Inclusion Reflects Spruce’s Momentum as the Company Advances Toward a Planned Biologics License Application (BLA) Submission and Potential Commercial Launch of Tralesinidase Alfa Enzyme Replacement Therapy (TA-ERT) for Sanfilippo Syndrome Type B (MPS IIIB)

Spruce Biosciences, Inc. (NASDAQ:SPRB), a late-stage biopharmaceutical company focused on developing and commercializing novel therapies for neurological disorders with significant unmet medical need, today announced that it has been added as a member of the Russell 3000^® Index, effective with the opening of U.S. equity markets today, in connection with the 2026 Russell U.S. Indexes Reconstitution.

The Russell 3000^® Index measures the performance of the largest U.S.-listed companies based on total market capitalization and is periodically reconstituted by FTSE Russell. Companies included in the Russell 3000^® Index are automatically included in the small-cap Russell 2000^® Index. Both indexes are widely used by investment managers and institutional investors for both index-based and active investment strategies, and serve as benchmarks against which the performance of investment products is measured.

"Our addition to the Russell 3000^® Index reflects the progress we have made as a precommercial organization preparing for the potential U.S. FDA approval and launch of TA-ERT for MPS IIIB," said Samir Gharib, President and Chief Financial Officer of Spruce Biosciences. "We believe inclusion in the index will enhance our visibility within the broader investment community, help broaden our shareholder base, and support trading liquidity as we advance toward a planned BLA submission of TA-ERT. We thank our shareholders for their continued support and remain focused on delivering value for the patients and families we serve."

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. Spruce’s lead product candidate, tralesinidase alfa enzyme replacement therapy (TA-ERT), is in late-stage development for the treatment of mucopolysaccharidoses type IIIB (MPS IIIB), or Sanfilippo Syndrome Type B, a devastating pediatric neurodegenerative disorder for which there are no FDA-approved therapies. TA-ERT has received Breakthrough Therapy Designation, Rare Pediatric Disease Designation, Fast Track Designation and Orphan Drug Designation from the FDA, as well as Orphan Drug Designation in the European Union. 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, anticipated benefits of Spruce’s inclusion in the Russell 3000^® Index, fulfillment of Spruce’s strategic business objectives, potential BLA submission, potential regulatory approval, planned commercial launch of TA-ERT, and TA-ERT’s potential to be the first disease-modifying treatment option for MPS IIIB. 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 "plan", "will", "believe", "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.

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Media

Carolyn Hawley

Inizio Evoke Comms

Carolyn.Hawley@inizioevoke.com

media@sprucebio.com

Investors

Monique Kosse

Gilmartin Group

Monique@GilmartinIR.com

investors@sprucebio.com