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一款因为公司破产差点被埋没的新药，现在准备冲刺上市了。 近日，Spruce公司宣布与FDA完成了pre-BLA会议，FDA认为其核心管线TA-ERT商业化生产变更后的可比性策略是合理的，且双方已就TA-ERT的BLA内容和格式达成一致。 公司将在年第四季度进行BLA提交。若能顺利获批，TA-ERT成为Sanfilippo综合征B型（MPS IIIB）首个获批的疗法，同时Spruce也有望因此获得一张优先审评券（PRV）。 被命运捉弄的Allievex tralesinidase alfa（TA-ERT）是一种酶替代疗法（ERT），旨在为缺乏α-N-乙酰氨基葡萄糖苷酶（NAGLU）的MPS IIIB患者提供重组人NAGLU酶（rhNAGLU），以清除在中枢神经系统中累积的有毒物质。目前，TA-ERT已获得FDA授予突破性疗法、快速通道、罕见儿科疾病和孤儿药资格等多项监管认定，还获得欧盟授予孤儿药资格认定。 该药物最初由BioMarin开发。2019年，BioMarin将其授权给了Allievex。然而到了Allievex手中之后，TA-ERT的监管推进之路相当不顺利，公司始终未能就“TA-ERT的加速审批路径”达成一致，FDA认为，公司需要开展新的对照临床试验来确认该药物的临床获益，而不仅仅依靠已有的数据。 这一监管挫折最终导致公司走向了破产，在2023年10月，Allievex宣布停止运营，并在2024年7月，正式进入资产清算程序。 然而颇具戏剧性的是，就在Allievex进入清算程序前几个月，情况发生了逆转。2024年3月，FDA在一次C类会议中，确认了脑脊液中的硫酸肝素非还原端（CSF HS-NRE）可作为预测临床获益的合理替代终点，支持申请加速批准。同时，FDA确认其已完成的临床和非临床研究足以支持BLA提交。 然而，对于资金已经耗尽的Allievex来说，这个好消息来得太晚了。而FDA这一立场的转变也让Spruce看到了机会，2024年10月，Spruce与Allievex的债权人受让人签订了资产购买协议，获得了TA-ERT的全球独家许可权益，以及Allievex全部的知识产权。为此，Spruce向Allievex支付了500万美元现金，并承担了约830万美元的负债。 而TA-ERT在到了Spruce之后，与FDA的监管沟通确是格外的顺利。在2025年12月和2026年1月，公司与FDA召开的两次B类会议中，均已就“TA-ERT的临床试验数据、监管策略以及CMC要求”等达成了一致。现在，公司准备加速将其推向市场。 公司的希望管线 对Spruce而言，这笔收购交易同样也是一次非常重要的机会。 在2024年底，Spruce也经历了核心管线失败的重大打击。该年12月，公司的核心管线tildacerfont治疗先天性肾上腺增生症（CAH）的两项关键临床试验—CAHmelia-204和CAHptain-205遭遇了失败，均未能达到试验的主要终点目标，公司随即终止了该管线的开发，并进行55%的裁员。 此外，公司还一度面临纳斯达克摘牌的风险，股价一度跌至约0.18美元，公司在2025年通过反向拆股（1:75）才得以维持上市合规。 在裁员重组之后，当时Spruce也正临管线空缺的困境。而收购TA-ERT刚好使其迅速获得了一个处于晚期开发阶段的且又具备加速批准潜力的资产。 现在TA-ERT是Spruce目前唯一的晚期管线，也是公司全部希望。为了推动TA-ERT上市，Spruce在今年进行了多次融资，包括今年1月公司寻求了贷款的支持（2026年1月，与Avenue Capital签署最高5000万美元定期贷款协议，首笔1500万美元已提取），2026年4月，公司又完成6900万美元的承销公开发行。 而根据Spruce今年上半年财报，截至2026年6月30日，公司现金及现金等价物为9630万美元，预计现有资金可支撑公司运营至2027年下半年。 最终TA-ERT能不能获批上市，对于Spruce而言也是一次生死考验。 参考出处： https://www.fiercebiotech.com/biotech/spruces-successful-fda-talks-plant-seeds-q4-filing-ultra-rare-disease-drug https://www.businesswire.com/news/home/20260824589114/en/Spruce-Biosciences-Announces-Positive-Pre-BLA-Meetings-with-FDA-and-Confirms-BLA-Submission-for-TA-ERT-on-Track-for-Q4-2026

Biologics License Application (BLA) for TA-ERT for the Treatment of MPS IIIB Anticipated in the Fourth Quarter of 2026 TrAnsform Confirmatory Study Required for Potential FDA Accelerated Approval of TA-ERT Expected to Initiate in the Fourth Quarter of 2026 Strengthened Leadership Team with the Appointments of Adrian Quartel, M.D., FFPM, as Chief Medical Officer and Jessica Cohen Pfeffer, M.D., as Vice President, Clinical Development SOUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)--Aug. 12, 2026-- 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 second quarter ended June 30, 2026, and provided corporate updates. “The second quarter was a period of significant execution as we advanced TA-ERT toward our planned BLA submission in the fourth quarter, which would be a transformative milestone for Spruce and for the children and families living with MPS IIIB,” said Javier Szwarcberg, M.D., M.P.H., Chief Executive Officer of Spruce Biosciences. “As we prepare for the submission, we are also preparing to initiate our TrAnsform confirmatory study in the fourth quarter of 2026. We are honored and grateful that Cure Sanfilippo Foundation and the National MPS Society have made a combined $5.5 million strategic investment to help broaden patient access to TA-ERT. We believe we are well positioned to advance TA-ERT through key regulatory milestones and prepare for a potential U.S. commercial launch next year.” TA-ERT Program Updates BLA submission for TA-ERT for the treatment of MPS IIIB anticipated in the fourth quarter of 2026: Spruce continues to advance manufacturing readiness, regulatory interactions and commercial planning to support an anticipated BLA submission in the fourth quarter of 2026, seeking accelerated approval based on cerebrospinal fluid heparan sulfate non-reducing end (CSF HS-NRE) as a reasonably likely surrogate endpoint of clinical benefit. There is currently no FDA-approved therapy for the treatment of MPS IIIB, and disease management consists of limited palliative care. TrAnsform confirmatory study required for potential FDA accelerated approval of TA-ERT expected to initiate in the fourth quarter of 2026: The planned TrAnsform confirmatory study is a randomized, single-blind, parallel-group, controlled, multicenter study evaluating the safety, tolerability and efficacy of intracerebroventricular (ICV)-administered TA-ERT compared to standard of care in children 1 to 5 years of age with severe (non-attenuated) MPS IIIB. The study is expected to enroll approximately 14 participants, with the primary objective of evaluating the effect of TA-ERT on cognition. As a condition of potential FDA accelerated approval of TA-ERT, the FDA requested that the company initiate the TrAnsform confirmatory study while the planned BLA submission for TA-ERT is under review. More information about the TrAnsform confirmatory study can be found at ClinicalTrials.gov. Strengthening Clinical Development and Medical Leadership During and subsequent to the quarter, Spruce further strengthened its clinical development and medical leadership with two senior appointments to support the planned TA-ERT BLA submission, potential FDA approval and commercial readiness: Adrian Quartel, M.D., FFPM, Chief Medical Officer: Dr. Quartel was appointed Chief Medical Officer effective July 27, 2026. He brings more than 25 years of international pharmaceutical experience across clinical development, pharmacovigilance and medical affairs, with a track record of advancing and launching enzyme replacement therapies for rare diseases. He joins Spruce from Zevra Therapeutics, where he served as Chief Medical Officer, and previously served as Chief Medical Officer of Acer Therapeutics and of Adamas Pharmaceuticals. Earlier, as Group Vice President of Global Medical Affairs at BioMarin Pharmaceutical, he helped lead the launch of six treatments for rare diseases and genetic disorders, including the enzyme replacement therapies NAGLAZYME®, VIMIZIM® and Brineura® (cerliponase alfa). Jessica Cohen Pfeffer, M.D., Vice President, Clinical Development: Dr. Cohen Pfeffer was appointed Vice President, Clinical Development effective August 3, 2026. She brings more than a decade of biopharmaceutical experience across clinical development, product portfolio development and medical affairs, including a track record of supporting global regulatory approvals for enzyme replacement therapies for rare pediatric neurodegenerative disorders. She joins Spruce from BioMarin Pharmaceutical, where she most recently served as Executive Medical Director and clinical sciences lead for Brineura® (cerliponase alfa). Strategic Investment from the Patient Advocacy Community Today, Spruce separately announced that Cure Sanfilippo Foundation and the National MPS Society have made a combined $5.5 million strategic investment in Spruce. The proceeds will be used to partially fund the TA-ERT Expanded Access Program (EAP), helping to broaden patient access to investigational TA-ERT for the treatment of MPS IIIB. The planned open-label, single-arm EAP is designed to provide TA-ERT to children in the United States with attenuated and severe MPS IIIB who are not eligible to enroll in the TrAnsform confirmatory study. The EAP is expected to enroll approximately 10 participants across U.S. sites, with TA-ERT administered weekly via an ICV delivery device. The EAP is expected to initiate in the fourth quarter of 2026. More information about the EAP can be found at ClinicalTrials.gov. Additional information regarding the strategic investment is available in a separate press release available in the “News” section of the company’s website. Second Quarter 2026 Financial Results Cash and Cash Equivalents: Cash and cash equivalents as of June 30, 2026 were $96.3 million, compared to $48.9 million as of December 31, 2025. Spruce believes that its cash and cash equivalents as of June 30, 2026 will be sufficient to fund its planned operations and debt obligations into the second half of 2027. Research and Development (R&D) Expenses: R&D expenses were $12.2 million for the second quarter of 2026 and $19.7 million for the first six months of 2026, compared to $10.4 million for the first six months of 2025. The increase was primarily attributable to increased expenses to advance TA-ERT, including manufacturing scale-up and clinical development, partially offset by lower one-time product acquisition costs and the discontinuation of the tildacerfont congenital adrenal hyperplasia development program. General and Administrative (G&A) Expenses: G&A expenses were $4.3 million for the second quarter of 2026 and $8.8 million for the first six months of 2026, compared to $6.8 million for the first six months of 2025. The increase was primarily due to increased personnel-related costs and professional fees to support the company’s growth and pre-launch activities. Total Operating Expenses: Total operating expenses were $16.5 million for the second quarter of 2026 and $28.5 million for the first six months of 2026, compared to $17.2 million for the first six months of 2025. Operating expenses include non-cash stock-based compensation expense of $0.9 million and $1.6 million for the three and six months ended June 30, 2026, respectively. Net Loss: Net loss was $16.2 million, or $(6.68) per basic and diluted share, for the second quarter of 2026, and $28.5 million, or $(14.96) per basic and diluted share, for the first six months of 2026, compared to a net loss of $16.1 million, or $(27.36) per basic and diluted share, for the first six months of 2025. 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. Spruce’s lead product candidate, tralesinidase alfa enzyme replacement therapy (TA-ERT), is in late-stage development for the treatment of mucopolysaccharidoses type IIIB (MPS IIIB), or Sanfilippo Syndrome Type B, a devastating pediatric neurodegenerative disorder for which there are no FDA-approved therapies. TA-ERT has received Breakthrough Therapy Designation, Rare Pediatric Disease Designation, Fast Track Designation and Orphan Drug Designation from the FDA, as well as Orphan Drug Designation in the European Union. 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 expected timing of a planned BLA submission for TA-ERT for the treatment of MPS IIIB and the pathway to potential accelerated approval; the expected timing, enrollment and conduct of the TrAnsform confirmatory study and the TA-ERT Expanded Access Program; the $5.5 million strategic investment from Cure Sanfilippo Foundation and the National MPS Society, including the expected use of proceeds; Spruce’s expectations regarding the sufficiency of its cash and cash equivalents to fund its planned operations and debt obligations into the second half of 2027; Spruce’s plans to advance TA-ERT through potential FDA approval and commercialization, if approved, including a potential U.S. commercial launch; the contributions and impact of recently appointed members of Spruce’s leadership team; and Spruce’s product candidate, strategy and regulatory matters. 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,” “plan,” “expect,” “believe” 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) June 30, December 31, 2026 2025 ASSETS Current assets: Cash and cash equivalents $ 96,295 $ 48,906 Prepaid expenses 4,625 353 Other current assets 234 2,853 Total current assets 101,154 52,112 Right-of-use assets 523 666 Other assets 1,175 243 Total assets $ 102,852 $ 53,021 LIABILITIES AND STOCKHOLDERS’ EQUITY Current liabilities: Accounts payable $ 1,209 $ 943 Accrued expenses and other current liabilities 7,254 9,143 Debt, current portion 2,500 — Total current liabilities 10,963 10,086 Lease liabilities, net of current portion 245 419 Debt, net of current portion 4,591 — Warrant liability 3,323 — Total liabilities 19,122 10,505 Commitments and contingencies Stockholders’ equity: Preferred stock, $0.0001 par value; 10,000,000 shares authorized and no shares issued or outstanding as of June 30, 2026 and December 31, 2025 — — Common stock, $0.0001 par value; 200,000,000 shares authorized as of June 30, 2026 and December 31, 2025; 2,752,810 and 1,372,043 shares issued and outstanding as of June 30, 2026 and December 31, 2025, respectively — — Additional paid-in capital 401,459 331,750 Accumulated deficit (317,729 ) (289,234 ) Total stockholders’ equity 83,730 42,516 Total liabilities and stockholders’ equity $ 102,852 $ 53,021 SPRUCE BIOSCIENCES, INC. CONDENSED STATEMENTS OF OPERATIONS AND COMPREHENSIVE LOSS (unaudited) (in thousands, except share and per share amounts) Three Months Ended June 30, Six Months Ended June 30, 2026 2025 2026 2025 Operating expenses: Research and development $ 12,163 $ (430 ) $ 19,738 $ 10,407 General and administrative 4,349 3,122 8,761 6,777 Total operating expenses 16,512 2,692 28,499 17,184 Loss from operations (16,512 ) (2,692 ) (28,499 ) (17,184 ) Interest expense (1,097 ) (29 ) (1,771 ) (65 ) Interest and other income, net 765 193 1,251 522 Change in fair value of warrant and conversion option liabilities 615 461 524 619 Net loss and comprehensive loss (16,229 ) (2,067 ) (28,495 ) (16,108 ) Net loss per share, basic and diluted $ (6.68 ) $ (3.50 ) $ (14.96 ) $ (27.36 ) Weighted-average shares of common stock outstanding, basic and diluted 2,431,075 591,137 1,904,505 588,653 View source version on businesswire.com: https://www.businesswire.com/news/home/20260812480178/en/ Media Heidi Chokeir Inizio Evoke Comms heidi.chokeir@inizioevoke.com media@sprucebio.com Investors Monique Kosse Gilmartin Group Monique@GilmartinIR.com investors@sprucebio.com Source: Spruce Biosciences, Inc.