Passage Bio公布FTD-GRN中upiFT-D研究的中期数据并提供业务更新-动脉网

Passage Bio Announces Interim Data from upliFT-D Study in FTD-GRN and Provides Business Updates

Passage Bio 等信源发布 2025-01-10 02:23

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可切换为仅中文

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PBFT02 demonstrated durable, elevated CSF PGRN levels and early evidence of reduction in plasma NfL levels, a disease progression biomarker, compared to published natural history data

与已发表的自然史数据相比，PBFT02表现出持久的脑脊液PGRN水平升高以及血浆NfL水平降低的早期证据，NfL是一种疾病进展的生物标志物

Evaluating Dose 2, 50% lower than Dose 1, in subsequent FTD-GRN and FTD-C9orf72 patients to allow for dose exploration and support regulatory strategy

在随后的FTD-GRN和FTD-C9orf72患者中评估剂量2，比剂量1低50%，以便进行剂量探索并支持监管策略

Expect to report 12-month data from Dose 1 and interim safety and biomarker data from Dose 2 in 2H 2025; plan to seek regulatory feedback on FTD-GRN pivotal trial design in 1H 2026

预计在2025年下半年报告剂量1的12个月数据和剂量2的临时安全性和生物标志物数据；计划在2026年上半年就FTD-GRN关键试验设计寻求监管反馈

Completed process development and scale-up of a high-productivity, suspension-based manufacturing process for PBFT02

完成PBFT02的高生产率、基于悬浮液的制造工艺的工艺开发和放大

Extended cash runway into 1Q 2027 by moving to outsourced analytical testing model and reducing operating expenses, allowing for the achievement of meaningful program milestones

通过转向外包分析测试模型和减少运营费用，将现金跑道延长至2027年第1季度，从而实现有意义的项目里程碑

PHILADELPHIA, Jan. 10, 2025 (GLOBE NEWSWIRE) -- Passage Bio, Inc. (Nasdaq: PASG), a clinical stage genetic medicines company focused on improving the lives of patients with neurodegenerative diseases, today reported updated data from the ongoing Phase 1/2 upliFT-D clinical trial evaluating PBFT02 for the treatment of frontotemporal dementia (FTD) with granulin (.

费城，2025年1月10日（环球通讯社）--Passage Bio，Inc.（纳斯达克：PASG），一家专注于改善神经退行性疾病患者生活的临床阶段遗传药物公司，今天报道了正在进行的1/2期UPLATION-D临床试验的最新数据，该试验评估了PBFT02用颗粒蛋白治疗额颞叶痴呆（FTD）。

GRN

) mutations and anticipated upcoming milestones. The company also announced the successful completion of process development and scale-up of a suspension-based manufacturing process for PBFT02. As the PBFT02 program continues to advance, the company reviewed its operating needs and will transition to an outsourced analytical testing model.

)突变和预期即将到来的里程碑。该公司还宣布成功完成PBFT02悬浮液制造工艺的工艺开发和放大。随着PBFT02计划的不断推进，该公司审查了其运营需求，并将过渡到外包的分析测试模型。

This action, coupled with an associated workforce reorganization and reductions in operating expenses, extends cash runway through meaningful program milestones into the first quarter of 2027..

这一行动，加上相关的劳动力重组和运营费用的减少，通过有意义的计划里程碑将现金跑道延长到2027年第一季度。。

“We are pleased to report updated interim data from our ongoing upliFT-D clinical trial in FTD-

“我们很高兴报告正在进行的FTD Uptive-D临床试验的最新中期数据-

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patients showing that Dose 1 PBFT02 consistently increased CSF PGRN expression and that this elevation translated to early signals of improvement in a disease progression biomarker when compared to published natural history data,” said Will Chou, M.D., president and chief executive officer of Passage Bio.

患者显示剂量1 PBFT02持续增加CSF PGRN表达，并且与公布的自然史数据相比，这种升高转化为疾病进展生物标志物改善的早期信号，”Passage Bio总裁兼首席执行官Will Chou医学博士说。

“Given the robust levels of CSF PGRN achieved with Dose 1 and to support future discussions with health authorities regarding the registrational pathway, we look forward to introducing Dose 2, which is fifty percent lower than Dose 1, for subsequent FTD-.

“鉴于剂量1达到的脑脊液PGRN水平很高，并且为了支持未来与卫生部门就注册途径进行的讨论，我们期待在随后的FTD中引入剂量2，该剂量比剂量1低50%-。

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and FTD-

和FTD-

C9orf72

patients. We remain focused on advancing the upliFT-D study in each of these patient populations and look forward to sharing additional data in the second half of 2025.”

患者。我们仍然专注于推进这些患者人群中每一个的UPLIGHT-D研究，并期待在2025年下半年分享更多数据。”

“As our PBFT02 program advances, we continue to assess our operating needs to ensure that we can deliver on meaningful program milestones as we endeavor to bring this promising therapy to the FTD patient community,” Dr. Chou continued. “After careful consideration, we will transition to an outsourced analytical testing model and have restructured our organization and reduced operating expenses accordingly.

“随着我们的PBFT02计划的推进，我们将继续评估我们的运营需求，以确保我们能够实现有意义的计划里程碑，同时努力将这种有前途的治疗方法带给FTD患者社区，”周博士继续说道。“经过仔细考虑，我们将过渡到外包的分析测试模型，并对我们的组织进行了重组，并相应降低了运营费用。

Following the implementation of these actions, we expect existing cash resources will be sufficient to fund operations into the first quarter of 2027, which will allow us to further validate the potential of PBFT02 and determine the registrational pathway for the program. We want to thank our talented team for their commitment and important contributions as we continue to pursue our mission of improving the lives of patients with neurodegenerative diseases.”.

实施这些行动后，我们预计现有现金资源将足以为2027年第一季度的运营提供资金，这将使我们能够进一步验证PBFT02的潜力，并确定该计划的注册途径。在我们继续追求改善神经退行性疾病患者生活的使命的过程中，我们要感谢我们有才能的团队的承诺和重要贡献。”。

Updated interim data from FTD-

FTD更新的中期数据-

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patients treated with Dose 1 PBFT02:

用剂量1 PBFT02治疗的患者：

Biomarkers

生物标志物

Dose 1 of PBFT02 treatment resulted in a robust and durable increase in PGRN expression.

PBFT02处理的剂量1导致PGRN表达的强烈且持久的增加。

PBFT02 consistently increased CSF PGRN expression in all patients from below 3 ng/mL at baseline to 13 – 27 ng/mL at six months (n=4) and 22 – 34 ng/mL at 12 months (n=2).

PBFT02持续增加所有患者的CSF PGRN表达，从基线时的3 ng/mL以下增加到6个月时的13–27 ng/mL（n=4），12个月时的22–34 ng/mL（n=2）。

CSF PGRN levels generally plateaued by month 6 and have remained durable through the longest available follow-up of 18 months (n=1).

。

Plasma NfL levels were 13% lower than baseline on average at 12 months (n=2) post-treatment.

治疗后12个月（n=2），血浆NfL水平平均比基线低13%。

In contrast, in untreated symptomatic FTD-

相反，在未经治疗的症状性FTD中-

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patients, plasma NfL levels are expected to increase by 29% per year, according to published natural history data

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Plasma PGRN expression remained below healthy reference levels across all patients.

所有患者的血浆PGRN表达均低于健康参考水平。

Safety

安全

(patient follow-up up to 18 months as of December 9, 2024, data cutoff)

（截至2024年12月9日，患者随访18个月，数据截止）

In 5 of 7 patients, all treatment emergent adverse events (AEs) were mild to moderate in severity.

在7名患者中，有5名患者的所有治疗紧急不良事件（AE）的严重程度均为轻度至中度。

2 of 7 patients experienced a total of 3 serious adverse events (SAEs). As previously disclosed, the first treated patient experienced the asymptomatic SAEs of venous sinus thrombosis (VST) and hepatotoxicity, leading to a revised immunosuppression regimen in all subsequent patients (1,000 mg IV methylprednisolone on days 1-3 followed by 60 mg oral prednisone through day 60).

7名患者中有2名经历了总共3次严重不良事件（SAE）。。

Patient 7 also experienced the SAE of VST, which was asymptomatic and completely resolved prior to day 30 following treatment with anticoagulants. This patient had no evidence of hepatotoxicity, immune response or other laboratory abnormalities and remains enrolled in the clinical study..

患者7也经历了VST的SAE，该SAE在抗凝剂治疗后第30天之前无症状且完全消退。该患者没有肝毒性，免疫反应或其他实验室异常的证据，仍在参加临床研究。。

No evidence of clinically significant immune responses in any patient who received the revised immunosuppression regimen.

没有证据表明接受修订后的免疫抑制方案的任何患者都有临床上显着的免疫反应。

No evidence of dorsal root ganglion (DRG) toxicity, as measured by nerve conduction studies, and no complications during intra cisterna magna (ICM) administration were observed across any of the seven treated patients.

通过神经传导研究测量，没有证据表明背根神经节（DRG）毒性，并且在七名接受治疗的患者中，没有观察到大池内（ICM）给药期间的并发症。

Recent Highlights:

最近的亮点：

Plan to evaluate Dose 2, a 50% lower dose than Dose 1, to allow for dose exploration and support program regulatory strategy:

计划评估剂量2（比剂量1低50%），以允许剂量探索和支持计划监管策略：

Given robust CSF PGRN expression achieved at Dose 1 and to aid future discussions with health authorities regarding the registrational study design, the company has introduced a lower dose level, Dose 2, which is fifty percent of Dose 1. Cohort 2, which consists of five FTD-

鉴于在剂量1时实现了强大的CSF PGRN表达，并有助于未来与卫生部门就注册研究设计进行讨论，该公司引入了较低的剂量水平，剂量2，即剂量1的50%。队列2，由五个FTD组成-

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patients, will be split between the dose levels; two patients have received Dose 1 and the remaining three patients in the cohort will receive Dose 2. The study is actively enrolling for treatment at Dose 2, and following completion of Cohort 2, the company plans to continue enrollment in the optional Cohort 3 (n=5).

患者，将在剂量水平之间分开；两名患者接受了剂量1，队列中其余三名患者将接受剂量2。该研究正在积极参加剂量2的治疗，并且在完成队列2后，该公司计划继续参加可选队列3（n=5）。

Completed process development and scale-up of a high-productivity, suspension-based manufacturing process for PBFT02:

完成PBFT02的高生产率、基于悬浮液的制造工艺的工艺开发和放大：

The company completed internal development of a suspension-based, GMP-ready manufacturing process for PBFT02 at 200-liter scale. This process is substantially more efficient than the current adherent-based process, with improved yield and the promise of a lower cost of goods. In addition, the company developed and aligned with FDA on the suitability of a potency assay for the release of PBFT02 for late-stage clinical studies and commercialization.

该公司完成了200升规模的PBFT02悬浮液生产工艺的内部开发。该过程比当前基于粘附的过程效率更高，产量更高，并且有望降低商品成本。此外，该公司开发了一种效力测定法，用于释放PBFT02用于晚期临床研究和商业化，并与FDA保持一致。

These two achievements position the PBFT02 program well for late-stage development..

这两项成就为PBFT02项目的后期开发奠定了良好的基础。。

Extended cash runway into 1Q 2027 by moving to outsourced analytical testing model and reducing operating expenses:

通过转向外包分析测试模型并减少运营费用，将现金跑道延长至2027年第一季度：

After assessing its operating needs to support the continued advancement of the PBFT02 program, the company will transition to an outsourced analytical testing model. This transition, coupled with an associated reduction in workforce of approximately 55% and reductions in operating expenses, is expected to extend cash runway into the first quarter of 2027.

在评估其运营需求以支持PBFT02计划的持续推进后，该公司将过渡到外包的分析测试模型。这一过渡，再加上相关的劳动力减少约55%和运营费用的减少，预计将把现金跑道延长到2027年第一季度。

The company will continue to focus on execution of the ongoing upliFT-D clinical trial in FTD-.

该公司将继续专注于在FTD中执行正在进行的UPLATION-D临床试验。

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and FTD-

和FTD-

C9orf72

and the advancement of its preclinical program in Huntington’s disease.

以及亨廷顿舞蹈病临床前项目的进展。

On track to initiate dosing of FTD-

C9orf72

patients in 1H 2025:

The company has amended the upliFT-D clinical trial protocol to include two cohorts of FTD-

该公司修改了UPLIGHT-D临床试验方案，以包括两组FTD-

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patients to be enrolled sequentially. Each cohort will consist of up to five symptomatic FTD patients with

患者按顺序登记。每个队列将由多达五名有症状的FTD患者组成

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gene mutations; initially, patients will receive Dose 2 PBFT02. The protocol amendment is under review at clinical trial sites and the company remains on track to dose the first FTD-

基因突变；最初，患者将接受剂量2 PBFT02。该协议修正案正在临床试验现场进行审查，该公司仍在按计划服用第一剂FTD-

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patient in the first half of 2025. FTD-

2025年上半年的病人。FTD公司-

C9orf72

is estimated to affect approximately 21,000 patients between the United States and Europe and there are currently no disease modifying therapies approved. Preclinical studies have demonstrated that increasing PGRN levels can slow neurodegeneration and reduce TDP-43 pathology, which underlies the disease..

据估计，美国和欧洲之间约有21000名患者受到影响，目前尚无批准的疾病缓解疗法。临床前研究表明，增加PGRN水平可以减缓神经退行性变并减少TDP-43病理，这是该疾病的基础。。

Anticipated Upcoming Milestones:

FTD-

FTD公司-

GRN

Report 12-month data from Dose 1 and interim safety and biomarker data from Dose 2 in 2H 2025

报告2025年下半年剂量1的12个月数据和剂量2的临时安全性和生物标志物数据

Seek regulatory feedback on registrational trial design in 1H 2026

在2026年上半年寻求注册试验设计的监管反馈

FTD-

FTD公司-

C9orf72

Initiate dosing of FTD-

开始服用FTD-

C9orf72

patients in 1H 2025

2025年上半年患者

About upliFT-D (NCT04747431)

关于Upload-D（NCT04747431）

upliFT-D is a Phase 1/2 global, multi-center, open-label clinical trial of PBFT02 administered by single injection into the cisterna magna in patients aged 35 to 75 years with FTD-

Uptive-D是一项针对35至75岁FTD患者的PBFT02的1/2期全球多中心开放标签临床试验，通过单次注射到大池中进行-

GRN

or FTD-

或FTD。

C9orf72

. The clinical trial will sequentially enroll three FTD-

临床试验将依次招募三名FTD-

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cohorts and two FTD-

队列和两个FTD-

C9orf72

cohorts. Enrollment is currently ongoing. The primary endpoint of the clinical trial is to evaluate the safety and tolerability of PBFT02. Secondary endpoints include disease biomarkers and clinical outcome measures. upliFT-D is a two-year clinical trial with a three-year safety extension.

队列。目前正在进行注册。。Uptive-D是一项为期两年的临床试验，安全性延长三年。

Passage Bio is pursuing several initiatives to support clinical trial recruitment and enrollment, including a collaborative partnership with InformedDNA to provide no-cost genetic counseling and testing for adults who have been diagnosed by their physicians with FTD. More information about upliFT-D .

Passage Bio正在采取多项举措来支持临床试验的招募和登记，包括与InformedDNA的合作伙伴关系，为医生诊断为FTD的成年人提供免费的遗传咨询和检测。有关Upload-D的更多信息。

can be found here.

可以在这里找到。

About PBFT02

关于PBFT02

PBFT02 is a gene replacement therapy that utilizes an AAV1 viral vector to deliver, through ICM administration, a functional

PBFT02是一种基因替代疗法，利用AAV1病毒载体通过ICM给药提供功能性

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gene that encodes PGRN. This vector construct and delivery approach aim to elevate PGRN levels in the central nervous system to alter the course of neurodegenerative diseases. Interim clinical data from the upliFT-D Phase 1/2 study in FTD-

编码PGRN的基因。这种载体构建和递送方法旨在提高中枢神经系统中PGRN的水平，以改变神经退行性疾病的进程。FTD中UPLATION-D 1/2期研究的中期临床数据-

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participants shows that ICM administration of PBFT02 resulted in robust PGRN elevations in the CSF.

参与者表明，ICM施用PBFT02导致脑脊液中PGRN强烈升高。

The potential clinical benefit of PBFT02 is supported by extensive preclinical studies. In non-human primates, a single ICM administration of PBFT02 led to broad vector distribution throughout the CNS, and robust, dose-dependent elevations in PGRN levels in CSF. An NHP study also demonstrated that AAV1 was particularly proficient at transducing ependymal cells.

广泛的临床前研究支持了PBFT02的潜在临床益处。在非人灵长类动物中，单次ICM施用PBFT02导致整个中枢神经系统的广泛载体分布，以及CSF中PGRN水平的强烈剂量依赖性升高。NHP的一项研究还表明，AAV1在转导室管膜细胞方面特别熟练。

In a murine FTD model, PBFT02 administration improved lysosomal function and reduced neuroinflammation..

在小鼠FTD模型中，PBFT02给药改善了溶酶体功能并减少了神经炎症。。

About Passage Bio

关于通道生物

Passage Bio (Nasdaq: PASG) is a clinical stage genetic medicines company on a mission to improve the lives of patients with neurodegenerative diseases. Our primary focus is the development and advancement of cutting-edge, one-time therapies designed to target the underlying pathology of these conditions.

Passage Bio（纳斯达克：PASG）是一家临床阶段遗传药物公司，其使命是改善神经退行性疾病患者的生活。我们的主要重点是开发和推进尖端的一次性疗法，旨在针对这些疾病的潜在病理。

Passage Bio’s lead product candidate, PBFT02, seeks to treat neurodegenerative conditions, including frontotemporal dementia, by elevating progranulin levels to restore lysosomal function and slow disease progression. .

Passage Bio的主要候选产品PBFT02旨在通过提高颗粒蛋白前体水平来恢复溶酶体功能和减缓疾病进展，从而治疗神经退行性疾病，包括额颞叶痴呆。。

To learn more about Passage Bio and our steadfast commitment to protecting patients and families against loss in neurodegenerative conditions, please visit:

要了解更多有关Passage Bio以及我们对保护患者和家属免受神经退行性疾病损失的坚定承诺，请访问：

passagebio.com

Forward-Looking Statements

前瞻性声明

This press release contains “forward-looking statements” within the meaning of, and made pursuant to the safe harbor provisions of, the Private Securities Litigation Reform Act of 1995, including, but not limited to: our expectations about timing and execution of anticipated milestones, including the outsource of our analytical testing model, the initiation of dosing of FTD-.

本新闻稿包含1995年《私人证券诉讼改革法案》安全港条款含义内的“前瞻性声明”，包括但不限于：我们对预期里程碑的时间安排和执行的预期，包括我们分析测试模型的外包，FTD剂量的开始。

C9orf72

patients, timing of feedback from regulatory authorities, the progress of clinical studies and the availability of clinical data from such trials; our expectations about our collaborators’ and partners’ ability to execute key initiatives; the financial impact of the restructuring and reduction in workforce and our expectations about cash runway; and the ability of our product candidates to treat their respective target CNS disorders.

患者，监管机构反馈的时间，临床研究的进展以及此类试验的临床数据的可用性；我们对合作者和合作伙伴执行关键计划的能力的期望；重组和裁员的财务影响以及我们对现金跑道的期望；以及我们的候选产品治疗各自靶向中枢神经系统疾病的能力。

These forward-looking statements may be accompanied by such words as “aim,” “anticipate,” “believe,” “could,” “estimate,” “expect,” “forecast,” “goal,” “intend,” “may,” “might,” “plan,” “potential,” “possible,” “will,” “would,” and other words and terms of similar meaning. These statements involve risks and uncertainties that could cause actual results to differ materially from those reflected in such statements, including: our ability to develop and obtain regulatory approval for our product candidates; the timing and results of preclinical studies and clinical trials; risks associated with clinical trials, including our ability to adequately manage clinical activities, unexpected concerns that may arise from additional data or analysis obtained during clinical trials, regulatory authorities may require additional information or further studies, or may fail to approve or may delay approval of our drug candidates; the occurrence of adverse safety events; the risk that positive results in a preclinical study or clinical trial may not be replicated in subsequent trials or success in early stage clinical trials may not be predictive of results in later stage clinical trials; failure to protect and enforce our intellectual property, and other proprietary rights; our dependence on collaborators and other third parties for the development and ma.

这些前瞻性陈述可能伴随着“目标”、“预期”、“相信”、“可能”、“估计”、“预期”、“预测”、“目标”、“打算”、“可能”、“可能”、“计划”、“潜在”、“可能”、“将会”、“将会”等词语以及其他含义相似的词语。这些声明涉及风险和不确定性，可能导致实际结果与此类声明中反映的结果存在重大差异，包括：我们为候选产品开发和获得监管批准的能力；临床前研究和临床试验的时间和结果；与临床试验相关的风险，包括我们充分管理临床活动的能力，临床试验期间获得的额外数据或分析可能引起的意外担忧，监管机构可能需要额外信息或进一步研究，或者可能无法批准或可能延迟批准我们的候选药物；不良安全事件的发生；临床前研究或临床试验中的阳性结果可能无法在后续试验中复制或早期临床试验成功的风险可能无法预测后期临床试验的结果；未能保护和执行我们的知识产权和其他专有权利；我们依赖合作者和其他第三方进行开发和并购。

For further information, please contact:

欲了解更多信息，请联系：

Investors:

投资者：

Stuart Henderson

斯图尔特·亨德森

Passage Bio

传代生物

267.866.0114

shenderson@passagebio.com

Media:

媒体：