Summary/Abstract Iron deficiency (ID) is a leading cause of anemia worldwide and affects more than 17 million children in the US alone. However, it is now recognized the even without anemia, ID adversely affects cognitive development, endocrine function, and physical and behavioral growth and development in children. While anemia in the US is prevalent in 3.4% of children ages 0.5-4 years old, the prevalence of non-anemic ID is much greater, estimated to be 15.1% in children from 12-23 months and 16.5% from 2-5 years. Ideally, a non-invasive point-of-care (POC) device to confidently diagnose ID would be of great interest to pediatricians. Hepcidin-25 has been shown to be the principal regulator of systemic iron homeostasis. Measurement of serum hepcidin is a reliable marker for assessment of iron status and can prove a valuable indicator of physiologic ID in adults and children. Urinary hepcidin is strongly correlated with serum hepcidin and would serve as an excellent marker to diagnose ID in children and adolescents employing the non-invasive POC device that we propose to commercialize. Intrinsic LifeSciences (ILS) is requesting Direct to Phase II funding to continue commercialization of a multiplexed POC lateral flow assay (LFA) to quantify urinary hepcidin normalized to urinary creatinine. We have successfully completed proof of principle research resulting in a working prototype of the LFA. To achieve this milestone, ILS contracted with a local San Diego company, NanoComposix (NCX), to utilize their ultra-bright gold nanoshell technology to dramatically enhance diagnostic sensitivity. Reader selection will be a critical next step in the commercial development of this device. End user design input will assist in selecting a suitable strip reader followed by optimization of lateral flow strip geometry for deployment in a cassette compatible with the selected reader. The hepcidin and creatinine assays will be multiplexed on a single strip, further optimization for sensitivity and precision will be undertaken and validation of the POC device will follow FDA industry guidelines for bioanalytical method validation. Our pediatric clinical collaborators will beta test the LFA POC prototype device in a research capacity to assess design control suitability before large scale manufacturing. Concurrently, ILS will procure matched serum and urine samples and perform receiver operator characteristic curve analysis to assess the diagnostic strength of the POC prototype device to predict ID. During pre-commercialization Phase IIB follow-on funding, the device would be tested in a multi-center clinical trial and the results submitted to the FDA for 510(k) clearance.

Project Narrative The consequence of untreated iron deficiency (ID) in children and adolescents can lead to irreversible neurodevelopmental delays and must be diagnosed as soon as possible. A non- invasive lateral flow Point-of-Care (POC) device, based on the quantitative measurement of urinary hepcidin, would be a novel medical advance to assist in the rapid diagnosis of ID. This POC device could cause a paradigm shift in the ability of pediatricians to rapidly diagnose and treat ID in children and adolescents and positively impact both national and global public health.