Brain Injuries

▎药明康德内容团队编辑多发性硬化（MS）是一种累及全身多个部位的神经系统脱髓鞘病变，也是青年人群中非创伤性神经性残疾的首要病因，其主要病理特征包括炎性脱髄鞘、神经胶质细胞增生和神经退行性病变。由于MS的临床表现具有高度的异质性，且治疗选择多样，如何为患者选择更适合的治疗方案成为了该病临床管理中的一大挑战。近期，德国科学家在《科学》杂志子刊Science Translational Medicine上发表了一项纳入了500多名早期MS患者的多中心队列研究，他们通过高维流式细胞术和血清蛋白组学的组合，结合无监督聚类分析，成功识别出三种不同的外周血免疫内表型（endophenotypes）。对这些队列进行的长期随访数据表明，这些内表型与炎症和早期结构性损伤的疾病进展轨迹相关联。研究人员建议在治疗MS患者前确定其外周血免疫内表型的分型，这将有助于预测其疾病发展轨迹，并指导个体化治疗策略的制定。在这项研究中，研究团队分析了在7个德国中心招募的309名（发现组）和232名（独立验证组）未接受治疗的MS患者，这些患者在疾病发作后的前两年内被招募入组。研究团队使用多参数流式细胞术对外周血单核细胞（PBMCs）进行检测，并对血清进行有针对性的蛋白质组学分析，结合手动和自动的无监督聚类分析，最终确定了384个细胞参数和1450个可溶性标志物，定义了患者个体的免疫特征。进一步的分析发现，MS患者的免疫特征可能由不同的疾病亚型造成，每种亚型都具有独特的免疫特征。通过对细胞特征的无监督聚类分析，研究人员最终确定了三种（E1、E2和E3）不同的免疫亚型，每种亚型都展现出不同的细胞特征模式。在随后4年的随访中，研究人员发现，每个亚型都有其自己的疾病轨迹。▲特定的细胞特征定义了MS的三种免疫亚型（图片来源：参考资料[2]）例如，E1亚型患者的CD4 T细胞亚群存在变化，这些辅助细胞能够激活其他免疫细胞，并且具有与自身免疫性疾病相关联的炎性蛋白。这一组患者与较早的结构性脑损伤、更严重的疾病和更高的残疾程度相关联。也就是说，这类患者从一开始就比其他亚型患者的病情更严重。E2亚型患者的自然杀伤细胞（一种能够清除问题细胞的细胞）与其它亚型的患者存在差异。而E3患者中存在着高毒性的CD8 T细胞，该亚型的炎症程度更高。此外，E3亚型患者在第一年内的复发率更高，MS病灶更多，并且脑脊液中有更多的免疫细胞。这些线索表明此类患者可能存在血脑屏障方面的问题。尽管这些亚型的某些特征存在着一些重叠，但研究人员认为这些亚型是不同的，可以帮助预测患者疾病的进展。这些不同的亚型还表明疾病可能是通过多种免疫系统途径引起的。这项研究中还有一些结果同样令研究人员感到兴奋，这些亚型对治疗的应答会随着时间的推移而不同，这有望为药物开发人员和临床医生提供宝贵见解。例如，E3亚型中的大部分患者不会对干扰素治疗产生积极应答，但接受单克隆抗体类药物（如alemtuzumab和ocrelizumab）治疗则会有所改善。不过，研究人员也指出，这些分型对于预测患者结局的能力还需要由其他研究人员在不同的MS患者人群中进行验证。目前，研究人员正在开发一种简单的测试，用来帮助临床医生区分不同的MS内表型，从而为患者找到最有效的治疗方案。大家都在看▲欲了解更多前沿技术在生物医药产业中的应用，请长按扫描上方二维码，即可访问“药明直播间”，观看相关话题的直播讨论与精彩回放参考资料：[1] Multiple sclerosis has distinct subtypes, study finds, pointing to different treatments. Retrieved March 28, 2024, from https://www.statnews.com/2024/03/27/multiple-sclerosis-subtypes-treatment/[2] Catharina C. Gross et al. ,Multiple sclerosis endophenotypes identified by high-dimensional blood signatures are associated with distinct disease trajectories.Sci. Transl. Med.16,eade8560(2024).DOI:10.1126/scitranslmed.ade8560免责声明：药明康德内容团队专注介绍全球生物医药健康研究进展。本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。版权说明：本文来自药明康德内容团队，欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权请在「药明康德」微信公众号回复“转载”，获取转载须知。分享，点赞，在看，聚焦全球生物医药健康创新

Emboline continues to build on the earliest and most comprehensive patent portfolio for aortic embolic protection, including debris deflector and full-body debris capture-and-removal filter technologies SANTA CRUZ, Calif., April 4, 2024 /PRNewswire/ -- Emboline, Inc., a privately held medical technology company based in Santa Cruz, CA, USA, announced today the acquisition of a significant portfolio of key intellectual property from SWAT Medical AB for aortic embolic protection during interventional cardiology procedures. This acquisition adds to Emboline's existing comprehensive portfolio of platform technologies that reduce the risk of stroke and ischemic damage to other organs resulting from embolic debris released into the bloodstream during minimally invasive procedures such as Transcatheter Aortic Valve Replacement (TAVR). The family of patents included in this acquisition include but are not limited to key technologies relating to deflection of debris from entering the three aortic arteries that provide the entire blood supply to the brain as well as alternative methods of embolic protection. Continue Reading The Emboliner® is the first device to provide complete brain and body protection from ischemic events such as stroke caused by embolic debris released into the bloodstream during transcatheter heart procedures. While transcatheter valve technology and techniques have continued to be refined over the past two decades since the introduction of TAVR, suffering a major debilitating stroke remains a real and persistent threat, and is often cited by patients as being feared more than death. Emboline Announces Acquisition of Significant Embolic Protection Intellectual Property Portfolio from SWAT Medical AB Post this "We filed our first patents for aortic embolic protection a few short months after Dr. Cribier demonstrated the very first human implant of a transcatheter aortic valve," said Dr. Amir Belson, founder of Emboline and the original inventor of the Emboliner. "We have continued to add to our extensive portfolio through the years with alternative approaches to addressing this critical need, including pioneering the field of transcatheter full-body embolic protection." "Emboline's #1 focus is reducing and ultimately eliminating the fear that patients and their physicians have today of a major debilitating stroke, and this key acquisition brings us closer to that goal," said Scott Russell, President and CEO of Emboline. "We already had the earliest, broadest and deepest intellectual property portfolio in this key field, and this acquisition further strengthens and extends that portfolio. As we approach the commercial launch of our ground-breaking Emboliner device, our intellectual property will remain a key differentiator for us in all critical markets around the world." Emboline is currently conducting the Protect the Head to Head IDE trial (NCT05684146), which is a prospective, randomized, open label, multicenter, 2-arm study to demonstrate safety and effectiveness of the Emboliner® Embolic Protection Catheter compared to a control device (Sentinel CPS) for patients undergoing TAVR. Enrollment began in May 2023 and is expected to be completed by the end of 2024. About Emboline Emboline, Inc., is a privately held medical technology company based in Santa Cruz, CA that has developed the Emboliner® Embolic Protection Catheter, the first embolic protection device to provide full brain and body embolic protection by capturing and removing all debris from transcatheter procedures that would otherwise travel to the brain, kidneys and other critical organs, and reducing the incidence of stroke, cerebral ischemia, cognitive decline and other adverse outcomes associated with procedure-related emboli. More information is available at . The Emboliner® is not commercially available and is intended for investigational use only. Emboliner is a registered trademark of Emboline, Inc. Media Contact for Emboline: [email protected] SOURCE Emboline, Inc.

VANCOUVER, British Columbia--(BUSINESS WIRE)-- Alpha Cognition Inc. (CSE: ACOG) (OTCQB: ACOGF) (“Alpha Cognition,” or the “Company”), a biopharmaceutical company committed to developing novel therapies with the potential to transform the lives of people with debilitating neurodegenerative disorders, today reported financial results for the fourth quarter and full year ended 2023 and provided a corporate update. “We recently achieved a significant milestone with the acceptance of our New Drug Application by the FDA in December with a product approval date in July of this year. Our team has worked in the last quarter to manage the regulatory process and engage with regulatory reviewers in a timely manner. We believe that ALPHA-1062 will offer a meaningful differentiated therapy for patients with Alzheimer’s dementia,” said Michael McFadden, the Company’s Chief Executive Officer. Recent Corporate Updates New Patent Filing The Company recently announced that it filed a new composition-of-matter patent that secures broad protection for its lead asset, ALPHA-1062, currently under review by the FDA for mild-to-moderate Alzheimer’s Disease. The present composition-of-matter patent application is filed for approval with the USPTO and may be extended to pursue protection throughout the world. If approved, the patent will secure composition-of-matter protection for an oral formulation of ALPHA-1062 into 2044, adding to other patent protection that currently protects ALPHA-1062 through 2042 in US and 2041 in other territories around the world. The filing was based on novel and unexpected findings in the clinical trial work the company completed and further demonstrates the uniqueness of ALPHA-1062. PPM Financing The Company announced in January 2024 that it had completed a final closing pursuant to its previously announced private placement of units of the Company. The gross proceeds of the private placement offerings received through closing were US$8.45 million, which included shares of the fully subscribed 30% overallotment. NDA Acceptance The Company announced in December 2023 that the U.S. Food and Drug Administration (FDA) has completed its filing review and has accepted the Company’s New Drug Application (NDA) for ALPHA-1062, a proprietary, patented, delayed release oral tablet formulation in development for the treatment of mild-to-moderate Alzheimer’s Disease. The NDA has been granted a Prescription Drug User Fee Act (PDUFA) goal date of July 27th, 2024. Commercial Strategy Upon FDA approval, the company plans to launch commercially in the Long Term Care (LTC) market segment. The LTC market covers more than 35% of the overall Alzheimer’s disease market representing a highly concentrated patient population with the lowest barriers to access. Alpha Cognition’s commercialization strategy includes our initial commercial launch in LTC, followed by expansion to the Neurology segment once payer reimbursement has been established. Pipeline The Company announced an additional product for Alzheimer’s disease, a sublingual formulation of ALPHA-1062 that will be utilized for patients with dysphagia or who have difficulties with oral formulations. A significant minority of Alzheimer’s patients could benefit from a non-oral formulation, representing a significant supplemental opportunity for the company. The new formulation has demonstrated active drug release in <30 seconds, 90% bioavailability, and a safe and well tolerated compound. Financial Highlights for Fourth Quarter and Full year ended December 31, 2023 (Expressed in United States Dollars) Research and development (R&D) expenses were $1.2 million for the three months ended December 31, 2023, and $5.0 million for the full year ended December 31, 2023, compared to $2.4 million and $8.8 million in the same periods in 2022, respectively. R&D expenses decreased from the prior year primarily due to the completion during 2022 of the main clinical trials for ALPHA-1062; expenses in 2023 were focused on R&D for the ALPHA-1062 NDA filing related costs. General and administrative (G&A) expenses, excluding non-cash expenses relating to accretion, amortization, depreciation, and share-based compensation, were $0.8 million for the three months ended December 31, 2023, and $3.0 million for the full year ended December 31, 2023, compared to from $0.8 million and $3.5 million in the same periods of 2022 respectively. The G&A expense increased full year ended December 31, 2023; expenses were lower primarily related to lower professional fees and financing costs, offset some by higher consulting fees. The overall G&A decrease year over year was due to the Company’s cost cutting efforts and focus on the advancement of its main asset, ALPHA-1062 in Alzheimer’s Disease. The Company recorded a loss on revaluation derivative liability for the three months ended December 31, 2023, of $3.6 million and $4.1 million for full year ended December 31, 2023, compared to a gain of $0.2 million and $1.8 million in the same periods of 2022 respectively. On August 31, 2023, the Company’s functional currency changed to the USD from the CAD; as such, the Company recorded a derivative liability on the warrants outstanding with previously issued CAD exercise prices. This derivative liability is being revalued at each reporting period. On August 31, 2023, the Company charged $4,541,545 to equity to reclassify the derivative liability for warrants with exercise prices denominated in CAD using the Black-Scholes Option Pricing Model. The initial reclassification resulted in a decrease in share capital of $4,541,545. Furthermore, in December 2023, 11,777,336 warrants were re-priced from CAD to USD denominated exercise price which resulted in $4,025,102 of the derivative liability being reclassified to equity. The derivative liability at December 31, 2023, was $4.5 million which related to the outstanding warrants priced in CAD. Share-based compensation was $0.4 million for the three months ended December 31, 2023, and $1.8 million for full year ended December 31, 2023, compared to $0.2 million and $1.2 million in the same periods of 2022, respectively. The 2023 increases were primarily related to new stock option grants issued in 2023, the repricing of previously issued stock options during the first quarter of 2023, and related fluctuations in the Company’s stock price over the periods. The Company incurred foreign exchange gains of $13k during the three months ended December 31, 2023, and less than $10k for the full year ended December 31, 2023, compared to a loss of $0.9 million and $0.3 million in the same periods of 2022, respectively. The fourth quarter of 2023 comprehensive net loss was $5.8 million, or a net loss of $0.05 per share, and for the full year ended December 31, 2023, the comprehensive net loss was $13.8 million, or a net loss of $0.15 per share, compared to the fourth quarter of 2022 comprehensive net loss of $3.2 million, or a net loss of $0.05 per share, and for the full year ended December 31, 2022, comprehensive net loss of $12.1 million, or a net loss of $0.18 per share. Cash and cash equivalents at December 31, 2023 were $1.5 million, including $0.1 million in restricted cash. Effective April 1, 2024, the Company and NLS agreed to an amendment to the promissory note pursuant to which the interest rate was increased from 5.5% to 7% and the maturity date was extended from July 2024 to July 2025. Additionally, $300,000 is now due on December 31, 2024, with the remaining principal balance due at maturity. Shares of common stock outstanding at December 31, 2023 were 118,208,989. About Alpha Cognition Inc. Alpha Cognition Inc. is a pre-commercial, biopharmaceutical company dedicated to developing treatments for patients suffering from neurodegenerative diseases, such as Alzheimer’s disease, for which there are limited or no treatment options. The Company is focused on the development of ALPHA-1062 for the treatment of mild-to-moderate Alzheimer’s disease following the recent New Drug Application (the “NDA”) submission and acceptance by FDA. ALPHA-1062, is a patented new innovative product being developed as a next generation acetylcholinesterase inhibitor for the treatment of Alzheimer’s disease, with expected minimal gastrointestinal side effects. ALPHA-1062’s active metabolite is differentiated from donepezil and rivastigmine in that it binds neuronal nicotinic receptors, most notably the alpha-7 subtype, which is known to have a positive effect on cognition. ALPHA-1062 is in development in combination with memantine to treat moderate to severe Alzheimer’s disease, in development with sublingual formulation for patients suffering from dysphagia and is being out-licensed to study an intranasal formulation for cognitive impairment with mTBI (otherwise known as concussion). Neither Canadian Securities Exchange (the “CSE”) or the OTC Markets Group, accepts responsibility for the adequacy or accuracy of this release. Forward-looking Statements This news release includes forward-looking statements within the meaning of applicable securities laws. Except for statements of historical fact, any information contained in this news release may be a forward‐looking statement that reflects the Company’s current views about future events and are subject to known and unknown risks, uncertainties, assumptions and other factors that may cause the actual results, levels of activity, performance or achievements to be materially different from the information expressed or implied by these forward-looking statements. In some cases, you can identify forward‐looking statements by the words “may,” “might,” “will,” “could,” “would,” “should,” “expect,” “intend,” “plan,” “objective,” “anticipate,” “believe,” “estimate,” “predict,” “project,” “potential,” “target,” “seek,” “contemplate,” “continue” and “ongoing,” or the negative of these terms, or other comparable terminology intended to identify statements about the future. Forward‐looking statements may include statements regarding the TBI out-licensing plan and associated financing, the availability of funding pursuant to financings, the Company’s business strategy, market size, potential growth opportunities, capital requirements, clinical development activities, the timing and results of clinical trials, regulatory submissions, potential regulatory approval and commercialization of the Company’s products. Although the Company believes to have a reasonable basis for each forward-looking statement, we caution you that these statements are based on a combination of facts and factors currently known by us and our expectations of the future, about which we cannot be certain. The Company cannot assure that the actual results will be consistent with these forward-looking statements. These forward‐looking statements speak only as of the date of this news release and the Company undertakes no obligation to revise or update any forward‐looking statements for any reason, even if new information becomes available in the future. Condensed Consolidated Statements of Operations (expressed in United States Dollars) Three months ended Dec. 31, Year ended Dec. 31, 2023 2022 2023 2022 Operating expenses $ (2,359,827) $ (3,420,717) $ (9,946,029) $ (13,638,504) Other income (expenses) (3,437,248) (696,114) (3,826,538) 1,523,806 Net loss for the year (5,797,075) (4,116,831) (13,772,567) (12,114,698) Currency translation adjustment - 873,874 (19,573) 16,806 Comprehensive loss $ (5,797,075) $ (3,242,957) $ (13,792,140) $ (12,097,892) Basic and diluted loss per common share $ (0.05) $ (0.05) $ (0.15) $ (0.18) Weighted average shares 107,601,407 68,023,450 94,355,476 67,972,194 Selected Consolidated Balance Sheet Data (expressed in United States Dollars) December 31, 2023 2022 Cash $ 1,404,160 $ 2,083,696 Working capital (deficiency) $ (706,463) $ (1,724,103) Adjusted working capital (deficiency) (1) $ (807,289) $ (1,724,103) Total assets $ 2,452,170 $ 2,950,951 Total long-term liabilities $ 4,539,872 $ 214,284 View source version on businesswire.com: Contacts For further information: Michael McFadden, CEO Tel: 1-858-344-4375 info@alphacognition.com Source: Alpha Cognition Inc. 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