Multi-Cytokine Inhibitor Platform

Our proprietary multi-cytokine platform generates rationally designed composite peptides that selectively block key cytokines at the shared receptor level targeting pathogenic cytokine redundancies and synergies while preserving non-pathogenic signaling.

This approach provides multi-cytokine inhibition at the receptor level and is expected to avoid the broad immuno-suppression and off-target safety liabilities of JAK inhibitors. Many immune-mediated diseases are driven by the same combination of dysregulated cytokines, and we believe identifying the key cytokines for these diseases will allow us to target and develop customized treatment strategies for multiple autoimmune diseases.

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Most MABs are targeted against one cytokine and do not address the disease pathology adequately if more than one cytokine is implicated in the disease process. JAK inhibitors lack specificity and inhibit the JAK/STAT signaling pathway that is utilized by all the cytokines regardless of their involvement in the disease. As the result, this class of compounds are often associated with serious side effects. Our peptides selectively block multiple disease driving cytokines while maintaining the healthy immune balance through the normal function of other family members.

cytokine diagram

Equillium's Multi-Cytokine Inhibitors Block the Pockets in the Common Receptor

EQ101 is a first-in-class, tri-specific inhibitor of IL-2, IL-9 and IL-15, three inflammatory cytokines implicated in multiple diseases. It selectively blocks those three key pathogenic cytokines while preserving non- pathogenic signaling related to IL-4, IL-7 and IL-21 and has demonstrated clinical proof-of-concept as a novel cytokine inhibitor through a completed Phase 1/2 study in cutaneous T cell lymphoma (CTCL), a dermato-oncology indication. EQ101 achieved its primary objective of safety and tolerability and showing clinically meaningful improvements in SWAT scores (modified severity-weighted assessment tool).

EQ101 was also shown to be well tolerated with a favorable safety profile with no drug-related SAEs and no dose-limiting toxicities. It is now Phase 2 ready in alopecia areata, a dermatological autoimmune disorder, and is Phase 2/3 ready in CTCL with open U.S. INDs for each indication, with an orphan designation for CTCL in the U.S. and Europe. EQ101 is currently formulated for intravenous administration, with subcutaneous formulation development underway. Equillium is planning to initially focus development of EQ101 in patients suffering from alopecia areata, where there are currently no drugs approved.

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thumbnail for about itolizumab video

EQ302 is a first-in-class, second generation, orally delivered stapled peptide inhibitor of IL-15 and IL-21 derived from EQ102, a subcutaneously administered molecule. It was developed by leveraging our in-silico, protein structure and molecular design expertise, and then employing clinically validated technologies to confer increased stability and permeability in the gastrointestinal (GI) tract. IL-15 and IL-21 are two cytokines central to T and B cell activity that exhibit biological synergy driving aggressive inflammatory responses in a number of gastrointestinal and skin diseases, highlighting the importance of dual inhibition.

Given the high degree of selectivity for bi-specific IL-15 and IL-21 inhibition supported by substantial pre-clinical and translational data, EQ302 is an attractive candidate for clinical testing in a variety of GI and skin diseases. The development of EQ302 also highlights the versatility and modularity of our Multi-Cytokine Platform to develop novel first-in-class therapeutic candidates with desired attributes to join a new wave of orally bioavailable, selective cytokine inhibitors.