ABP-745 is a novel colchicine analog with multi-faceted anti-inflammatory and anti-atherosclerotic activities, including inhibition of foam cell formation and inflammatory cell accumulation in atherosclerotic plaques. ABP-745 is currently in global multicenter Phase 2 clinical trials for treatment of atherosclerotic cardiovascular disease (ASCVD), laying a solid foundation for subsequent Phase 3 development and potentially establishing a new benchmark in the treatment of ASCVD.

Atherosclerosis is a leading cause of death worldwide, claiming approximately 18 million lives annually and remaining closely linked to major cardiovascular events such as myocardial infarction, ischemic stroke, and peripheral artery disease (PAD). At its core, the disease is characterized by the progressive accumulation of arterial plaques, driven primarily by the retention of low-density lipoprotein (LDL) and triglyceride (TG)-rich lipoproteins within the vessel wall, a process that is further exacerbated by chronic inflammation in regions of disturbed blood flow. As plaques accumulate, arterial elasticity is progressively compromised and blood flow is impaired, ultimately resulting in chronic hypoxia in vital organs such as the heart and brain [1].

Currently, pharmacological treatment of ASCVD is primarily focused on lipid lowering. Statins, as the first-line treatment, remain the cornerstone of lipid-lowering therapy. However, statins cannot directly address plaque inflammation or fully eliminate residual cardiovascular risk, and they also carry a risk of rhabdomyolysis. Substantial evidence from evidence-based medicine indicates that even when low-density lipoprotein cholesterol (LDL-C) is controlled below guideline-recommended target levels, more than 50% of patients continue to face a residual risk of cardiovascular events [2].

Colchicine (LODOCO^®, 0.5 mg once daily) has established clinical proof of concept in ASCVD. When added to standard-of-care therapy, colchicine demonstrated a 31% reduction in the risk of major adverse cardiovascular events (MACE), with no observed increase in the risk of serious infections [3]. The EKSTROM trial further demonstrated a significant reduction in atherosclerotic plaque burden, highlighting the potential of colchicine to directly address residual atherosclerotic disease [4]. However, gastrointestinal and other tolerability-related adverse effects, as well as drug-drug interactions, may limit the broader clinical adoption and patient benefit of colchicine, underscoring the need for next-generation therapies with improved tolerability [5].

ABP-745 has demonstrated broad inhibitory activity against multiple pathological processes underlying atherosclerosis including foam cell formation, inflammatory cell accumulation within atherosclerotic plaques, NLRP3 inflammasome activation, and the production and release of key inflammatory cytokines, including IL-6, IL-18, IL-1β, TNF-α, and C-reactive protein (CRP). In an ApoE^-/- mouse model, combination treatment with ABP-745 and atorvastatin reduced aortic plaque area by more than 75%, significantly greater than the 50.1% reduction observed with atorvastatin monotherapy. Furthermore, ABP-745 has no adverse drug-drug interactions with commonly used cardiovascular medications, including statins, antiplatelet agents, and β-blockers.

In Phase 1 clinical trials in both China and the U.S., ABP-745 demonstrated a favorable safety and tolerability profile. Compared with colchicine, which is approved for treating ASCVD, ABP-745 has a wider therapeutic window. It also remained safe and well tolerated at plasma concentrations exceeding 200 ng/mL, whereas significant toxic reactions were observed when plasma colchicine concentrations exceeded 5 ng/mL.