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CAHmelia-203 Study of Tildacerfont in Adult Classic Congenital Adrenal Hyperplasia (CAH) with Severe Hyperandrogenemia Did Not Meet Primary Efficacy Endpoint Positive Data from CAHptain-205 Study of Tildacerfont in Pediatric Classic CAH Supports Further Dose-Ranging Across Additional Dosing Cohorts Topline Results from CAHmelia-204 Study of Tildacerfont in Adult Classic CAH Evaluating Glucocorticoid (GC) Reduction Anticipated in Third Quarter of 2024 Resource Prioritization and Cost Reductions Extend Cash Runway Through End of 2025 Conference Call Today at 4:30 p.m. ET SOUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)-- Spruce Biosciences, Inc. (Nasdaq: SPRB), a late-stage biopharmaceutical company focused on developing and commercializing novel therapies for rare endocrine disorders with significant unmet medical need, today reported financial results for the year ended December 31, 2023 and provided corporate updates. “We are grateful to all the patients, families, study team and investigators who supported the CAHmelia-203 clinical trial,” said Javier Szwarcberg, M.D., M.P.H., Chief Executive Officer, Spruce Biosciences. “CAHmelia-203 is the first study of its kind to address a difficult-to-treat CAH patient population with severe and more refractory hyperandrogenemia, which is often attributed to challenging real-life compliance with daily GCs. We garnered important data from this study which will inform ongoing development of tildacerfont in adult classic CAH.” Dr. Szwarcberg added, “Looking ahead to the third quarter of 2024, we are eager to report topline results from CAHmelia-204, which is focused on assessing GC reduction, a potentially registrational endpoint, in a different population of adult CAH patients with relatively controlled A4 levels and historically better adherence to GC therapy. Assuming positive results from CAHmelia-204 and CAHptain-205, we plan to meet with the U.S. Food and Drug Administration (FDA) and comparable foreign regulatory authorities in early 2025 to outline the design of a registrational clinical program in adult and pediatric classic CAH. Finally, we have made the difficult but necessary decision to streamline our operations and implement cost reduction measures, which has extended our cash runway through the end of 2025. I want to thank all of our employees, including those departing Spruce, for their dedication to advancing our mission of bringing forward novel therapies for CAH and other rare endocrine disorders.” Recent Corporate Updates CAHmelia-203 Study of Tildacerfont in Adult Classic Congenital Adrenal Hyperplasia (CAH) with Severe Hyperandrogenemia Did Not Meet Primary Efficacy Endpoint. CAHmelia-203 enrolled 96 subjects with a mean baseline androstenedione (A4) level of 1,151 ng/dL, which is more than five times above the upper limit of normal (ULN). The clinical trial did not achieve the primary efficacy endpoint of the assessment of dose-response for the change in A4 from baseline to week 12. 200mg QD of tildacerfont demonstrated a placebo-adjusted reduction from baseline in A4 of -2.6% with a non-significant p-value at week 12. Compliance with study medication and glucocorticoid (GC) was low with only 50% of patients reporting 80% or greater compliance, resulting in lower-than-expected tildacerfont exposure. Tildacerfont was generally safe and well tolerated at all doses, with no treatment-related serious adverse events (SAEs). Most adverse events were reported as mild to moderate. Positive Data from CAHptain-205 Study of Tildacerfont in Pediatric Classic CAH Supports Further Dose-Ranging Across Additional Dosing Cohorts. CAHptain-205 enrolled 30 children between two and 17 years of age with a mean baseline GC dose of 14 mg/m2/day and mean baseline A4 level of 372 ng/dL. The study characterized the safety and pharmacokinetic profiles of tildacerfont, as well as changes in androgen levels over 12 weeks of treatment, and the ability to reduce daily GC dose upon A4 normalization. Tildacerfont was generally safe and well tolerated at all dose ranges with no treatment-related SAEs reported. Preliminary pharmacokinetic analysis suggests that tildacerfont is cleared more rapidly in children than in adult CAH patients. 73% of all patients (22 of 30 patients) met the efficacy endpoint of A4 or GC reduction from baseline at 12 weeks of treatment with tildacerfont. 70% of patients with elevated baseline A4 values (16 of 23 patients) demonstrated an A4 reduction at week 4. Anticipated Upcoming Milestones Topline results from the CAHmelia-204 clinical trial in adult classic CAH patients on supraphysiologic doses of glucocorticoids with normal or near normal levels of A4 in the third quarter of 2024 Topline results from additional dose-ranging in the Phase 2 CAHptain clinical trial in the fourth quarter of 2024 End of Phase 2 (EOP2) meeting with the U.S. FDA in the first quarter of 2025 Full Year 2023 Financial Results Cash and Cash Equivalents: Cash and cash equivalents as of December 31, 2023 were $96.3 million. The company currently has over $81 million in cash and cash equivalents. Resource prioritization and cost reductions, including termination of the CAHmelia-203 clinical trial and a reduction in force of approximately 21%, extend cash runway through the end of 2025, including beyond anticipated topline results from CAHmelia-204 and additional dose-ranging data from CAHptain-205. Collaboration Revenue: Collaboration revenue for the year ended December 31, 2023 was $10.1 million compared to nil in 2022, reflecting the partial recognition of the $15.0 million upfront payment received from Kaken Pharmaceutical (“Kaken”) in connection with the company’s strategic collaboration with Kaken to develop and commercialize tildacerfont for the treatment of classic CAH in Japan. Research and Development (R&D) Expenses: R&D expenses for the year ended December 31, 2023 were $49.4 million compared to $35.2 million in 2022. The overall increase in R&D expenses was primarily related to progressing clinical development of tildacerfont in adult classic CAH, pediatric classic CAH and polycystic ovary syndrome (PCOS). General and Administrative (G&A) Expenses: G&A expenses for the year ended December 31, 2023 were $12.7 million compared to $12.1 million in 2022. Total Operating Expenses: Total operating expenses for the year ended December 31, 2023 were $62.1 million compared to $47.3 million in 2022. Non-cash stock-based compensation expense for the year ended December 31, 2023 was $4.6 million compared to $3.6 million in 2022. Net Loss: Net loss for the year ended December 31, 2023 was $47.9 million compared to $46.2 million in 2022. Conference Call Details Spruce’s management team and key study investigators will host a conference call today at 4:30 p.m. ET to discuss the topline results of the CAHmelia-203 and CAHptain-205 clinical studies. Analysts and investors can participate in the conference call by registering here or dialing (866) 777-2509. An archived copy of the call will be available on the events section of the company’s investor relations website for approximately 90 days. About Spruce Biosciences Spruce Biosciences is a late-stage biopharmaceutical company focused on developing and commercializing novel therapies for rare endocrine disorders with significant unmet medical need. Spruce is initially developing its wholly-owned product candidate, tildacerfont, as the potential first non-steroidal, once-daily therapy for patients suffering from classic congenital adrenal hyperplasia (CAH) and other endocrine disorders. To learn more, visit 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 design, results, conduct, progress and timing of Spruce’s clinical trials; tildacerfont’s potential to be a novel treatment option that improves long-term health outcomes for patients with CAH; Spruce’s expectations regarding reporting results of its clinical trials in 2024; Spruce’s plans to meet with the FDA and comparable foreign regulatory authorities to discuss the potential registrational path forward of tildacerfont for adult and pediatric classic CAH; the impact of cost savings initiatives and the length of Spruce’s anticipated cash runway; 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” 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. BALANCE SHEETS (in thousands, except share and per share amounts) December 31, 2023 2022 ASSETS Current assets: Cash and cash equivalents $ 96,339 $ 24,487 Short-term investments — 54,590 Prepaid expenses 3,876 3,320 Other current assets 1,968 1,211 Total current assets 102,183 83,608 Right-of-use assets 1,181 1,400 Other assets 582 640 Total assets $ 103,946 $ 85,648 LIABILITIES AND STOCKHOLDERS’ EQUITY Current liabilities: Accounts payable $ 3,332 $ 1,426 Accrued expenses and other current liabilities 14,600 9,399 Term loan, current portion 1,622 1,622 Deferred revenue 4,911 — Total current liabilities 24,465 12,447 Lease liabilities, net of current portion 1,019 1,261 Term loan, net of current portion 1,717 3,293 Other liabilities 236 161 Total liabilities 27,437 17,162 Commitments and contingencies Stockholders’ equity: Preferred stock, $0.0001 par value; 10,000,000 shares authorized and no shares issued or outstanding as of December 31, 2023 and 2022 — — Common stock, $0.0001 par value; 200,000,000 shares authorized as of December 31, 2023 and 2022; 41,029,832 and 23,601,004 shares issued and outstanding as of December 31, 2023 and 2022, respectively 4 3 Additional paid-in capital 273,737 218,354 Accumulated other comprehensive loss — (558 ) Accumulated deficit (197,232 ) (149,313 ) Total stockholders’ equity 76,509 68,486 Total liabilities and stockholders’ equity $ 103,946 $ 85,648 SPRUCE BIOSCIENCES, INC. STATEMENTS OF OPERATIONS AND COMPREHENSIVE LOSS (in thousands, except share and per share amounts) Year Ended December 31, 2023 2022 Collaboration revenue $ 10,089 $ — Operating expenses: Research and development 49,432 35,198 General and administrative 12,650 12,085 Total operating expenses 62,082 47,283 Loss from operations (51,993 ) (47,283 ) Interest expense (483 ) (420 ) Interest and other income, net 4,557 1,523 Net loss (47,919 ) (46,180 ) Other comprehensive gain (loss), net of tax: Unrealized gain (loss) on available for sale securities 558 (374 ) Total comprehensive loss $ (47,361 ) $ (46,554 ) Net loss per share, basic and diluted $ (1.24 ) $ (1.96 ) Weighted-average shares of common stock outstanding, basic and diluted 38,510,220 23,527,116

100 Patients Enrolled, Exceeding Target Enrollment of 90 Patients Topline Results for CAHmelia-204 Anticipated in the Third Quarter of 2024 SOUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)-- Spruce Biosciences, Inc. (Nasdaq: SPRB), a late-stage biopharmaceutical company focused on developing and commercializing novel therapies for rare endocrine disorders with significant unmet medical need, today announced completion of enrollment in its CAHmelia-204 clinical trial of tildacerfont for the treatment of adult classic congenital adrenal hyperplasia (CAH). “Completing enrollment in our CAHmelia-204 clinical trial marks a significant milestone in our adult classic CAH program. This achievement reinforces the continued momentum within our tildacerfont program and positions us favorably to report topline results in the third quarter of 2024,” said Javier Szwarcberg, M.D., M.P.H., Chief Executive Officer of Spruce Biosciences. “Thanks to positive engagement from our patient community and study investigators alike, the CAHmelia-204 clinical trial enrolled 100 patients, exceeding target enrollment of 90 patients.” Dr. Szwarcberg continued, “Looking ahead, assuming positive results from CAHmelia-203 in March and CAHmelia-204 in the third quarter, we plan to meet with the U.S. Food and Drug Administration (FDA) and comparable foreign regulatory authorities to discuss the potential registrational path forward for tildacerfont as a treatment for adult classic CAH.” CAHmelia-204 is a randomized, double-blind, placebo-controlled clinical trial to evaluate the safety and efficacy of tildacerfont, a potentially novel, once-daily, non-steroidal treatment option, in reducing glucocorticoid usage in 100 adults with classic CAH on supraphysiologic doses of glucocorticoids with normal or near normal levels of androstenedione (A4) at baseline. The primary endpoint of this clinical trial is the absolute change in daily glucocorticoid dose in hydrocortisone equivalents (HCe) from baseline at week 24. About CAHmelia-203 CAHmelia-203 is a randomized, double-blind, placebo-controlled, dose ranging Phase 2b clinical trial evaluating the safety and efficacy of tildacerfont in adults with classic CAH and highly elevated levels of A4 at baseline while on stable glucocorticoid dosing. This clinical trial enrolled 96 subjects with elevated levels of A4. For the first six weeks, patients will receive blinded placebo to assess their adherence to their existing glucocorticoid therapy. Patients who continue to meet all eligibility criteria at the end of this period will enter a three-part treatment period. During the placebo-controlled treatment period, patients will be randomized in a blinded manner to receive placebo, 50mg, 100mg, or 200mg tildacerfont once daily. Dosing in the placebo-controlled treatment period will continue for 12 weeks. The primary endpoint of the clinical trial is the percentage change in A4 from baseline to week 12. Following the placebo-controlled treatment period, all patients will receive tildacerfont following a dose-escalation protocol that allows dose increase to 200mg once daily over 12 weeks. Following the 12-week dose-escalation period, all patients will continue receiving tildacerfont at 200mg once daily for an additional 46 weeks. Patients who achieve control of A4 while on supraphysiologic glucocorticoid treatment will have the opportunity to reduce their glucocorticoid dosing in the open-label period according to a pre-specified algorithm in the protocol. For more information about the CAHmelia program, please visit . About CAHmelia-204 CAHmelia-204 is a randomized, double-blind, placebo-controlled Phase 2b clinical trial to evaluate the safety and efficacy of tildacerfont in reducing glucocorticoid usage in 100 adults with classic CAH on supraphysiologic doses of glucocorticoids with normal or near normal levels of A4 at baseline. This clinical trial is designed in two parts. In the first part of the clinical trial, patients will be randomized to receive 200mg tildacerfont once daily or placebo for 24 weeks. During the second part of the clinical trial, all patients will receive open-label 200mg tildacerfont once daily for 52 weeks. Throughout the trial, tapering of glucocorticoids will be guided according to a pre-specified algorithm and continue to the lowest level possible (physiologic replacement levels), as long as patients remain well controlled based on standard biomarkers and clinical assessments. The primary endpoint of this clinical trial is the absolute change in daily glucocorticoid dose in HCe from baseline at week 24. For more information about the CAHmelia program, please visit . About Congenital Adrenal Hyperplasia (CAH) CAH is an autosomal recessive disease, driven by a mutation in the gene that encodes an enzyme necessary for the synthesis of key adrenal hormones. In CAH patients, the body is not able to produce cortisol, leading to serious health consequences. The absence of cortisol alters the normal feedback cycle of the hypothalamic-pituitary-adrenal (HPA) axis and leads to excess secretion of adrenocorticotropic hormone (ACTH), hyperplasia of the adrenal gland, and consequently high levels of adrenal androgen production. As a result, CAH patients suffer from premature puberty, impaired fertility, hirsutism, acne, the development of adrenal rest tumors, and an impaired quality of life, and additionally for females, virilized genitalia and menstrual irregularities. Currently, the only way to downregulate the production of excess androgens in CAH patients is to administer supraphysiologic doses of glucocorticoids, which present specific side effects, including increased risks of developing diabetes, cardiovascular disease, stunted growth, osteoporosis, thin skin, gastrointestinal disorders, and decreased lifespan. About Tildacerfont Tildacerfont is a potent and highly selective, non-steroidal, once-daily oral antagonist of the CRF1 receptor, which is the receptor for corticotropin-releasing factor (CRF), a hormone that is secreted by the hypothalamus. The CRF1 receptor is abundantly expressed in the pituitary gland where it is the primary regulator of the HPA axis. By blocking the CRF1 receptor, tildacerfont has the potential to address the uncontrolled cortisol feedback regulatory pathway in CAH, and in turn reduce the production of ACTH in the pituitary, limiting the amount of androgen produced downstream from the adrenal gland. By controlling excess adrenal androgens through an independent mechanism, tildacerfont has the potential to reduce the unwanted clinical symptoms associated with high androgen exposure and could also enable treating physicians to lower the supraphysiologic glucocorticoid doses given to CAH patients to near physiologic levels. Tildacerfont has been evaluated in over 200 subjects across nine completed clinical trials in which it has been generally well tolerated. No drug-related serious adverse events have been reported related to tildacerfont treatment in completed studies. About Spruce Biosciences Spruce Biosciences is a late-stage biopharmaceutical company focused on developing and commercializing novel therapies for rare endocrine disorders with significant unmet medical need. Spruce is initially developing its wholly-owned product candidate, tildacerfont, as the potential first non-steroidal, once-daily therapy for patients suffering from classic congenital adrenal hyperplasia (CAH) and other endocrine disorders. To learn more, visit 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 results, conduct, progress and timing of Spruce’s clinical trials; Spruce’s expectations regarding reporting results of its clinical trials in 2024; and Spruce’s plans to meet with the FDA and comparable foreign regulatory authorities to discuss the potential registrational path forward of tildacerfont for adult classic CAH. 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” 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.

Baseline Characteristics Reinforce Study Enrichment Strategy in Adult Classic Congenital Adrenal Hyperplasia (CAH) Program SOUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)-- Spruce Biosciences, Inc. (Nasdaq: SPRB), a late-stage biopharmaceutical company focused on developing and commercializing novel therapies for rare endocrine disorders with significant unmet medical need, today reported baseline characteristics of patients enrolled in the CAHmelia-203 and CAHmelia-204 clinical studies of tildacerfont for the treatment of adult classic congenital adrenal hyperplasia (CAH). “The baseline characteristics of patients enrolled in our CAHmelia-203 and CAHmelia-204 studies reinforce our adult CAH program enrichment strategy and underscore the clinical significance of both hyperandrogenemia and hypercortisolemia within this patient population,” said Javier Szwarcberg, M.D., M.P.H., Chief Executive Officer of Spruce Biosciences. “In particular, patients in CAHmelia-203, which is assessing the change in androstenedione (A4) from baseline at week 12, enrolled with mean baseline A4 levels nearly six times above the upper limit of normal on a mean baseline daily glucocorticoid (GC) dose of 27 mg hydrocortisone equivalents (HCe).” Dr. Szwarcberg continued: “By contrast, patients in CAHmelia-204, which is assessing the absolute change in GC dose from baseline at week 24, enrolled with a mean baseline daily GC dose of 35 mg HCe and suppressed levels of A4. Collectively, we are encouraged by these baseline characteristics and look forward to reporting topline results from CAHmelia-203 in March, followed by CAHmelia-204 in the third quarter.” CAHmelia Adult Classic CAH Program Baseline Characteristics Study Characteristics CAHmelia-203 (N = 96) CAHmelia-204 (N = 98)1 Male/Female (Proportion of Total Subjects) 47% Male 53% Female 47% Male 53% Female Average Age Age Ranges 32 Years Old (18 – 65 Years Old) 33 Years Old (18 – 64 Years Old) Average Baseline Glucocorticoid (GC) Dose2 27 mg/day (14 mg/m2/day) 35 mg/day (19 mg/m2/day) Average Baseline Androstenedione (A4) Level3 1,149 ng/dL 214 ng/dL Body Mass Index (BMI) 50% Obese (BMI ≥ 30 kg/m2) 53% Obese (BMI ≥ 30 kg/m2) 1 Patients enrolled as of December 20, 2023. Final enrollment is anticipated to be completed in January 2024 and projected between 98 and 100 patients. 2 In hydrocortisone equivalents (HCe) 3 Pre-GC dose. About Congenital Adrenal Hyperplasia (CAH) CAH is an autosomal recessive disease, driven by a mutation in the gene that encodes an enzyme necessary for the synthesis of key adrenal hormones. In CAH patients, the body is not able to produce cortisol, leading to serious health consequences. The absence of cortisol alters the normal feedback cycle of the hypothalamic-pituitary-adrenal (HPA) axis and leads to excess secretion of adrenocorticotropic hormone (ACTH), hyperplasia of the adrenal gland, and consequently high levels of adrenal androgen production. As a result, CAH patients suffer from premature puberty, impaired fertility, hirsutism, acne, the development of adrenal rest tumors, and an impaired quality of life, and additionally for females, virilized genitalia and menstrual irregularities. Currently, the only way to downregulate the production of excess androgens in CAH patients is to administer supraphysiologic doses of glucocorticoids, which present specific side effects, including increased risks of developing diabetes, cardiovascular disease, stunted growth, osteoporosis, thin skin, gastrointestinal disorders, and decreased lifespan. About Tildacerfont Tildacerfont is a potent and highly selective, non-steroidal, once-daily oral antagonist of the CRF1 receptor, which is the receptor for corticotropin-releasing factor (CRF), a hormone that is secreted by the hypothalamus. The CRF1 receptor is abundantly expressed in the pituitary gland where it is the primary regulator of the HPA axis. By blocking the CRF1 receptor, tildacerfont has the potential to address the uncontrolled cortisol feedback regulatory pathway in CAH, and in turn reduce the production of ACTH in the pituitary, limiting the amount of androgen produced downstream from the adrenal gland. By controlling excess adrenal androgens through an independent mechanism, tildacerfont has the potential to reduce the unwanted clinical symptoms associated with high androgen exposure and could also enable treating physicians to lower the supraphysiologic glucocorticoid doses given to CAH patients to near physiologic levels. Tildacerfont has been evaluated in over 200 subjects across nine completed clinical trials in which it has been generally well tolerated. No drug-related serious adverse events have been reported related to tildacerfont treatment in completed studies. About CAHmelia-203 CAHmelia-203 is a randomized, double-blind, placebo-controlled, dose ranging Phase 2b clinical trial evaluating the safety and efficacy of tildacerfont in adults with classic CAH and highly elevated levels of A4 at baseline while on stable glucocorticoid dosing. This clinical trial enrolled 96 subjects with elevated levels of A4. For the first six weeks, patients will receive blinded placebo to assess their adherence to their existing glucocorticoid therapy. Patients who continue to meet all eligibility criteria at the end of this period will enter a three-part treatment period. During the placebo-controlled treatment period, patients will be randomized in a blinded manner to receive placebo, 50mg, 100mg, or 200mg tildacerfont once daily. Dosing in the placebo-controlled treatment period will continue for 12 weeks. The primary endpoint of the clinical trial is the percentage change in A4 from baseline to week 12 with secondary endpoints including the proportion of patients with levels of 17-OHP and A4 within the target and normal range, respectively, and change in lesion volume of TARTs in men. Following the placebo-controlled treatment period, all patients will receive tildacerfont following a dose-escalation protocol that allows dose increase to 200mg once daily over 12 weeks. Following the 12-week dose-escalation period, all patients will continue receiving tildacerfont at 200mg once daily for an additional 46 weeks. Patients who achieve control of A4 while on supraphysiologic glucocorticoid treatment will have the opportunity to reduce their glucocorticoid dosing in the open-label period according to a pre-specified algorithm in the protocol. Additional endpoints include clinical outcomes and patient and clinician reported outcomes. For more information about the CAHmelia program, please visit . About CAHmelia-204 CAHmelia-204 is a randomized, double-blind, placebo-controlled clinical trial to evaluate the safety and efficacy of tildacerfont in reducing supraphysiologic glucocorticoid usage in approximately 90 adults with classic CAH in patients on supraphysiologic doses of glucocorticoids with normal or near normal levels of A4 at baseline. This clinical trial is designed in two parts. In the first part of the clinical trial, patients will be randomized to receive 200mg tildacerfont once daily or placebo for 24 weeks. During the second part of the clinical trial, all patients will receive open-label 200mg tildacerfont once daily for 52 weeks. Throughout the trial, tapering of glucocorticoids will be guided according to a pre-specified algorithm and continue to the lowest level possible (physiologic replacement levels), as long as patients remain well controlled based on standard biomarkers and clinical assessments. The primary endpoint of this clinical trial is the absolute change in daily glucocorticoid dose in hydrocortisone equivalents (HCe) from baseline at week 24. The percent change in glucocorticoid dose from baseline to week 24 will be assessed as a secondary endpoint. Median total cumulative GC dose (HCe) at week 24, change from baseline in insulin resistance at week 24, and percent change from baseline in weight at week 24 and after 52 weeks of tildacerfont treatment will also be assessed as secondary endpoints. Effects on insulin resistance, weight, waist circumference, bone mineral density after 52 weeks of tildacerfont treatment will be assessed as exploratory endpoints. For more information about the CAHmelia program, please visit . About Spruce Biosciences Spruce Biosciences is a late-stage biopharmaceutical company focused on developing and commercializing novel therapies for rare endocrine disorders with significant unmet medical need. Spruce is initially developing its wholly-owned product candidate, tildacerfont, as the potential first non-steroidal, once-daily therapy for patients suffering from classic congenital adrenal hyperplasia (CAH) and other endocrine disorders. To learn more, visit 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 results, conduct, progress and timing of Spruce’s clinical trials. 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” 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.