Attach_4_Initial_Task_Order_SOW_10.16.18.pdf

Attachment 4 N01CN87006-18

Initial Task Order Statement of Work Page 1

Initial Task Order Statement of Work: cGMP Production of Vaccines and Biologicals for

Cancer Prevention

Independently and not as an agent of the Government, the Contractor shall furnish all the necessary services, qualified personnel, materials, equipment, and facilities, not otherwise provided by the

Government, as needed to perform the Statement of Work.

Initial Task Order Title: Manufacture of a Vaccine Targeting Frame-Shift Mutations

Characteristic of Tumors with Microsatellite Instability

I. Background

The potential for targeting frame-shift mutations for treatment of patients with microsatellite unstable colon cancer has been previously reported, including preliminary results from a Phase I trial (1). The National Cancer Institute (NCI) plans to conduct a Phase I trial for cancer prevention with a trivalent, frame-shift peptide vaccine based on the same peptide sequences.

Rather than cancer patients, asymptomatic carriers of DNA mis-match repair mutations (Lynch

Syndrome carriers) will be vaccinated and monitored for safety and immunogenicity.

Biomarkers for use as secondary endpoints are under development. For ease of production, some of the N-terminal wild-type peptide sequence has been eliminated. For clinical administration, it is expected that the vialed and labeled tripeptide solution will be combined with adjuvant either at the bedside or hospital pharmacy.

II. Objectives

The overall objective of the Task Order is to manufacture a trivalent, frame-shift peptide antigen solution for use in Phase I clinical trials in the US and a possible site in Germany. Specific requirements of this Task Order are listed below. The Contractor shall:

(1) Synthesize or procure the three peptides shown below in compliance with cGMP guidelines.

o TAFB(-1): NRGLKKKTILKKAGIGMCVKVSSIFFINKQKP o AIM2(-1): VIKAKKKHREVKRTNSSQLV o HT001(-1): RSNSKKKGRRNRIPAVLRTEGEPLHTPSVGMRETTGLGC

(2) Develop required analytical methods, and characterize the manufactured peptides.

(3) Formulate the peptides as a sterile solution in vaccine-stoppered single-use vials. To support IND-enabling toxicology studies, stability analyses, and Phase I clinical testing, 1,500 vials containing 400 mcg of each peptide/ml (0.7 ml fill volume) will be required.

(4) Establish release criteria, and provide all data, information, and executed batch records required for CMC information and all other documents related to IND submission.

(5) Provide a CMC Package. All regulatory authorities require information related to the manufacture and testing of the product when reviewing an Investigational New Drug

(IND) application (or the equivalent) or a marketing application. For the FDA, this is captured in the Chemistry, Manufacturing and Controls (CMC) section. CMC information is required when submitting an IND, a NDA, an ANDA and their Annual

Initial Task Order Statement of Work Page 2

Reports. The required content varies depending on the type of drug substance or drug product. The Contractor shall be responsible for the preparation, assembly and review of the required documentation and reports for its products. As CMC-related queries from

US and international health authorities arise, the queries will be forwarded to the

Contractor from the NCI-designated Regulatory Contractor. The Contractor shall address all CMC-related queries and send responses back to the NCI-designated Regulatory

Contractor. The Contractor shall also schedule and participate in meetings as necessary to resolve scientific, technical, and regulatory issues resulting from a review of a submission or a compliance action.

(6) Develop and validate methods for stability testing of formulated product. The Contractor shall also conduct stability testing to cover the anticipated duration of the clinical trial (up to three years after release of the drug product). The Contractor shall test the drug product for stability on a quarterly basis through the end of the task order period of performance.

The Contractor shall also transfer the product to the DCP Repository for long-term storage.

References:

1.Vaccination of MSI-H colorectal cancer patients with frameshift peptide antigens: A phase

I/IIa clinical trial. By: Kloor, Matthias; Reuschenbach, Miriam; Karbach, Julia; et al.

Conference: Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) / Clinical

Science Symposium on Predicting and Improving Adverse Outcomes in Older Adults with

Cancer Location: Chicago, IL Date: MAY 29-JUN 02, 2015.

JOURNAL OF CLINICAL ONCOLOGY Volume: 33 Issue: 15 Supplement: S Meeting

Abstract: 3020 Published: MAY 20 2015

III. Project Management

There are no additional requirements to this Task Order beyond those included in the base contract.

IV. Quality Management

V. Facilities, Equipment, and Other Resources

VI. Storage and Shipping http://apps.webofknowledge.com/full_record.do?product=WOS&search_mode=GeneralSearch&qid=3&SID=6DPPPVzWJb2wYjHwSvR&page=1&doc=1 http://apps.webofknowledge.com/full_record.do?product=WOS&search_mode=GeneralSearch&qid=3&SID=6DPPPVzWJb2wYjHwSvR&page=1&doc=1

Initial Task Order Statement of Work Page 3

VII. Transition

VIII. Deliverables

The Contractor shall deliver the following items in addition to the deliverables listed under the

Base Contract (see the base SOW):

Item# Deliverables Brief Description Recipient(s) and Delivery

Schedule

Project Management Plan

(PMP)

Narrative description of the PMP including milestones and Gantt charts

To COR: within 30 calendar days after task order award.

Review and if necessary, update PMP at least monthly

Analytical assay development report

Detailed description of the analytical methods and their validation

To COR: within 30 calendar days after task completion

3 Production plan

Detailed description of the production plan, including manufacturing timeline, proposed milestones and milestone completion criteria

To COR: within 7 calendar days after task completion

4 Master production records

Batch records suitable for cGMP documentation of the product as well as

QA documentation

To COR: within 30 calendar days after task completion

Released drug substance

(DS)

Characterization of the drug substance to include identity and concentration.

As directed by COR: within

30 calendar days after task completion

Released drug product

(DP) (final product)

Characterization of the vialed product to include identity and concentration.

As directed by COR: within

30 calendar days after task completion

7 Stability reports

Detailed description of the identity of the peptides and peptide concentrations.

To COR: within 30 calendar days after task completion

Initial Task Order Statement of Work Page 4

X. Other Requirements

There are no other additional requirements for this Task Order beyond those required under the

Base Contract.