FALLS CHURCH, Va.--(BUSINESS WIRE)--Response Pharmaceuticals, Inc., a clinical stage company focused on weight management and metabolic health in high-risk populations, today announced positive topline results from its Phase 1b clinical trial evaluating the safety and efficacy of RDX-002, a first-in-class candidate treatment for the prevention of the rapid weight gain associated with the leading antipsychotic medications.

弗吉尼亚州福尔斯彻奇市——（商业新闻短讯）——Response Pharmaceuticals，Inc.，一家专注于高危人群体重管理和代谢健康的临床阶段公司，今天宣布了其1b期临床试验的积极结果，该试验评估了RDX-002的安全性和有效性，RDX-002是一种一流的候选治疗方法，用于预防与主要抗精神病药物相关的体重快速增加。

Antipsychotic-induced weight gain (AIWG) is a drug-induced epidemic within the already vulnerable population of patients with severe mental illness, including schizophrenia, depression and bipolar disorder, with patients experiencing rapid increases in body weight, hyperlipidemia and hyperglycemia..

抗精神病药物引起的体重增加（AIWG）是一种药物引起的流行病，在患有严重精神疾病（包括精神分裂症，抑郁症和双相情感障碍）的已经脆弱的人群中，患者体重迅速增加，高脂血症和高血糖症。。

“Antipsychotic medications are essential treatments that help millions of patients live better lives, but can be associated with rapid weight gain and obesity. This often leads to poor adherence to treatment and reduced quality of life, and contributes to long term cardiometabolic morbidities including decreased life expectancy” explained Joseph T.

“抗精神病药物是帮助数百万患者过上更好生活的基本治疗方法，但可能与体重迅速增加和肥胖有关。这通常会导致治疗依从性差和生活质量下降，并导致长期心脏代谢疾病，包括预期寿命缩短”，Joseph T解释道。

Coyle, MD, Emeritus Chair of Psychiatry and Neuroscience at Harvard Medical School. “The results of this trial suggest that RDX-002 may provide a unique therapeutic solution to address AIWG and the adverse metabolic changes that are associated with this weight gain.”.

科伊尔医学博士，哈佛医学院精神病学和神经科学名誉主席。“这项试验的结果表明，RDX-002可能提供一种独特的治疗方案，以解决AIWG以及与体重增加相关的不良代谢变化。”。

In the 2-week open-label trial, 24 healthy, antipsychotic-naïve volunteers were initially treated for 1 week with olanzapine, a highly efficacious antipsychotic, usage of which is associated with AIWG. Subjects were randomized at the outset of the study to either add RDX-002 orally twice a day to OLAN, or continue on OLAN alone during week two.

在为期2周的开放标签试验中，24名健康的未服用抗精神病药物的志愿者最初接受了奥氮平治疗1周，奥氮平是一种高效的抗精神病药物，其使用与AIWG有关。在研究开始时，受试者被随机分配，每天两次口服RDX-002至OLAN，或在第二周继续单独使用OLAN。

Subjects in the RDX-002 cohort met the primary endpoint for efficacy, lowering postprandial triglycerides (ppTGs). In an exploratory analysis of AIWG, subjects receiving OLAN alone saw significant weight gain during the first and second weeks of treatment whereas there was no significant weight change in the RDX-002 cohort in week 2..

RDX-002队列中的受试者达到了疗效的主要终点，降低了餐后甘油三酯（ppTGs）。在对AIWG的探索性分析中，仅接受OLAN治疗的受试者在治疗的第一周和第二周体重明显增加，而RDX-002队列在第二周体重没有明显变化。。

Subjects receiving olanzapine treatment showed a 54% increase in mean AUC postprandial triglycerides on Day 8 vs Day 1 (p=0.009) and remained elevated on Day 15. The olanzapine/RDX-002 cohort saw a decrease of 81.6% (p<0.001) in mean AUC ppTG on Day 15 vs Day 8. Overall RDX-002 was well-tolerated, with adverse events restricted to mostly mild to moderate GI effects, with no serious adverse events or treatment-related discontinuation during the study..

接受奥氮平治疗的受试者在第8天与第1天的平均AUC餐后甘油三酯增加54%（p=0.009），并在第15天保持升高。奥氮平/RDX-002队列在第15天与第8天的平均AUC ppTG下降了81.6%（p<0.001）。总体而言，RDX-002耐受性良好，不良事件仅限于轻度至中度胃肠道反应，研究期间无严重不良事件或治疗相关停药。。

In exploratory analyses, OLAN alone resulted in a mean increase in body weight of 1.6 kg (2.1%) (p<0.001 vs Day 1) in the first week of treatment and an additional 1.7 kg (2.2%) (p=0.016 vs Day 8) in the second week. Subjects receiving RDX-002 in the second week saw only a 0.4 kg increase (p=0.443 vs Day 8).

在探索性分析中，单独使用OLAN在治疗的第一周导致体重平均增加1.6公斤（2.1%）（与第1天相比p<0.001），第二周增加1.7公斤（2.2%）（p=0.016 vs第8天）。在第二周接受RDX-002的受试者仅增加0.4公斤（与第8天相比，p=0.443）。

Additionally, subjects in the OLAN-only group in the second week saw an increase in LDLc of 24.8% (p=0.016), while subjects receiving RDX-002 experienced and increase of 4.3% (p=NS). While exploratory, these findings support results seen in other trials where RDX-002 has demonstrated an impact on body weight, hyperlipidemia and hyperglycemia..

此外，仅OLAN组的受试者在第二周的LDLc增加了24.8%（p=0.016），而接受RDX-002的受试者则增加了4.3%（p=NS）。虽然是探索性的，但这些发现支持了RDX-002对体重，高脂血症和高血糖有影响的其他试验的结果。。

“This study provides the first clinical evidence of increased post-prandial lipids with antipsychotic medications, suggesting upregulation in iMTP from antipsychotics may play a role in the rapid weight gain associated with these medications” said Response Pharmaceuticals Chief Science Officer and lead inventor of RDX-002 Dr.

Response Pharmaceuticals首席科学官兼RDX-002 Dr的主要发明人说：“这项研究首次提供了抗精神病药物增加餐后血脂的临床证据，表明抗精神病药物对iMTP的上调可能在与这些药物相关的快速体重增加中起作用。”。

Paul Sweetnam. “Treatment with the iMTP-inhibitor RDX-002 significantly reduced ppTGs and blunted the weight gain in OLAN-treated subjects indicating a potential role in the treatment and prevention of AIWG. We expect to be presenting our detailed data set at an upcoming medical conference and in a scientific publication.”.

保罗·斯威特南。“用iMTP抑制剂RDX-002治疗可显着降低PPTG，并减缓OLAN治疗受试者的体重增加，表明其在治疗和预防AIWG中具有潜在作用。我们预计将在即将举行的医学会议和科学出版物中提供我们的详细数据集。”。

“This is very promising news for patients who have long fought to manage not only severe mental illness, but also the syndrome of AIWG and its associated morbidities. This early evidence feeds our drive to help patients around the world, including the approximately 58 million Americans suffering from mental illness according to the NIH,” said Response Pharmaceuticals CEO Eric Keller.

Response Pharmaceuticals首席执行官埃里克·凯勒（Eric Keller）表示：“对于那些长期以来不仅致力于治疗严重精神疾病，而且致力于治疗AIWG综合征及其相关疾病的患者来说，这是一个非常有希望的消息。这一早期证据为我们帮助世界各地的患者提供了动力，其中包括美国国家卫生研究院（NIH）统计的约5800万患有精神疾病的美国人。”。

“Response is actively engaged in preparing for next-stage clinical trials in AIWG, as well as development into other indications suited to the metabolic impact of the unique iMTP mechanism of action of RDX-002.”.

“Response积极参与AIWG下一阶段临床试验的准备工作，并开发出适合RDX-002独特iMTP作用机制代谢影响的其他适应症。”。

The planned Phase 2 clinical trial of RDX-002 will be a placebo-controlled 12-week study assessing weight gain and postprandial triglyceride changes in patients initiating olanzapine therapy for bipolar depression and schizophrenia. Response Pharmaceuticals is currently in the Series B funding stage..

RDX-002计划的2期临床试验将是一项为期12周的安慰剂对照研究，评估开始奥氮平治疗双相抑郁和精神分裂症患者的体重增加和餐后甘油三酯变化。Response Pharmaceuticals目前处于B系列资助阶段。。

About Antipsychotic-Induced Weight Gain

关于抗精神病药物引起的体重增加

Antipsychotic-Induced Weight Gain affects millions of people worldwide. While current antipsychotic medications, such as olanzapine, quetiapine and clozapine, have been transformational for patients’ lives, a frequent side effect associated with these treatments is rapid, clinically meaningful weight gain, often occurring in the first few weeks of treatment and sometimes continuing for years.

抗精神病药物引起的体重增加影响着全世界数百万人。虽然目前的抗精神病药物，如奥氮平，喹硫平和氯氮平，已经改变了患者的生活，但与这些治疗相关的常见副作用是快速，临床上有意义的体重增加，通常发生在治疗的前几周，有时持续数年。

This results in high rates of medication discontinuation or a change to a less efficacious medication, and often leads to relapse and hospitalization. Along with clinically meaningful weight gain, atypical antipsychotics are known to cause other serious effects, including elevated serum triglycerides, increased LDL cholesterol, and blood sugar, each of which contribute to an increased risk of cardiovascular disease and diabetes, resulting in higher mortality rates and up to 17.5 years’ reduced life expectancy..

这导致停药率很高或改用疗效较差的药物，并经常导致复发和住院治疗。除了临床上有意义的体重增加外，非典型抗精神病药物还会引起其他严重影响，包括血清甘油三酯升高，低密度脂蛋白胆固醇升高和血糖升高，每种药物都会增加心血管疾病和糖尿病的风险，导致死亡率更高，预期寿命缩短17.5年。。

About the Study

关于这项研究

The Phase 1B study was a single-center, open-label 15-day study in 24 healthy volunteers receiving OLAN. During the first week of treatment all subjects received OLAN alone and were randomized to either remain on OLAN alone or OLAN+RDX-002 during the second week of treatment. The primary endpoint was postprandial (pp)TG AUC measured on Day 1 (pre-OLAN), Day 8 and Day 15 after consumption of a meal standardized for total and fat calorie content.

1B期研究是一项针对24名接受OLAN的健康志愿者的单中心开放标签15天研究。在治疗的第一周内，所有受试者均单独接受OLAN治疗，并在治疗的第二周内随机接受OLAN治疗或OLAN+RDX-002治疗。主要终点是在第1天（OLAN前），第8天和第15天测量的餐后（pp）TG AUC，该餐是根据总热量和脂肪卡路里含量标准化的。

Secondary and exploratory endpoints included changes in fasting lipids and body weight as well as OLAN PK and safety..

次要和探索性终点包括空腹血脂和体重的变化以及OLAN PK和安全性。。

About RDX-002

关于RDX-002

RDX-002, Response Pharmaceuticals’ lead candidate, is a first-in-class, potent, selective, and gut-specific small molecule inhibitor of microsomal triglyceride transfer protein (MTP). The overall effect of MTP inhibition is a decrease in the amount of triglycerides and cholesterol delivered to the body after a meal.

RDX-002是Response Pharmaceuticals的主要候选药物，是微粒体甘油三酯转移蛋白（MTP）的一流，有效，选择性和肠道特异性小分子抑制剂。MTP抑制的总体效果是餐后输送到体内的甘油三酯和胆固醇的量减少。

RDX-002 has been studied in multiple Phase 1 and Phase 2 clinical trials including 496 healthy subjects and patients dosed for up to 84 days. In these studies, RDX-002 lowered post-prandial triglyceride levels, circulating levels of low-density lipoprotein cholesterol (LDLc), and reduced weight. RDX-002 is being developed as an adjunctive therapy for patients taking atypical antipsychotic therapy, as well as a potential treatment in other settings in which clinically significant weight gain and/or adverse metabolic changes are prevalent.

RDX-002已在多个1期和2期临床试验中进行了研究，包括496名健康受试者和服用长达84天的患者。在这些研究中，RDX-002降低了餐后甘油三酯水平，低密度脂蛋白胆固醇（LDLc）的循环水平和体重减轻。RDX-002正在开发作为服用非典型抗精神病药物治疗的患者的辅助治疗，以及在临床上显着体重增加和/或不良代谢变化普遍存在的其他环境中的潜在治疗方法。

RDX-002 is being developed under an exclusive world-wide license from Sanofi S.A..

RDX-002是在赛诺菲公司的全球独家许可下开发的。。

About Response Pharmaceuticals

关于Response Pharmaceuticals

Response Pharmaceuticals is a clinical-stage biotechnology company focused on developing treatments for weight management and metabolic health in high-need patient populations. The company is building its portfolio with an initial focus on helping those taking antipsychotic medications for disabling mental illnesses to combat weight gain and metabolic dysregulation associated with these treatments.

Response Pharmaceuticals是一家临床阶段的生物技术公司，专注于开发针对高需求患者人群的体重管理和代谢健康治疗方法。该公司正在建立其投资组合，最初的重点是帮助那些服用抗精神病药物治疗致残精神疾病的人，以对抗与这些治疗相关的体重增加和代谢失调。