Tildacerfont

SOUTH SAN FRANCISCO, Calif.--( BUSINESS WIRE )-- Spruce Biosciences, Inc . (Nasdaq: SPRB), a late-stage biopharmaceutical company focused on developing and commercializing novel therapies for neurological and endocrine disorders with significant unmet medical need, today announced topline results from its CAHmelia-204 study of tildacerfont in adult CAH and its CAHptain-205 study of tildacerfont in adult and pediatric CAH. “ We are very grateful to all the patients, families, investigators, and the entire CAH community who supported the CAHmelia-204 and CAHptain-205 clinical trials. We garnered invaluable safety and exposure response data on tildacerfont from these studies, which suggests that higher doses and more frequent dosing may be necessary for efficacy in CAH,” said Javier Szwarcberg, M.D., M.P.H., Chief Executive Officer of Spruce. “ Moving forward, we plan to evaluate a full range of strategic options for Spruce in addressing diseases with serious unmet need for patients. In the interim, the CAHmelia-204 and CAHptain-205 clinical trials will be discontinued, and we will be winding down Spruce’s investment in tildacerfont for the treatment of CAH as we conserve financial resources and look to maximize shareholder value.” CAHmelia-204 was a Phase 2b, randomized, double-blind, placebo-controlled clinical trial that evaluated the safety and efficacy of tildacerfont in reducing supraphysiologic GC usage in 100 adults with classic CAH on a mean GC dose of 35mg/day of hydrocortisone equivalents (HCe) (19mg/m 2 /day) and mean androstenedione (A4) level of 214 ng/dL at baseline. The clinical trial did not achieve the primary efficacy endpoint of the absolute change in daily GC dose from baseline at week 24. 200mg QD of tildacerfont demonstrated a placebo-adjusted reduction from baseline in daily GC dose of 0.7mg HCe (95% CI: -4.3 to 2.9, p=0.7). Approximately 98% of patients were highly compliant with study drug. Tildacerfont was generally safe and well tolerated with no serious adverse events (SAEs). “ Although the study missed its primary endpoint, the data offers valuable insights that will shape the future of CAH management and research,” said Jung Hee Kim, M.D., M.S., Ph.D., Principal Investigator and Associate Professor of Internal Medicine, Seoul National University Hospital and College of Medicine. “ I am grateful to the nearly 400 CAH patients who shared their information with us and look forward to presenting our findings at upcoming conferences in 2025.” CAHptain-205 was a Phase 2 open-label, 4-week, sequential cohort clinical trial, that evaluated the safety, pharmacodynamics (changes in A4 levels), and pharmacokinetics of QD and BID doses of tildacerfont from 50mg QD to 400mg BID in pediatric and adult patients with CAH. A trend was observed of larger reductions from baseline in A4 levels with higher BID doses of tildacerfont. Tildacerfont was generally safe and well tolerated across all doses with no drug-related SAEs. “ This study was well-run with excellent compliance,” said Paul Thornton, M.B.B.S., Principal Investigator and Medical Director of the Endocrine and Diabetes Program at a CAH Center of Excellence. “ The data suggests that a twice-daily dosing may be more effective.” About CAHmelia-204 CAHmelia-204 was a Phase 2b, randomized, double-blind, placebo-controlled clinical trial that evaluated the safety and efficacy of tildacerfont in reducing supraphysiologic glucocorticoid (GC) usage in 100 adults with classic congenital adrenal hyperplasia (CAH) on supraphysiologic doses of GCs with normal or near normal levels of androstenedione (A4) at baseline. In the first part of the clinical trial, patients were randomized to receive 200mg of tildacerfont once-daily (QD) or placebo for 24 weeks. During the second part of the clinical trial, all patients received 200mg of tildacerfont QD for 52 weeks. Throughout the trial, tapering of GCs was guided according to a pre-specified algorithm based on A4 normalization. The primary endpoint of the clinical trial was the absolute change in daily GC dose in hydrocortisone equivalents (HCe) from baseline through week 24. About CAHptain-205 CAHptain-205 was a Phase 2 open-label clinical trial, which utilized a sequential nine cohort design, to evaluate the safety, efficacy, and pharmacokinetics of tildacerfont in adults and children between two and 17 years of age with CAH. Cohorts 1-3 evaluated weight-adjusted doses of tildacerfont between 50mg QD and 200mg QD in pediatric CAH patients between two and 17 years of age and assessed changes in androgen levels over 12 weeks of treatment as well as the ability to reduce daily GC dose based on A4 normalization. Cohorts 4-9 evaluated weight-adjusted doses of tildacerfont of 200mg twice-daily (BID) and 400mg BID in adults and children between two and 17 years of age with CAH to assess changes in androgen levels over four weeks of treatment. 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 may 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 GCs, 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 CRF 1 receptor, which is the receptor for corticotropin-releasing factor (CRF), a hormone that is secreted by the hypothalamus. The CRF 1 receptor is abundantly expressed in the pituitary gland where it is the primary regulator of the HPA axis. By blocking the CRF 1 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 GC doses given to CAH patients to near physiologic levels. 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 neurological and endocrine disorders with significant unmet medical need. To learn more, visit www.sprucebio.com 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 Company’s plans to evaluate a full range of strategic options, the discontinuance of the CAHmelia-204 and CAHptain-205 clinical trials, and the wind-down of the Company’s investment in tildacerfont for the treatment of 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”, “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.

SOUTH SAN FRANCISCO, Calif.--( BUSINESS WIRE )-- Spruce Biosciences, Inc . (Nasdaq: SPRB), a late-stage biopharmaceutical company focused on developing and commercializing novel therapies for endocrine and neurological disorders with significant unmet medical need, today reported financial results for the third quarter ended September 30, 2024 and provided corporate updates. “ We remain on track to report primary efficacy and safety data plus interim data from the open-label extension of the CAHmelia-204 study of tildacerfont in adult CAH patients in December 2024. At the same time, we will also report topline dose-ranging efficacy and safety data from the CAHptain-205 study of tildacerfont in adult and pediatric CAH patients,” said Javier Szwarcberg, M.D., M.P.H., Chief Executive Officer of Spruce. “ It is an honor to continue partnering with the CAH community to open a new chapter in the management of CAH. We recognize the potentially transformative impact of tildacerfont, and we have a strong sense of urgency to deliver on our commitment to CAH patients.” Corporate Updates CAHmelia-204 Study of Tildacerfont in Adult CAH : CAHmelia-204 is a Phase 2b, randomized, double-blind, placebo-controlled clinical trial to evaluate the safety and efficacy of tildacerfont in reducing supraphysiologic glucocorticoid (GC) usage, a potentially registrational endpoint, in 90 adults with classic CAH on supraphysiologic doses of GCs with normal or near normal levels of androstenedione (A4) at baseline. In the first part of the clinical trial, patients were randomized to receive 200mg of tildacerfont once-daily (QD) or placebo for 24 weeks. During the second part of the clinical trial, all patients received 200mg of tildacerfont QD for 52 weeks. Throughout the trial, tapering of GCs is guided according to a pre-specified algorithm and continue to 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 GC dose in hydrocortisone equivalents (HCe) from baseline through week 24. CAHptain-205 Study of Tildacerfont in Adult and Pediatric CAH : CAHptain-205 is a Phase 2 open-label clinical trial, which utilizes a sequential nine cohort design, to evaluate the safety, efficacy, and pharmacokinetics of tildacerfont in adults and children between two and 17 years of age. Cohorts 1-3 evaluated weight-adjusted doses of tildacerfont between 50mg QD and 200mg QD in pediatric CAH patients between two and 17 years of age, and assessed changes in androgen levels over 12 weeks of treatment as well as the ability to reduce daily GC dose based on A4 normalization. Cohorts 4-9 are evaluating weight-adjusted doses of tildacerfont of 200mg twice-daily (BID) and 400mg BID in adults and children between two and 17 years of age and is assessing changes in androgen levels over four weeks of treatment. An optional open-label extension period will provide additional open-label treatment with tildacerfont to provide long-term safety data for up to two years. Anticipated Upcoming Milestones Topline results from the CAHmelia-204 clinical trial of tildacerfont 200mg QD in adult classic CAH patients on supraphysiologic doses of GCs with normal or near normal levels of A4 anticipated in December 2024 Topline results from the CAHptain-205 clinical trial of tildacerfont 200mg BID and 400mg BID adult and pediatric cohorts anticipated in December 2024 End of Phase 2 (EOP2) meeting with the U.S. Food and Drug Administration anticipated in the first half of 2025 Third Quarter 2024 Financial Results Cash and Cash Equivalents: Cash and cash equivalents as of September 30, 2024 were $60.1 million. Cash and cash equivalents are expected to allow the company to fund its current operating plan through the end of 2025. Collaboration Revenue: Collaboration revenue was $0.6 million and $4.2 million for the three and nine months ended September 30, 2024, respectively, compared to $3.1 million and $7.2 million for the same periods in 2023. The collaboration revenue reflects the partial recognition of the $15.0 million upfront payment the company received in April 2023 in connection with the collaboration and license agreement with Kaken Pharmaceutical. Research and Development (R&D) Expenses: R&D expenses for the three and nine months ended September 30, 2024 were $6.6 million and $25.0 million, respectively, compared to $13.5 million and $38.3 million for the same periods in 2023. The overall decrease in R&D expenses was primarily driven by the decrease in clinical development and manufacturing expenses related to the termination of the CAHmelia-203 study, completion of enrollment in the company’s CAHmelia-204 study, and completion of the Phase 2 POWER study in polycystic ovary syndrome, offset by an increase in expenses related to the ongoing CAHptain-205 study. General and Administrative (G&A) Expenses: G&A expenses for the three and nine months ended September 30, 2024 were $3.5 million and $11.3 million, respectively, compared to $3.2 million and $9.7 million for the same periods in 2023. Total Operating Expenses: Total operating expenses for the three and nine months ended September 30, 2024 were $10.0 million and $36.3 million, respectively, compared to $16.7 million and $48.0 million for the same periods in 2023. Operating expenses include non-cash stock-based compensation expenses of $1.1 million and $4.4 million for the three and nine months ended September 30, 2024, respectively, compared to $1.1 million and $3.4 million for the same periods in 2023. Net Loss: Net loss for the three and nine months ended September 30, 2024 was $8.7 million and $29.5 million, respectively, compared to $12.4 million and $38.0 million for the same periods in 2023. Upcoming Investor Conferences Javier Szwarcberg, M.D., M.P.H., Chief Executive Officer, will present at the Guggenheim Securities Healthcare Innovation Conference on November 11, 2024, at 3:30 p.m. ET. Interested parties can access the live webcast here . An archived copy of the webcast 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 endocrine and neurological disorders with significant unmet medical need. Spruce is developing its product candidate, tildacerfont, an oral, second-generation CRF 1 receptor antagonist, for the treatment of congenital adrenal hyperplasia (CAH), polycystic ovary syndrome (PCOS) and major depressive disorder (MDD). To learn more, visit www.sprucebio.com 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; Spruce’s expectations regarding reporting results of its clinical trials in 2024; Spruce’s plans to meet with the FDA to discuss the potential registrational path forward of tildacerfont for adult and pediatric classic CAH; 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,” “continue,” “will,” “potential,” “on track,” 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. CONDENSED BALANCE SHEETS (unaudited) (in thousands, except share and per share amounts) September 30, December 31, 2024 2023 ASSETS Current assets: Cash and cash equivalents $ 60,055 $ 96,339 Prepaid expenses 2,658 3,876 Other current assets 860 1,968 Total current assets 63,573 102,183 Right-of-use assets 998 1,181 Other assets 531 582 Total assets $ 65,102 $ 103,946 LIABILITIES AND STOCKHOLDERS’ EQUITY Current liabilities: Accounts payable $ 1,799 $ 3,332 Accrued expenses and other current liabilities 7,740 14,600 Term loan, current portion 1,622 1,622 Deferred revenue, current portion 697 4,911 Total current liabilities 11,858 24,465 Lease liabilities, net of current portion 809 1,019 Term loan, net of current portion 524 1,717 Other liabilities 273 236 Total liabilities 13,464 27,437 Commitments and contingencies Stockholders’ equity: Preferred stock, $0.0001 par value; 10,000,000 shares authorized and no shares issued or outstanding as of September 30, 2024 and December 31, 2023 — — Common stock, $0.0001 par value; 200,000,000 shares authorized as of September 30, 2024 and December 31, 2023; 41,302,599 and 41,029,832 shares issued and outstanding as of September 30, 2024 and December 31, 2023, respectively 4 4 Additional paid-in capital 278,343 273,737 Accumulated deficit (226,709 ) (197,232 ) Total stockholders’ equity 51,638 76,509 Total liabilities and stockholders’ equity $ 65,102 $ 103,946 SPRUCE BIOSCIENCES, INC. CONDENSED STATEMENTS OF OPERATIONS AND COMPREHENSIVE LOSS (unaudited) (in thousands, except share and per share amounts) Three Months Ended September 30, Nine Months Ended September 30, 2024 2023 2024 2023 Collaboration revenue $ 602 $ 3,073 $ 4,214 $ 7,202 Operating expenses: Research and development 6,554 13,494 24,961 38,332 General and administrative 3,456 3,237 11,330 9,699 Total operating expenses 10,010 16,731 36,291 48,031 Loss from operations (9,408 ) (13,658 ) (32,077 ) (40,829 ) Interest expense (71 ) (119 ) (251 ) (377 ) Interest income and other expense, net 808 1,423 2,851 3,237 Net loss (8,671 ) (12,354 ) (29,477 ) (37,969 ) Other comprehensive gain, net of tax: Unrealized gain on available for sale securities — 52 — 555 Total comprehensive loss $ (8,671 ) $ (12,302 ) $ (29,477 ) $ (37,414 ) Net loss per share, basic and diluted $ (0.21 ) $ (0.30 ) $ (0.72 ) $ (1.01 ) Weighted-average shares of common stock outstanding, basic and diluted 41,302,599 40,710,692 41,187,766 37,751,865