Polycystic Ovary Syndrome

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

The COVID vaccine is safe to administer during pregnancy, researchers report in an important finding on the safety of the vaccine in infants -- despite widespread fear and misinformation. Landmark study contradicts misinformation about brain development and conditions like autism in children. The COVID vaccine is safe to administer during pregnancy, reports UC San Francisco in an important finding on the safety of the vaccine in infants -- despite widespread fear and misinformation. The study, published in JAMA Pediatrics, is the first scientific inquiry into whether infants are at increased risk of neurodevelopmental impairments as a result of maternal vaccination. The landmark study of more than 2,200 infants from across the country found that in utero exposure to the vaccine caused no abnormal delays when the infants were tested at 12 months and again at 18 months. "This is a very reassuring finding -- pregnant women have been facing unanswered questions around COVID vaccinations for several years," said first author Eleni Jaswa, MD, MSc, a reproductive endocrinologist and fertility specialist at UCSF Health, noting the investigation started in April 2020. She is also an assistant professor in the UCSF Department of Obstetrics, Gynecology & Reproductive Sciences. First meaningful evidence of maternal vaccination safety during pregnancy Although pregnant women are considered at increased risk of severe illness with COVID-19, some chose not to get the COVID vaccine due to safety concerns around potential risks to their unborn children. Some 34% of the participants in the study were vaccinated in the first trimester, about 45% in the second trimester, and nearly 21% in the third trimester. They were asked to complete a 30-item questionnaire assessing whether their infants performed expected milestones. After adjusting for such factors as maternal age, race, ethnicity, education, income and maternal depression, the researchers found no difference in the risk of infant neurodevelopment at either 12 months or 18 months. They noted an increased risk of delay among male infants at 12 months but the difference was not observed at 18 months. The study is ongoing. "Understandably, there's been concern about the potential impact of maternal vaccination on offspring," said senior author Heather Huddleston, MD, a UCSF Health reproductive endocrinologist and director of the UCSF Polycystic Ovary Syndrome Clinic (PCOS). "Despite early safety data as well as recommendations from physicians and health organizations, vaccine hesitancy is still preventing universal use," she said. "To this day, misinformation continues to abound. People are concerned about such issues as brain development and conditions like autism in children. This is the first meaningful evidence into the safety of vaccination from the standpoint of early offspring neurodevelopment." Co-authors: All from UCSF, the paper's co-authors are Marcelle Cedars, MD; Karla Lindquist, PhD; Somer Bishop, PhD; Young-Shin Kim, MD, MPH, PhD; Amy Kaing, MD; Mary Prahl, MD; Stephanie Gaw, MD, PhD; Jamie Corley, BS; Elena Hoskin, MS; Yoon Jae Cho, MD; and Elizabeth Rogers, MD.

The Biden Administration, through the Advanced Research Projects Agency for Health, has committed to invest $100 million into womens health research, First Lady Jill Biden announced Wednesday.The investment is part of the White House Initiative on Womens Health Research, launched by Jill Biden last year to draw forth more funding to womens health research through partnerships between the federal government and the private sector. The Advanced Research Projects Agency for Health, or ARPA-H, will oversee distribution of funds through its Sprint for Womens Health program.We have a clear goal: to fundamentally change how our nation approaches and funds womens health research, Biden said in remarks in Cambridge, Massachusetts. There are big gaps in research on diseases and conditions that only affect women, that disproportionately affect women, or that affect women and men differently.Research and development for conditions that affect women, such as endometriosis and polycystic ovary syndrome, has often been neglected. Drug development for these kinds of diseases receives less funding from biopharmaceutical companies than others that mainly affect men, too.Recent political developments, like ongoing litigation over the abortion pill mifepristone, have brought increased attention to womens health research, however.ARPA-H program managers will soon announce a list of specific topics for which theyll solicit proposals for tools, products or platforms that can improve womens health outcomes.As part of that process, ARPA-H will gather a group of experts to create a range of investments that encompass disease-agnostic and non-traditional research approaches.ARPA-H director Renee Wegrzyn said the program will aim to radically accelerate the next generation of discoveries that range from early laboratory proofs of concept that may impact future generations, to products that are ready to be commercialized and launched to start improving womens health today.The agency is holding a virtual meeting that it describes as a Proposers Day in March to share more information about the program.Launched in 2022, ARPA-H was modeled after the Department of Defense agency DARPA and is designed to catalyze cutting-edge health research. '