Advancing Soluble Epoxide Hydrolase Inhibitors Through the Valley of Death into Phase 1 Clinical Trials for Treating Painful Diabetic Neuropathy by Utilizing University Partnerships, Collaborations, and NIH Support

• DOI: 10.1096/fasebj.30.1_supplement.1272.6
• Publication Date: 2023-11-26T16:51:37Z
• Authors: Cindy McReynolds; William K Schmidt; Karen Wagner; Bruce D Hammock
• Keywords: Epoxide hydrolase 2

Soluble epoxide hydrolase (sEH) inhibitors function to stabilize biologically active lipid metabolites responsible for regulating homeostatic biological processes. The presence of these beneficial in tissues and their metabolism by sEH into less diols was first reported 30 years ago, many subsequent advances were facilitated several academic laboratories, principally University California at Davis. These efforts led the identification a large chemical library potent inhibitors. Researchers correlated enzyme potency with vivo efficacy using Ki target occupancy identify lead compounds that then tested variety models identified as potential promising therapy human pathologies including but not limited pain, seizure, chronic obstructive pulmonary disorder, arthritis. Consequently, research positioned translation clinical development. EicOsis formed incorporated license technology from navigate through ‘Valley Death’ – term coined describe funding challenges between basic proof humans. In order move this stage, successfully used creative strategies capitalized on small business’ ability quickly efficiently, leveraged existing collaborations advance optimization start‐up environment. characterized physical properties found they had poor solubility high melting point. Slight modifications structure significantly lowered point improved which resulted new IP. tested, either in‐house or collaborators, traditional safety, PK pain studies, well assays differentiated peripherally acting those central nervous system. Ultimately, restricted candidate back‐up is both centrally active. Both have an safety profile rodents exceeding FDA approved neuropathic drugs, opioids, NSAIDs, without adverse effects system, cardiovascular GI Preclinical data also indicate there unlikely be addiction liability. Here, we present overview results culminated successive rounds non‐dilutive NIH support development Phase 1 trials healthy volunteers. Given represent very novel drug still largely unknown investors venture capital community, provides essential future 2 proof‐of‐concept diabetic painful neuropathy. Support Funding Information R43/44ES025598UH2NS094258