Substantial reductions seen in lyso-Gb1, an established biomarker of clinical response, in patients with persistently high levels despite years of treatment with currently approved therapies

尽管使用了目前批准的疗法进行了多年的治疗，但持续高水平的患者中，已确定的临床反应生物标志物lyso-Gb1的显着降低

Early signs of clinical improvement observed in bone marrow burden and fatigue, supporting FLT201’s potential to improve patient outcomes over standard of care with a one-time therapy

在骨髓负荷和疲劳方面观察到临床改善的早期迹象，支持FLT201通过一次性治疗改善患者预后的潜力

FLT201 granted Regenerative Medicine Advanced Therapy designation by FDA and Priority Medicines Designation by EMA

FLT201被FDA授予再生医学高级治疗称号，被EMA授予优先药物称号

Freeline also presenting promising in vitro and in vivo data on its GBA1 Parkinson’s disease gene therapy program, leveraging same longer-acting engineered GCase enzyme as FLT201

Freeline还利用与FLT201相同的长效工程化GCase酶，在其GBA1帕金森氏病基因治疗计划中提供了有希望的体外和体内数据

LONDON, May 09, 2024 (GLOBE NEWSWIRE) -- Freeline Therapeutics today announced new clinical data from its ongoing Phase 1/2 GALILEO-1 trial of FLT201, its adeno-associated virus (AAV) gene therapy candidate for Gaucher disease, showing substantial reductions in glucosylsphinogsine (lyso-Gb1), one of the best predictors of clinical response, in patients with persistently high levels despite years of treatment with currently approved therapies, as well as early signs of clinical improvements in bone marrow burden and fatigue.

伦敦，2024年5月9日（环球通讯社）--Freeline Therapeutics今天宣布了其正在进行的FLT201 1/2期GALILEO-1试验的新临床数据，该试验是其腺相关病毒（AAV）基因治疗戈谢病的候选药物，显示尽管使用目前批准的疗法进行了多年的治疗，但持续高水平的患者中葡萄糖基鞘氨醇（lyso-Gb1）的显着降低，这是临床反应的最佳预测因子之一，以及骨髓负荷和疲劳临床改善的早期迹象。

FLT201 continues to demonstrate a favorable safety and tolerability profile. These data are being showcased in a late-breaking oral presentation at the American Society of Gene and Cell Therapy (ASGCT) 27th Annual Meeting taking place in Baltimore, Maryland..

FLT201继续显示出良好的安全性和耐受性。在马里兰州巴尔的摩举行的美国基因与细胞治疗学会（ASGCT）第27届年会上，这些数据在最新的口头报告中得到了展示。。

Gaucher disease is caused by a mutation in the GBA1 gene, which leads to a deficiency of the glucocerebrosidase (GCase) enzyme. As a result, substrates build up in cells and organs throughout the body, causing symptoms including enlarged spleen and liver, low blood counts, bone pain, fatigue and reduced lung function.

高雪氏病是由GBA1基因突变引起的，该突变导致葡萄糖脑苷脂酶（GCase）酶缺乏。因此，底物在整个身体的细胞和器官中积累，引起症状，包括脾脏和肝脏肿大，血细胞计数低，骨痛，疲劳和肺功能下降。

FLT201 delivers a rationally engineered version of the GCase enzyme (GCase85) with greater stability than wildtype GCase, designed to stay in cells longer to more effectively clear substrates and penetrate difficult-to-reach tissues, including bone, that currently approved therapies poorly address. Reductions in lyso-Gb1 levels in the blood are highly correlated with substrate reduction in disease-affected tissues and positive clinical outcomes in Gaucher disease..

FLT201提供了一种合理设计的GCase酶（GCase85），比野生型GCase具有更高的稳定性，旨在在细胞中停留更长时间，以更有效地清除底物并穿透目前批准的疗法难以解决的难以到达的组织，包括骨骼。血液中lyso-Gb1水平的降低与受疾病影响的组织中底物的减少以及高雪氏病的积极临床结果高度相关。。

“Gaucher disease, the most common lysosomal storage disorder, is severe and progressive when not treated. Currently approved treatments have made a significant difference for people with Gaucher disease, but there is not an existing cure. Patients require life-long treatment and many continue to experience symptoms, including enlarged organs, chronic bone pain and fatigue,” said Ozlem Goker-Alpan, M.D., founder and CEO of the Lysosomal and Rare Disorder Research and Treatment Center (LDRTC) and an investigator in the Phase 1/2 GALILEO-1 trial of FLT201.

溶酶体和罕见疾病研究与治疗中心（LDRTC）创始人兼首席执行官、FLT201伽利略-1期1/2试验的研究者Ozlem Goker Alpan医学博士说：“高雪氏病是最常见的溶酶体贮积病，如果不治疗，它会变得严重和进行性。目前批准的治疗方法对高雪氏病患者产生了重大影响，但尚无治愈方法。患者需要终身治疗，许多患者会继续出现症状，包括器官肿大、慢性骨痛和疲劳。”。

“A gene therapy that could deliver the same or better efficacy than currently available treatments, while freeing people from an ongoing treatment burden, would mark a significant advance in the treatment paradigm for Gaucher disease. I am very encouraged by the clinical data to date for FLT201.”.

“一种基因疗法可以提供与目前可用的治疗相同或更好的疗效，同时使人们摆脱持续的治疗负担，这将标志着高雪氏病治疗范式的重大进步。迄今为止，FLT201的临床数据令我非常鼓舞。”。

Positive New Clinical Data for FLT201

FLT201的积极新临床数据

Today’s presentation will include updated data on safety, tolerability, GCase activity and lyso-GB1, hemoglobin and platelet levels, as well as new data on bone marrow burden and fatigue from GALILEO-1, a first-in-human, international, multicenter dose-finding study in adults with Gaucher disease Type 1.

今天的演讲将包括关于安全性，耐受性，GCase活性和lyso-GB1，血红蛋白和血小板水平的最新数据，以及GALILEO-1的骨髓负荷和疲劳的新数据，GALILEO-1是第一个在人类，国际，多中心剂量研究中对1型高雪氏病成人进行的研究。

The data being reported are from the four patients in the trial who have come off their prior therapies as of the February 19, 2024 data cutoff. These four patients have remained off their prior therapies and range in follow up from 14 to 32 weeks after dosing. All patients were treated with a single dose of 4.5x1011 vg/kg..

报告的数据来自试验中的四名患者，截至2024年2月19日，他们已经停止了先前的治疗。这四名患者在给药后14至32周的随访中一直没有接受先前的治疗。所有患者均接受单剂量4.5x1011 vg/kg的治疗。。

The data demonstrated:

数据显示：

Favorable safety and tolerability, with no infusion reactions and no serious adverse events. Modest alanine-transaminase (ALT) elevations in some patients were managed with immune therapy, with no impact to efficacy. Non-serious adverse events were all mild or moderate in severity.

良好的安全性和耐受性，无输液反应，无严重不良事件。一些患者的丙氨酸转氨酶（ALT）适度升高是通过免疫治疗来控制的，对疗效没有影响。非严重不良事件的严重程度均为轻度或中度。

Robust and continuous expression in plasma GCase, with clear evidence of cellular uptake of GCase from the plasma as measured by GCase activity in the leukocytes. Leukocytes are established indicators for broad cellular uptake in Gaucher disease.

血浆GCase中稳定且连续的表达，通过白细胞中的GCase活性测量，有明确的证据表明细胞从血浆中摄取GCase。白细胞是高雪氏病中广泛细胞摄取的既定指标。

Substantial reductions in lyso-Gb1 in patients who entered the trial with persistently high lyso-Gb1 levels despite years on prior treatment with enzyme replacement therapy (ERT) or substrate reduction therapy (SRT). Low lyso-Gb1 levels were maintained in one patient who entered the trial with well-controlled levels..

尽管多年来一直使用酶替代疗法（ERT）或底物还原疗法（SRT）进行治疗，但进入试验的患者中lyso-Gb1水平持续较高。一名以良好控制水平进入试验的患者维持了低lyso-Gb1水平。。

Maintenance of hemoglobin levels, an established endpoint for Gaucher disease clinical trials, was observed post withdrawal of treatment with ERT or SRT. Improvement or maintenance of platelet counts was also seen post withdrawal of treatment with ERT or SRT.

在停用ERT或SRT治疗后，观察到血红蛋白水平的维持，这是高雪氏病临床试验的既定终点。停用ERT或SRT治疗后，血小板计数也有所改善或维持。

Emerging late-breaking data as of April 8, 2024, also demonstrated:

截至2024年4月8日的最新数据也表明：

Reductions in bone marrow burden in the first four patients as of 12 to 38 weeks post-dosing, indicating clearance of substrate from the bone marrow and reappearance of healthy, fatty marrow.

给药后12至38周，前四名患者的骨髓负荷减少，表明基质从骨髓中清除，健康脂肪骨髓再次出现。

Clinically meaningful improvement in fatigue in the first patient dosed, which led to increased functioning and ability to perform daily activities. The patient demonstrated a 21-point improvement on the Functional Assessment of Chronic Illness Therapy (FACIT) fatigue scale, with a 2.8 to 6.8-point improvement being considered clinically meaningful in chronic illnesses.

在第一次给药的患者中，疲劳有临床意义的改善，这导致功能和日常活动能力的提高。该患者在慢性病治疗功能评估（FACIT）疲劳量表上表现出21分的改善，其中2.8至6.8分的改善被认为对慢性病具有临床意义。

As of the data cut, this patient was the only patient with sufficient follow-up data for a meaningful FACIT assessment..

截至数据截止，该患者是唯一有足够随访数据进行有意义的FACIT评估的患者。。

Freeline today also announced that FLT201 has been granted Regenerative Medicine Advanced Therapy (RMAT) designation by the US Food and Drug Administration and Priority Medicines (PRIME) Designation by the European Medicines Agency (EMA). Both RMAT and PRIME designations are designed to expedite the drug development and review process for investigational therapies intended to treat, modify, reverse or cure a serious or life-threatening disease.

Freeline今天还宣布，FLT201已被美国食品和药物管理局（FDA）授予再生医学高级治疗（RMT）称号，并被欧洲药品管理局（EMA）授予优先药物（PRIME）称号。RMAT和主要名称旨在加速旨在治疗，改变，逆转或治愈严重或危及生命的疾病的研究疗法的药物开发和审查过程。

The investigational therapy must be supported by preliminary clinical evidence that the therapy has the potential to address unmet medical needs for the disease. RMAT and PRIME provide the benefits of intensive guidance from the FDA and EMA, respectively, on efficient drug development, including the ability for early interactions to discuss surrogate or intermediate endpoints, potential ways to support accelerated approval and satisfy post-approval requirements, and potential priority review of the biologics license application..

研究性治疗必须得到初步临床证据的支持，即该疗法有可能解决该疾病未满足的医疗需求。RMAT和PRIME分别提供了FDA和EMA对有效药物开发的深入指导的好处，包括早期互动讨论替代或中间终点的能力，支持加速批准和满足批准后要求的潜在方法，以及生物制剂许可证申请的潜在优先审查。。

“FLT201 is a potentially first- and best-in-class gene therapy for Gaucher disease,” said Pamela Foulds, M.D., Freeline’s Chief Medical Officer. “It is designed to deliver a continuous supply of the enzyme missing in people with Gaucher disease and to deliver a more stable version of that enzyme, with the aim of getting enzyme into all disease-affected tissues and increasing the amount of time the enzyme is in those tissues to do its job of clearing harmful substrates.

Freeline首席医疗官Pamela Foulds医学博士说：“FLT201可能是治疗高雪氏病的一流且最好的基因疗法。”。“它旨在持续供应高雪氏病患者所缺少的酶，并提供该酶的更稳定版本，目的是使酶进入所有受疾病影响的组织，并增加酶在这些组织中的时间，以完成清除有害底物的工作。

The clinical data to date strengthen our conviction in the life-changing potential of FLT201. They also support our strategy of extending the therapeutic potential of our GCase85 enzyme into a genetically linked subset of Parkinson’s disease patients with GBA1 mutations, and we are excited to share promising new data from that program.”.

迄今为止的临床数据增强了我们对FLT201改变生活潜力的信念。他们还支持我们将GCase85酶的治疗潜力扩展到具有GBA1突变的帕金森氏病患者的遗传相关子集的策略，我们很高兴分享该计划中有希望的新数据。”。

Highlights from GBA1 Parkinson’s Disease Research Program

GBA1帕金森病研究计划的亮点

In a separate poster presentation at ASGCT, Freeline is presenting in vitro and in vivo data from its Parkinson’s disease research program. The program builds on its work with Gaucher disease, leveraging the enhanced stability of GCase85 to develop a gene therapy candidate for a subset of Parkinson’s disease patients with mutations in the GBA1 gene.

在ASGCT的另一个海报展示中，Freeline展示了其帕金森病研究计划的体外和体内数据。该计划以其对高雪氏病的研究为基础，利用GCase85增强的稳定性，为GBA1基因突变的帕金森氏病患者的一部分开发基因治疗候选药物。

As in Gaucher disease, the GBA1 mutations lead to a deficiency of GCase and the accumulation of harmful substrates, greatly increasing the risk of developing Parkinson’s disease. GBA1 mutations are also associated with earlier onset of disease, more severe symptoms and increased likelihood of progression to dementia..

与高雪氏病一样，GBA1突变导致GCase缺乏和有害底物的积累，大大增加了患帕金森氏病的风险。GBA1突变也与疾病的早期发作，更严重的症状和进展为痴呆症的可能性增加有关。。

The findings demonstrate that:

调查结果表明：

GCase85 results in an order of magnitude higher GCase activity compared to wildtype in both in vitro and in vivo studies.

在体外和体内研究中，与野生型相比，GCase85导致GCase活性高出一个数量级。

Direct injection into the caudate putamen region of the brain using an AAV9 vector is effectively distributed to the target cells of the substantia nigra, which is a key area of the brain affected by Parkinson’s disease.

使用AAV9载体直接注射到大脑的尾状壳区域可以有效地分布到黑质的靶细胞，黑质是受帕金森氏病影响的大脑的关键区域。

An AAV9-GBA1-85 construct results in stronger expression and broader GCase distribution in the brain than a wildtype AAV9-GBA1 construct when directly injected into the brain in mice.

当直接注射到小鼠的大脑中时，AAV9-GBA1-85构建体比野生型AAV9-GBA1构建体在大脑中产生更强的表达和更广泛的GCase分布。

Both the late-breaking oral presentation and the poster presentation are now available on the News & Events section of Freeline’s website.

最新的口头演示和海报演示现在都可以在Freeline网站的新闻和事件部分找到。

About FLT201

关于FLT201

FLT201 is an adeno-associated virus (AAV) gene therapy candidate that is currently being investigated in the Phase 1/2 GALILEO-1 clinical trial in adults with Gaucher disease Type 1. FLT201 is designed to generate durable increases in glucocerebrosidase (GCase) and reduce the accumulation of harmful substrates, with the aim of providing a one-time treatment that can stop disease progression, improve outcomes, and free people from lifelong treatment.

FLT201是一种腺相关病毒（AAV）基因治疗候选药物，目前正在1/2期GALILEO-1临床试验中对1型高雪氏病成人进行研究。FLT201旨在产生葡萄糖脑苷脂酶（GCase）的持久增加并减少有害底物的积累，目的是提供一种一次性治疗，可以阻止疾病进展，改善预后，并使人们免于终身治疗。

FLT201 uses Freeline’s proprietary AAVS3 capsid to introduce a novel transgene into liver cells to produce a rationally engineered GCase variant. In preclinical studies, the GCase variant has demonstrated a greater than 20-fold increase in half-life at lysosomal pH conditions compared to wildtype human GCase.

FLT201使用Freeline专有的AAVS3衣壳将新型转基因引入肝细胞，以产生合理工程化的GCase变体。在临床前研究中，与野生型人GCase相比，GCase变体在溶酶体pH条件下的半衰期增加了20倍以上。

Preclinically, FLT201 has shown robust GCase expression, leading to significant GCase uptake and substrate reduction in key tissues. For more information about the GALILEO-1 trial, please visit clinicaltrials.gov (NCT05324943)..

临床前，FLT201已显示出强大的GCase表达，导致关键组织中GCase的显着摄取和底物减少。有关GALILEO-1试验的更多信息，请访问clinicaltrials.gov（NCT05324943）。。

About Gaucher Disease

关于高雪氏病

Gaucher disease is caused by a mutation in the GBA1 gene that results in abnormally low levels of glucocerebrosidase (GCase), an enzyme needed to metabolize a certain type of lipid. As a result, harmful substrates glucosylceramide (Gb-1) and glucosylsphingosine (lyso-Gb1) build up in cells that then accumulate in various organs, causing inflammation and dysfunction.

高雪氏病是由GBA1基因突变引起的，该突变导致葡萄糖脑苷脂酶（GCase）水平异常低，GCase是代谢某种脂质所需的酶。因此，有害底物葡糖神经酰胺（Gb-1）和葡糖基鞘氨醇（lyso-Gb1）在细胞中积累，然后在各种器官中积累，引起炎症和功能障碍。

Gaucher disease is hereditary and presents in various subtypes. Freeline is currently focused on Gaucher disease Type 1, the most common form of the disease, which affects the health of the spleen, liver, bone and lung. Despite treatment with existing therapies, many people with Gaucher disease continue to experience symptoms and disease progression.

高雪氏病是遗传性的，存在于各种亚型中。Freeline目前专注于高雪氏病1型，这是该病最常见的形式，会影响脾脏，肝脏，骨骼和肺部的健康。尽管使用现有疗法进行治疗，但许多高雪氏病患者仍会继续出现症状和疾病进展。

Gaucher disease affects approximately 18,000 people in the United States, United Kingdom, France, Germany, Spain, Italy and Israel..

高雪氏病影响了美国、英国、法国、德国、西班牙、意大利和以色列约18000人。。

About GBA1-linked Parkinson’s Disease

关于GBA1相关性帕金森病

Parkinson’s disease (PD) is a progressive neurodegenerative disorder that results in tremors, muscle rigidity, difficulty walking, anxiety, depression and cognitive impairments. Approximately 5-15% of PD patients have mutations in the GBA1 gene, which encodes for the glucocerebrosidase (GCase) enzyme.

帕金森氏病（PD）是一种进行性神经退行性疾病，可导致震颤，肌肉僵硬，行走困难，焦虑，抑郁和认知障碍。大约5-15%的PD患者的GBA1基因突变，该基因编码葡萄糖脑苷脂酶（GCase）酶。

The most common genetic risk factor for PD, GBA1 mutations increase the risk of developing PD by 5- to 30-fold. GBA1 mutations are also associated with earlier onset and more severe disease. There are no approved disease-modifying therapies for PD, and current treatments, which focus on managing symptoms, become less effective over time.

GBA1突变是PD最常见的遗传危险因素，使患PD的风险增加5至30倍。GBA1突变也与较早发作和更严重的疾病有关。目前还没有批准的PD疾病缓解疗法，目前专注于控制症状的治疗方法随着时间的推移变得不那么有效。

Freeline estimates GBA1-linked PD affects approximately 190,000 patients in the United States, United Kingdom, France, Germany, Spain and Italy..

Freeline估计，美国、英国、法国、德国、西班牙和意大利约有190000名与GBA1相关的PD患者。。

About Freeline Therapeutics

关于Freeline Therapeutics

Freeline is a clinical-stage biotechnology company focused on developing transformative gene therapies for chronic debilitating diseases. Freeline is currently advancing FLT201, a highly differentiated gene therapy candidate that delivers a novel transgene, in a Phase 1/2 clinical trial in people with Gaucher disease type 1.

Freeline是一家临床阶段的生物技术公司，专注于开发针对慢性衰弱性疾病的转化基因疗法。Freeline目前正在一项针对1型高雪氏病患者的1/2期临床试验中推进FLT201，这是一种高度分化的基因治疗候选药物，可提供一种新型转基因。

Freeline has additional programs in research, including one focused on GBA1-linked Parkinson’s disease that leverages the same novel transgene as FLT201. Freeline is headquartered in the UK and has operations in the United States. For more information, visit www.freeline.life or connect with Freeline on LinkedIn and X..

Freeline还有其他研究项目，包括一个专注于GBA1连锁帕金森氏病的项目，该项目利用了与FLT201相同的新型转基因。Freeline总部位于英国，在美国有业务。有关更多信息，请访问www.freeline.life或在LinkedIn和X上与freeline连接。。

Media Contact:

媒体联系人：

Naomi Aoki

青木直美

naomi.aoki@freeline.life

naomi.aoki@freeline.life

+ 1 617 283 4298

+ 1 617 283 4298