[IL2112] CXCR 7 Agonist for Fibrotic Diseases 

• First-in-class, orally available, small molecule, chemokine receptor type 7 (CXCR7) agonist for treatment of various fibrotic and autoimmune diseases.

•  Chemokines play crucial roles in many physiological and pathological processes. Chemokine receptor 7 (CXCR7) is a receptor that binds to CXCL12, a known pro-inflammatory factor under pathological conditions such as inflammation, hypoxia, tumor, autoimmune disease and it activates angiogenesis and regeneration process as a part of the repair mechanism.

• In acute tissue (e.g. lung, liver) injuries, CXCR7 is upregulated to stimulate endothelial proliferation in lung and promotes hepatocyte proliferation in liver as a part of repair process. However, with chronic injuries, CXCR7 is downregulated, leading to a decreased repair function of injured tissues and promotes binding of CXCL12 with CXCR4 in fibroblasts, which contributes to the fibrotic process.

• iLeadBMS is developing a first-in-class CXCR7 agonist that reduces CXCL12 levels and currently, there are no other CXCR7 agonists in development (in any stage), on a global basis.

• Unlike CXCR4 antagonists, which are being researched and/or developed for various inflammatory & fibrotic diseases, CXCR7 agonist can activate the β-arrestin signal which in turn activates tissue regeneration & cell proliferation function (evidence shown in cardiac research) for a potentially disease modifying properties.

• The lead candidate has favorable oral pharmacokinetic profile including a long half-life and therefore, once-a-day formulation will be possible.

• Our CXCR7 agonist demonstrated superior efficacy over reference drugs In the bleomycin mouse IPF (both prevention and therapeutic) & CCl4-induced liver fibrosis mouse models. Also, additional in vivo efficacy models including bleomycin induced skin fibrosis, kidney fibrosis, BDL liver fibrosis, PAH & ischemia reperfusion (I/R) models are in progress.

• Novel MoA allows potential expansion to a broad type of indications ranging from fibrotic diseases to autoimmune, and CNS disorders. 

• This candidate is ready for IND-enabling GLP toxicity studies.