SUPPLEMENT

to the

Loan and Security Agreement

dated as of January 7, 2026

among

SPRUCE BIOSCIENCES, INC. (“Borrower”)

and

AVENUE CAPITAL MANAGEMENT II, L.P.,

a Delaware limited partnership,

as administrative agent and collateral agent (in such capacity “Agent”)

and

AVENUE VENTURE OPPORTUNITIES FUND, L.P. II,

a Delaware limited partnership (“Avenue 2”), as a lender

and

any Person from time to time party hereto

as a lender (in such capacity, with Avenue 2, each a “Lender” and collectively, “Lenders”)

This is a Supplement identified in the document entitled Loan and Security Agreement, dated as of January 7, 2026 (as amended, restated, supplemented and modified from time to time, the “Loan and Security Agreement”), by and among Borrower, Lenders and Agent. All capitalized terms used in this Supplement and not otherwise defined in this Supplement have the meanings ascribed to them in the Loan and Security Agreement, which is incorporated in its entirety into this Supplement. In the event of any inconsistency between the provisions of the Loan and Security Agreement and this Supplement, this Supplement is controlling.

In addition to the provisions of the Loan and Security Agreement, the parties agree as follows:

“Amortization Period” means the period commencing on the first day of the first full calendar month following the Interest-only Period and continuing until the Maturity Date.

“BLA” means a biologics license application submitted pursuant to Section 351(a) of the Public Health Service Act (42 U.S.C. § 262(a)) and 21 C.F.R. Part 601, or any successor statute or regulation.

“Commitment” means, subject to the terms and conditions set forth in the Loan and Security Agreement and this Supplement, the commitment of Lenders to make Growth Capital Loans to Borrower up to an aggregate original principal amount of Fifteen Million Dollars ($15,000,000) (“Tranche 1”) within 5 Business Days after the Closing Date, up to Ten Million Dollars ($10,000,000) to be funded between March 1, 2026 and September 30, 2026, subject to the conditions in Section 1(a)(i) of Part 2 (“Tranche 2”) and up to Fifteen Million Dollars ($15,000,000) to be funded between September 1, 2026 and March 31, 2027, subject to the conditions in Section 1(a)(ii) of Part 2 (“Tranche 3”). Upon the mutual agreement of Lenders and Borrower, Lenders may make additional Growth Capital Loans to Borrower of up to an additional Ten Million Dollars ($10,000,000) (the “Discretionary Tranche 4”) to be funded between October 1, 2027 and June 30, 2028, as Borrower and Lenders may mutually agree, subject to the conditions in Section 1(a)(iii) of Part 2 and approval from Lenders’ Investment Committees, in their sole discretion; provided that, as of the Closing Date, Discretionary Tranche 4 shall not be considered, and is not, committed hereunder by any Lender and there shall be no fees associated with the Discretionary Tranche 4 until any Growth Capital Loans to be made under such tranche are committed by Lenders.

“Designated Rate” means, for each Growth Capital Loan, a variable rate of interest per annum equal to the greater of (A) the Prime Rate plus five and one-quarter percent (5.25%) and (B) twelve and one-quarter percent

(12.25%). Changes to the Designated Rate based on changes to the Prime Rate shall be effective as of the next scheduled interest payment date immediately following such change.

“FDA” means the United States Food and Drug Administration or any successor thereto.

“Final Payment” means a payment (in addition to and not a substitution for the regular monthly payments of principal plus accrued interest) equal to four percent (4.00%) of the original Commitment amount of Forty Million Dollars ($40,000,000); provided that if Borrower requests and Lenders agree to fund Discretionary Tranche 4, the Final Payment shall be equal to four percent (4.00%) of the Commitment amount of Fifty Million Dollars ($50,000,000).

“Discretionary Tranche 4 Availability Milestone” means [***].

“Growth Capital Loan” means any Loan requested by Borrower and funded by a Lender under its Commitment for general corporate purposes of Borrower.

“Interest-only Milestone 1” means [***].

“Interest-only Milestone 2” means [***].

“Interest-only Period” means the period commencing on the Closing Date and continuing until the twelve (12) month anniversary of the Closing Date; provided, however, that such period shall be extended for six (6) months if as of the last day of the Interest-only Period then in effect Borrower has achieved Interest-only Milestone 1; provided, further, that such period shall be extended for an additional twelve (12) months if as of the last day of the Interest-only Period then in effect Borrower has achieved Interest-only Milestone 2; provided, further, however, that the Interest-only Period shall not exceed thirty (30) months; and provided, further, however, that no extension of the Interest-only Period shall be available if as of the last day of the Interest-only Period then in effect an Event of Default shall have occurred and be continuing.

“Loan” or “Loans” mean, as the context may require, individually a Growth Capital Loan, and collectively, the Growth Capital Loans.

“Loan Commencement Date” means, with respect to each Growth Capital Loan: (a) the first day of the first full calendar month following the Borrowing Date of such Loan if such Borrowing Date is not the first day of a month; or (b) the same day as the Borrowing Date if the Borrowing Date is the first day of a month.

“LTM Product Revenue” means, as of the last day of any calendar month, Borrower’s Product Revenue for the trailing twelve (12) month period ending on such date.

“Maturity Date” means July 1, 2029.

“Prepayment Fee” means, with respect to any prepayment of the Loans:

(i) if the prepayment occurs during the period commencing on the Closing Date and ending on (and including) the one-year anniversary of the Closing Date, an amount equal to the principal amount of the Loans prepaid multiplied by three percent (3.00%);

(ii) if the prepayment occurs during the period commencing on the day immediately following the one-year anniversary of the Closing Date and ending on (and including) the two-year anniversary of the Closing Date, an amount equal to the principal amount of the Loans prepaid multiplied by two percent (2.00%); and

(iii) if the prepayment occurs at any time after the date immediately following the two-year anniversary of the Closing Date (but excluding the Maturity Date), an amount equal to the principal amount of the Loans prepaid multiplied by one percent (1.00%).

“Prime Rate” is the rate of interest per annum from time to time published in the money rates section of The Wall Street Journal or any successor publication thereto as the “prime rate” then in effect; provided that, in the event such rate of interest is less than zero, such rate shall be deemed to be zero for purposes of this Supplement; and provided further that if such rate of interest, as set forth from time to time in the money rates section of The Wall Street Journal, becomes unavailable for any reason as determined by Agent, the “Prime Rate” shall mean the rate of interest per annum announced by Wells Fargo Bank as its prime rate in effect at its principal office in the State of California (such announced Prime Rate not being intended to be the lowest rate of interest charged by such institution in connection with extensions of credit to debtors); provided that, in the event such rate of interest is less than zero, such rate shall be deemed to be zero for purposes of this Supplement.

“Principal Trading Market” means the principal trading market for the Company’s Common Stock. The “Principal Trading Market” for the Common Stock is the Nasdaq Capital Market (or any successor thereof).

“Product Revenue” means, for any month, Borrower’s total Revenue from the sale of TA-ERT for such month determined on a consolidated basis in accordance with GAAP.

“Revenue” means, as of any date of determination, Borrower’s revenue determined in accordance with GAAP.

“TA-ERT” means Borrower’s therapeutic product for tralesinidase alfa enzyme replacement therapy.

“Termination Date” means the earlier of: (i) the date Lender may terminate making Growth Capital Loans or extending other credit pursuant to the rights of Lender under Article 7 of the Loan and Security Agreement; (ii) with respect to Tranche 2, September 30, 2026; (iii) with respect to Tranche 3, March 31, 2027; and (iv) with respect to Discretionary Tranche 4, June 30, 2028.

“Tranche 2 Availability Milestone” means [***].

“Tranche 3 Availability Milestone” means [***].

“Threshold Amount” means Two Hundred Fifty Thousand Dollars ($250,000).

“Warrant” is defined in Part 2, Section 3(a) hereof.

Subject to satisfaction of the conditions precedent specified in Sections 4.1 and Section 4.2 of the Loan and Security Agreement and this Supplement, each Lender agrees to make Growth Capital Loans to Borrower under Lender’s Commitment from time to time from and after the Closing Date up to and including the Termination Date in

an aggregate, original principal amount up to, but not exceeding, then then-unfunded portion of such Lender’s Commitment.

Borrower represents and warrants that as of the Closing Date and, subject to any written updates of the information set forth below by Borrower to each Lender and Agent, each Borrowing Date:

Form of Promissory Note Exhibit “A”

Form of Borrowing Request Exhibit “B”

Form of Compliance Certificate Exhibit “C”

Form of Warrant Exhibit “D”

[Remainder of this page intentionally left blank; signature page follows]

[Signature page to Supplement to Loan and Security Agreement]

IN WITNESS WHEREOF, the parties have executed this Supplement as of the date first above written.

BORROWER:

SPRUCE BIOSCIENCES, INC.

By: /s/ Samir Gharib

Name: Samir Gharib

Title: President and Chief Financial Officer

Address for Notices: 611 Gateway Boulevard, Suite 740

South San Francisco, CA 94080

Attn: Chief Executive Officer

Email:

AGENT:

AVENUE CAPITAL MANAGEMENT II, L.P.

By: Avenue Capital Management II GenPar, LLC

Its: General Partner

By: /s/ Sonia Gardner

Name: Sonia Gardner

Title: Member

Address for Notices: [***]

LENDER:

AVENUE VENTURE OPPORTUNITIES FUND II, L.P.

By: Avenue Venture Opportunities Partners II, LLC

Its: General Partner

By: /s/ Sonia Gardner

Name: Sonia Gardner

Title: Authorized Signatory

Address for Notices: [***]

EXHIBIT “A”

FORM OF PROMISSORY NOTE

Note No. X‑XXX

$15,000,000 January 7, 2026

The undersigned (“Borrower”) promises to pay to the order of [AVENUE VENTURE OPPORTUNITIES FUND II, L.P.], a Delaware limited partnership (“Lender”), at such place as Lender may designate in writing, in lawful money of the United States of America, the principal sum of ______________________________ Dollars ($__________), with interest thereon from the date hereof until maturity, whether scheduled or accelerated, at a variable rate per annum equal to the greater of (A) the Prime Rate plus five and one-quarter percent (5.25%) and (B) twelve and one quarter percent (12.25%). (the “Designated Rate”), according to the payment schedule described herein, except as otherwise provided herein. In addition, on the Maturity Date, the Borrower promises to pay to the order of Lender (i) all principal and accrued interest then remaining unpaid and (ii) the Final Payment (as defined in the Loan Agreement (as defined herein)).

This Note is one of the Notes referred to in, and is entitled to all the benefits of, a Loan and Security Agreement, dated as of January 7, 2026, among Borrower, Lender, the other lender party thereto and Agent (as the same has been and may be amended, restated or supplemented from time to time, the “Loan Agreement”). Each capitalized term not otherwise defined herein shall have the meaning set forth in the Loan Agreement. The Loan Agreement contains provisions for the acceleration of the maturity of this Note upon the happening of certain stated events.

Principal of and interest on this Note shall be payable as provided under Section 2 of Part 2 of the Supplement to the Loan Agreement.

This Note may be prepaid only as permitted under Section 2 of Part 2 of the Supplement to the Loan Agreement.

Any unpaid payments of principal or interest on this Note shall bear interest from their respective maturities, whether scheduled or accelerated, at a rate per annum equal to the Default Rate, compounded monthly. Borrower shall pay such interest on demand.

Interest, charges and fees shall be calculated for actual days elapsed on the basis of a 360‑day year, which results in higher interest, charge or fee payments than if a 365‑day year were used. In no event shall Borrower be obligated to pay interest, charges or fees at a rate in excess of the highest rate permitted by applicable law from time to time in effect.

If Borrower is late in making any scheduled payment under this Note by more than five (5) days, Borrower agrees to pay a “late charge” of five percent (5%) of the installment due, but not less than fifty dollars ($50) for any one such delinquent payment. This late charge may be charged by Lender for the purpose of defraying the expenses incidental to the handling of such delinquent amounts. Borrower acknowledges that such late charge represents a reasonable sum considering all of the circumstances existing on the date of this Note and represents a fair and reasonable estimate of the costs that will be sustained by Lender due to the failure of Borrower to make timely payments. Borrower further agrees that proof of actual damages would be costly and inconvenient. Such late charge shall be paid without prejudice to the right of Lender to collect any other amounts provided to be paid or to declare a default under this Note or any of the other Loan Documents or from exercising any other rights and remedies of Lender.

[Signature page to Promissory Note]

This Note shall be governed by, and construed in accordance with, the laws of the State of California, excluding those laws that direct the application of the laws of another jurisdiction.

Borrower’s execution and delivery of this Note via facsimile, electronic mail (including pdf or any electronic signature complying with the U.S. federal ESIGN Act of 2000, e.g., www.docusign.com) shall constitute effective execution and delivery of this Note and agreement to and acceptance of the terms hereof for all purposes. The fact that this Note is executed, signed, stored or delivered electronically shall not prevent the assignment or transfer by Lender of this Note pursuant to the terms of the Loan Agreement or the enforcement of the terms hereof. Physical possession of the original of this Note or any paper copy thereof shall confer no special status to the bearer thereof. In no event shall an original ink-signed paper copy of this Note be required for any exercise of Lender’s rights hereunder.

SPRUCE BIOSCIENCES, INC.

By: ________________________

Name: Samir Gharib

Title: President and Chief Financial Officer

EXHIBIT “B”

FORM OF BORROWING REQUEST

January 7, 2026

AVENUE CAPITAL MANAGEMENT II, L.P.

[***]

Re: SPRUCE BIOSCIENCES, INC.

Ladies and Gentlemen:

Reference is made to the Loan and Security Agreement, January 7, 2026 (as amended, restated or supplemented from time to time, the “Loan Agreement”; the capitalized terms used herein as defined therein), among Avenue Capital Management II, L.P. (“Agent”), as administrative agent and collateral agent (in such capacity, “Agent”), Avenue Venture Opportunities Fund II, L.P., as a lender (“Avenue 2”), each Person from time to time party hereto as a lender (together with Avenue 2, collectively, “Lenders”, and each a “Lender”), and Spruce Biosciences, Inc. (“Borrower”).

The undersigned is the ____________________ of Borrower and hereby requests on behalf of Borrower a Loan under the Loan Agreement, and in that connection certifies as follows:

1. The amount of the proposed Loan is Fifteen Million Dollars ($15,000,000). The Borrowing Date of the proposed Loan is January [•], 2026 (the “Borrowing Date”).

(a) On the Borrowing Date,

(i) Avenue 2 will wire $[_________] less fees and expenses to be deducted on the Borrowing Date of (a) [$___] in respect to the Commitment Fee, of which $ has been paid to Avenue prior to the date hereof, (b) $[_________] in respect to the interest fee, and (c) $[_________] in respect to the legal fees for net proceeds of $[___________], and

(ii) Avenue 3 will wire $[_________] less fees and expenses to be deducted on the Borrowing Date of (a) [$___] in respect to the Commitment Fee, of which [$___] has been paid to Avenue 2 prior to the date hereof, (b) $[_________] in respect to the interest fee, and (c) $[_________] in respect to the legal fees for net proceeds of $[___________],

to Borrower pursuant to the following wire instructions:

(b) On the Borrowing Date, i) Avenue will wire $[__________], and (ii) Avenue 2 will wire $[__________] to Manatt, Phelps & Phillips, LLP for fees and expenses pursuant to the following wire instructions:

2. As of this date, no Default or Event of Default has occurred and is continuing, or will result from the making of the proposed Loan, the representations and warranties of Borrower contained in Article 3 of the Loan Agreement and Part 3 of the Supplement are true and correct in all material respects other than those representations and warranties expressly referring to a specific date which are true and correct in all material respects as of such date, and the conditions precedent described in Sections 4.1 and/or 4.2 of the Loan Agreement and Part 2 of the Supplement, as applicable, have been met.

3. No event has occurred that has had or could reasonably be expected to have a Material Adverse Change.

4. Borrower’s most recent financial statements, financial projections or business plan dated ____________, as reviewed by Borrower’s Board of Directors, are enclosed herewith in the event such financial statements, financial projections or business plan have not been previously provided to Agent.

[Signature page to Borrowing Request]

Borrower shall notify you promptly before the funding of the Loan if any of the matters to which I have certified above shall not be true and correct on the Borrowing Date.

Very truly yours,

SPRUCE BIOSCIENCES, INC.

By: ________________________

Name: Samir Gharib

Title: President and Chief Financial Officer

Address for Notices: 611 Gateway Boulevard, Suite 740

South San Francisco, CA 94080

Attn: President and Chief Financial Officer

Email:

EXHIBIT “C”

FORM OF

COMPLIANCE CERTIFICATE

AVENUE CAPITAL MANAGEMENT II, L.P., as Agent

[***]

Re: SPRUCE BIOSCIENCES, INC.

Ladies and Gentlemen:

Reference is made to the Loan and Security Agreement, dated as of January 7, 2026 (as the same has been and may be supplemented, amended and modified from time to time, the “Loan Agreement,” the capitalized terms used herein as defined therein), among Avenue Capital Management II, L.P. (“Agent”), as administrative agent and collateral agent (in such capacity, “Agent”), Avenue Venture Opportunities Fund II, L.P., as a lender (“Avenue 2”), each Person from time to time party hereto as a lender (together with Avenue 2, collectively, “Lenders”, and each a “Lender”), and Spruce Biosciences, Inc. (“Borrower”).

The undersigned authorized representative of Borrower hereby certifies in such capacity that in accordance with the terms and conditions of the Loan Agreement, (i) no Default or Event of Default has occurred and is continuing, except as noted below, and (ii) Borrower is in compliance for the financial reporting period ending ____________________________ with all required financial reporting under the Loan Agreement, except as noted below. Attached herewith are the required documents supporting the foregoing certification. The undersigned authorized representative of Borrower further certifies in such capacity that: (a) the accompanying financial statements have been prepared in accordance with Borrower’s past practices applied on a consistent basis, or in such manner as otherwise disclosed in writing to Agent, throughout the periods indicated; and (b) the financial statements fairly present in all material respects the financial condition and operating results of Borrower and its Subsidiaries, if any, as of the dates, and for the periods, indicated therein, subject to the absence of footnotes and normal year-end audit adjustments (in the case of interim monthly financial statements), except as explained below.

Please provide the following requested information and

indicate compliance status by circling (or otherwise indicating) Yes/No under “Included/Complies”:

REPORTING REQUIREMENT REQUIRED INCLUDED/COMPLIES

Balance Sheet, Income Statement & Monthly, within 30 days YES / NO / N/A

Cash Flow Statement

Operating Budgets, 409(A) Valuations &

Updated Capitalization Tables As modified YES / NO / N/A

Annual Financial Statements Annually, within 90 day of fiscal year-end YES / NO / N/A

Board Packages As modified YES / NO / N/A

Date of most recent Board-approved

budget/plan ________________

Any change in budget/plan since version most recently

delivered to Agent YES / NO / N/A

If Yes, please attach

EQUITY & CONVERTIBLE NOTE FINANCINGS

Please provide the following information (if applicable) regarding Borrower’s most-recent equity and/or convertible note financing each time this Certificate is delivered to Agent

Date of Last Raise: _____________

Has there been any new financing since the last Compliance Certificate submitted? YES / NO

Date Closed: ______________ Per Share Price: $_________________

Amount Raised: _______________

Any stock splits since date of last report? YES / NO

If yes, please provide any information on stock splits which would affect valuation:

Any dividends since date of last report? YES / NO

If yes, please provide any information on dividends which would affect valuation:

Any unusual terms? (i.e., Anti-dilution, multiple preference, etc.) YES / NO

If yes, please explain:

ACCOUNT CONTROL AGREEMENTS

Pursuant to Section 6.11 of the Loan Agreement, Borrower represents and warrants that: (i) as of the date hereof, it maintains only those deposit and investment accounts set forth below; and (ii) to the extent required by Section 6.11 of the Loan Agreement, a control agreement has been executed and delivered to Agent with respect to each such account [Note: If Borrower has established any new account(s) since the date of the last compliance certificate, please so indicate].

Deposit Accounts1

Investment Accounts2

AGREEMENTS WITH PERSONS IN POSSESSION OF TANGIBLE COLLATERAL

Pursuant to Section 5.9(e) of the Loan Agreement, Borrower represents and warrants that: (i) as of the date hereof, tangible Collateral is located at the addresses set forth below; and (ii) to the extent required by Section 5.9(e) of the Loan Agreement, a Waiver has been executed and delivered to Agent, or such Waiver has been waived by Agent, [Note: If Borrower has located Collateral at any new location since the date of the last compliance certificate, please so indicate].

SUBSIDIARIES AND OTHER PERSONS

Pursuant to Section 6.14(a) of the Loan Agreement, Borrower represents and warrants that: (i) as of the date hereof, it has directly or indirectly acquired or created, or it intends to directly or indirectly acquire or create, each Subsidiary or other Person described below; and (ii) such Subsidiary or Person has been made a co-borrower under the Loan Agreement or a guarantor of the Obligations [Note: If Borrower has acquired or created any Subsidiary since the date of the last compliance certificate, please so indicate].

EXPLANATIONS

[Remainder of this page intentionally left blank; signature page follows]

[Signature page to Compliance Certificate]

Very truly yours,

SPRUCE BIOSCIENCES, INC.

By: ________________________

Name: Samir Gharib

Title: President and Chief Financial Officer