Ciprofloxacin

CAMBRIDGE, Mass., Dec. 18, 2024 /PRNewswire/ -- NeuroSense Therapeutics Ltd. (Nasdaq: NRSN) ("NeuroSense"), a late-stage clinical biotechnology company developing novel treatments for severe neurodegenerative diseases, today provided business update with corporate highlights to date and third quarter financial results. "The completion of the 18-month Phase 2b PARADIGM study was a major milestone for NeuroSense. The results highlight PrimeC's potential impact on slowing disease progression and survival benefits in people living with ALS. Furthermore, the positive feedback from a Type C meeting with the FDA on the pivotal study design has the Company on track to commence a Phase 3 study in mid-2025. In parallel, the Company is taking steps toward early commercialization in Canada, with an anticipated potential launch in 2026, bringing us closer to delivering a much-needed solution to the ALS community," stated Alon Ben-Noon, CEO of NeuroSense. Upcoming Corporate Highlights for H1 2025 include: Additional results from the 18-month Phase 2b PARADIGM study Meeting with EMEA Dossier Submission to Health Canada Phase 3 study commencement Secured $5 Million Private Placement In December 2024, NeuroSense announced a $5 million private placement at premium to market price. The Company entered into a definitive agreement with a single investor and with NeuroSense's Chief Executive Officer, Mr. Alon Ben-Noon, to purchase an aggregate of $5,000,000 of ordinary shares (or ordinary share equivalents) and warrants in a private placement. The transaction closed in December 2024. Phase 2b Results Presented at the 2024 ALS/MND & ALS ONE Research Symposiums At the 2024 International Symposium on ALS/MND on December 6-8, 2024, in Montreal, Canada, Prof. Merit Cudkowicz, Chair of Neurology at Massachusetts General Hospital, Director of the Sean M. Healey & AMG Center for ALS, and the Julieanne Dorn Professor of Neurology at Harvard Medical School, presented the compelling results of the 18-month Phase 2b PARADIGM read-out. "The data strongly support the advancement of PrimeC to a Phase 3 trial," stated Prof. Cudkowicz, following her presentation. In addition, Prof. Cudkowicz and Dr. Shiran Zimri, NeuroSense's VP of R&D, presented the results from PARADIGM at the 7th Annual ALS ONE Research Symposium on November 14th, 2024. Positive FDA Feedback on Future Phase 3 study In November 2024, the Company concluded a Type C meeting with the U.S. Food and Drug Administration (FDA) for PrimeC in the treatment of ALS. The Company received positive feedback on the design of a proposed Phase 3 clinical study and the plan for submission of an eventual 505(b)(2) marketing application. Study Completion Concludes PrimeC's Disease-modifying Potential In October 2024, NeuroSense completed PARADIGM (NCT05357950), a multinational, randomized, double-blind, placebo-controlled, 18-month Phase 2b clinical trial of PrimeC in ALS. In participants who received PrimeC compared to those who were initially on placebo before transitioning to PrimeC, disease progression was slowed by 33% (p=0.007), demonstrated in a 58% improvement in survival rates. The 18-month results indicate the potential for PrimeC to deliver disease-modifying effects, with earlier treatment initiation possibly leading to more favorable outcomes. Plans to File for Early Commercialization in Canada The Company estimates that the potential market opportunity in Canada is between $100M to $150M in peak annual revenue. As such, NeuroSense has initiated the regulatory process to seek early commercialization approval for PrimeC under Health Canada. The Company expects to submit a dossier in Q2 2025, with a regulatory decision expected by Q1 2026. Participation in 2024 Annual Northeastern Amyotrophic Lateral Sclerosis (NEALS) Consortium Meeting NeuroSense presented two abstracts highlighting the groundbreaking data from the Phase 2b PARADIGM study at the NEALS Consortium meeting on October 21-24, 2024. Clinical outcomes were delivered by renowned clinician Prof. Cudkowicz. Biomarker analysis was presented by Dr. Cristian Lunetta, a leading neurologist and ALS specialist from the NeuroMuscular Omnicentre (NEMO) in Milan, Italy. Key U.S. Patent Granted for Novel Formulation In September 2024, a pivotal patent was granted by the United States Patent and Trademark Office (USPTO), entitled "Compositions comprising Ciprofloxacin and Celecoxib" (US Patent No. US 12,097,185), relating to the novel formulation of PrimeC. This patent is expected to extend PrimeC's protection by an additional four years, with coverage until 2042. Encouraging Biomarker Data from the Phase 2b PARADIGM Study Underscores Drug's Target Engagement PrimeC Significantly Improves Key miRNAs In collaboration with Professor Noam Shomron, a world-leading scientist in the field of genetics from Tel Aviv University, PrimeC demonstrated beneficial regulation of key miRNAs, supporting the therapeutic potential to engage critical genetic targets involved in ALS progression. The two-fold reduction of several microRNAs (miRNAs) following PrimeC treatment is particularly striking, offering both a powerful biomarker for tracking ALS and a potential pathway for new therapeutic strategies. PrimeC Regulates Iron Metabolism Data from the 12-month read-out of the PARADIGM study confirmed our hypothesis that positive changes in iron metabolism are aligned with improved clinical outcomes. Patients on PrimeC demonstrated a significant decrease in ferritin levels and an increase in transferrin levels, corresponding to slowing of disease progression. This new analysis highlights PrimeC's ability to regulate the iron in people living with ALS, underscoring the drug's target engagement. Q3 2024 F inancial R esults: Research and development expenses for the nine months ended September 30, 2024 and 2023 were $4.61 and $5.39 million, respectively. Research and development expenses decreased by 0.78 million, or 14%, primarily due to a decrease in expenses to subcontractors and consultants as well as share-based compensation expenses. NeuroSense expects research and development expenses to remain steady through the remainder of 2024 as a result of the conclusion activities of the Phase 2b ALS clinical study and the ongoing of the Phase 2 AD study. General and administrative expenses for the nine months ended September 30, 2024 and 2023 were $3.52 and $3.62 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 an increase in professional services. NeuroSense expects general and administrative expenses to remain steady through the remainder of 2024. Operating expenses for the nine months ended September 30, 2024 and 2023 were $8.1 and $9 million, respectively due to the reasons described above. As of September 30, 2024, NeuroSense had cash of $0.34 million, which does not include gross proceeds of $5 million from the financing completed in December 2024. As of the date of this report, the Company believes it has shareholders' equity above the $2.5 million required by Nasdaq's Listing Rule 5550(b) requiring a minimum stockholders' equity of $2.5 million ("Equity Rule"). Therefore, the Company believes it has regained compliance with the Equity Rule and awaits Nasdaq's confirmation that the Company has evidenced compliance with the Equity Rule and that the matter has been closed. A summary of NeuroSense's unaudited consolidated financial results is included in the tables below. Ben-Noon concluded, "The most recent capital raise has strengthened our near-term financial position and supports the continuation of our clinical development plan. We are making steady progress toward partnering opportunities that will enable the pivotal Phase 3 study and advance efforts to bring PrimeC to the Canadian market. With significant milestones achieved this quarter, the coming months hold great potential for the Company to reach a key inflection point and move into the next phase of development." 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 people are diagnosed with ALS in the U.S. alone, with an annual disease burden of $1 billion. The number of people living 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. During the first 6 months of the trial, 45 participants were randomized to receive PrimeC, and 23 participants were randomized to receive placebo. This was followed by a 12-month open-label extension with all participants receiving PrimeC in a blinded manner, where neither the participants nor the clinical staff were aware of the initial treatment allocation. 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, YouTube and X. Information that may be important to investors may be routinely posted on our website and these social media channels. 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 submission of regulatory submissions to the FDA or other regulatory authorites, the timing of commencement of enrollment for clinical trials, if any, the market opportunity in Canada for PrimeC, timing of anticipated commencement of commercialization in Canada and the belief that the Company has regained compliance with the Equity Rule. 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 the risk of a delay in commencement of enrollment for the Phase 3 trial, if any, or a delay in regulatory submissions with the FDA, the risk that the trial will not be completed, lower than anticipated market opportunity in Canada, a delay in timing of anticipated commencement of commercialization in Canada, if any, meet regulatory expectations or provide sufficient data for drug approval, unexpected changes in trial design, delay in submission by the Company of its regulatory dossier, that regulatory approvals for PrimeC will be delayed or not obtained in the U.S., Canada or elsewhere; the risk of delisting from Nasdaq; unsuccessful results of the Phase 3 trial, unexpected R&D costs or operating expenses, insufficient capital to complete development of PrimeC, 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 and Health Canada 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 WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

那一次的意外跌伤，竟是她噩梦的开始。 来源 | 医脉通 作者 | 昼辞 重症监护室外，正围聚着一群家属，断断续续的啜泣声不停地在走廊里回响。 一张张病危通知书从病房里下达，家属们已经变得有些麻木了，每次都会毫不犹豫地签下自己的名字，医生到底讲了什么，他们已经听不进去了。 “那次摔倒之后，没想到只是痛苦的开始，我真恨不得代替她受苦……”家属叹息道，他们深知，监护室内外两隔，可能就是生死相别。 01 四年前的袁大妈，年已古稀，因为一次雨天意外的跌伤，导致了右侧股骨骨折。 众所周知，老人摔跤可不是一件小事，生活质量很可能会随之直线下降，所以袁大妈很快就被家人送到了大医院，做了右侧全髋关节置换手术，术后逐渐恢复了行走，基本可以生活自理。 但命运总是喜欢琢磨人，术后两年，袁大妈右髋关节开始无端地疼痛，最后甚至影响到了行走。在附近医院检查后，医生考虑是“关节置换处感染”，便给予其止疼和抗感染治疗。 开始症状稍有好转，偶尔会发作疼痛，但经过一段保守治疗之后，袁大妈的症状逐渐无法被药物所控制，甚至还出现了几次低烧，为了进一步明确病因，所以又住进了上级医院的骨科病房。 常规的针对性检查结果很快就出来了： ➤下肢X片提示右侧髋关节置换术后改变，左侧股骨缺血性坏死。 ➤骨密度提示骨质疏松。 ➤血象、CRP等炎症指标明显升高。 医生初步考虑患者右髋关节疼痛也是感染所引起，所以准备施行超声引导下关节腔穿刺获取病理学证据。 但实际上，袁大妈的右髋关节查体并未触及明显红肿及波动感，而后超声下穿刺也未抽取到关节腔液体，这究竟是怎么回事呢？同时，医生不忘留取三条组织条送检组织病原学培养。 就在众人等待培养结果期间，感染就像梦魇一般悄然布局。 02 在查房时，袁大妈自诉小便时火辣辣地疼，而后在尿培养中检测出“克氏柠檬酸杆菌”。 这是一种革兰氏阴性杆菌，属于肠道内的正常菌群，它如果在肠道内，不会导致疾病；但如果转移到其他器官定植，比如泌尿系统，则会导致疾病。 医生对因选择了左氧氟沙星进行抗感染治疗，袁大妈没想到出现了寒颤等输液反应，所以医生只能再改用为头孢哌酮舒巴坦钠进行抗炎。 与此同时，袁大妈的右髋关节疼痛也在加剧，很快便出现了高热、畏冷寒战等表现，复查的血液指标也提示感染加重。于是，医生又升级抗生素为“利奈唑胺+头孢哌酮舒巴坦钠”，同时给予补充白蛋白、止痛等支持治疗。 几天抗感染后，袁大妈的体温高峰才有所下降。 考虑患者右髋关节症状反复发作，联合光谱抗生素后血象未见明显下降；考虑右髋人工关节感染，假体周围生物膜形成，抗生素效果差。主刀医生建议行手术探查取出假体，并取组织标本送检。 家属很快地同意了。 虽然手术进行地很顺利，也留取到了相应的病原学标本，但对于袁大妈而言，术后的难关才是真正的重重考验。 首先是术后引流出了血性液体，血红蛋白也不足70g/L，营养状况极差，这些都不利于患者身体的恢复来对抗病魔，只有给予加强支持治疗后，袁大妈的情况才稍有稳定。 很快，术中留取的组织培养有了结果：表皮葡萄球菌。 这种菌为耐甲氧西林株，对所有β内酰胺类药物耐药。幸运的是，目前使用利奈唑胺敏感，可以继续使用利奈唑胺进行治疗。 03 原以来使用了敏感的抗生素后，袁大妈可以很快病愈。 没想到，她又再次出现高热，复查的炎症指标也一路飙升，粪便常规中又检出了真菌，这难道是还合并了真菌感染？ 请感染科医生会诊后，建议排查结核及布鲁氏杆菌感染，在继续使用利奈唑胺的基础上又加用了利福喷汀和氟康唑治疗。 抗感染方案刚刚调整，患者的其他系统也开始“崩盘”：急性心力衰竭、呼吸衰竭、胃潴留、肝功能异常…… 很明显，这是重症感染引起了多器官功能障碍，为今之计，只能又转入重症监护室进行各脏器系统的支持治疗。 尽管家属对于转重症很犹豫，但更担心患者逐渐加重的病情，由此天人永隔，所以还是想尽力一试，祈祷奇迹能够出现。 袁大妈转入重症监护室后，医生主要针对以下几个方面入手： ➤感染方面：动态复查相关指标以评估患者病情，留取血液、尿液送检病原学检查，治疗上给予利奈唑胺抗感染等。 ➤循环方面：患者诉气促，胸部CT示心衰肺水肿改变，考虑重症感染继发急性心力衰竭，查血气分析示乳酸明显升高，考虑组织灌注严重不足，床旁超声评估提示容量呈过负荷状态，治疗上给予经鼻高流量加温加湿给氧、强心、扩血管，呋塞米利尿、减轻心脏前后负荷改善心功能、降低心率减少心脏氧耗、维持出入量负平衡等处理。 ➤期间痰培养回报铜绿假单胞菌、肺炎克雷伯杆菌，由于患者对环丙沙星均敏感，于是给予“利奈唑胺+环丙沙星”方案进行抗感染治疗。 ➤而后利奈唑胺治疗满疗程后予以停用，紧接着尿培养检出产ESBL肺炎克雷伯杆菌对环丙沙星耐药，且为泌尿道致病菌，于是又加用哌拉西林他唑巴坦治疗，停用环丙沙星。 经过反复调整抗感染方案后，袁大妈情况时好时坏。 在一次连续发热三天之后，复查右髋关节X片。骨科医生在阅片后表示患者右髋关节软组织密度不均，不能排除局部脓肿或肉芽形成，现感染控制不佳，建议行“右髋关节软组织清创探查术”。 需要再次做手术，家属这回表示需要考虑一下。 04 患者病情进展到这里，大家是不是已经被各个部位的感染和耐药病原体搞得眼花缭乱了？ 如果面对已经覆盖较为全面的抗感染方案治疗下，患者仍有发热、炎症指标的升高，我们就不能固执地只往感染性疾病方面思考了。 非感染性疾病引起的发热，不在少数。虽然袁大妈的各项病史都指向了感染性疾病，但事已至此，不得不发散思维了。 主管医生团队开始讨论病情： ➤感染性发热方面：首先，患者除了右髋关节软组织感染，还有可能是软组织感染导致邻近骨质破坏，继而出现骨髓炎，必要时可完善骨髓穿刺术协诊；其次是肺炎，但经治疗后症状好转，复查胸部CT提示肺部实变较前吸收，因此肺炎导致高热可能性小；第三是泌尿系感染，虽然早有出现，但经治疗后现尿色澄清，复查尿常规提示尿白细胞及尿细菌数均不高，考虑泌尿系感染好转；最后还有导管相关性血流感染可能。 ➤非感染性发热方面：最终考虑自身免疫性疾病（SLB、血管炎性疾病、结缔组织病）、肿瘤性疾病（血液系统肿瘤加淋巴瘤、白血病、骨髓增生性异常综合征等、其他系统肿瘤如肝癌、肾癌等）、理化损伤、神经源性发热、内脏血管栓塞或痛风、甲亢疾病等方面。 就在医生们一筹莫展之际，每两天复查一次的血常规给了一条重要指示：白细胞数值明显高于炎症反应的表现，白细胞计数高达58.1×109/L。 白细胞的失控到底是怎么一回事呢？这是在提醒大家要警惕重症感染导致的类白血病细胞反应。 简而言之就是类白血病反应，指机体对某些刺激因素所产生的类似白血病表现的血象反应，周围血中白细胞数大多明显升高，并可有数量不等的幼稚细胞出现，当病因除去后，类白血病反应也逐渐消失。 引起类白血病反应的病因有很多，以感染及恶性肿瘤最为多见。 这样看来，原本只是为排查骨髓炎的骨髓穿刺术就显得十分重要了。果然，根据骨髓病理提示间变大T细胞淋巴瘤，但患者目前感染如此之重，也无法耐受血液科的化学治疗。 不过令人疑惑的是，骨折术后是如何发展成血液病的呢？二者是相互独立还是有因果关系？ 05 最终在请国内相关专家远程会诊后，得出了一个论断： 患者老年女性，右侧髋关节置换术后4年，局部疼痛2年，此次右侧髋臼骨质破坏行假体取出清创，术后高热、类白血病反应、高炎症状态、脓毒血症、多器官功能不全，病理为ALK-ALCL，乳腺假体植入尤其毛面假体可能导致ALK-ALCL。此患者虽然不是乳腺假体，但其发生机制相似，虽然患者目前明确为SIRS，但不除外有肿瘤的因素引起强烈的高炎症症状，建议给予维布妥昔单药治疗，如果感染可以控制，三周后再酌情联合化疗，并需要积极抗感染，维持脏器功能。 故事的最后，虽然治疗为医生打开了新的思路和方法，但袁大妈还是由于多脏器功能衰竭离开了人世，没能等到病情好转的那天，希望她在另一个世界里不再饱受病痛的煎熬。 参考资料： [1] 潘祥林,王鸿利.实用诊断学（第2版）[M].北京:人民卫生出版社,2017,11. [2] 陈淑萍.恶性肿瘤合并类白血病反应3例临床分析[J].肿瘤基础与临床,2011,24(4):355-356. 责编｜米子 阿泰 封面图来源｜视觉中国 HIV感染者因检验结果互认被拒诊？官方回应：已通知信息屏蔽！网友辣评：医生的命不是命？ 患儿死亡，医院赔偿53万余元后，家属又选择报了警……历时6年法院判决！丨医眼看法 医脉通是专业的在线医生平台，“感知世界医学脉搏，助力中国临床决策”是平台的使命。医脉通旗下拥有「临床指南」「用药参考」「医学文献王」「医知源」「e研通」「e脉播」等系列产品，全面满足医学工作者临床决策、获取新知及提升科研效率等方面的需求。 ☟戳这里，更有料！