Clinical Trials and Development - Tildacerfont achieved approximately 80% reductions in key adrenal hormone indicators in a 12-week Phase 2a clinical trial for classic CAH patients [81]. - The company initiated CAHmelia-203 and CAHmelia-204 Phase 2b clinical trials, with topline results expected in the second half of 2023 and 2024, respectively [82]. - A Phase 2 open-label clinical trial for tildacerfont in children aged 6 to 17 with classic CAH is underway, with topline safety results anticipated in the first half of 2023 [83]. - Tildacerfont is also being investigated for potential use in treating polycystic ovary syndrome (PCOS), with a Phase 2 proof-of-concept trial initiated [84]. - The company anticipates significant increases in research and development expenses as tildacerfont advances in late-stage studies for classic CAH in adult patients [128]. Financial Performance - As of September 30, 2022, the company reported a net loss of $35.0 million and an accumulated deficit of $138.2 million [87]. - The company incurred a net loss of $11.401 million for the three months ended September 30, 2022, compared to a net loss of $11.447 million for the same period in 2021, showing an improvement of $46,000 [112]. - For the nine months ended September 30, 2022, net cash used in operating activities was $29.9 million, compared to $26.1 million for the same period in 2021 [139][141]. - The company has not generated any revenue and does not expect to do so until regulatory approval and commercialization of tildacerfont or future product candidates [127]. Expenses and Cash Flow - The company reported total operating expenses of $11.557 million for the three months ended September 30, 2022, compared to $11.400 million for the same period in 2021, reflecting an increase of $157,000 [112]. - Research and development expenses for the three months ended September 30, 2022, were $8.791 million, an increase of $184,000 from $8.607 million in the same period in 2021 [114]. - For the nine months ended September 30, 2022, total operating expenses were $35.173 million, an increase of $2.242 million from $32.931 million in the same period in 2021 [118]. - The company expects to continue incurring significant losses and does not anticipate positive cash flows from operations in the foreseeable future [87]. - The company expects to require substantial additional capital to fund operations and development efforts, with the timing and amount depending on various factors [129]. Capital and Funding - The company has raised a total of $224.5 million since inception, including $93.4 million from its IPO in October 2020 [88]. - The company has raised aggregate gross proceeds of $224.5 million since inception, including $103.5 million from its IPO in October 2020 [123]. - The company plans to build a specialized commercial organization to support the potential commercialization of tildacerfont in the U.S. and Europe [85]. Operational Risks - The ongoing COVID-19 pandemic and macroeconomic uncertainties may adversely affect the company's clinical trials and overall business operations [92]. - Inflation has increased labor and clinical trial costs, but the company does not expect significant impacts on future financial results due to inflation [153]. - The ongoing military conflict between Ukraine and Russia, along with related sanctions, is contributing to record inflation, yet the company anticipates no material effect on its business [153]. - The company relies on third parties for the manufacture and distribution of tildacerfont, which allows for a more efficient operational structure [86]. Financial Obligations - The company has obligations under a License Agreement that may require up to $23.0 million in milestone payments upon achieving specified milestones [137]. - Future payments of principal and interest on the Term Loan, commencing in January 2023, total $5.6 million [134]. - As of September 30, 2022, the company had total lease liabilities of $1.4 million for non-cancelable operating leases [135]. Cash Position - The company had cash, cash equivalents, and investments of $90.4 million as of September 30, 2022, down from $121.4 million as of December 31, 2021 [123]. - Cash provided by investing activities for the nine months ended September 30, 2022, was $9.1 million, primarily from proceeds of $43.0 million from maturities of investments [142]. - The company holds $90.4 million in cash, cash equivalents, and short-term investments as of September 30, 2022 [150]. Interest and Currency Risks - Interest and other income, net increased by $225,000 to $266,000 for the three months ended September 30, 2022, compared to $41,000 in the same period in 2021 [112]. - A hypothetical 1% change in interest rates would not have a material effect on the company's financial statements as of September 30, 2022 [151]. - The company's operations are exposed to foreign currency exchange rate fluctuations, but there was no material impact on results for the periods presented [152].

SPI'UCEBIOSCIENCES Focused on developing and commercializing novel therapies for rare endocrine disorders with significant unmet medical need Corporate Presentation August 10, 2022 FORWARD-LOOKING STATEMENTS This presentation contains forward-looking statements about Spruce Biosciences, Inc. ("we," "Spruce" or the "Company"). All statements other than statements of historical facts contained in this presentation are forward-looking statements, including statements about our strategy, our expectations regard ...

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 June 30, 2022 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) ...

spruceBlosciences Focused on developing and commercializing novel therapies for rare endocrine disorders with significant unmet medical need Corporate Presentation May 11, 2022 FORWARD-LOOKING STATEMENTS This presentation contains forward-looking statements about Spruce Biosciences, Inc. ("we," "Spruce" or the "Company"). All statements other than statements of historical facts contained in this presentation are forward-looking statements, including statements about our strategy, our expectations regarding ...

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, 2022 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 ...

SPI'UCEBIOSCIENCES Focused on developing and commercializing novel therapies for rare endocrine disorders with significant unmet medical need Corporate Presentation March 14, 2022 FORWARD-LOOKING STATEMENTS This presentation contains forward-looking statements about Spruce Biosciences, Inc. ("we," "Spruce" or the "Company"). All statements other than statements of historical facts contained in this presentation are forward-looking statements, including statements about our strategy, our expectations regardi ...

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 September 30, 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 cha ...

SPI'UCEBIOSCIENCES Focused on developing and commercializing novel therapies for rare endocrine disorders with significant unmet medical need Corporate Presentation S e p t e m b e r 1 5 , 2 0 2 1 FORWARD-LOOKING STATEMENTS This presentation contains forward-looking statements about Spruce Biosciences, Inc. ("we," "Spruce" or the "Company"). All statements other than statements of historical facts contained in this presentation are forward-looking statements, including statements about our strategy, our exp ...

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 June 30, 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) ...