BOULDER, Colo.--(BUSINESS WIRE)--Crestone, Inc. (“Crestone”) today announced positive topline results from the Phase 2 clinical trial evaluating CRS3123 in patients with Clostridioides difficile infection (CDI). CRS3123 is a novel drug candidate that has demonstrated narrow spectrum and minimal disruption of normal gut microbiota in preclinical and Phase 1 studies.

科罗拉多州博尔德市——（商业新闻短讯）——Crestone，Inc.（“Crestone”）今天宣布，评估艰难梭菌感染（CDI）患者CRS3123的2期临床试验的阳性结果。CRS3123是一种新型候选药物，在临床前和1期研究中表现出窄谱和对正常肠道微生物群的最小破坏。

Among the 43 patients in the primary intent-to-treat (ITT) analysis population, clinical cure rates at the day 12 test-of-cure visit were comparable in all three treatment groups, including 28/29 (97%) in patients receiving one of two dosages of CRS3123 versus 13/14 (93%) in those receiving vancomycin.

在主要意向治疗（ITT）分析人群中的43名患者中，所有三个治疗组在第12天的治愈率测试中的临床治愈率相当，其中28/29（97%）接受两种剂量CRS3123中的一种的患者接受万古霉素治疗的患者为13/14（93%）。

There were no clinical failures at the day 12 time point; the results in two patients were indeterminate..

在第12天的时间点没有临床失败；两名患者的结果不确定。。

Importantly, rates of CDI recurrence were considerably lower in those patients who received CRS3123. For example, at day 40 recurrence rates were 4% for CRS3123 versus 23% for vancomycin. CRS3123 was well tolerated, with no serious treatment-emergent adverse events. Crestone plans to present the results from the Phase 2 trial at an upcoming medical conference..

重要的是，接受CRS3123的患者的CDI复发率要低得多。例如，在第40天，CRS3123的复发率为4%，而万古霉素的复发率为23%。CRS3123耐受性良好，没有严重的治疗紧急不良事件。Crestone计划在即将举行的医学会议上介绍第二阶段试验的结果。。

CDI is the most common hospital-acquired infection in the U.S. and is now even more prevalent in the community, including in younger patients. In the U.S. there are almost half a million infections each year and approximately 30,000 deaths.

CDI是美国最常见的医院获得性感染，现在在社区中甚至更为普遍，包括年轻患者。在美国，每年有近50万人感染，约30000人死亡。

Dr. Thomas Louie of University of Calgary, Canada, principal investigator for this study, stated: “Treatment of C. difficile infection remains in urgent need of agents that spare normal gut microbes, so they can reconstitute the microbiome and prevent further recurrences of CDI. The findings of this study support CRS3123 as such a candidate for further development.”.

加拿大卡尔加里大学的Thomas Louie博士是这项研究的首席研究员，他表示：“艰难梭菌感染的治疗仍然迫切需要保留正常肠道微生物的药物，因此它们可以重建微生物组并防止CDI的进一步复发。这项研究的结果支持CRS3123作为进一步发展的候选者。”。

Epidemiology analysis and toxin testing for this study were performed at the University of Leeds. Dr. Mark Wilcox, Professor at Leeds Teaching Hospitals and University of Leeds and Lead on CDI for UK Health Security Agency, stated: “It is now abundantly clear that curbing C. difficile while preserving healthy intestinal flora is what we want in a CDI therapeutic.

这项研究的流行病学分析和毒素测试是在利兹大学进行的。。

The outcome of this phase 2 study further reinforces that goal.”.

这项第二阶段研究的结果进一步强化了这一目标。”。

“We are very pleased with these results,” said Dr. Jon Bruss, Acting Chief Medical Officer to Crestone. “This was a challenging study to execute given pandemic disruptions to healthcare. We want to sincerely thank all the patients, families, clinicians and collaborators who contributed to the generation of these important data.”.

Crestone代理首席医疗官JonBruss博士说：“我们对这些结果非常满意。”。“鉴于大流行对医疗保健的破坏，这是一项具有挑战性的研究。我们要衷心感谢所有为产生这些重要数据做出贡献的患者，家属，临床医生和合作者。”。

The company also announced that, based upon the results of this study, the National Institute of Allergy and Infectious Diseases (NIAID) has exercised its option under an existing agreement with Crestone to provide $4.5 million in new funding for microbiome analyses, manufacturing process optimization and other phase 2 supporting studies.

该公司还宣布，根据这项研究的结果，美国国家过敏与传染病研究所（NIAID）已根据与Crestone的现有协议行使其选择权，为微生物组分析，制造过程优化和其他第二阶段支持研究提供450万美元的新资金。

This project has been funded with federal funds from NIAID, National Institutes of Health, Department of Health and Human Services, under Contract No. 75N93019C00056..

根据75N93019C00056号合同，该项目由NIAID、国立卫生研究院、卫生与公众服务部的联邦资金资助。。

“We very much appreciate NIAID’s scientific input and the more than $28 million in funding for phase 2 development of CRS3123,” said Urs Ochsner, PhD, co-Founder, Vice President of R&D and CEO at Crestone. “With these topline data and further data to come in the next few months, we look forward to discussions with the FDA and prospective development partners and investors about accelerating into pivotal CDI studies with CRS3123,” said Dr.

Crestone联合创始人、研发副总裁兼首席执行官Urs Ochsner博士表示：“我们非常感谢NIAID的科学投入以及CRS3123第二阶段开发的2800多万美元资金。”。“有了这些主要数据和未来几个月的进一步数据，我们期待着与FDA和潜在的发展合作伙伴和投资者进行讨论，以加速与CRS3123进行关键的CDI研究，”Dr。

Ochsner..

奥克斯纳。。。

About the Phase 2 Clinical Trial of CRS3123

关于CRS3123的2期临床试验

The Phase 2, randomized, double-blind, comparator-controlled, multicenter study evaluated safety and efficacy of two dosages of CRS3123 (200 mg and 400 mg) administered twice-daily compared with vancomycin 125 mg administered four times daily in 43 adults diagnosed with a primary episode or first recurrence of CDI.

第二阶段，随机，双盲，比较对照，多中心研究评估了两种剂量的CRS3123（200 mg和400 mg）每日两次的安全性和有效性，而万古霉素125 mg每日四次在43名诊断为原发性CDI发作或首次复发的成年人中。

The duration of treatment for all study treatment arms was 10 days. Patients with clinically documented, toxin-positive CDI were enrolled at sites in the U.S. and Canada. The primary endpoint was defined as the rate of clinical cure at day 12 in the ITT population. Secondary and exploratory endpoints included rates of recurrence and global cure, time to resolution of diarrhea and the effect of CRS3123 on commensal bacteria in the gut..

所有研究治疗组的治疗持续时间为10天。临床记录的毒素阳性CDI患者在美国和加拿大的网站登记。。次要和探索性终点包括复发率和整体治愈率，腹泻消退时间以及CRS3123对肠道共生细菌的影响。。

About C. difficile Infection

关于艰难梭菌感染

CDI has been identified by the Centers for Disease Control and Prevention (CDC) as an “urgent” threat. CDI is an infection of the gut with symptoms of painful diarrhea, associated mental anguish and sometimes toxic megacolon or death. Currently, most patients are treated with suboptimal, broad-spectrum antibiotics that prevent healthy gut microbiota from recovering, contributing to CDI recurrence rates of 20-40%.

。CDI是一种肠道感染，症状为腹泻疼痛，伴有精神痛苦，有时还会出现中毒性巨结肠或死亡。目前，大多数患者接受次优的广谱抗生素治疗，这些抗生素会阻止健康的肠道微生物群恢复，导致CDI复发率为20-40%。

Once CDI recurs, it is more likely to recur again and again even after further treatment with existing therapeutics, leading to substantially increased morbidity and mortality. 30-day CDI mortality rates ranging from 6% to 11% have been reported by CDC and multiple other sources. Among Medicare beneficiaries over 65 with a first CDI episode, mortality from all causes within 12 months was between 35% and 45%.

一旦CDI复发，即使在用现有疗法进一步治疗后，也更有可能一次又一次复发，导致发病率和死亡率显着增加。CDC和其他多个来源报道了30天CDI死亡率从6%到11%不等。在65岁以上首次发生CDI的医疗保险受益人中，12个月内所有原因的死亡率在35%至45%之间。

An effective therapy that treats CDI while preventing recurrent CDI continues to be urgently needed..

仍然迫切需要一种治疗CDI同时预防复发性CDI的有效疗法。。

About CRS3123

关于CRS3123

CRS3123 is a small molecule that selectively inhibits one form of the bacterial methionyl-tRNA synthetase, which is the mechanistic basis of its narrow spectrum. This target is not present in human cells, nor in other important bacterial species that are part of the normal microbiota of the gut. As a protein synthesis inhibitor, CRS3123 blocks not only C.

CRS3123是一种小分子，可选择性抑制一种形式的细菌甲硫氨酰-tRNA合成酶，这是其窄谱的机理基础。该靶标不存在于人类细胞中，也不存在于作为肠道正常微生物群一部分的其他重要细菌物种中。作为蛋白质合成抑制剂，CRS3123不仅阻断C。

difficile growth, but also toxin production and spore formation. In Phase 1 trials in healthy subjects and in this Phase 2 trial in CDI patients, CRS3123 achieved high intestinal concentrations, low systemic exposure and was generally safe and well tolerated. The FDA has granted QIDP and Fast Track designations to CRS3123 for the treatment of CDI..

艰难生长，但也产生毒素和孢子形成。在健康受试者的第一阶段试验和CDI患者的第二阶段试验中，CRS3123实现了高肠道浓度，低全身暴露，并且通常安全且耐受性良好。FDA已将QIDP和快速通道指定给CRS3123用于治疗CDI。。

About Crestone, Inc.

关于Crestone，Inc。

Boulder, Colorado-based Crestone, Inc. is a clinical stage biopharmaceutical company focused on inventing and developing novel mechanism of action, small molecule antimicrobial drugs. Its pipeline includes CRS3123 in clinical development to treat CDI and under investigation to treat symptoms of autism spectrum disorder, symptoms of Pitt Hopkins Syndrome (a rare genetic disease), prevention of graft versus host disease (GvHD) and other indications.

总部位于科罗拉多州博尔德的Crestone公司是一家临床阶段的生物制药公司，专注于发明和开发新型作用机制的小分子抗菌药物。它的管道包括临床开发中的CRS3123，用于治疗CDI，正在研究中用于治疗自闭症谱系障碍的症状，皮特·霍普金斯综合征（一种罕见的遗传病）的症状，预防移植物抗宿主病（GvHD）和其他适应症。

The pipeline also includes CRS0540 to treat resistant Gram-positive infections such as methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE), and other programs directed at nontuberculous mycobacterial (NTM) disease and other bacterial and viral diseases. The company has been funded primarily through multiple research and development grants and contracts worth more than $50 million, including two ongoing NIAID contracts for CRS3123 and CRS0540, respectively.

该管道还包括CRS0540，用于治疗耐甲氧西林金黄色葡萄球菌（MRSA）和耐万古霉素肠球菌（VRE）等耐药革兰氏阳性感染，以及其他针对非结核分枝杆菌（NTM）疾病和其他细菌和病毒疾病的计划。该公司主要通过多项研发拨款和价值超过5000万美元的合同获得资金，其中包括分别针对CRS3123和CRS0540的两项正在进行的NIAID合同。

The company is owned by its scientific founders and staff and currently retains worldwide, royalty-free rights to both programs..

该公司由其科学创始人和员工所有，目前在全球范围内保留这两个项目的免版税权利。。