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

Amendment / Modification

This amendment (Amendment 2) to the ARPA-H-SOL-26-139 solicitation introduces several updates:

• Incorporated Link to FAQ Portal: A link to the Frequently Asked Questions portal has been added.
• Replaced Program Leads with Project Leads: The terminology for leadership roles has been updated.
• Section 1.6.1 Clarification: Language in Section 1.6.1 has been clarified.
• Section 1.6.4 Update: The phrase "and cover costs for patients" has been inserted into Section 1.6.4.
• Table 2 Update: The entry "TA2" has been added to Table 2.
• Section 1.7.2 Update: The phrase "and justify budget" has been inserted into Section 1.7.2.
• Section 1.16.2 Update: Instructions under "Model Other Transaction Agreement" have been updated.

All changes are highlighted in yellow within the document.

• Section 1.6.1
• Section 1.6.4
• Table 2
• Section 1.7.2
• Section 1.16.2
• FAQ Portal link
• Program/Project Lead terminology

This amendment does not appear to alter the proposal submission deadlines or core requirements, but it does provide updated information and clarifications that proposers should review.

Amendment / Modification

This document, Amendment 2, changes the designation from "Program Lead" to "Project Lead" within the solicitation documents.

• The title "Program Lead" has been updated to "Project Lead" throughout the relevant documents.

• No changes to proposal submission deadlines, requirements, or evaluation factors are indicated by this amendment. It is primarily a terminology update.

Amendment / Modification

This amendment (Amendment 1) to Solicitation ARPA-H-SOL-26-139 makes the following changes:

• The proposal submission date has been changed to Thursday, May 28, 2026.

• The term "Office of Commercialization (OC)" has been replaced with "ARPA-H".

• All changes are highlighted in yellow within the document.

• Proposal submission deadline.

• References to "Office of Commercialization (OC)" have been updated to "ARPA-H".

• The proposal submission deadline has been extended to Thursday, May 28, 2026.

Solicitation / RFP / RFQ

This Innovative Solutions Opening (ISO) solicits proposals for the Critical Illness Immunological Reprogramming and Control Point Learning Engine (CIRCLE) program. The goal is to reduce ICU time and improve outcomes for critically ill patients by developing a system to assess, predict, and modulate immuno-inflammatory processes. This aims to lead to personalized immunotherapy and improved patient outcomes, potentially reducing average ICU stay by 25%.

The CIRCLE program is structured around three Technical Areas (TAs) and three Acceleration Platforms (APs):

• TA1: Measure - Dynamic Immune Descriptor: Develop real-time, tissue-specific immuno-inflammation biomarker sensors and diagnostics.

• TA2: Model - Digital Twin Generator: Develop personalized computational models (digital twins) to predict critical illness trajectories and identify control points.

• TA3: Modulate - Rational Immune Reprogrammer: Develop and test interventions to modulate the immune response to control critical illness.

• APs (AP1, AP2, AP3): Provide independent verification, validation, data analysis, FDA-compliant modeling platforms, and clinical trial support.

• This is a 5-year, 3-phase program.

• Awards will be Other Transactions (OTs).

• Multiple awards are anticipated.

• Key Dates:

  • Proposers' Day: March 11, 2026
  • Solution Summary Submission: March 30, 2026, 1:00 PM
  • Q&A Submission: May 22, 2026, 1:00 PM
  • Proposal Submission: May 29, 2026, 1:00 PM

• Proposals will be evaluated on Overall Scientific and Technical Merit, Proposer's Capabilities and/or Related Experience, Price/Value Analysis, and Relevance to the ARPA-H Mission.

• Universities, non-profit organizations, small businesses, and other than small businesses are eligible.

• Federally Funded Research and Development Centers (FFRDCs) and U.S. Government entities are not permitted to participate as prime or sub-performers.

• Non-U.S. entities may participate if they comply with applicable regulations.

• Proposers must submit a solution summary prior to submitting a full proposal.

• Proposals must include a commercialization strategy narrative.

• Open-source technologies are encouraged.

Form / Attachment / Pricing Sheet

This document is an Excel workbook designed to assist proposers in developing their cost proposals, specifically for opportunities utilizing a Resource Sharing agreement. It provides a structured template for detailing labor rates, indirect costs, and overall project costs across multiple fiscal years and phases.

• Instructions Tab: Provides guidance on how to use the workbook, including data entry procedures, cell definitions, and how to manage labor categories, indirect rates, and fiscal year accounting periods.
• Constants Tab: Defines various labor groups, labor categories, indirect rate categories (Fringe, Overhead, G&A, F&A, Profit/Fee), SBIR/STTR phase choices, and small business size estimates.
• Labor Rates Tab: A critical section where proposers input individual personnel details, their assigned labor categories, and their corresponding fully loaded labor rates and escalation rates.
• Phase Cost Tabs (e.g., Phase 1 Costs, Phase 2 Costs): These sheets allow for the detailed breakdown of costs by fiscal year, including direct labor hours and costs, subcontractor costs, consultant costs, other direct costs (ODCs), material handling, G&A, and Facilities Capital Cost of Money (FCCM).
• Task Cost Tabs (e.g., Ph 1 Task $, Ph 2 Task $): These sheets require proposers to break down costs by the tasks identified in the Statement of Work.
• Summary Cost Table: Aggregates costs across all phases and fiscal years.
• Supporting Sheets: Includes templates for Subproposer data, Consultant details, Travel costs, Materials/Supplies, Equipment, ODC Details, Expenditures by Month, Animal/Human Use, Animal Related Costs, Human Subjects Research Costs, and Milestones/Deliverables.

This workbook is essential for any bidder responding to an opportunity that requires a detailed cost proposal under a Resource Sharing agreement. It dictates the format and content required for cost submissions, including specific instructions on how to define labor categories, apply indirect rates, and allocate costs across project phases and tasks. Proposers must use this template to ensure their cost proposals are complete, accurate, and compliant with the solicitation's requirements.

Form / Attachment

This document, "Att B - VOLUME 1_TECH - MANAGEMENT - CIRCLE.docx," provides detailed instructions and a template for preparing the Technical & Management volume of a proposal in response to Solicitation Number ARPA-H-SOL-26-139. It outlines formatting requirements, page limits, and the specific content expected for each section of the technical and management proposal.

• Formatting Requirements: Proposals must be submitted in .pdf, .odx, .doc, or .docx formats, in English, on 8-1/2 x 11-inch paper with 1-inch margins, and a sans serif font size not smaller than 12 point (8 or 10 point for figures/tables/charts).
• Page Limits:
  • Type A proposals (addressing all three technical areas): Not to exceed forty (40) pages.
  • Type B proposals (addressing one acceleration platform): Not to exceed thirty (30) pages.
  • Exclusions from page count: Technical figures, tables, charts, Cover Sheet, Table of Contents, Resumes, Bibliography (Optional), Letters of Support (Optional).
• Required Sections: The document details content for the Cover Sheet (including Solicitation Number, Proposer Organization Name, UEI, POCs, Proposed Cost, Place(s) of Performance), Sub-Awardee and Consultant Team Members, Table of Contents, Proposal Summary, Goals and Impact, Technical Plan, and Capabilities/Management Plan.
• Specific Guidance: Provides questions for the Proposal Summary, structure for the Technical Plan (Type A vs. Type B), and details for the Management Plan (including data sharing alignment with FAIR principles). A Commercialization Strategy Narrative is required for Type A proposals.
• References: Proposers are directed to the "CIRCLE ISO" (sections 1.5.2, 1.7.2, 1.7.3, 1.6.5, 4.3.1, and sections 4 and 5) for additional requirements, evaluation criteria, and definitions of conforming/non-conforming proposals.

This attachment is crucial for bidders to ensure their Technical & Management proposal volume is fully compliant with all submission requirements, formatting standards, and content expectations. Adherence to these instructions, including page limits and section content, is essential for a conforming and evaluable proposal.

Form / Attachment / Pricing Sheet

This document is a template for bidders to use when preparing their Solution Summary for the ARPA-H CIRCLE Innovative Solutions Opening (ISO) # ARPA-H-SOL-26-139. It provides the required structure and content guidance for submissions.

• Cover Sheet: Includes fields for organization name, submission type (Type A or Type B), contact information (Technical and Administrative POCs), Government and Performer Share amounts, Rough Order of Magnitude (ROM), Place(s) of Performance, and Other Team Members.
• Section 1: Project Concept Summary: Requires a description of the project concept and how it addresses the ISO's goals.
• Section 2: Innovation and Impact: Requires a description of the proposed solution's innovation, potential impact, and disruptive capabilities.
• Section 3: Proposed Work: Requires details on deliverables, milestones, technical approach, alternative approaches considered, supporting data/citations, Digital Twin models, commercialization plans, and technical risks.
• Section 4: Team Organization and Capabilities: Requires identification of team members, roles, responsibilities, and partnerships.
• Section 5: Rough Order of Magnitude (ROM): Requires a detailed budget breakdown using provided tables for non-commercialization and commercialization-related costs.

Bidders must use this template to structure their Solution Summary. Key instructions include:

• Submissions must be in English with 12-point Avenir Next LT Pro font (smaller for figures/tables).
• All formatting and content instructions (in blue font) must be deleted prior to submission.
• Page limits apply: 4 pages for Type A, 3 pages for Type B (excluding Cover Page, Citations, and ROM).
• Only one document should be uploaded per submission.
• Proposers must ensure their content aligns with the evaluation criteria stated in the ISO.

Form / Attachment

This document, titled "Att C - VOLUME 1_Task Description Document - CIRCLE.docx," is a required template for bidders to describe their planned technical tasks and subtasks when submitting a proposal to ARPA-H. It provides a structured format to ensure all necessary technical details are included.

• Bidders must provide the general objective of their proposal and a detailed list of tasks and subtasks.
• For each task and subtask, the template requires:
  • A general objective and detailed description of the approach.
  • Identification of the performance location (e.g., commercial lab, non-profit, academic institution).
  • Identification of the primary responsible organization (prime, sub-awardee, consultant).
  • A list of all deliverables (data, reports, software) to be provided to the government, including associated Intellectual Property (IP) assertions.
  • Indication of whether human- and/or animal subjects research is involved, with a description if applicable.
  • Measurable milestones (e.g., demonstrations, events).
• The template also includes sections for program management tasks (e.g., subcontractor management, status reports) and meeting/travel requirements, referencing the CIRCLE ISO.

This template is mandatory for structuring the technical volume of the proposal. Bidders must use this format to clearly articulate their technical approach, deliverables, and milestones, ensuring consistency and completeness for evaluation. It also highlights the need to align the described tasks and subtasks with the spreadsheets in the appropriate Cost Workbook.

Other / Unclassified

This document is a sample "Other Transaction Agreement" (OTA) template used by the Advanced Research Projects Agency for Health (ARPA-H). It outlines the standard terms and conditions for agreements that are not traditional FAR-based contracts. The template includes placeholders for specific program details, performer information, and financial terms. It details various articles covering the scope of the agreement, term, management, administration, payment, disputes, intellectual property rights, foreign access, tangible property, public release, civil rights, security, applicable law, order of precedence, execution, survival, prohibitions on certain telecommunications equipment, research security, and special terms and conditions.

This document provides potential bidders with insight into the contractual framework ARPA-H uses for its Other Transaction Agreements. It highlights key areas such as:

• Scope and Objectives: Outlines how the program's purpose, current state of the art, and benefits will be defined.
• Term and Phases: Details the potential multi-phase structure of the agreement (Phase I, II, III) and their durations.
• Management and Reporting: Specifies roles of ARPA-H personnel (PM, AO, AOR) and the Performer, along with reporting requirements (monthly status, special technical reports, milestone reports).
• Payment Structure: Explains the fixed milestone payment system and the requirement to use Payment Management Services (PMS).
• Intellectual Property (IP) Rights: Crucially defines how IP developed under the agreement will be handled, including performer retention, government purpose rights, and disclosure requirements.
• Data Rights: Clarifies the government's rights to data generated, including Government Purpose Rights and Unlimited Rights for reports.
• Foreign Access and Security: Addresses restrictions on foreign access to IP and research security requirements, including foreign talent recruitment program prohibitions.
• Special Terms: Includes limitations on salary rates and specific requirements for Human Subjects Research (HSR) and data collection/sharing (FAIR principles, deidentification, public access).

Understanding these terms is essential for bidders to assess the feasibility and implications of participating in an ARPA-H OTA opportunity.

Form / Attachment / Pricing Sheet

This document is the "Administrative & National Policy Requirements Document" which must be completed in full and included as part of the proposal submission. It requires specific formatting and content related to organizational details, personnel, conflicts of interest, research security, intellectual property, human/animal subjects research, tax liability, cybersecurity, and biosecurity.

• Cover Page: Proposal Title, Proposer Organization, Technical and Administrative POCs, Submission Date, Proposal Validity Period.
• Team Member Identification: Listing of all organizations involved (prime, sub-awardees, contractors, vendors).
• Senior/Key Personnel: Details on personnel, including confirmation of attached Biographical Sketches and Current & Pending Support.
• FFRDC Participation: Disclosure of any Federally Funded Research and Development Center involvement.
• Organizational Conflict of Interest (OCI) Affirmations and Disclosure: Requirements for disclosing potential conflicts and commitments, including specific questions about support to ARPA-H and mitigation plans.
• Research Security Disclosure: Questions regarding participation in foreign talent recruitment programs, ownership by foreign entities, and research execution within foreign countries of concern.
• Novelty of Proposed Work: Disclosure if the work has been submitted to other solicitations or already funded.
• Intellectual Property (IP): Detailed section for asserting background IP and data rights, including specific categories (Unlimited, Government Purpose, Limited, Specially Negotiated/Other Rights).
• Human Subjects Research (HSR) & Animal Subjects Research (ASR): Requirements for documentation and approval from Institutional Review Boards (IRB) and Institutional Animal Care and Use Committees (IACUC).
• Representations Regarding Unpaid Delinquent Tax Liability or Felony Conviction: Specific representations required from the proposer.
• Cybersecurity: Description of the organization's cybersecurity program and experience with Controlled Unclassified Information (CUI).
• Biosecurity: Disclosure regarding dangerous gain-of-function research and procurement of synthetic nucleic acids or related equipment.

This document is critical for proposal preparation. Bidders must complete all sections accurately and adhere to formatting requirements (8-1/2 by 11-inch paper, 1-inch margins, 11-point sans-serif font). Failure to complete this document in full may impact proposal submission and evaluation. It requires significant detail regarding team composition, personnel qualifications, potential conflicts, IP assertions, and compliance with security and ethical research practices.