORK (SERVICES)

(SOW)

GENERAL INFORMATION

Title of Project: CYP450 and Transporters assessment for CD206 receptor agonist project.

Statement of Need and Purpose: The CD206 receptor agonist project aims to support the lead compound NCGC00413972 for FDA filing. For that, we are requesting comprehensive studies on CYP450 phenotyping, CYP inhibition, CYP induction, and transporter substrate and inhibition is critical for the successful progression of the drug candidate for the CD206 receptor agonist project (NCGC00413972) towards FDA submission. The drug development process requires thorough understanding and documentation of the drug's metabolic profile and interaction potential. Such information is essential for predicting drug-drug interactions, optimizing dosing regimens, and ensuring patient safety. Therefore, it is a standard procedure to conduct these studies to meet regulatory requirements and support the safe and effective use of our drug candidate in clinical settings.

Background Information and Objective: NCGC00413972 is being developed as a novel cancer immunotherapy targeting immunologically cold tumors, with a particular focus on pancreatic cancer, which represents a significant unmet medical need. This first-in-class small molecule agonist of the CD206 receptor aims to reprogram dormant, infiltrating macrophages (M2-like) within solid tumors into their active M1 state. These activated M1 macrophages exhibit phagocytic activity against the tumor cells, thereby functioning as an immunotherapy for solid tumors that have previously been very difficult to treat.

As part of the drug development process, it is essential to thoroughly characterize the pharmacokinetic and pharmacodynamic properties of the drug candidate. Previous preclinical studies have demonstrated promising efficacy and safety profiles, paving the way for further investigation. To move forward with the regulatory approval process, comprehensive studies on the drug’s metabolism and interaction potential are required.

Cytochrome P450 (CYP450) enzymes play a crucial role in the metabolism of many drugs.

Understanding which specific CYP450 enzymes are involved in the metabolism of the drug candidate is essential for predicting possible drug-drug interactions and optimizing dosage regimens, especially for cancer treatment in which combination therapy occurs frequently. Additionally, it is important to assess whether the drug candidate can inhibit or induce these enzymes, as such interactions can significantly impact the drug’s efficacy and safety profile.

Furthermore, drug transporters are integral to the absorption, distribution, and elimination of drugs within the body. Identifying the interaction of the drug candidate with key transporters will provide insight into its pharmacokinetic behavior and potential for transporter-mediated drug interactions.

The data generated from these studies will support the preparation of regulatory documents for submission to the FDA, including the Investigational New Drug (IND) application and subsequent New Drug Application (NDA). The ultimate goal is to ensure the safe and effective use of the drug candidate in clinical practice, addressing an unmet medical need for patients with solid tumors.

Period of Performance: 6 months after the receipt of award.

SCOPE OF WORK

General Requirements: The Contract Research Organization (CRO) selected to perform this SOW is required to provide assessment of NCGC00413972 regarding:

• CYP450 phenotyping and inhibition of the major CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP3A4/5 through the use of appropriate probes. LC-MS/MS method development for detection of probes and test article and appropriate controls.

• CYP450 induction of CYP1A2,2B6,3A4 through mRNA fold changes

• Transporters substrate and inhibitor potential of OATP1B1, OATP1B3, OAT1, OAT3, OCT2, MATE1, MATE2-K, P-gp, BCRP through cellular uptake or transport assays, proper controls, and detection methods.

• The assays and analysis for all the CYP450 or Transporters studies should follow standard procedures that, at minimum, fulfill the requirements stated in the FDA guidance for DDI Studies (In Vitro Drug Interaction Studies — Cytochrome P450 Enzyme- and Transporter- Mediated Drug Interactions Guidance for Industry, January 2020).

• Provide comprehensive reports of the assays and results.

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: The assessment of the endpoints described in “General Requirements” according to FDA guidance for DDI studies (U.S. Food and Drug Administration. (2020). Clinical Drug Interaction Studies — Cytochrome P450 Enzyme- and Transporter-Mediated Drug Interactions:

Guidance for Industry).

LEVEL OF EFFORT:

Not Applicable

GOVERNMENT RESPONSIBILITIES

The Government will provide the Test Article in powder form to the CRO within 14 days after contract award. The Government will review and approve reports.

DELIVERY OR DELIVERABLES

The Government expects the delivery of a research plan, draft reports, and final reports with the results of the assays requested and scientific data interpretation of the data obtained.

REPORTING REQUIREMENTS

The Government expects the delivery of a research plan, draft reports, and final reports with the results of the assays requested and scientific data interpretation of the data obtained.

The contractor shall provide the protocol, experiment data and report for the contents of this Statement of Work electronically to the Government.

OTHER CONSIDERATIONS

Travel: Not Applicable

Key Personnel: Scientists, managers of personnel and contracting agents.

Information System Security Plan: Not Applicable

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.

Section 508—Electronic and Information Technology Standards: Not Applicable

Publications and Publicity: The contractor will prepare reports containing the results of the assays performed and data interpretation. The contractor will not write and publish articles of data produced as a result of the requirements of the SOW.

Confidentiality of Information: The contractor will not receive the structure or proper identification of the compound structure. No confidential data will be shared in the performance of this SOW.