– Results showing significant reductions in liver fat content and body weight, no loss of lean muscle mass, and improvement in key markers of metabolism and inflammation published in The Lancet Gastroenterology & Hepatology –

-结果显示，肝脏脂肪含量和体重显著减少，瘦肌肉质量没有减少，代谢和炎症的关键标志物也有所改善

– HU6 was well tolerated at once-daily oral doses with adverse events mainly mild or moderate in severity –

-HU6耐受性良好，每日口服一次，不良事件主要为轻度或中度-

CHARLOTTESVILLE, Va. and SAN FRANCISCO, Oct. 5, 2023 /PRNewswire/ -- Rivus Pharmaceuticals Inc., a clinical-stage biopharmaceutical company dedicated to improving cardiometabolic health, today announced publication in The Lancet Gastroenterology & Hepatology of the results of a Phase 2a metabolic study of HU6, an investigational first-in-class controlled metabolic accelerator (CMA), in patients with nonalcoholic fatty liver disease (NAFLD), also known as metabolic dysfunction-associated steatotic liver disease (MASLD), and a high body mass index (BMI)..

弗吉尼亚州夏洛茨维尔和旧金山，2023年10月5日/PRNewswire/-Rivus Pharmaceuticals Inc.，一家致力于改善心脏代谢健康的临床阶段生物制药公司，今天在“柳叶刀胃肠病学和肝病学”杂志上公布了一项2a期代谢研究HU6，一种研究性一流的受控代谢促进剂（CMA），在患有非酒精性脂肪性肝病（NAFLD）的患者中，也称为代谢功能障碍相关的脂肪性肝病（MASLD）和高体重指数（BMI）。。

Results showed that HU6 significantly reduced liver fat compared with placebo in both the overall study population and in study participants at increased risk of Type 2 diabetes. HU6 also reduced body weight, with no loss of lean muscle mass, and improved measures of metabolism and systemic inflammation.

结果显示，与安慰剂相比，HU6在整体研究人群和2型糖尿病风险增加的研究参与者中显着降低了肝脏脂肪。HU6还减轻了体重，没有减少瘦肌肉量，并改善了新陈代谢和全身炎症的措施。

HU6, the company's lead medicine, is an oral, controlled metabolic accelerator in Phase 2 clinical development..

HU6是该公司的主要药物，是2期临床开发中的口服受控代谢促进剂。。

'The positive efficacy and safety results of this Phase 2a metabolic clinical trial of HU6 give us confidence that this first-in-class therapy has the potential to provide an effective, well-tolerated treatment for a broad range of cardiometabolic diseases associated with obesity,' said Mazen Noureddin, M.D., hepatologist at Houston Research Institute and Houston Methodist Hospital and lead author of the publication.

“HU6 2a期代谢临床试验的积极疗效和安全性结果使我们相信，这种一流的治疗方法有可能为与肥胖相关的广泛的心脏代谢疾病提供有效的、耐受性良好的治疗，”Mazen Noureddin，M.D。，休斯顿研究所和休斯顿卫理公会医院的肝病学家，该出版物的主要作者。

'A broad range of investigational therapies have been studied in patients with NAFLD/MASLD, but there are still not many options that are able to effectively manage this disease in patients with obesity and elevated liver fat. The significant reductions in liver fat, coupled with greater than expected reductions in inflammatory markers, make HU6 a promising new approach.'.

“在NAFLD/MASLD患者中已经研究了广泛的研究性治疗方法，但是在肥胖和肝脏脂肪升高的患者中仍然没有很多能够有效控制这种疾病的选择。肝脏脂肪的显着减少，加上炎症标志物的减少超过预期，使HU6成为一种有前途的新方法。

'There is growing evidence that HU6 can speed up metabolism in a safe and controlled manner that enables fat-specific weight loss, while lowering inflammation,' said Jayson Dallas, M.D., chief executive officer, Rivus Pharmaceuticals. 'We are highly encouraged by the Phase 2a metabolic study results and are continuing to evaluate HU6 broadly to improve cardiometabolic health in people with obesity, one of the most challenging health issues we face in society today.'.

Rivus Pharmaceuticals首席执行官Jayson Dallas博士说：“越来越多的证据表明，HU6可以以安全和可控的方式加速新陈代谢，使脂肪特异性体重减轻，同时降低炎症。”我们受到2a期代谢研究结果的高度鼓励，并继续广泛评估HU6，以改善肥胖人群的心脏代谢健康，这是我们当今社会面临的最具挑战性的健康问题之一。

The company is presently enrolling patients with obese phenotype of heart failure with preserved injection fraction (HFpEF) in the Phase 2a HuMAIN study (ClinicalTrials.gov, NCT05284617) and patients with obesity and Type 2 diabetes at risk of metabolic dysfunction associated steatohepatitis (MASH) in the Phase 2b M-ACCEL trial (ClinicalTrials.gov, NCT05979779)..

该公司目前正在2a期HuMAIN研究（ClinicalTrials.gov，NCT05284617）和肥胖和2型糖尿病患者中招募具有保留注射分数（HFpEF）的肥胖心力衰竭表型的患者，这些患者有代谢功能障碍相关的脂肪性肝炎（MASH）在2b期M-ACCEL试验（ClinicalTrials.gov，NCT05979779）中。。

Phase 2a Study Design and ResultsThe 61-day randomized, double-blind, placebo-controlled Phase 2a metabolic trial (ClinicalTrials.gov, NCT04874233) was designed to evaluate the safety and efficacy of once-daily HU6 at three dose levels (150 mg, 300 mg and 450 mg) in 80 patients age 28 to 65 years with NAFLD, elevated liver fat (greater than 8%) and a BMI of 28 to 45 kg/m2.

2a期研究设计和结果61天随机，双盲，安慰剂对照的2a期代谢试验（ClinicalTrials.gov，NCT04874233）旨在评估三种剂量水平（150 mg，300 mg）每日一次HU6的安全性和有效性。mg和450mg）在80名28至65岁的NAFLD患者，肝脏脂肪升高（大于8%）和BMI为28至45kg/m 2的患者中。

These doses correlate to a 10%, 20% and 30% increase in resting metabolic rate, respectively, all within the range of normal daily fluctuations. A subset of study participants (40%) had elevated HbA1C levels, placing them at increased risk of Type 2 diabetes. The primary efficacy endpoint was the relative change in liver fat content from baseline to day 61 as assessed by MRI-proton density fat fraction (MRI-PDFF).

这些剂量分别与静息代谢率增加10%，20%和30%相关，均在正常日常波动范围内。一部分研究参与者（40%）的HbA1C水平升高，使他们患2型糖尿病的风险增加。主要疗效终点是通过MRI-质子密度脂肪分数（MRI-PDFF）评估的从基线至第61天的肝脏脂肪含量的相对变化。

The study was conducted at a single community site in the United States..

这项研究是在美国的一个社区进行的。。

The published results demonstrated the following:

公布的结果如下：

Liver fat content (primary endpoint): A significant decrease from baseline to day 61 as assessed by MRI-PDFF was observed with all HU6 doses compared with placebo (p<0.0001) in the overall study population and in the elevated HbA1c subgroup (p<0.0001).

肝脏脂肪含量（主要终点）：在整个研究人群和升高的HbA1c亚组中，与安慰剂（p<0.0001）相比，在所有HU6剂量下观察到通过MRI-PDFF评估的从基线至第61天的显着降低（p<0.0001）<0.0001）。

>30% reduction in liver fat: Overall, 61% of study participants treated with any dose of HU6 had at least a 30% reduction in liver fat from baseline to day 61 as assessed by MRI-PDFF. Among the HU6 150 mg, 300 mg and 450 mg dosing groups, the percentages were 40%, 71% and 72%, respectively, versus 5% of those receiving placebo; all p<0.0001).

>肝脏脂肪减少30%：总体而言，通过MRI-PDFF评估，用任何剂量的HU6治疗的研究参与者中有61%从基线至第61天肝脏脂肪减少至少30%。在HU6 150 mg，300 mg和450 mg给药组中，百分比分别为40%，71%和72%，而安慰剂组为5%；全部p<0.0001）。

Similar results were observed in study participants in the HbA1c subset (43%, 75% and 86%, respectively, versus 0% of those receiving placebo; all p<0.0001)..

在HbA1c亚组的研究参与者中观察到类似的结果（分别为43%，75%和86%，而接受安慰剂的患者为0%；所有p<0.0001）。。

Body weight: HU6 300 mg and 450 mg were associated with significant weight loss at day 61 and at the follow-up visit, with no loss of lean body mass or skeletal muscle mass. Notably, the elevated HbA1c subgroup had a greater overall weight loss than the total population.

体重：HU6 300 mg和450 mg与第61天和随访时体重明显减轻相关，没有瘦体重或骨骼肌质量的减少。值得注意的是，HbA1c亚组总体体重增加损失高于总人口。

Inflammatory and metabolic markers: HU6 300 mg and 450 mg significantly reduced systemic high sensitivity C-reactive protein (hsCRP), a systemic marker of inflammation, compared with placebo. The hsCRP reductions were four-fold greater than expected for the observed weight loss, due to the independent effect of HU6 on reducing oxidative stress.

炎症和代谢标志物：与安慰剂相比，HU6 300 mg和450 mg显着降低全身高敏C反应蛋白（hsCRP），这是炎症的全身标志物。由于HU6对减少氧化应激的独立作用，hsCRP降低比观察到的体重减轻预期高4倍。

HU6 also was associated with significant improvement in glycemic control, with glycated albumin significantly reduced by HU6 450 mg versus placebo in the HbA1c subgroup..

HU6也与血糖控制的显着改善相关，在HbA1c亚组中，HU6 450 mg与安慰剂相比，糖化白蛋白显着降低。。

Safety: HU6 was well tolerated at once-daily doses of 150 mg, 300 mg and 450 mg for up to 61 days. Treatment-emergent adverse events (TEAEs) occurred in 65% of participants who received HU6 and in 35% of study participants who received placebo. Adverse events were mainly mild or moderate in severity.

安全性：HU6在150mg，300mg和450mg的每日一次剂量下耐受良好，持续长达61天。65%接受HU6的参与者和35%接受安慰剂的研究参与者发生治疗紧急不良事件（TEAE）。不良事件的严重程度主要为轻度或中度。

No serious TEAEs were reported. In those treated with HU6, the most frequently reported TEAEs were flushing (32% of participants), diarrhea (25% of participants), and palpitations (12% participants). In the placebo arm, 10% of participants had flushing, none had diarrhea, and 5% had palpitations. No effects of HU6 were observed on body temperature or on any of the precursors to an elevated body temperature.

没有报告严重的TEAE。在用HU6治疗的患者中，最常报告的TEAE是潮红（32%的参与者），腹泻（25%的参与者）和心悸（12%的参与者）。在安慰剂组中，10%的参与者潮红，没有腹泻，5%有心悸。没有观察到HU6对体温或任何升高体温的前体的影响。

Side effects commonly associated with incretin therapies, such as nausea and vomiting, were not observed with HU6. No patients discontinued for any reason at the high dose of 450 mg of HU6..

HU6未观察到通常与肠降血糖素治疗相关的副作用，例如恶心和呕吐。没有患者因高剂量450 mg HU6而因任何原因停药。。

About Controlled Metabolic Accelerators (CMAs)Rivus is advancing a new class of therapies, called controlled metabolic accelerators (CMAs). CMAs have the potential to improve metabolic health and reduce cardiovascular risk and mortality. As oral small molecules, CMAs are designed to address excess fat and treat a broad range of cardiometabolic diseases by safely leveraging mitochondrial uncoupling, a natural metabolic process by which the body generates heat.

关于受控代谢加速器（CMA），Rivus正在推进一类新的疗法，称为受控代谢加速器（CMA）。CMA有可能改善代谢健康并降低心血管风险和死亡率。作为口服小分子，CMA被设计用于通过安全地利用线粒体解偶联来解决多余的脂肪并治疗广泛的心脏代谢疾病，线粒体解偶联是身体产生热量的自然代谢过程。

Within the mitochondria, sugars and fats are broken down by biochemical processes to help regulate the body's metabolism. CMAs cue the increased oxidation of sugars and fats by metabolic processes in the mitochondria while maintaining the same baseline production of adenosine triphosphate (ATP), the body's primary source for energy production, resulting in a sustained, imperceivable increase in the resting metabolic rate throughout the day and night.

在线粒体内，糖和脂肪通过生化过程分解，以帮助调节身体的新陈代谢。CMA通过线粒体中的代谢过程提示糖和脂肪的氧化增加，同时保持三磷酸腺苷（ATP）的相同基线产生，三磷酸腺苷是人体能量产生的主要来源，导致整个静息代谢率持续，不可思议的增加。白天和晚上。

Activating this process results in the reduction of accumulated fat and sugars throughout the body, while preserving, or even improving, lean muscle mass. CMAs provide a novel, measured approach to activating this natural process, resulting in weight loss, reduction of liver fat, improved insulin sensitivity and a significant reduction in oxidative stress and inflammation..

激活这一过程可以减少全身脂肪和糖分的积累，同时保持甚至改善瘦肌肉质量.CMA提供了一种新颖的测量方法来激活这一自然过程，从而减轻体重，减少肝脏脂肪，改善胰岛素敏感性，显着降低氧化应激和炎症。。

About HU6HU6 is the most advanced CMA in clinical development and was purposefully designed to control both absorption and metabolism. The proprietary mechanism of HU6 increases the body's resting metabolic rate without any perceived or actual increases in body temperature. In clinical trials, HU6 has shown potential for inducing fat-specific weight loss, preservation of lean muscle mass and significant improvements in measures of metabolic health.

关于HU6HU6是临床开发中最先进的CMA，旨在控制吸收和代谢。HU6的专有机制增加了身体的静息代谢率，而没有任何感知或实际的体温升高。在临床试验中，HU6显示出诱导脂肪特异性体重减轻，保持瘦肌肉质量和显着改善代谢健康措施的潜力。

Treatment with HU6 could potentially significantly reduce systemic inflammation by decreasing the production of reactive oxygen species within the cell. Rivus is pursuing clinical development programs for HU6 in heart failure with preserved ejection fraction (HFpEF), metabolic dysfunction associated steatohepatitis (MASH), Type 2 diabetes and obesity..

用HU6治疗可能通过减少细胞内活性氧的产生而显着减少全身炎症。Rivus正在开展心力衰竭患者HU6的临床开发项目，其中包括射血分数（HFpEF），代谢功能障碍相关性脂肪性肝炎（MASH），2型糖尿病和肥胖。。

About Rivus PharmaceuticalsRivus Pharmaceuticals, Inc., a leader in mitochondrial biology, is dedicated to improving cardiometabolic health by advancing a new class of medicines called controlled metabolic accelerators (CMAs). Rivus' investigational first-in-class small molecule therapy, HU6, represents a tremendous opportunity to empower patients on their journey to better health when facing a broad range of conditions, including obesity, heart failure with preserved ejection fraction (HFpEF), metabolic dysfunction-associated steatotic liver disease (MASLD) / metabolic dysfunction-associated steatohepatitis (MASH), Type 2 diabetes and obesity.

关于Rivus PharmaceuticalsRivus Pharmaceuticals，Inc。是线粒体生物学的领导者，致力于通过推进一类称为受控代谢加速器（CMA）的新型药物来改善心脏代谢健康。Rivus的一流小分子疗法研究HU6代表了一个巨大的机会，可以让患者在面对各种疾病时获得更好的健康状况，包括肥胖，射血分数保留的心力衰竭（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），2型糖尿病和肥胖。

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

欲了解更多信息，请访问www.rivuspharma.com。。

Contact:Alana RocklandReal Chemistry[email protected] +1-301-537-5392

联系方式：Alana RocklandReal化学[电子邮件保护]+1-301-537-5392

SOURCE Rivus Pharmaceuticals

来源Rivus Pharmaceuticals