ARPA-H - Critical Illness Immunological Reprogramming and Control Point Learning Engine (CIRCLE)

Below is a brief summary. Please check the full solicitation before applying (link in resources section).

Executive Summary:

The Advanced Research Projects Agency for Health (ARPA-H), Resilient Systems Office (RSO), has released an Innovative Solutions Opening (ISO) for the Critical Illness Immunological Reprogramming and Control Point Learning Engine (CIRCLE) (Solicitation Number: ARPA-H-SOL-26-139, Amendment 1).

CIRCLE seeks to reduce ICU stay length and improve outcomes by developing integrated systems that:

• Measure tissue-specific immuno-inflammatory biomarkers in near real time

• Build mechanistic, patient-specific computational “digital twin” models

• Modulate immune dysfunction using personalized therapeutic interventions

The program aims for a 25% reduction in average ICU stay length and progression toward FDA-compliant systems and clinical adoption.

Solution Summaries are due March 30th.

How much funding would I receive?

The solicitation states that multiple awards are anticipated.

• Awards will be made as Other Transaction (OT) agreements.

• The number of awards will depend on the quality of proposals and the availability of funds.

• Individual award amounts are not specified in the solicitation.

• Cost share requirements are not specified in the solicitation.

ARPA-H reserves the right to:

• Fund proposals in phases

• Segregate portions into pre-priced options

• Make partial awards

• Make no awards at all

What could I use the funding for?

Funding supports the integrated development of a Measure–Model–Modulate system for critical illness, including:

TA1 – Measurement

• Biomarker discovery and validation

• Tissue-specific immune monitoring technologies

• Data generation suitable for mechanistic modeling

TA2 – Modeling

• Mechanistic computational digital twin models

• In silico clinical trials

• FDA-compliant digital twin platforms

TA3 – Modulation

• Repurposing FDA-approved immunomodulatory therapies

• Development of novel immune-modulating approaches (if justified)

• Pre-clinical and clinical validation

Associate Performers (AP1, AP2, AP3)

• Data infrastructure and standards (AP1)

• Regulatory-compliant digital twin validation environment (AP2)

• ICU-realistic validation infrastructure and clinical trial support (AP3)

Projects must focus on immuno-inflammatory mechanisms common across critical illness and integrate into ICU workflows.

Are there any additional benefits I would receive?

CIRCLE performers will receive:

• Access to ARPA-H resources supporting regulatory approval

• Access to clinical trial consortia to accelerate FDA approvals

• Integration into a shared CIRCLE database that will ultimately become a public resource

• Structured cross-team collaboration across TAs and APs

• Government Purpose Rights (GPR) for certain deliverables

• Potential flexible IP treatment for commercially sensitive technologies (with approval)

Open-source development is highly encouraged using permissive licenses (e.g., CC-BY, BSD, MIT, Apache 2.0).

What is the timeline to apply and when would I receive funding?

Key deadlines (Eastern Time):

• Proposers’ Day: Wednesday, March 11, 2026

• Solution summary submission: Monday, March 30, 2026, 1:00 PM

• Questions & Answers (Q&A) submission: Friday, May 22, 2026, 1:00 PM

• Proposal submission: Thursday, May 28, 2026, 1:00 PM

Deadlines will be strictly enforced.

Period of Performance

The program includes milestones extending up to 5 years from award date, including:

• 3 months: Coordination plans and metric establishment

• 6 months: Research plan finalization and approvals

• 1–3 years: Model development, calibration, validation

• 4–5 years: Integrated system validation and first-in-human adaptive platform trial

Funding timing after selection is not specified in the solicitation.

Where does this funding come from?

Funding comes from:

• Advanced Research Projects Agency for Health (ARPA-H)

• Resilient Systems Office (RSO)

Solicitation Number: ARPA-H-SOL-26-139 (Amendment 1)

Awards will be issued as Other Transaction (OT) agreements.

Who is eligible to apply?

Eligible proposers include:

• Universities

• Non-profit organizations

• Small businesses

• Other than small businesses

FFRDCs and U.S. Government entities:

• May not respond as prime or sub-performers

• May engage with ARPA-H separately under specific conditions

Non-U.S. entities:

• May participate if compliant with applicable laws and regulations

• Awards will not be made to entities organized under the laws of a covered foreign country, foreign entities of concern (per CHIPS and Science Act), or individuals involved in a Malign Foreign Talent Recruitment Program.

All proposers must disclose Organizational Conflicts of Interest (OCI).

What companies and projects are likely to win?

Selectable proposals will:

• Directly address CIRCLE’s goals and objectives

• Integrate measurement, modeling, and modulation components

• Present realistic commercialization plans (for TA proposals)

• Demonstrate regulatory strategy and transition planning

• Provide strong interdisciplinary integration

• Include complete and realistic budgets

Proposals are evaluated individually (not comparatively) based solely on published evaluation criteria.

Budgets that are unrealistically high will be viewed unfavorably.

Are there any restrictions I should know about?

Key restrictions include:

• Funding cannot be used for human subjects research until all approvals are granted.

• Animal research requires IACUC approval prior to incurring costs.

• Performers must comply with federal human subjects and animal welfare regulations.

• Certain software and system components must be delivered with Government Purpose Rights.

• ARPA-H may impose publication restrictions if research involves sensitive information.

• All APIs must use open standards (e.g., REST, JSON, JSON-LD) unless otherwise approved.

• Existing data standards (e.g., HL7, FHIR, DICOM, LOINC, SNOMED CT) must be used where applicable.

Non-conforming proposals may be rejected without further review.

How long will it take me to prepare an application?

The solicitation warns that parts of the submission process may take from one business day to one month to complete.

Given the complexity of:

• Multi-TA integration

• Regulatory planning

• Data standards compliance

• Commercialization strategy

• Cross-team coordination

Companies should expect a significant preparation effort. The exact preparation time will depend on team readiness and prior integration planning.

How can BW&CO help?

BW&CO can support you by:

• Structuring your technical narrative around the Measure–Model–Modulate framework

• Stress-testing alignment with evaluation criteria

• Translating complex science into a fundable ARPA-H narrative

• Designing commercialization and transition strategies

• Supporting budget justification and value positioning

• Coordinating multi-institutional team structures

• Preparing for OT negotiation

CIRCLE is a systems-level, high-integration program. Positioning and coherence across TAs and AP interfaces will be critical.

How much would BW&CO Charge?

We have both fractional engagements ($250 an hour) and full engagements for submitting the Solution Summary ($7,500) available.

Additional Resources

Review the solicitation here.

ARPA-H SSO: “AGENTIC AI-ENABLED CARDIOVASCULAR CARE TRANSFORMATION” (ADVOCATE)

Below is a brief summary. Please check the full solicitation before applying (link in resources section).

Executive Summary:

ARPA-H is now accepting proposals for ADVOCATE: Agentic AI-Enabled Cardiovascular Care Transformation, a major new Innovative Solutions Opening (ISO) focused on deploying autonomous, FDA-regulated clinical AI agents for cardiovascular disease (CVD) care at national scale.

This program is designed to fund teams that can build, validate, and deploy patient-facing AI agents, paired with independent supervisory AI, and integrate them directly into real healthcare systems. Selected performers will work closely with FDA, large health systems, and ARPA-H leadership to establish a blueprint for scalable, reimbursable agentic AI in healthcare. A Solution Summary is mandatory and is due February 27, 2026, at 5:00 PM EST. Full proposals are by invitation only and are due April 1, 2026, at 5:00 PM EST.

How much funding would I receive?

• Total award size: Not specified in the solicitation

• Number of awards: Multiple awards anticipated

• Funding mechanism: Other Transaction (OT) Agreements

• Program length: Up to 39 months

  • Phase 1A: 12 months

  • Phase 1B: 12 months (option)

  • Phase 2: 15 months (option)

What could I use the funding for?

Funding must support development, validation, and deployment of agentic AI systems for cardiovascular care, aligned to one or more of the following Technical Areas (TAs):

TA1 — CVD Agent (Patient-Facing Clinical AI)

• Autonomous or semi-autonomous AI agents that:

  • Provide diagnostic and treatment assistance

  • Adjust prescriptions for CV conditions (FDA medical device)

  • Integrate real-time EHR and wearable data

  • Deliver 24/7 outpatient care management

• Clinical reasoning using multimodal inputs (text, voice, image, video)

• FDA regulatory engagement and authorization

• Deployment into real health systems for scalability studies

TA2 — Supervisory Agent (AI Oversight & Control)

• Disease-agnostic AI that:

  • Monitors safety, accuracy, uncertainty, and risk of clinical AI

  • Enables real-time control and auditability

  • Supports FDA Medical Device Development Tool (MDDT) qualification

• Continuous post-market monitoring functionality

• Strong preference for open-source solutions

TA3 — Scaled Implementation (Health Systems Only)

• Integration of TA1 and TA2 agents into live clinical workflows

• Access to EHR production and pre-production environments

• Execution of large-scale Scalability Studies

• Clinical outcome, cost, and reimbursement evidence generation

Are there any additional benefits I would receive?

Selected teams receive:

• Direct engagement with FDA throughout development

• Access to real EHR data, clinicians, and patients (via TA3 performers)

• Participation in large, ARPA-H-funded scalability studies

• Validation by an independent IV&V partner

• Visibility with payers and CMS-relevant evidence generation

• Potential facilitation of investor engagement by ARPA-H

What is the timeline to apply and when would I receive funding?

Key dates (firm):

• Posting date: January 13, 2026

• Proposers’ Day: January 23, 2026 (8:30 AM – 5:00 PM EST)

• Proposers’ Day registration deadline:

  • In-person: January 21, 2026, at 5:00 PM EST

  • Virtual: January 21, 2026, at 5:00 PM EST

• Solution Summary due: February 27, 2026, at 5:00 PM EST

• Full proposal due (if invited): April 1, 2026, at 5:00 PM EST

Funding timing after submission is not specified and is contingent on negotiations and down-selection decisions.

Where does this funding come from?

• Agency: Advanced Research Projects Agency for Health (ARPA-H)

• Office: Scalable Solutions Office (SSO)

• Authority: Other Transaction (OT)

Who is eligible to apply?

Eligible applicants include:

• U.S. startups and growth-stage companies

• Universities and academic teams

• Non-profit organizations

• Non-federal research organizations

Not eligible:

• Federally Funded Research and Development Centers (FFRDCs)

• Federal government entities or employees (as performers)

• Entities from covered foreign countries or foreign entities of concern

• Organizations with unmitigable ARPA-H conflicts of interest

TA3 applicants cannot apply to TA1 or TA2.

What companies and projects are likely to win?

ARPA-H is explicitly seeking teams that:

• Are building agentic (not rules-based) clinical AI

• Can meet FDA medical device or MDDT requirements

• Have real experience integrating with EHRs and health systems

• Can demonstrate a path to non-inferiority vs cardiologists

• Are prepared for open data sharing and multi-party collaboration

• Can scale beyond pilots into national deployment

Incremental clinical decision support tools are unlikely to be competitive.

Are there any restrictions I should know about?

Key restrictions include:

• Foundation models cannot be developed from scratch

• Solutions must be interoperable with other agents

• Clinical AI must pursue FDA authorization or qualification

• Extensive data-sharing and collaboration are mandatory

• Foreign talent, ownership, or funding risks are heavily scrutinized

• TA1 and TA2 proposals must remain technically independent

How long will it take me to prepare an application?

• Solution Summary: ~2–4 weeks for competitive teams

• Full Proposal: ~6–10 weeks if invited

Team formation, regulatory strategy, and data architecture must be addressed early.

How can BW&CO help?

BW&CO helps teams:

• Translate ADVOCATE requirements into a clear, fundable narrative

• Position technical capabilities against TA-specific metrics

• Shape FDA and commercialization strategy language

• Design compliant multi-party teaming structures

• Avoid common ARPA-H disqualifiers

How much would BW&CO Charge?

Fractional support is $300 per hour.

For startups, we offer a discounted rate of $250 per hour to make top-tier consulting more accessible while maintaining the same level of strategic guidance and proposal quality.

Additional Resources

Review the solicitation here.