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

The Advanced Research Projects Agency for Health (ARPA-H) is seeking innovative proposals through an Innovative Solutions Opening (ISO) under solicitation ARPA-H-SOL-26-139 to advance the CIRCLE Program, which aims to develop a Control Point Validation Engine capable of assessing, predicting, and intervening in immuno-inflammatory dysregulation before it leads to organ failure in critically ill patients. The program targets improved intensive care unit outcomes and reduced hospital stays by integrating dynamic immune monitoring, detailed patient immune state modeling, and targeted immune reprogramming interventions across three Technical Areas: TA1 for rapid, tissue-localizable immune data collection; TA2 for computational modeling of immune states; and TA3 for control point modulation and intervention. Proposals must be submitted as either Type A, covering all three Technical Areas, or Type B, focusing on one Associate Performer role, using mandatory templates provided in Attachments A through F. The submission process requires a Solution Summary by March 30, 2026, followed by a Full Proposal due by May 28, 2026, both via the ARPA-H Solution Site, with no additional questions being answered after initial postings. Proposals will be evaluated based equally on Overall Scientific and Technical Merit (50%) and Proposer’s Capabilities and Related Experience (50%), with emphasis on innovation, feasibility, risk mitigation, intellectual property structure, and the technical team’s proven expertise. The award instrument is an Other Transaction Agreement, governed by a Model OT Agreement in Attachment E, which allows proposers to propose non-administrative edits with supporting rationale—otherwise, acceptance of all terms is assumed. All proposers must be registered in SAM.gov with an active UEI and provide a good faith representation of IP ownership or licensing rights. The program spans five years and includes mandatory milestones such as establishing metrics and agreements within three months of award, finalizing research protocols within six months, and meeting annual performance targets. Payment is milestone-based via the Payment Management System, contingent on verification by ARPA-H staff, and requires compliance with human subjects research regulations, security assessments for covered personnel, and controlled information handling standards. No set-aside is in place, and awards will be made based on proposal quality and funding availability, with no cost or contract value pre-established, and proposers required to submit custom budget details through the provided workbook.