Tildacerfont

Integrated Long-Term Clinical Data of Tralesinidase Alfa Enzyme Replacement Therapy (TA-ERT) Demonstrates Profound and Durable Efficacy and Safety in Patients with Sanfilippo Syndrome Type B (MPS IIIB) Biologics License Application Submission of TA-ERT for MPS IIIB Anticipated in First Quarter of 2026 First Patient Dosed in Phase 2 TAMARIND Trial of Tildacerfont for Major Depressive Disorder (MDD) with Topline Results Anticipated in 1H 2026 Nasdaq Capital Market Relisting Anticipated Following Compliance with Minimum Bid Price for 20 Consecutive Trading Days SOUTH SAN FRANCISCO, Calif. --(BUSINESS WIRE)--Aug. 14, 2025-- Spruce Biosciences, Inc. (OTCQB: SPRB), a late-stage biopharmaceutical company focused on developing and commercializing novel therapies for neurological disorders with significant unmet medical need, today reported financial results for the second quarter ended June 30, 2025 and provided corporate updates. “We remain steadfast in our efforts to advance TA-ERT as a potential first-to-market treatment for children diagnosed with Sanfilippo Syndrome Type B (MPS IIIB). We have a strong sense of urgency to deliver on our commitment to patients and families suffering with MPS IIIB and remain on track to submit the biologics license application under the accelerated approval pathway in the first quarter of 2026,” said Javier Szwarcberg , M.D., M.P.H., Chief Executive Officer of Spruce Biosciences . “The integrated long-term clinical data of TA-ERT reinforces its potentially transformative clinical impact and compelling value proposition. TA-ERT has the potential to be the first disease-modifying therapy to treat MPS IIIB and could provide a novel option for families impacted by this devastating condition.” Corporate Updates Integrated Long-Term Clinical Data of TA-ERT Demonstrates Profound and Durable Efficacy and Safety in Patients with MPS IIIB. Earlier today, Spruce announced integrated group-level efficacy data for cerebral spinal fluid heparan-sulfate non-reducing end (CSF HS-NRE), cortical grey matter volume (CGMV), and Bayley-III Cognitive Raw Score (BSID-C), the cognitive subscale of the Bayley Scales of Infant and Toddler Development - Third Edition, as well as safety data over a five-year period from clinical studies 201, 202, and 401. Data from treated patients (n=22) in the studies 201, 202, and 401 was compared with data from untreated patients with MPS IIIB in natural history studies 901 and 902. Integrated group-level data from clinical studies 201, 202, and 401 demonstrate that TA-ERT therapy significantly reduced to normal or near normal CSF HS-NRE levels over a five-year period. At 240 weeks, CSF HS-NRE decreased 91.5 ng/mL from baseline (95% CI: -102.10, -80.90; p<0.0001). TA-ERT was also associated with stabilized cognition. Untreated children in the natural history studies showed a decline in cognition beginning at approximately five years of age that progressively worsened over time, while cognition in the TA-ERT treated group remained stable. Using a model-based approach, the mean (95% CI) BSID-C over six to 10 years of age was significantly higher in patients treated with TA-ERT, relative to untreated, age-matched children, with differences evident at six years of age (group difference: 10.67, 95% CI: 3.23, 18.11; p=0.005). At 10 years of age, the difference in BSID-C scores between groups increased to 34.66 (95% CI: 24.38, 44.93; p<0.0001). TA-ERT therapy was also associated with stabilization of CGMV, relative to the decline in CGMV observed in untreated children due to the progressive neurodegenerative nature of MPS IIIB. While CGMV should increase with age in children up to five years of age, there was an average loss of ~32 mL over 48 weeks in untreated children with MPS IIIB observed in study 901. Consistent with TA-ERT’s mechanism of action, decreases in CGMV were observed during the initial 24 weeks of TA-ERT treatment, likely reflecting intracellular clearance of cerebral spinal fluid heparan sulfate (CSF HS) and CSF HS-NRE. CGMV stabilized from weeks 48 to 240 with TA-ERT treatment. TA-ERT therapy exposure for up to 7.3 years has demonstrated an adequate safety profile in a serious and fatal disease for which no treatment is currently available. First Patient Dosed in Phase 2 TAMARIND Trial of Tildacerfont for MDD with Topline Results Anticipated in 1H 2026. In 2024, Spruce entered into a license, development, and option agreement (the “HMNC Agreement”) with HMNC Holding GmbH (HMNC). Under the terms of the HMNC Agreement, HMNC will fund and conduct a Phase 2 proof-of-concept study of tildacerfont, a potent and highly selective, oral, small-molecule antagonist of the CRF1 receptor, in patients with MDD who will be screened using Cortibon, HMNC’s proprietary genetic test. HMNC has initiated the Phase 2 TAMARIND study, which will explore the efficacy of 400mg twice-daily tildacerfont versus placebo in improving depressive symptoms in MDD patients. TAMARIND targets a biologically distinct subtype of MDD patients linked to hypothalamic-pituitary-adrenal (HPA) axis dysregulation. Tildacerfont has the potential to address hyperactive brain corticotropin-releasing factor neurotransmission and aberrant functioning of the HPA axis in patients with MDD by blocking the CRF1 receptor. Additionally, by utilizing genetic markers, HMNC’s companion diagnostic aims to identify MDD patients who are more likely to respond to CRF1 receptor antagonism. Topline results from TAMARIND are anticipated in the first half of 2026. Nasdaq Capital Market Relisting Anticipated Following Compliance with Minimum Bid Price for 20 Consecutive Trading Days. The company implemented a 1-for-75 reverse stock split of its issued and outstanding shares of common stock (“Reverse Stock Split”). The Reverse Stock Split was intended to bring the company into compliance with the minimum bid price requirement for continued listing on the Nasdaq Capital Market. The company’s common stock began trading on a split-adjusted basis on the OTCQB on August 7, 2025 . The company’s common stock will resume trading on the Nasdaq Capital Market so long as the company remains in compliance with the minimum bid price requirement under Nasdaq Listing Rule 5450(a)(1) for 20 consecutive trading days. Second Quarter 2025 Financial Results Cash and Cash Equivalents: Cash and cash equivalents as of June 30, 2025 were $16.4 million . Cash and cash equivalents are expected to allow the company to fund its current operating plan through the end of 2025. Research and Development (R&D) Expenses: R&D expenses for the three and six months ended June 30, 2025 were $(0.4) million and $10.4 million , respectively, compared to $8.1 million and $18.4 million for the same periods in 2024. R&D expenses for the three months ended June 30, 2025 include a reduction in recorded liabilities of $3.3 million and increase in receivables of $0.7 million associated with the acquisition of TA-ERT. R&D expenses for the six months ended June 30, 2025 also include a reduction in recorded liabilities of $3.4 million and increase in receivables of $0.7 million associated with the acquisition of TA-ERT, offset by $5.7 million in costs related to the acquisition of SPR202, an anti-corticotrophin releasing hormone monoclonal antibody for the treatment of congenital adrenal hyperplasia. General and Administrative (G&A) Expenses: G&A expenses for the three and six months ended June 30, 2025 were $3.1 million and $6.8 million , respectively, compared to $3.6 million and $7.9 million for the same periods in 2024, primarily driven by a decrease in stock-based compensation expense. Total Operating Expenses: Total operating expenses for the three and six months ended June 30, 2025 were $2.7 million and $17.2 million , respectively, compared to $11.6 million and $26.3 million for the same periods in 2024. Operating expenses include non-cash stock-based compensation expenses of $(0.1) million and $0.5 million for the three and six months ended June 30, 2025 , respectively, compared to $1.7 million and $3.2 million for the same periods in 2024. Net Loss: Net loss for the three and six months ended June 30, 2025 was $2.1 million and $16.1 million , respectively, compared to $9.2 million and $20.8 million for the same periods in 2024. About Spruce Biosciences Spruce Biosciences is a late-stage biopharmaceutical company focused on developing and commercializing novel therapies for neurological 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 ability to seek accelerated approval of TA-ERT for MPS IIIB based on existing clinical data; the timing and likelihood of regulatory filings and approvals for TA-ERT, including the anticipated biologics license application submission of TA-ERT for MPS IIIB in the first quarter of 2026; the potentially transformative clinical impact and compelling value proposition for TA-ERT; TA-ERT’s potential to be the first disease-modifying therapy to treat MPS IIIB as a novel treatment option; Spruce’s expectation that topline results from the TAMARIND study will be available in the first half of 2026; and the resumption of trading on the Nasdaq Capital Market. 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”, “intend”, “expect” 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) June 30 , December 31 , 2025 2024 ASSETS Current assets: Cash and cash equivalents $ 16,387 $ 38,753 Prepaid expenses 1,868 3,177 Other current assets 2,698 2,276 Total current assets 20,953 44,206 Right-of-use assets 803 934 Other assets 64 69 Total assets $ 21,820 $ 45,209 LIABILITIES, REDEEMABLE PREFERRED STOCK, AND STOCKHOLDERS’ EQUITY Current liabilities: Accounts payable $ 807 $ 1,295 Accrued expenses and other current liabilities 6,310 12,329 Term loan, current portion 943 1,622 Total current liabilities 8,060 15,246 Lease liabilities, net of current portion 580 736 Term loan, net of current portion — 124 Other liabilities — 282 Total liabilities 8,640 16,388 Commitments and contingencies Series A redeemable preferred stock, $0.0001 par value; 1 share authorized, issued and outstanding as of June 30, 2025 ; no shares authorized, issued or outstanding as of December 31, 2024 — — Stockholders’ equity: Preferred stock, $0.0001 par value; 10,000,000 shares authorized and no shares issued or outstanding as of June 30, 2025 and December 31, 2024 — — Common stock, $0.0001 par value; 200,000,000 shares authorized as of June 30, 2025 and December 31, 2024 ; 563,042 shares issued and outstanding as of June 30, 2025 and December 31, 2024 — — Additional paid-in capital 279,556 279,089 Accumulated deficit (266,376 ) (250,268 ) Total stockholders’ equity 13,180 28,821 Total liabilities, redeemable preferred stock, and stockholders’ equity $ 21,820 $ 45,209 SPRUCE BIOSCIENCES, INC. CONDENSED STATEMENTS OF OPERATIONS AND COMPREHENSIVE LOSS (unaudited) (in thousands, except share and per share amounts) Three Months Ended June 30 , Six Months Ended June 30 , 2025 2024 2025 2024 Collaboration revenue $ — $ 1,610 $ — $ 3,612 Operating expenses: Research and development (430 ) 8,090 10,407 18,407 General and administrative 3,122 3,556 6,777 7,874 Total operating expenses 2,692 11,646 17,184 26,281 Loss from operations (2,692 ) (10,036 ) (17,184 ) (22,669 ) Interest expense (29 ) (83 ) (65 ) (180 ) Interest and other income, net 654 938 1,141 2,043 Net loss and comprehensive loss (2,067 ) (9,181 ) (16,108 ) (20,806 ) Net loss per share, basic and diluted $ (3.50 ) $ (16.73 ) $ (27.36 ) $ (37.94 ) Weighted-average shares of common stock outstanding, basic and diluted 591,137 548,789 588,653 548,344 View source version on businesswire.com: https://www.businesswire.com/news/home/20250814987753/en/ Media Katie Beach Oltsik Inizio Evoke Comms (937) 232-4889 Katie.Beach@inizioevoke.com media@sprucebio.com Investors Samir Gharib President and CFO Spruce Biosciences, Inc. investors@sprucebio.com Source: Spruce Biosciences, Inc.

Today’s deal is a good fit for Tokyo-based Kaken, which scooped up the Japan rights to another late-stage HAE asset in April.\n Kaken Pharmaceutical is paying $16 million upfront for the Japanese rights to Astria Therapeutics’ phase 3-stage hereditary angioedema (HAE) drug.Astria took the candidate, a monoclonal antibody inhibitor of plasma kallikrein called navenibart, into a late-stage study off the back of a phase 1b/2 trial last year that tied the drug to up to a 92% reduction in HAE attacks at six months.In return for the rights to develop and commercialize navenibart in its home territory of Japan, Kaken is handing over $16 million upfront, with potentially another $16 million to follow in commercialization and sales milestones. Astria could also be in line for tiered royalties on net sales and partial reimbursement for its phase 3 costs.“We are thrilled to partner with Kaken for the development and commercialization of navenibart in Japan, which advances our strategy to enable broad access to navenibart globally,” Astria CEO Jill Milne, Ph.D., said in an August 6 release.“In addition to our shared values that put patients first, Kaken brings strong relationships with the Japanese medical community that we believe will support both our phase 3 Alpha-Orbit trial as well as the potential commercialization of navenibart in the future,” Milne added.HAE is a genetic disease marked by low levels or dysfunction of the C1 inhibitor. Patients can be struck with bouts of severe swelling across the body, and attacks can be fatal if they impact the lungs.CSL’s HAE preventative treatment Andembry was approved in Japan earlier this year, before gaining the go-ahead from the FDA in June. It set up CSL to take on Takeda’s blockbuster Takhzyro and BioCryst Pharmaceuticals’ fast-rising Orladeyo in a competitive market to treat patients with the rare genetic condition.Today’s deal is a good fit for Tokyo-based Kaken, which scooped up the Japan rights to another late-stage HAE asset in April in the form of KalVista Pharmaceuticals’ sebetralstat. The drug was approved by the FDA last month under the brand name Ekterly.  Earlier in the year, Kaken also acquired the Japanese rights to develop Alumis’ late-stage tyrosine kinase 2 (TYK2) inhibitor as a dermatology treatment in Japan.Kaken already markets a variety of products in Japan, including hyaluronate sodium for osteoarthritis and Fiblast for skin ulcers. The company has also licensed a number of drugs from other companies, including seladelpar for primary biliary cholangitis from CymaBay Therapeutics and tildacerfont from Spruce Biosciences for congenital adrenal hyperplasia.“Our partnership with Astria for the development and commercialization of navenibart supports our strategy of providing therapies that address unmet medical needs in the Japanese community,” Kaken’s president, Hiroyuki Horiuchi, said in today’s release.“We believe that navenibart is a complementary fit with our HAE portfolio, providing patients in Japan with the potential for low-burden treatments to better manage their disease,” Horiuchi added.