[S-3] Equillium, Inc. Shelf Registration Statement

Rhea-AI Filing Summary

Equillium, Inc. filed an S-3 shelf registration to register common stock for resale by selling stockholders, including shares issuable upon exercise of pre-funded warrants sold in a recent private placement. The prospectus identifies multiple institutional holders (including Adage, ADAR1 Entities, Coastlands Capital and Janus) and shows specific share counts and warrants subject to beneficial ownership blockers that exclude certain exercisable shares from pre-offering ownership figures. The filing lists exhibits (e.g., merger agreement, charter documents, Registration Rights Agreement dated August 12, 2025 and pre-funded warrant form dated August 11, 2025) and incorporates prior SEC reports by reference. The total filing fee shown aggregates to $81,562.

Positive

• Registers shares and warrants for resale, enabling liquidity for selling stockholders
• Detailed exhibit list including Registration Rights Agreement (August 12, 2025) and warrant form (August 11, 2025)
• Incorporation by reference of prior SEC filings provides additional disclosure context
• Filing fee disclosed total of $81,562

Negative

• Significant number of pre-funded warrants could increase outstanding shares if exercised, creating dilution risk
• Beneficial ownership blockers complicate pre-offering ownership figures and may affect voting/ownership calculations
• Large institutional holders identified intend to resell shares, which could increase float and put downward pressure on market liquidity

Insights

Securities Analyst

TL;DR: Routine shelf registration enabling selling stockholders to resell common stock and shares from pre-funded warrants; watch potential dilution from exercised warrants.

The S-3 registers shares held by multiple institutional investors and shares issuable upon exercise of pre-funded warrants from a private placement. The filing discloses beneficial ownership blockers that alter pre-offering counts and specifies precise share and warrant amounts for major holders (e.g., Adage, ADAR1, Coastlands, Janus). Exhibits include a Registration Rights Agreement (August 12, 2025) and warrant forms (August 11, 2025). This is primarily a liquidity and resale-enabling filing rather than an operating-results disclosure; the material investor implication is potential increase in freely tradable shares if warrants are exercised.

Corporate Governance Expert

TL;DR: Filing documents governance instruments and third-party agreements; disclosure of investor rights and exhibit references is thorough and standard for a resale shelf.

The prospectus carefully lists governance documents (amended charter and bylaws), the merger agreement, and legal opinions and consents filed as exhibits. The Registration Rights Agreement and the listing of permitted transferees/successors-in-interest clarify resale mechanics. Signatures from executive officers and directors dated September 9, 2025 are included. The disclosure of beneficial ownership limitations for pre-funded warrants ensures accurate compliance reporting for ownership thresholds.

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As filed with the Securities and Exchange Commission on September 9, 2025

Registration No. 333-   

UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

Washington, D.C. 20549

FORM S-3

REGISTRATION STATEMENT

UNDER

THE SECURITIES ACT OF 1933

Equillium, Inc.

(Exact name of registrant as specified in its charter)

Delaware		82-1554746
(State or other jurisdiction of incorporation or organization)		(I.R.S. Employer Identification Number)

2223 Avenida de la Playa, Suite 105

La Jolla, California 92037

(858) 240-1200

(Address, including zip code, and telephone number, including area code, of registrant’s principal executive offices)

Bruce D. Steel

President and Chief Executive Officer

Equillium, Inc.

2223 Avenida de la Playa, Suite 105

La Jolla, California 92037

(858) 240-1200

(Name, address, including zip code, and telephone number, including area code, of agent for service)

Copies to:

Thomas A. Coll

Dylan S. Kornbluth

Cooley LLP

10265 Science Center Drive

San Diego, CA 92121

(858) 550-6000

Approximate date of commencement of proposed sale to the public: From time to time after the effective date of this Registration Statement.

If the only securities being registered on this Form are being offered pursuant to dividend or interest reinvestment plans, please check the following box: ☐

If any of the securities being registered on this Form are to be offered on a delayed or continuous basis pursuant to Rule 415 under the Securities Act of 1933, as amended, other than securities offered only in connection with dividend or interest reinvestment plans, check the following box: ☒

If this Form is filed to register additional securities for an offering pursuant to Rule 462(b) under the Securities Act, please check the following box and list the Securities Act registration statement number of the earlier effective registration statement for the same offering. ☐

If this Form is a post-effective amendment filed pursuant to Rule 462(c) under the Securities Act, check the following box and list the Securities Act registration statement number of the earlier effective registration statement for the same offering. ☐

If this Form is a registration statement pursuant to General Instruction I.D. or a post-effective amendment thereto that shall become effective upon filing with the Commission pursuant to Rule 462(e) under the Securities Act, check the following box. ☐

If this Form is a post-effective amendment to a registration statement filed pursuant to General Instruction I.D. filed to register additional securities or additional classes of securities pursuant to Rule 413(b) under the Securities Act, check the following box. ☐

Indicate by check mark whether the registrant is a large accelerated filer, an accelerated filer, a non-accelerated filer, a smaller reporting company, or an emerging growth company. See the definitions of “large accelerated filer,” “accelerated filer,” “smaller reporting company” and “emerging growth company” in Rule 12b-2 of the Exchange Act.

Large accelerated filer		☐		Accelerated filer		☐
Non-accelerated filer		☒		Smaller reporting company		☒
				Emerging growth company		☐

If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 7(a)(2)(B) of the Securities Act. ☐

The registrant hereby amends this registration statement on such date or dates as may be necessary to delay its effective date until the registrant shall file a further amendment that specifically states that this registration statement shall thereafter become effective in accordance with Section 8(a) of the Securities Act of 1933, as amended, or until the registration statement shall become effective on such date as the Securities and Exchange Commission, acting pursuant to said Section 8(a), may determine.

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The information in this prospectus is not complete and may be changed. The selling stockholders may not sell these securities until the registration statement filed with the Securities and Exchange Commission is effective. This prospectus is not an offer to sell these securities and it is not soliciting an offer to buy these securities in any state where the offer or sale is not permitted.

SUBJECT TO COMPLETION, DATED SEPTEMBER 9, 2025

PROSPECTUS

52,631,579 Shares of Common Stock

This prospectus covers the offer and resale by the selling stockholders (the “selling stockholders”) identified in this prospectus of up to an aggregate of 52,631,579 shares of our common stock, par value $0.0001 per share (the “common stock”), which includes 30,816,705 shares issuable upon the exercise of pre-funded warrants. An aggregate of 21,814,874 shares of common stock and pre-funded warrants to purchase 30,816,705 shares of common stock were sold to the selling stockholders in a private placement that closed on August 12, 2025 (the “Private Placement”).

We are not selling any shares of common stock under this prospectus and will not receive any proceeds from the sale by the selling stockholders of such shares.

Sales of the shares by the selling stockholders may occur at fixed prices, at market prices prevailing at the time of sale, at prices related to prevailing market prices or at negotiated prices. The selling stockholders may sell the shares to or through underwriters, broker-dealers or agents, who may receive compensation in the form of discounts, concessions or commissions from the selling stockholders, the purchasers of the shares, or both.

We are paying the cost of registering the shares of common stock covered by this prospectus as well as various related expenses. The selling stockholders are responsible for all selling commissions, transfer taxes and other costs related to the offer and sale of their shares. See “Plan of Distribution” for more information about how the selling stockholders may sell or dispose of their shares.

Our common stock is listed on Nasdaq Capital Market under the symbol “EQ.” On September 8, 2025, the last reported sale price of our common stock was $1.88 per share.

Investing in our common stock involves a high degree of risk. Before making an investment decision, please read the information under “Risk Factors” on page 4 of this prospectus and under similar headings in any amendment or supplement to this prospectus or in any filing with the Securities and Exchange Commission that is incorporated by reference herein.

Neither the Securities and Exchange Commission nor any state securities commission has approved or disapproved of these securities or determined if this prospectus is truthful or complete. Any representation to the contrary is a criminal offense.

The date of this prospectus is    , 2025

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Page

ABOUT THIS PROSPECTUS			ii
SPECIAL NOTE REGARDING FORWARD-LOOKING STATEMENTS			iii
PROSPECTUS SUMMARY			1
RISK FACTORS			4
USE OF PROCEEDS			5
SELLING STOCKHOLDERS			6
PLAN OF DISTRIBUTION			9
EXPERTS			11
LEGAL MATTERS			11
WHERE YOU CAN FIND ADDITIONAL INFORMATION			11
INCORPORATION OF CERTAIN INFORMATION BY REFERENCE			12

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ABOUT THIS PROSPECTUS

This prospectus is part of a registration statement on Form S-3 that we filed with the Securities and Exchange Commission (“SEC”), using a “shelf” registration process. Under this registration statement, the selling stockholders may sell from time to time in one or more offerings the common stock described in this prospectus.

We have not authorized anyone to provide you with information other than the information that we have provided or incorporated by reference in this prospectus and your reliance on any unauthorized information or representation is at your own risk. This prospectus may be used only in jurisdictions where offers and sales of these securities are permitted. You should assume that the information appearing in this prospectus is accurate only as of the date of this prospectus and that any information we have incorporated by reference is accurate only as of the date of the document incorporated by reference, regardless of the time of delivery of this prospectus, or any sale of our common stock. Our business, financial condition and results of operations may have changed since those dates.

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SPECIAL NOTE REGARDING FORWARD-LOOKING STATEMENTS

This prospectus and any applicable prospectus supplement or free writing prospectus, including the documents that we incorporate by reference herein and therein, contain “forward-looking statements” within the meaning of Section 27A of the Securities Act of 1933, as amended (the “Securities Act”), and Section 21E of the Securities Exchange Act of 1934, as amended (the “Exchange Act”). These statements relate to future events or to our future operating or financial performance and involve known and unknown risks, uncertainties and other factors which may cause our actual results, performance or achievements to be materially different from any future results, performances or achievements expressed or implied by the forward-looking statements.

In some cases, you can identify forward-looking statements by terms such as “may,” “will,” “should,” “could,” “would,” “expects,” “plans,” “anticipates,” “believes,” “estimates,” “projects,” “predicts,” “potential” and similar expressions intended to identify forward-looking statements. These statements reflect our current views with respect to future events and are based on assumptions and are subject to risks and uncertainties. As such, our actual results may differ significantly from those expressed in any forward-looking statements. Given these uncertainties, you should not place undue reliance on these forward-looking statements. In addition, statements indicating that “we believe” and similar statements reflect our beliefs and opinions on the relevant subject. These statements are based upon information available to us as of the date they were made, and while we believe such information formed a reasonable basis for such statements, such information may be limited or incomplete, and our statements should not be read to indicate that we have conducted an exhaustive inquiry into, or review of, all potentially available relevant information. These statements are inherently uncertain and investors are cautioned not to unduly rely upon these statements.

We discuss many of these risks in greater detail under “Risk Factors” in this prospectus and in the “Risk Factors,” “Business” and “Management’s Discussion and Analysis of Financial Condition and Results of Operations” sections incorporated by reference from our most recent Annual Report on Form 10-K and in our Quarterly Reports on Form 10-Q for the quarterly periods ended subsequent to our filing of such Annual Report on Form 10-K, as well as any amendments thereto reflected in subsequent filings with the SEC.

Also, these forward-looking statements represent our estimates and assumptions only as of the date of the document containing the applicable statement. Unless required by law, we undertake no obligation to update or revise any forward-looking statements to reflect new information or future events or developments. Thus, you should not assume that our silence over time means that actual events are bearing out as expressed or implied in such forward-looking statements. You should read this prospectus, any applicable prospectus supplement, together with the documents that we have filed with the SEC that are incorporated by reference and any free writing prospectus we have authorized for use in connection with this offering, completely and with the understanding that our actual future results may be materially different from what we expect. We qualify all of the forward-looking statements in the foregoing documents by these cautionary statements.

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PROSPECTUS SUMMARY

This summary highlights certain information about us, the Private Placement (as defined below) and selected information contained elsewhere in or incorporated by reference into this prospectus. This summary is not complete and does not contain all of the information that you should consider before making an investment decision. For a more complete understanding of our company, you should read and consider carefully the more detailed information included or incorporated by reference in this prospectus and any applicable prospectus supplement, including the factors described under the heading “Risk Factors” on page 4 of this prospectus, as well as the information incorporated herein by reference, before making an investment decision.

Unless otherwise stated, all references in this prospectus to “we,” “us,” “our,” “Equillium,” the “Company” and similar designations refer to Equillium, Inc.

Company Overview

We are a biotechnology innovator developing novel therapies to treat severe autoimmune and inflammatory disorders with the mission to develop life-changing therapeutics for patients. Our primary goal is to advance EQ504, our novel aryl hydrocarbon receptor modulator, into and through clinical development.

Company Information

We were originally incorporated as Attenuate Biopharmaceuticals, Inc. in Delaware in March 2017 and subsequently changed our name to Equillium, Inc. in May 2017. Our principal executive offices are located at 2223 Avenida de la Playa, Suite 105, La Jolla, CA 92037. We have three wholly-owned subsidiaries, Bioniz Therapeutics, Inc., a Delaware corporation, Ariagen, Inc., a Delaware corporation, and Equillium Australia Pty LTD, an Australian proprietary limited corporation. Our telephone number is (858) 240-1200. Our website address is www.equilliumbio.com. Information found on, or accessible through, our website is not a part of, and is not incorporated into, this prospectus, and you should not consider it as part of this prospectus. Our website address is included in this prospectus as an inactive textual reference only.

All brand names or trademarks appearing in this prospectus are the property of their respective holders. Use or display by us of other parties’ trademarks, trade dress, or products in this prospectus is not intended to, and does not, imply a relationship with, or endorsements or sponsorship of, us by the trademark or trade dress owners.

Private Placement

On August 10, 2025, we entered into a Securities Purchase Agreement (the “Purchase Agreement”) with the selling stockholders named in this prospectus, pursuant to which we sold and issued, in a private placement transaction, 21,814,874 shares of common stock and pre-funded warrants, in lieu thereof, to purchase up to 30,816,705 shares of common stock at an initial closing on August 12, 2025. Each share of common stock was sold at a price of $0.57 per share and each pre-funded warrant was sold at a price of $0.5699. The pre-funded warrants have a per share exercise price of $0.0001. The total purchase price paid by the selling stockholders was approximately $30.0 million. The pre-funded warrants are exercisable at any time and will not expire until exercised in full. The pre-funded warrants may not be exercised if the aggregate number of shares of common stock beneficially owned by the holder thereof immediately following such exercise would exceed a specified beneficial ownership limitation. Subject to the occurrence of certain events, the Purchase Agreement obligates the selling stockholders named in this prospectus to purchase at a subsequent closing up to 35,087,717 shares of common stock or pre-funded warrants in lieu thereof at $0.57 per share or $0.5699 per pre-funded warrant for aggregate gross proceeds of $20.0 million. For additional information regarding the Purchase Agreement, refer to the summary included under Item 1.01 of our Current Report on Form 8-K filed with the SEC on August 11, 2025, which is incorporated by reference herein.

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On August 12, 2025, we entered into a Registration Rights Agreement (the “Registration Rights Agreement”) with the selling stockholders named in this prospectus, pursuant to which we agreed to prepare and file, within 30 days after the initial closing of the Private Placement, one or more registration statements with the SEC to register for resale the shares of our common stock issued at the initial closing under the Purchase Agreement and the shares of common stock issuable upon exercise of the pre-funded warrants, and generally to cause the applicable registration statements to promptly become effective. For additional information regarding the Registration Rights Agreement, refer to the summary included under Item 1.01 of our Current Report on Form 8-K filed with the SEC on August 11, 2025, which is incorporated by reference herein.

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The Offering

Common stock offered by the selling stockholders 52,631,579 shares⁽¹⁾

Terms of the offering Each selling stockholder will determine when and how it will sell the common stock offered in this prospectus, as described in “Plan of Distribution.”

Use of proceeds We will not receive any proceeds from the sale of the shares of common stock covered by this prospectus.

Risk factors See “Risk Factors” on page 4 for a discussion of factors you should carefully consider before deciding to invest in our common stock.

Nasdaq Capital Market symbol EQ

⁽¹⁾  Includes 30,816,705 shares of common stock issuable upon the exercise of pre-funded warrants held by the selling stockholders named in this prospectus.

The selling stockholders named in this prospectus may offer and sell up to 52,631,579 shares of our common stock. Our common stock is currently listed on Nasdaq Capital Market under the symbol “EQ.” Shares of our common stock that may be offered under this prospectus are fully paid and non-assessable. We will not receive any of the proceeds of sales by the selling stockholders of any of the common stock covered by this prospectus. Throughout this prospectus, when we refer to the shares of our common stock being registered on behalf of the selling stockholders for offer and resale, we are referring to the shares of common stock that have been issued to the selling stockholders and the shares of common stock issuable upon exercise of the pre-funded warrants issued in the Private Placement as described above. When we refer to the selling stockholders in this prospectus, we are referring to the selling stockholders identified in this prospectus and, as applicable, their permitted transferees or other successors-in-interest that may be identified in a supplement to this prospectus or, if required, a post-effective amendment to the registration statement of which this prospectus is a part.

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RISK FACTORS

Investing in our common stock involves a high degree of risk. Before making an investment decision, you should carefully consider the risks described in the sections entitled “Risk Factors” in our most recent Annual Report on Form 10-K and subsequent Quarterly Reports on Form 10-Q, as filed with the SEC, which are incorporated herein by reference in their entirety, as well any amendment or updates to our risk factors reflected in subsequent filings with the SEC, including any applicable prospectus supplement. Our business, financial condition, results of operations or prospects could be materially adversely affected by any of these risks. The trading price of our securities could decline due to any of these risks, and you may lose all or part of your investment. This prospectus and the documents incorporated herein by reference also contain forward-looking statements that involve risks and uncertainties. Our actual results could differ materially from those anticipated in these forward-looking statements as a result of certain factors, including the risks mentioned elsewhere in this prospectus. For more information, see the section entitled “Where You Can Find Additional Information.” Please also read carefully the section entitled “Special Note Regarding Forward-Looking Statements.”

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USE OF PROCEEDS

We will not receive any of the proceeds from the sale or other disposition of shares of our common stock held by the selling stockholders pursuant to this prospectus. We will bear the out-of-pocket costs, expenses and fees incurred in connection with the registration of shares of our common stock to be sold by the selling stockholders pursuant to this prospectus. Other than registration expenses, the selling stockholders will bear underwriting discounts, commissions, placement agent fees or other similar expenses payable with respect to sales of shares of our common stock.

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SELLING STOCKHOLDERS

The selling stockholders may sell some, all or none of their shares. We do not know how long the selling stockholders will hold the shares before selling them, and we currently have no agreements, arrangements or understandings with the selling stockholders regarding the sale or other disposition of any of the shares. The shares covered hereby may be offered from time to time by the selling stockholders. As a result, we cannot estimate the number of shares of common stock each of the selling stockholders will beneficially own after termination of sales under this prospectus. In addition, each of the selling stockholders may have sold, transferred or otherwise disposed of all or a portion of its shares of common stock since the date on which it provided information for the table below.

Beneficial ownership is determined in accordance with the rules of the SEC and includes voting or investment power with respect to our common stock. Generally, a person “beneficially owns” shares of our common stock if the person has or shares with others the right to vote those shares or to dispose of them, or if the person has the right to acquire voting or disposition rights within 60 days.

The information in the table below and the footnotes thereto regarding shares of common stock to be beneficially owned after the offering assumes the sale of all shares being offered by the selling stockholders under this prospectus. This information has been obtained from the selling stockholders or in Schedules 13G or 13D and other public documents filed with the SEC. The percentage of shares owned after the offering is based on 59,503,223 shares outstanding as of August 12, 2025 and for each selling stockholder who is selling shares of common stock issuable upon exercise of pre-funded warrants, the percentage of shares owned after the offering is based on 59,503,223 shares outstanding as of August 12, 2025 plus the shares of common stock issuable upon exercise of the pre-funded warrants held by such selling stockholder.

		Before Offering								After Offering
Name		Number of Shares Beneficially Owned				Number of Shares Offered				Number of Shares Beneficially Owned				Percentage of Shares Beneficially Owned
Adage Capital Partners, LP(1)			6,012,625				8,771,930				—				*
Entities affiliated with ADAR1 Partners, LP(2)			5,984,390				8,771,930				246,392				*
Coastlands Capital Partners LP(3)			3,031,823				7,017,544				—				*
Entities affiliated with Janus Henderson Investors US LLC(4)			5,953,491				24,561,404				—				*
Woodline Master Fund LP(5)			3,508,771				3,508,771				—				*

* Less than one percent.

(1) Consists of 5,329,416 shares of common stock and 683,209 shares of common stock issuable upon the exercise of pre-funded warrants held by Adage Capital Partners LP (“Adage”). Due to a beneficial ownership blocker in the pre-funded warrants, the number of shares beneficially owned before the offering excludes 2,759,305 shares of common stock issuable upon the exercise of pre-funded warrants held by Adage. The number of shares offered consists of 5,329,416 shares of common stock and 3,442,514 shares of common stock issuable upon the exercise of pre-funded warrants held by Adage. Bob Atchinson and Phillip Gross are the managing members of Adage Capital Advisors, L.L.C., which is the managing member of Adage Capital Partners GP, L.L.C., which is the general partner of Adage, and each such person or entity, as the case may be, has shared voting and/or investment power over the securities held by Adage Capital Partners, LP and may be deemed the beneficial owner of such shares, and each such person or entity, as the case may be, disclaims beneficial ownership of such securities except to the extent of their respective pecuniary interest therein and other than for purposes of determining their obligations under Section 13(d) of the Exchange Act.

(2) Consists of (i) 4,107,145 shares of common stock and 400,578 shares of common stock issuable upon the exercise of pre-funded warrants held by ADAR1 Partners, LP (“ADAR1 Partners”); (ii) 533,742 shares of common stock held by ADAR1 SPV I, LP (“ADAR1 SPV”) and (iii) 696,533 shares of common stock held by Spearhead Insurance Solutions IDF, LLC – Series ADAR1 (“Spearhead”, and together with ADAR1

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Partners and ADAR1 SPV, the “ADAR1 Entities”). Due to a beneficial ownership blocker in the pre-funded warrants, the number of shares beneficially owned before the offering excludes (i) 2,242,277 shares of common stock issuable upon the exercise of pre-funded warrants held by ADAR1 Partners; (ii) 343,451 shares of common stock issuable upon the exercise of pre-funded warrants held by ADAR1 SPV; and (iii) 448,204 shares of common stock issuable upon the exercise of pre-funded warrants held by Spearhead. The number of shares offered consists of 5,337,420 shares of common stock and 3,434,510 shares of common stock issuable upon the exercise of pre-funded warrants held by the ADAR1 Entities. ADAR1 Capital Management, LLC serves as the investment manager of ADAR1 Partners and ADAR1 SPV and as the sub-advisor of Spearhead. As the manager of ADAR1 Capital Management, LLC, Daniel Pawel Schneeberger may be deemed to indirectly beneficially own securities held by the ADAR1 Entities.

(3) Consists of 1,777,055 shares of common stock and 1,254,768 shares of common stock issuable upon the exercise of pre-funded warrants held by Coastlands Capital Partners LP (“Coastlands Capital”). Due to a beneficial ownership blocker in the pre-funded warrants, the number of shares beneficially owned before the offering excludes 3,985,721 shares of common stock issuable upon the exercise of pre-funded warrants held by Coastlands Partners. The number of shares offered consists of 1,777,055 shares of common stock and 5,240,489 shares of common stock issuable upon the exercise of pre-funded warrants held by Coastlands Capital, without giving effect to the beneficial ownership blocker. Coastlands Capital LP is the investment adviser to Coastlands Capital and Coastlands Capital GP LLC (“Coastlands GP”) is the general partner of Coastlands Capital. Coastlands Capital LLC (the “General Partner” and together with Coastlands Capital, Coastlands Capital LP and Coastlands GP, the “Coastlands Entities”) is the general partner of Coastlands Capital LP. Matthew D. Perry is the control person of the Coastlands Entities. The Coastlands Entities and Mr. Perry each disclaim membership in a group. The Coastlands Entities and Mr. Perry also each disclaim beneficial ownership of the shares of common stock except to the extent of such entity or person’s pecuniary interest therein.

(4) Janus Henderson Investors US LLC (“Janus”), is an investment adviser registered under the Investment Advisers Act of 1940, that acts as investment adviser for each of Janus Henderson Biotech Innovation Master Fund Limited (“JHBIF”) and Janus Henderson Biotech Innovation Master Fund II Limited (“BIF2” and together with JHBIF, the “Janus Entities”). The securities reported herein consist of (i) 5,036,469 shares of common stock and 91,279 shares of common stock issuable upon the exercise of pre-funded warrants held by JHBIF and (ii) 825,743 shares of common stock held by BIF2. Due to the Beneficial Ownership Limitation, the securities reported in the second column excludes (i) 15,973,969 shares of common stock issuable upon the exercise of pre-funded warrants held by JHBIF and (ii) 2,633,944 shares of common stock issuable upon the exercise of pre-funded warrants held by BIF2. The securities reported in the third column consists of an aggregate of 5,953,491 shares of common stock and 24,561,404 shares of common stock issuable upon the exercise of pre-funded warrants held by the Janus Entities. Janus has the ability to make decisions with respect to the voting and disposition of the securities subject to the oversight of the board of directors of each of the Janus Entities. Under the terms of its management contract with each of the Janus Entities, Janus has overall responsibility for directing the investments of each of the Janus Entities in accordance with the investment objective, policies and limitations of each of the Janus Entities. Each of the Janus Entities has one or more portfolio managers appointed by and serving at the pleasure of Janus whom makes decisions with respect to the disposition of the securities offered hereby. The portfolio managers for each of the Janus Entities are: Andrew Acker, Daniel S. Lyons and Agustin Mohedas.

(5) Consists of shares of common stock. Woodline Partners LP serves as the investment manager of Woodline Master Fund LP and may be deemed to be the beneficial owner of the shares. Woodline Partners LP disclaims any beneficial ownership of these shares, other than for purposes of determining its obligations under Section 13(d) of the Exchange Act.

Relationship with Selling Stockholders

As discussed in greater detail above under the section “Prospectus Summary—Private Placement,” on August 10, 2025, we entered into the Purchase Agreement with the selling stockholders pursuant to which we sold shares of common stock and pre-funded warrants to the selling stockholders and, pursuant to the

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Registration Rights Agreement, agreed with the selling stockholders to file a registration statement to enable the resale of the shares of common stock covered by this prospectus. None of the selling stockholders or any persons having control over such selling stockholders has held any position or office with us or our affiliates within the last three years or has had a material relationship with us or any of our predecessors or affiliates within the past three years, other than as a result of the ownership of our shares or other securities.

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PLAN OF DISTRIBUTION

The selling stockholders, which as used herein includes donees, pledgees, transferees or other successors-in-interest selling shares of common stock or interests in shares of common stock received after the date of this prospectus from a selling stockholder as a gift, pledge, partnership distribution or other transfer, may, from time to time, sell, transfer or otherwise dispose of any or all of their shares of common stock or interests in shares of common stock on any stock exchange, market or trading facility on which the shares are traded or in private transactions. These dispositions may be at fixed prices, at prevailing market prices at the time of sale, at prices related to the prevailing market price, at varying prices determined at the time of sale, or at negotiated prices.

The selling stockholders may use any one or more of the following methods when disposing of shares or interests therein:

• distributions to members, partners, stockholders or other equityholders of the selling stockholders;

• ordinary brokerage transactions and transactions in which the broker-dealer solicits purchasers;

• block trades in which the broker-dealer will attempt to sell the shares as agent, but may position and resell a portion of the block as principal to facilitate the transaction;

• purchases by a broker-dealer as principal and resale by the broker-dealer for its account;

• an exchange distribution in accordance with the rules of the applicable exchange;

• privately negotiated transactions;

• short sales and settlement of short sales entered into after the effective date of the registration statement of which this prospectus is a part;

• through the writing or settlement of options or other hedging transactions, whether through an options exchange or otherwise;

• broker-dealers may agree with the selling stockholders to sell a specified number of such shares at a stipulated price per share;

• a combination of any such methods of sale; and

• any other method permitted pursuant to applicable law.

The selling stockholders may, from time to time, pledge or grant a security interest in some or all of the shares of common stock owned by them and, if they default in the performance of their secured obligations, the pledgees or secured parties may offer and sell the shares of common stock, from time to time, under this prospectus, or under an amendment to this prospectus under Rule 424(b)(3) or other applicable provision of the Securities Act, amending the list of selling stockholders to include the pledgee, transferee or other successors in interest as selling stockholders under this prospectus. The selling stockholders also may transfer the shares of common stock in other circumstances, in which case the transferees, pledgees or other successors in interest will be the selling stockholders for purposes of this prospectus.

In connection with the sale of our common stock or interests therein, the selling stockholders may enter into hedging transactions with broker-dealers or other financial institutions, which may in turn engage in short sales of the common stock in the course of hedging the positions they assume. The selling stockholders may also sell shares of our common stock short and deliver these securities to close out their short positions, or loan or pledge the common stock to broker-dealers that in turn may sell these securities. The selling stockholders may also enter into option or other transactions with broker-dealers or other financial institutions or the creation of one or more derivative securities which require the delivery to such broker-dealer or other financial institution of shares offered by this prospectus, which shares such broker-dealer or other financial institution may resell pursuant to this prospectus (as supplemented or amended to reflect such transaction).

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The aggregate proceeds to the selling stockholders from the sale of the common stock offered by them will be the purchase price of the common stock less discounts or commissions, if any. Each of the selling stockholders reserves the right to accept and, together with their agents from time to time, to reject, in whole or in part, any proposed purchase of common stock to be made directly or through agents. We will not receive any of the proceeds from this offering. Upon any exercise of the pre-funded warrants by payment of cash, however, we will receive the nominal exercise price of the pre-funded warrants.

The selling stockholders also may resell all or a portion of the shares in open market transactions in reliance upon Rule 144 under the Securities Act, provided that they meet the criteria and conform to the requirements of that rule, or another available exemption from the registration requirements under the Securities Act.

The selling stockholders and any underwriters, broker-dealers or agents that participate in the sale of the common stock or interests therein may be “underwriters” within the meaning of Section 2(a)(11) of the Securities Act (it being understood that the selling stockholders shall not be deemed to be underwriters solely as a result of their participation in this offering). Any discounts, commissions, concessions or profit they earn on any resale of the shares may be underwriting discounts and commissions under the Securities Act. Selling stockholders who are “underwriters” within the meaning of Section 2(a)(11) of the Securities Act will be subject to the prospectus delivery requirements of the Securities Act.

To the extent required, the shares of our common stock to be sold, the names of the selling stockholders, the respective purchase prices and public offering prices, the names of any agent, dealer or underwriter, and any applicable commissions or discounts with respect to a particular offer will be set forth in an accompanying prospectus supplement or, if appropriate, a post-effective amendment to the registration statement that includes this prospectus.

In order to comply with the securities laws of some states, if applicable, the common stock may be sold in these jurisdictions only through registered or licensed brokers or dealers. In addition, in some states the common stock may not be sold unless it has been registered or qualified for sale or an exemption from registration or qualification requirements is available and is complied with.

We have advised the selling stockholders that the anti-manipulation rules of Regulation M under the Exchange Act may apply to sales of shares in the market and to the activities of the selling stockholders and their affiliates. In addition, to the extent applicable, we will make copies of this prospectus (as it may be supplemented or amended from time to time) available to the selling stockholders for the purpose of satisfying the prospectus delivery requirements of the Securities Act. The selling stockholders may indemnify any broker-dealer that participates in transactions involving the sale of the shares against certain liabilities, including liabilities arising under the Securities Act.

We have agreed to indemnify the selling stockholders against liabilities, including liabilities under the Securities Act and state securities laws, relating to the registration of the shares offered by this prospectus.

We have agreed with the selling stockholders to use commercially reasonable efforts to cause the registration statement of which this prospectus constitutes a part to become effective and to remain continuously effective until the earlier of: (i) the date on which the selling stockholders shall have resold or otherwise disposed of all the shares covered by this prospectus and (ii) the date on which the shares covered by this prospectus no longer constitute “Registrable Securities” as such term is defined in the Registration Rights Agreement, such that they may be resold by the selling stockholders without registration and without regard to any volume or manner-of-sale limitations and without current public information pursuant to Rule 144 under the Securities Act or any other rule of similar effect.

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EXPERTS

The consolidated financial statements of Equillium, Inc. as of December 31, 2024 and 2023, and for each of the years in the two-year period ended December 31, 2024, have been incorporated by reference herein and in the registration statement in reliance upon the report of KPMG LLP, independent registered public accounting firm, incorporated by reference herein, and upon the authority of said firm as experts in accounting and auditing.

LEGAL MATTERS

Certain legal matters, including the validity of the shares of common stock offered pursuant to this registration statement, will be passed upon for us by Cooley LLP, San Diego, California.

WHERE YOU CAN FIND ADDITIONAL INFORMATION

We must comply with the informational requirements of the Exchange Act, and we are required to file reports and proxy statements and other information with the SEC. You may read and copy these reports, proxy statements and other information on the SEC’s website at http://www.sec.gov, which contains reports, proxy and information statements and other information regarding issuers like us that file electronically with the SEC. We maintain a website at www.equilliumbio.com. The information contained in, or that can be accessed through, our website is not incorporated by reference herein and is not part of this prospectus.

Statements contained in this prospectus as to the contents of any contract or other document are not necessarily complete, and in each instance we refer you to the copy of the contract or document filed as an exhibit to the registration statement, each such statement being qualified in all respects by such reference.

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INCORPORATION OF CERTAIN INFORMATION BY REFERENCE

The SEC allows us to “incorporate by reference” information that we file with it, which means that we can disclose important information to you by referring you to those documents. The information incorporated by reference is an important part of this prospectus. Information in this prospectus supersedes information incorporated by reference that we filed with the SEC prior to the date of this prospectus, while information that we file later with the SEC will automatically update and supersede the information in this prospectus. We also incorporate by reference into this prospectus the documents listed below and any future filings made by us with the SEC (in each case, other than current reports or portions thereof furnished under Item 2.02 or Item 7.01 of Form 8-K and exhibits filed on such form that are related to such items and other portions of documents that are furnished, but not filed, or are otherwise not incorporated into registration statements pursuant to applicable rules promulgated by the SEC) that are filed by us with the SEC pursuant to Sections 13(a), 13(c), 14 or 15(d) of the Exchange Act (i) after the date of the initial filing of the registration statement of which this prospectus is a part and prior to effectiveness of the registration statement, and (ii) after the effectiveness of the registration statement but prior to the termination of the offering of the securities covered by this prospectus:

• our Annual Report on Form 10-K for the year ended December 31, 2024, filed with the SEC on March 27, 2025;

• the information specifically incorporated by reference into our Annual Report on Form 10-K for the year ended December  31, 2024 from our definitive proxy statement on Schedule 14A, filed with the SEC on April  10, 2025, as revised April 30, 2025; and

• our Quarterly Reports on Form 10-Q for the quarters ended March 31, 2025 and June 30, 2025, filed with the SEC on May  14, 2025 and August 14, 2025, respectively;

• our Current Reports on Form 8-K filed with the SEC on February  6, 2025, May  22, 2025, June  13, 2025, August  4, 2025 and August 11, 2025, respectively, in each case other than information furnished under Item 2.02 or 7.01 of Form 8-K (and exhibits filed on such form that are related to such items); and

• the description of our common stock filed as Exhibit 4.4 to our Annual Report on Form 10-K for the fiscal year ended December 31, 2019, filed with the SEC on March 26, 2020.

We will furnish without charge to each person, including any beneficial owner, to whom this prospectus is delivered, upon written or oral request, a copy of any document incorporated by reference at no cost. Requests should be addressed to 2223 Avenida de la Playa, Suite 105, La Jolla, CA 92037, Attn: Chief Executive Officer or may be made telephonically at (858) 240-1200.

In accordance with Rule 412 of the Securities Act, any statement contained in a document incorporated by reference herein shall be deemed modified or superseded to the extent that a statement contained herein or in any other subsequently filed document which also is or is deemed to be incorporated by reference herein modifies or supersedes such statement.

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PART II

INFORMATION NOT REQUIRED IN THE PROSPECTUS

Item 14. Other Expenses of Issuance and Distribution.

The following is a statement of the estimated expenses to be incurred by us in connection with the registration of the securities under this registration statement, all of which will be borne by us. All the amounts shown are estimates, except for the SEC registration fee.

SEC Registration Fee		$	14,062
Legal Fees and Expenses		$	40,000
Accounting Fees and Expenses		$	20,000
Miscellaneous		$	7,500
Total		$	81,562

Item 15. Indemnification of Directors and Officers.

Section 145 of the General Corporation Law of the State of Delaware (the “DGCL”), authorizes a court to award, or a corporation’s board of directors to grant, indemnity to directors and executive officers in terms sufficiently broad to permit such indemnification under certain circumstances for liabilities, including reimbursement for expenses incurred, arising under the Securities Act. Our certificate of incorporation permits indemnification of our directors, officers, employees and other agents to the maximum extent permitted by the DGCL, and our bylaws provide that we will indemnify our directors and executive officers and permit us to indemnify our employees and other agents, in each case to the maximum extent permitted by the DGCL.

We have entered into indemnification agreements with our directors and executive officers, whereby we have agreed to indemnify our directors and executive officers to the fullest extent permitted by law, including indemnification against expenses and liabilities incurred in legal proceedings to which the director or executive officer was, or is threatened to be made, a party by reason of the fact that such director or executive officer is or was a director, executive officer, employee, or agent of ours, provided that such director or executive officer acted in good faith and in a manner that the director or executive officer reasonably believed to be in, or not opposed to, our best interest.

At present, there is no pending litigation or proceeding involving a director or executive officer of ours regarding which indemnification is sought, nor is the registrant aware of any threatened litigation that may result in claims for indemnification.

We maintain insurance policies that indemnify our directors and officers against various liabilities arising under the Securities Act and the Exchange Act, that might be incurred by any director or officer in his capacity as such. Insofar as indemnification for liabilities arising under the Securities Act may be permitted for directors, executive officers or persons controlling us, we have been informed that in the opinion of the SEC, such indemnification is against public policy as expressed in the Securities Act and is therefore unenforceable.

The indemnification agreements also set forth certain procedures, presumptions and remedies that will apply in the event of a claim for indemnification thereunder.

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Item 16. Exhibit Index.

EXHIBIT INDEX

Incorporation by Reference

Exhibit Number

Exhibit Description

Form

File Number

Exhibit/ Appendix Reference

Filing Date

Filed Herewith

2.1 *†

Agreement and Plan of Merger, dated February  14, 2022, by and among Equillium, Inc., Bioniz Therapeutics, Inc., Project JetFuel Merger Sub, Inc. and Kevin Green, solely in his capacity as Securityholders’ Representative.

8-K

001-38692

2.1

February 16, 2022

4.1

Amended and Restated Certificate of Incorporation of Equillium, Inc.

8-K

001-38692

3.1

October 16, 2018

4.2

Amended and Restated Bylaws of Equillium, Inc.

8-K

001-38692

3.2

October 16, 2018

4.3*

Registration Rights Agreement, dated August 12, 2025, by and among Equillium, Inc. and the investors named therein.

10-Q

001-38692

4.5

August 14, 2025

4.4

Form of Pre-Funded Warrant to Purchase Common Stock.

8-K

001-38692

4.2

August 11, 2025

5.1

Opinion of Cooley LLP

X

23.1

Consent of Independent Registered Public Accounting Firm

X

23.2

Consent of Cooley LLP (See Exhibit 5.1)

X

24.1

Power of Attorney (See signature page)

X

107

Filing Fee Table

X

* Schedules and exhibits to the agreement have been omitted pursuant to Item 601 of Regulation S-K. A copy of any omitted schedule and/or exhibit will be furnished to the Securities and Exchange Commission upon request.

† Certain information in this exhibit has been omitted pursuant to Item 601 of Regulation S-K.

Item 17. Undertakings.

The undersigned registrant hereby undertakes:

(a) (1) To file, during any period in which offers or sales are being made, a post-effective amendment to this registration statement:

(i) To include any prospectus required by Section 10(a)(3) of the Securities Act;

(ii) To reflect in the prospectus any facts or events arising after the effective date of the registration statement (or the most recent post-effective amendment thereof) which, individually or in the aggregate, represent a fundamental change in the information set forth in the registration statement. Notwithstanding the foregoing, any increase or decrease in volume of securities offered (if the total dollar value

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of securities offered would not exceed that which was registered) and any deviation from the low or high end of the estimated maximum offering range may be reflected in the form of prospectus filed with the SEC pursuant to Rule 424(b) if, in the aggregate, the changes in volume and price represent no more than a 20% change in the maximum aggregate offering price set forth in the “Calculation of Registration Fee” table in the effective registration statement; and

(iii) To include any material information with respect to the plan of distribution not previously disclosed in the registration statement or any material change to such information in the registration statement;

provided, however, that the undertakings set forth in paragraphs (1)(i), (1)(ii) and (1)(iii) above do not apply if the information required to be included in a post-effective amendment by those paragraphs is contained in reports filed with or furnished to the SEC by the registrant pursuant to Section 13 or Section 15(d) of the Exchange Act, that are incorporated by reference in this registration statement, or are contained in a form of prospectus filed pursuant to Rule 424(b) that is part of this registration statement.

(2) That, for the purpose of determining any liability under the Securities Act, each such post-effective amendment shall be deemed to be a new registration statement relating to the securities offered therein, and the offering of such securities at that time shall be deemed to be the initial bona fide offering thereof.

(3) To remove from registration by means of a post-effective amendment any of the securities being registered which remain unsold at the termination of the offering.

(4) That, for the purpose of determining liability under the Securities Act to any purchaser:

(i) Each prospectus filed by the registrant pursuant to Rule 424(b)(3) shall be deemed to be part of the registration statement as of the date the filed prospectus was deemed part of and included in the registration statement; and

(ii) Each prospectus required to be filed pursuant to Rule 424(b)(2), (b)(5) or (b)(7) as part of a registration statement in reliance on Rule 430B relating to an offering made pursuant to Rule 415(a)(1)(i), (vii) or (x) for the purpose of providing the information required by Section 10(a) of the Securities Act shall be deemed to be part of and included in the registration statement as of the earlier of the date such form of prospectus is first used after effectiveness or the date of the first contract of sale of securities in the offering described in the prospectus. As provided in Rule 430B, for liability purposes of the issuer and any person that is at that date an underwriter, such date shall be deemed to be a new effective date of the registration statement relating to the securities in the registration statement to which the prospectus relates, and the offering of such securities at that time shall be deemed to be the initial bona fide offering thereof. Provided, however, that no statement made in a registration statement or prospectus that is part of the registration statement or made in a document incorporated or deemed incorporated by reference into the registration statement or prospectus that is part of the registration statement will, as to a purchaser with a time of contract of sale prior to such effective date, supersede or modify any statement that was made in the registration statement or prospectus that was part of the registration statement or made in any such document immediately prior to such effective date.

(b) That, for purposes of determining any liability under the Securities Act, each filing of the registrant’s annual report pursuant to Section 13(a) or 15(d) of the Exchange Act (and, where applicable, each filing of an employee benefit plan’s annual report pursuant to Section 15(d) of the Exchange Act) that is incorporated by reference in the registration statement shall be deemed to be a new registration statement relating to the securities offered therein, and the offering of such securities at that time shall be deemed to be the initial bona fide offering thereof.

(c) Insofar as indemnification for liabilities arising under the Securities Act may be permitted to directors, officers, and controlling persons of the registrant pursuant to the foregoing provisions, or otherwise, the registrant has been advised that in the opinion of the SEC such indemnification is against public policy as expressed in the

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Securities Act and is, therefore, unenforceable. In the event that a claim for indemnification against such liabilities (other than the payment by the registrant of expenses incurred or paid by a director, officer, or controlling person of the registrant in the successful defense of any action, suit, or proceeding) is asserted by such director, officer, or controlling person of the registrant in connection with the securities being registered, the registrant will, unless in the opinion of its counsel the matter has been settled by controlling precedent, submit to a court of appropriate jurisdiction the question whether such indemnification by it is against public policy as expressed in the Securities Act and will be governed by the final adjudication of such issue.

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SIGNATURES

Pursuant to the requirements of the Securities Act, the registrant certifies that it has reasonable grounds to believe that it meets all of the requirements for filing on Form S-3 and has duly caused this registration statement to be signed on its behalf by the undersigned, thereunto duly authorized, in the city of La Jolla, State of California, on September 9, 2025.

Equillium, Inc.
By:		/s/ Bruce D. Steel
		Bruce D. Steel, CPA
		President and Chief Executive Officer

POWER OF ATTORNEY

Each person whose signature appears below constitutes and appoints Bruce D. Steel and Christine Zedelmayer, and each of them, as his/her true and lawful attorney-in-fact and agent, each acting alone, with full power of substitution and resubstitution, for him/her and in his/her name, place and stead, in any and all capacities, to sign any or all amendments (including post-effective amendments) to this registration statement on Form S-3, and to file the same, with all exhibits thereto, and all documents in connection therewith, with the Securities and Exchange Commission, granting unto said attorneys-in-fact and agents, full power and authority to do and perform each and every act and thing requisite and necessary to be done in and about the premises, as fully to all intents and purposes as he or she might or could do in person, hereby ratifying and confirming all that said attorneys-in-fact and agents, or his/her substitute or substitutes, may lawfully do or cause to be done by virtue hereof.

Pursuant to the requirements of the Securities Act, this registration statement has been signed by the following persons in the capacities and on the dates indicated.

Signature		Title		Date
/s/ Bruce D. Steel Bruce D. Steel, CPA		President, Chief Executive Officer and Director (Principal Executive Officer and Principal Financial Officer)		September 9, 2025
/s/ Penny Tom Penny Tom		Senior Vice President, Finance (Principal Accounting Officer)		September 9, 2025
/s/ Daniel M. Bradbury Daniel M. Bradbury		Chair of the Board of Directors		September 9, 2025
/s/ Peter Colabuono Peter Colabuono		Director		September 9, 2025
/s/ Stephen Connelly, Ph.D. Stephen Connelly, Ph.D.		Director		September 9, 2025
/s/ Martha J. Demski Martha J. Demski		Director		September 9, 2025

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Signature		Title		Date
/s/ Bala Manian, Ph.D. Bala Manian, Ph.D.		Director		September 9, 2025
/s/ Charles McDermott Charles McDermott		Director		September 9, 2025
/s/ Mark Pruzanski, M.D. Mark Pruzanski, M.D.		Director		September 9, 2025
/s/ Barbara Troupin, M.D. Barbara Troupin, M.D.		Director		September 9, 2025

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FAQ

What securities are being registered in the Equillium (EQ) S-3 filing?

The prospectus registers common stock for resale by selling stockholders and shares issuable upon exercise of pre-funded warrants issued in the private placement.

Who are major selling stockholders named in the filing?

Major entities identified include Adage Capital Partners, the ADAR1 Entities, Coastlands Capital, and Janus entities, with specified share and warrant amounts disclosed.

Does the filing disclose any agreements governing resale rights?

Yes. The filing references a Registration Rights Agreement dated August 12, 2025 and related exhibits that govern resale mechanics.

Are there any ownership limitations noted for the warrants?

Yes. The prospectus discloses beneficial ownership blockers (limitations) that exclude certain exercisable shares from pre-offering beneficial ownership counts for several holders.

What exhibits and governance documents are included or referenced?

Exhibits include an Agreement and Plan of Merger (Feb 14, 2022), amended charter and bylaws, the Registration Rights Agreement, form of pre-funded warrant, legal opinions, and consents.

How much was the filing fee for this registration?

The filing fee amounts listed aggregate to $81,562.