A statistically significant, 37.4% difference (P=0.03), slowing of disease progression in ALSFRS-R, in patients treated with PrimeC compared to placebo, in the pre-specified Per Protocol (PP) population analysis

在预先指定的按方案（PP）人群分析中，与安慰剂相比，接受PrimeC治疗的患者的ALSFRS-R疾病进展减慢，差异有统计学意义（37.4%（P=0.03）

Neurofilament biomarker results from Biogen collaboration expected in January 2024

预计2024年1月Biogen合作的神经丝生物标志物结果

Primary biomarker endpoints, TDP-43 and Prostagladin2, are expected in H1 2024

主要生物标志物终点TDP-43和前列腺素2预计在2024年上半年

PrimeC's meaningful effect magnitude, strong safety profile, and unique mechanism of action will be discussed with the FDA and other regulatory agencies in an End of Phase 2 meeting in H1 2024

在2024年上半年第二阶段会议结束时，将与FDA和其他监管机构讨论PrimeC的有意义的影响程度、强大的安全性和独特的作用机制

CAMBRIDGE, Mass., Dec. 14, 2023 /PRNewswire/ -- NeuroSense Therapeutics Ltd. (Nasdaq: NRSN) ('NeuroSense'), a company developing treatments for severe neurodegenerative diseases, today reported additional positive efficacy data from further evaluation of its Phase 2b trial (PARADIGM) with NeuroSense's lead drug candidate for amyotrophic lateral sclerosis ('ALS'), PrimeC..

马萨诸塞州剑桥市，2023年12月14日/PRNewswire/--NeuroSense Therapeutics Ltd.（纳斯达克：NRSN）（“NeuroSense”）是一家开发严重神经退行性疾病治疗方法的公司，今天报道了进一步评估其2b期试验（PARADIGM）与NeuroSense肌萎缩侧索硬化症（ALS）的主要候选药物PrimeC的额外积极疗效数据。。

Evaluation of the pre-specified Per Protocol (PP) population analysis of the recent top-line results from PARADIGM revealed a statistically significant slowing of disease progression with a 37.4% (p=0.03) difference in the gold standard ALS tracking measure, the ALS Functional Rating Scale-Revised ('ALSFRS-R'), in favor of PrimeC vs placebo, and 17.2% (p=0.39) difference in Slow Vital Capacity ('SVC'), in favor of PrimeC vs placebo.

对PARADIGM最近顶线结果的预先指定的按方案（PP）人群分析的评估显示，疾病进展在统计学上显着减慢，金标准ALS跟踪测量，ALS功能评定量表修订版（“ALSFRS-R”）的差异为37.4%（p=0.03），有利于PrimeC与安慰剂，慢肺活量（“SVC”）的差异为17.2%（p=0.39），有利于PrimeC与安慰剂。

The PP analysis population includes all participants who adhered to the trial protocol and treatment plan without any major protocol deviations. The goal of a PP analysis in clinical trials is to assess the efficacy of a treatment under optimal conditions, thereby providing a clearer understanding of how well the treatment works when implemented as intended, contributing to a more comprehensive view of the trial results.  PARADIGM's PP population analysis is pre-defined in the trial's statistical analysis plan, which includes 62 patients (43 active and 19 placebo) compared to 68 patients in the Intent to Treat (ITT) population (45 active and 23 placebo)..

PP分析人群包括遵守试验方案和治疗计划的所有参与者，没有任何重大方案偏差。临床试验中PP分析的目的是评估最佳条件下治疗的疗效，从而更清楚地了解按预期实施治疗的效果，有助于更全面地了解试验结果。PARADIGM的PP人群分析是在试验的统计分析计划中预先定义的，其中包括62名患者（43名活动患者和19名安慰剂），而意向治疗（ITT）人群中有68名患者（45名活动患者和23名安慰剂患者）。。

PARADIGM is a prospective, multinational, randomized, double-blind, placebo-controlled Phase 2b (NCT05357950) clinical trial. The trial's primary endpoints include: safety and tolerability, and ALS-related biomarkers TDP-43 and Prostagladin2. The trial's secondary endpoints include: clinical efficacy outcome measures, ALSFRS-R and SVC.

PARADIGM是一项前瞻性，多国，随机，双盲，安慰剂对照的2b期临床试验（NCT05357950）。该试验的主要终点包括：安全性和耐受性，以及与ALS相关的生物标志物TDP-43和前列腺素2。该试验的次要终点包括：临床疗效结果测量，ALSFRS-R和SVC。

ALSFRS-R is the most widely used ALS tracking tool accepted by the FDA, utilized by neurologists treating ALS patients, in clinical trials, and by other regulators to determine disease progression. It tracks 12 changes in a person's physical abilities over time including functions such as: speech, walking, climbing stairs, dressing/hygiene, handwriting, turning in bed, cutting food, salivation, swallowing, and breathing.

ALSFRS-R是FDA接受的最广泛使用的ALS跟踪工具，用于治疗ALS患者的神经科医生，临床试验和其他监管机构确定疾病进展。它跟踪一个人身体能力随时间的12个变化，包括功能，如：言语、行走、爬楼梯、穿衣/卫生、书写、床上翻身、切食物、流涎、吞咽和呼吸。

SVC is a measurement of respiratory function. .

SVC是呼吸功能的测量。。

While PARADIGM is powered to demonstrate statistically significant changes in the trial's primary endpoints, the highly favorable clinical results seen in the PP analysis achieved an unexpected statistical significance.

虽然PARADIGM能够证明试验主要终点的统计学显着变化，但在PP分析中看到的非常有利的临床结果取得了意想不到的统计学意义。

The new data reported today comes on the heels of recent positive top-line safety and efficacy data of PARADIGM announced by NeuroSense. An analysis of the ITT top-line data from the 6-month double-blind segment of the trial showed clinically meaningful signs of efficacy with a 29% difference in ALSFRS-R (p=0.12) and a 13% difference in SVC (p=0.5), both in favor of PrimeC vs placebo.

今天报道的新数据紧跟着NeuroSense最近公布的PARADIGM积极的顶级安全性和有效性数据。对来自该试验6个月双盲部分的ITT顶线数据的分析显示，临床上有意义的疗效迹象，ALSFRS-R差异29%（p=0.12），SVC差异13%（p=0.5），均支持PrimeC与安慰剂。

These data include all 68 people living with ALS enrolled in Canada, Italy, and Israel, with the exclusion of one patient who was misdiagnosed. Most patients enrolled in both the active and placebo arms of trial were concurrently treated with Riluzole, the ALS standard of care medication, indicating PrimeC slowed disease progression well beyond the level afforded by the FDA approved ALS drug.   .

这些数据包括加拿大，意大利和以色列登记的所有68名ALS患者，不包括一名被误诊的患者。参加活性和安慰剂试验的大多数患者同时接受了利鲁唑（ALS标准治疗药物）的治疗，这表明PrimeC减缓了疾病进展，远远超过了FDA批准的ALS药物所提供的水平。。

In addition, the trial met its primary endpoint of safety and tolerability with results comparable to placebo, establishing a solid safety profile for PrimeC. 96% of the trial participants who completed the 6-month double-blind portion of the trial chose to receive treatment with PrimeC through a 12-month open label extension.

此外，该试验达到了安全性和耐受性的主要终点，结果与安慰剂相当，为PrimeC建立了可靠的安全性。完成6个月双盲部分试验的96%的试验参与者选择通过12个月的开放标签延长接受PrimeC治疗。

Furthermore, to date, all participants that completed the 18-month trial treatment duration requested to continue taking PrimeC, which is provided to them via an Investigator Initiated Trial. .

此外，迄今为止，所有完成18个月试验治疗期的参与者都要求继续服用PrimeC，这是通过研究者发起的试验提供给他们的。。

NeuroSense expects to report results from a strategic collaboration with Biogen in January 2024, evaluating the impact of PrimeC on neurofilament levels in participants enrolled in PARADIGM. Upon receipt of results, Biogen has the right of first refusal to co-develop/ commercialize PrimeC for the treatment of ALS for a limited time following the results.

NeuroSense预计将于2024年1月报告与Biogen的战略合作结果，评估PrimeC对PARADIGM参与者神经丝水平的影响。收到结果后，Biogen有权在结果公布后的有限时间内优先拒绝共同开发/商业化PrimeC治疗ALS。

The Company expects to report primary biomarker endpoints of ALS hallmarks TDP-43 and Prostagladin2, to evaluate PrimeC's biological activity and target engagement, in the first half of 2024 following the completion of the analysis of participants' plasma..

该公司预计在2024年上半年完成参与者血浆分析后，报告ALS标志物TDP-43和前列腺素2的主要生物标志物终点，以评估PrimeC的生物活性和目标参与度。。

An End of Phase 2 meeting with the FDA and a Scientific Advice meeting with European Medicines Agency (EMA) to discuss these results and to determine the best path forward for PrimeC's development is expected in the first half of 2024.

预计2024年上半年将与FDA举行第二阶段会议，并与欧洲药品管理局（EMA）举行科学咨询会议，讨论这些结果，确定PrimeC发展的最佳途径。

'As we analyze the PARADIGM trial results, we continue to gain a better understanding of PrimeC's potential to render a significant and meaningful clinical benefit to people living with ALS. Today we are eager to share these new data with the ALS community, as we believe the PP analysis, demonstrating a statistically significant 37.4% difference in ALSFRS-R in patients treated with PrimeC vs.

“当我们分析PARADIGM试验结果时，我们继续更好地了解PrimeC为ALS患者带来重大而有意义的临床益处的潜力。今天，我们渴望与ALS社区分享这些新数据，因为我们相信PP分析表明，在接受PrimeC治疗的患者中，ALSFRS-R的统计学显着差异为37.4%。

placebo, is an exceptional result,' stated Alon Ben-Noon, NeuroSense's CEO.  'This data, in conjunction with hopefully correlative neurofilament readouts, will create a regulatory opportunity to advance PrimeC's development in a breakthrough manner toward the market.'.

NeuroSense首席执行官阿隆·本·诺恩（AlonBenNoon）表示，安慰剂是一个特殊的结果。“这些数据，再加上相关的神经丝读数，将创造一个监管机会，推动PrimeC以突破性的方式向市场发展。”。

About ALS

关于ALS

Amyotrophic lateral sclerosis ('ALS') is an incurable neurodegenerative disease that causes complete paralysis and death within 2-5 years from diagnosis. Every year, more than 5,000 patients are diagnosed with ALS in the U.S. alone, with an annual disease burden of $1 billion. The number of patients with ALS is expected to grow by 24% by 2040 in the U.S.

肌萎缩侧索硬化症（ALS）是一种无法治愈的神经退行性疾病，在诊断后2-5年内导致完全瘫痪和死亡。仅在美国，每年就有5000多名患者被诊断出患有ALS，每年的疾病负担为10亿美元。预计到2040年，美国ALS患者人数将增长24%。

and EU..

和欧盟。。

About PrimeC

PrimeC关于PrimeC

PrimeC, NeuroSense's lead drug candidate, is a novel extended-release oral formulation composed of a unique fixed-dose combination of two FDA-approved drugs: ciprofloxacin and celecoxib. PrimeC is designed to synergistically target several key mechanisms of ALS that contribute to motor neuron degeneration, inflammation, iron accumulation and impaired ribonucleic acid ('RNA') regulation to potentially inhibit the progression of ALS.

PrimeC是NeuroSense的主要候选药物，是一种新型缓释口服制剂，由两种FDA批准的药物环丙沙星和塞来昔布的独特固定剂量组合组成。PrimeC旨在协同靶向ALS的几种关键机制，这些机制有助于运动神经元变性，炎症，铁积累和核糖核酸（“RNA”）调节受损，从而可能抑制ALS的进展。

NeuroSense completed the 6-month double-blind portion of its Phase 2b ALS clinical trial which met its safety and tolerability endpoints, as well as showing a statistically significant slowing of disease progression in the pre-specified Per Protocol (PP) population. Additional data from the Phase 2b trial are expected H1 2024.

NeuroSense完成了其2b期ALS临床试验的6个月双盲部分，该试验符合其安全性和耐受性终点，并且在预先指定的每个方案（PP）人群中显示出统计学上显着的疾病进展减慢。预计2024年上半年将获得2b期试验的其他数据。

PrimeC was granted Orphan Drug Designation by the U.S. Food and Drug Administration and the European Medicines Agency..

PrimeC被美国食品和药物管理局和欧洲药品管理局授予孤儿药称号。。

About NeuroSense

关于NeuroSense

NeuroSense Therapeutics, Ltd. is a clinical-stage biotechnology company focused on discovering and developing treatments for patients suffering from debilitating neurodegenerative diseases. NeuroSense believes that these diseases, which include amyotrophic lateral sclerosis (ALS), Alzheimer's disease and Parkinson's disease, among others, represent one of the most significant unmet medical needs of our time, with limited effective therapeutic options available for patients to date.

NeuroSense Therapeutics，Ltd.是一家临床阶段生物技术公司，专注于为患有衰弱性神经退行性疾病的患者发现和开发治疗方法。NeuroSense认为，这些疾病，包括肌萎缩侧索硬化症（ALS），阿尔茨海默氏病和帕金森氏病等，代表了我们这个时代最重要的未满足的医疗需求之一，迄今为止，患者可用的有效治疗选择有限。

Due to the complexity of neurodegenerative diseases and based on strong scientific research on a large panel of related biomarkers, NeuroSense's strategy is to develop combined therapies targeting multiple pathways associated with these diseases..

由于神经退行性疾病的复杂性，并且基于对大量相关生物标志物的强大科学研究，NeuroSense的策略是开发针对与这些疾病相关的多种途径的联合疗法。。

For additional information, we invite you to visit our website and follow us on LinkedIn and X (Twitter).

有关更多信息，我们邀请您访问我们的网站，并在LinkedIn和X（Twitter）上关注我们。

Forward-Looking Statements

前瞻性声明

This press release contains 'forward-looking statements' that are subject to substantial risks and uncertainties. All statements, other than statements of historical fact, contained in this press release are forward-looking statements. Forward-looking statements contained in this press release may be identified by the use of words such as 'anticipate,' 'believe,' 'contemplate,' 'could,' 'estimate,' 'expect,' 'intend,' 'seek,' 'may,' 'might,' 'plan,' 'potential,' 'predict,' 'project,' 'target,' 'aim,' 'should,' 'will' 'would,' or the negative of these words or other similar expressions, although not all forward-looking statements contain these words.

本新闻稿包含具有重大风险和不确定性的“前瞻性声明”。除历史事实声明外，本新闻稿中的所有声明均为前瞻性声明。本新闻稿中包含的前瞻性陈述可以通过使用诸如“预期”、“相信”、“沉思”、“可能”、“估计”、“期望”、“打算”、“寻求”、“可能”、“可能”、“计划”、“潜力”、“预测”、“项目”、“目标”、“目标”、“应该”、“将会”等词语或其他类似词语的否定词来识别，尽管并非所有前瞻性声明都包含这些词语。

Forward-looking statements are based on NeuroSense Therapeutics' current expectations and are subject to inherent uncertainties, risks and assumptions that are difficult to predict and include statements regarding PrimeC as a potential treatment for people with ALS, the timing for release of additional results from PARADIGM clinical trial, and other regulatory milestones, the timing for release of results from the Company's strategic collaboration with Biogen, the cash runway of the Company, the timing of a Phase 2 trial for Alzheimer's disease and patient enrollment regarding a Phase 3 pivotal ALS trial of PrimeC.

前瞻性陈述基于NeuroSense Therapeutics当前的预期，并受到难以预测的固有不确定性，风险和假设的影响，其中包括关于PrimeC作为ALS患者潜在治疗方法的陈述，PARADIGM临床试验额外结果发布的时间以及其他监管里程碑，该公司与Biogen战略合作的结果发布时间，该公司的现金跑道，阿尔茨海默病2期试验的时间以及PrimeC 3期关键ALS试验的患者登记。

Further, certain forward-looking statements are based on assumptions as to future events that may not prove to be accurate. The future events and trends may not occur and actual results could differ materially and adversely from those anticipated or implied in the forward looking statements. These risks include unexpected R&D costs or operating expenses, a delay in the reporting of additional results from PARADIGM clinical trial, a delay in the reporting of results from the Company's strategic collaboration with B.

此外，某些前瞻性陈述基于对未来事件的假设，这些假设可能不准确。未来的事件和趋势可能不会发生，实际结果可能与前瞻性声明中预期或暗示的结果存在重大不利差异。这些风险包括意外的研发成本或运营费用，PARADIGM临床试验额外结果报告的延迟，公司与B的战略合作结果报告的延迟。

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SOURCE NeuroSense

源神经感觉