Core Insights - HMNC Brain Health and Spruce Biosciences have initiated the Phase 2 clinical trial named TAMARIND to evaluate tildacerfont as a treatment for major depressive disorder (MDD) [2][3] - The trial aims to redefine depression treatment by targeting biological roots and utilizing a proprietary patient selection tool to identify patients likely to respond to the treatment [4][7] - Topline results from the TAMARIND trial are expected in the first half of 2026 [5] Company Overview - HMNC Brain Health is a global precision psychiatry biopharmaceutical company focused on developing personalized therapies for MDD [8] - Spruce Biosciences is a late-stage biopharmaceutical company that develops novel therapies for neurological disorders with significant unmet medical needs [8] Clinical Trial Details - The TAMARIND trial is a randomized, double-blind, placebo-controlled study involving 88 adults with MDD, selected using HMNC's proprietary patient selection tool [5] - The primary endpoint is the change in depression total scores from baseline using the Hamilton Depression Rating Scale, with secondary endpoints assessing functional impairment and overall quality of life [5] Treatment Mechanism - Tildacerfont is a selective, non-steroidal oral antagonist of the CRF1 receptor, which regulates the HPA axis and is implicated in MDD [6] - By blocking the CRF1 receptor, tildacerfont may address hyperactive CRF neurotransmission and HPA axis dysfunction in MDD patients [6] Patient Selection Tool - HMNC's investigational-stage patient selection tool uses genetic markers to identify MDD patients who are more likely to benefit from CRF1 receptor antagonism [7] - This approach aims to improve treatment efficacy and reduce costs and time by moving away from a trial-and-error treatment paradigm [7]

[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

Table of Contents UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 10-K (Mark One) ☒ ANNUAL REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the fiscal year ended December 31, 2021 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) Delaware 81-2154263 (State or ...

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, 2021 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 ...

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 September 30, 2020 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 cha ...