PROJECT ABSTRACT East River BioSolutions is developing novel cell culture substrates aimed at improving predictive in vitro models of idiopathic pulmonary fibrosis (IPF) to empower the investigation of IPF pathobiology and to accelerate drug development and testing of new effective IPF drugs. IPF is a devastating, intractable, and life-threatening interstitial lung disease characterized by obliteration of pulmonary alveoli and progressive loss of respiratory function. Over 50,000 new cases of IPF are diagnosed each year. Median survival is 3–4 years, and annual mortality in the US exceeds 40,000. The etiology and pathogenesis of IPF remain largely unknown. Predictive animal and in vitro models of IPF for basic science research and drug development/testing are severely lacking, leaving a significant need and market opportunity for physiologically relevant experimental in vitro models and tools that enable quantitative mechanistic studies of IPF. This Phase I SBIR will bring a much-needed commercial research tool into IPF research in the form of a fully humanized 3D cell culture platform comprised of intact extracellular matrix (ECM) that recapitulates the IPF disease environment in vitro. The technological innovation is the set of proprietary methods for isolating acellular fibrotic human lung matrix with the intact structure, composition, and biomechanics associated with human IPF lung tissue. The associated long term goal is development and validation of a standard fully humanized fibrotic lung ECM scaffold (3D cell culture substrate) for predictive in vitro models of IPF in order to greatly reduce dependence on animal models and enable more meaningful and relevant results for scientists working to bring new life-saving IPF drugs to market. The hypothesis for Phase I is that fibrotic human lung ECM scaffolds can recapitulate the disease-specific cellular environment of human IPF with approximately 80% similarity to the proteomic and biomechanical properties of fibrotic lung tissue, thereby enabling significantly more relevant and predictive in vitro testing of novel IPF drugs. Specific aims are to determine primary molecular components and biomechanical properties of fibrotic lung ECM scaffolds and assess fibrotic scaffolds’ ability to support diseased fibroblast phenotype and IPF drug testing. Once Phase I aims are achieved, assessing consistency of manufactured lots will be essential for commercialization. Thus, in Phase II, we will assess lot-to-lot consistency by quantitative quality control assays to inform development of a commercial manufacturing process. East River Bio will then make fibrotic ECM scaffolds commercially available through its online marketplace to scientists and companies in need of predictive IPF disease models for drug discovery and developmental testing aimed at improving treatment options for the more than 100,000 sufferers of IPF. This product will become part of the rapidly growing cell culture market, valued at $7.5B in 2016 and estimated to reach $11.3B by 2022.

Narrative In this Phase I SBIR, East River BioSolutions plans to develop a tissue-specific biomaterial that will help scientists build more predictive in vitro models of pulmonary fibrosis, thus enabling more accurate and actionable results aimed at accelerating drug development towards more effective treatment options. Predictive models for pulmonary fibrosis drug development and testing are lacking, thus leaving a significant need for experimental models enabling quantitative and mechanistic studies. The ability to conduct more biologically faithful research will enable deeper scientific understanding by providing researchers with the ability to increase high-impact discoveries toward saving patient lives, providing enormous potential to improve health outcomes.