Novel Cyclic Peptide for Therapy of Autoimmune Uveitis

Gilon Chaim, HUJI, Faculty of Science, The Institute of Chemistry
Hoffman Amnon, HUJI, School of Medicine - IMRIC, School of Pharmacy- Institute for Drug Research
Lazarovici Philip, HUJI, School of Medicine - IMRIC, School of Pharmacy- Institute for Drug Research


Uveitis is inflammation inside the eye, specifically affecting one or more of the three parts of the eye that make up the uvea. It is induced by eye infiltration of T lymphocytes capable of recognizing retinal antigens. Uveitis is estimated to be responsible for approximately 10%-20% of blindness in the United States. Its global treatment market was valued at $478 million in 2018, and is projected to reach $687 million by 2026, registering a Compound Annual Rate of Growth (CAGR) of 4.6% from 2019 to 2026.

Today, uveitis is treated mostly by steroids and immunosuppressive medications, which have significant unwanted side effects. Therefore, there is an unmet clinical need to develop novel "corticosteroid like" drugs, targeting activated T cell lymphocytes which infiltrate the eye.

Calreticulin is a membranal protein of activated T lymphocytes involved in inflammation, by increasing lymphocyte intracellular calcium and modulating gene activity. The invention presents a novel corticosteroid partial mimetic cyclic peptide, an antagonist of Calreticulin, as a potential treatment to uveitis, which may overcome the challenges of the current treatments.

Our innovation
The suggested new drug for uveitis is a novel backbone cyclic peptide which acts by inhibiting the Calreticulin function. Calreticulin is expressed at the cell surface of activated human peripheral blood T lymphocytes. Its level increases after inflammation, making Calreticulin an important anti-inflammatory target. The researchers developed a lipophilic prodrug of the peptide with enhanced properties to permeate through biologic membrane, thus enabling different administration modalities including oral administration.

Uveitis is mostly treated today by corticosteroids. Although their side-effects of long-term high dosage is well known to clinicians, corticosteroids are still used, as they have a profound effect on decreasing inflammation. Despite attempts to dissociate the molecular activities of corticosteroids, it has not been possible to produce a steroid that has profound anti-inflammatory effects without long-term detrimental effects.

The present invention for the treatment of uveitis aims to keep the therapeutic effect of corticosteroids, without the unwanted side effects. It suggests a novel peptide that demonstrates a corticosteroid-like activity, in a more specific mode of action which may reduce the side effects. In preliminary studies using EAU mice model, repeated treatment using a lead peptide reduced inflammatory response by 50%, measured by EAU retinal score.

Contact for more information:

Keren-Or Amar
VP, Business Development, Healthcare