Tralesinidase Alfa (TA-ERT) for MPS IIIB - Tralesinidase Alfa 预计在 2026 年上半年提交 BLA 申请，该项目已准备就绪[8] - MPS IIIB 是一种影响 1/200,000 新生儿的常染色体隐性遗传病[14] - Tralesinidase Alfa 显著且持久地使脑脊液 HS 和 HS-NRE 水平正常化[22] - 早期使用 Tralesinidase Alfa 可稳定 MPS IIIB 患者的认知能力下降[29] - 在为期 48 周的初步研究及其扩展研究中，共进行了约 6,000 次给药，Tralesinidase Alfa 通常具有良好的耐受性[32] Tildacerfont + Cortibon for Major Depressive Disorder (MDD) - Tildacerfont + Cortibon 治疗重度抑郁症 (MDD) 的 2 期研究的顶线数据预计在 2026 年上半年公布[8] - Cortibon 是一种基因选择工具，可基于遗传标记识别 CRHR1 拮抗剂的应答者和非应答者[40] - Cortibon 挑选出约 50% 的显示 HPA 轴功能障碍迹象的 MDD 患者亚群[43] - 在 Cortibon 选择的 MDD 患者群体中，Cohen's d 效应量显著[46] SPR202 & SPR204 - SPR202 是一种用于治疗先天性肾上腺皮质增生症 (CAH) 的抗促肾上腺皮质激素释放激素 (CRH) 单克隆抗体，目前处于 IND 申报阶段[58, 63] - SPR204 是一种用于治疗减重手术后低血糖症的 GLP-1 受体拮抗剂单克隆抗体，目前处于 IND 申报阶段[64, 71] Financials - 截至 2025 年 3 月 31 日，公司拥有 2561.5 万美元的现金和现金等价物，以及 140.2 万美元的债务[74]

Table of Contents UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, D.C. 20549 FORM 10-Q (Mark One) ☒ QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the quarterly period ended March 31, 2025 OR ☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the transition period from ___________ to ____________ Commission File Number: 001-39594 Spruce Biosciences, Inc. (Exact name of registrant as specified in its charter ...

Financial Position - Spruce Biosciences reported a cash and cash equivalents balance of $38.8 million as of December 31, 2024[6] Corporate Developments - The company announced the acquisition of tralesinidase alfa enzyme replacement therapy for the treatment of Sanfilippo Syndrome Type B[6] - A corporate update was provided, highlighting new corporate strategies and anticipated upcoming milestones[6] - The presentation titled "Tralesinidase Alfa Enzyme Replacement Therapy for the Treatment of Sanfilippo Syndrome Type B (MPSIIIB)" was shared to outline the new strategy[8]

Filing Information - Spruce Biosciences, Inc. filed a Notification of Late Filing on Form 12b-25 regarding its Annual Report for the fiscal year ended December 31, 2024[6]. - The Notification of Late Filing was submitted to the SEC on March 31, 2025[6]. - The report emphasizes that the information provided is not deemed "filed" under the Exchange Act[7]. Financial Estimates - The filing includes certain estimates about the Company's results of operations and financial condition for the fiscal year ended December 31, 2024[6]. - The filing does not include specific financial metrics or performance data for the fiscal year ended December 31, 2024[6]. - The Company has not yet provided detailed guidance or future outlook in this filing[6]. Company Classification and Trading - The Company is classified as an emerging growth company under the Securities Act of 1933[5]. - The Company’s common stock is traded on the Nasdaq Capital Market under the symbol SPRB[5]. Company Information - The Company’s principal executive offices are located in South San Francisco, California[2]. - There are no mentions of new products, technologies, market expansions, or acquisitions in the current report[6].

Core Viewpoint - Spruce Biosciences, Inc. (SPRB) has received an upgrade to a Zacks Rank 2 (Buy), indicating a positive outlook on its earnings estimates, which is a significant factor influencing stock prices [1][3]. Earnings Estimates and Stock Price Impact - The Zacks rating system is based on changes in earnings estimates, which are strongly correlated with near-term stock price movements [4][6]. - An increase in earnings estimates typically leads to institutional investors adjusting their valuations, resulting in buying or selling actions that affect stock prices [4]. Company Performance Indicators - For the fiscal year ending December 2024, Spruce Biosciences is expected to earn -$1.03 per share, reflecting a 16.9% change from the previous year [8]. - Over the past three months, the Zacks Consensus Estimate for Spruce Biosciences has increased by 8.3%, indicating a positive trend in earnings expectations [8]. Zacks Rank System - The Zacks Rank system classifies stocks into five groups based on earnings estimates, with a strong historical performance, particularly for Zacks Rank 1 stocks, which have generated an average annual return of +25% since 1988 [7]. - The upgrade to Zacks Rank 2 places Spruce Biosciences in the top 20% of Zacks-covered stocks, suggesting potential for market-beating returns in the near term [10][11].

Clinical Trials and Efficacy - Tildacerfont, an oral antagonist of the CRF1 receptor, is being developed for classic congenital adrenal hyperplasia (CAH), polycystic ovary syndrome (PCOS), and major depressive disorder (MDD) with over 400 subjects administered in clinical trials[54] - In the CAHmelia-203 trial, 96 subjects had a mean baseline androstenedione (A4) level of 1,151 ng/dL, but the primary efficacy endpoint was not achieved, showing a placebo-adjusted reduction of -2.6% at week 12[54] - The CAHmelia-204 trial is ongoing with 100 adult patients, and topline results are expected in December 2024, with a mean baseline A4 level of 224 ng/dL[54] - In the CAHptain-205 trial for pediatric patients, 73% of 30 children met the efficacy endpoint of A4 or glucocorticoid reduction at 12 weeks[54] - Tildacerfont showed significant reduction in DHEAS levels in women with PCOS, with a p-value of 0.020, and an increase in sex hormone binding globulin (SHBG) with a p-value of 0.012[54] - A license agreement with HMNC Holding GmbH was established for a Phase 2 study of tildacerfont in MDD patients, utilizing the Cortibon Genetic Selection Tool[54] - The Pediatric Committee of the European Medicines Agency endorsed the proposed pediatric investigational plan for tildacerfont in children with classic CAH[56] Financial Performance and Revenue - The company has not generated any product revenue to date and continues to incur significant research and development expenses[54] - The company incurred net losses of $29.5 million and $38.0 million for the nine months ended September 30, 2024 and 2023, respectively, with cash used in operations of $35.3 million and $22.1 million[58] - As of September 30, 2024, the company had an accumulated deficit of $226.7 million, up from $197.2 million as of December 31, 2023[58] - The company raised aggregate gross proceeds of $293.1 million since inception, including $15.0 million from the Kaken License Agreement in April 2023[58] - The company expects to continue incurring significant losses and does not anticipate positive cash flows from operations for the foreseeable future[58] - Collaboration revenue for the three months ended September 30, 2024, was $0.6 million, down from $3.1 million in the same period of 2023, a decrease of $2.5 million[71] - For the nine months ended September 30, 2024, collaboration revenue was $4.2 million, down from $7.2 million in the same period of 2023, a decrease of $2.99 million[73] Operating Expenses - Total operating expenses for the three months ended September 30, 2024, were $10.0 million, a decrease of $6.7 million compared to $16.7 million in the same period of 2023[70] - Research and development expenses decreased by $6.9 million to $6.6 million for the three months ended September 30, 2024, primarily due to reduced clinical development and manufacturing expenses[71] - General and administrative expenses increased by $0.2 million to $3.5 million for the three months ended September 30, 2024, mainly due to higher legal professional services[72] - Total operating expenses for the nine months ended September 30, 2024, were $36.3 million, a decrease of $11.7 million compared to $48.0 million in the same period of 2023[73] - Research and development expenses for the nine months ended September 30, 2024, were $25.0 million, down $13.4 million from $38.3 million in the same period of 2023[74] Cash Position and Funding - As of September 30, 2024, the company had cash and cash equivalents of $60.1 million, down from $96.3 million as of December 31, 2023[58] - The company anticipates that its cash and cash equivalents will be sufficient to fund operations for at least 12 months following the issuance date of the financial statements[76] - The company has entered into a Loan Agreement with Silicon Valley Bank, with an outstanding principal of $2.2 million as of September 30, 2024[65] - The company reported a net cash used in operating activities of $35.3 million for the nine months ended September 30, 2024, an increase of $13.2 million compared to the same period in 2023[85] - The company had no net cash provided by investing activities for the nine months ended September 30, 2024, compared to $46.5 million in the same period in 2023[85] - As of September 30, 2024, cash and cash equivalents amount to $60.1 million, primarily in bank deposits and money market funds[91] - The company has not generated any revenues from the commercial sale of approved products and does not expect to do so in the foreseeable future[66] - The company anticipates significant increases in research and development expenses as it advances clinical trials for tildacerfont, particularly for classic CAH[79] - Future funding requirements will depend on various factors, including clinical trial progress and regulatory approval timelines[81] Regulatory and Strategic Plans - Plans to build a specialized commercial organization for tildacerfont's potential commercialization in the U.S. are underway, targeting endocrinologists and specialists[54] - The company aims to leverage strategic collaborations for resources in relevant disease areas and geographies outside the U.S.[54] - Under the Kaken License Agreement, the company is entitled to receive up to approximately $65.0 million upon achieving specified milestones related to tildacerfont in Japan[62] - The company will receive tiered double-digit royalties on net sales of tildacerfont in Japan, with rates potentially reaching the mid-twenties[62] Economic Factors - The company does not expect inflation to have a material effect on its business or financial condition in future reporting periods[93] - Inflation has increased costs related to labor and clinical trials, but is not expected to materially affect future financial results[93] - The company anticipates continued record inflation due to geopolitical and macroeconomic events, but does not expect significant impacts on business operations[93] - A hypothetical 1% change in interest rates would not have a material effect on the financial statements as of September 30, 2024, and December 31, 2023[91] - The company does not currently engage in hedging transactions to manage exposure to interest rate risk[91] - There was no material impact on operating results due to foreign currency exchange rate fluctuations[92]

Financial Performance - Collaboration revenue for Q3 2024 was $0.6 million, a decrease of 80.5% compared to $3.1 million in Q3 2023[5] - Research and development (R&D) expenses for Q3 2024 were $6.6 million, down 51.3% from $13.5 million in Q3 2023[5] - General and administrative (G&A) expenses for Q3 2024 were $3.5 million, an increase of 9.4% compared to $3.2 million in Q3 2023[5] - Total operating expenses for Q3 2024 were $10.0 million, a decrease of 40.0% from $16.7 million in Q3 2023[5] - Net loss for Q3 2024 was $8.7 million, a reduction of 30.0% compared to $12.4 million in Q3 2023[5] Cash Position - Cash and cash equivalents as of September 30, 2024, were $60.1 million, expected to fund operations through the end of 2025[4] Clinical Trials - Topline data from the CAHmelia-204 study of tildacerfont in adult congenital adrenal hyperplasia (CAH) is anticipated in December 2024[1] - Topline results from the CAHptain-205 clinical trial are also anticipated in December 2024[3] - The end of Phase 2 meeting with the U.S. FDA is anticipated in the first half of 2025[3] Product Development - The company is developing tildacerfont for the treatment of CAH, polycystic ovary syndrome (PCOS), and major depressive disorder (MDD)[7]

Group 1 - Spruce Biosciences reported a quarterly loss of $0.21 per share, better than the Zacks Consensus Estimate of a loss of $0.27, and an improvement from a loss of $0.30 per share a year ago, resulting in an earnings surprise of 22.22% [1] - The company posted revenues of $0.6 million for the quarter ended September 2024, missing the Zacks Consensus Estimate by 66.56%, and a significant decline from year-ago revenues of $3.07 million [2] - Spruce Biosciences shares have declined approximately 81.7% since the beginning of the year, contrasting with the S&P 500's gain of 25.7% [3] Group 2 - The current consensus EPS estimate for the upcoming quarter is -$0.28 on revenues of $1.55 million, and for the current fiscal year, it is -$1.12 on revenues of $5.8 million [7] - The Medical - Biomedical and Genetics industry, to which Spruce Biosciences belongs, is currently ranked in the top 31% of over 250 Zacks industries, indicating a favorable outlook compared to lower-ranked industries [8]

Group 1 - Spruce Biosciences reported a quarterly loss of $0.22 per share, better than the Zacks Consensus Estimate of a loss of $0.33, representing an earnings surprise of 33.33% [1] - The company posted revenues of $1.61 million for the quarter ended June 2024, surpassing the Zacks Consensus Estimate by 3.87%, although this is a decline from $2.17 million in the same quarter last year [2] - Spruce Biosciences has surpassed consensus EPS estimates for four consecutive quarters [2] Group 2 - The stock has underperformed significantly, losing about 85.1% since the beginning of the year, while the S&P 500 has gained 12% [3] - The current consensus EPS estimate for the upcoming quarter is -$0.32 on revenues of $1.8 million, and for the current fiscal year, it is -$1.24 on revenues of $5.27 million [7] - The Medical - Biomedical and Genetics industry, to which Spruce Biosciences belongs, is currently in the top 30% of Zacks industries, indicating a favorable outlook for the sector [8]

Clinical Development - Tildacerfont, an oral antagonist of the CRF1 receptor, is being developed for classic congenital adrenal hyperplasia (CAH), polycystic ovary syndrome (PCOS), and major depressive disorder (MDD) with over 400 subjects administered in clinical trials[49] - In the CAHmelia-203 trial, 96 subjects had a mean baseline androstenedione (A4) level of 1,151 ng/dL, but the primary efficacy endpoint was not achieved, showing a placebo-adjusted reduction of -2.6% at week 12[49] - The CAHmelia-204 trial is ongoing with 100 adult patients, and topline results are expected in Q4 2024, with a mean baseline A4 level of 224 ng/dL[50] - The CAHptain-205 trial for pediatric patients showed that 73% of 30 children met the efficacy endpoint of A4 or glucocorticoid reduction at 12 weeks[50] - Tildacerfont demonstrated significant reduction in DHEAS levels in women with PCOS, with a p-value of 0.020, and an increase in sex hormone binding globulin (SHBG) with a p-value of 0.012[50] - A license agreement with HMNC Holding GmbH will fund a Phase 2 study of tildacerfont in MDD patients, utilizing the Cortibon Genetic Selection Tool for patient screening[50] - The company is advancing clinical development of tildacerfont in additional indications, including PCOS and MDD, and plans to build a specialized commercial organization if approved[51] Financial Performance - The company has no products approved for commercial sale and has not generated any product revenue to date, continuing to incur significant research and development expenses[50] - The company incurred net losses of $20.8 million and $25.6 million for the six months ended June 30, 2024 and 2023, respectively, with cash used in operations of $26.1 million and $9.8 million[51] - As of June 30, 2024, the company had an accumulated deficit of $218.0 million, up from $197.2 million as of December 31, 2023[51] - The company raised aggregate gross proceeds of $293.1 million since inception, including $15.0 million from the Kaken License Agreement in April 2023[51] - The company expects to continue incurring significant losses and does not anticipate positive cash flows from operations for the foreseeable future[51] - The company has cash and cash equivalents of $69.7 million as of June 30, 2024, which is projected to fund operations for at least 12 months[51] - The company has not generated any revenues from the commercial sale of approved products and does not expect to do so in the foreseeable future[57] - Collaboration revenue for the three months ended June 30, 2024, was $1.6 million, down from $2.2 million in the same period of 2023, a decrease of 26%[62] - Research and development expenses decreased by $5.0 million to $8.1 million for the three months ended June 30, 2024, compared to $13.1 million in 2023, a reduction of 38%[62] - General and administrative expenses increased by $0.5 million to $3.6 million for the three months ended June 30, 2024, compared to $3.0 million in 2023, an increase of 18%[63] - Net loss for the three months ended June 30, 2024, was $9.2 million, improved from a net loss of $12.8 million in the same period of 2023, a reduction of 28%[61] - Total operating expenses for the three months ended June 30, 2024, were $11.6 million, down from $16.1 million in 2023, a decrease of 28%[61] - For the six months ended June 30, 2024, collaboration revenue was $3.6 million, down from $4.1 million in 2023, a decrease of 12%[65] - Research and development expenses for the six months ended June 30, 2024, were $18.4 million, down from $24.8 million in 2023, a decrease of 26%[65] - General and administrative expenses increased by $1.4 million to $7.9 million for the six months ended June 30, 2024, compared to $6.5 million in 2023, an increase of 22%[66] - As of June 30, 2024, the company had cash and cash equivalents of $69.7 million, down from $96.3 million as of December 31, 2023[69] - The company expects its cash and cash equivalents will be sufficient to fund operations for at least 12 months following the issuance date of the financial statements[69] - Net cash used in operating activities increased by $16.3 million for the six months ended June 30, 2024, compared to the same period in 2023[76] - The company anticipates significant increases in research and development expenses as it continues to invest in tildacerfont[72] Licensing and Royalties - Under the Kaken License Agreement, the company is entitled to receive up to approximately $65.0 million upon achieving specified milestones related to tildacerfont in Japan[54] - The company will receive tiered double-digit royalties on net sales of tildacerfont in Japan, with rates based on annual sales[54] - The company is obligated to make up to $23.0 million in milestone payments under the Lilly License Agreement[75] Debt and Financing - The company has entered into a Loan Agreement with Silicon Valley Bank, with an outstanding principal of $2.6 million as of June 30, 2024[56] - Future payments of principal and interest on the Term Loan as of June 30, 2024, were $2.8 million[74] - The company has total undiscounted lease payments for its non-cancelable operating lease of $1.3 million as of June 30, 2024[75] - The SEC declared effective a Shelf Registration covering the sale of up to $200.0 million of securities in February 2022[70] - In February 2023, the company sold 16,116,000 shares of common stock and warrants for gross proceeds of $53.6 million[71] Economic Factors - The company does not expect anticipated changes in inflation to have a material effect on its business or financial condition[85] - Inflation has increased costs related to labor and clinical trials, but is not expected to have a significant impact on future financial results[85] - The company anticipates continued record inflation due to geopolitical and macroeconomic events, but does not expect it to materially affect business operations[85] - There was no material impact on operating results due to foreign currency exchange rate fluctuations[84] - A hypothetical 1% change in interest rates would not have a material effect on the financial statements as of June 30, 2024, and December 31, 2023[83] - The company does not currently engage in hedging transactions to manage exposure to interest rate risk[83]