One Brave Idea is interested in a variety of scalable traditional and non-traditional phenotypes as entry points into new biology, as contributors to biomarker signatures that stratify individuals for clinical or translational research, and as clinically informative assessments.

Our latest Phenotype Phorum grappled with the related challenge of new biomarker discovery for the clinical development and regulatory approval of novel therapeutics. We welcomed three speakers from the NIMBLE Consortium (Non-Invasive Biomarkers of Metabolic Liver Disease): its academic and industry co-chairs, Dr. Arun Sanyal (Prof. of Medicine, Virginia Commonwealth University) and Dr. Roberto Calle (Executive Director, Pfizer Internal Medicine Research Unit), as well as Dr. Tania Kamphaus (Scientific Program Manager, FNIH).

The burden of NASH, or Non-Alcoholic Steatohepatitis, is rapidly increasing: it now affects 5% of the US population, including 600,000 patients with NASH-related cirrhosis. While NASH is the subject of intense R&D efforts, a critical barrier to clinical development is the fact that the gold standard for disease activity and staging is a liver biopsy, which suffers from significant morbidity and mortality, sampling variability and inter-observer variability, and high resource requirements.

To address this challenge, the NIMBLE Consortium was created as a pre-competitive, public-private partnership between FNIH, academia and industry to develop non-invasive biomarkers or biomarker panels that can accelerate the development of novel NASH therapeutics. The first phase is to retrospectively validate a subset of the available imaging, functional and circulating biomarkers, with meticulous attention to QC and correlation with available clinical factors, outcomes and biopsies. From these studies, biomarkers will be nominated for further prospective study and potential FDA qualification for specific “contexts of use” (COU).

NIMBLE is part of FNIH’s Biomarkers Consortium, which supports public-private collaborations in several disease areas. In its 12 years, the Biomarkers Consortium has successfully qualified a novel clinical safety biomarker, and developed 9 clinical tools that have contributed to the development of 14 therapeutics. This impressive track record highlights the importance (and challenges) of convening multi-stakeholder teams, and driving milestone-based team science with a pre-competitive framework for intellectual property.