What is the clinical evidence from this study?

Study design: Other. Population: Heart failure. Intervention: HM17321 vs. Vehicle. Primary outcome: Left ventricular mass in HFpEF mice.

What does this research mean for the field?

The novel UCN2 analog HM17321 improves cardiac function, attenuates pathological cardiac remodeling, and reduces blood pressure in preclinical rodent and non-human primate models of heart failure and obesity. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.NEUTRAL.

What question did this study set out to answer?

This study aims to evaluate the cardioprotective effects of HM17321 in heart failure models, including rodent and non-human primate models.

June 7, 2026

2872-LB: Cardioprotective Effects of HM17321, a Novel UCN2 Analog, in Rodent Heart Failure Models and a Translational Nonhuman Primate Model

Key Result

HM17321 significantly reduced left ventricular mass (132.2 mg vs 177.6 mg) in HFpEF mice and reduced blood pressure (114/54 vs 140/69 mmHg) in obese rhesus monkeys compared to vehicle.

Key Points

This study aims to evaluate the cardioprotective effects of HM17321 in heart failure models, including rodent and non-human primate models.
Evaluated HM17321 in obesity and hypertension-driven HFpEF mouse model, monocrotaline-induced HF rat model, and obese rhesus monkey model.
Administered HM17321 for 2-5 weeks in rodents and 13 weeks in non-human primates.
Assessed cardiac structure and function through echocardiography and exercise capacity measurements.
In HFpEF mice, HM17321 reduced left ventricular hypertrophy (LV mass: 132.2 mg vs. 177.6 mg) and improved diastolic function (MV E/E′ ratio: 22.8 vs. 28.7).
In MCT-induced HF rats, HM17321 improved exercise capacity, arterial oxygen saturation, and myocardial fibrosis.
In obese rhesus monkeys, HM17321 reduced systolic and diastolic blood pressure (114/54 mmHg vs. 140/69 mmHg, vehicle) without increasing heart rate.

Structured PICO

Does HM17321 improve cardiac function and structure in preclinical models of heart failure?

Population

Preclinical study evaluating HM17321 in rodent heart failure models and middle-aged obese rhesus monkeys followed for 2 to 13 weeks.

Intervention

HM17321 (a CRFR2-selective UCN2 analog) administered for 2 to 5 weeks in rodents and for 13 weeks in non-human primates.

Comparator

Vehicle

Outcome

Cardiac structure and function (echocardiography) and exercise capacitysurrogate

HM17321, a novel UCN2 analog, improves cardiac function and attenuates pathological remodeling in preclinical rodent and non-human primate models of heart failure.

Main Result

Absolute Event Rate: 132.2% vs 177.6%

Abstract

Introduction and Objective: Heart failure (HF) is a major global cause of mortality, and its prevalence is increasing with rising obesity rates, particularly in HFpEF. Urocortin-2 (UCN2) exerts beneficial cardiovascular effects, including vasodilation and improved cardiac function in HF. HM17321 is a CRFR2-selective UCN2 analog currently in phase 1 clinical development as an anti-obesity therapy with improved weight loss quality (WLQ). This study evaluated the therapeutic potential of HM17321 in rodent HF models and a translational non-human primate model. Methods: Cardioprotective effects of HM17321 were evaluated in three preclinical models, including an obesity and hypertension driven HFpEF mouse model (HFD/L-NAME), a monocrotaline (MCT)-induced HF rat model, and middle-aged obese rhesus monkeys. HM17321 was administered for 2 to 5 weeks in rodents and for 13 weeks in non-human primates. Cardiac structure and function (echocardiography) and exercise capacity were assessed. Results: In HFpEF mice, HM17321 significantly reduced left ventricular (LV) hypertrophy with decreased LV mass and wall thickness compared to vehicle (LV mass: 132.2 mg vs. 177.6 mg; wall thickness: 0.88 mm vs. 1.05 mm). HM17321 also decreased MV E/E′ ratio and shortened IVRT compared to vehicle, suggesting improved diastolic function (MV E/E′ ratio: 22.8 vs. 28.7; IVRT: 16.2 ms vs. 20.5 ms). In MCT-induced HF rat model, HM17321 markedly improved exercise capacity, arterial oxygen saturation, and myocardial fibrosis. In obese rhesus monkeys, HM17321 significantly reduced systolic and diastolic blood pressure (114/54 mmHg vs. 140/69 mmHg, vehicle) without increasing heart rate. Conclusion: HM17321 improved cardiac function and attenuated pathological cardiac remodeling in rodent HF models and a non-human primate model. These findings suggest that HM17321, developed as an anti-obesity therapy for improved WLQ, may also represent a novel therapeutic option for HF, supported by cardiovascular effects observed in primates. Disclosure B. Ye: Employee; Current; Hanmi Pharm. Co., Ltd. W. Kim: Employee; Current; Hanmi Pharm. Co., Ltd. H. Kwon: Employee; Current; Hanmi Pharm. Co., Ltd. Y. Kim: None. S. Lee: None. J. Kim: Employee; Current; Hanmi Pharm. Co., Ltd. J. Kim: None. S. Bae: None. S. Lee: Employee; Current; Hanmi Pharm. Co., Ltd. I. Choi: None.

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