Critical illness can evolve rapidly, with a patient's immune and inflammatory responses changing faster than conventional testing can capture. Prolonged ICU stays carry significant consequences for patients and health systems. ARPA-H's CIRCLE aims to change that by giving clinicians a more continuous view of immune dynamics. The program combines advanced biological measurement, mechanistic computational modeling, and patient-specific digital twins to guide earlier and more precise intervention.

Novelna is one of three teams selected for CIRCLE's technical areas and the only of those teams led by a company. The multi-year transformative award brings together a national consortium led by Novelna. It includes 11 leading academic institutions and three industry partners, spanning immune measurement, mechanistic modeling, clinical trial design, and regulatory strategy.

INFLECT will develop a dual-channel, multiplex sensor for high-frequency, tissue-localizable immune measurement. These measurements will inform an ensemble digital twin that incorporates multiple mechanistic model structures. The digital twin will identify and rank therapeutic control points for FDA-approved and novel interventions. Together, these components form a continuous measure-model-modulate feedback loop at the bedside.

INFLECT builds on Novelna's core capabilities in proteomics, biomarker discovery, and artificial intelligence (AI), extending them from early disease detection into longitudinal monitoring and therapeutic decision support. The architecture is being developed with broader applicability in mind, so the underlying sensing and modeling capabilities may be adapted to additional immune-mediated conditions over time.

"INFLECT reflects where Novelna's platform is headed: from detecting disease earlier to understanding how biology changes over time and how those changes can guide care," said Ashkan Afshin, M.D., Sc.D., Founder and CEO of Novelna and Principal Investigator of INFLECT. "By combining proteomics, AI, continuous sensing, and patient-specific mechanistic modeling, we aim to help clinicians act earlier and more precisely for critically ill patients. We are grateful to ARPA-H for creating CIRCLE and proud to work alongside an exceptional group of academic and industry partners. Critical care is an important first application, but the underlying platform has the potential to reach far beyond the ICU."

Read the ARPA-H CIRCLE announcement here.

This research is funded, in part, by the Advanced Research Projects Agency for Health (ARPA-H). The views and conclusions contained herein are those of Novelna and should not be interpreted as representing the official policies, either expressed or implied, of the U.S. Government.