Critical Illness Immunological Reprogramming and Control Point Learning Engine (CIRCLE) Innovative Solutions Opening (ISO)

The Advanced Research Projects Agency for Health (ARPA-H) issued an Innovative Solutions Opening (ISO) Amendment 2 for the Critical Illness Immunological Reprogramming and Control Point Learning Engine (CIRCLE) program. This initiative seeks to revolutionize critical care by shifting from reactive organ support to proactive treatment of immune dysfunction. The program aims to develop diagnostic modalities, patient-specific computational models (digital twins), and immunomodulatory therapies to reduce ICU stays by 25% and improve patient outcomes. It is structured into three Technical Areas (TAs): Measure, Model, and Modulate, supported by three Acceleration Platforms (APs) for data, FDA-compliant digital twin testing, and clinical trials. The 5-year, 3-phase program emphasizes integrated team efforts, data sharing, and commercialization, with strict milestones and metrics for progression and award termination for non-compliance.

ARPA-H's Innovative Solutions Opening (ISO) for the Critical Illness Immunological Reprogramming and Control Point Learning Engine (CIRCLE) program, Amendment 4, seeks to transform critical care by reducing ICU stays, morbidity, mortality, and costs. The program aims to develop personalized immunotherapies through rapid assessment of immuno-inflammatory biomarkers, patient-specific computational 'digital twin' models, and rational modulation of immune dysregulation. This 5-year, 3-phase program involves integrated Technical Area (TA) teams focusing on Measurement, Modeling, and Modulation, supported by Acceleration Platforms (APs) for data, FDA-compliant digital twin platforms, and clinical trials. The initiative, offering multiple awards, prioritizes commercial transition and aims for FDA approvals, with a target of a 25% reduction in average ICU stay length.

The ARPA-H Standard Cost Proposal Workbook (Resource Sharing) provides comprehensive instructions for proposers and subproposers to complete cost proposals under an Other Transaction with a Resource Sharing agreement. The workbook is structured with colored tabs for linked spreadsheets and uncolored tabs for standalone cost details. Users must start by filling out the 'General' and 'Proposer Constants' tabs, followed by 'Labor Rates,' 'Phase # Costs,' and 'Ph # Task $'. Key guidelines include not deleting tabs or rows to maintain workbook structure, using pick-lists for selections, and carefully adding new lines while ensuring formulas carry forward. The document emphasizes the proposer's responsibility for providing accurate, complete, and supportable cost data to facilitate government review and negotiation.

The Advanced Research Projects Agency for Health (ARPA-H) has issued an Innovative Solutions Opening (ISO) for the Critical Illness Immunological Reprogramming and Control Point Learning Engine (CIRCLE) program (ARPA-H-SOL-26-139). This initiative seeks to reduce intensive care unit (ICU) stays, morbidity, mortality, and costs associated with critical illness by developing novel diagnostic and therapeutic approaches. The program aims to create a Critical Illness Control Point Validation Engine that assesses, predicts, and treats immuno-inflammatory dysregulation before organ failure.CIRCLE is a five-year, three-phase program structured around three Technical Areas (TAs): Measure (TA1) for dynamic immune biomarker data, Model (TA2) for patient-specific digital twin models, and Modulate (TA3) for rational immune reprogramming. These TAs will be supported by three Acceleration Platforms (APs) providing data, FDA-compliant model testing, and clinical trial infrastructure. The program emphasizes integrated team efforts, rapid data acquisition, and the repurposing of FDA-approved therapies, with a target of a 25% reduction in average ICU stay length. Proposals are due by May 29, 2026.

This document outlines the required "Solution Summary Template" for submissions to the ARPA-H CIRCLE Innovative Solutions Opening (ISO) #ARPA-H-SOL-26-139. Proposers must submit a single summary, either Type A (consolidated TA1, TA2, TA3 proposal) or Type B (AP1, AP2, or AP3 proposal), adhering to strict formatting guidelines and page limits (4 pages for Type A, 3 for Type B, excluding cover page, citations, and Rough Order of Magnitude (ROM)). The summary must cover the project concept, innovation and impact, proposed work including deliverables and technical approach, team organization and capabilities, and a detailed ROM estimate broken down by non-commercialization and commercialization-related costs. The purpose is to guide proposers in developing content that meets evaluation criteria for federal government RFPs, specifically for the ARPA-H CIRCLE program.

The document outlines instructions for preparing a Technical & Management Document for government proposals, likely for federal grants or RFPs. It details formatting requirements, page limits for different proposal types (Type A: 40 pages, Type B: 30 pages), and content that is excluded from page counts like cover sheets and resumes. Key sections include a Proposal Summary, Goals and Impact, Technical Plan, and Capabilities/Management Plan. Specific guidance is provided for Type A proposals, which require a Commercialization Strategy Narrative and an Integrator section within the Technical Plan, and for Type B proposals, which focus on supporting other performers and independent validation. The document emphasizes aligning proposals with the CIRCLE ISO's evaluation criteria, particularly regarding technical requirements, conforming proposals, and data sharing in line with FAIR principles.

The provided document, "ATTACHMENT 3 TASK DESCRIPTION DOCUMENT (TDD) TEMPLATE," outlines the mandatory format for proposals submitted to ARPA-H, focusing on detailed technical task and subtask descriptions. Proposers must provide a general objective, a task list, and specific information for each task and subtask within structured tables. This includes a detailed approach, performance location, responsible organization (prime or sub-awardee), deliverables with intellectual property assertions, and identification of human or animal subjects research. Each task and subtask requires measurable milestones. The template also mandates inclusion of program management, subcontractor management, status reports, and meeting and travel requirements, ensuring alignment with cost workbook spreadsheets. This template ensures comprehensive and standardized proposal submissions for ARPA-H projects.

The ARPA-H Standard Cost Proposal Workbook (June 2025 version) provides instructions for preparing cost proposals, specifically for 'Other Transactions' involving 'Resource Sharing agreements.' It is mandatory for both Prime and Subproposers, with prime proposers being able to submit all workbooks. The workbook comprises colored tabs (linked spreadsheets) and non-colored tabs (standalone spreadsheets for detailed cost entries like travel and materials). Users are instructed to complete the 'General,' 'Proposer Constants,' and 'Labor Rates' tabs first, followed by 'Phase # Costs' and 'Ph # Task $' tabs. Key instructions include not deleting tabs, spreadsheets, rows, or columns to maintain the workbook’s structure, utilizing the 'Hide' function instead. Unshaded cells are for data entry, while shaded cells contain formulas that should not be altered unless they conflict with the proposing organization’s business rules. Proposers must ensure any changes do not disrupt the workbook’s flow. The workbook provides up to six fiscal years per phase, with a strong emphasis on providing thorough supporting data for all proposed costs to facilitate government review and negotiation.

This document outlines an Other Transaction Agreement (OTA) between the Advanced Research Projects Agency for Health (ARPA-H) and a performer, focusing on research and technology goals. It details the agreement's scope, including program vision, technological context, market potential, and commercialization goals. Key provisions cover the agreement's term, management structure, and modification procedures. Financial aspects specify fixed payments for milestones, the use of Payment Management Services (PMS), and financial record-keeping. Intellectual Property (IP) rights are extensively defined, allocating ownership and licensing between ARPA-H and the performer, with special conditions for foreign access to IP and data rights. Other articles address tangible property, public information release, civil rights, security requirements (including cybersecurity and controlled unclassified information), applicable law, and prohibitions on certain telecommunications equipment from covered foreign countries. The agreement emphasizes good faith efforts, timely communication, and outlines dispute resolution procedures, limiting damages to direct costs.

The Administrative & National Policy Requirements Document is a critical component for federal government proposal submissions, particularly for RFPs and grants. It outlines essential administrative and national policy requirements that proposers must address. Key sections include detailed team member identification, disclosures regarding Federally Funded Research and Development Center (FFRDC) participation, and comprehensive Organizational Conflict of Interest (OCI) affirmations and mitigation plans. The document also mandates a thorough research security disclosure to prevent unwanted knowledge transfer, requiring information on foreign talent recruitment programs and foreign ownership. Proposers must disclose the novelty of their work, provide extensive details on intellectual property (IP) and data rights, and confirm compliance with human and animal subjects research regulations. Additionally, it covers representations regarding tax liability and felony convictions, cybersecurity program implementation, and biosecurity measures, including dangerous gain-of-function research. All submissions must adhere to specific formatting guidelines and be submitted in English, ensuring transparency and compliance with federal policies.

The Advanced Research Projects Agency for Health (ARPA-H) issued Amendment 1 to the Innovative Solutions Opening (ISO) ARPA-H-SOL-26-139, titled “Critical Illness Immunological Reprogramming and Control Point Learning Engine (CIRCLE).” The amendment changes the proposal submission date to May 28, 2026, and replaces “Office of Commercialization (OC)” with “ARPA-H.” The CIRCLE program aims to reduce ICU stay times, morbidity, mortality, and costs associated with critical illness by developing a “Control Point Validation Engine.” This engine will assess, predict, and treat immuno-inflammatory dysregulation before organ failure occurs. The program seeks to achieve this through rapid assessment of immuno-inflammatory biomarkers, informing patient-specific computational models (digital twins) to identify control points for personalized immunotherapy. The program is structured into three Technical Areas (TAs): Measure (TA1), Model (TA2), and Modulate (TA3), supported by three Acceleration Platforms (APs) for data, FDA-compliant digital twin testing, and clinical trials. This five-year, three-phase program anticipates multiple awards for integrated TA teams and single awards for each AP, emphasizing rapid clinical translation and commercialization.

ARPA-H's Innovative Solutions Opening (ISO) for the Critical Illness Immunological Reprogramming and Control Point Learning Engine (CIRCLE) program seeks to transform critical care. This initiative, detailed in Amendment 3, aims to improve ICU outcomes by predicting and treating immuno-inflammatory dysregulation before organ failure. The CIRCLE program, a 5-year, 3-phase effort, will develop rapid diagnostic modalities, patient-specific computational 'digital twin' models to identify therapeutic control points, and targeted immunotherapies. The program is structured into three Technical Areas (TAs)—Measure, Model, and Modulate—and three Acceleration Platforms (APs) for support and independent verification/validation. Proposals are sought for integrated TA teams or individual AP components. Key milestones include establishing biomarker sets, digital twin validation, and pilot clinical studies, with a target of reducing ICU stay length by 25% and improving post-hospitalization outcomes. Collaboration, data sharing, and commercial transition are central to the program's success, with financial commitments from commercialization partners required in later phases.

This document outlines instructions and requirements for submitting proposals related to the ARPA-H-SOL-26-139 solicitation. Proposals must adhere to specific formatting guidelines, including page limits (40 pages for Type A, 30 for Type B) that exclude cover sheets, tables of contents, resumes, bibliographies, and letters of support. The Technical & Management Document requires a cover sheet with solicitation details, proposer information, and cost breakdown, along with sections for sub-awardee and consultant team members. The core content includes a Proposal Summary addressing project goals, health outcomes, innovations, risks, and impact; a Goals and Impact section detailing qualitative and quantitative differences; and a Technical Plan outlining project goals, challenges, milestones, and schedules. A Capabilities/Management Plan is also required, focusing on team expertise, a designated Project Lead, and management strategies for both Type A and Type B proposals, including data sharing alignment with FAIR principles. Optional sections include a Commercialization Strategy (for Type A), Resumes, and a Bibliography. The document emphasizes the importance of conciseness, descriptive examples, and alignment with evaluation criteria in the CIRCLE ISO.