Puberty, Precocious

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.

The Establishment of the Facility Demonstrates the Company's Commitment to Delivering Differentiated Solutions to Gynecology and Pediatrics Challenges SHANGHAI, Dec. 22, 2023 /PRNewswire/ -- Changchun GeneScience Pharmaceutical ("GenSci"), a subsidiary of Changchun High-Tech Industries (Group), held a groundbreaking ceremony for its new global headquarters and research & development (R&D) center at Shanghai Zhangjiang International Medical Park on December 15th. With an increasing focus on women`s and children`s health, the Chinese government has been intensifying efforts to improve healthcare services for these demographics, embedding their care within the wider framework of the country's economic and social development policies. The establishment of the R&D center sets the stage for GenSci to further advance the convergence of industry, academia, research and the medical community. By leveraging cutting-edge R&D capabilities and the application of artificial intelligence technologies, GenSci is well-positioned to provide premium health solutions for women and children. The initiative aligns with GenSci's commitment to harnessing science and technology to protect and enhance the health of these vulnerable groups. Continue Reading Changchun GeneScience Pharmaceutical Co., Ltd. The construction of this facility is progressing as planned, and it is expected to be fully operational by 2027, providing a capacity to accommodate up to 2,000 R&D professionals. Supporting the Healthy China Initiative: Focusing on the Health Needs of Women and Children Recognizing the pivotal role of women and children's health in the nation's overall well-being, the government has designated this field as a critical priority. This is evident in the implementation of significant strategic initiatives such as the Healthy China Initiative (2019-2030), the Outline for Children's Development in China (2021-2030), and the Outline for Women's Development in China (2021-2030). These key documents underscore our unwavering commitment to enhancing nationwide awareness regarding the specific needs of women and children, with an overarching objective of safeguarding their health. The health of women and children confronted with new challenges. While the incidence of common childhood diseases has decreased, there is a rise in lifestyle-related health issues in children, including early puberty, myopia, growth deficiencies, body image concerns, immune system abnormalities, and mental health disorders. In addition, women are generally grappling with reproductive health issues and the effects of menopause that can significantly impact their quality of life. Moreover, the periods of pregnancy and early childhood present vital opportunities to avert diseases that can develop later in life. Enhanced health management for women and children during these key stages can help prevent long-term health issues, carrying significant implications for the broader society. Providing Premier Global Maternal and Child Health Solutions through Distinctive Innovation Aligned with national healthcare directives, GenSci has ramped up its R&D investments to address the unmet health needs of women and children. The company has already developed the capability to innovate across various product categories, including biopharmaceuticals, chemical drugs, live bacterial preparations (LBPs) and medical devices. The GenSci general manager, Dr. Jin, pointed out that their product innovations are designed to deliver substantial unique benefits. The establishment of the Zhangjiang R&D center is a testament to GenSci's commitment to independent innovation. Since its founding in 1997, GenSci has introduced several groundbreaking therapies, including the GenSci Recombinant Human Growth Hormone, GenSci Heng Recombinant Human Follicle-Stimulating Hormone and Jinfuning Recombinant Human Granulocyte-Stimulating Factor Gel. The company's proprietary innovations and outstanding contribution in the field of child growth and development were recognized when its "Development and Industrialization of Recombinant Human Growth Hormone Series Products" project won the Second Prize of the 2015 National Science and Technology Progress Award. The accolade underscores GenSci's expertise in independent innovation within China's pharmaceutical sector. With an ongoing focus on growth disorders in children, GenSci has expanded its attention to the broader spectrum of children's health. This includes addressing concerns such as abnormal sexual development, obesity, respiratory and digestive health, allergies and autoimmune disorders, neurological and speech development, as well as concerns related to body image. As an illustration, GenSci has been develop an industry-leading ultra-long-acting growth hormone that is administered monthly since 2020, as well as innovative oral treatments for short stature. The company has also been creating comprehensive range of solutions designed to diagnose and treat precocious puberty, including rapid sex hormone tests and long-acting gonadotropin-releasing hormone analogs for treating central precocious puberty. Furthermore, GenSci has been adopting a comprehensive approach that addresses women's health needs throughout their life cycle. This initiative includes support for assisted reproduction, menopausal health, and the treatment of prevalent gynecological conditions. Significantly, the company has been developing the world's first lytic enzyme and live bacterial preparation (LBP) for treating vaginitis caused by drug-resistant bacteria, offering an alternative to antibiotics and addressing the issue of drug resistance. "GenSci has built a globally innovative and competitive R&D product pipeline," Dr. Jin declared. "By 2025, the firm will boast an extensive portfolio, with the expectation of launching more than four top-tier innovative drugs and five novel medical devices annually in the years to come." Enhancing Collaboration Across Industry, Academia, Research, and Healthcare Providers to Tackle Key Issues in Women's and Children's Health GenSci, through a combination of proprietary R&D and collaborative efforts with partners, has developed a suite of sophisticated R&D technology platforms that drive forward-thinking product development. The platforms focus on the protein drug sustained-release technology, mucosal delivery systems for nucleic acid medications, antibody-drug conjugate (ADC) technology, and innovations in ultrasound and hydrogel technologies. Integrating AI technology, GenSci covers the entire drug innovation process, from initial design and screening to process development and formulation. Moreover, the company promotes the introduction and adoption of cutting-edge concepts and technologies by facilitating synergistic integration of industry, academia, research and the medical community, ensuring effective cooperation among these stakeholders. GenSci has formed enduring and robust partnerships with nearly 20 prominent universities, including Shanghai Jiao Tong University and Zhejiang University. The company has also engaged in various scientific research collaborations with institutions such as Shanghai Jiao Tong University, Shandong University, and the Center for Excellence in Brain Science and Intelligence Technology at the Chinese Academy of Sciences. Additionally, GenSci has joined forces with numerous maternity and pediatric departments within both general and specialized hospitals through multicenter clinical trials and joint applications for national projects. As part of these alliances, the company contributes its substantial technical expertise and digital platform capabilities — skills acquired during product development — to these hospitals at no cost. Frontline doctors are engaged to review and provide feedback on these tools, aiding the ongoing enhancement of GenSci's research and digital capabilities in gynecology and pediatrics. Additionally, GenSci has established collaborations with numerous hospitals in the development of digital medical assistance systems，it actively engages in medical research to achieve technological breakthroughs and plays a pivotal role as a high-tech innovation platform in specialized treatment fields. Through deep cooperation and extensive coverage, it truly realizes co-creation and win-win outcomes in medical research. The groundbreaking of GenSci's global innovation hub and R&D center enpowers the company to fully utilize its expertise in gynecology and pediatrics. GenSci intends to introduce innovative therapies for oncology, immunology, hearing loss, and drug-resistant bacterial infections, aiming to address unmet clinical needs. With its advanced strategic positioning, substantial investment in R&D, and unwavering commitment to product innovation, GenSci continues to strive towards tackling significant medical challenges while providing exceptional exceptional treatment options for healthcare professionals and patients. SOURCE Changchun GeneScience Pharmaceutical Co., Ltd.