ASAH1

Virtual Webinar to Take Place October 11, 2023 at 2:00pm ETPRINCETON, N.J., Oct. 04, 2023 (GLOBE NEWSWIRE) -- Acasti Pharma Inc. (Nasdaq: ACST) (Acasti or the Company), a late-stage, biopharma company advancing GTX-104, its novel formulation of nimodipine that addresses the high unmet medical needs for a rare disease, aneurysmal subarachnoid hemorrhage (aSAH), today announced that it will host a virtual KOL event titled GTX-104: a potential new treatment standard for rare and life-threatening aSAH on Wednesday, October 11, 2023 at 2:00pm ET. To register, click here. The event will feature W. Taylor Kimberly, MD, PhD (Massachusetts General Hospital) who will discuss the high unmet medical need and current treatment landscape for patients suffering from aSAH, a medical emergency in which bleeding occurs over the surface of the brain in the subarachnoid space between the brain and skull. The event will highlight Acasti's lead clinical asset, GTX-104, a novel formulation of nimodipine currently in Phase 3 targeting aSAH as an intravenous infusion. Acasti leadership will provide insight into trial design, market dynamics, and future directions. A live question and answer session will follow the formal presentations. About W. Taylor Kimberly, MD, PhD Dr. Kimberly is Chief of the Division of Neurocritical Care, and a stroke and critical care neurologist in the Department of Neurology at Massachusetts General Hospital. Clinically, he primarily cares for patients in the Neuroscience ICU as part of an integrated and multi-disciplinary team, coordinating care with Neurosurgery and Neuroendovascular specialists. He also sees Neuro ICU patients in follow-up in outpatient clinic as part of the NeuroRecovery clinical team. He serves on several hospital-based and national committees that focus on clinical guideline development and care improvement. Dr. Kimberly’s research group is located in the Center for Genomic Medicine (Kimberly Lab), and studies metabolomic and neuroimaging biomarkers of subarachnoid hemorrhage, stroke and cerebral edema. The goal of his research is to identify novel pathways and candidate therapeutic targets for the treatment of acute brain injury. Dr. Kimberly has co-led multi-site, randomized, placebo-controlled trials in the prevention of brain edema, and currently co-leads an international phase 3 trial evaluating the safety and efficacy of intravenous glibenclamide for the prevention of brain edema after large hemispheric stroke. About Acasti Acasti is a late-stage biopharma company with drug candidates addressing rare and orphan diseases. Acasti's novel drug delivery technologies have the potential to improve the performance of currently marketed drugs by achieving faster onset of action, enhanced efficacy, reduced side effects, and more convenient drug delivery. Acasti's lead clinical assets have each been granted Orphan Drug Designation by the FDA, which provides seven years of marketing exclusivity post-launch in the United States, and additional intellectual property protection with over 40 granted and pending patents. Acasti's lead clinical asset, GTX-104, is an intravenous infusion targeting aneurysmal Subarachnoid Hemorrhage (aSAH), a rare and life-threatening medical emergency in which bleeding occurs over the surface of the brain in the subarachnoid space between the brain and skull. Forward-Looking Statements Statements in this press release that are not statements of historical or current fact constitute "forward-looking statements" within the meaning of the U.S. Private Securities Litigation Reform Act of 1995, as amended, Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended, and "forward-looking information" within the meaning of Canadian securities laws (collectively, "forward-looking statements"). Such forward looking statements involve known and unknown risks, uncertainties, and other factors that could cause the actual results of Acasti to be materially different from historical results or from any future results expressed or implied by such forward-looking statements. In addition to statements which explicitly describe such risks and uncertainties, readers are urged to consider statements containing the terms "believes," "belief," "expects," "intends," "anticipates," "estimates", "potential," "should," "may," "will," "plans," "continue", "targeted" or other similar expressions to be uncertain and forward-looking. Readers are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date of this press release. The forward-looking statements in this press release, including statements regarding GTX-104's potential to bring enhanced treatment options to patients suffering from aSAH are based upon Acasti's current expectations and involve assumptions that may never materialize or may prove to be incorrect. Actual results and the timing of events could differ materially from those anticipated in such forward-looking statements as a result of various risks and uncertainties, including, without limitation: (i) the success and timing of regulatory submissions of the planned Phase 3 safety study for GTX-104; (ii) regulatory requirements or developments and the outcome and timing of the proposed IND application for GTX-104; (iii) changes to clinical trial designs and regulatory pathways; (iv) legislative, regulatory, political and economic developments; and (v) actual costs associated with Acasti's clinical trials as compared to management's current expectations. The foregoing list of important factors that could cause actual events to differ from expectations should not be construed as exhaustive and should be read in conjunction with statements that are included herein and elsewhere, including the risk factors detailed in documents that have been and are filed by Acasti from time to time with the Securities and Exchange Commission and Canadian securities regulators. All forward-looking statements contained in this press release speak only as of the date on which they were made. Acasti undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made, except as required by applicable securities laws. Acasti Contact:Prashant KohliChief Executive OfficerTel: 450-686-4555Email: info@acastipharma.comwww.acasti.com Investor Relations:LifeSci AdvisorsMike MoyerManaging DirectorPhone: 617-308-4306Email: mmoyer@lifesciadvisors.com

PRINCETON, N.J., Oct. 04, 2023 (GLOBE NEWSWIRE) --Acasti Pharma Inc. (Nasdaq: ACST) (Acasti or the Company), a late-stage, biopharma company advancing GTX-104, its novel formulation of nimodipine that addresses the high unmet medical needs for a rare disease, aneurysmal subarachnoid hemorrhage (aSAH), today announced that it will host a virtual KOL event titled GTX-104: a potential new treatment standard for rare and life-threatening aSAH on Wednesday, October 11, 2023 at 2:00pm ET. To register, click here. The event will feature W. Taylor Kimberly, MD, PhD (Massachusetts General Hospital) who will discuss the high unmet medical need and current treatment landscape for patients suffering from aSAH, a medical emergency in which bleeding occurs over the surface of the brain in the subarachnoid space between the brain and skull. The event will highlight Acasti's lead clinical asset, GTX-104, a novel formulation of nimodipine currently in Phase 3 targeting aSAH as an intravenous infusion. Acasti leadership will provide insight into trial design, market dynamics, and future directions. A live question and answer session will follow the formal presentations. About W. Taylor Kimberly, MD, PhD Dr. Kimberly is Chief of the Division of Neurocritical Care, and a stroke and critical care neurologist in the Department of Neurology at Massachusetts General Hospital. Clinically, he primarily cares for patients in the Neuroscience ICU as part of an integrated and multi-disciplinary team, coordinating care with Neurosurgery and Neuroendovascular specialists. He also sees Neuro ICU patients in follow-up in outpatient clinic as part of the NeuroRecovery clinical team. He serves on several hospital-based and national committees that focus on clinical guideline development and care improvement. Dr. Kimberly’s research group is located in the Center for Genomic Medicine (Kimberly Lab), and studies metabolomic and neuroimaging biomarkers of subarachnoid hemorrhage, stroke and cerebral edema. The goal of his research is to identify novel pathways and candidate therapeutic targets for the treatment of acute brain injury. Dr. Kimberly has co-led multi-site, randomized, placebo-controlled trials in the prevention of brain edema, and currently co-leads an international phase 3 trial evaluating the safety and efficacy of intravenous glibenclamide for the prevention of brain edema after large hemispheric stroke. About Acasti Acasti is a late-stage biopharma company with drug candidates addressing rare and orphan diseases. Acasti's novel drug delivery technologies have the potential to improve the performance of currently marketed drugs by achieving faster onset of action, enhanced efficacy, reduced side effects, and more convenient drug delivery. Acasti's lead clinical assets have each been granted Orphan Drug Designation by the FDA, which provides seven years of marketing exclusivity post-launch in the United States, and additional intellectual property protection with over 40 granted and pending patents. Acasti's lead clinical asset, GTX-104, is an intravenous infusion targeting aneurysmal Subarachnoid Hemorrhage (aSAH), a rare and life-threatening medical emergency in which bleeding occurs over the surface of the brain in the subarachnoid space between the brain and skull. Forward-Looking Statements Statements in this press release that are not statements of historical or current fact constitute "forward-looking statements" within the meaning of the U.S. Private Securities Litigation Reform Act of 1995, as amended, Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended, and "forward-looking information" within the meaning of Canadian securities laws (collectively, "forward-looking statements"). Such forward looking statements involve known and unknown risks, uncertainties, and other factors that could cause the actual results of Acasti to be materially different from historical results or from any future results expressed or implied by such forward-looking statements. In addition to statements which explicitly describe such risks and uncertainties, readers are urged to consider statements containing the terms "believes," "belief," "expects," "intends," "anticipates," "estimates", "potential," "should," "may," "will," "plans," "continue", "targeted" or other similar expressions to be uncertain and forward-looking. Readers are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date of this press release. The forward-looking statements in this press release, including statements regarding GTX-104's potential to bring enhanced treatment options to patients suffering from aSAH are based upon Acasti's current expectations and involve assumptions that may never materialize or may prove to be incorrect. Actual results and the timing of events could differ materially from those anticipated in such forward-looking statements as a result of various risks and uncertainties, including, without limitation: (i) the success and timing of regulatory submissions of the planned Phase 3 safety study for GTX-104; (ii) regulatory requirements or developments and the outcome and timing of the proposed IND application for GTX-104; (iii) changes to clinical trial designs and regulatory pathways; (iv) legislative, regulatory, political and economic developments; and (v) actual costs associated with Acasti's clinical trials as compared to management's current expectations. The foregoing list of important factors that could cause actual events to differ from expectations should not be construed as exhaustive and should be read in conjunction with statements that are included herein and elsewhere, including the risk factors detailed in documents that have been and are filed by Acasti from time to time with the Securities and Exchange Commission and Canadian securities regulators. All forward-looking statements contained in this press release speak only as of the date on which they were made. Acasti undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made, except as required by applicable securities laws. Acasti Contact: Prashant Kohli Chief Executive Officer Tel: 450-686-4555 Email: info@acastipharma.com Investor Relations: LifeSci Advisors Mike Moyer Managing Director Phone: 617-308-4306 Email: mmoyer@lifesciadvisors.com

更进一步的探索显示，S1P通过提高肠道中asah-1基因的转录来发挥代际遗传中的调控作用。 近期，《自然·细胞生物学》杂志上，莫纳什大学Roger Pocock教授带领的研究团队发表了一项研究成果，揭示了母亲的饮食对后代，甚至后代的后代的轴突保护作用，研究的第一作者为王文悦博士。 他们基于秀丽隐杆线虫模型发现，母亲补充熊果酸可以改善两代后代的轴突运输，减少轴突断裂，并且揭示了其中机制和关键的介导因子——一种名为鞘氨醇-1-磷酸的鞘脂[1]。 轴突对于维持健康的神经元非常重要，蛋白质和脂质等物质都需要轴突运输，而其中的微管是实现轴突运输、运输物质移动的重要机制之一，随着年龄增长，轴突会逐渐变得脆弱，这也是大脑功能障碍和神经变性的原因之一。 研究团队希望能找到保护轴突，避免轴突随年龄增长而断裂的天然物质，在筛选过程中，他们锁定了熊果酸，这种在苹果，以及罗勒、迷迭香和百里香等草本植物中存在的物质能够抑制轴突脆弱性，线虫母亲补充后，后代的后外侧机械感觉（PLM）神经元轴突断裂显著减少，发挥功能的时期在卵母细胞产生和成熟期间，对后代轴突的保护可以跨越两代。 线虫母亲补充熊果酸（UA）后，两代后代（F1和F2）的神经元轴突断裂显著减少 确定了熊果酸的保护作用后，接下来就是要搞清楚其中的机制。 由于功能时期为卵母细胞产生和成熟期间，研究人员猜测，熊果酸可能影响了卵黄对卵母细胞的供给。线虫肠道中合成的卵黄含有脂质和脂蛋白，可以为卵母细胞和胚胎发育提供营养，卵母细胞通过内吞作用吸收卵黄，需要RME-2受体介导，研究人员也确实发现，RME-2是熊果酸降低神经元脆弱性所必需的，为肠道-卵母细胞的运输提供了必要的支持。 补充熊果酸增加了鞘脂生物合成酶——酸性神经酰胺酶-1（asah-1）基因的表达，由两个转录因子PQM-1和CEH-60调控。 包括神经酰胺在内的鞘脂具有多种细胞功能，实验显示，神经酰胺或其衍生物对轴突健康很重要。鞘脂稳态通过从头合成或补救途径维持，在补救途径中，神经酰胺被ASAH水解产生鞘氨醇，再由鞘氨醇激酶（SphK）磷酸化产生鞘氨醇-1-磷酸（S1P），SphK-1的表达减少了轴突断裂，反之，则抑制了ASAH-1对轴突的保护作用。这表明，熊果酸对轴突的保护作用要依赖于S1P。 S1P的直接补充显著降低了轴突脆弱性，功能时期和代际效应与熊果酸相同，并且依赖于RME-2介导的肠道-卵母细胞运输。 线虫母亲直接补充S1P后对后代的轴突保护作用与补充熊果酸类似 从具体的功能表现上来说，在遗传因素导致的轴突微管不稳定情况下，熊果酸和S1P促进了蛋白质沿轴突的运输，即使在遗传因素基础上继续施加化学物质影响，熊果酸和S1P也可以减少轴突断裂，也就是说，即使存在两种脆弱因素，熊果酸和S1P仍然可以稳健地降低轴突脆弱性。 不但如此，这种对轴突的保护效果还具有普遍性，在不同的遗传模型，以及D型GABA能运动神经元和PVQ中间神经元中，熊果酸和S1P均减少了轴突断裂。 更进一步的探索显示，S1P通过提高肠道中asah-1基因的转录来发挥代际遗传中的调控作用。 也就是说，线虫母亲补充天然物质熊果酸后产生的保护性分子可以由肠道转运至卵母细胞，在两代后代中改善轴突脆弱性，并且这种保护作用具有普遍性，可以跨遗传因素和神经元类型发挥作用。 Pocock教授表示，这是首次证实脂质/脂肪是可遗传的，此外，这一研究结果意味着，母亲的饮食不仅会影响自身后代的大脑，还可能产生潜在的连续代际影响，支持了孕期健康饮食以赋予后代最佳大脑发育和健康的重要性[2]。 参考文献： [1] Wang W, Sherry T, Cheng X, et al. An intestinal sphingolipid confers intergenerational neuroprotection[J]. Nature Cell Biology, 2023: 1-12. [2] https://www.monash.edu/news/articles/a-mothers-diet-can-protect-her-grandchildrens-brains-study