Amendment_3_-_Addition_of_Research_Area_004_Characterizing_and_Improving_Humanized_Immune_System_Mouse_Models_(IMM-HIS).pdf

Amendment of Solicitation: HHS-NIH-NIAID-BAA2019-1

AMENDMENT THREE (3)

OFFICE OF ACQUISITONS: National Institute of Allergy and Infectious Diseases

5601 Fishers Lane, Suite 300, Rockville, MD 20852

Date of Solicitation Issuance: 02/22/2019 Date of Amendment No.1 Issuance: 05/01/2019

Date of Amendment No.2 Issuance: 05/09/2019

Date of Amendment No.3 Issuance: 05/23/2019 Number of Pages: 17

Attachment: HHS-NIH-NIAID-BAA2019-1 – Amendment 3

Point of Contact: Division of Allergy, Immunology, and Transplantation (DAIT)

Research Area 004: Characterizing and Improving Humanized Immune System Mouse Models

(IMM-HIS)

Liem Nguyen, Contracting Officer Phone: (240) 669-5144; E-mail: liem.nguyen@nih.gov Offerors must acknowledge receipt of the amendment by Amendment number(s) and date of the amendment. Include a statement of acknowledgement in your proposal submission.

Failure of acknowledgement may result in rejection of your offer.

Except as provided herein, all terms and conditions of the solicitation remain unchanged and in full force and effect.

Purpose of Amendment 3:

The purpose of Amendment 3 is twofold:

1. To add RESEARCH AREA 004, “Characterizing and Improving Humanized Immune

System Mouse Models (IMM-HIS)” to the 2019 Omnibus Broad Agency Announcement:

RESEARCH

AREA

NIAID

DIVISION TITLE

RECEIPT

DATE AND

TIME:

004 DAIT Characterizing and Improving Humanized Immune System Mouse Models (IMM-HIS)”

09/16/2019 * mailto:liem.nguyen@nih.gov

* Proposals must be received before 3:00 PM Eastern Time on the date specified herein.

Please see the Proposal Submission Instructions for more information.

Offers will be valid for 240 days unless a different period is specified by the Offeror on the Attachment entitled, "Proposal Summary and Data Record, NIH 2043.

2. To provide the revised solicitation: “HHS-NIH-NIAID-BAA2019-1 – Amendment Three”, attached hereto, incorporating Amendment 2 receipt date and time and Research Area 004 identified above.

Accordingly, SECTIONS 2 and 3 of the solicitation are revised as follows:

SECTION 2. - CONTRACTING OFFICER POINTS OF CONTACT, Division of Allergy, Immunology, and Transplantation (DAIT) is revised as follows:

Division of Microbiology and Infectious Diseases (DMID) and Division of Allergy, Immunology, and Transplantation (DAIT)

Research Area 001: Development of Radiation/Nuclear Medical Countermeasures

(MCMs)

Research Area 004: Characterizing and Improving Humanized Immune System Mouse Models (IMM-HIS)

Liem Nguyen Contracting Officer Phone: (240) 669-5144 E-mail: Liem.Nguyen@nih.gov

SECTION 3. – RESEARCH AREAS AND TECHNICAL OBJECTIVES, is revised to add

SECTION 3.3 – DIVISION OF ALLERGY, IMMUNOLOGY, AND TRANSPLANTATION

(DAIT), NIAID: Research Area 004 – Characterizing and Improving Humanized Immune System Mouse Models (IMM-HIS), as follows:

SECTION 3. - RESEARCH AREAS AND TECHNICAL OBJECTIVES

3.3 - DIVISION OF ALLERGY, IMMUNOLOGY, AND TRANSPLANTATION (DAIT),

NIAID: Research Area 004 – Characterizing and Improving Humanized Immune System Mouse Models (IMM-HIS)

3.3.1 – BACKGROUND

Research supported by the National Institute of Allergy and Infectious Disease (NIAID), National Institutes of Health (NIH), Department of Health and Human Services (DHHS) seeks to understand, treat, and eventually prevent the myriad of infectious, immunologic, and allergic diseases that threaten millions of human lives. This includes research to mailto:Liem.Nguyen@nih.gov understand basic biologic and immunologic mechanisms that lead to the development of new therapies, vaccines, diagnostics, and other technologies that improve the health of individuals in the United States and around the world. NIH also supports development and distribution of research resources, including reagents, animal models, and tissue samples to support investigators with their research.

Animal models play an important role in: 1) understanding the development and function of the immune system; 2) exploring the pathogenesis of infectious and immune mediated diseases; and 3) developing and evaluating new modalities for treatment and prevention.

Mice have central roles in various aspects of these endeavors and in biomedical research more generally; however, genetic and physiologic differences between mice and humans can present challenges in translating results from studies conducted in mice to humans.

Some of the differences include expression of innate immune molecules, such as TLR11, TLR12, TLR13, which are present in mice but not humans; and the species-specificity of certain cytokines, signaling molecules; similarly, susceptibility to pathogens or responsiveness to drugs and biologics may differ across species. The development of mice reconstituted with functional human cells or tissues (i.e., humanized mice) permits the analysis of many human biological mechanisms in a small animal model. Humanized mice are an important tool in studying fundamental immunology, infectious and immune-mediated diseases, and in evaluating therapeutics and vaccines.

Humanized Immune System (HIS) mice are engrafted with human immune cells or tissues, resulting in an immune system that is partially to primarily replaced with human cells and tissues. The first HIS mouse models were developed in 1988 using a single immunodeficient mouse strain and several different sources of human hematopoietic stem cells. Eight humanized mouse strains currently constitute the major platforms used to generate HIS mice. These platforms can be generated with a variety of fetal and non-fetal derived human immune cells and tissues including: bone marrow-liver-thymus (BLT) explants; adult peripheral blood mononuclear cells; human CD34+ hematopoietic stem cells (HSC); and neonatal thymus. Major scientific advances have been made in understanding infectious disease pathogenesis and development of therapeutics, for pathogens that include Human Immunodeficiency Virus (HIV), Zika Virus (Zika) and Epstein-Barr Virus (EBV), using HIS mouse models made with human fetal tissue.

While no single HIS model is appropriate or optimal for all applications, each model has its strengths and limitations, and the optimal choice may depend on the questions to be answered. Promising improvements in humanized mouse models have been achieved since their development in 1988, but additional advances are required to recapitulate many aspects of human immune system development and function. For example, various models can recapitulate key aspects of human T cell immunity, but are less able to recapitulate human innate immunity and antibody responses, regardless of the human tissue source. In addition, most mouse cytokines do not fully support human lymphoid and myeloid development, resulting in impaired lymph node development and lymphoid architecture. In addition, few direct comparisons have been conducted of HIS mice derived using fetal vs. non-fetal human tissue sources (https://www.niaid.nih.gov/research/humanized-mouse-model-workshop).

The goal of the Characterizing and Improving Human Immune System Mouse Models (IMM-HIS) program is to conduct systematic, comprehensive, and direct comparisons of leading models derived from fetal vs. non-fetal sources; and develop, improve, evaluate, and characterize HIS mouse models derived from fetal vs. non-fetal tissues. Realizing https://www.niaid.nih.gov/research/humanized-mouse-model-workshop

3.3.2 - Research Area 004 – Characterizing and Improving Humanized Immune System Mouse Models (IMM-HIS) that not all aspects of human immunity may be reflected in a single HIS mouse model, models may be created to improve cell-cell interactions, support differentiation, and induce maturation of human cells to create a model that faithfully recapitulates a functional human immune system.

All qualified offerors are invited to apply to this solicitation. Investigators supported through the IMM-HIS program will be expected to collaborate with each other, share novel research resources, and share both positive and negative results in order to help guide basic research and development activities within the broader scientific community.

These post-award collaborations minimally are expected to include sharing of HIS animal models and participation in direct comparisons of different HIS animal models across contractor sites (please see Section 3.3.6: Advance Understandings).

NIAID recognizes that a single organization or institution may not have the expertise and facilities required to perform all parts of the technical plan, and that it may be necessary for the Contractor to subcontract portions of the work. The Contractor shall be responsible for all work performed under this contract, including that performed by any subcontractor.

Each offeror is required to address all Technical Objectives described below. However, NIAID reserves the right to award all or any portion of a particular offeror’s proposed activities based on technical merit, scientific priority, programmatic balance, and the availability of funds. Clinical trials are not permitted under this solicitation.

3.3.2.1 - Budget and Award Information

NIAID estimates that the average annual total cost (direct and indirect costs combined) is $500,000-$700,000 per award, with an estimate to support 2-4 contracts. However, it is anticipated that the total cost for the award(s) may vary depending upon the scope of the project and the technical objectives of the award(s). The length of time for which funding is requested should be consistent with the nature and complexity of the proposed research. The period of performance proposed by an offeror should not exceed 3 years;

funding beyond the first award year will depend upon successful completion of milestones.

3.3.2.2 – Research and Technical Objectives

The overall goals of the Characterizing and Improving HIS Mouse Models (IMM-HIS) program are to conduct direct comparisons and detailed immunologic analyses of HIS mice derived from fetal vs. non-fetal human tissue sources, and to optimize and/or develop, evaluate, and characterize HIS mouse models derived from non-fetal sources of human cells/tissue that better recapitulate systemic and tissue-specific human innate and adaptive immunity and lymphoid tissue development.

To achieve the IMM-HIS program goals, Contractors will be responsible for all of the following activities:

A. Direct immunologic comparisons of HIS mice derived from fetal and non-fetal sources of human cells/tissues, including:

a. HIS platform(s) selection and model characterization;

b. Evaluation of primary and secondary lymphoid tissue development, architecture, and function; and

c. Systemic and tissue-specific innate and adaptive immune cell development and function.

B. HIS mouse model development and/or optimization using non-fetal sources of human cells/tissues, including:

a. Validation and reproducibility analysis;

b. Comprehensive evaluation of immune system development and function; and

c. Comparison with an appropriate HIS mouse model generated using human fetal tissue.

C. Training: Development and implementation of training sessions to teach investigators (e.g., other Contractors, broader scientific community) how to engraft, characterize and use the HIS mouse models developed and/or optimized under the contract.

These activities can be performed in the context of specific research areas supported by NIAID; these areas are: HIV or other infectious diseases; allergy/asthma;

transplantation immunology and autoimmunity.

NOTE: This contract will not provide funds to support:

· Development of vaccines or therapeutics for infectious or immune-mediated diseases or cancer.

· Utilization/optimization of human fetal tissue for regenerative medicine or engraftment of cells/tissues that are not part of or required for optimal development/function of the human immune system.

3.3.3 - RESEARCH AREA 004 - Additional Technical Proposal Instructions

The following information supplements Section 4 – Instructions, Conditions, and Notices to Offerors of this solicitation, and should be used for preparing proposals in response to Research Area 004.

It is strongly recommended that offerors use the following template as the format for the Technical Proposal. All information presented in the Technical Proposal should be presented in the order specified below.

These Additional Technical Proposal Instructions reflect the requirements of Research Area 004 of the BAA and provide specific instructions and formatting for the Technical Proposal. While Section 4 of the BAA provides a generic set of Technical Proposal Instructions applicable to all NIH R&D solicitations, these Additional Technical Proposal Instructions are tailored to the specific requirements of this Research Area.

The information requested in these instructions should be used along with Section 4 of the BAA to format and prepare the Technical Proposal, and should be used as a Table of Contents for your Technical Proposal. Offerors should follow the instructions in Section 4 of the BAA, and include the information requested here.

Offerors are advised to give careful consideration to the Broad Agency Announcement Research Area 004 Description, Background and Introduction, Research and Technical Objectives, all reference materials and attachments, the Technical Evaluation Criteria in Section 6, and the BAA as a whole in the development of their Technical Proposals.

Offerors proposing subcontracts and/or consultants to perform portions of the proposed Statement of Work should clearly identify the specific tasks for which they plan to utilize subcontractors and/or consultants, as well as the method and level of integration/coordination between the prime Contractor and all proposed subcontractors and/or consultants, and the expected advantages of such an approach.

Offerors must refer to Section 4.3.2.1 of the BAA, entitled “Proposal Submission Instructions,” which details strict guidelines, including page limitations, formatting and layout of proposals, and prohibits the offerors use of links to internet web site addresses (URLs) to direct readers to alternate sources of information.

TECHNICAL PROPOSAL – TABLE OF CONTENTS

SECTION 1:

1) PROPOSAL TITLE PAGE. Include BAA title and number, name of organization, DUNS number, and identify if the proposal is an original or a copy. Offerors that include data in their proposals that they do not want disclosed to the public for any purpose, or used by the Government except for evaluation purposes, shall also include the legend regarding Restriction on Disclosure and Use of Data prescribed by FAR 52.215-1 (e).

2) TABLE OF CONTENTS

SECTION 2: TECHNICAL PROPOSAL OVERVIEW (suggested 3-page maximum)

Provide a brief description of the proposed project, including:

1) 1-2 sentence summary describing the concept the offeror is proposing.

2) A summary describing the scope of the activities proposed.

https://www.acquisition.gov/sites/default/files/current/far/html/52_215.html

3) A brief description of the activities proposed by the offeror and all proposed subcontractors, including identification of all proposed subcontractors and a list of key personnel for the offeror and the proposed subcontractors with degrees, titles and role in the project.

4) By area of expertise, provide the total number of staff, the number available to be assigned to the contract for the offeror and all proposed subcontractors, and total number of additional staff to be hired and trained.

5) A brief description of the facilities and other resources to be made available by the proposed prime Contractor (offeror) and any proposed subcontractors.

SECTION 3: STATEMENT OF WORK FORMAT (suggested maximum of 10 pages)

Offeror(s) are required to provide a Statement of Work in their proposal. The Statement of Work shall be developed by each offeror based on the information in this Research Area’s Section entitled “Research and Technical Objectives,” and shall consist of two parts: (1) Scope, and (2) Technical Requirements. Provided below is an outline of the Statement of Work format that should be used by all offeror(s) in the preparation of their Technical Proposals. The headers and subheaders may be adjusted to match the requirements as proposed in each offeror’s individual technical proposal. In addition, the Scope and Technical Requirements sections should be broken out into research stages/activities that align with project milestones.

Contracts awarded as a result of this BAA will include the Statement of Work proposed by the offeror, as negotiated and accepted by the Government. Offeror(s) will be required to perform the activities and provide the resources appropriate to the scope of their specific negotiated Statement of Work.

The opening paragraph under the Technical Requirements section of the Statement of Work shall be followed by a description of all activities that the Contractor shall perform after the award of the contract. The Technical Requirements shall include all activities required to effectively implement the project and shall include a description of all items to be delivered to the Government during performance of the contract, such as progress reports, financial reports, end products, and other deliverables, along with a timetable for their delivery.

NOTE TO OFFEROR: Each offeror shall provide detailed specifications of the requirement utilizing the following sample outline of tasks and subtasks. Any tasks or subtasks that are not applicable to your proposed effort should be deleted. Any tasks or subtasks specific to your proposed effort not addressed below shall be added.

SAMPLE STATEMENT OF WORK

1. SCOPE

Instruction to offerors: Provide a brief description (one to two paragraphs) of the overall project and objectives in broad terms that indicates the size and magnitude of the proposed effort.

2. TECHNICAL REQUIREMENTS

[NOTE TO OFFEROR: The Technical Requirements shall begin with the following introductory paragraph.]

Independently, and not as an agent of the Government, the Contractor shall furnish all necessary services, qualified professional, technical, and administrative personnel, material, equipment and facilities, not otherwise provided by the Government under the terms of this contract, as needed to perform the tasks set forth below. Specifically, the Contractor shall:

A. PROVIDE OR PERFORM DIRECT COMPARISON OF HIS MICE MADE

WITH FETAL AND NON-FETAL CELLS/TISSUES

1. HIS Platform(s) Selection and Analysis Methods, including General Analyses of the Model

2. Comparison Methods, including: Evaluation of Primary and Secondary Lymphoid Tissue Development, Architecture, and Function; Analysis of Systemic and Tissue-Specific Innate Immune Cell Development and Function;

and Analysis of Systemic and Tissue-Specific Adaptive Immune Cell Development and Function: T cell and B cell

B. DEVELOP/OPTIMIZE HIS MOUSE MODELS USING NON-FETAL

HUMAN CELL/TISSUE SOURCES

1. Evaluate Primary and Secondary Lymphoid Tissue Development, Architecture, and Function

2. Analyze Innate Immune Cell Development and Function

3. Analyze Adaptive Immune Cell Development and Function: T cell and B cell

4. Conduct Validation and Reproducibility Analysis

5. Determine suitability of the model for specific research areas, e.g., HIV or other infectious diseases, transplantation immunology, autoimmunity, etc.

C. PROVIDE TRAINING FOR ENGRAFTMENT AND USE OF HIS MOUSE

MODELS DEVELOPED/OPTIMIZED UNDER THE CONTRACT

D. PROVIDE SCIENTIFIC AND TECHNICAL PERSONNEL

E. DEMONSTRATE EXPERTISE IN PROJECT MANAGEMENT

F. PROVIDE APPROPRIATE FACILITIES, EQUIPMENT, AND OTHER

RESOURCES

SECTION 4: TECHNICAL DISCUSSIONS

In addition to the guidance in Section 4 of the BAA, this section of your technical proposal should include documentation to demonstrate how you will accomplish the work detailed in your proposed Statement of Work. It is recommended that your proposal be organized in accordance with the order of your Statement of Work and the technical evaluation criteria provided in Section 6.

Additionally, please ensure that your Technical Proposal addresses the following:

The Technical Requirements should be organized into research stages/activities that align with project milestones and timelines.

Organizational Experience:

In addition to the information requested under Section 4.3.3.1.15 “Qualifications of the Offeror”, all offerors are requested to include in their technical proposals a description of at least two examples of similar projects performed by your organization that are of comparable size and scope and/or related to the effort proposed in response to this BAA.

The projects may be either completed or ongoing.

Provide a detailed description of the procedures that will be used to accomplish the program objectives listed below:

A. DIRECT COMPARISON OF HIS MICE MADE WITH FETAL AND NON-FETAL

CELLS/TISSUES, including:

a. The rationale for HIS platform(s) selection and general model analyses, including:

i. Percent human immune reconstitution in blood, lymphoid and non-lymphoid tissues; and methods/standards used to ensure reproducible reconstitution

ii. Maintenance of reconstitution over time

iii. Emergence of graft versus host disease or other pathology of incompatibility

iv. Percentage of mice achieving standard of reconstitution

b. Analyses that will be used for evaluation of primary and secondary lymphoid tissue development, architecture, and function; systemic and tissue-specific innate immune cell development and function; and systemic and tissue-specific adaptive immune cell development and function.

c. Documentation of ability to obtain and use required human tissue/cell sources, including the capacity to obtain sufficient samples to accomplish the proposed studies; and all required institutional approvals, Material Transfer Agreements, Letters of Support, or other documents necessary to proceed, without delay, should an award be made.

B. HIS MOUSE MODEL DEVELOPMENT/OPTIMIZATION USING NON-FETAL

HUMAN CELL/TISSUE SOURCES, including: methods for model development/optimization, validation and reproducibility; and the methods that will be used for full evaluation of immune system development and function (e.g. primary and secondary lymphoid tissue development, architecture, and function; systemic and tissue-specific innate and adaptive immune cell development and function).

C. TRAINING: Provide a detailed description of the training sessions that will be developed and implemented in order to teach investigators (e.g., other Contractors, broader scientific community) how to engraft, characterize and use the HIS mouse models developed and/or optimized under the contract.

These activities also can be performed in the context of specific research areas supported by NIAID; these areas are: HIV or other infectious diseases;

allergy/asthma; transplantation immunology and autoimmunity.

SECTION 5: SCIENTIFIC AND TECHNICAL PERSONNEL

Provide information relevant to document individual training, experience, qualifications and expertise necessary for the successful completion of the proposed Statement of Work. Limit CVs to 2-3 pages and provide selected references for publications relevant to the scope of the contract.

1) Principal Investigator (PI): Describe the experience, training, expertise, and qualifications, and level of effort of the proposed Principal Investigator to lead and direct the activities to be carried out under the proposed Statement of Work. In particular, address scientific and technical expertise in: development and/or use of HIS animal models for immunologic analyses.

2) Other Key Scientific and Technical Personnel: Describe the experience, training, expertise and qualifications, as well as the level of effort, for all proposed key scientific and technical personnel. Specific areas of expertise include: development, use and optimization of HIS mouse models derived from fetal or non-fetal sources of human tissue; and broad immunology expertise that covers all required components of the immune system for characterization of HIS mice.

SECTION 6: PROJECT MANAGEMENT

1) Provide a Project Management Plan for the overall organization that addresses the planning, initiation, implementation, conduct, monitoring and completion of tasks identified in the proposed Statement of Work. If consultants and/or subcontractors are proposed, include a plan to manage, coordinate, and oversee the work performed by consultants and/or subcontractor(s).

2) Provide a Staffing Plan that describes roles, responsibilities, and level of effort for all scientific and technical personnel, including all proposed subcontractors and consultants. Provide an administrative and technical framework indicating clear lines of authority and responsibility for all proposed personnel. Include a chart of the proposed organizational/management structure for the project.

3) Describe the project management systems that will be used to track activities and to keep multiple activities on time and budget. The plan must include a description of the quality control methods that will be used to ensure the effective and efficient initiation, implementation, management, and oversight of contract requirements.

4) Outline how the PI (or Project Manager) will communicate with the Contracting Officer’s Representative and Contracting Officer and how the PI (or Project Manager) will communicate, monitor, and manage the project both internally and externally (at subcontractor facilities).

5) Outline specific activities and decision points that align with milestones and timelines using a Gantt chart.

SECTION 7: FACILITIES, EQUIPMENT, AND OTHER RESOURCES

The Technical Proposal should document availability and adequacy of facilities, equipment, space and other resources necessary to carry out the proposed Statement of Work, including:

1) Location and features of facilities including a floor plan and a list of equipment, resources, training, and adequate throughput capacity required to implement the Statement of Work in compliance with all Federal and NIH regulations, and provide documentation for the availability of these resources dedicated to the project for the prime Contractor and any proposed subcontractors (lease or ownership information should be provided).

2) Identification and description of ALL support resources (including Information

Technology systems, computing and analytical services, training and other resources) that will be required to effectively complete the proposed Statement of Work.

3) Documentation of the availability of reagents that are not commercially available, such as reliable sources of human cells and tissues that will be used for HIS mouse model generation.

4) The care and housing of laboratory animals, including:

a. appropriate veterinary coverage;

b. availability of appropriate facilities and capacity for proposed studies; and

c. provisions for complying with NIH guidelines for the housing and humane care and use of laboratory animals as delineated by the Office of Laboratory Animal Welfare (OLAW; http://grants.nih.gov/grants/olaw/olaw.htm).

5) Adherence to NIH regulations on human subjects research, where applicable.

SECTION 8: OTHER CONSIDERATIONS

Other than those detailed in the Government Furnished Property clause or otherwise publicly available, the offeror shall not propose government furnished resources, to include government employees, facilities, intellectual property or biological materials. If you propose government furnished resources your proposal will not be considered further for award.

This section of the Technical Proposal should document other resources not covered in 1 through 4 above necessary to carry out the proposed Statement of Work.

This section of the Technical Proposal should document how the offeror will ensure compliance with the post-award activities described below.

1. Kick-off and Annual Review Meetings

Contractors are required to attend a contract initiation meeting within three (3) months of contract award and annual review meetings, thereafter to be held near or in Rockville, Maryland.

Contract Initiation Meeting: The purpose of the 1-day contract initiation meeting is to establish working relationships and discuss project plans with all of the awarded investigators.

Annual Program Progress Meetings: The purpose of the 2-day annual meetings is for the Contractors to provide:

· Updates on results of activities undertaken or completed since the last review meeting;

· Updates on milestones and timelines, including an updated Gantt chart; and

· A description of any problems encountered or anticipated; a discussion of potential approaches to overcoming problems; and a description of activities to be undertaken in the coming year.

The Contractor PI shall provide a copy of any slide presentations to the COR not later than 3 days before the annual meeting. All Contractor PIs, Project Managers, and other key contract investigators including subcontractor personnel, shall attend these meetings, along with the NIAID COR, the Contracting Officer, and other designated NIAID staff.

The COR may invite other Extramural Program Staff from NIH to attend these meetings as well as investigators from other related NIAID-funded programs. All participants shall be subject to a confidentiality agreement prepared by the NIAID. Meetings will be closed to the public and shall involve oral and electronic presentations by the Contractors, and NIAID staff, as necessary.

2. Site Visits

Within 90 calendar days of the effective date of the contract, the Contractor shall plan, conduct and be responsible for the logistical arrangements for annual site visit meeting at the Contractor’s facility. The Principal Investigator, Project Manager, all key investigators, key subcontractor personnel, the COR, and other designated NIAID staff, shall attend this meeting. The purpose of this meeting shall be to review the Technical Plan and to coordinate activities and communication between the Contractor and the NIAID. The Contractor PI shall provide a copy of any slide presentations to the COR not later than 3 days before the annual meeting. The Contracting Officer or COR may request site visits at the Contractor site(s) annually or as needed.

3. Teleconferences

The Contractor shall plan and conduct monthly teleconference meetings with the COR, and other designated NIAID staff, during the first year of the contract period of performance, to discuss technical progress and financial invoices. A teleconference schedule for subsequent years will be established by the COR. One week prior to the teleconference, the Contractor shall submit an agenda to the COR. Within one week after the teleconference, the Contractor shall provide a meeting summary of the teleconference to the COR. The timing of the monthly teleconference meetings may be altered or adjusted by the COR as needed to address progress on the contract.

4. Additional Contract Meetings/Teleconferences

The PI, Project Manager, key investigators, and key subcontractor personnel shall attend additional meetings or teleconferences at the request of the COR. Such meetings will be requested, as necessary, to discuss contract specific issues and to review recommended changes or deviations from milestones and timelines in the Statement of Work.

3.3.4 – ADDITIONAL BUSINESS PROPOSAL INSTRUCTIONS AND UNIFORM

COST ASSUMPTIONS

In addition to the instructions and format requirements for the proposal that are contained in Section 4 of the BAA, the information presented in this attachment is intended to provide uniform cost assumptions and business clarifications.

Offerors are advised to give careful consideration to the Broad Agency Announcement Description, Background and Introduction, Research and Technical Objectives, all reference material provided as attachments, the technical evaluation criteria, and, the BAA as a whole, in the development of your proposal. The information requested here should be used as further guidance for the development of your proposal. Offerors should consider and include the information provided below in the development of their Technical and Business Proposal.

BUSINESS PROPOSAL – TABLE OF CONTENTS

SECTION 1 – PROPOSAL COVER SHEET (use form NIH 2043 identified in Section 7 of the solicitation)

SECTION 2 – COST OR PRICE SUPPORT

Section 4 of the BAA specifies the minimum documentation requirements for cost data and all cost related support. All related documentation should be included in a clearly marked section of the proposal.

SECTION 3 – UNIFORM COST ASSUMPTIONS

1) Technical Cost Assumptions

A. Training: Assume three (3) one-to-two-week training sessions per year to teach investigators how to use the HIS models developed/optimized under the contract. These training sessions will be held at the Contractor’s site, beginning in year 2 of the contract and continue through the duration of the contract award. The Contractor minimally will provide all reagents and resources to be used at their site, and may offer to cover some travel expenses for the trainees (assume 3-5 trainees/session).

B. Milestones: Prepare the budget to align with specific research activities, milestones, and timelines outlined in the Gantt chart.

2) Travel

A. Contract Initiation Meeting: Assume one meeting in Rockville, Maryland within three months after the effective date of the contract to discuss contract initiation. Assume that this meeting will require a two-night stay and shall be attended by the Contractor’s key personnel, with a total attendee limit of five (5) per contract, including subcontractors.

B. Annual Program Progress Meeting: Assume one meeting in Rockville, Maryland per year, including year 1, to discuss contract progress and future plans. Assume that this meeting will require a two-night stay and shall be attended by the Contractor’s key personnel, with a total attendee limit of five

(5) per contract, including subcontractors..

C. Annual Site Visits: Assume annual one-day site visits at the Contractor’s facilities to be attended by the Principal Investigator, Project Manager, all key investigators, key subcontractor personnel, the COR, and other designated NIAID staff, shall attend this meeting. Travel and per diem costs for Government personnel shall not be provided by the contract.

D. Scientific meetings: Offerors may include one meeting per year for up to three (3) Contractor’s key investigators.

3) Government Furnished Property

No Government Furnished Property is offered for this acquisition.

The purchase of Government Furnished Property will not be authorized as a direct charge under the resultant contract.

SECTION 4 – OPTIONS

Each Option must be budgeted separately within the Business Proposal. All uniform cost assumptions associated with Options are to be delineated here.

SECTION 5 - TABLE OF CONTENTS FOR DOCUMENTATION REQUIRED

UNDER SECTION 4 OF THE BAA

Refer to Section 4 of the BAA for documentation requirements. All relevant documentation should be included in a clearly marked section of the proposal.

3.3.5 - RESEARCH AREA 004 – Reporting Requirements and Deliverables

3.3.5.1 - Reporting Requirements

In addition to reporting requirements and deliverables identified elsewhere in this solicitation, it is expected that awards resulting from Research Area 004 will include the following reports and deliverables:

a. Quarterly Progress Reports

This report shall include a description of the activities during the reporting period and the activities planned for the ensuing reporting period. The first reporting period consists of the first full three months of performance including any fractional part of the initial month. Thereafter, the reporting period shall consist of three full calendar months.

b. Annual Progress Reports

This report includes a summation of the results of the entire contract work for the period covered. An Annual Progress Report will not be required for the period when the Final Report is due. A Quarterly Progress Report shall not be submitted when an Annual Progress Report is due.

c. Annual Technical Progress Report for Clinical Research Study Populations

d. Final Report

This report is to include a summation of the work performed and the results obtained for the entire contract period of performance. This report shall be in sufficient detail to describe comprehensively the results achieved. The Final Report shall be submitted in accordance with the DELIVERIES Article in SECTION F of the contract. An Annual Progress Report will not be required for the period when the Final Report is due.

The Contractor shall provide the Contracting Officer’s Representative and Contracting Officer with an electronic copy of the Final Report in draft form 90 calendar days prior to the completion date of this contract. The Contracting Officer’s Representative will review the draft report and provide the Contracting Officer with comments within 30 calendar days after receipt. The Final Report shall be corrected by the Contractor, if necessary and the final version delivered as specified in the above paragraph.

e. Summary of Salient Results

The Contractor shall submit, with the Final Report, a summary (not to exceed 200 words) of salient results achieved during the performance of the contract.

f. Ad hoc Milestone Completion Report

This report shall be submitted when the Contractor has completed a scientific milestone(s) or a decision point regarding development of proposed HIS mouse model(s). Sufficient detail and data shall be provided to explain the results achieved. Offerors shall propose the timing of these reports to coincide with the decision points and timelines specified in their Statement of Work, Technical

Requirements, and Gantt chart. The timing of these reports will be determined post-award.

g. Human Subject IRB Annual Report (Form OMB No. 0990-0263)

h. Section 508 Annual Report

i. Invention Reporting

j. Other Reports and Deliverables

Other Reports and Deliverables may be required. This may include special reports required by regulation or policy and deliverables such as data, mouse models, etc. These will be developed after proposal receipt as a result of finalization of the Statement of Work during negotiations. Special instructions, if applicable, is provided to offerors in Section 3.3.3 “Additional Technical Proposal Instructions.”

Minimally, the Contractor(s) shall provide all data, cell lines, animal models, computational models, protocols and others related resources, developed or optimized through this contract, to public repositories or other facilities designated by the Government.

3.3.5.2 - Deliverables

PACKAGING, MARKING, AND SHIPPING

If special instructions regarding packaging, marking and shipping are required, these will be developed after receipt of proposals as a result of finalization of the Statement of Work during negotiations. Special instructions, if applicable, is provided to offerors in Section 3.3.3 “Additional Technical Proposal Instructions.”

DELIVERY SCHEDULE

Delivery of other reports and deliverables will be proposed by the offerors in their technical proposal. They will be developed further after receipt of proposals as a result of finalization of the Statement of Work and other terms and conditions of any resultant contract during negotiations. Specific instructions, if applicable, is provided to offerors in Section 3.3.3 “Additional Technical Proposal Instructions.”

3.3.6 - RESEARCH AREA 004 – Advance Understandings

NIAID will work with the Contractors after award to foster information, data, resource, and animal model sharing, and direct HIS model comparisons amongst the funded investigators. In addition, while offerors may not include government furnished resources/collaborations in their proposals, NIAID reserves the right to establish collaborations between Contractors and Federal employees (e.g., FDA or NIH intramural researchers) and provide access to Federal facilities/resources after award.

-- END OF SECTION 3.3 - DIVISION OF ALLERGY, IMMUNOLOGY, AND TRANSPLANTATION

(DAIT)- Research Area 004 --

End of Amendment 3

3.3.2.2 – Research and Technical Objectives