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]

[PART I. FINANCIAL INFORMATION](index=6&type=section&id=PART%20I.%20FINANCIAL%20INFORMATION) [Item 1. Unaudited Condensed Financial Statements](index=6&type=section&id=Item%201.%20Unaudited%20Condensed%20Financial%20Statements) The company reports a Q1 2025 net loss of $14.0 million and declining cash reserves, raising substantial doubt about its ability to continue as a going concern Condensed Balance Sheet Data (in thousands) | | March 31, 2025 | December 31, 2024 | | :--- | :--- | :--- | | **Cash and cash equivalents** | $25,615 | $38,753 | | **Total current assets** | $30,576 | $44,206 | | **Total assets** | $31,649 | $45,209 | | **Total current liabilities** | $15,666 | $15,246 | | **Total liabilities** | $16,325 | $16,388 | | **Total stockholders' equity** | $15,324 | $28,821 | | **Accumulated deficit** | $(264,309) | $(250,268) | Condensed Statements of Operations (in thousands) | | Three Months Ended March 31, 2025 | Three Months Ended March 31, 2024 | | :--- | :--- | :--- | | Collaboration revenue | $0 | $2,002 | | Research and development | $10,837 | $10,317 | | General and administrative | $3,655 | $4,318 | | **Loss from operations** | **$(14,492)** | **$(12,633)** | | **Net loss** | **$(14,041)** | **$(11,625)** | | **Net loss per share** | **$(0.32)** | **$(0.28)** | - The company's cash and cash equivalents of **$25.6 million** as of March 31, 2025, are insufficient to fund planned operations for the next 12 months, raising **substantial doubt about its ability to continue as a going concern**[24](index=24&type=chunk) - On April 21, 2025, the company approved a **55% workforce reduction** to prioritize the development of tralesinidase alfa, expecting to incur approximately **$0.9 million** in related charges[97](index=97&type=chunk)[98](index=98&type=chunk) - On April 22, 2025, the company received a delisting notice from Nasdaq and its common stock began trading on the **OTC Pink Marketplace** on April 29, 2025[5](index=5&type=chunk)[101](index=101&type=chunk) [Item 2. Management's Discussion and Analysis of Financial Condition and Results of Operations](index=27&type=section&id=Item%202.%20Management's%20Discussion%20and%20Analysis%20of%20Financial%20Condition%20and%20Results%20of%20Operations) Management discusses the strategic shift to tralesinidase alfa, an increased Q1 net loss, and reiterates going concern doubts due to insufficient cash - The company has shifted its focus from tildacerfont to the development of **tralesinidase alfa ("TA-ERT")** for neurological disorders with significant unmet medical need[109](index=109&type=chunk)[110](index=110&type=chunk) Results of Operations Comparison (in thousands) | | Three Months Ended March 31, 2025 | Three Months Ended March 31, 2024 | Change | | :--- | :--- | :--- | :--- | | Collaboration revenue | $0 | $2,002 | $(2,002) | | Research and development | $10,837 | $10,317 | $520 | | General and administrative | $3,655 | $4,318 | $(663) | | **Net loss** | **$(14,041)** | **$(11,625)** | **$(2,416)** | - R&D expenses increased by $0.5 million, primarily due to a **$5.7 million cost for acquiring SPR202**, offset by a $3.4 million decrease in clinical activities for the discontinued tildacerfont CAH program and a $1.5 million decrease in personnel costs[136](index=136&type=chunk) - The company's cash and cash equivalents as of March 31, 2025, are **insufficient to fund operations** and debt obligations for at least 12 months, raising **substantial doubt about its ability to continue as a going concern**[142](index=142&type=chunk)[218](index=218&type=chunk) Cash Flow Summary (in thousands) | | Three Months Ended March 31, 2025 | Three Months Ended March 31, 2024 | | :--- | :--- | :--- | | Net cash used in operating activities | $(12,727) | $(14,958) | | Net cash used in financing activities | $(411) | $(227) | | **Net decrease in cash** | **$(13,138)** | **$(15,185)** | [Item 3. Quantitative and Qualitative Disclosures About Market Risk](index=38&type=section&id=Item%203.%20Quantitative%20and%20Qualitative%20Disclosures%20About%20Market%20Risk) The company's primary market risk is interest rate fluctuations, though management believes the potential impact on financial statements is not material - The company's primary market risk is **interest rate risk** on its cash equivalents and variable-rate term loan, but a hypothetical 1% change is not expected to have a material effect[162](index=162&type=chunk)[163](index=163&type=chunk) - Foreign currency exchange risk and inflation are not believed to have had a significant impact on the company's results of operations[164](index=164&type=chunk)[165](index=165&type=chunk) [Item 4. Controls and Procedures](index=38&type=section&id=Item%204.%20Controls%20and%20Procedures) Management concluded that the company's disclosure controls and procedures were effective as of the end of the quarter, with no material changes - Management concluded that as of March 31, 2025, the company's **disclosure controls and procedures were effective**[166](index=166&type=chunk) - No changes in internal control over financial reporting occurred during the quarter ended March 31, 2025, that have materially affected, or are reasonably likely to materially affect, internal controls[167](index=167&type=chunk) [PART II. OTHER INFORMATION](index=39&type=section&id=PART%20II.%20OTHER%20INFORMATION) [Item 1. Legal Proceedings](index=39&type=section&id=Item%201.%20Legal%20Proceedings) The company is not currently a party to any material legal proceedings but acknowledges that litigation can arise in the ordinary course of business - As of the filing date, the company is **not a party to any material legal proceedings**[170](index=170&type=chunk) [Item 1A. Risk Factors](index=39&type=section&id=Item%201A.%20Risk%20Factors) The company outlines significant risks including Nasdaq delisting, ongoing financial losses, going concern doubts, and reliance on third parties [Risks Related to Ownership of Our Common Stock](index=39&type=section&id=Risks%20Related%20to%20Ownership%20of%20Our%20Common%20Stock) Stockholder risks include reduced liquidity from Nasdaq delisting, high price volatility, and no anticipated dividends - The company's common stock was **delisted from Nasdaq** on April 29, 2025, and now trades on the OTC market, which could adversely affect liquidity and stock price[173](index=173&type=chunk)[175](index=175&type=chunk)[176](index=176&type=chunk) - The stock price is **highly volatile**, with a closing price range from $0.07 to $0.43 between January 1, 2025, and May 1, 2025[179](index=179&type=chunk) - The company has **never paid dividends** and does not anticipate doing so, with the Loan Agreement also prohibiting such payments without lender consent[184](index=184&type=chunk) [Risks Related to Our Business and Industry](index=50&type=section&id=Risks%20Related%20to%20Our%20Business%20and%20Industry) The company faces fundamental business risks from its history of losses, insufficient capital, and uncertainty in clinical development and competition - The company has a history of significant net losses, reporting a **loss of $14.0 million for Q1 2025** and an **accumulated deficit of $264.3 million** as of March 31, 2025[211](index=211&type=chunk) - There is **substantial doubt about the company's ability to continue as a going concern**, as its cash of $25.6 million is insufficient to fund operations for the next twelve months[218](index=218&type=chunk) - The company intends to seek **accelerated approval for TA-ERT** for MPSIIIB based on a biomarker, but this pathway is not guaranteed and requires a confirmatory Phase 3 trial[225](index=225&type=chunk)[230](index=230&type=chunk) - The company faces **significant competition** from other biopharmaceutical companies with greater financial and technical resources[234](index=234&type=chunk) - Patient enrollment for clinical trials is challenging, especially for rare diseases like MPS-IIIB, which has an estimated **U.S. population of less than 200 patients**[241](index=241&type=chunk) [Risks Related to Our Reliance on Third Parties](index=103&type=section&id=Risks%20Related%20to%20Our%20Reliance%20on%20Third%20Parties) The company's operations are highly dependent on third parties for intellectual property, clinical trials, and single-source manufacturing - The company is dependent on **intellectual property licensed from Eli Lilly, BioMarin, HBM, and Twist**, and termination of these licenses could halt product development[373](index=373&type=chunk) - The company relies on third-party CROs to conduct its clinical trials and is responsible for ensuring their compliance with GCPs, with failures potentially delaying development[375](index=375&type=chunk) - The company relies completely on **third-party manufacturers**, including single-source suppliers for drug substance and product, for its clinical supplies[380](index=380&type=chunk)[381](index=381&type=chunk) [Risks Related to Our Intellectual Property](index=107&type=section&id=Risks%20Related%20to%20Our%20Intellectual%20Property) Success depends on obtaining and defending patents, a complex and uncertain process, with risks of infringement claims and challenges to existing IP - The company's ability to commercialize its products depends on obtaining and maintaining **sufficient patent protection**, a highly uncertain and complex process[387](index=387&type=chunk)[388](index=388&type=chunk)[389](index=389&type=chunk) - The company may not be able to protect its intellectual property rights throughout the world, as **patent laws and enforcement vary significantly** by country[415](index=415&type=chunk) - The company may be subject to **third-party claims of patent infringement**, which could result in costly litigation and block commercialization of its product candidates[430](index=430&type=chunk)[432](index=432&type=chunk) - The company is currently a party to **post-grant reviews and opposition proceedings** challenging the validity of its patents, which could result in the loss of exclusivity[449](index=449&type=chunk) - The company relies on **trade secrets and confidentiality agreements**, but these may not provide adequate protection against unauthorized disclosure[454](index=454&type=chunk) [Item 2. Unregistered Sales of Equity Securities and Use of Proceeds](index=136&type=section&id=Item%202.%20Unregistered%20Sales%20of%20Equity%20Securities%20and%20Use%20of%20Proceeds) The company's Loan Agreement with Silicon Valley Bank prohibits the payment of cash dividends without prior written consent - The company is **prohibited from paying cash dividends** without the prior written consent of Silicon Valley Bank, as per the terms of its Loan Agreement[462](index=462&type=chunk) [Item 3. Defaults Upon Senior Securities](index=136&type=section&id=Item%203.%20Defaults%20Upon%20Senior%20Securities) The company reports that this item is not applicable - Not Applicable[463](index=463&type=chunk) [Item 4. Mine Safety Disclosures](index=136&type=section&id=Item%204.%20Mine%20Safety%20Disclosures) The company reports that this item is not applicable - Not Applicable[464](index=464&type=chunk) [Item 5. Other Information](index=136&type=section&id=Item%205.%20Other%20Information) The company reports no other information for disclosure under this item - None[465](index=465&type=chunk) [Item 6. Exhibits](index=137&type=section&id=Item%206.%20Exhibits) This section lists exhibits filed with the report, including corporate governance documents, agreements, and officer certifications

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].

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]

Financial Performance - Spruce Biosciences reported cash and cash equivalents of $69.7 million as of June 30, 2024, which is expected to fund operations through the end of 2025[4] - Collaboration revenue for Q2 2024 was $1.6 million, a decrease from $2.2 million in Q2 2023, while total collaboration revenue for the first half of 2024 was $3.6 million compared to $4.1 million in the same period last year[4] - Research and Development (R&D) expenses decreased to $8.1 million for Q2 2024 from $13.1 million in Q2 2023, primarily due to reduced clinical development costs[4] - General and Administrative (G&A) expenses increased to $3.6 million for Q2 2024 from $3.0 million in Q2 2023[4] - Total operating expenses for Q2 2024 were $11.6 million, down from $16.1 million in Q2 2023[4] - The net loss for Q2 2024 was $9.2 million, compared to a net loss of $12.8 million in Q2 2023[4] Strategic Collaborations - Spruce announced a strategic collaboration with HMNC to develop tildacerfont for Major Depressive Disorder (MDD), with HMNC funding a Phase 2 study[2] Clinical Development - Topline data from the CAHmelia-204 study of tildacerfont is anticipated in Q4 2024, along with data from the CAHptain-205 study[1] - The company plans to meet with the U.S. FDA in the first half of 2025 to discuss the potential registrational path for tildacerfont[4] - Tildacerfont demonstrated the ability to reduce dehydroepiandrosterone sulfate levels in women with Polycystic Ovary Syndrome (PCOS) during the Phase 2 POWER study[2]