Atom Therapeutics Launches Phase 2 Trial of ABP-745 for Atherosclerotic Cardiovascular Disease
Key Insights
Atom Therapeutics (search) received FDA approval to launch a multi-regional Phase 2 trial of ABP-745, a novel anti-inflammatory agent targeting atherosclerosis (search).
ABP-745 inhibits the NLRP3 inflammasome (search) and demonstrated up to 56.1% reduction in aortic plaque area in mouse studies, with over 75% reduction when combined with statins (search).
The oral drug offers advantages over colchicine with a wider therapeutic safety window and no risk of drug-drug interactions.
Atom Therapeutics (search) announced FDA approval of a Phase II clinical trial application for ABP-745, a novel anti-inflammatory agent designed to treat atherosclerotic cardiovascular disease (search) (ASCVD). The clinical-stage biotechnology company has launched a multi-regional Phase II trial globally, marking a significant expansion of the drug's therapeutic applications beyond its current development for acute gout (search).
Addressing a Critical Medical Need
Atherosclerosis (search) represents a major global health burden, causing approximately 18 million deaths worldwide each year through cardiovascular diseases. The condition involves a complex pathological process where risk factors including hypertension, hyperlipidemia, hyperglycemia, and chronic inflammation damage the vascular endothelium. This damage prompts the deposition and oxidation of low-density lipoprotein (LDL) and cholesterol, triggering local inflammatory responses that lead to foam cell formation and lipid-rich plaque development.
The progression ultimately results in vascular narrowing, hardening, reduced elasticity, and potential plaque rupture. When unstable plaques rupture, they trigger thrombosis and acute vascular stenosis, potentially causing severe outcomes including myocardial infarction (search), stroke (search), and death.
Current Treatment Limitations
Existing atherosclerosis (search) treatments primarily rely on lipid-lowering therapies, including statins (search), ezetimibe, and PCSK9 inhibitors (search). However, precise targeted intervention against inflammation pathways associated with plaque formation has not yet been achieved. Chronic inflammation participates in every stage of atherosclerosis, with inflammatory mediators further aggravating endothelial injury, promoting lipid deposition, increasing plaque instability, and elevating rupture risk.
Colchicine became the first anti-inflammatory drug approved by the FDA in 2023 for cardiovascular disease (search) treatment. When added to standard lipid-lowering therapy, colchicine reduced the risk of major adverse cardiovascular events (MACE) by 31% through its anti-inflammatory mechanism. Recent clinical studies demonstrated that colchicine combined with standard treatment significantly reduces atherosclerotic plaque burden, with 1% regression in plaque volume associated with a 25% reduction in MACE odds.
Despite these benefits, colchicine's clinical application remains limited due to its narrow therapeutic window, which restricts dosage, and potential for drug-drug interactions. Co-administration with certain statins (search) can increase rhabdomyolysis risk, limiting broader clinical use.
ABP-745's Therapeutic Advantages
ABP-745 offers several advantages over existing anti-inflammatory treatments. The orally administered drug poses no risk of drug-drug interactions, and animal studies demonstrate a significantly wider therapeutic safety window compared to colchicine.
The drug's mechanism of action targets the NLRP3 inflammasome (search), suppressing inflammatory cell recruitment to plaque sites and potently inhibiting multiple key inflammatory cytokines, including IL-1β (search), IL-6, IL-18 (search), TNF-α (search), and CRP (search). This comprehensive approach covers the full inflammatory cascade of atherosclerosis (search) from endothelial injury to plaque rupture.
Preclinical Efficacy Data
Mouse studies revealed impressive efficacy results for ABP-745. Administration of the drug resulted in up to 56.1% reduction in aortic plaque area compared with the model group. In combination therapy studies, ABP-745 with statins (search) reduced aortic plaque area by more than 75%, demonstrating robust plaque-lowering effects.
Clinical Development Progress
ABP-745 has completed Phase I trials in the United States and China, establishing a favorable safety, tolerability, and pharmacokinetic profile. The drug is currently advancing through a multi-regional Phase II trial for acute gout (search) flares across the United States, Australia, and China.
Dr. William Dongfang Shi, Founder, Chairman and CEO of Atom Therapeutics (search), commented, "ABP-745's entry into Phase II clinical trials for atherosclerosis (search) represents a pivotal milestone, marking its expansion into diseases driven by chronic inflammation. This milestone enables Atom Therapeutics to establish a strategic foothold in the dual therapeutic areas of metabolism and cardiovascular diseases, thereby substantially strengthening the company's core competitive edge in inflammatory diseases."
Company Pipeline
Atom Therapeutics (search) focuses on developing best-in-class small molecule therapeutics for inflammatory and metabolic diseases. The company's lead product, lingdolinurad (ABP-671), is in late-stage clinical development for chronic gout (search) treatment, while ABP-745 advances through global Phase 2 trials for both acute gout (search) and now atherosclerotic cardiovascular disease (search).