Tildacerfont

Granted Breakthrough Therapy Designation for Tralesinidase Alfa Enzyme Replacement Therapy (TA-ERT) for the Treatment of Sanfillipo Syndrome Type B (MPS IIIB) Biologics License Application Submission of TA-ERT for the Treatment of MPS IIIB on Track for the First Quarter of 2026 Completed $50.0 Million Private Placement Financing Backed by Dedicated Healthcare Investors SOUTH SAN FRANCISCO, Calif. --(BUSINESS WIRE)--Nov. 10, 2025-- Spruce Biosciences, Inc. (Nasdaq: SPRB), a late-stage biopharmaceutical company focused on developing and commercializing novel therapies for neurological disorders with significant unmet medical need, today reported financial results for the third quarter ended September 30, 2025 and provided corporate updates. “We have made significant progress this year with the receipt of Breakthrough Therapy Designation from the U.S. Food and Drug Administration (FDA) for our tralesinidase alfa enzyme replacement therapy (TA-ERT), followed by the syndication of a $50 million private placement financing backed by an impressive group of healthcare investors. These important corporate milestones underscore the transformative moments in our collective efforts to advance TA-ERT as potentially the first disease-modifying therapy to treat children with MPS IIIB,” said Javier Szwarcberg , M.D., M.P.H., Chief Executive Officer of Spruce Biosciences . “The recent financing provides the capital resources to advance TA-ERT well beyond a biologics license application (BLA) submission expected in the first quarter of 2026.” Dr. Szwarcberg continued, “I am very proud of our team for the advancements we have made this year, appreciative of the unwavering support from our Board and investors, and grateful to the patients and families who took part in the TA-ERT clinical trials. We look forward to an impactful 2026 as we move towards bringing to market a new, life-changing treatment option for children affected by MPS IIIB.” Corporate Updates $50.0 Million Private Placement Financing Backed by Dedicated Healthcare Investors . In October 2025 , the company entered into a definitive securities purchase agreement for a private placement that resulted in gross proceeds of approximately $50.0 million , before deducting offering expenses. Under the securities purchase agreement, the investors purchased 502,181 shares of the company’s common stock. In lieu of shares of common stock, as a portion of their investment, certain investors purchased prefunded warrants to purchase up to 233,144 shares of common stock. The prefunded warrants are exercisable for a period of five years following the date of issuance. U.S. FDA Breakthrough Therapy Designation Granted to TA-ERT for the Treatment of MPS IIIB. Granted to Spruce in October 2025 , the FDA Breakthrough Therapy Designation is designed to expedite the development and regulatory review of promising therapies for serious or life-threatening conditions where preliminary clinical evidence suggests the potential for substantial improvement over existing treatments. The designation facilitates more intensive FDA guidance, cross-disciplinary collaboration, and eligibility for rolling submission and priority review. Relisted “SPRB” on the Nasdaq Capital Market. In September 2025 , the company resumed trading on the Nasdaq Capital Market under the ticker symbol “SPRB” and CUSIP 85209E 208, following a one-for-75 reverse stock split. Third Quarter 2025 Financial Results Cash and Cash Equivalents: Cash and cash equivalents as of September 30, 2025 , were $10.7 million , which does not include approximately $50.0 million in gross proceeds from the October 2025 private placement financing. Cash and cash equivalents as of September 30, 2025 , plus proceeds from the October 2025 private placement financing are expected to fund the company’s current operating plan into the fourth quarter of 2026. Research and Development (R&D) Expenses: R&D expenses for the three and nine months ended September 30, 2025 , were $5.0 million and $15.4 million , respectively, compared to $6.6 million and $25.0 million for the same periods in 2024. The decrease in R&D expenses was primarily related to the cessation of development activities of tildacerfont for the treatment of congenital adrenal hyperplasia (CAH), offset by development activities related to TA-ERT for the treatment of MPS IIIB. General and Administrative (G&A) Expenses: G&A expenses for the three and nine months ended September 30, 2025 , were $3.2 million and $10.0 million , respectively, compared to $3.5 million and $11.3 million for the same periods in 2024, primarily driven by a decrease in stock-based compensation expense. Total Operating Expenses: Total operating expenses for the three and nine months ended September 30, 2025 , were $8.2 million and $25.4 million , respectively, compared to $10.0 million and $36.3 million for the same periods in 2024. Operating expenses include non-cash stock-based compensation expenses of $0.4 million and $0.9 million for the three and nine months ended September 30, 2025 , respectively, compared to $1.1 million and $4.4 million for the same periods in 2024. Net Loss: Net loss for the three and nine months ended September 30, 2025 , was $8.2 million and $24.3 million , respectively, compared to $8.7 million and $29.5 million for the same periods in 2024. Capital Structure: Common shares outstanding as of September 30, 2025 , were 563,491, which excludes 25,512 outstanding restricted stock units and 28,118 outstanding prefunded warrants to purchase common stock. In connection with the October 2025 private placement financing, 502,181 shares of common stock and 233,144 prefunded warrants to purchase common stock were issued to certain investors. About Spruce Biosciences Spruce Biosciences is a late-stage biopharmaceutical company focused on developing and commercializing novel therapies for neurological disorders with significant unmet medical need. To learn more, visit www.sprucebio.com and follow us on X, LinkedIn, Facebook and YouTube. Forward-Looking Statements Statements contained in this press release regarding matters that are not historical facts are “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. Such forward-looking statements include statements regarding, among other things, the timing and likelihood of regulatory filings and approvals for TA-ERT, including the anticipated biologics license application submission of TA-ERT for MPS IIIB in the first quarter of 2026; TA-ERT’s potential to be the first disease-modifying therapy to treat MPS IIIB; TA-ERT’s potential to be a new, life-changing treatment option for children affected by MPS IIIB; and the Company’s ability to fund its operating plan into the fourth quarter of 2026. Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. Words such as “anticipate”, “will”, “potential”, “intend”, “expect” and similar expressions are intended to identify forward-looking statements. These forward-looking statements are based upon Spruce’s current expectations and involve assumptions that may never materialize or may prove to be incorrect. Actual results could differ materially from those anticipated in such forward-looking statements as a result of various risks and uncertainties, which include, without limitation, risks and uncertainties associated with Spruce’s business in general, the impact of geopolitical and macroeconomic events, and the other risks described in Spruce’s filings with the U.S. Securities and Exchange Commission. All forward-looking statements contained in this press release speak only as of the date on which they were made and are based on management’s assumptions and estimates as of such date. Spruce 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 law. SPRUCE BIOSCIENCES, INC. CONDENSED BALANCE SHEETS (unaudited) (in thousands, except share and per share amounts) September 30 , December 31 , 2025 2024 ASSETS Current assets: Cash and cash equivalents $ 10,669 $ 38,753 Prepaid expenses 932 3,177 Other current assets 2,915 2,276 Total current assets 14,516 44,206 Right-of-use assets 735 934 Other assets 62 69 Total assets $ 15,313 $ 45,209 LIABILITIES AND STOCKHOLDERS’ EQUITY Current liabilities: Accounts payable $ 1,386 $ 1,295 Accrued expenses and other current liabilities 7,502 12,329 Term loan, current portion 539 1,622 Total current liabilities 9,427 15,246 Lease liabilities, net of current portion 500 736 Term loan, net of current portion — 124 Other liabilities — 282 Total liabilities 9,927 16,388 Commitments and contingencies Stockholders’ equity: Preferred stock, $0.0001 par value; 10,000,000 shares authorized and no shares issued or outstanding as of September 30, 2025 and December 31, 2024 — — Common stock, $0.0001 par value; 200,000,000 shares authorized as of September 30, 2025 and December 31, 2024 ; 563,491 and 563,042 shares issued and outstanding as of September 30, 2025 and December 31, 2024 , respectively — — Additional paid-in capital 279,974 279,089 Accumulated deficit (274,588 ) (250,268 ) Total stockholders’ equity 5,386 28,821 Total liabilities and stockholders’ equity $ 15,313 $ 45,209 SPRUCE BIOSCIENCES, INC. CONDENSED STATEMENTS OF OPERATIONS AND COMPREHENSIVE LOSS (unaudited) (in thousands, except share and per share amounts) Three Months Ended September 30 , Nine Months Ended September 30 , 2025 2024 2025 2024 Collaboration revenue $ — $ 602 $ — $ 4,214 Operating expenses: Research and development 5,011 6,554 15,418 24,961 General and administrative 3,218 3,456 9,995 11,330 Total operating expenses 8,229 10,010 25,413 36,291 Loss from operations (8,229 ) (9,408 ) (25,413 ) (32,077 ) Interest expense (19 ) (71 ) (84 ) (251 ) Interest and other income, net 36 808 1,177 2,851 Net loss and comprehensive loss (8,212 ) (8,671 ) (24,320 ) (29,477 ) Net loss per share, basic and diluted $ (14.58 ) $ (15.75 ) $ (41.25 ) $ (53.68 ) Weighted-average shares of common stock outstanding, basic and diluted 563,066 550,645 589,520 549,116 View source version on businesswire.com: https://www.businesswire.com/news/home/20251110552861/en/ Media Carolyn Hawley Inizio Evoke Comms Carolyn.Hawley@inizioevoke.com media@sprucebio.com Investors Samir Gharib President and CFO Spruce Biosciences, Inc. investors@sprucebio.com Source: Spruce Biosciences, Inc.

中国科学院最新研究发现，一种名为"瓣膜模型"的新机制可能为抗抑郁药物研发带来全新方向，数百万抑郁患者曙光在前。中国科学院上海药物研究所与临港实验室的联合科研团队，近日在国际顶尖学术期刊《细胞》上发表了一项开创性研究，首次系统揭示了去甲肾上腺素转运体的精细工作机制，并提出了创新的"瓣膜模型"。 这一发现不仅深化了我们对抑郁症机制的理解，更带来了具有抗抑郁潜力的新型小分子F3288-0031，为靶向NET的抗抑郁药物开发打开了全新思路。1.抑郁难题:传统治疗的局限全球范围内，抑郁症已成为严重的公共卫生问题。据世界卫生组织数据显示，全球有3.8%的人口患有抑郁症，数亿人受到这一疾病困扰。抑郁症既是一种精神上的疾病，也是生理上的疾病。其发病机制与遗传、神经生化、神经内分泌、免疫炎症、脑结构和脑功能异常等多种因素密切相关。传统抗抑郁药物虽然有效，但存在明显局限性:起效缓慢，通常需要4-6周时间；副作用常见，包括恶心、体重增加、性功能障碍等；治疗阻力大，约三分之一患者对现有药物反应不佳。2.关键靶点:去甲肾上腺素转运体的核心作用在抑郁症的神经生物学机制中，去甲肾上腺素转运体(NET)扮演着关键角色。NET是单胺转运体家族的重要成员，负责再摄取大脑突触间隙的去甲肾上腺素和多巴胺。它与血清素转运体及多巴胺转运体共同工作，维持突触单胺类神经递质的稳态，在调节情绪、注意力及应激反应中发挥关键作用。正因为NET的重要功能，它成为治疗重度抑郁症和注意缺陷多动障碍等神经精神疾病的重要药物靶点。然而，NET如何被不同药物精准调控，尤其是其构象选择性与变构调控机制，长期以来尚未明确。3.机制突破:"瓣膜模型"的创新发现面对这一科学难题，中国研究团队取得了关键突破。他们解析了人源NET分别与三种抗抑郁药物结合的冷冻电镜结构，分辨率高2.44-2.52埃。研究显示，这三种复合物中NET均呈现内向开放构象。更重要的是，团队发现左米那普仑结合于一个NET内向开放构象特异的新型变构位点，被命名为S3位点。基于结构分析，团队提出了NET抑制剂识别的"瓣膜模型"——NET内向开放空腔中的两个关键苯丙氨酸残基F72和F329如同"心脏瓣膜"，将内向开放空腔分隔为内室与外室两个区域。不同化学结构的抑制剂被"瓣膜"引导结合至不同区域，这一发现解释了NET如何特异性识别结构多样的抑制剂。蒋轶研究员表示:"这一模型为理解NET及其他单胺类转运体的配体调控机制奠定了重要的结构基础，也为开发靶向单胺转运体的抗抑郁药物提供了新思路"。4.实践成果:高效抗抑郁小分子的发现基于"瓣膜模型"，研究团队展开了实践探索。他们对包含超过52万种小分子的化合物库进行了针对NET内向开放构象的虚拟筛选。经过多轮筛选与生物学验证，最终获得活性化合物F3288-0031。实验结果表明，该化合物在体外表现出强效的NET抑制活性，并在小鼠强迫游泳实验中显示出明确的抗抑郁样效果。进一步研究证实F3288-0031能够有效入脑，主要通过抑制NET和血清素转运体发挥治疗作用，且与其他关键神经靶点的交叉反应性较低，显示出良好的成药性与安全性。这一成功验证了靶向NET内向开放构象开发高选择性抑制剂的可行性。 5.快速起效:新型治疗技术的探索除了"瓣膜模型"的研究，抑郁症治疗领域还有其他令人振奋的进展。在海外，一项名为Tamarind(tildacerfont)的抗抑郁候选药物已进入Phase2试验，标志着"精准精神病学"迈出重要一步。该试验针对下丘脑-垂体-肾上腺轴调节异常的重度抑郁障碍亚型，使用遗传生物标志物来识别患有corticotropin-releasing factor type1(CRF1)受体过度活跃的患者。(HMNC Brain Health)的科学顾问委员会主席(FlorianHolsboer)解释说:"数十年的研究已经揭示，大脑中CRF的过度释放与应激反应有关，并可能导致相当一部分患者患上抑郁症。这一项目体现了我们将精准患者选择与新疗法配对的策略，为患者提供更个性化的解决方案"。另一方面，中国团队也在探索神经调控新策略。毛之奇教授团队与罗敏敏教授团队合作，开发出一种全新的前扣带回靶向深部脑刺激策略——抑制性DBS(i-DBS)。仅需约2小时短时刺激，即可在抑郁小鼠模型中快速缓解症状，并维持长达数天。这一"短时-长效"的刺激范式，有望显著减少患者对设备的依赖，降低副作用风险。6.希望在前:抑郁症治疗的未来展望抑郁症治疗领域正朝着更加精准、高效的方向发展。除了前述研究，其他创新疗法也在不断涌现：RTMS技术(重复经颅磁刺激)在青少年抑郁症治疗中显示出显著效果，一项涵盖1295名患者的研究证实，它能有效减轻抑郁症状，且安全性良好。艾司氯胺酮在不同类型的抑郁症治疗中都显示出效果，包括重度抑郁症、产后抑郁和围手术期抑郁。静脉给药方式在治疗耐药性抑郁症和预防产后抑郁方面效果最为显著。双重食欲素受体拮抗剂虽然对抑郁症状的直接改善效果有限，但能显著改善抑郁症患者的睡眠参数，包括睡眠潜伏期、入睡后觉醒时间和总睡眠时间。提示:随着"瓣膜模型"的提出、快速抗抑郁技术的探索以及精准医疗策略的应用，抑郁症治疗正迎来一个全新的时代。越来越多的科学家和医生相信，通过持续的科学探索和创新，我们终将找到更有效的方法，帮助患者走出抑郁的阴霾，重拾生活的光彩。无论是新模型的发现还是新药物的研发，这些进步都在向我们传达一个明确的信号:对抗抑郁症的道路虽然曲折，但希望就在前方。