INDIANAPOLIS--(BUSINESS WIRE)--Gate Neurosciences, a clinical-stage biotechnology company using precision medicine approaches to develop next-generation neuroscience therapies, today announced positive topline qEEG biomarker and safety results from its Phase 1 multiple ascending dose study of apimostinel in healthy volunteers..

INDIANAPOLIS-（BUSINESS WIRE）-Gate Neurosciences，一家临床阶段的生物技术公司，使用精准医学方法开发下一代神经科学疗法，今天宣布了apimostinel的1期多剂量递增剂量研究的积极topline qEEG生物标志物和安全性结果在健康志愿者中。。

Results demonstrated a dose-dependent increase in qEEG pharmacodynamic biomarkers of NMDA receptor target activation from baseline, compared with subjects who received placebo. Maximal qEEG effects were observed at dose levels consistent with antidepressant efficacy observed in a prior Phase 2a proof of concept (POC) study of apimostinel, validating the biomarker for informing dose selection in future clinical efficacy studies across the class of molecules.

结果表明，与接受安慰剂的受试者相比，NMDA受体靶标激活的qEEG药效学生物标志物从基线开始呈剂量依赖性增加。在与apimostinel的先前2a期概念验证（POC）研究中观察到的抗抑郁效力一致的剂量水平下观察到最大qEEG效应，验证生物标志物用于在跨分子类别的未来临床功效研究中通知剂量选择。

Apimostinel was also generally well-tolerated with no ketamine-like dissociative side effects, highlighting its novel mechanistic approach of enhancing synaptic function..

Apimostinel通常也具有良好的耐受性，没有氯胺酮样解离副作用，突出了其增强突触功能的新机制。。

The positive human qEEG biomarker results with apimostinel are consistent with prior biomarker observations with zelquistinel, Gate’s lead program, which is currently being developed as a rapid-acting, once weekly, oral treatment for major depressive disorder (MDD).

使用apimostinel的阳性人类qEEG生物标志物结果与之前使用Gate's lead program zelquistinel的生物标志物观察结果一致，该计划目前正在开发为针对重度抑郁症（MDD）的快速作用，每周一次的口服治疗。

“We are very excited to see a consistent, objective biomarker of receptor activation across two independent clinical programs in both apimostinel and zelquistinel. These new positive qEEG results further advance our confidence in dose selection and our understanding of how this novel class of molecules achieves rapid and durable effects through event-driven pharmacology,” said Mike McCully, CEO of Gate Neurosciences.

“我们非常高兴在apimostinel和zelquistinel的两个独立临床项目中看到受体激活的一致，客观的生物标志物。这些新的阳性qEEG结果进一步提高了我们对剂量选择的信心，以及我们对这类新型分子如何实现的理解。通过事件驱动的药理学实现快速持久的效果，“Mike McCully说，Gate Neurosciences首席执行官。

“We now have even more conviction in our upcoming Phase 2 depression study of zelquistinel, our lead rapid-acting oral program.”.

“我们现在对即将开展的我们领先的速效口腔项目zelquistinel的2期抑郁症研究更加信念。”。

Summary of Apimostinel Phase 1 Safety and qEEG Topline Results:

Apimostinel Phase 1安全性和qEEG Topline结果摘要：

Safety & Tolerability

安全性和耐受性

Apimostinel was generally safe and well-tolerated across three ascending dose cohorts (1, 5, and 10 mg) receiving multiple doses and one single dose cohort (25 mg), in a total of 40 healthy volunteers.

在总共40名健康志愿者中，Apimostinel在接受多剂量和一个单剂量组（25mg）的三个递增剂量组（1,5和10mg）中通常是安全且耐受良好的。

No observation of ketamine-like psychotomimetic or dissociative effects, consistent with safety from two prior clinical trials and reflective of apimostinel’s novel and differentiated NMDA receptor mechanism.

没有观察到氯胺酮样拟精神病或解离作用，这与之前两项临床试验的安全性一致，反映了apimostinel新颖且分化的NMDA受体机制。

qEEG Biomarker of Target Activation

靶向激活的qEEG生物标志物

qEEG analysis showed a dose-dependent increase in pharmacodynamic biomarkers of NMDA receptor activation compared to placebo after IV administration, adjusted from baseline, at all evaluated timepoints.

qEEG分析显示，在所有评估的时间点，静脉内施用后，与安慰剂相比，NMDA受体活化的药效学生物标志物的剂量依赖性增加，从基线调整。

Maximal enhancement of qEEG signature was observed with apimostinel 10mg:

用apimostinel 10mg观察到qEEG特征的最大增强：

qEEG dose response was consistent with drug CSF concentrations that maximally enhance the NMDA receptor in nonclinical studies.

qEEG剂量反应与在非临床研究中最大程度地增强NMDA受体的药物CSF浓度一致。

qEEG dose response was consistent with antidepressant efficacy observed in a prior POC clinical study, where a single 10mg IV dose of apimostinel demonstrated rapid, statistically significant antidepressant effects at 24 hours.

qEEG剂量反应与先前POC临床研究中观察到的抗抑郁功效一致，其中单次10mg IV剂量的apimostinel在24小时显示出快速，统计学显着的抗抑郁作用。

Results validate similar qEEG biomarker observations with zelquistinel in prior clinical studies, confirming a class effect of these compounds, and inform dose selection in the next efficacy studies.

结果验证了先前临床研究中使用zelquistinel的类似qEEG生物标志物观察结果，证实了这些化合物的类效应，并在下一个疗效研究中告知剂量选择。

Apimostinel is a rapid-acting injectable program behind the company’s lead oral small molecule zelquistinel, both of which are novel positive modulators of the NMDA receptor designed to enhance synaptic function in patients with mood and cognitive disorders. Gate plans to initiate a Phase 2 study of zelquistinel to confirm efficacy in MDD in Q1 2024..

Apimostinel是该公司领先的口服小分子zelquistinel背后的快速注射程序，两者都是NMDA受体的新型正调节剂，旨在增强情绪和认知障碍患者的突触功能。Gate计划启动zelquistinel的2期研究，以确认2024年第一季度MDD的疗效。。

About Gate Neurosciences

关于门神经科学

Gate Neurosciences, headquartered in Indianapolis, is a precision medicine biotechnology company focused on advancing next-generation central nervous system (CNS) treatments that address the growing needs in mental health. The company is developing a portfolio of novel mechanisms of action that enhance synaptic function to address neuropsychiatric and neurocognitive diseases, including major depressive disorder.

Gate Neurosciences总部设在印第安纳波利斯，是一家精准医学生物技术公司，致力于推进下一代中枢神经系统（CNS）治疗，以满足日益增长的心理健康需求。该公司正在开发一系列增强突触功能的新型作用机制，以解决神经精神疾病和神经认知疾病，包括重度抑郁症。

Using learnings from extensive clinical, preclinical and translational data, along with a better understanding of CNS development challenges, the company is advancing its clinical pipeline using evidence-driven, precision psychiatry approaches..

利用广泛的临床，临床前和转化数据的学习，以及对CNS发展挑战的更好理解，该公司正在使用证据驱动的精确精神病学方法推进其临床流程。。