APPENDIX 2

PROJECT DESCRIPTION/STATEMENT OF OBJECTIVES

PROJECT TITLE

Vaccine Acceleration by Modular Progression (VAMP) - Prophylactic Platform Technology

Medical Countermeasures (MCMs) Against Chemical, Biological, Radiological, and Nuclear

(CBRN) Threats

BACKGROUND/DESCRIPTION

The Portfolio Management Executive for Chemical, Biological, Radiological, and Nuclear

Defense (PME CBRND), Joint Program Manager – CBRN Medical (JPM-M) Accelerated Defense

Pharmaceuticals (ADP) Product Office, is requesting from product developers the design, manufacture, non-clinical and clinical testing of advanced platform technology for prophylaxis against one or more specific CBRN threats of concern. The Government is interested in approaches that will support the development of prophylactic platform technology using traditional or non-traditional administration as well as immune modulating approaches.

The VAMP program evaluates platform technologies against disease/injury caused by CBRN threats in appropriate animal models and human clinical trials for safety, immune response, and effectiveness while using data-driven decision and processes to bridge capability gaps for the warfighter. The goal of the program is to expedite the development of these prophylactic MCMs through a Phase I or Phase II clinical trial. To achieve this, the VAMP program utilizes a modular approach incorporating Go/No-Go checkpoints at each applicable non-clinical, clinical, CMC and regulatory phases to facilitate generation of an Investigational New Drug Application, end of Phase

1, or end of Phase 2 data packages supporting further advancement as warranted.

As part of the current MCM environment to protect against CBRN threat agents listed in Appendix

1, the Government is interested in furthering the development of prototype candidates using either traditional (intramuscular injection) or alternative routes of administration (i.e., microneedles, intranasal, etc., and defined below as non-traditional administration). In addition, MCMs that can enhance and modulate the immune system (biological response modifiers) expand the

Government’s toolbox of MCMs while building the warfighter’s bio-armor.

To be eligible for funding, Offerors shall have a demonstrated, successful history of designing, manufacturing, and clinical testing of prophylactic MCM platform as well as experience working with the U.S. Food and Drug Administration (FDA). Additionally, Offerors will have expertise in all aspects of platform manufacturing under current Good Manufacturing Practices (cGMP) and prophylactic platform development with the intent to obtain licensure. Pending the outcome of program modules, the Government may consider further development and/or procurement of successful prophylaxes under a separate agreement.

PROGRAM OBJECTIVES

1) Performance Objectives

a. Program Objectives

The project objectives include design, development, non-clinical testing, manufacturing and human clinical trials for mature prophylactic platform technologies.

The project will result in successful prototype candidates that are safe to administer to humans to protect against Department of War (DoW) priority threats; work can be targeted to a threat or threats which could pivot and expand to other threat agents of interest upon a negotiated mutual modification.

This includes complete product development and required stage-appropriate studies of these candidates against CBRN threats in Appendix 1. First-in-human products should include submission of an Investigational New Drug (IND), and all studies necessary through a Phase I clinical trial, as soon as possible.

The prophylactic platform candidates, utilizing a traditional or non-traditional route of administration developed for this project, must target at least one of the CBRN threats of interest to the Government (preferably broad spectrum). Specifically, the Offeror is responsible for:

Module 1: Design a prophylactic medical product candidate targeting one or more

CBRN threats listed in Appendix 1.

• Design a prophylactic medical product on manufacturable platform technology and formulate final candidate (prototype product) for clinical evaluation – This includes all methods and assays associated with the optimization, selection, and evaluation of an immunogenic platform construct, suitable for cGMP manufacture at development stage- appropriate levels, and human studies.

• All aspects of construction and formulation of the platform candidate for delivery – Traditional delivery formulation methods/processes shall be supported by historical safety and immunogenicity data and align with selected mode of delivery. Non-traditional routes of administration shall be supported by technical testing and/or formulation for specific non-traditional route of administration, as applicable.

• Acceptable modes of delivery include intramuscular injection and needle-free delivery (such as transdermal/microneedle skin patch, intranasal formulation, etc.).

• Demonstrate established platform technology cGMP manufacturing, as needed.

• Development of any lot release testing needed for cGMP production.

• Stability testing of the prototype product to support human clinical use.

Module 2: Animal studies, including toxicity and efficacy, as applicable. Initiated upon completion of prototype product design and formulation.

• Perform pre-clinical studies to support submission of an IND in the effort for the prototype product.

• Develop and establish stage-appropriate (i.e., qualified vs. validated) assays and methods suitable for intended use to measure the immunogenicity of the prototype product in humans and animals (i.e., non-human primates) demonstrated suitable for bridging animal efficacy outcomes to human clinical trial immunogenicity data. All immune assays to measure clinical endpoints are expected to be well-controlled (i.e., qualified or validated based on the phase of clinical study) prior to clinical sample testing of the prototype product.

• Generate stage-appropriate animal efficacy data using methods and measures suitable for intended use to evaluate outcomes for the chosen CBRN threat(s) when the prototype product is used.

Module 3: Manufacturing of prophylactic medical product candidate suitable for human use. Initiated upon completion of prototype product candidate design and formulation.

• All aspects of the stage-appropriate cGMP manufacturing, fill-finish, lot release testing, required stability testing, and storage of manufactured lot(s).

Module 4: Regulatory interactions. All activities required to submit and support an IND through Biologics License Application (BLA).

• Request of pre-IND meeting and holding a pre-IND meeting with the Food and

Drug Administration (FDA), as needed.

• Submission of IND ahead of first in human clinical trial.

• Support and maintenance of the IND through life of the program.

• Expanded Access Protocol (EAP) or pre-Emergency Use Authorization (pre-

EUA), as needed.

Module 5: Human studies.

• To initiate completion of appropriate tasks in Modules 2, 3, and 4, as required, for conduct of a human clinical trial (i.e. Phases 1-2, excludes Phase 3) for the prototype product. The Offeror shall manufacturer and release sufficient quantities of the prototype product for clinical trial use and provide oversight all human clinical trials following Good Clinical Practice (GCP) guidelines.

b. Regulatory Objectives

(1) The Offeror shall serve as regulatory product sponsor for any FDA submissions.

(2) The Offeror shall be responsible for authoring acceptable regulatory documents for submission and electronic Common Technical Document (eCTD) filings with the FDA in support of IND. Example filings: chemical manufacturing and non-clinical reports.

(3) If applicable, the Offeror must submit to the Government all point papers, briefings, Target Product Profiles (TPP), Program Development Plans (PDP), Regulatory Strategy, Letter(s) of Authorization from the candidate sponsor, technology transfer report and gap analysis, formulation development, feasibility and optimization reports, U.S. Army Medical Research and

Development Command, Animal Care and Use Review Office (USAMRDC

ACURO) approvals, USAMRDC Office of Human Research Oversight

(OHRO) approvals, Human Resources Operations Branch (HROB) approvals, technical presentations and publications, and any formal technical reports that have been prepared for eventual submission to FDA or other regulatory agencies. Examples include the following reports related, but not limited to:

prophylactic platform technology development, manufacturing development, manufacturing validation, completed batch records, certificates of analysis, analytical development and validation, prophylactic platform stability, non-clinical testing, clinical testing, data management plan, and statistical analysis plan.

a. Regulatory Strategy: For each prototype product the Offeror shall generate and maintain a comprehensive Regulatory Strategy that outlines the specific non-clinical, clinical, and CMC pathway required for FDA approval. Candidate will not be FDA approved under VAMP, but should be developed with this end goal in mind.

b. Target Product Profile: The Offeror shall generate and maintain a TPP for CBRN Medical use on an annual basis for each prototype product supported. The TPP shall define the prototype product key target criteria including non-clinical, clinical, and manufacturing characteristics integrated into the regulatory stage of development. The TPP will be used to guide the operational development and decision-making throughout the product lifecycle. At a minimum, the TPP must define the target criteria for:

i. Efficacy to include targeted immune measures and clinical endpoints in suitable models (e.g., survival percentage, reduction in symptoms)

1. Time/Onset to protective immunity (schedule for primary series)

2. Duration of Protection (preferably from a single dose)

ii. Safety

iii. Route of Administration (e.g., intramuscular, oral)

iv. Shelf-life and Stability Requirements

v. Booster requirements, if any

(4) The Offeror shall cross-reference all applicable IND(s), Master Files, BLAs, and/or New Drug Applications (NDAs) prior to the conduct of the prototype product clinical trial, and shall allow cross-referencing by CBRN Medical of associated documents with this effort when appropriate.

(5) The Offeror shall be responsible for ensuring that all non-clinical and clinical studies are approved in accordance with the ACURO and the OHRO, respectively, prior to initiating any studies.

(6) The Offeror shall assign the appropriate Government representative(s) co-contact status on documents in (4) associated with this effort.

(7) The Offeror shall authorize the FDA to share with the Government and its designated representatives, all information on the IND(s) associated with this effort, in accordance with Public Law 115-92.

(8) The Government reserves the right to review and approve all formal regulatory submissions, briefing packages, and significant correspondence prior to their submission to the FDA.

c. Project Management Objectives

It is anticipated that the performer will be required to submit a number of documents to capture the progression of the project, post-award. Requirements may include, but are not limited to the following:

Reporting –

(1) Each month, the Offeror shall deliver a technical and financial report documenting accomplishments, difficulties, and risks/issues with associated mitigations and/or outcomes. The Offeror shall also provide a detailed progress report with monthly status updates covering all activities associated with conduct of the study, to include an integrated master schedule utilizing

Microsoft Project. These reports will be used by the Government to assess both technical and schedule performance and will serve as milestones to allow invoicing for work to date. Quarterly and annual reports shall also be provided, and the Offeror shall provide a technical summary of progress over the associated time-period, as well as summary analysis of any risks/issues/opportunities. When submitted, the quarterly and annual reports may take the place of the monthly report. At the end of the effort, the Offeror shall provide a detailed clinical study report, and a final technical and business report. The Offeror shall deliver an updated monthly Spend Plan outlining obligated or expended funds throughout the project lifecycle tied to specific deliverables or WBSes along with Earned Value Management metrics.

(2) Additional deliverables will include:

(a) Draft and final non-clinical and clinical study reports, to include appropriately formatted datasets (SEND and CDISC - Clinical Data

Interchange Standards Consortium compliant).

(b) Inclusion of the U.S. Government in FDA meetings.

(c) Submission of all read-ahead packages for FDA meetings ahead of time.

(d) Records of any and all communications with the FDA.

Meetings –

(1) The Offeror shall schedule regular, recurring meetings with the Government program manager (typically weekly for the duration of the effort), to discuss progress on the project.

(2) The Offeror shall schedule regular, recurring monthly meetings with the broader Government team for high-level updates and discussions.

(3) The Government may request additional ad hoc meetings, as needed.

(4) The meeting agenda shall be submitted to the Government three (3) business days prior to any regular meetings.

(5) Draft minutes shall be submitted to the Government five (5) business days following any meetings. The Government will review and provide comments on the draft minutes within five (5) business days of receipt; lack of comments will be taken as concurrence. The Offeror shall submit final minutes within three (3) business days of Government comment.

d. Logistics Objectives

(1) The Offeror shall be responsible for (sub) contracting or executing all intellectual property, materiel, and sample shipments and maintenance of all associated records and permits.

(2) The Offeror shall ensure the security of all project data, including Controlled

Unclassified Information (CUI) and potential Secret Information.

2) Performance Requirements

Submission and maintenance of non-clinical and clinical documentation for regulatory filings (pre-IND/IND) that support a regulatory strategy to achieve FDA licensure.

3) Operational Constraints/Limitations/Restrictions

Not Applicable

DOWNSELECTION CRITERIA

These criteria will be taken into account when assessing products in addition to the targeted threats of interest:

1) Manufacturing – process development/process capability

2) Characterization Assays – presence of qualified/validated assays

3) Product Safety and Use – safety and tolerability in humans; feasibility of use

(dose/schedule) in rapid response

4) Efficacy of Product – appropriate animal model(s); mechanism of action of the drug against the toxicity; likely or known correlate(s) of protection in animals or humans;

suitable methodology to bridge animal efficacy to human datasets, as applicable

5) Performer Past FDA Experience – proposed regulatory pathway; interactions with the

FDA/existing Master File; experience with GLP/GMP/GCP

6) Performer Past Experience – industrial base/commercial market; manufacturing, clinical trial, and/or regulatory experience at advanced QRLs

7) Schedule – timeline for getting into proposed Phase 1 or 2 clinical trial

8) System of Systems – is the platform plug and play; broadly applicable across pathogens;

alternative delivery method(s) as well as use of Biological Response Modifiers to improve product performance

PERIOD AND PLACE OF PERFORMANCE

The anticipated Period of Performance for this effort is up to four (4) years from date of award for design, manufacturing, non-clinical testing, and clinical trials. Specific dates to be negotiated. It is anticipated that the primary place of performance will be the contractors’ facilities, however this aspect can be negotiated as part of each Offerors’ submission.

DELIVERABLES

The Offeror will be required to provide a number of deliverables throughout the course of this project, categorized as either Data or Prototype.

DATA DELIVERABLES

Data deliverables include, but are not limited to the following:

1) Draft minutes shall be submitted to the Government five (5) business days following the meeting. The Government will review and provide comment on the draft minutes within five (5) business days of receipt; lack of comments will be taken as concurrence. The

Offeror shall submit final minutes within three (3) business days of Government comment.

2) Monthly financial status and expenditure forecast report (Spend Plan).

3) Monthly progress report.

4) Risk Management Plan.

5) Final prototype project report.

6) Patents-reporting of subject inventions.

7) Regulatory documentation.

8) Appropriate non-clinical and clinical datasets to inform the build of FDA Animal Rule compliant computational models in alignment with Model Informed Drug Development

(MIDD). Human datasets to be de-identified for CBRN Medical use.

9) Miscellaneous data submissions.

10) Work Breakdown Structure (WBS).

11) Integrated Master Schedule (IMS).

Note: Technical data deliverables described herein shall be delivered to the Government with

Unlimited data rights.

PROTOTYPE DELIVERABLES

The Offeror shall provide data packages and assessments for a safe and effective prophylactic platform prototype candidate, targeting a CBRN threat in Appendix 1, that demonstrates technical feasibility and military utility.

AGREEMENTS OFFICER’S REPRESENTATIVE (AOR)

Name: Emily Cisney

Telephone: 520-672-7566

E-mail: emily.d.cisney.civ@army.mil

Office Symbol: JPM CBRN Medical

ALTERNATE AOR

Name: Andrew Glenn

Telephone: 301-619-8439

E-mail: andrew.m.glenn7.civ@army.mil

Office Symbol: JPM CBRN Medical

Requiring Activity mailto:andrew.m.glenn7.civ@army.mil

Portfolio Management Executive for Chemical, Biological, Radiological, and Nuclear

Defense (PME CBRND), Joint Program Manager – CBRN Medical (JPM-M) ADP Product

Office