BOSTON--(BUSINESS WIRE)--Seaport Therapeutics, a clinical-stage biopharmaceutical company that is charting a proven path in neuropsychiatry, today announced two poster presentations detailing the results from multiple clinical trials of SPT-300 at the Society of Biological Psychiatry (SOBP) Annual Meeting in Austin, TX.

波士顿--（商业新闻短讯）--Seaport Therapeutics是一家临床阶段的生物制药公司，正在绘制神经精神病学的成熟路径，今天在德克萨斯州奥斯汀举行的生物精神病学学会（SOBP）年会上宣布了两张海报，详细介绍了SPT-300多项临床试验的结果。

SPT-300 has been shown to retain the activity and potency of natural allopregnanolone in an oral form and has the potential to capture the breadth of the naturally occurring neurosteroid, which is believed to have significant therapeutic potential in a range of mood and anxiety disorders, including anxious depression.

SPT-300已被证明可以保留口服形式的天然别孕烯醇酮的活性和效力，并有可能捕获天然存在的神经甾体的广度，据信它在一系列情绪和焦虑症（包括焦虑性抑郁症）中具有显着的治疗潜力。

The presentations detail data from the first-in-human, multi-part Phase 1 trial of SPT-300 and the Phase 2a trial of SPT-300 in the Trier Social Stress Test (TSST), a validated clinical model of anxiety in healthy volunteers, and include assessment of safety, tolerability, efficacy, oral bioavailability and GABAA receptor target engagement..

这些演讲详细介绍了Trier社交压力测试（TSST）中SPT-300的首次人体多部分1期试验和SPT-300的2a期试验的数据，这是一种经过验证的健康志愿者焦虑临床模型，包括安全性，耐受性，疗效，口服生物利用度和GABAA受体靶标参与度的评估。。

“These data summarize some of the evidence supporting the core mechanisms of SPT-300 as we advance to later-stage clinical studies. Our proprietary Glyph™ platform allows SPT-300 to be absorbed like a dietary fat through the intestinal lymphatic system and transported into circulation. We believe this will address allopregnanolone’s naturally low bioavailability but retain its endogenous mechanism and range of potential therapeutic effects,” said Michael Chen, Ph.D., Co-founder and Chief Scientific Officer of Seaport Therapeutics.

“随着我们进入后期临床研究，这些数据总结了支持SPT-300核心机制的一些证据。我们专有的Glyph™平台允许SPT-300像膳食脂肪一样通过肠道淋巴系统吸收并运输到循环中。我们相信这将解决别孕烯醇酮天然生物利用度低的问题，但保留其内源性机制和潜在的治疗效果范围，”Seaport Therapeutics联合创始人兼首席科学官迈克尔·陈博士说。

“These data validate that SPT-300 has the potential to make a difference for patients suffering from depression, anxiety and other neuropsychiatric conditions and also provides further validation for our Glyph platform as an elegant solution to multiple key obstacles in neuropsychiatric drug development.”.

“这些数据验证了SPT-300有可能为患有抑郁症，焦虑症和其他神经精神疾病的患者带来改变，并且还为我们的Glyph平台提供了进一步的验证，作为神经精神药物开发中多个关键障碍的优雅解决方案。”。

Details of the poster presentations at SOBP

SOBP海报展示的细节

Title: A First-in-Human Phase 1 Study of SPT-300, A First-in-Class Orally Bioavailable Prodrug of the Neurosteroid Allopregnanolone that is Absorbed via the Lymphatic System

标题：SPT-300的首次人体1期研究，SPT-300是神经甾体别孕烯醇酮的一流口服生物可利用前药，可通过淋巴系统吸收

Presenter: Michael C. Chen, Ph.D.

主持人：Michael C.Chen博士。

The topline results from the completed, multi-part Phase 1 trial of SPT-300 were reported in December 2022. Overall, the Phase 1 trial was well tolerated and evaluated oral bioavailability, safety, tolerability, pharmacokinetics and GABAA target engagement. This study included double-blind single ascending dose, multiple ascending dose and open-label food effect parts..

2022年12月报告了SPT-300完成的多部分第一阶段试验的最终结果。总体而言，1期试验耐受性良好，并评估了口服生物利用度，安全性，耐受性，药代动力学和GABAA靶标参与。本研究包括双盲单次递增剂量，多次递增剂量和开放标签食物效应部分。。

Allopregnanolone is an endogenous neurosteroid of GABAA positive allosteric modulator with validated anti-depressant and anxiolytic activity, but orally administered allopregnanolone is poorly bioavailable. SPT-300 is absorbed through the intestinal lymphatic system, allowing it to avoid first-pass metabolism.

别孕烯醇酮是GABAA阳性变构调节剂的内源性神经甾体，具有有效的抗抑郁和抗焦虑活性，但口服别孕烯醇酮的生物利用度较差。SPT-300通过肠道淋巴系统吸收，从而避免首过代谢。

Out of 99 participants enrolled in the first-in-human study, allopregnanolone exposure from SPT-300 was approximately nine times greater than published data for oral allopregnanolone. SPT-300 was generally well-tolerated and resulted in pharmacodynamic effects consistent with GABAA positive allosteric modulation.

在参加第一项人体研究的99名参与者中，SPT-300的别孕烯醇酮暴露量比口服别孕烯醇酮的公布数据大约高9倍。SPT-300通常耐受性良好，并产生与GABAA阳性变构调节一致的药效学作用。

The pharmacodynamic and pharmacokinetic properties demonstrated warrant further clinical development. No treatment-related severe or serious adverse events (AE) were reported, and the most common AE was somnolence, which was mild in all cases..

所证明的药效学和药代动力学特性值得进一步的临床开发。没有报告与治疗相关的严重或严重不良事件（AE），最常见的AE是嗜睡，在所有情况下都是轻微的。。

Title: SPT-300, an Oral Prodrug of Allopregnanolone, Potentially Reduces Salivary Cortisol Response to the Trier Social Stress Test in a Randomized, Placebo-Controlled Trial in Healthy Participants

标题：SPT-300是一种口服别孕烯醇酮前药，在一项针对健康参与者的随机安慰剂对照试验中，可能会降低唾液皮质醇对Trier社交压力测试的反应

Presenter: Michael C. Chen, Ph.D.

主持人：Michael C.Chen博士。

The topline results from Seaport’s SPT-300 Phase 2a proof-of-concept trial were reported in November 2023. The potential of SPT-300 to reduce physiological stress was tested in a randomized, placebo-controlled study using the TSST, a validated clinical model of anxiety in healthy volunteers exposed to unpredictable, novel, anticipatory and social stress..

Seaport的SPT-300 2a期概念验证试验的最终结果于2023年11月报告。SPT-300减轻生理压力的潜力在一项随机安慰剂对照研究中进行了测试，该研究使用TSST，这是一种经过验证的健康志愿者焦虑临床模型，暴露于不可预测的，新颖的，预期的和社会压力中。。

Among the enrolled healthy volunteers, SPT-300 substantially reduced salivary cortisol at all post-TSST timepoints compared to placebo and SPT-300 treated participants had significantly reduced cortisol versus placebo from baseline to peak (p=0.0001), meeting the study’s primary endpoint and demonstrating that SPT-300 regulates hypothalamic-pituitary-adrenal axis reactivity to acute stress.

在登记的健康志愿者中，与安慰剂相比，SPT-300在TSST后所有时间点均显着降低唾液皮质醇，并且SPT-300治疗的参与者与安慰剂相比，皮质醇从基线到峰值显着降低（p=0.0001），符合研究的主要终点，并证明SPT-300调节下丘脑-垂体-肾上腺轴对急性应激的反应性。

The most common treatment-emergent adverse event was somnolence (29% SPT-300 vs. 13% placebo), which was transient and mild or moderate. SPT-300 was generally well-tolerated and demonstrated GABA modulatory pharmacological activity that merits further investigation in stress-related mood and anxiety disorders, including anxious depression..

最常见的治疗紧急不良事件是嗜睡（29%的SPT-300与13%的安慰剂），这是短暂的，轻度或中度的。SPT-300通常具有良好的耐受性，并显示出GABA调节药理活性，值得进一步研究与压力相关的情绪和焦虑症，包括焦虑抑郁。。

About SPT-300

关于SPT-300

SPT-300 (Glyph-allopregnanolone), an oral prodrug of allopregnanolone, an endogenous neurosteroid, is in clinical stage development for the treatment of mood and anxiety disorders, including anxious depression. Allopregnanolone has demonstrated therapeutic benefit in a range of neuropsychiatric conditions, but it is only approved as an intravenous infusion, which has limited the scope of its clinical use.

SPT-300（Glyph allopregnanolone）是一种内源性神经甾体allopregnanolone的口服前药，正在临床阶段开发，用于治疗情绪和焦虑症，包括焦虑抑郁。别孕烯醇酮在一系列神经精神疾病中表现出治疗益处，但它仅被批准为静脉输注，这限制了其临床应用范围。

Using the Glyph platform, SPT-300 retains the activity and potency of endogenous allopregnanolone in an oral form and has the potential to capture the breadth of the natural biological response. In a Phase 2a clinical trial, SPT-300 demonstrated proof-of-concept in a validated clinical model of anxiety in healthy volunteers.

使用Glyph平台，SPT-300保留了口服形式的内源性别孕烯醇酮的活性和效力，并有可能捕获自然生物反应的广度。在一项2a期临床试验中，SPT-300在健康志愿者焦虑的有效临床模型中证明了概念验证。

SPT-300 also demonstrated oral bioavailability, tolerability and γ-aminobutyric-acid type A (GABAA) receptor target engagement in healthy volunteers in a Phase 1 clinical trial..

在1期临床试验中，SPT-300还证明了健康志愿者的口服生物利用度，耐受性和γ-氨基丁酸A型（GABAA）受体靶标参与。。

About the Glyph™ Platform

关于Glyph™平台

Glyph is Seaport's proprietary technology platform which uses the lymphatic system to enable and enhance the oral administration of drugs. With the Glyph platform, drugs are absorbed like dietary fats through the intestinal lymphatic system and transported into circulation. Seaport believes the Glyph technology has the potential to be widely applied to many therapeutic molecules that have high first-pass metabolism leading to low bioavailability and/or side effects, including hepatotoxicity.

Glyph是Seaport的专有技术平台，它使用淋巴系统来实现和增强药物的口服给药。通过Glyph平台，药物像膳食脂肪一样通过肠道淋巴系统被吸收并运输到循环中。Seaport认为，Glyph技术有潜力广泛应用于许多具有高首过代谢导致低生物利用度和/或副作用（包括肝毒性）的治疗分子。

The Glyph platform has been refined at Seaport to efficiently generate multiple therapeutic candidates within the company’s pipeline. Seaport has exclusively licensed this technology from Monash University based on the pioneering research of the Porter research group, along with the co-inventors from PureTech Health and Seaport.

Glyph平台已经在海港进行了改进，以有效地在公司的管道内产生多个候选治疗药物。Seaport根据Porter研究小组的开创性研究以及PureTech Health和Seaport的共同发明人，从莫纳什大学独家许可了这项技术。

The group and its collaborators have published research in Nature Metabolism, Frontiers in Pharmacology and the Journal of Controlled Release supporting the Glyph platform's capabilities..

该小组及其合作者在《自然代谢》、《药理学前沿》和《控制释放杂志》上发表了支持Glyph平台功能的研究。。

About Seaport Therapeutics

关于海港疗法

Seaport Therapeutics is a clinical-stage biopharmaceutical company advancing the development of novel neuropsychiatric medicines in areas of high unmet patient needs. The Company has a proven strategy of advancing clinically validated mechanisms previously held back by limitations that are overcome with its proprietary Glyph™ technology platform.

Seaport Therapeutics是一家临床阶段的生物制药公司，致力于在高度未满足患者需求的领域开发新型神经精神药物。该公司有一个行之有效的策略，即推进临床验证机制，该机制先前因其专有的Glyph™技术平台所克服的局限性而受到阻碍。

All the therapeutic candidates in its pipeline of first and best-in-class medicines are based on the Glyph platform, which is uniquely designed to enable oral bioavailability, bypass first-pass metabolism and reduce hepatotoxicity and other side effects. Seaport is led by an experienced team that was involved in inventing and advancing KarXT and other neuropsychiatric medicines and are guided by an extensive network of renowned scientists, clinicians and key opinion leaders across neurological specialties.

其一流和一流药物管道中的所有候选治疗药物均基于Glyph平台，该平台经过独特设计，可实现口服生物利用度，绕过首过代谢并减少肝毒性和其他副作用。Seaport由一支经验丰富的团队领导，该团队参与发明和开发KarXT和其他神经精神病学药物，并由著名科学家，临床医生和神经专业关键意见领袖组成的广泛网络指导。

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

有关更多信息，请访问www.seaporttx.com。。

Footnotes

脚注

1 U.S. Food and Drug Administration. (2018). FDA drug approval package: Zulresso (Application No. 211,371)

1美国食品和药物管理局。（2018年）。FDA药物批准包：Zulresso（申请号211371）

2 SPT-300, formerly known as LYT-300

2 SPT-300，原名LYT-300