Data on novel IL-1 inhibitor protein for topical treatment of dry eye disease published

(Press-News.org) Cambridge, MA, February xx, 2013 – Eleven Biotherapeutics, a biopharmaceutical company creating novel and differentiated protein-based biotherapeutics, has published preclinical data in Proceedings of the National Academy of Sciences (PNAS) showing beneficial effects of EBI-005, the first rationally-designed topically administered IL-1 protein for the treatment of ocular diseases. In the paper entitled "Design of a superior cytokine antagonist for topical ophthalmic use," the scientists, including drug developers from Eleven Biotherapeutics and collaborators from Howard Hughes Medical Institute and Stanford University School of Medicine, describe how EBI-005 was designed to specifically bind more tightly to its target than IL-1Ra providing a dramatic increase in potency in vivo. EBI-005 was also shown to have substantially greater stability, potentially providing the convenience of room temperature storage.

"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.

### About Dry Eye Disease 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.

About EBI-005 Eleven Biotherapeutics' lead product candidate, EBI-005, is a novel, interleukin-1 receptor antagonist currently in Phase 1 clinical development as rationally designed topical protein for the treatment of inflammatory diseases at the surface of the eye. The mechanism of action for EBI-005 was validated in a clinical proof-of-concept study in which IL-1 blockade was generally safe and well-tolerated with significant improvements in both signs and symptoms of dry eye disease. EBI-005 has been designed to have superior physical, pharmaceutical and therapeutic properties including topical ophthalmic administration for the treatment of ocular diseases including dry eye and severe ocular allergy. In preclinical studies, EBI-005 demonstrated optimal properties for the treatment of dry eye disease, such as high potency, very low systemic exposure, which minimizes the potential for adverse effects and thermal stability, providing for a room-temperature stabile product.

About Eleven Biotherapeutics Eleven Biotherapeutics creates novel and differentiated biotherapeutics: first-of-a-kind protein-based drugs with significantly improved physical, pharmaceutical, and therapeutic benefits. The company's AMP-Rx™ product engine brings capabilities beyond conventional approaches for making protein therapeutics, opening up new territory for the products to have novel structures, enhanced biophysical properties, and more effective targeting in disease pathways. Eleven's success is built on designing proteins 'fit for purpose' that are rationally designed to have ideal therapeutic characteristics and result in best-in-class biotherapeutic products for a wide range of diseases. The Cambridge, Mass.-based company was founded in 2010 by life science investors Flagship Ventures and Third Rock Ventures and world-renowned scientific experts. For more information, please visit www.elevenbio.com.