DARPA-BAA-15-21_FINAL_PAO.pdf

Broad Agency Announcement

Technologies for Host Resilience (THoR)

BIOLOGICAL TECHNOLOGIES OFFICE

DARPA-BAA-15-21

March 31, 2015

DARPA-BAA-15-21, Technologies for Host Resilience

TABLE OF CONTENTS

Part One: Overview Information

Part Two: Full Text of Announcement

1. Funding Opportunity Description

1.1. Program Overview

1.2 Schedule and Milestones

1.3 References

2. Award Information

3. Eligibility Information

3.1 Eligible Applicants

3.1.1 Federally Funded Research and Development Centers (FFRDCs) and Government Entities

3.1.2 Non-U.S. Organizations

3.2 Procurement Integrity, Standards of Conduct, Ethical Considerations, and Organizational Conflicts of Interest

3.3 Cost Sharing/Matching

3.4 Other Eligibility Requirements

3.4.1 Collaborative Efforts

4. Application and Submission Information

4.1 Address to Request Application Package

4.2. Content and Form of Application Submission

4.2.1 Security and Proprietary Issues

4.2.2 Proposal Information

4.2.3 Restrictive Markings on Proposals

4.3 Proposal Instructions

4.3.1 Proposal Format

4.4 Submission Dates and Times

4.4.1 Full Proposal Submission Deadline

4.5 Funding Restrictions

4.6 Other Submission Requirements

5. Application Review Information

5.1 Evaluation Criteria

5.1.1 Overall Scientific and Technical Merit

5.1.2 Proposer’s Capabilities, Facilities and/or Related Experience

5.1.3 Cost Realism

5.1.4 Potential Contribution and Relevance to the DARPA Mission

5.2 Review and Selection Process

6. Award Administration Information

6.1 Selection Notices

6.2 Administrative and National Policy Requirements

6.2.1 Meeting and Travel Requirements

6.2.2 Human Subjects Research

6.2.3 Animal Use

6.2.4 Export Control

6.2.5 Subcontracting

6.2.6 Electronic and Information Technology

6.2.7 Employment Eligibility Verification

6.2.8 System for Award Management (SAM) Registration and Universal Identifier Requirements

6.2.9 Reporting Executive Compensation and First-Tier Subcontract Awards

6.2.10 Updates of Information Regarding Responsibility Matters

6.2.11 Representation by Corporations Regarding an Unpaid Delinquent Tax Liability or a Felony Conviction under any Federal Law

6.2.12 Cost Accounting Standards (CAS) Notice and Certification

6.2.13 Controlled Unclassified Information (CUI) on Non-DoD Information Systems 41

6.2.14 Safeguarding of Unclassified Controlled Technical Information

6.3 Reporting

6.4 Electronic Systems

6.4.1 Representations and Certifications

6.4.2 Wide Area Work Flow (WAWF)

6.4.3 i-EDISON

7. Other Information

7.1 Intellectual Property

7.1.1 Procurement Contract Proposers

7.1.1.2 Commercial Items (Technical Data and Computer Software)

7.1.2 Non-Procurement Contract Proposers - Noncommercial and Commercial Items (Technical Data and Computer Software)

7.1.3 All Proposers – Patents

7.1.4 All Proposers-Intellectual Property Representations

8. APPENDIX 1 – Volume II Checklist

Part One: Overview Information

• Federal Agency Name – Defense Advanced Research Projects Agency (DARPA), Biological Technologies Office

• Funding Opportunity Title – Technologies for Host Resilience (THoR)

• Announcement Type –Initial Announcement

• Funding Opportunity Number – DARPA-BAA-15-21

• Catalog of Federal Domestic Assistance Numbers (CFDA) – Not Applicable

• Dates o Posting Date: March 31, 2015 o Proposal Due Date: May 19, 2015, 4:00 PM ET o BAA Closing Date: September 31, 2015

• Concise description of the funding opportunity – This program strives to discover host tolerance mechanisms in order to identify a suite of interventions suitable for use in humans to mitigate the deleterious effects of infectious diseases. THoR is seeking novel methods and technologies to discover and understand these responses in hosts that are resilient when exposed to infectious diseases. Specifically, DARPA aims to discover the fundamental biological relationships that underlie host tolerance to infection in animal populations in order to provide the foundational knowledge required to develop interventions for potential transition into clinical use. This program is organized into three Technical Areas (TAs): 1) Identification and characterization of animal hosts with tolerant phenotypes; 2) Discovery of biological mechanisms that underlie tolerance; and 3) Identification of interventions that utilize tolerance mechanisms with the goal of reducing morbidity and mortality due to infection. This BAA will focus specifically on understanding tolerance mechanisms in prospective animal studies in conjunction with the analysis of retrospective pre-clinical and human clinical datasets.

• Total amount of money to be awarded - It is anticipated that approximately $36M may be available under this solicitation. The actual amount of resources available under this BAA will depend on the quality of proposals received and availability of funds.

• Anticipated individual awards - Multiple awards are anticipated at different funding levels.

• Anticipated funding type - 6.1 and 6.2

• Types of instruments that may be awarded - Procurement Contract and Other Transactions

• Any cost sharing requirements – None

• Agency contact:

COL Matthew Hepburn, M.D., Program Manager Biological Technologies Office (BTO)

The BAA Coordinator for this effort may be reached at:

DARPA-BAA-15-21@darpa.mil

DARPA/BTO

ATTN: DARPA-BAA-15-21

675 North Randolph Street Arlington, VA 22203-2114

Part Two: Full Text of Announcement

1. Funding Opportunity Description

The Defense Advanced Research Projects Agency often selects research efforts through the Broad Agency Announcement (BAA) process. This BAA is being issued, and any resultant selection will be made, using procedures under Federal Acquisition Regulation (FAR) 35.016.

Any negotiations and/or awards will use procedures under FAR 15.4, Contract Pricing, as specified in the BAA. Proposals received as a result of this BAA shall be evaluated in accordance with evaluation criteria specified herein through a scientific review process.

DARPA BAAs are posted on the Federal Business Opportunities (FedBizOpps) website, https://www.fbo.gov/. The following information is for those wishing to respond to the BAA.

DARPA is soliciting innovative research proposals in the area of understanding host tolerance in response to infection. Proposed research should incorporate advancements in the key fundamental scientific areas of pathogen-host interactions, infectious diseases, bioinformatics, and host-centric drug discovery to meet the goals of this BAA. Specifically excluded from this solicitation is research that results in incremental improvements to the existing state of practice and advanced drug development.

1.1. Program Overview

THoR seeks to discover the fundamental biological relationships between molecules, genes, proteins, and pathways that underlie host tolerance to infection in animal populations. Within this solicitation we refer to tolerance of infection as the maintenance of host fitness in the presence of pathogen burden. This concept of tolerance is in contrast to host response mechanisms based on resistance, which refers to the host’s ability to maintain fitness through reduction of pathogen load. Under this program, approaches and methodologies will be developed in order to identify mechanisms of tolerance along with the characterization of the key biological drivers responsible for that response. Furthermore, DARPA aims to recapitulate these pro-tolerance mechanisms in susceptible hosts by applying a single or combination of interventions in order to improve health and reduce mortality to infections. This BAA will develop the tools and methodologies necessary for identification of tolerant populations, discovery of tolerance mechanisms, and identification of pro-tolerance interventions.

Specifically, DARPA aims to discover and leverage the fundamental biological relationships between molecules, genes, proteins, and pathways that underlie host tolerance to infection in animal populations.

https://www.fbo.gov/

The development of medical countermeasures to address emerging threats and drug-resistant pathogens is a national security priority. Traditional treatments for infection focus primarily on pathogen inhibition and eradication within the host with the premise that increased pathogen load negatively impacts host fitness. This approach frequently relies on a priori knowledge of the pathogen, is limited to a discrete set of pathogens, and has imposed evolutionary pressures leading to the increased prevalence of drug-resistant organisms. THoR seeks to discover biological mechanisms of tolerance to catalyze the development of novel host-based interventions against emerging pathogens and potential biological threat agents. If successful, this program has the potential to expand upon the existing medical countermeasures available to combat multi-drug resistant pathogens and emerging infectious diseases threats thereby improving warfighter health and military readiness.

Several publications in the literature describe tolerance mechanisms to infectious diseases within animals (see Section 1.3 “References”). DARPA is seeking out novel and/or under-characterized tolerance mechanisms for further investigation. Note, DARPA is specifically interested in examining animal populations that are tolerant to infection, i.e. they carry a significant pathogen load, but exhibit no appreciable decrease in fitness. Proposers are encouraged to examine novel mechanisms of tolerance, which may extend beyond the canonical host immune system. DARPA is not interested in host-defense mechanisms that promote pathogen elimination (i.e., resistance mechanisms), and pathogen-centric solutions encompassing disruption of processes in the pathogen such as virulence (e.g., toxin production), signaling, and replication.

It is expected that biological tolerance mechanisms will be examined across multiple biological scales, e.g., species, tissues, and cells, and molecules, including but not limited to:

1) Genomic (genes and associated polymorphisms): Specific genes, single nucleotide polymorphisms (SNPs), and genetic copy number variation (CNV) influence susceptibility and response to infectious diseases. Exploration of animal populations may identify genes that are responsible for tolerance. These genes are of interest only if the gene product itself is functional, active in humans, and “druggable” (e.g. can be modulated with specific biochemical interventions). Note, proposals that include genomic engineering of the host will be considered non-responsive to this solicitation.

2) Transcriptomic (gene expression): It is anticipated that certain mechanisms and pathways may be differentially regulated in the presence of a pathogen to provide tolerance. In these cases, levels of gene expression should be examined before, during, and after the course of infection in healthy, susceptible, and tolerant species for comprehensive characterization of the host response.

3) Epigenomic: Epigenetic regulation (DNA methylation, histone modification, miRNA and other non-coding RNAs, etc.) may be evaluated for tolerance patterns as variable gene expression levels may provide transient or inheritable tolerance. These epigenetic responses may provide additional insights into tolerance patterns.

4) Proteomic (protein expression): Certain proteins in tolerant individuals may be expressed at higher or lower concentrations, or be differentially modified (e.g., phosphorylation) resulting in novel functions, as compared to non-tolerant populations.

5) Small molecules (signaling components, metabolites, etc.): Small molecules or compounds may be examined to determine the relationship between cellular processes and tolerance.

6) Commensal relationships: The effects of the host microflora (e.g. microbiome) and viral contributions (e.g. virome) on tolerance may be influential in the response to infection.

DARPA is interested in research that specifically examines interactions that modulate host tolerance mechanisms. Proposals that solely address microflora effects on pathogens directly will be considered non-responsive.

This program is organized into three Technical Areas (TAs): 1) Discover Tolerant Populations;

2) Identify Biological Mechanisms of Tolerance; and 3) Identify and Validate Pro-Tolerance Interventions (see Figure 1). The long term objective of the THoR program is to integrate the aforementioned methods and tools into an end-to-end pipeline for discovering novel host-centric countermeasures against infectious diseases. DARPA anticipates that a future BAA may be established to integrate the component technologies developed under TA 1, TA 2 and TA 3 into an end-to-end pipeline that may be utilized for novel medical countermeasure discovery for a broad range of pathogens (e.g., bacteria, viruses, fungi, parasites, etc.).

Figure 1. A graphical depiction of the main Technical Areas of the THoR program

Proposers must apply to all three Technical Areas. It is expected that proposers will consist of multi-disciplinary teams (immunology, microbiology, medical infectious diseases, computational biology, bioinformatics, veterinary medicine, and molecular biology) in order to have the appropriate capability to be responsive to all three Technical Areas. Ultimately, this program strives to discover host tolerance mechanisms in order to identify a suite of novel pro-tolerance host-based interventions suitable for use in humans to mitigate the deleterious effects of infectious diseases. While DARPA anticipates proposals to this BAA to include pre-clinical in vitro and in vivo animal studies, human clinical testing and advanced drug development efforts is beyond the scope of this program and will not be supported under this solicitation.

Data Sharing and Access

DARPA anticipates that large amounts of data will be generated under this program by each performer and that the analyses and validation may be greatly strengthened by compiling and integrating information for access to all program participants. As such, a DARPA-designated secure data-sharing infrastructure will be established, and participants will be required to share data within this program. Performers should anticipate establishing the appropriate agreements to enable collaboration and data sharing. DARPA anticipates that all data developed through prospective animal studies under funding for this program will be shared on such a database infrastructure and be available to all participants in this program. DARPA encourages sharing of pre-existing data including those generated through funding by other sources, although this is not a requirement of the program.

Description of Technical Areas

Technical Area 1 (TA 1): Discover Tolerant Populations

Proposers will perform animal studies to examine intra- and inter-species differences in host fitness using a model of infection that incites an acute host response resulting in severe pathology. The objective of TA 1 is to identify and study at least three tolerant animal species, one of which must be a mammal (preferably large, e.g. porcine, non-human primate). It is preferred that at least one of the animals selected have prior supporting evidence demonstrating tolerance to infection (see Section 1.2 Schedule and Milestones for the detailed requirements). It is likely that each animal species selected will exhibit a range of tolerance. Proposers may elect to perform an initial set of exploratory animal studies with various species to identify the three populations of most interest for in-depth analysis. Proposers should offer methods and tools to correlate symptoms with pathogen load before, during, and after infection in order to determine the healthy versus sick and tolerant versus resistant animal sub-types. In addition, disease characterization should include the collection, banking, and measurement of molecular, physiological, serological, and other appropriate correlates of fitness from multiple tissue and cell types.

Figure 2. Technical Area 1: Discover Tolerant Populations

The organisms selected for investigation should be human pathogens that incite an acute host response resulting in severe pathology. Examples include organisms that cause septic shock and acute respiratory distress syndrome (ARDS). For this solicitation, both antibiotic-susceptible and antibiotic-resistant organisms may be examined. Clinically relevant drug-resistant organisms are of particular interest. Animal models for infections that cause chronic disease in humans are not of interest.

Proposers must define and characterize the appropriate control group that will serve as the basis for comparison during the identification of tolerant groups. All data collected including pathogen load, host fitness, and multi-omic data (genomics, metabolomics, transcriptomics, proteomics, etc.) of multiple cell types should be comprehensive and enable the discovery and assessment of tolerant mechanisms as described in Technical Area 2. It should be noted that tolerance is a transient property and continuous measurements should be made at a frequency and resolution sufficient to capture the dynamics of a tolerant response. It is anticipated that the animal experimental design (e.g., number of animals within a species, or number of species) may vary depending on the whether genomic, transcriptomic, or other data types are sought to determine tolerance. Proposers should include a detailed explanation of methods and design of experiments in their response. Data collected under this TA will be used to populate a DARPA-designated database for use by all program participants under TA 2.

Pathogen load should be correlated with host fitness throughout the course of infection in order to differentiate tolerant versus resistant responses. Longitudinal studies may be required that include pathogen load characterization using techniques that may include, but are not limited to:

(1) pathogen levels at a particular time post-infection, (2) peak pathogen burden, (3) average of pathogen burden over time, (4) inoculation dose, and/or (5) pathogen burden of individuals infected at different time points but sampled at a fixed time. DARPA does not advocate for a specific approach. Any approach that distinguishes tolerant versus a resistant population must be supported with scientific justification.

All animal study vendors must be identified, have ability to work under the appropriate biosafety level (BSL), and provide a letter of intent for each subcontractor at the time of proposal.

Contracted service vendors should demonstrate the capability to accommodate the potential breadth in animal species that may be tested under this program, including small and large animals.

Technical Area 2 (TA 2): Identify Biological Mechanisms of Tolerance

Bioinformatics tools will enable analysis of tolerance mechanisms utilizing data collected in TA

1. Modern high-throughput technologies have enabled the collection of a vast amount of biological data within short time periods. Furthermore, recent advances in bioinformatics and systems biology have allowed for integration of biological data and other external metadata to form sophisticated system-wide models of disease. Within this Technical Area, the underlying mechanisms of tolerance (including relationships involving molecules, genes, proteins, and pathways) will be identified using data generated by all teams in TA 1. In addition, proposers are encouraged to utilize any accessible pre-existing retrospective datasets from animal and human infectious diseases studies that may assist in the analysis and validation of potential tolerance mechanisms. Proposers will need to collect, curate, integrate, and analyze these datasets in order to form a comprehensive picture of tolerance. Analytic approaches and statistical methodologies should be described in detail and justified based on ability to determine biological relationships that underlie tolerance across large heterogeneous sets of data. Proposers should offer methods and techniques to evaluate the potential broader applicability of the identified mechanisms across various host species and various infectious diseases.

Figure 3. Technical Area 2: Identify Patterns of Tolerance

Proposers are encouraged to describe the methodology they will employ in order to construct the networks that define the basis for tolerance across multiple biological scales i.e., species, tissues, and cells. A process for defining the molecular parameters believed to characterize a tolerant state should be outlined. While raw bioinformatic analysis will be critical to the success of this Technical Area, DARPA is also interested in the development of computational tools that will enable a broader class of researchers to investigate and manipulate biological data without requiring extensive programming expertise. In addition, methods and tools should be employed and/or developed to visualize high-dimensional datasets in order to facilitate analysis by domain experts.

Proposers should leverage the data provided on the DARPA-designated THoR database in addition to utilizing accessible public and other proprietary databases to augment the analysis.

Any experimental biases should be accounted for and the proposer should describe how patterns of tolerance may be generalized to other categories of infectious diseases. It is important that proposers perform rigorous cross-study analyses on the integrated datasets, not only to increase statistical relevance, but to validate findings and to account for differences in methods of data collection.

Technical Area 3 (TA 3): Identify and Validate Pro-Tolerance Interventions

Within this Technical Area, interventions that recapitulate the pro-tolerance mechanisms in susceptible hosts will be identified and validated in at least two animal models. It is encouraged that at least one of the animals selected be large (e.g. porcine, non-human primate). Proposers should provide a detailed animal experimentation plan and justification for the selected animal species and infecting organism. Proposers are encouraged to utilize existing tools that may provide insights into mechanisms of potential drug candidate actions. In contrast to current state-of-the-art practice of pathogen-centric strategies, this BAA is soliciting the development of approaches that discover interventions capable of regulating host tolerance. The specific intervention implemented will be determined by the mechanisms identified in TA 2. These may include re-purposed drugs or molecules from established libraries as well as novel rationally designed synthetic molecules. Interventions are not limited to small molecule drug classes and may include novel recombinant proteins, development of scavengers, and/or methods to deplete products.

Figure 4. Technical Area 3: Discover and Validate Interventions

Potential interventions require validation of both safety and efficacy in animal populations demonstrating the ability to create pro-tolerance phenotypes. Validation will be performed within in vitro cellular models and in vivo models of infection. Challenge studies must demonstrate that the chosen model incites acute symptoms and severe pathology. Interventions that are based on gene therapy or genetic manipulation of host genes are not of interest and will be considered non-responsive to this solicitation. There will be no human clinical trials conducted under this BAA. Therefore, in vivo validation shall be performed in animals only. Interventions that may be suitable for future drug development and human use are encouraged.

Program Plan

This BAA consists of three Technical Areas with a total period of performance of 36 months.

Proposers should therefore define the exact period of performance needed for each Technical Area and anticipated dependency or overlap in time that may occur amongst the three Technical areas. Tasks should support all of the following Technical Areas: (1) Discover tolerant animal populations (2) Identify tolerance mechanisms and (3) Identify and validate pro-tolerance interventions. Proposers must provide a plan for sharing and transferring data to the DARPA designated database infrastructure. A management plan must be included describing how the proposed team will work together with subcontractors and service providers across all three Technical Areas in order to meet the goals of the project.

1.2 Schedule and Milestones

To enable on-going evaluation by the Government of the proposed project, the following Technical Area deliverables must be provided in the proposal. These milestones will serve as the basis for evaluating progress and to warrant continued funding within the program. Proposers are required to propose timelines to meet these deliverables as well as propose additional milestones and quantitative metrics to accomplish the goals of the Technical Areas. Interim milestones and metrics should be proposed at a minimum interval of every 6 months for the period of performance in each Technical Area. The proposer-defined interim milestones and metrics should align with the major milestones and will enable the Government to gauge progress towards the stated objectives of the program and continuation into the latter phases of the program. All proposals should describe a detailed account in the technical narrative of how their approach will meet all milestones.

Due to the exploratory nature of this BAA, proposers are required to submit a detailed description and explanation of the proposed design of experiments with a scope and schedule that is realistic and supports the objectives of the program. The total period of performance shall not exceed 36 months.

Technical Area 1: Discover Tolerant Populations

Phase 1 Major Milestones (Due no later than 12 months from start of TA 1):

• Complete an exploratory screen of susceptible animals to infection and select three animal species for further in-depth analysis. At least one of the three animals must be a mammal, preferably large (e.g. porcine, non-human primate). It is encouraged that one of the three animals must have a known mechanism of tolerance supported by prior scientific evidence.

• Distinguish between the tolerant (high pathogen load) versus resistant (reduced pathogen load) phenotypes in the proposed model(s) of infection.

• Upload interim experimental data to the DARPA designated database in a format that is conducive for analysis by other program participants.

Phase 2 Major Milestones (Due at end of TA 1):

• Identify tolerant sub-populations in no fewer than three susceptible animal species, at least one of which must be a mammal, within the proposed model of infection.

• Upload experimental data to the DARPA designated database in a format that is conducive for analysis by other program participants.

Technical Area 2: Identify Tolerance Mechanisms

Phase 1 Major Milestones (Due no later than 12 months from start of TA 2):

• Identify at least five (5) different tolerance mechanisms across the various levels of molecular biology (genes, transcripts, molecules, proteins, etc.) from tolerant animal populations.

• Validate algorithms and analytical tools to facilitate the discovery of tolerance mechanisms.

• Collect, curate, and integrate retrospective datasets into the analysis of tolerance mechanisms.

Phase 2 Major Milestones (Due at end of TA 2):

• Identify at least ten (10) different tolerance mechanisms across the various levels of molecular biology (genes, transcripts, molecules, proteins, etc.) from tolerant animal populations.

• Validate identified tolerance mechanisms through bioinformatic analysis across data generated within TA 1, retrospective datasets, and data generated by other THoR program participants.

Technical Area 3: Identify and Validate Pro-Tolerance Interventions

Phase 1 Major Milestones (Due no later than 12 months from start of TA 3):

• Identify at least five (5) interventions that recapitulate pro-tolerance mechanisms in susceptible populations.

• Validate interventions with in silico and in vitro experiments to determine ability to modulate tolerance mechanism.

• Validate interventions in an appropriate first animal model susceptible to the proposed infectious organisms and demonstrate increased survival.

Phase 2 Major Milestones (Due at end of TA 3):

• Validate interventions in an appropriate second animal model susceptible to the proposed infectious organisms and demonstrate increased survival (large animal is encouraged e.g., porcine, non-human primate).

1.3 References

Ayres, J. S., & Schneider, D. S. (2012). Tolerance of Infections. Annual Review of Immunology, 271-294.

Bessede, A., Gargaro, M., Pallotta, M. T., Matino, D., Servillo, G., Brunacci, C., et al. (2014).

Aryl Hydrocarbon Receptor Control of a Disease Tolerance Defence Pathway. Nature, 184-190.

Best, A., White, A., & Boots, M. (2014). The Coevolutionary Implications of Host Tolerance.

Evolution, 1426-1435.

Doeschl-Wilson, A. B. (2012). The First Step Toward Genetic Selection for Host Tolerance to Infectious Pathogens: Obtaining the Tolerance Phenotype Through Group Estimates. Frontiers in Genetics, 7-17.

Kanaan, Z., Barnett, R., Gardner, S., Keskey, B., Druen, D., Billeter, A., et al. (2012).

Differential microRNA (miRNA) expression could explain microbial tolerance in a novel chronic peritonitis model. Innate Immunity, 203-212.

Kidd, B. A., Peters, L. A., Schadt, E. E., & Dudley, J. T. (2014). Unifying Immunology with Informatics and Mutliscale Biology. Nature Immunology, 118-127.

Medzhitov, R., Schneider, D. S., & Soares, M. P. (2012). Disease Tolerance as a Defense Strategy. Science, 936-941.

Vale, P. F., Fenton, A., & Brown, S. P. (2014). Limiting Damage during Infection: Lessons from Infection Tolerance for Novel Therapeutics. PLoS Biology, 1-9.

Warren, H. S., Fitting, C., Hoff, E., Adib-Conquy, M., Beasley-Topliffe, L., Tesini, B., et al.

(2010). Resilience to Bacterial Infection: Difference between Species Could Be Due to Proteins in Serum. The Journal of Infectious Diseases, 223-232.

2. Award Information

Multiple awards are possible. The amount of resources made available under this BAA will depend on the quality of the proposals received and the availability of funds.

The Government reserves the right to select for negotiation all, some, one, or none of the proposals received in response to this solicitation, and to make awards without discussions with proposers. The Government also reserves the right to conduct discussions if it is later determined to be necessary. If warranted, portions of resulting awards may be segregated into pre-priced options. Additionally, DARPA reserves the right to accept proposals in their entirety or to select only portions of proposals for award. In the event that DARPA desires to award only portions of a proposal, negotiations may be opened with that proposer. The Government reserves the right to fund proposals in phases with options for continued work at the end of one or more of the phases.

Awards under this BAA will be made to proposers on the basis of the evaluation criteria listed below (see Section 5 “Application Review Information”), and program balance to provide overall value to the Government. The Government reserves the right to request any additional, necessary documentation once it makes the award instrument determination. Such additional information may include but is not limited to Representations and Certifications. The Government reserves the right to remove proposers from award consideration should the parties fail to reach agreement on award terms, conditions and cost/price within a reasonable time or the proposer fails to timely provide requested additional information. Proposals identified for negotiation may result in a procurement contract or Other Transaction depending upon the nature of the work proposed, the required degree of interaction between parties, whether or not the research is classified as Fundamental Research, and other factors.

In all cases, the Government contracting officer shall have sole discretion to select award instrument type and to negotiate all instrument terms and conditions with selectees. DARPA will apply publication or other restrictions, as necessary, if it determines that the research resulting from the proposed effort will present a high likelihood of disclosing performance characteristics of military systems or manufacturing technologies that are unique and critical to defense. Any award resulting from such a determination will include a requirement for DARPA permission before publishing any information or results on the program. For more information on publication restrictions, see the Section below on Fundamental Research.

Fundamental Research

It is DoD policy that the publication of products of fundamental research will remain unrestricted to the maximum extent possible. National Security Decision Directive (NSDD) 189 established the national policy for controlling the flow of scientific, technical, and engineering information produced in federally funded fundamental research at colleges, universities, and laboratories. The Directive defines fundamental research as follows:

Fundamental research means basic or applied research in science and engineering, the results of which ordinarily are published and shared broadly within the scientific community, as distinguished from proprietary research and from industrial development, design, production, and product utilization the results of which ordinarily are restricted for proprietary or national security reasons.

As of the date of publication of this BAA, the Government expects that program goals as described herein may be met by proposers intending to perform fundamental research. The Government does not anticipate applying publication restrictions of any kind to individual awards for Fundamental Research that may result from this BAA. Notwithstanding this statement of expectation, the Government is not prohibited from considering and selecting research proposals that, while perhaps not qualifying as fundamental research under the foregoing definition, still meet the BAA criteria for submissions. If proposals are selected for award that offer other than a fundamental research solution, the Government will either work with the proposer to modify the proposed statement of work to bring the research back into line with fundamental research or else the proposer will agree to restrictions in order to receive an award.

Proposers should indicate in their proposal whether they believe the scope of the research included in their proposal is fundamental or not. While proposers should clearly explain the intended results of their research, the Government shall have sole discretion to select award instrument type and to negotiate all instrument terms and conditions with selectees. Appropriate clauses will be included in resultant awards for non-fundamental research to prescribe publication requirements and other restrictions, as appropriate.

For certain research projects, it may be possible that although the research being performed by the prime contractor is restricted research, a subcontractor may be conducting contracted fundamental research. In those cases, it is the prime contractor’s responsibility to explain in their proposal why its subcontractor’s effort is contracted fundamental research.

The following statement or similar provision will be incorporated into any resultant non-fundamental research procurement contract or Other Transaction:

There shall be no dissemination or publication, except within and between the contractor and any subcontractors, of information developed under this contract or contained in the reports to be furnished pursuant to this contract without prior written approval of DARPA’s Public Release Center (DARPA/PRC). All technical reports will be given proper review by appropriate authority to determine which Distribution Statement is to be applied prior to the initial distribution of these reports by the contractor. With regard to subcontractor proposals for Contracted Fundamental Research, papers resulting from unclassified contracted fundamental research are exempt from prepublication controls and this review requirement, pursuant to DoD Instruction 5230.27 dated October 6, 1987.

When submitting material for written approval for open publication, the contractor/awardee must submit a request for public release to the PRC and include the following information: (1) Document Information: document title, document author, short plain-language description of technology discussed in the material (approx. 30 words), number of pages (or minutes of video) and document type (e.g., briefing, report, abstract, article, or paper); (2) Event Information: event type (conference, principal investigator meeting, article or paper), event date, desired date for DARPA's approval;

(3) DARPA Sponsor: DARPA Program Manager, DARPA office, and contract number;

and (4) Contractor/Awardee's Information: POC name, e-mail and phone. Allow four weeks for processing; due dates under four weeks require a justification. Unusual electronic file formats may require additional processing time. Requests may be sent either by-mail to prc@darpa.mil or via 675 North Randolph Street, Arlington VA 22203- 2114, telephone (571) 218-4235. Refer to the following for link for information about DARPA’s public release process:

http://www.darpa.mil/NewsEvents/Public_Release_Center/Public_Release_Center.aspx

3. Eligibility Information

All responsible sources capable of satisfying the Government’s needs may submit a proposal that shall be considered by DARPA.

mailto:prc@darpa.mil

3.1 Eligible Applicants

3.1.1 Federally Funded Research and Development Centers (FFRDCs) and Government Entities

FFRDCs and Government entities (e.g., Government/National laboratories, military educational institutions, etc.) are subject to applicable direct competition limitations and cannot propose to this BAA in any capacity unless they meet the following conditions: (1) FFRDCs must clearly demonstrate that the proposed work is not otherwise available from the private sector (2) FFRDCs must provide a letter on official letterhead from their sponsoring organization citing the specific authority establishing their eligibility to propose to Government solicitations and compete with industry, and their compliance with the associated FFRDC sponsor agreement and terms and conditions. This information is required for FFRDCs proposing to be prime contractors or subcontractors. Government entities must clearly demonstrate that the work is not otherwise available from the private sector and provide written documentation citing the specific statutory authority and contractual authority, if relevant, establishing their ability to propose to Government solicitations. At the present time, DARPA does not consider 15 U.S.C.§ 3710a to be sufficient legal authority to show eligibility. While 10 U.S.C. § 2539b may be the appropriate statutory starting point for some entities, specific supporting regulatory guidance, together with evidence of agency approval, will still be required to fully establish eligibility. DARPA will consider FFRDC eligibility submissions on a case-by-case basis; however, the burden to prove eligibility for all team members rests solely with the proposer.

3.1.2 Non-U.S. Organizations

Non-U.S. organizations are/or individuals may participate to the extent that such participants comply with any necessary nondisclosure agreements, security regulations, export control laws, and other governing statutes applicable under the circumstances. See Section 4.2 “Security and Proprietary Issues” regarding the proposers capabilities to perform research and development at the classification level they propose.

3.2 Procurement Integrity, Standards of Conduct, Ethical

Considerations, and Organizational Conflicts of Interest

Current federal employees are prohibited from participating in particular matters involving conflicting financial, employment, and representational interests (18 U.S.C.§ 203, 205, and 208).

Once the proposals have been received, and prior to the start of proposal evaluations, the Government will assess potential conflicts of interest and will promptly notify the Proposer if any appear to exist. The Government assessment does NOT affect, offset, or mitigate the proposer’s responsibility to give full notice and planned mitigation for all potential organizational conflicts, as discussed below.

Without prior approval or a waiver from the DARPA Director, in accordance with FAR 9.503, a contractor cannot simultaneously provide scientific, engineering, technical assistance (SETA) or similar support and also be a technical performer. As part of the proposal submission, all members of the proposed team (prime proposers, proposed subcontractors, and consultants) must affirm whether they (their organizations and individual team members) are providing SETA or similar support to any DARPA technical office(s) through an active contract or subcontract. All affirmations must state which office(s) the proposer, subcontractor, consultant, or individual supports and identify the prime contract number(s). All facts relevant to the existence or potential existence of organizational conflicts of interest (FAR 9.5) must be disclosed. The disclosure must include a description of the action the proposer has taken or proposes to take to avoid, neutralize, or mitigate such conflict. If in the sole opinion of the Government after full consideration of the circumstances, a proposal fails to fully disclose potential conflicts of interest and/or any identified conflict situation cannot be effectively mitigated, the proposal will be rejected without technical evaluation and withdrawn from further consideration for award.

If a prospective Proposer believes a conflict of interest exists or may exist (whether organizational or otherwise) or has questions on what constitutes a conflict of interest, the proposer should send his/her contact information and a summary of the potential conflict to the DARPA-BAA-15-21 mailbox before time and effort are expended in preparing a proposal and mitigation plan.

3.3 Cost Sharing/Matching

Cost sharing is not required; however, it will be carefully considered where there is an applicable statutory condition relating to the selected funding instrument (e.g., for any Other Transactions under the authority of 10 U.S.C.§2371). Cost sharing is encouraged where there is a reasonable probability of a potential commercial application related to the proposed research and development effort.

3.4 Other Eligibility Requirements

3.4.1 Collaborative Efforts

It is anticipated that successful proposals will be comprised of multi-disciplinary teams led by a prime contractor managing several sub-contractors. Teams may be led by industrial, academic, or non-profit entities, among others. It is expected that the proposed leadership team will include individuals with significant experience and expertise in each of the Technical Areas. Successful proposals will couple computational and experimental methodologies in order to identify successful solutions. Proposers are encouraged to build teams with experience in fields such as immunology, microbiology, medical infectious diseases, computational biology, bioinformatics, veterinary medicine, and molecular biology.

4. Application and Submission Information

4.1 Address to Request Application Package

This solicitation contains all information required to submit a proposal. No additional forms, kits, or other materials are needed. This notice constitutes the total solicitation. No additional information is available, except as provided at FBO.gov, nor will a formal Request for Proposal (RFP) or additional solicitation regarding this announcement be issued. Requests for the same will be disregarded.

4.2. Content and Form of Application Submission

4.2.1 Security and Proprietary Issues

The Government anticipates proposals submitted under this BAA will be unclassified.

Proprietary Data: All proposals containing proprietary data should have the cover page and each page containing proprietary data clearly marked as containing proprietary data. It is the proposer’s responsibility to clearly define to the Government what is considered proprietary data. It is the policy of DARPA to treat all proposals as competitive information, and to disclose their contents only for the purpose of evaluation. Proposals will not be returned. The original of each proposal received will be retained at DARPA and all other non-required copies destroyed. A certification of destruction may be requested, provided the formal request is received at this office within 5 days after unsuccessful notification.

4.2.2 Proposal Information

The typical proposal should express a consolidated effort in support of one or more related technical concepts or ideas. Disjointed efforts should not be included into a single proposal.

Restrictive notices notwithstanding, proposals may be handled, for administrative purposes only, by a support contractor. This support contractor is prohibited from competition in DARPA technical research and is bound by appropriate nondisclosure requirements. Proposals may not be submitted by fax or e-mail; any so sent will be disregarded.

Proposals not meeting the format described in the BAA may not be reviewed.

Full proposals sent in response to DARPA-BAA-15-21 may be submitted via DARPA’s BAA Website (https://baa.darpa.mil). Visit the website to complete the two-step registration process.

Submitters will need to register for an Extranet account (via the form at the URL listed above) and wait for two separate e-mails containing a username and temporary password. After https://baa.darpa.mil/ accessing the Extranet, submitters may then create an account for the DARPA BAA website (via the “Register your Organization” link along the left side of the homepage), view submission instructions, and upload/finalize the proposal.

Technical support for DARPA’s BAA Website may be reached at action@darpa.mil, and is typically available during regular business hours, (9:00 AM- 5:00 PM EST Monday – Friday).

Proposers using the DARPA BAA Website may encounter heavy traffic on the submission deadline date; it is highly advised that submission process be started as early as possible.

All administrative correspondence and questions on this solicitation, including requests for information on how to submit a proposal to this BAA, should be directed to one of the administrative addresses below; e-mail is preferred.

BAA Administrator E-mail: DARPA-BAA-15-21@darpa.mil

DARPA/BTO

ATTN: DARPA-BAA-15-21

675 North Randolph Street Arlington, VA 22203-2114

Office Website: http://www.darpa.mil/Our_Work/BTO/

Solicitations Page: http://www.darpa.mil/Opportunities/Solicitations/BTO_Solicitations.aspx

DARPA intends to use electronic mail for correspondence regarding DARPA-BAA-15-21.

Proposals may not be submitted by fax or e-mail; any so sent will be disregarded. DARPA encourages use of the Internet for retrieving the BAA and any other related information that may subsequently be provided.

4.2.3 Restrictive Markings on Proposals

All proposals should clearly indicate limitations on the disclosure of their contents. Proposers who include in their proposals data that they do not want disclosed to the public for any purpose, or used by the Government except for evaluation purposes, shall-

(1) Mark the title page with the following legend:

This proposal includes data that shall not be disclosed outside the Government and shall not be duplicated, used, or disclosed-in whole or in part-for any purpose other than to evaluate this proposal. If, however, a contract is awarded to this proposer as a result of, or in connection with, the submission of this data, the Government shall have the right to duplicate, use, or disclose the data to the extent provided in the resulting contract. This restriction does not limit the Government's right to use information contained in this data if mailto:action@darpa.mil mailto:action@darpa.mil http://www.darpa.mil/Our_Work/BTO/ http://www.darpa.mil/Opportunities/Solicitations/BTO_Solicitations.aspx it is obtained from another source without restriction. The data subject to this restriction are contained in sheets [insert numbers or other identification of sheets]; and

(2) Mark each sheet of data it wishes to restrict with the following legend:

Use or disclosure of data contained on this sheet is subject to the restriction on the title page of this proposal.

Markings like "Company Confidential" or other phrases that may be confused with national security classifications shall be avoided.

4.3 Proposal Instructions

4.3.1 Proposal Format

The maximum page count for Volume 1 is 20 pages (8.5̋ x 11̋ paper, 11 point Times New Roman font, single line spacing), including all figures, tables and charts but not including the cover sheet, table of contents or appendices. A submission letter is optional and is not included in the page count. Volume I should include the following components:

4.3.1.1 Volume I, Technical and Management Proposal

Section I. Administrative

A. Cover Sheet (LABELED “PROPOSAL: VOLUME I”):

1. BAA number (DARPA-BAA-15-21);

2. Lead organization (prime contractor);

3. Type of organization, selected from among the following categories: “LARGE

BUSINESS,” “SMALL DISADVANTAGED BUSINESS,” “OTHER SMALL

BUSINESS,” “HBCU,” “MI,” “OTHER EDUCATIONAL,” OR “OTHER

NONPROFIT”;

4. Proposer’s reference number (if any);

5. Other team members (if applicable) and type of business for each;

6. Proposal title;

7. Technical point of contact (Program Manager or Principle Investigator) to include:

salutation, last name, first name, street address, city, state, zip code, telephone, fax, e-mail;

8. Contracting Officer to include: salutation, last name, first name, street address, city, state, zip code, telephone, fax, e-mail;

9. Award instrument requested: cost-plus-fixed-free (CPFF), cost-contract—no fee, firm-fixed-price, or Other Transaction;

10. Place(s) and period(s) of performance ;

11. Proposal validity…