On June 6, 2025, the Advanced Research Projects Agency for Health (ARPA-H) issued Amendment 02 to its four flagship Innovation Solutions Opening (ISO) solicitations: Health Science Futures (HSF), Proactive Health Office (PHO), Resilient Systems Office (RSO), and Scalable Solutions Office (SSO). These ISOs represent the core operational arms of ARPA-H’s mission to fund transformative, high-risk, high-reward biomedical and health research. The updated solicitations reflect the agency’s intent to refine priorities, clarify expectations, and attract projects that truly stretch the frontier of what’s technically possible in health innovation.
Each ISO targets a specific axis of health advancement, from proactive care and systems resilience to scientific breakthrough and scalable distribution. Across all amendments, ARPA-H continues to emphasize solutions that are disease-agnostic, multidisciplinary, and unsuitable for traditional funding channels. Below is a summary of each mission office’s renewed direction.
Health Science Futures (HSF): Accelerating Breakthroughs at the Biological Frontier
The HSF office has reaffirmed its goal to dismantle scientific and technical bottlenecks that prevent scalable, equitable health interventions. Amendment 02 outlines a bold agenda focused on:
- Breakthrough Technologies: Funding will support paradigm-shifting approaches in maternal-fetal health, regenerative and personalized medicine, chronic disease cures, and neurobiological tools for diagnosing and treating mental health and systemic diseases.
- Transformative Tools: High interest in tools that counter off-target drug effects, biohybrid devices for restorative function, and synthetic biology approaches that enable programmable diagnosis and therapy.
- Platform Systems: Emphasis on adaptable, multi-use platforms spanning molecular delivery platforms, AI- and quantum-enabled biomolecule design, cellular engineering, and next-generation omics, to accelerate discovery and expand therapeutic reach across diverse disease states.
HSF’s update emphasizes targeting of diseases with high societal burden, including diabetes, neurodegenerative disorders, and pediatric health, while maintaining a strong preference for platform technologies and tools that transcend disease silos.
Proactive Health Office (PHO): Shifting the System from Reactive to Preventive
PHO’s latest amendment makes a strong case for moving upstream in the health continuum. The office seeks projects that proactively extend health spans and delay disease onset, with three strategic areas:
- Novel Prevention and Detection Tools: Proposals should advance low-cost, scalable sensing technologies and prophylactic strategies for early detection and prevention at the population level.
- Behavioral and Wellness Promotion: ARPA-H is interested in incentives, educational methods, and resilience-building approaches that boost mental and physical well-being.
- System-Level Innovation: Priority is given to systems that validate long-term intervention impact and new delivery or reimbursement models for preventive care.
PHO encourages disease-agnostic tools but also welcomes bold approaches to prevent and preempt high-impact conditions, including cancer, cardiovascular disease, and infectious disease.
Resilient Systems Office (RSO): Engineering Stability into the Health Ecosystem
RSO is focused on reinforcing the backbone of healthcare by funding innovations that strengthen system reliability, interoperability, and adaptability. This ISO prioritizes:
- Fortification of Systems: Proposals should deliver modular designs that improve performance durability particularly in digital health platforms and socio-technical systems.
- System Efficiency and Transparency: ARPA-H is seeking disruptive innovations that streamline workflows, enhance interoperability, and reduce cognitive and procedural friction across healthcare settings.
- Disruption Readiness: Emphasis is placed on agile interventions to stabilize healthcare delivery during health system disruptions such as cyber threats, disasters, and supply chain breakdowns.
Notably, RSO is seeking systems biology, biophysical systems, and sociotechnical innovations that address structural inefficiencies at scale, beyond clinical endpoints alone.
Scalable Solutions Office (SSO): Delivering Equitable Health at Scale
SSO’s amendment clearly defines a vision to democratize access to advanced healthcare technologies and interventions, particularly in underserved or remote areas. Key themes include:
- Healthcare Access and Affordability: Technologies that adapt to demographic and geographic constraints, such as modular diagnostics, pediatric-specific therapies, and localized care models, are strongly encouraged.
- Distribution and Delivery Innovation: Solutions that enable “last mile” delivery, remote treatment support, and scalable diagnostics are of particular interest.
- Biomanufacturing Advancements: ARPA-H is prioritizing proposals that reduce cold-chain dependencies, enhance domestic production of critical materials, and integrate predictive analytics for process optimization.
Applicants should frame their proposals around rapid innovation, infrastructure-resilient delivery systems, and cross-sector delivery models that support broad, equitable reach.
Key Dates to Know
All four ISO solicitations share the following timeline and submission structure:
- Solicitation Release: March 14, 2024
- Amendment 02 Released: June 6, 2025
- Closing Date: March 5, 2029
- Rolling Submissions: Proposers must first submit a Solution Summary and receive ARPA-H feedback. If encouraged, a full proposal must be submitted within 45 days of feedback.
Each ISO remains open on a rolling basis, allowing proposers to align submissions with internal R&D readiness and strategic objectives.
Funding and Proposal Structure
ARPA-H anticipates multiple awards under each ISO, issued as Other Transactions (OTs). Each proposal must include:
- A 20-page technical & management narrative
- A task description document
- Cost proposals, including a workbook
- An administrative & national policy compliance attachment
All entities are eligible to apply, though performers must first register in SAM.gov and obtain a Unique Entity Identifier (UEI).
Driving Human Health Forward: A National Opportunity
These ISO amendments collectively sharpen ARPA-H’s intent to fund revolutionary, not incremental, change. By doubling down on high-impact, unconventional strategies, the agency is opening new doors for researchers and developers eager to solve enduring health challenges through novel science and scalable technology.
Whether your expertise lies in synthetic biology, resilient supply chains, behavioral science, or health IT, these solicitations offer a unique platform to elevate your ideas to national relevance.
If your company has considered applying for federal funding, your federal funding journey starts here. EverGlade Consulting is a national firm that helps organizations win and manage federal awards. We offer services ranging from Pursuit, Proposal and Post-Award support to comply with federal regulations at agencies including BARDA, ARPA-H, NIH, DTRA, JPEO, DOD, DIU, DOE, and DARPA.
