– Study evaluating HU6 in patients with obesity-related heart failure with preserved ejection fraction is on track to report topline data in the second half of 2024 –

–一项评估射血分数保留的肥胖相关性心力衰竭患者HU6的研究有望在2024年下半年报告基线数据-

– HU6, a novel Controlled Metabolic Accelerator, is a new class of investigational medicines designed to reduce weight while preserving muscle –

–HU6是一种新型受控代谢促进剂，是一类新型研究药物，旨在减轻体重，同时保留肌肉–

CHARLOTTESVILLE, Va. and SAN FRANCISCO, June 26, 2024 /PRNewswire/ -- Rivus Pharmaceuticals Inc., a clinical-stage biopharmaceutical company dedicated to improving metabolic health, today announced publication of the rationale and design of the company's Phase 2a HuMAIN trial in the European Journal of Heart Failure.

弗吉尼亚州夏洛茨维尔和旧金山，2024年6月26日/PRNewswire/--致力于改善代谢健康的临床阶段生物制药公司Rivus Pharmaceuticals Inc.今天宣布在《欧洲心力衰竭杂志》上公布该公司2a期HuMAIN试验的基本原理和设计。

Rivus has completed patient enrollment in this clinical trial of HU6, an investigational Controlled Metabolic Accelerator (CMA), in patients with obesity-related heart failure with preserved ejection fraction (HFpEF) and expects to report topline data in the second half of 2024..

Rivus已经完成了HU6（一种研究控制的代谢促进剂（CMA））临床试验的患者登记，该试验用于保留射血分数（HFpEF）的肥胖相关性心力衰竭患者，预计将在2024年下半年报告topline数据。。

'HuMAIN is the first clinical trial to evaluate the effects of a CMA in patients with obesity-related HFpEF, who have a median survival rate of around two years following hospitalization,' said Jayson Dallas, M.D., chief executive officer, Rivus Pharmaceuticals. 'HU6 has the potential to be the first disease-modifying treatment for HFpEF.

Rivus Pharmaceuticals首席执行官杰森·达拉斯（Jayson Dallas）医学博士说：“HuMAIN是第一个评估CMA对肥胖相关HFpEF患者影响的临床试验，这些患者住院后的中位生存率约为两年。”HU6有可能成为HFpEF的第一种疾病缓解治疗方法。

We look forward to further evaluating the potential benefits of HU6 in this large and growing patient population and sharing topline results in the second half of 2024.'.

我们期待着在2024年下半年进一步评估HU6在这个庞大且不断增长的患者群体中的潜在益处，并分享topline结果。”。

HFpEF is a chronic debilitating syndrome characterized by severely reduced exercise capacity, which degrades quality of life. Obesity is a major independent risk factor for HFpEF and key contributor to the increasing worldwide prevalence of this disorder, with as many as 80% of patients with HFpEF in Western countries either overweight or obese.

HFpEF是一种慢性衰弱综合征，其特征是运动能力严重降低，从而降低生活质量。肥胖是HFpEF的主要独立危险因素，也是全球HFpEF患病率上升的关键因素，西方国家多达80%的HFpEF患者超重或肥胖。

Weight loss approaches that involve dieting, bariatric surgery and GLP-1 agonists work by decreasing energy intake rather than by increasing energy expenditure. In addition to loss of fat, these approaches result in marked reductions in muscle mass, which can lead to impaired function in patients with HFpEF, who are typically elderly and frail and already have reduced muscle mass..

涉及节食，减肥手术和GLP-1激动剂的减肥方法通过减少能量摄入而不是增加能量消耗来起作用。除了减少脂肪外，这些方法还导致肌肉质量明显减少，这可能导致HFpEF患者的功能受损，这些患者通常是老年人和体弱者，并且已经减少了肌肉质量。。

'Given the limitations of current options for patients with obesity-related HFpEF, novel disease-modifying treatments are urgently needed,' said Dalane W. Kitzman, M.D., lead author of the publication and professor of internal medicine and cardiovascular medicine at Wake Forest University School of Medicine.

“鉴于肥胖相关HFpEF患者目前选择的局限性，迫切需要新的疾病缓解治疗方法，”该出版物的主要作者、维克森林大学医学院内科和心血管医学教授Dalane W.Kitzman医学博士说。

'As detailed in this new publication, HU6 reduces fat, which is pivotal to the development of HFpEF, by increasing energy expenditure while preserving muscle. The Phase 2a trial will examine HU6's potential to improve key outcomes in HFpEF, including increasing exercise capacity and quality of life, reducing systemic inflammation, and improving blood pressure and glucose metabolism.'.

正如这份新出版物所详述的那样，HU6通过增加能量消耗同时保留肌肉来减少脂肪，这对HFpEF的发展至关重要。2a期试验将研究HU6改善HFpEF关键结局的潜力，包括提高运动能力和生活质量，减少全身炎症，改善血压和葡萄糖代谢。”。

About the Phase 2a HuMAIN Trial

关于2a期HuMAIN试验

The randomized, double-blind, placebo-controlled, parallel-group, dose-escalation Phase 2a HuMAIN study (ClinicalTrials.gov: NCT05284617) is evaluating the safety, tolerability, pharmacodynamics and pharmacokinetics of ascending doses of HU6 (150 mg, 300 mg, 450 mg daily) in patients with obesity-related HFpEF.

随机，双盲，安慰剂对照，平行组，剂量递增2a期HuMAIN研究（ClinicalTrials.gov:NCT05284617）正在评估递增剂量HU6（150 mg，300 mg，450 mg）的安全性，耐受性，药效学和药代动力学。肥胖相关HFpEF患者。

A total of 65 study participants (37 women and 28 men) age 30 or older with a body mass index (BMI) >30 kg/m2 were randomized to 134 days of daily dosing with HU6 or placebo..

共有65名年龄在30岁或以上且体重指数（BMI）>30 kg/m2的研究参与者（37名女性和28名男性）被随机分配到每天134天的HU6或安慰剂剂量。。

The primary efficacy endpoint is weight reduction (as measured by the change from baseline in body weight at Day 134). The key secondary efficacy endpoint is exercise capacity (as measured by the change from baseline in peak VO2 [mL/kg/min] during a standardized, noninvasive cardiopulmonary exercise test at Day 134).

主要疗效终点是体重减轻（通过第134天体重从基线的变化来衡量）。关键的次要疗效终点是运动能力（通过在第134天的标准化无创心肺运动试验期间峰值VO2（mL/kg/min）与基线的变化来衡量）。

The effects of HU6 on disease-specific quality of life, changes in body composition and cardiac function/structure, and markers of cardiometabolic dysfunction (e.g., changes in blood pressure and pulse, glucose control, inflammation, lipid levels and liver fat and liver enzymes) are also being evaluated.

HU6对疾病特异性生活质量，身体成分和心脏功能/结构变化以及心脏代谢功能障碍标志物（例如血压和脉搏变化，血糖控制，炎症，脂质水平以及肝脏脂肪和肝酶）的影响也正在评估中。

The study is designed to identify the optimal dose of HU6 for Phase 3 trials. HuMAIN is being conducted at 22 clinical sites in the United States..

该研究旨在确定HU6在3期试验中的最佳剂量。HuMAIN正在美国的22个临床地点进行。。

About Controlled Metabolic Accelerators (CMAs)

关于受控代谢促进剂（CMA）

Rivus is advancing a new class of investigational medicines called Controlled Metabolic Accelerators (CMAs) that have the potential to improve metabolic health for people with obesity and associated metabolic diseases. CMAs are oral small molecules designed to increase resting metabolic rate, which results in increased consumption of energy, primarily from fat.

Rivus正在开发一种新的研究药物，称为受控代谢促进剂（CMAs），它有可能改善肥胖和相关代谢疾病患者的代谢健康。CMA是口服小分子，旨在提高静息代谢率，从而导致能量消耗增加，主要来自脂肪。

The loss in fat mass addresses multiple cardiometabolic conditions driven by adiposity. CMAs increase metabolism in a continuous and imperceptible manner by leveraging the natural metabolic process of mitochondrial uncoupling. Uncoupling accounts for 20%-40% of resting caloric consumption. A key advantage of this mechanism for increasing energy expenditure is that the resulting weight loss is fat selective with preservation of muscle mass.

脂肪量的减少解决了由肥胖驱动的多种心脏代谢状况。CMA通过利用线粒体解偶联的自然代谢过程，以连续且不易察觉的方式增加代谢。解偶联占静息热量消耗的20%-40%。这种增加能量消耗的机制的一个关键优点是，由此产生的体重减轻是脂肪选择性的，同时保留了肌肉质量。

In contrast, caloric-restriction strategies reduce energy input and result in loss of fat as well as muscle mass. Initial data in humans has demonstrated that CMAs provide fat-selective weight loss, improved insulin sensitivity, and a significant reduction in oxidative stress and inflammation..

相比之下，热量限制策略会减少能量输入，导致脂肪和肌肉质量的减少。人类的初步数据表明，CMA可以提供脂肪选择性减肥，改善胰岛素敏感性，并显着降低氧化应激和炎症。。

About HU6

关于HU6

HU6, an oral, once-daily investigational medicine, is Rivus' lead CMA. It is a purposely designed investigational oral small molecule that is intended to be a foundational monotherapy for cardiac, liver, diabetes and obesity indications. HU6 promotes sustained weight loss by gently, safely and imperceptibly increasing resting metabolism, which results in fat burn, while preserving muscle mass.

HU6是一种口服，每日一次的研究药物，是Rivus的首席CMA。它是一种专门设计的研究性口服小分子，旨在成为心脏，肝脏，糖尿病和肥胖适应症的基础单一疗法。HU6通过温和、安全和潜移默化地增加静息代谢来促进持续减肥，从而导致脂肪燃烧，同时保持肌肉质量。

Phase 2 results in patients with a high body mass index (BMI) and metabolic dysfunction-associated steatotic liver disease (MASLD) showed that once-daily HU6 significantly reduced liver fat content and body weight with no loss of lean muscle mass and improved key markers of systemic inflammation and metabolism.1 HU6 was well tolerated; side effects were mainly mild or moderate in severity..

高体重指数（BMI）和代谢功能障碍相关脂肪变性肝病（MASLD）患者的2期结果显示，每天一次的HU6可显着降低肝脏脂肪含量和体重，而不会减少瘦肌肉质量，并改善全身炎症和代谢的关键标志物。HU6耐受性良好；副作用的严重程度主要为轻度或中度。。

The current clinical development of HU6 is focused on metabolic diseases with the most morbidity and greatest treatment needs: heart failure with preserved ejection fraction (HFpEF) and metabolic dysfunction-associated steatohepatitis (MASH)/MASLD.

HU6目前的临床发展集中在发病率最高和治疗需求最大的代谢性疾病上：射血分数保留的心力衰竭（HFpEF）和代谢功能障碍相关的脂肪性肝炎（MASH）/MASLD。

About Rivus Pharmaceuticals

关于Rivus Pharmaceuticals

Rivus Pharmaceuticals, Inc., a leader in mitochondrial biology, is dedicated to improving metabolic health by advancing a new class of investigational medicines called Controlled Metabolic Accelerators (CMAs). Rivus' lead CMA is the investigational small molecule HU6 in development to treat heart failure with preserved ejection fraction (HFpEF), metabolic dysfunction-associated steatotic liver disease (MASLD)/metabolic dysfunction-associated steatohepatitis (MASH) and Type 2 diabetes.

线粒体生物学的领导者Rivus Pharmaceuticals，Inc.致力于通过推进一类称为受控代谢促进剂（CMA）的新型研究药物来改善代谢健康。Rivus的首席CMA是正在开发的研究性小分子HU6，用于治疗射血分数（HFpEF），代谢功能障碍相关脂肪性肝病（MASLD）/代谢功能障碍相关脂肪性肝炎（MASH）和2型糖尿病的心力衰竭。

For more information, please visit www.rivuspharma.com..

欲了解更多信息，请访问www.rivuspharma.com。。

Contact:

联系人：

Meredith Mallen

Meredith Mallen。

Real Chemistry

真正的化学

mmallen@realchemistry.com

mmallen@realchemistry.com

+1-516-987-2313

+1-516-987-2313

References

参考文献

Noureddin M, Khan S, Portell F, et al. Safety and efficacy of once-daily HU6 versus placebo in people with non-alcoholic fatty liver disease and high BMI: a randomised, double-blind, placebo-controlled phase 2a trial. Lancet Gastroenterol Hepatol. 2023.

Noureddin M，Khan S，Portell F等。非酒精性脂肪肝病和高BMI患者每日一次HU6与安慰剂的安全性和有效性：一项随机，双盲，安慰剂对照的2a期试验。柳叶刀胃肠肝。2023

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