Novel Cyclic Peptide Drug to Inhibit MyD88 for Autoimmune Diseases and Cancer

Nussbaum Gabriel, HUJI, Faculty of Dental Medicine, Institute of Dental Sciences
Gilon Chaim, HUJI, Faculty of Science, The Institute of Chemistry
Hoffman Amnon, HUJI, School of Medicine - IMRIC, School of Pharmacy- Institute for Drug Research

Development of a novel cyclic peptide drug to inhibit MyD88 as a key signalling molecule in innate immunity, with application to autoimmune central nervous system disease



Autoimmune disease, Inflammation, Oncology

Development Stage

In vitro and preclinical animal model proof of concept; ongoing research

Patent Status

PCT application filed


Unmet medical need in autoimmunity and oncology


MyD88 is a central protein in the signalling of innate immune receptors and receptors of the IL-1 superfamily.

Absence of MyD88 is protective in multiple models of autoimmunity, sepsis, and inflammation related cancer.

Activating mutations are responsible for driving proliferation in most of Waldenstrom Macroglobulinemia lymphoma patients.

Our Innovation

We developed a metabolically stable cyclic peptide based on a specific short sequence of the MyD88 TIR domain. This compound blocks activation of inflammatory signalling downstream of TLR and IL1 receptors. Activity is through binding to the TIR domain of MyD88 and inhibiting MyD88 multimerization.
The compound significantly reduces clinical disease in the animal model of Multiple Sclerosis.

Development Milestones

·         Seeking funding for development of lead compound towards an IND application. This will include preclinical toxicity, PK studies, formulation and finalization of CMC package.

The Opportunity

▪       MyD88 is an attractive target for controlling pathological inflammation due to its central role in signaling of the IL-1 receptor family and the TLRs.

▪       We selected a lead drug candidate that blocks MyD88 multimerization and reduces clinical scores in the EAE model.

▪       MyD88 is an attractive target for treatment of lymphoma patients carrying the MyD88 L265P mutation.  

Researcher Information

Gabriel Nussbaum, MD, PhD

gabrieln@ekmd.huji.ac.il  ·  +972-2-675-8581  ·

Patent Status

Published WO 2017/212477 A1

Contact for more information:

Ariela Markel
VP, Business Development, Healthcare