Hermes_BAA_DRAFT_4.3.24.docx

Hermes (DRAFT)

DRAFT

Broad Agency Announcement Hermes Biological Technologies Office

This publication constitutes a Broad Agency Announcement (BAA) as contemplated in Federal Acquisition Regulation (FAR) 6.102(d)(2) and 35.016 and 2 CFR § 200.203. Any resultant award negotiations will follow all pertinent law and regulation, and any negotiations and/or awards for procurement contracts will use procedures under FAR 15.4, Contract Pricing, as specified in the BAA.

Overview Information:

NOTE – this is a DRAFT version of the Hermes Broad Agency Announcement. To that end, the information listed below (and throughout) are subject to change before the final opportunity is posted.

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

· Funding Opportunity Title – Hermes

· Announcement Type – DRAFT

· Assistance Listing Number: Not applicable

· Dates/Time - All Times are Eastern Time Zone (ET)

· Posting Date: #Posting Date (MMMM DD, YYYY)

· Industry Day: April 8, 2024 https://sam.gov/opp/eeeaa6d9305942fdb1a4340695d77806/view

· Anticipated individual awards - Multiple awards are anticipated.

· Types of instruments that may be awarded – Procurement contract, cooperative agreement, or other transaction.

· NAICS Code: 541714

· Agency contact

· Technical PoC: Dr. Shannon Greene, Program Manager, DARPA/BTO

· Contracting Officer: Ms. Filza Hall, DARPA/Contracts Management Office

· E-Mail:

· Mailing Address:

Funding Opportunity Description

The Defense Advanced Research Projects Agency (DARPA) is soliciting innovative proposals to develop systemic drug delivery platforms for therapeutic cargo. The Hermes program is explicitly seeking transformative approaches enabling the development of delivery platforms with systemic biodistribution, exceptional endosomal escape efficiency, and minimal toxicity. Successful proposals will include a detailed description of the proposed delivery platform including 1) screening pipeline, 2) reporter systems for monitoring biodistribution and expression in animal models, 3) methods to monitor immunogenicity/toxicity, and 4) chosen therapeutic cargo and justification. Systemic delivery platforms developed under the Hermes effort will be transferred to U.S. Government stakeholders for further development.

Program Overview Although efforts to develop novel therapeutics and prophylactics have provided critical resources to enable warfighter readiness and counter existing and emerging biothreats, current delivery platforms hinder the efficacy and rapid deployment of these therapeutics. Unlike traditional small molecule pharmaceuticals, biologics are large, complex molecules that can be exceptionally effective, but are challenging to administer and deliver in sufficient quantities to requisite cell and tissue types throughout the body. Many delivery platforms result in preferential liver accumulation, thus limiting the accessibility and effectiveness of therapeutics in alternative cell and tissue types.[footnoteRef:1] In addition, the rapid clearance of biologics from the bloodstream poses another obstacle—the immune system’s vigilant response leads to the swift elimination of these large molecules, reducing their concentration and therapeutic efficacy. Developing new delivery technologies that expand access to multiple cell and tissue types concurrently, along with accommodating the increasing complexity of therapeutic cargo, is critical to strengthen and augment biosecurity preparedness. By developing versatile, efficient, and accessible delivery platforms, the Department of Defense (DoD) will create new capabilities to protect the warfighter from the emerging threat landscape. [1: Kim, J., Eygeris, Y., Ryals, R. C., Jozić, A., & Sahay, G. (2023). Strategies for non-viral vectors targeting organs beyond the liver. Nature Nanotechnology, 1-20.]

Previous DARPA efforts such as the Pandemic Prevention Platform (P3) and the PRemptive Expression of Protective Alleles and Response Elements (PREPARE) programs resulted in the development of highly efficacious monoclonal antibodies[footnoteRef:2] and novel CRISPR-based therapeutics[footnoteRef:3], respectively, against viral, bacterial, and chemical threat agents. In addition, these programs advanced the state of the art (SOA) of nucleic acid-based delivery platforms, but further fundamental research and development is required. By developing versatile, efficient, and accessible delivery platforms, Hermes will enable the DoD to move beyond the current paradigm of one drug, one formulation. The goal of the Hermes program is to overcome the challenges associated with broad, intracellular delivery of biologics to diverse cell and tissue types by developing new delivery modalities that provide systemic distribution with limited negative side effects. [2: Zost, S. J., Gilchuk, P., Case, J. B., Binshtein, E., Chen, R. E., Nkolola, J. P., ... & Crowe Jr, J. E. (2020). Potently neutralizing and protective human antibodies against SARS-CoV-2. Nature, 584(7821), 443-449.] [3: Rotolo, L., Vanover, D., Bruno, N. C., Peck, H. E., Zurla, C., Murray, J., ... & Santangelo, P. J. (2023). Species-agnostic polymeric formulations for inhalable messenger RNA delivery to the lung. Nature Materials, 22(3), 369-379.]

To advance the DoD’s ability to respond to current and emerging biothreats, Hermes will address the following drug delivery challenges: (1) developing novel platforms and formulations capable of encapsulating large, complex cargos with limited immunogenicity; and (2) effective biodistribution to, and expression in, multiple cell and tissue types concurrently. The Hermes program will produce flexible platforms capable of delivering diverse types of therapeutic cargo to multiple cell and tissue types to prepare for any biothreat. Next generation delivery platforms developed during the program should offer unprecedented efficiency with minimal toxicity and immunogenicity. Delivery vehicles developed under the Hermes program must be capable of delivering nucleic acids, but approaches that are also compatible with proteins, small molecules, and/or combinations of these cargos are strongly preferred.

Successful proposals must provide a detailed scientific and technical justification for a drug delivery platform capable of broad, systemic distribution to, and transfection of, multiple cell and tissue types concurrently, that includes the following:

· A comprehensive discovery pipeline including appropriate reporter systems for assessing biodistribution, endosomal escape, and functional expression of therapeutic cargo.

· Detailed methods and approaches evaluating immunogenicity and toxicity of formulated delivery platforms, along with approaches to mitigating toxicity.

· Ability of chosen drug delivery platform to achieve program metrics and compatibility with scalable, current Good Manufacturing Practice (cGMP) manufacturing.

· Rationale for chosen therapeutic cargo and description of how chosen cargo will contribute to the overall goals of the program.

Specifically excluded are proposals that involve:

· Approaches that include human subjects research (HSR).

· Final delivery modalities that rely on intravenous administration. Proposals that incorporate intravenous administration as a comparator method or development model are allowed, but DARPA is primarily interested in delivery modalities that would enable field forward capabilities.

· Immunostimulatory or immunogenic approaches.

· Approaches that only incrementally improve on the current state of the art of nucleic acid delivery.

· Delivery platforms that, with further development through the course of the program, are not capable of packaging nucleic acids greater than 5kb.

· Tissue/cell type specific delivery modalities that cannot be co-formulated/co-administered into a single product.

· Approaches that are not amenable to cGMP regulations enforced by the FDA.

· Integrative delivery platforms (e.g. lentiviral vectors for gene therapy)

Technical Approach Current biological threats, such as Ebola virus[footnoteRef:4] or Rift Valley Fever virus[footnoteRef:5], are notorious for broad tissue tropism that contributes to the wide range of disease symptoms, morbidity, and mortality observed during infection. In addition, recent disruptive technology advancements in the fields of synthetic biology and artificial intelligence have facilitated the design and development of novel biological threats that may emerge quickly, potentially demanding a rapid response before a deep understanding of affected tissues or cells is available. The sheer number of potential tissues that are targets for current, and potentially novel, biological threats necessitates a versatile delivery platform capable of reaching various cell and tissue types concurrently throughout the body. Additionally, threat-agnostic delivery platforms could be integrated with existing pipelines for pandemic response—enabling coverage of a range of pathogenic threats with different tropisms. To effectively prepare for the emergence of any biological threat, the Hermes program seeks to develop a versatile threat agnostic platform capable of delivering diverse therapeutic cargo to broad cell and tissue types to protect the warfighter. [4: Furuyama, W., & Marzi, A. (2019). Ebola virus: pathogenesis and countermeasure development. Annual review of virology, 6, 435-458.] [5: Ikegami, T., & Makino, S. (2011). The pathogenesis of Rift Valley fever. Viruses, 3(5), 493-519.]

Foundational investments related to the delivery of nucleic acid-based cargos have resulted in new prophylactic and therapeutic capabilities such as mRNA lipid nanoparticle (LNP) based COVID-19 vaccines. However, high immunogenicity of the LNP delivery vehicles limits broad therapeutic potential beyond vaccine applications. Development of new capabilities enabling the high-efficiency introduction of diverse cargos to include large nucleic acid cargos, functional antibodies, and therapeutic enzymes to a broad range of cell and tissue types would create new therapeutic avenues towards biological and chemical threats that are currently inaccessible. The realization of these capabilities would potentially transform a wide variety of non-biodefense applications to include novel therapeutics for cancer, autoimmune disorder, and gene therapies. Significant investments towards these goals are already advancing delivery technologies to specific tissues, including the development of engineered virus-like particles[footnoteRef:6], selective organ targeted LNPs[footnoteRef:7], and ligand conjugated LNPs for hematopoietic stem cell editing[footnoteRef:8]. In contrast to current approaches focused on disease-centered strategies tailored for delivery to specific cell and tissue types, Hermes seeks to develop platform capabilities capable of widespread delivery of diverse cargos in a disease agnostic manner. Performers may utilize a variety of approaches to address delivery and formulation considerations for medical countermeasure cargo, including but not limited to: [6: An, Meirui, Aditya Raguram, Samuel W. Du, Samagya Banskota, Jessie R. Davis, Gregory A. Newby, Paul Z. Chen, Krzysztof Palczewski, and David R. Liu. "Engineered virus-like particles for transient delivery of prime editor ribonucleoprotein complexes in vivo." Nature Biotechnology (2024): 1-12.] [7: Cheng, Q., Wei, T., Farbiak, L., Johnson, L. T., Dilliard, S. A., & Siegwart, D. J. (2020). Selective organ targeting (SORT) nanoparticles for tissue-specific mRNA delivery and CRISPR–Cas gene editing. Nature nanotechnology, 15(4), 313-320.] [8: Breda, Laura, Tyler E. Papp, Michael P. Triebwasser, Amir Yadegari, Megan T. Fedorky, Naoto Tanaka, Osheiza Abdulmalik et al. "In vivo hematopoietic stem cell modification by mRNA delivery." Science 381, no. 6656 (2023): 436-443.

· Lipid-based formulations

· Polymer-based formulations

· Virus-like particles

· Extracellular vesicles

· Viral vectors Proposed delivery platforms should be minimally capable of delivering any nucleic acid-based cargos (i.e. DNA or RNA) intracellularly, but offerors are encouraged to propose platforms capable of delivering other cargos (e.g. proteins, small molecules, etc.). Systemic delivery may be achieved through a single platform formulation capable of targeting multiple relevant cell and tissue types concurrently, or a co-formulation of multiple delivery platforms with specific targets. The co-formulation approach must be stable and deliverable through no more than two administrations (e.g. two intramuscular injections; or one intramuscular injection and one nebulization; etc.). For clarification on required and desired specifications, see Table 1.

Table 1. Target Product Profile

Proposals that include incremental improvements of well-established delivery technologies, modalities, and formulations are not encouraged.

To meet the program requirements, proposers should employ a delivery platform discovery pipeline to identify and characterize lead candidates. Proposers must sufficiently detail the assays, reporter systems, and benchmarks comprising the pipeline chosen to measure key performance metrics to include cellular uptake and endosomal escape efficiency, cargo half-life/turnover, and biodistribution in vivo. For nucleic acid encoded cargo, assays and reporter systems must be capable of quantifying the level and durability of protein expression in different cell and tissue types in vivo. To address concerns regarding tolerability, immunological responses, and potential adverse side effects, a detailed plan for assessing immunogenicity and toxicity in vivo (e.g. immunohistochemistry, RNA sequencing, anti-drug antibody assay, weight loss, etc.) should be included in the proposal.

Proposers must clearly indicate how their selected delivery formulation approach will address and mitigate risk associated with potential failure modes, such as immunogenicity (adaptive and pre-existing) that would interfere with re-administration/multi-dosing treatment regimens, endosomal escape, toxicity, lack of cell tropism diversity, suboptimal absorption, distribution, metabolism and excretion (ADME) kinetics, cargo size limitations, ultralow temperature storage requirements, and compatibility with established manufacturing and scale-up practices.

Although scaled or cGMP manufacturing is out of scope in the Hermes program, proposals should include a viable plan for small-scale production of lead drug delivery platforms for delivery to U.S. Government stakeholders and transition partners for follow-on technology development (see Section 1.3), as well as a discussion of future pre-clinical testing and regulatory considerations to enable potential pathway towards future FDA regulatory filings. Proposers are encouraged to incorporate appropriate analytic capabilities for assessing platform characteristics to ensure compliance with FDA regulations and scale-up manufacturing throughout their period of performance.

In addition to technical details, the proposal must describe the organizational structure of the team, including project management, distribution of responsibilities, data capture, curation, and storage, animal use and care, along with project management and reporting structure. Teaming is highly encouraged as desired solutions will likely require integration of expertise from multiple disciplines (e.g. incorporation of a dedicated toxicologist or pathologist). The proposal must also describe a structure to communicate and engage with the Government sponsor, Government stakeholders, and relevant prospective regulatory agencies to facilitate a feasible path towards future clinical translation, as well as pathways to commercialization of technologies developed during the Hermes program.

Performers will need to demonstrate distribution to and intracellular delivery of therapeutic cargo to multiple tissue/cell types concurrently in vivo. The therapeutic cargo may be performer defined based on the expertise and capability of the offeror’s team. However, a therapeutic agent with a relevant DoD-use case is highly encouraged. Delivery platforms with demonstrated capability for large cargos (e.g. >5kb or >100kDa) and/or compatible with multiple types of macromolecules are also highly encouraged and should be considered when proposing. Proposals must clearly describe the reporter systems and therapeutic cargos of choice and a justification of relevancy to the program goals. Some examples DoD-relevant therapeutic targets could include, but are not limited to:

· Inhibitors of post-entry viral processes for viruses with broad tropism, such as Rift Valley Fever virus, Ebola, poxviruses, etc. expressed in affected tissues (e.g. liver, lung, spleen/lymph nodes, gastrointestinal tract, kidney, vascular epithelial cells, bone marrow, skin, eye, etc.)

· Inhibitors of protein-based toxins such as ricin, Shiga toxin, Anthrax toxin etc. delivered intracellularly to relevant cell and tissue types (e.g. gastrointestinal tract, kidney, lungs, central nervous system, etc.)

· Therapeutics for diseases caused by intracellular bacteria (e.g., legionella, tuberculosis) and parasites (e.g., malaria, Chagas) delivered to diverse cells and tissues (e.g., macrophages, fibroblasts, nervous system, muscular system, lymphatic system, red cells, etc.)

· Delivery of drug products such as leukocyte growth factors, pro-survival anti-neutropenia cytokines, and other supportive therapies to treat injuries and symptoms from acute exposure to ionizing radiation to targets such as endothelial, vascular, gastrointestinal, pulmonary, and related tissues.

The goal of the Hermes program is to develop a systemic drug delivery vehicle for therapeutic cargos with exceptional tolerability. Due to risks associated with balancing systemic efficiency and toxicity, immunostimulatory delivery approaches (e.g. vaccine designs) are considered out of scope of the Hermes program.

Program Structure The Hermes program is structured in two sequential Phases of increasing technical complexity (see Table 2). Phase I (Base, 20 months) will focus on developing the delivery platform screening pipeline, optimization of lead candidates, and evaluating delivery efficiency of chosen therapeutic cargo. Phase II (Option, 10 months) and will focus on adapting platforms to deliver a government-defined therapeutic cargo to demonstrate platform flexibility. Performers will conduct a Capability Demonstration (CD) at the end of each Phase, see Section 1.4. Progression to Phase II depends on performance towards prior Phase-specific goals as described below. If the team achieves the outlined metrics prior to the end of the Phase, performers may progress to subsequent Phases at the discretion of DARPA.

Table 2. Program Schedule Phase I:

20 Months (Base) Milestone: Proof of concept for performer-defined therapeutic cargo

· Months 0-20: Negotiated intermediate metrics based on individual performer approaches and goals

· Month 1: Program kickoff

· Month 17-19: Demonstrate effective, broad delivery of chosen therapeutic cargo in vivo (CD1)

· Month 20: CD1 performance review

Phase II:

10 Months (Option 1) Milestone: Delivery of government-defined medical countermeasure

· Months 21- 30: Negotiated intermediate metrics for optimization and testing of lead drug delivery vehicles

· Month 21: Notification of therapeutic cargo and target tissue/cell types by government team

· Month 27-29: Demonstrate effective, broad delivery of government-defined therapeutic cargo in vivo (CD2)

· Option 2: Small-scale manufacturing for government evaluation

Phase II’:

~2-6 Months (Option 2) Milestone: Small-scale manufacturing for testing and evaluation.

· Month ~24-30: scale-up manufacturing of delivery vehicle sufficient for ~500 doses in mice.

Phase I (Base, 20 months): Proof of concept for performer-defined therapeutic cargo in vivo (0-20 Months): Phase I is intended to generate a lead drug delivery platform that is capable of intracellular delivery of cargos to multiple cell and tissue types in vivo. Proposers will screen drug delivery vehicles, or combinations thereof, for lead candidates to progress to in vivo testing and optimization. Delivery vehicles should demonstrate the ability to be introduced in animal models (e.g. murine, rat, hamster, rabbit, ferret, non-human primates etc.) through simple administration routes (e.g. intramuscular, intranasal, oral, etc.). Three months prior to the end of Phase I, performers will begin CD1, and a final report representing the outcome of CD1 will be submitted to the government team one month prior to the end of Phase I. Performer advancement to Phase II will be determined by DARPA.

Phase II (Priced Option 1, 10 months): Delivery of government-defined therapeutic cargo in vivo (21-30 Months): The goal of the Hermes program is to develop a threat and cargo agnostic delivery vehicle; thus, performers will be challenged to deliver a government-defined therapeutic cargo in Phase II. The goal of Phase II will be a demonstration that the delivery vehicle developed in Phase I can be adapted to carry a different cargo and expand targeting to additional tissue/cell types not demonstrated in Phase I. Performers will be notified of the government-defined cargo and the intended target cell and tissue types at the beginning of Phase II, and must initiate CD2 at least 3 months prior to the end of Phase II. During Phase II, performers should demonstrate enhanced performance of the delivery capability (e.g. increase in total cargo capacity, improvement in intracellular delivery efficiency, etc.) beyond achievements in Phase I. A final report will be due at the end of Phase II.

Quantitative and qualitative metrics must be met at the end of each phase and will be defined at negotiation (as described below in Section 1.4). At the end of the program, it is anticipated that performers will transfer technologies developed under the Hermes program to DARPA and Government stakeholders for independent verification, validation, and DoD-specific test and evaluation. Proposals must include a detailed plan for data storage, curation, and sharing with the Government, along with a plan to document protocols, formulations, reagents, and all other materials needed to support technology transition. Transition plans that include technology transition and commercialization to private industry are also highly encouraged.

Priced Option 2: Small-scale manufacturing for testing and evaluation: Pending performance against program metrics and at the discretion of DARPA and government stakeholders, an optional task for manufacturing and transferring small scale material for downstream animal studies could be exercised. Material should be sufficient for a small-scale animal study; the exact quantities produced, and the duration of this Option will be determined in collaboration with DARPA and the Government team based on the proposed technical approach. For budgetary purposes, 500 doses for a mouse model may be used as an estimate. This Option, if exercised, would be executed within Phase II during approximately months 24-30.

Metrics and Milestones Proposers to the Hermes program must define ambitious, specific, and progressive quantitative metrics in support of program goals and specific to their proposed therapeutic cargo and drug delivery platform, including intermediate metrics for each Phase of the program to help evaluate technology development progress. Suggested milestones are included below for proposer consideration but are not meant to be prescriptive. Final metrics are to be determined at time of award negotiation and are subject to DARPA approval. Proposers should note that program metrics may serve as the basis for determining whether satisfactory progress is being made to warrant continued funding of the program.

Proposers should define metrics associated with milestones for each Phase, Capability Demonstration (CD), and overall effort. Although specific program metrics will depend on the therapeutic cargos chosen, examples of broad qualitative milestones and associated quantitative metrics for the overall program include, but are not limited to:

· Develop high-throughput, combinatorial pipeline screening with delivery formulations in vivo or in an appropriate cell, organoid, or tissue system in vitro.

· Develop novel reporter systems and demonstrate ability to monitor biodistribution and cargo release in real time.

· Demonstrate formulations that deliver reporters/therapeutic cargos intracellularly and target multiple cells, tissue, and organs concurrently in vivo.

· Metric: Achieve high transfection efficiency (measured at >95% cells) in vivo in 5+ tissue types

· Metric: Achieve sustained in vivo expression and/or protection of >3 months before return to a wildtype state (i.e., no genomic integration and undetectable by ADME profiling).

· Demonstrate ability to package large and complex cargos.

· Metric: Package cargos > 10 kb nucleic acid, >200 kDa protein

· Demonstrate loading of drug delivery vehicle with multiple unique cargo types.

· Metric: Package at least 2 cargo types (e.g. capable of carrying DNA, RNA, protein, small molecules, etc.) in a single vehicle.

· Demonstrate exceptional safety profile (e.g., minimal adverse effects in a healthy animal model)

· Metric: Change in weight less than 5%, animals exhibit normal behaviors (e.g., well-groomed, normal posture/gait, explores environment, eats/drinks readily).

· Metric: No reactivity detected for anti-vehicle antibodies at pg/mL sensitivity for IgG, IgM, IgE for repeated dose testing

· Metric: No adverse effects in toxicity studies after repeated dose testing

· Administer drug delivery platform through non-invasive administration route (e.g. intramuscular, sub-cutaneous, oral, intranasal).

· Demonstrate exceptional stability of drug delivery platform.

· Metric: Demonstrate stability at -20°C, or preferably lyophilization and storage at room temperature, for 6 months in real time and 18 months in accelerated aging studies.

Capability Demonstrations. At the end of each Phase, performers will complete a CD, and proposers must clearly indicate their target performance metrics for each CD. For the first CD, metrics must describe the state of art (SOA) drug delivery platform that will be used to benchmark performance, and must define, in quantitative and qualitative terms, what is considered efficient delivery in vivo, and describe how it will be measured (e.g. % fluorescently positive cells, target concentration of protective gene product in tissue). Although the proposal must include current information for the SOA benchmark, proposers should anticipate adjusting benchmarks to keep pace with evolving SOA over the course of the Hermes program. Example metrics for each CD are provided in Table 3.

For animal models, offerors may propose to simply provide an efficacious dose as defined by SOA or complete a therapeutic study in a relevant animal model. Proposers may select any animal model of choice, but must provide justification for the selection especially if proposing large animal studies (e.g. non-human primates).

Table 3. Example Metrics

Metric

*Specific tissue types of interest: Lung, liver, spleen, heart, kidney, gastrointestinal tract, bone marrow, muscle, eye, brain/central nervous system **Simple administration refers to quick, minimally invasive administration performed by a healthcare provider (e.g. intramuscular injection, sub-cutaneous injection, nebulization), while self-administration refers to oral, auto-injector, inhaler, patch, etc. delivery approaches.

† As measured by in vivo weight loss, immunohistochemistry, RNAseq for innate immune response (for example)

Evaluation Criteria

· Proposals will be evaluated using, at a minimum, the following criteria listed in descending order of importance: Overall Scientific and Technical Merit; Potential Contribution and Relevance to the DARPA Mission; and Cost Realism.

· Overall Scientific and Technical Merit: The proposed technical approach is innovative, feasible, achievable, and complete. The proposed technical team has the expertise and experience to accomplish the proposed tasks, with prior experience in similar efforts that clearly demonstrates an ability to deliver products that meet the proposed technical performance within the proposed budget and schedule. Similar efforts completed/ongoing by the proposer in this area are fully described including identification of other Government sponsors. Task descriptions and associated technical elements provided are complete and in a logical sequence with all proposed deliverables clearly defined such that a final outcome that achieves the goal can be expected as a result of award. The proposal identifies major technical risks and planned mitigation efforts are clearly defined and feasible.

· Potential Contribution and Relevance to the DARPA Mission: The potential contributions of the proposed effort bolster the national security technology base and support DARPA’s mission to make pivotal early technology investments that create or prevent technological surprise. The proposed intellectual property restrictions (if any) will not significantly impact the Government’s ability to transition the technology.

· Cost Realism: The proposed costs are realistic for the technical and management approach and accurately reflect the technical goals and objectives of the solicitation. The proposed costs are consistent with the proposer's Statement of Work and reflect a sufficient understanding of the costs and level of effort needed to successfully accomplish the proposed technical approach. The costs for the prime proposer and proposed sub awardees are substantiated by the details provided in the proposal (e.g., the type and number of labor hours proposed per task, the types and quantities of materials, equipment and fabrication costs, travel and any other applicable costs and the basis for the estimates).

It is expected that the effort will leverage all available relevant prior research in order to obtain the maximum benefit from the available funding. For efforts with a likelihood of commercial application, appropriate direct cost sharing may be a positive factor in the evaluation. DARPA recognizes that undue emphasis on cost may motivate proposers to offer low-risk ideas with minimum uncertainty and to staff the effort with junior personnel in order to be in a more competitive posture. DARPA discourages such cost strategies.

· Unless otherwise specified in this announcement, for additional information on how DARPA reviews and evaluates proposals through the Scientific Review Process, please visit: Proposer Instructions and General Terms and Conditions.

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