CIRCLE, REST, and BREATHE. They may sound like instructions from a yoga class, but they are actually the names of programs funded by the Advanced Research Projects Agency for Health (ARPA-H). Their calming connotations stand in sharp contrast to an agency designed for speed, bold experimentation, and ambitious biomedical innovation.
Established in 2022, ARPA-H was created to pursue solutions to some of the nation’s most difficult health challenges by adopting a model inspired by the Defense Advanced Research Projects Agency (DARPA). Like its defense counterpart, ARPA-H emphasizes transformational advances over incremental progress, convening experts from government, academia, industry, and other sectors to tackle problems that have resisted conventional approaches.
Congress created ARPA-H to complement the National Institutes of Health’s investigator-initiated approach to biomedical research. Rather than broadly supporting scientific inquiry, ARPA-H was designed to pursue mission-driven solutions to defined health challenges. The Consolidated Appropriations Act, 2022 (Public Law 117-103) established the agency with its director reporting directly to the HHS Secretary, reflecting Congress’s intent to provide the flexibility and autonomy needed to pursue ambitious, time-limited initiatives. The result is a research agency that inaugural director Renee Wegrzyn described as “nimble” and current director Alicia Jackson has likened to a “time machine” for health.
The combination of autonomy and nimbleness is reflected in ARPA-H’s operating model.
Rather than funding investigator-initiated biomedical research, the agency organizes its work around clearly defined problems with measurable objectives. It pursues bold, high-risk, time-limited programs designed to achieve breakthroughs rather than incremental progress. Success is measured not simply by scientific publications but by whether projects produce solutions that change how diseases are prevented, diagnosed, or treated. ARPA-H expects some projects to fail because ambitious research inevitably carries risk. The agency emphasizes rigorous evaluation, measurable milestones, and the quick termination of unsuccessful efforts so resources can be redirected to more promising approaches.
ARPA-H’s program managers are central to this philosophy. Recruited from academia, industry, government, and other parts of the innovation ecosystem, they serve limited appointments and are responsible for identifying important health challenges, designing ambitious research programs, and assembling multidisciplinary teams to pursue them.
Program managers actively oversee their portfolios, monitor progress against defined milestones, and adjust or terminate projects based on the evidence. ARPA-H describes them as “full contact” leaders who challenge conventional thinking, quickly master new technical areas, and bring together experts from multiple disciplines to pursue breakthrough solutions.
The concept of an ARPA-style health research agency had been discussed for years before ARPA-H was established in 2022. Although the agency has sometimes been associated with President Joe Biden’s Cancer Moonshot initiative, Congress created it as a permanent component of HHS, with a mission that extends well beyond any single disease area. Its DARPA-inspired structure was designed to pursue breakthrough solutions to pressing health challenges, allowing successive administrations to apply that model to evolving national priorities.
Under the Trump administration, ARPA-H is being tasked with advancing research priorities identified through executive action. Recent executive orders have variously called on the agency to accelerate research into treatments for serious mental illness—including emerging approaches such as psychedelics—and to prioritize technologies that reduce reliance on conventional chemical crop protection tools as part of a broader effort to improve food and human health. The assignments illustrate how an agency designed around a flexible operating model can be applied to a wide range of national challenges. At BIO 2026 in San Diego in June, ARPA-H hosted an Investor & Commercialization Partner Showcase and meet-ups on fertility and lymphatics.
ARPA-H’s portfolio spans cancer, neuroscience, artificial intelligence, women’s health, infectious diseases, and other fields. Programs with names such as CIRCLE, REST, and BREATHE are memorable, but they also reflect the agency’s willingness to pursue ideas that might once have seemed too ambitious or too uncertain for traditional funding mechanisms: in these cases,Critical Illness Immunological Reprogramming and Control Point Learning Engine, Restorative & health-Enhancing Sleep Time, and Building Resilient Environments for Air and Total Health.
Andy Kilianski, an ARPA-H program manager, who oversees a portfolio focused on translating early-stage biomedical discoveries into real-world health tools, including computational biology and novel therapeutic platforms, recently posted about an ARPA-H project on LinkedIn.
In May 2026, a company in Kilianski’s portfolio, still operating in stealth mode, struck a deal with Eli Lilly worth up to $1.55 billion for its underlying technology platform. Kilianski credited ARPA-H’s due diligence process, paired with what he called the agency’s “moonshot science goals,” for helping the company de-risk its technology enough to attract that scale of investment.
In sharing Kilianski’s post, Director Jackson framed the deal as validation of the agency’s broader model. She wrote that no other federal agency could have produced this outcome, describing ARPA-H as lean, fast, and conviction-driven, willing to back science that is too applied for traditional government funding and too risky for private investors. “This is the model working exactly as designed,” Jackson said.
Indeed, such successes are exactly what ARPA-H was created to produce.
Whether ARPA-H continues to fulfill its promise remains to be seen. By design, it success will be measured not by the number of grants it awards or papers it publishes, but by whether its unconventional approach can deliver solutions to health challenges that have resisted decades of incremental progress.
