1. Project profile

Target: CCL17

Modality：mAb

Indications: Moderate to severe knee osteoarthritis pain, Chronic pain

Research phase: CMC

Cooperation demands: license out or co-development

2.GM-CSF–CCL17 axis in inflammatory OA pain and disease

Preclinical studies have shown that the granulocyte–macrophage colony-stimulating factor (GM-CSF)-chemokine (c-c motif) ligand 17 (CCL17)-CCR4 pathway is important for developing inflammation and pain;

GM-CSF drives the production of CCL17 in monocytes and macrophages through transcription factor IRF4 and demethylase JMJD3. CCL17 can indirectly result in inflammation and tissue remodeling in arthritic joints and the development of pain, requiring a contribution from prostaglandin E2 (PGE2). Blocking CCL17 via anti-CCL17 monoclonal antibodies (mAb) or CCL17 knocking-out reduced arthritis pain and joint diseases in animal models.

3.Data and results

Asset binds to CCL17, but not CCL22 protein;

Unlike GSK3858279, Asset does not bind to human CCL22, a close family member of CCL17.

Assetblocked human CCL17-induced calcium flux in HEK293 cells transfected with human CCR4 and G Protein subunit alpha 15 (GNA15).

Asset can reducepain in mouse diabetic peripheral neuropathic pain model

Asset achieved a T1/2 as long as 196 hours (8.2 days) in cynomolgus monkeys, compared to only 85.9 hours 3.6 days) for GSK3858279 in human, which was administered at 240 mg dose weekly in the Phase Ib clinical trial