BOSTON--(BUSINESS WIRE)--PureTech Health plc (Nasdaq: PRTC, LSE: PRTC) ('PureTech' or the 'Company'), a clinical-stage biotherapeutics company dedicated to changing the lives of patients with devastating diseases, today announced topline results from its Phase 2a, randomized, placebo-controlled, proof-of-concept trial of LYT-300 (oral allopregnanolone).

BOSTON-（BUSINESS WIRE）-PureTech Health plc（纳斯达克股票代码：PRTC，LSE:PRTC）（'PureTech'或'公司'），一家致力于改变破坏性疾病患者生活的临床阶段生物治疗公司，今天宣布了LYT-300（口服异孕烷醇酮）2a期，随机，安慰剂对照，概念验证试验的结果。

The trial was designed to evaluate the salivary cortisol response in the Trier Social Stress Test (TSST), a validated clinical model of anxiety in healthy volunteers..

该试验旨在评估Trier社会压力测试（TSST）中的唾液皮质醇反应，这是一种经过验证的健康志愿者焦虑临床模型。。

Oral administration of LYT-300 achieved the trial’s primary endpoint of a statistically significant reduction versus placebo in the increase from baseline to peak levels of the stress hormone salivary cortisol (p=0.0001). The LYT-300 treatment effect size versus placebo was 0.72, as measured by Cohen’s d, which is one of the most common ways to measure effect size.

LYT-300的口服给药达到了试验的主要终点，即与安慰剂相比，应激激素唾液皮质醇从基线到峰值水平的增加具有统计学显着的降低（p=0.0001）.LYT-300治疗效果大小与安慰剂相比为0.72，由Cohen's d测量，这是测量效应大小的最常用方法之一。

LYT-300 showed a similar effect size to previously observed results for alprazolam, a benzodiazepine drug indicated for treatment of anxiety disorders, when assessed following the TSST procedure2. An increase in cortisol levels after the TSST is a physiological response and an objective biomarker of acute stress.

当按照TSST程序评估时，LYT-300显示出与先前观察到的阿普唑仑（一种用于治疗焦虑症的苯二氮卓类药物）的结果相似的效应大小2。TSST后皮质醇水平的增加是生理反应和急性应激的客观生物标志物。

Eighty healthy volunteers were randomized and treated with either LYT-300 or placebo in a 1:1 ratio. LYT-300 was well tolerated, with all treatment-related adverse events transient, mild or moderate and consistent with the known pharmacology profile of allopregnanolone. Additional data from the study will be presented in a scientific forum..

将80名健康志愿者随机分组，并以1:1的比例用LYT-300或安慰剂治疗。LYT-300耐受性良好，所有治疗相关不良事件均为短暂，轻度或中度，与别孕烯醇酮的已知药理学特征一致。该研究的其他数据将在科学论坛上发表。。

“Anxiety disorders are an area of significant unmet medical need and current standard-of-care treatments leave much room for improvement due to inconsistent efficacy and adverse events. We know that benzodiazepines, like alprazolam, can reduce the salivary cortisol response to stress in the TSST. Cortisol is an important marker of the physiological response to stress, and reduction of stress overreactivity may be an important mechanism for treating anxiety and stress-related disorders,” said Murray Stein, MD, MPH, FRCPC, Distinguished Professor of Psychiatry and Public Health at the University of California San Diego and an advisor to PureTech.

“焦虑症是一个重大的未满足的医疗需求领域，目前的护理标准治疗由于不一致的疗效和不良事件而留下了很大的改善空间。我们知道苯二氮卓类药物，如阿普唑仑，可以减少TSST中唾液皮质醇对压力的反应。皮质醇是生理反应的重要标志，可以减轻压力erreactivity可能是治疗焦虑和压力相关疾病的重要机制，“加州大学圣地亚哥分校精神病学和公共卫生杰出教授兼PureTech顾问Murray Stein博士，MPH，FRCPC说。

“LYT-300, a non-benzodiazepine neurosteroid, blunts this stress response, highlighting its novel pharmacology and potential for helping patients in serious need of new treatment options.”.

“LYT-300是一种非苯二氮卓类神经甾体，可减弱这种应激反应，突出其新的药理学和帮助严重需要新治疗方案的患者的潜力。”。

“These data validate that LYT-300 has potential to make a difference for people living with anxiety, where there’s been a dearth of innovation and existing treatments have drawbacks,” said Daphne Zohar, Founder and Chief Executive Officer of PureTech Health. “The successful outcome of this trial builds on our strategy of identifying drugs with proven clinical efficacy but with historical limitations that have held back their therapeutic use, and then applying an innovative solution to enhance their potential for patients.

PureTech Health的创始人兼首席执行官Daphne Zohar说：“这些数据证实LYT-300有可能对焦虑症患者产生影响，因为缺乏创新，现有治疗方法存在缺陷。”。“这项试验的成功结果建立在我们的策略之上，即确定具有已证实的临床疗效但具有阻碍其治疗用途的历史局限性的药物，然后应用创新的解决方案来增强其对患者的潜力。

In the CNS arena, we previously applied this strategy to invent KarXT for the treatment of schizophrenia. Building on this approach, we now have seven wholly owned CNS programs powered by our Glyph™ platform, which is designed to enable the oral bioavailability of drugs with high first-pass metabolism and resolve hepatotoxicity.”.

在中枢神经系统领域，我们以前应用这一策略来发明KarXT治疗精神分裂症。基于这种方法，我们现在有七个由我们的Glyph支持的国有CNS程序™ 平台，旨在实现首过代谢高的药物的口服生物利用度，解决肝毒性问题。

LYT-300 is an oral prodrug of allopregnanolone, an endogenous neurosteroid. Allopregnanolone has been recognized for its potential to treat a range of neurological and neuropsychiatric indications with a well-established rapid onset of action in mood disorders. The major hurdles associated with endogenous neurosteroids in the past have been their lack of oral bioavailability and inability to chronically administer them to patients, which means they otherwise can only be administered via a long, cumbersome intravenous infusion.

LYT-300是allopregnanolone（一种内源性神经甾体）的口服前药。Allopregnanolone已被公认为具有治疗一系列神经和神经精神适应症的潜力，并在情绪障碍中迅速起效。过去与内源性神经甾体相关的主要障碍是它们缺乏口服生物利用度并且不能长期将它们给予患者，这意味着它们否则只能通过长而麻烦的静脉内输注来施用。

To overcome the challenges with this method of administration, medicinal chemistry approaches have been applied to synthesize orally bioavailable chemical analogs of allopregnanolone. These oral analogs may have different pharmacological effects than endogenous allopregnanolone and therefore may not capture its full therapeutic potential.

为了克服这种给药方法的挑战，已经应用药物化学方法来合成别孕烯醇酮的口服生物可利用的化学类似物。这些口服类似物可能具有与内源性别孕烯醇酮不同的药理作用，因此可能无法捕获其全部治疗潜力。

LYT-300 is designed to achieve oral administration of an endogenous allopregnanolone that has the potential to capture the breadth of the natural biological response..

LYT-300旨在实现内源性别孕烯醇酮的口服给药，其有可能捕获天然生物反应的广度。。

“The data generated with PureTech’s LYT-300 suggest this may be a promising treatment for anxiety disorders, as well as a range of related neurological and neuropsychiatric conditions,” said Maurizio Fava, MD, Psychiatrist-in-Chief at Massachusetts General Hospital and an advisor to PureTech. “The Glyph platform and the therapeutic candidates being developed at PureTech have the potential to treat a range of central nervous system disorders.”.

马萨诸塞州总医院精神病医生兼顾问Maurizio Fava博士说：“使用PureTech的LYT-300生成的数据表明，这可能是治疗焦虑症以及一系列相关神经和神经精神疾病的有希望的治疗方法。到PureTech。“PureTech正在开发的Glyph平台和治疗候选药物具有治疗一系列中枢神经系统疾病的潜力。”。

These results further validate PureTech’s Glyph platform, which is designed to employ the lymphatic system's natural lipid absorption and transport process to enable the oral administration of certain therapeutics that otherwise cannot be administered orally. PureTech has generated seven CNS programs based on its Glyph platform, including LYT-300 and LYT-310 (oral cannabidiol), which is currently in development for the treatment of epilepsies and other neurological indications..

这些结果进一步验证了PureTech的Glyph平台，该平台旨在利用淋巴系统的天然脂质吸收和转运过程，使口服某些不能口服的治疗药物成为可能。PureTech基于其Glyph平台生成了七个CNS程序，包括LYT-300和LYT-310（口服大麻二酚），目前正在开发用于治疗癫痫和其他神经系统适应症。。

As part of an overall development strategy in anxiety-related indications, PureTech will be conducting additional studies in 2024. Further guidance will be provided regarding 2024 catalysts associated with the planned studies.

作为焦虑相关适应症总体发展战略的一部分，PureTech将于2024年进行更多研究。将提供关于与计划研究相关的2024种催化剂的进一步指导。

About LYT-300

关于LIST-300

LYT-300 is a clinical-stage therapeutic candidate that is in development as a potential treatment for neurological and neuropsychiatric conditions, including anxiety disorders, mood disorders and Fragile X-associated Tremor/Ataxia Syndrome. Developed using PureTech’s Glyph™ technology platform, LYT-300 is an oral prodrug of endogenous allopregnanolone that is designed to overcome its poor oral bioavailability.

LYT-300是一种临床阶段治疗候选药物，正在开发作为神经和神经精神疾病（包括焦虑症，情绪障碍和脆性X相关震颤/共济失调综合征）的潜在治疗药物。使用PureTech的Glyph开发™ 技术平台，LYT-300是内源性别孕烯醇酮的口服前药，旨在克服其口服生物利用度差的问题。

PureTech completed a randomized, placebo-controlled, Phase 2a, proof-of-concept trial of LYT-300 using a validated clinical model of anxiety in healthy volunteers in 2023, which demonstrated a statistically significant reduction in stress response, as measured by salivary cortisol. PureTech also completed a Phase 1 clinical trial of LYT-300 in 2022, which demonstrated oral bioavailability, tolerability and γ-aminobutyric-acid type A (GABAA) receptor target engagement in healthy volunteers..

PureTech于2023年使用经过验证的健康志愿者焦虑临床模型完成了LYT-300的随机，安慰剂对照，2a期概念验证试验，该试验证明了应激反应的统计学显着降低，如通过唾液皮质醇。PureTech还在2022年完成了LYT-300的1期临床试验，该试验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

关于草甘膦™ 站台

Glyph is PureTech's lymphatic-targeting platform which is designed to employ the lymphatic system's natural lipid absorption and transport process to enable the oral administration of certain therapeutics. Glyph reversibly links a drug to a dietary fat molecule, creating a novel prodrug. The linked fat molecule re-routes the drug's normal path to the systemic circulation, bypassing the liver and instead moving from the gut into the lymphatic vessels that normally process dietary fats.

Glyph是PureTech的淋巴靶向平台，旨在利用淋巴系统的天然脂质吸收和转运过程，实现某些治疗药物的口服给药。Glyph可逆地将药物与膳食脂肪分子联系起来，创造出一种新型前药。连接的脂肪分子将药物的正常路径重新引导至体循环，绕过肝脏，而是从肠道移动到通常处理膳食脂肪的淋巴管中。

PureTech believes this technology has the potential to provide a broadly applicable means of enhancing the bioavailability of certain orally administered drugs that would otherwise be limited by first-pass liver metabolism. PureTech is accelerating development of a Glyph portfolio that leverages validated efficacy, prioritizing highly characterized drugs to evaluate the ability of the Glyph technology to improve oral bioavailability or lymphatic targeting.

PureTech认为，该技术有可能提供广泛适用的手段，以提高某些口服药物的生物利用度，否则这些药物将受到首过肝脏代谢的限制。PureTech正在加速Glyph产品组合的开发，该产品组合利用经过验证的功效，优先考虑高度表征的药物，以评估Glyph技术改善口服生物利用度或淋巴靶向的能力。

PureTech's lead Glyph therapeutic candidate, LYT-300 (oral allopregnanolone), completed a randomized placebo-controlled, Phase 2a, proof-of-concept trial using a validated clinical model of anxiety in healthy volunteers in 2023. A Phase 2 clinical trial of LYT-300 in FXTAS in collaboration with the University of California, Davis, is expected to initiate in 2024.

PureTech的主要Glyph治疗候选药物LYT-300（口服别孕烯醇酮）于2023年使用经过验证的健康志愿者焦虑临床模型完成了随机安慰剂对照，2a期概念验证试验。LYT-300在FXTAS中与加州大学戴维斯分校合作进行的2期临床试验预计将于2024年启动。

PureTech has now generated seven CNS programs based on the Glyph platform. PureTech has a robust intellectual property (IP) portfolio that includes licensed patents as well as wholly owned IP, covering the Glyph technology platform, which is based on the pioneering research of Christopher Porter, PhD, and his research group at the Monash Institute of Pharmaceutical Sciences at Monash University.

PureTech现在已经基于Glyph平台生成了七个CNS程序。PureTech拥有强大的知识产权（IP）组合，其中包括许可专利和国有知识产权，涵盖Glyph技术平台，该平台基于Christopher Porter博士及其在莫纳什研究所的研究小组的开创性研究。莫纳什大学药学系。

The Porter Research Group and collaborators have published research in Nature Metabo.

波特研究小组和合作者在Nature Metabo上发表了研究成果。

About the Trier Social Stress Test

关于特里尔社会压力测试

The Trier Social Stress Test (TSST; Kirschbaum, Pirke, & Hellhammer, 1993) is a validated clinical model of anxiety. It is a widely used and well-established psychological and physiological laboratory test designed to induce acute psychosocial stress in human participants. It is considered the gold standard in human experimental stress research and is used by researchers to investigate how individuals respond to acute stressors, how stress affects cognitive and emotional processes, and how stress might contribute to various psychological and physiological conditions.

特里尔社会压力测试（TSST；Kirschbaum，Pirke，＆Hellhammer，1993）是一种经过验证的焦虑临床模型。它是一种广泛使用且完善的心理和生理实验室测试，旨在诱导人类参与者的急性心理社会压力。它被认为是人类实验压力研究的黄金标准，研究人员用来研究个体对急性压力源的反应，压力如何影响认知和情绪过程，以及压力如何促成各种心理和生理状况。

The TSST puts the participant in situations designed to elicit unpredictable, novel, anticipatory, and social stress such as preparing and giving a speech, performing arithmetic, and being observed by judges. It models stress reactivity, which is an important component in many mood, stress and anxiety disorders, and the TSST robustly increases physiological markers of stress including salivary cortisol.

TSST将参与者置于旨在引发不可预测，新颖，预期和社会压力的情境中，例如准备和发表演讲，进行算术和由法官观察。它模拟压力反应性，这是许多情绪，压力和焦虑症的重要组成部分，TSST强有力地增加压力的生理标志，包括唾液皮质醇。

Benzodiazepines, a clinically effective drug class indicated for the treatment of anxiety, reliably blunt the increased salivary cortisol in the TSST..

苯二氮卓类药物是一种临床上有效的治疗焦虑症的药物，可以可靠地钝化TSST中唾液皮质醇的增加。。

Juliane Hellhammer, PhD, founder and CEO of daacro (a contract research organization specialized on psychotropic drug effects) and recognized expert on the Trier Social Stress Test, is an advisor to PureTech.

Juliane Hellhammer博士是daacro（一家专门研究精神药物作用的合同研究组织）的创始人兼首席执行官，也是特里尔社会压力测试的公认专家，是PureTech的顾问。

About PureTech Health

关于PureTech健康

PureTech is a clinical-stage biotherapeutics company dedicated to giving life to new classes of medicine to change the lives of patients with devastating diseases. The Company has created a broad and deep pipeline through its experienced research and development team and its extensive network of scientists, clinicians and industry leaders that is being advanced both internally and through its Founded Entities.

PureTech是一家临床阶段的生物治疗公司，致力于为新型药物提供生命，以改变患有破坏性疾病的患者的生活。该公司通过其经验丰富的研发团队及其广泛的科学家，临床医生和行业领导者网络，建立了广泛而深入的渠道，该网络正在内部和通过其创始实体进行发展。

PureTech's R&D engine has resulted in the development of 27 therapeutics and therapeutic candidates, including two (Plenity® and EndeavorRx®) that have received both US FDA clearance and European marketing authorization and a third (KarXT) that has been filed for FDA approval. A number of these programs are being advanced by PureTech or its Founded Entities in various indications and stages of clinical development, including registration enabling studies.

PureTech的研发引擎已经开发出27种治疗药物和治疗候选药物，其中两种（Plenity®和EndeavorRx®）已获得美国FDA批准和欧洲上市许可，第三种（KarXT）已提交FDA批准。PureTech或其创始实体正在临床开发的各种适应症和阶段推进其中一些计划，包括注册研究。

All of the underlying programs and platforms that resulted in this pipeline of therapeutic candidates were initially identified or discovered and then advanced by the PureTech team through key validation points..

所有导致这一治疗候选药物管道的基础程序和平台最初都被识别或发现，然后由PureTech团队通过关键验证点推进。。

For more information, visit www.puretechhealth.com or connect with us on X (formerly Twitter) @puretechh.

欲了解更多信息，请访问www.puretechhealth.com或在X（以前称为Twitter）@puretech上与我们联系。

Cautionary Note Regarding Forward-Looking Statements

关于前瞻性陈述的警示

This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements contained in this press release that do not relate to matters of historical fact should be considered forward-looking statements, including without limitation those statements that relate to our expectations around the design of and the timelines and key milestones associated with clinical trials for LYT-300 and other programs from the Glyph™ platform, including in anxiety-related indications, the therapeutic potential of LYT-300, our expectations regarding the Glyph platform including the potential for new treatment applications, our therapeutic candidates and approach towards addressing major diseases, and our future prospects, developments, and strategies.

本新闻稿包含1995年“私人证券诉讼改革法”含义内的前瞻性声明。本新闻稿中包含的与历史事实无关的所有陈述均应视为前瞻性陈述，包括但不限于与我们对LYT临床试验相关的设计和时间表及关键里程碑的期望相关的陈述-300和Glyph的其他程序™ 平台，包括焦虑相关适应症，LYT-300的治疗潜力，我们对Glyph平台的期望，包括新治疗应用的潜力，我们的治疗候选人和解决主要疾病的方法，以及我们未来的前景，发展和战略。

The forward-looking statements are based on current expectations and are subject to known and unknown risks, uncertainties and other important factors that could cause actual results, performance and achievements to differ materially from current expectations, including, but not limited to, those risks, uncertainties and other important factors described under the caption 'Risk Factors' in our Annual Report on Form 20-F for the year ended December 31, 2022 filed with the SEC and in our other regulatory filings.

前瞻性陈述基于当前预期，并受到已知和未知风险，不确定性和其他重要因素的影响，这些因素可能导致实际结果，绩效和成就与当前预期有很大差异，包括但不限于这些风险，在我们向SEC和我们的其他监管文件提交的截至2022年12月31日的年度20-F年度报告中，“风险因素”标题下描述的不确定性和其他重要因素。

These forward-looking statements are based on assumptions regarding the present and future business strategies of the Company and the environment in which it will operate in the future. Each forward-looking statement speaks only as at the date of this press release. Except as required by law and regulatory requirements, we disclaim any obligation to update or revise these forward-looking statements, whether as a result of new information, future events or otherwise.

这些前瞻性声明基于对公司当前和未来业务策略及其未来运营环境的假设。每个前瞻性声明仅在本新闻稿发布之日才发表。除法律和法规要求外，我们不承担任何更新或修改这些前瞻性声明的义务，无论是由于新信息，未来事件还是其他原因。

1] Any Anxiety Disorder. (n.d.). National Institute of Mental Health (NIMH). https://www.nimh.nih.gov/health/statistics/any-anxiety-disorder

1] 任何焦虑症。（n.d.）。国家精神卫生研究所（NIMH）。https://www.nimh.nih.gov/health/statistics/any-anxiety-disorder

2] Psychoneuroendocrinology, 31(10), 1278–1288. https://doi.org/10.1016/j.psyneuen.2006.09.009 . ​

2] Psychoneuroendocrinology, 31(10), 1278–1288. https://doi.org/10.1016/j.psyneuen.2006.09.009 . ​