"To date, blocking of IL-1 has only taken the conventional form of proteins as injectable therapies." said Thomas M. Barnes, Vice President of Discovery at Eleven Biotherapeutics and lead author of the PNAS publication. "These published data reflect the basis of our innovative approach to rationally design proteins with ideal therapeutic properties, including the specificity to target and block IL-1 providing localized treatment of ocular diseases through topical administration."
"EBI-005 is unique in that it is rationally designed to be a topically-administered protein with IL-1α and IL-1β blocking capabilities and other ideal pharmacologic and pharmaceutical properties," said Abbie Celniker, PhD, Chief Executive Officer of Eleven Biotherapeutics. "We are currently evaluating the potential of EBI-005 in a multi-center Phase 1b clinical study in patients with dry eye disease and plan to report top line data in the second half of 2013."
Key findings include:
- EBI-005 binds to its target, IL-1R1, 85-fold more tightly than IL-Ra, translating into a 100-fold increase in potency in vivo.
- EBI-005 is more thermally stable than IL-1Ra, indicating potential for a room temperature-stable product.
- EBI-005 has been rationally designed by chimerizing two IL-1 receptor ligands, IL-1β and IL-1Ra, to create an optimized receptor antagonist, for topical ocular administration.
- As a rationally-designed antagonist, EBI-005 represents a novel approach to therapeutic design that can potentially be exploited for other proteins in the IL-1 and FGF families.
Dry eye disease (DED) is an ocular surface inflammatory condition caused by a dysfunction of tears. The dysfunction can occur through decreased tear production or excessive tear evaporation, both of which result in drying of the eye surface (desiccating stress). The stressed ocular surface induces an inflammatory cascade regulated by IL-1. Dry eye disease affects approximately 10% of individuals between 30 to 60 years of age, and up to 15% of those over 65. Despite its prevalence and impact on quality of life, dry eye disease is under-diagnosed, under-treated, and has few safe and effective treatment options.