Riluzole

Following positive 6-month clinical outcomes from phase 2b (PARADIGM) clinical trial, Company expects additional biomarker and 12-month clinical in the near term CAMBRIDGE, Mass., June 24, 2024 /PRNewswire/ -- NeuroSense Therapeutics Ltd. (NASDAQ: NRSN) ("NeuroSense"), a company developing novel treatments for severe neurodegenerative diseases, today provides a corporate update following its recently announced analyses from its Phase 2b PARADIGM clinical trial, which demonstrated a statistically significant slowing of disease progression in high-risk ALS patients treated with PrimeC by 43% (p=0.02) as compared to placebo in the pre-specified per protocol (PP) population analysis after six months of treatment.[1] As previously indicated, the slowing of disease progression demonstrated by PrimeC versus placebo translates to a 5.04-point difference in the ALSFRS-R in favor of PrimeC (Confidence Interval: 0.862, 9.214; n=38). Corporate Highlights for the near term include: 12-month clinical results, including survival, expected in June 2024 FDA meeting anticipated in Q3 2024 Started preparations for Phase 3 clinical trial in the US, including protocol submission expected by year-end 2024 NeuroSense CEO Alon Ben-Noon states, "We are continuing to see additional results coming in from the PARADIGM trial and as they are being analyzed and verified, we intend to share them with shareholders. We anticipate sharing 12-month survival data, ALSFRS-R –as well as providing some additional biomarker data. These will include iron, ferritin and transferrin. We are looking forward to presenting target-engagement biomarkers alongside the clinical outcomes. In the meantime, we continue our discussions with several potential partners in order to drive our clinical programs forward efficiently." In addition, the Company hereby provides its Q1 2024 financial results: Research and development expenses for the three months ended March 31, 2024 and 2023 were $1.88 and $1.85 million, respectively. Research and development expenses remained at the same level primarily due to an increase in expenses to subcontractors and consultants as well as salaries and social benefits as a result of the progression of the Phase 2b ALS clinical study, which were fully offset by a decrease in share-based compensation expenses. NeuroSense expects research and development expenses to remain steady through the remainder of 2024 as a result of the open label extension of the Phase 2b ALS clinical study and the ongoing of the Phase 2 AD study. General and administrative expenses for the three months ended March 31, 2024 and 2023 were $1.11 and $1.14 million, respectively. General and administrative expenses remained at the same level primarily due to a decrease in salaries and social benefits, share-based compensation and insurance expenses, which were fully offset by increase in professional services. NeuroSense expects general and administrative expenses to remain steady through the remainder of 2024. Operating expenses for the three months ended March 31, 2024 and 2023 were $3 million due to the reasons described above. As of March 31, 2024, NeuroSense had cash of $0.74 million, which does not include gross proceeds of approximately $4.5 million from a financing that the Company completed in April 2024. As part of the transaction, the Company entered into a securities purchase agreement, pursuant to which the Company issued in a registered direct offering (i) 1,732,000 ordinary shares; (ii)pre-funded warrants to purchase 1,248,000 ordinary shares at an exercise price of $0.0001, exercisable at any time upon their issuance until exercised in full and (iii) warrants to purchase 2,980,000 ordinary shares at an exercise price of $1.50. Following the end of the first quarter of 2024, the Company determined to change its accounting method from IFRS to U.S. GAAP and accordingly has reissued its audited financial statements for all periods covered by its 2023 financial statements under U.S. GAAP. A copy of the reissued financial statements and accompanying financial data has been filed with the Securities and Exchange Commission on Form 6-K. The Company's unaudited consolidated financial results for the three months ended March 31, 2024 are presented in accordance with US GAAP Reporting Standards. A summary of NeuroSense's unaudited consolidated financial results is included in the tables below. Ben-Noon concluded, "We continue to build strong clinical evidence for PrimeC and are looking forward to upcoming announcements. Concurrently, we are working to safeguard our financial future and ability to continue our clinical activities so as to ensure that there is adequate cash on the balance sheet to complete these milestones. We plan to meet with the FDA in Q3 2024 to discuss the clinical path forward towards an NDA submission, which we believe will be a major inflection point for NeuroSense. The coming months hold tremendous potential, and we are optimistic about the outcomes and the future for NeuroSense Therapeutics." [1] High-risk patients, defined by the European Network for the Cure of ALS (ENCALS) Risk Factor as those with a higher risk for rapid disease progression, comprise approximately 50% of the total ALS population. About 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. and EU. About PARADIGM PARADIGM is a prospective, multinational, randomized, double-blind, placebo-controlled Phase 2b (NCT05357950) clinical trial of PrimeC in ALS. The trial included 68 participants living with ALS in Canada, Italy, and Israel. 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. Furthermore, to date all participants that completed the 18-month trial treatment duration, requested to continue PrimeC, which is provided to them in an Investigator Initiated Trial, not limited with time. As previously reported, 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 in analysis of the intent to treat (ITT) population. These data include all 68 people living with ALS enrolled in Canada, Italy, and Israel, with the exclusion of one patient who was misdiagnosed. In the PP top-line analysis from PARADIGM, a statistically significant slowing of disease progression was observed with a 37.4% (p=0.03) difference in ALSFRS-R in favor of PrimeC vs placebo. Most patients enrolled in both the active and placebo arms of the 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. About 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. NeuroSense completed a Phase 2a clinical trial which met its safety and efficacy endpoints including reducing functional and respiratory deterioration and statistically significant changes in ALS-related biological markers indicating PrimeC's biological activity. PrimeC was granted Orphan Drug Designation by the U.S. Food and Drug Administration and the European Medicines Agency. About 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. 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. For additional information, we invite you to visit our website and follow us on LinkedIn and X. Forward-Looking Statements 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. 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 the timing of top-line results and regulatory meetings and submissions. 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, the timing of expected regulatory and business milestones, risks associated with meeting with the FDA to determine the best path forward following the results from PARADIGM clinical trial, including a delay in any such meeting; the potential for PrimeC to safely and effectively target ALS; preclinical and clinical data for PrimeC; the uncertainty regarding outcomes and the timing of current and future clinical trials; timing for reporting data; the development and commercial potential of any product candidates of Neurosense; the ability of NeuroSense to remain listed on Nasdaq; and other risks and uncertainties set forth in NeuroSense's filings with the Securities and Exchange Commission (SEC). You should not rely on these statements as representing our views in the future. More information about the risks and uncertainties affecting NeuroSense is contained under the heading "Risk Factors" in the Annual Report on Form 20-F filed with the Securities and Exchange Commission on April 4, 2024 and NeuroSense's subsequent filings with the SEC. Forward-looking statements contained in this announcement are made as of this date, and NeuroSense undertakes no duty to update such information except as required under applicable law. Logo: SOURCE NeuroSense

2024年6月21日是第24个世界渐冻人日，也恰逢中国农历的夏至节气。在这个炎热的日子里，我们需要再次关注渐冻人这一逐渐被“冻住”的群体。 什么是“渐冻人”？ 肌萎缩侧索硬化(ALS)俗称“渐冻人”，发病后随着病情的进展会逐渐丧失运动能力，多因呼吸肌无力导致呼吸衰竭而死亡。由于在整个病程当中患者始终保持清醒的思维意识，仿佛一点点被冻结在身体内，因此被称为“渐冻人”。ALS发病率为2.6-3.0/10万，是我国首批罕见病之一，既往因患者群体小，社会各界关注度较低，随着冰桶挑战赛的风靡全球，这一特殊疾病的残酷逐渐引起各界广泛关注。 ALS的病理特征表现为进行性运动神经元变性、死亡，临床上表现为四肢、躯干及球部肌无力和肌萎缩，发病后出现进展四肢无力、肌肉萎缩，3-5年后因呼吸衰竭死亡，让家庭和社会背负沉重的负担。 ALS的发病机制是什么？ 遗憾的是，ALS发病机制依然不明确。有关ALS发病机制的研究主要集中在分子遗传机制、氧化应激、兴奋性氨基酸神经元毒性、神经免疫炎症、线粒体功能障碍、轴突运输障碍等方面。 ALS如何诊断？ ALS早期隐匿起病，从出现症状到确诊平均需要12个月的时间，甚至有些地区更长。早诊断早治疗能够使得ALS患者避免创伤性的检查和手术治疗，结合实际情况与有经验的医生共同制定科学合理的治疗方案，具有极强的临床价值。 现阶段ALS患者的诊断过程是由临床医生详细的病史追溯、全面系统的神经系统体格检查和神经电生理检查（主要是针电极肌电图）等确定的，主要在脑干和脊髓（颈、胸和腰骶段）共计4个体区中去寻找上、下运动神经元病变的证据。 需要注意的是，在发病早期诊断的ALS，尤其当临床症状不典型或缺乏疾病进展证据时，需要患者定期（建议每3个月）门诊随诊，随着病程延长不断地由临床医生评估之前的ALS诊断是否确立。对于有阳性家族史的ALS患者应该注意基因检测。 ALS治疗方法有哪些？ ALS无法治愈，缺乏有效的治疗手段。不同阶段的ALS患者，治疗的需求和护理支持不同，所以ALS患者确诊后最好由家人与综合多学科的专业团队共同实现长程管理，需要神经病学家、心理学家、营养学家、呼吸治疗师、语言康复师、护士等专业人员组成，更好的应对差异化、个体化的治疗需求，提高生存质量、延长生存时间，减轻照料者负担。 ALS治疗包括药物治疗和非药物治疗。 药物治疗中，经FDA认证的对ALS有治疗作用的药物有： 利鲁唑：于上世纪九十年代上市，主要针对于谷氨酸毒性对于运动神经元的损伤，调节中枢神经系统中谷氨酸的水平，临床证明可延长存活期和/或推迟气管切开的时间，患者可以根据吞咽情况选择片剂或混悬液。 依达拉奉：2017年5月5日上市，是自由基清除剂，能够缓解氧化应激的影响，使用方法为静脉注射。 靶向基因治疗：2023年批准上市的首款靶向SOD1突变反义核苷酸疗法Tofersen上市，主要是用于治疗超氧化物歧化酶1（SOD1）突变所致的ALS患者。 非药物治疗包括： 营养支持:ALS患者的营养支持在全病程管理中非常重要，需要根据的患者吞咽功能选择半流食、流食，注意补充充足的蛋白和热量，养成定期监测体重的习惯；必要时进行经皮内镜下胃造瘘或使用鼻胃管进食。 呼吸支持：需要定期检查肺功能，及时给予无创通气，有助于能够提高存活率、改善生活质量，延长ALS患者生存时间。 护理看护：缓解肌肉萎缩、无力带来的不适，比如给患者被动活动、局部热敷、局部按摩等，在能够运动的时候，就尽量动。要最大程度维持病人的运动机能。 编者按： 渐冻症，这一罕见病领域的挑战，由于患者数量有限，市场空间狭窄，加之研发周期漫长、资金投入巨大，使得企业在追求盈利的道路上步履维艰。但是近年来，国家对罕见病领域的支持力度不断加强，为这些患者带来了一线希望。随着越来越多企业的加入，渐冻症治疗领域的市场潜力将逐渐释放，巨大的临床需求也将得到更好的满足。让我们共同期待这一领域的美好未来！ 文章来源：西安交通大学第一附属医院 点击下方“药渡“，关注更多精彩内容 免责声明 “药渡”公众号所转载该篇文章来源于其他公众号平台，主要目的在于分享行业相关知识，传递当前最新资讯。图片、文章版权均属于原作者所有，如有侵权，请及时告知，我们会在24小时内删除相关信息。 微信公众号的推送规则又双叒叕改啦，如果您不点个“在看”或者没设为"星标"，我们可能就消散在茫茫文海之中~点这里，千万不要错过药渡的最新消息哦！