Razuprotafib

每年超过50万人因脑型疟疾失去生命，即便幸存下来，许多人也要面对癫痫、言语障碍或行动障碍等终身残疾。为什么这种由疟原虫引起的疾病如此致命？它究竟是如何破坏我们大脑的？ 近日，巴塞罗那欧洲分子生物学实验室(EMBL)的研究团队在《EMBO分子医学》杂志上发表了一项突破性研究，他们不仅成功构建了三维人体血脑屏障模型，更发现了脑周细胞在脑疟疾中的关键作用，为开发新疗法带来了曙光。 大脑中数以亿计的微小"守卫者"正在被悄然瓦解，导致大脑的保护屏障崩溃，这就是脑型疟疾患者大脑内正在上演的"灾难现场"。研究人员发现，这些"守卫者"正是周细胞——分布在毛细血管壁上的重要细胞，它们与血管生成素-Tie信号通路协同工作，维持着血脑屏障的稳定与完整。 在健康状态下，周细胞会分泌一种名为血管生成素-1(Ang-1)的保护性分子，帮助血管保持紧密和稳定。然而，当脑型疟疾来袭，这种精妙的平衡被打破：保护性分子Ang-1急剧减少，而不稳定分子血管生成素-2却大量增加，导致血脑屏障出现"渗漏"，让有害物质侵入大脑组织。 在欧洲分子生物学实验室（EMBL）海德堡电子显微镜核心设施，使用串行块面扫描电子显微镜拍摄的微血管图像。内皮微血管呈灰色，内皮表面有许多周细胞（不同颜色代表单个周细胞） 为了深入探究这一过程，研究团队巧妙地在芯片上构建了一个3D人类血脑屏障模型，精确模拟了大脑微血管环境。当他们将这个精密模型暴露于疟原虫副产物时，惊人的一幕出现了：周细胞停止分泌Ang-1，血管开始渗漏，血脑屏障完整性遭到破坏。更令人意想不到的是，当研究人员重新添加Ang-1后，血管稳定性得到了部分恢复，这直接证实了Ang-1减少与血脑屏障破坏之间的因果关系。 巴塞罗那欧洲分子生物学实验室伯纳乌组的博士后研究员、该研究的第一作者Rory Long表示，他们在研究中生成了一个先进的3D人脑微血管模型，该模型能够再现人脑内皮细胞和周细胞之间重要的体内相互作用。他发现，破坏周细胞在保护和修复血管方面的关键作用会导致脑疟疾期间血脑屏障受损。 面对这一发现，研究团队没有止步于基础研究，而是迅速将目光投向潜在治疗方案。他们测试了一种名为AKB-9778的药物——该药物目前正在进行糖尿病视网膜病变的临床试验，能够增强Tie-2受体活性。实验结果令人鼓舞：对3D血脑屏障模型进行短暂的AKB-9778预处理，能够部分阻止疟疾感染的红细胞对血管完整性的破坏。 EMBL小组负责人兼该出版物的资深作者Maria Bernabeu指出，他们的生物工程血管模型是一个生理相关的平台，可以用于测试脑疟疾的其他疗法。她解释说，实验性啮齿动物研究对于治疗发现并不理想，因为疟疾对不同物种的影响存在显著差异，而他们的研究结果为寻找脑型疟疾患者的新疗法铺平了道路。 这项研究的意义远不止于揭示脑型疟疾的发病机制。它不仅为开发针对周细胞保护的新疗法指明了方向，更重要的是提供了一个可靠的人类疾病模型，避免了动物模型与人类疾病反应不一致的问题。随着全球气候变化可能扩大疟疾传播区域，这一发现显得尤为及时和重要。 当前，尽管已有有效的抗疟药物和疫苗研发进展，但脑型疟疾依然夺走大量生命，特别是在医疗资源有限的地区。这项研究将AKB-9778以及更广泛意义上的周细胞稳态功能恢复，确定为脑型疟疾治疗的一个令人兴奋的新途径，有望在未来挽救数十万生命，并减少幸存者的长期残疾。 文章来源：EMBO Molecular Medicine (2025) DOI: 10.1038/s44321-025-00319-y 入 群 欢迎加入｜welcome 生物医药交流群 免责声明：文章内容仅供参考，不构成投资建议。投资者据此操作，风险自担, 关于对文中陈述、观点判断保持中立，不对所包含内容的准确性、可靠性或完整性提供任何明示或暗示的保证。请读者仅作参考，并请自行承担全部责任。本公众号发布的各类文章重在分享，如有侵权请联系我们，我们将会删除。

– Enrollment continues to exceed expectations in DURAVYU™ Phase 3 wet AMD clinical trials with over 90% of patients randomized into the LUGANO trial and over 50% into the LUCIA trial, reinforcing confidence in enrollment completion in 2H 2025 and expected first-to-market advantage – – $318 million of cash, cash equivalents and marketable securities as of March 31, 2025, provides cash runway into 2027, beyond topline data for both Phase 3 wet AMD trials expected in 2026 – WATERTOWN, Mass., May 07, 2025 (GLOBE NEWSWIRE) -- EyePoint Pharmaceuticals, Inc. (Nasdaq: EYPT), a company committed to developing and commercializing innovative therapeutics to improve the lives of patients with serious retinal diseases, today announced financial results for the first quarter ended March 31, 2025, and highlighted recent corporate developments. “We continue to make outstanding progress with our two Phase 3 pivotal trials for DURAVYU in wet age-related macular degeneration (AMD) and have already randomized over 90% of patients into the LUGANO trial and over 50% of patients into the LUCIA trial, reinforcing our previous guidance to complete enrollment of both trials in the second half of 2025,” said Jay S. Duker, M.D., President and Chief Executive Officer of EyePoint. “The rapid trial enrollment highlights physician and patient enthusiasm for DURAVYU, driven by an established and familiar trial design, robust Phase 2 clinical data, and a strong safety profile. Moreover, it underscores the significant unmet medical need faced by this large patient population. With both Phase 3 trials due to complete enrollment in the second half of this year, and topline data expected in the second half of 2026, we believe DURAVYU is on track to be the first-to-market of the current investigational sustained release treatments for wet AMD.” “In addition, we reported compelling efficacy and safety data from our Phase 2 VERONA trial in diabetic macular edema (DME) earlier this year, further reinforcing our confidence in DURAVYU as a potential paradigm-shifting treatment for patients suffering from serious retinal diseases. DURAVYU has the most robust efficacy profile and favorable safety dataset across all sustained release programs in development in two blockbuster indications. The impressive data for DURAVYU, along with a strong cash position, and proven Durasert® technology further positions EyePoint as the leader in ocular sustained drug delivery,” added Dr. Duker. R&D Highlights and Updates Phase 3 pivotal LUGANO and LUCIA trials for DURAVYU in wet AMD are exceeding enrollment expectations and the Company is on track to complete enrollment for both in the second half of 2025. The rapid enrollment to date continues to exceed the observed recruitment rates of comparable historical and ongoing wet AMD clinical trials with LUGANO and LUCIA having randomized over 90% and 50% of patients, respectively, into the trials. LUGANO and LUCIA are identical, global non-inferiority trials with every six-month re-dosing following a clear and recognized pathway for regulatory and commercial success, positioning DURAVYU to become a potential blockbuster franchise.The Phase 2 VERONA clinical trial of DURAVYU in DME met both primary and secondary endpoints. The 24-week data demonstrated a meaningful and sustained improvement in vision and anatomical control with a continued favorable safety profile.A subgroup analyses of supplement-free patients from the VERONA trial in DME demonstrated that DURAVYU 2.7mg significantly and rapidly (by week 4) improved vision and reduced fluid levels, demonstrating a BCVA improvement of +10.3 letters versus +3.0 letters for aflibercept control and a CST improvement of 117.4 microns versus 43.7 microns for aflibercept control at week 24. These results further underscore the differentiated profile of DURAVYU with compelling efficacy, favorable safety, and strong durability.Presented multiple datasets at the Association for Research in Vision and Ophthalmology (ARVO) Annual Meeting in early May 2025, demonstrating DURAVYU’s potential real-world application in multiple retinal disease indications and de-risked trial designs that position DURAVYU for clinical and commercial success. Presentations included: An assessment of the treatment burden in wet AMD treated with DURAVYU versus aflibercept from the Phase 2 DAVIO 2 clinical trialTrial design of the global LUGANO and LUCIA pivotal Phase 3 trials in wet AMDA 24-month Good Laboratory Practice (GLP) repeat-dose toxicology study of vorolanib intravitreal insert The 24-week topline results from the Phase 2 VERONA study in DME were accepted for presentation at the Retina World Congress in May 2025, which will highlight DURAVYU’s potential to transform the treatment landscape in the second largest retinal disease market with its best-in-class safety and efficacy profile. Review of Results for the First Quarter Ended March 31, 2025 For the first quarter ended March 31, 2025, total net revenue was $24.5 million compared to $11.7 million for the quarter ended March 31, 2024. Net product revenue for the first quarter was $0.7 million, consistent with the first quarter ended March 31, 2024. Net revenue from license and royalties for the first quarter ended March 31, 2025, totaled $23.7 million compared to $11.0 million in the corresponding period in 2024. The increase was primarily driven by the recognition of deferred revenue from the out license of YUTIQ US rights in 2023. Operating expenses for the first quarter ended March 31, 2025, totaled $73.3 million versus $45.0 million in the prior year period. This increase was primarily driven by costs associated with ongoing LUGANO and LUCIA Phase 3 trials for DURAVYU in wet AMD as enrollment is tracking ahead of expectations. Net non-operating income totaled $3.6 million and net loss was $45.2 million, or ($0.65) per share, compared to a net loss of $29.3 million, or ($0.55) per share, for the corresponding period in 2024. Cash, cash equivalents, and marketable securities as of March 31, 2025 totaled $318.2 million compared to $371 million as of December 31, 2024. Financial OutlookEyePoint expects its cash, cash equivalents, and marketable securities as of March 31, 2025 will enable the Company to fund operations into 2027 beyond topline Phase 3 data for DURAVYU in wet AMD expected in 2026. Conference Call Information EyePoint management will host a conference call today at 8:30 a.m. ET to discuss the results for the first quarter ended March 31, 2025, and recent corporate developments. To access the live conference call, please register at https://register-conf.media-server.com/register/BI0695874f15d442e59e2fb362d4491cac. A live audio webcast of the event can be accessed via the Investors section of the Company website at www.eyepointpharma.com. A webcast replay will also be available on the corporate website at the conclusion of the call. About EyePoint EyePoint Pharmaceuticals, Inc. (Nasdaq: EYPT) is a clinical-stage biopharmaceutical company committed to developing and commercializing innovative therapeutics to help improve the lives of patients with serious retinal diseases. The Company's pipeline leverages its proprietary bioerodible Durasert E™ technology for sustained intraocular drug delivery. The Company’s lead product candidate, DURAVYU™ is an investigational sustained delivery treatment for VEGF-mediated retinal diseases combining vorolanib, a selective and patent-protected tyrosine kinase inhibitor with bioerodible Durasert E™. Supported by robust safety and efficacy data to date, DURAVYU is presently in Phase 3 global, pivotal clinical trials for wet age-related macular degeneration (wet AMD), the leading cause of vision loss among people 50 years of age and older in the United States and recently completed a Phase 2 clinical trial in diabetic macular edema (DME). Pipeline programs include EYP-2301, a TIE-2 agonist, razuprotafib, formulated in Durasert E™ to potentially improve outcomes in serious retinal diseases. The proven Durasert® drug delivery technology has been safely administered to thousands of patient eyes across four U.S. FDA approved products in multiple disease indications. EyePoint is headquartered in Watertown, Massachusetts, and operates a commercial-ready manufacturing facility in Northbridge, Massachusetts. Vorolanib is licensed to EyePoint exclusively by Equinox Sciences, a Betta Pharmaceuticals affiliate, for the localized treatment of all ophthalmic diseases outside of China, Macao, Hong Kong and Taiwan. DURAVYU™ has been conditionally accepted by the FDA as the proprietary name for EYP-1901. DURAVYU is an investigational product candidate; it has not been approved by the FDA. FDA approval and the timeline for potential approval is uncertain. Forward Looking Statements EYEPOINT PHARMACEUTICALS SAFE HARBOR STATEMENTS UNDER THE PRIVATE SECURITIES LITIGATION ACT OF 1995: To the extent any statements made in this press release deal with information that is not historical, these are forward-looking statements under the Private Securities Litigation Reform Act of 1995. Such statements include, but are not limited to, statements regarding our expectations regarding our clinical development and regulatory plans of DURAVYU™; our belief that DURAVYU™ is on track to be the first-to-market of the current investigational sustained release treatments for wet AMD; our belief that DURAVYU™ has two potential blockbuster indications; our belief that DURAVYU™’s potential real-world application in multiple retinal disease indications and de-risked trial designs position DURAVYU™ for clinical and commercial success; our expectations regarding timing for the completion of clinical trial enrollment and the timing of the availability and release of clinical data; our belief that rapid trial enrollment in LUGANO and LUCIA highlights physician and patient enthusiasm for DURAVYU™, which we believe is driven by an established and familiar trial design, robust Phase 2 data, and a strong safety profile; our expectations regarding cash runway; our optimism that that DURAVYU™ has the potential to shift the treatment paradigm in wet AMD and DME and improve patient outcomes; our expectations regarding clinical development of our other product candidates, including EYP-2301; our belief that we are well positioned as the leader in ocular sustained drug delivery; our business strategies and objectives; and other statements regarding the Company’s future plans, objectives, strategies and beliefs, as identified by words such as “will,” “potential,” “could,” “can,” “believe,” “intends,” “continue,” “plans,” “expects,” “anticipates,” “estimates,” “may,” or other words of similar meaning or the use of future dates. Forward-looking statements by their nature address matters that are, to different degrees, uncertain. Uncertainties and risks may cause EyePoint’s actual results to be materially different than those expressed in or implied by EyePoint’s forward-looking statements. For EyePoint, these risks and uncertainties include the timing, progress and results of the company’s clinical development activities, including DURAVYU™; uncertainties and delays relating to communications with the U.S. Food and Drug Administration and the ability to obtain regulatory approval from FDA for the commercialization of DURAVYU™; unanticipated costs and expenses; the Company’s cash and cash equivalents may not be sufficient to support its operating plan for as long as anticipated; the risk that results of clinical trials may not be predictive of future results, and interim and preliminary data are subject to further analysis and may change as more data becomes available; unexpected safety or efficacy data observed during clinical trials; uncertainties related to the regulatory authorization or approval process, and available development and regulatory pathways for approval of the Company’s product candidates; changes in the regulatory environment; disruptions at the FDA, including due to a reduction in the FDA’s workforce and/or inadequate funding for the FDA; changes in U.S. and international trade policies; changes in expected or existing competition; the success of current and future license agreements; our dependence on contract research organizations, and other outside vendors and service providers; product liability; the impact of general business and economic conditions; protection of our intellectual property and avoiding intellectual property infringement; retention of key personnel; delays, interruptions or failures in the manufacture and supply of our product candidates; the availability of and the need for additional financing; the company’s ability to obtain additional funding to support its clinical development programs; uncertainties regarding the timing and results of the August 2022 subpoena from the U.S. Attorney’s Office for the District of Massachusetts; uncertainties regarding the FDA warning letter pertaining to the company’s Watertown, MA manufacturing facility; and other factors described in our filings with the Securities and Exchange Commission. We cannot guarantee that the results and other expectations expressed, anticipated or implied in any forward-looking statement will be realized. A variety of factors, including these risks, could cause our actual results and other expectations to differ materially from the anticipated results or other expectations expressed, anticipated or implied in our forward-looking statements. Should known or unknown risks materialize, or should underlying assumptions prove inaccurate, actual results could differ materially from past results and those anticipated, estimated or projected in the forward-looking statements. You should bear this in mind as you consider any forward-looking statements. A more complete discussion of the risks and uncertainties that may cause our actual results to differ materially from those expressed or implied in the forward-looking statements in this press release are described under the heading "Risk Factors" in our most recent Annual Report on Form 10-K, in our other filings with the Securities and Exchange Commission (SEC) and in our future reports to be filed with the SEC, which are available at www.sec.gov. Our forward-looking statements speak only as of the dates on which they are made. EyePoint undertakes no obligation to update or revise any forward-looking statement, whether as a result of new information, future events, or otherwise. Investors: Christina TartagliaPrecision AQ Direct: 212-698-8700christina.tartaglia@precisionaq.com Media Contact: Amy PhillipsGreen Room CommunicationsDirect: 412-327-9499aphillips@greenroompr.com EYEPOINT PHARMACEUTICALS, INC. AND SUBSIDIARIES CONSOLIDATED BALANCE SHEETS (In thousands) March 31, December 31, 2025 2024 Assets Current assets: Cash and cash equivalents $85,158 $99,704 Marketable securities 233,036 271,209 Accounts and other receivables, net 442 607 Prepaid expenses and other current assets 6,218 9,481 Inventory 2,129 2,305 Total current assets 326,983 383,306 Operating lease right-of-use assets 21,510 21,000 Other assets 14,071 14,159 Total assets $362,564 $418,465 Liabilities and stockholders' equity Current liabilities: Accounts payable and accrued expenses $34,597 $29,824 Deferred revenue 5,115 17,784 Other current liabilities 1,965 1,440 Total current liabilities 41,677 49,048 Deferred revenue - noncurrent - 10,853 Operating lease liabilities - noncurrent 22,314 21,858 Other noncurrent liabilities 177 205 Total liabilities 64,168 81,964 Stockholders' equity: Capital 1,215,684 1,208,489 Accumulated deficit (918,211) (873,016) Accumulated other comprehensive income 923 1,028 Total stockholders' equity 298,396 336,501 Total liabilities and stockholders' equity $362,564 $418,465 EYEPOINT PHARMACEUTICALS, INC. AND SUBSIDIARIES CONSOLIDATED STATEMENTS OF OPERATIONS (In thousands, except per share data) Three Months Ended March 31, 2025 2024 Revenues: Product sales, net $715 $658 License and collaboration agreements 11,049 10,563 Royalty income 12,689 463 Total revenues 24,453 11,684 Operating expenses: Cost of sales 805 759 Research and development 58,574 30,139 Sales and marketing 35 6 General and administrative 13,876 14,101 Total operating expenses 73,290 45,005 Loss from operations (48,837) (33,321) Other income (expense): Interest and other income, net 3,642 4,037 Total other income, net 3,642 4,037 Net loss $(45,195) $(29,284) Net loss per common share - basic and diluted $(0.65) $(0.55) Weighted average common shares outstanding - basic and diluted 69,767 52,913