ABP-745 is being developed for heart failure with preserved ejection fraction (HFpEF), a form of heart failure primarily characterized by impaired cardiac diastolic function. HFpEF is generally defined by a left ventricular ejection fraction (LVEF) of ≥50%, accompanied by symptoms and/or signs of heart failure and objective evidence of elevated cardiac filling pressures or relevant structural or functional cardiac abnormalities. Its major clinical manifestations and consequences include exertional dyspnea, fatigue, pulmonary congestion, edema, recurrent heart failure hospitalizations, and an increased risk of death. Renal dysfunction, atrial fibrillation, pulmonary vascular and right ventricular involvement, and frailty may further compromise patients’ quality of life [1].

HFpEF accounts for approximately 50% of all patients with HF. Approximately 32 million people worldwide are affected by HFpEF, including approximately 3.4 million patients with HFpEF in the United States. Patients with HFpEF experience an average of approximately 1.4 hospitalizations per year, with an annual mortality rate of approximately 15% and a 5-year mortality rate of approximately 50% [2, 3].

Inflammation, adverse myocardial remodeling and fibrosis are important disease drivers in HFpEF. Cardiometabolic comorbidities, including obesity, hypertension, and diabetes, may promote chronic inflammation and coronary microvascular dysfunction, leading to cardiomyocyte stiffness, cardiac fibroblast activation, and excessive extracellular matrix deposition [4, 5]. Approximately half of patients with HFpEF exhibiting left ventricular hypertrophy or concentric remodeling [6].

Historically, few therapies improved outcomes in HFpEF. Empagliflozin (February 2022) and dapagliflozin (May 2023) are approved by the FDA to reduce the risk of cardiovascular death and heart failure hospitalization in adults with heart failure across the ejection fraction spectrum, including HFpEF [7, 8]; the nonsteroidal mineralocorticoid receptor antagonist finerenone was subsequently approved (July 2025) for adults with heart failure and LVEF ≥40% [9]. Despite these advances, residual morbidity and mortality remain high, and treatments are complicated by the management of congestion and comorbidities [1].

Notably, Colchicine significantly improved Kansas City Cardiomyopathy Questionnaire (KCCQ) scores in a self-controlled before-and-after clinical study of patients with HFpEF [10]. Furthermore, a real-world study using the TriNetX database found that colchicine treatment was associated with significantly lower 1-year and 3-year all-cause mortality among patients with HFpEF and coronary artery disease [11].

ABP-745 is a novel small-molecule drug. It is a chemical analogue of colchicine, developed by structural optimization using colchicine as the lead compound, with the aim of preserving its potential therapeutic effects while improving safety and reducing clinical adverse effects. Like colchicine, ABP-745 has multiple mechanisms of action, including anti-inflammatory effects, attenuation of adverse myocardial remodeling and fibrosis.

In preclinical studies using HFpEF models induced by hypertension, obesity, or metabolic dysfunction, ABP-745 improved cardiac diastolic function, attenuated adverse cardiac remodeling, and reduced myocardial fibrosis, addressing key pathophysiological features of HFpEF. In addition, ABP-745 reduced the heart failure biomarker NT-proBNP, suppressed the inflammatory marker CRP, and improved exercise capacity in animal models of heart failure.