Supplemental Prospectus (Form 424B3)

Filed Pursuant to Rule 424(b)(3)
Registration No. 333-296917

SENTI BIOSCIENCES HOLDINGS, INC.

25,555,024 Shares of Common Stock Offered by the Selling Securityholders

This prospectus relates to the offer and sale from time to time by the selling securityholders (the "Selling Securityholders") or their permitted transferees, of up to 25,555,024 shares (the "Resale Shares") of the common stock, par value $0.0001 per share (the, "Common Stock"), of Senti Biosciences Holdings, Inc. (the "Company") issuable upon the exchange of the Senior Secured Convertible Notes of Senti Holdings, Inc. ("Midco"), our subsidiary (the "Notes"). Unless the context otherwise requires, for purposes of this prospectus, the terms "we," "us," "our," etc. refer to the Company.

The Resale Shares, and the Notes from which such Resale Shares are exchangeable, were collectively issued and sold to two accredited investors in a private placement transaction. The Notes were issued on May 20, 2026, August 14, 2026 and September 3, 2026. We are registering the offer and sale of the Resale Shares held by the Selling Securityholders to satisfy the registration rights granted pursuant to the Amended Purchase Agreement (as defined below) and Registration Rights Agreement (as defined below). While we will not receive any proceeds from the sale of Resale Shares by the Selling Securityholders pursuant to this prospectus, we have received approximately $15.5 million in aggregate net proceeds from the issuances of the Notes.

This prospectus provides you with a general description of such securities and the general manner in which the Selling Securityholders or their pledgees, assignees or successors-in-interest may offer or sell the securities. More specific terms of any securities that the Selling Securityholders may offer or sell may be provided in a prospectus supplement that describes, among other things, the specific amounts and prices of the securities being offered and the terms of the offering. The prospectus supplement may also add, update or change information contained in this prospectus.

Our registration of the Resale Shares covered by this prospectus does not mean that either we or the Selling Securityholders will issue, offer or sell, as applicable, any of the Resale Shares. The Selling Securityholders may offer and sell the Resale Shares covered by this prospectus in a number of different ways and at varying prices. We provide more information about how the Selling Securityholders may sell the Resale Shares in the section entitled "Plan of Distribution." The Selling Securityholders may be deemed to be "underwriters", within the meaning of the Securities Act, of the Resale Shares that it is offering pursuant to this prospectus. The Selling Securityholders will bear all commissions and discounts, if any, attributable to their sales of the Resale Shares hereunder. We will bear all costs, expenses and fees in connection with the registration of the Resale Shares. We will not be paying any underwriting discounts or commissions in this offering.

The Resale Shares represent a substantial percentage of our total outstanding Common Stock as of September 9, 2026. The Resale Shares being offered for resale in this prospectus represent 82.1% of our current total outstanding Common Stock. Such shares of Common Stock will represent a substantial portion of our public float. If the Notes are exchanged for Common Stock, such shares of Common Stock will be significantly dilutive and may cause a decline in the market price of our securities.

You should read this prospectus and any prospectus supplement or amendment carefully before you invest in our securities.

Our Common Stock is listed on the Nasdaq Capital Market, or Nasdaq, under the symbol "SNTI". On September 23, 2026, the last quoted sale price for the Common Stock as reported on Nasdaq was $0.3380 per share.

We are an "emerging growth company" and a "smaller reporting company" under applicable federal securities laws and will be subject to reduced public company reporting requirements for so long as we remain an emerging growth company or a smaller reporting company.

Investing in our securities involves a high degree of risk. Before buying any securities, you should carefully read the discussion of the risks of investing in our securities in "Risk Factors" beginning on page 17 of this prospectus and any other risk factors contained in any applicable prospectus supplement and in the documents incorporated by reference herein and therein.

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

The date of this prospectus is September 24, 2026.

TABLE OF CONTENTS

SELECTED DEFINITIONS

As used in this prospectus, unless otherwise noted or the context otherwise requires, references to the following capitalized terms have the meanings set forth below:

"Business Combination Agreement" means the Business Combination Agreement, dated as of December 19, 2021, as amended or modified from time to time, including as amended by Amendment No. 1 to Business Combination Agreement, dated as of February 12, 2022, and Amendment No. 2, dated as of May 19, 2022, in each case, by and among Dynamics Special Purpose Corp., Explore Merger Sub, Inc. and our predecessor, Senti Biosciences, Inc.

"Board" means our board of directors.

"Bylaws" means the Amended and Restated Bylaws of the Company.

"Certificate of Incorporation" means the Amended and Restated Certificate of Incorporation of the Company, as amended and / or restated from time to time.

"DGCL" means the Delaware General Corporation Law, as may be amended from time to time.

"Exchange Act" means the Securities Exchange Act of 1934, as amended.

"JOBS Act" means the Jumpstart Our Business Startups Act of 2012.

"SEC" means the U.S. Securities and Exchange Commission.

"Securities Act" means the Securities Act of 1933, as amended.

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CAUTIONARY NOTE REGARDING FORWARD-LOOKING STATEMENTS

This prospectus and some of the information incorporated by reference includes forward-looking statements within the meaning of Section 27A of the Securities Act and Section 21E of the Exchange Act regarding, among other things, our plans, strategies, and prospects, both business and financial. These statements are based on the beliefs and assumptions of our management. Although we believe that our respective plans, intentions, and expectations reflected in or suggested by these forward-looking statements are reasonable, we cannot assure you that we will achieve or realize these plans, intentions, or expectations. Forward-looking statements are inherently subject to risks, uncertainties, and assumptions. We make such forward-looking statements pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995 and other federal securities laws. Generally, statements that are not historical facts, including statements concerning possible or assumed future actions, business strategies, events or results of operations, and any statements that refer to projections, forecasts, or other characterizations of future events or circumstances, including any underlying assumptions, are forward-looking statements. These statements may be preceded by, followed by or include the words "believes", "estimates", "expects", "projects", "forecasts", "may", "might", "will", "should", "seeks", "plans", "scheduled", "possible", "anticipates", "intends", "aims", "works", "focuses", "aspires", "strives" or "sets out" or similar expressions. Forward-looking statements are not guarantees of performance. You should not put undue reliance on these statements which speak only as of the date hereof. Forward-looking statements contained in this prospectus include, for example, statements about:

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These and other factors that could cause actual results to differ from those implied by the forward-looking statements in this prospectus described under the heading "Risk Factors" and elsewhere in this prospectus. The risks described under the heading "Risk Factors" are not exhaustive. New risk factors emerge from time to time and it is not possible to predict all such risk factors, nor can we assess the impact of all such risk factors on our business or the extent to which any factor or combination of factors may cause actual results to differ materially from those contained in any forward-looking statements. All forward-looking statements attributable to us or to persons acting on our behalf are expressly qualified in their entirety by the foregoing cautionary statements. We undertake no obligations to update or revise publicly any forward-looking statements, whether as a result of new information, future events, or otherwise, except as required by law.

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ABOUT THIS PROSPECTUS

This prospectus is part of a registration statement on Form S-3 that we filed with the SEC using the "shelf" registration process. Under this shelf registration process, the Selling Securityholders may, from time to time, sell the Resale Shares in one or more offerings through any means described in the section entitled "Plan of Distribution." While we will not receive any proceeds from the sale of Resale Shares by the Selling Securityholders pursuant to this prospectus, we have received approximately $15.5 million in aggregate net proceeds from the issuances of the Notes.

A prospectus supplement may add, update or change information included in this prospectus. Any statement contained in this prospectus will be deemed to be modified or superseded for purposes of this prospectus to the extent that a statement contained in such prospectus supplement modifies or supersedes such statement. Any statement so modified will be deemed to constitute a part of this prospectus only as so modified, and any statement so superseded will be deemed not to constitute a part of this prospectus. You should rely only on the information contained in, or incorporated by reference into, this prospectus, and any applicable prospectus supplement. You should read both this prospectus and any applicable prospectus supplement or post-effective amendment to the registration statement together with the additional information to which we refer you in the sections of this prospectus entitled "Where You Can Find More Information."

Neither we nor any Selling Securityholder have authorized anyone to provide you with any information or to make any representations other than those contained in this prospectus or any applicable prospectus supplement or any free writing prospectuses prepared by or on behalf of us or to which we have referred you. Neither we nor any Selling Securityholder take responsibility for, and can provide no assurance as to the reliability of, any other information that others may give you.

This prospectus is an offer to sell only the securities offered hereby and only under circumstances and in jurisdictions where it is lawful to do so. No dealer, salesperson or other person is authorized to give any information or to represent anything not contained in this prospectus, any applicable prospectus supplement or any related free writing prospectus. This prospectus is not an offer to sell securities, and it is not soliciting an offer to buy securities, in any jurisdiction where the offer or sale is not permitted. You should assume that the information appearing in this prospectus or any prospectus supplement is accurate only as of the date on the front of those documents and 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 applicable prospectus supplement, or any sale of a security. Our business, financial condition, results of operations and prospects may have changed since those dates.

For investors outside the United States: neither we nor any Selling Securityholder have done anything that would permit this offering or possession or distribution of this prospectus in any jurisdiction where action for that purpose is required, other than in the United States. Persons outside the United States who come into possession of this prospectus must inform themselves about, and observe any restrictions relating to, the offering of our securities and the distribution of this prospectus outside the United States.

This prospectus contains summaries of certain provisions contained in some of the documents described herein, but reference is made to the actual documents for complete information. All of the summaries are qualified in their entirety by the actual documents. Copies of some of the documents referred to herein have been filed, will be filed or will be incorporated by reference as exhibits to the registration statement of which this prospectus is a part, and you may obtain copies of those documents as described below under "Where You Can Find More Information."

This prospectus contains references to trademarks, trade names and service marks belonging to other entities. Solely for convenience, trademarks, trade names and service marks referred to in this prospectus may appear without the ^® or ^TM symbols, but such references are not intended to indicate, in any way, that

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the applicable licensor will not assert, to the fullest extent under applicable law, its rights to these trademarks and trade names. We do not intend our use or display of other companies' trade names, trademarks or service marks to imply a relationship with, or endorsement or sponsorship of us by, any other companies.

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RISK FACTORS

Investing in the Common Stock involves a high degree of risk. You should carefully consider the risk factors incorporated by reference to our most recent Annual Report on Form 10-K, any subsequent Quarterly Reports on Form 10-Q or Current Reports on Form 8-K, including the risks related to the proposed Merger and the transactions contemplated by the Merger Agreement disclosed in Exhibit 99.2 to the Current Report on Form 8-K filed on July 15, 2026, and all other information contained or incorporated by reference into this prospectus, as updated by our subsequent filings under the Exchange Act, and the risk factors and other information contained in any applicable prospectus supplement before making an investment decision. The risks described in these documents are not the only ones we face. Additional risks and uncertainties not presently known to us or that we currently deem immaterial also may impair our business operations. Past financial performance may not be a reliable indicator of future performance, and historical trends should not be used to anticipate results or trends in future periods. If any of these risks actually occurs, our business, financial condition, results of operations or cash flow could be materially adversely affected. This could cause the trading price of our securities to decline, resulting in a loss of all or part of your investment. Please also carefully read the section titled "Cautionary Note Regarding Forward-Looking Statements."

Risks Related to this Offering by the Selling Securityholders

The sale of the securities registered for resale hereunder and future sales of substantial amounts of our securities in the public market (including the shares of Common Stock issuable upon exchange of the Notes), or the perception that such sales may occur, in particular by a significant and/or controlling stockholder, may cause the market price of our securities to decline significantly.

We are registering for resale 25,555,024 shares of Common Stock. The shares of Common Stock offered for resale by the Selling Securityholders in this prospectus represent approximately 82.0% of our total Common Stock outstanding as of June 30, 2026. Together with its affiliates, the Lead Investor is currently our largest stockholder, and assuming the Issuance Approval and the immediate exchange of the $14.0 million in aggregate principal amount of Notes currently held by the Lead Investor for shares of Common Stock, the Lead Investor would, based on the Celadon 13D/A filed on July 16, 2026 and the subsequent sale of $4.0 million of notes to the Lead Investor, beneficially own 60.0% of our common stock and become our controlling stockholder. As of the date of this prospectus, there are $16.0 million in aggregate principal amount of Notes outstanding. Assuming the Issuance Approval, the exchange of all outstanding Notes for shares of Common Stock would result in the issuance of approximately 25,555,024 shares of common stock (based on the initial exchange price of $0.6261 per share), which would increase our common stock outstanding as of June 30, 2026 from 31,144,754 shares to 56,699,778 shares (an increase of 82.1%).

Pursuant to the Amended Purchase Agreement, although we are not obligated to issue or sell any more Notes, we may choose to sell up to a total of $24.0 million in aggregate principal amount of Notes pursuant to the Amended Purchase Agreement. Assuming that we sell $24.0 million in aggregate principal amount of Notes to the Lead Investor, the Issuance Approval is obtained and Celadon immediately exchanges all of its Notes for shares of our common stock, Celadon would beneficially own 76.7% of our common stock. Assuming the Issuance Approval, the exchange of all $40.0 million in aggregate principal amount of Notes for shares of Common Stock would result in the issuance of 63,887,558 shares of common stock, which would increase our common stock outstanding as of June 30, 2026 from 31,144,754 shares to 95,032,312 shares (an increase of 205.1%). In addition, pursuant to the terms of the Notes, if the Merger closes, we have the right to force the exchange of all outstanding Notes for shares of our common stock. Any such issuance could result in substantial dilution to our existing shareholders and could cause our stock price to decline.

The shares of Common Stock underlying the Notes offered for resale by the Selling Securityholders under this prospectus are not subject to volume limitations pursuant to Rule 144 under the Securities Act. We cannot predict

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if and when any Selling Securityholder may sell such shares in the public markets. Furthermore, in the future, we may issue additional shares of Common Stock or other equity or debt securities convertible into shares of Common Stock.

Pursuant to the terms of the Notes and the rules of the Nasdaq Capital Market, we may not issue greater than 6,225,836 shares of Common Stock upon exchange of the Notes until we obtain the Issuance Approval in accordance with the rules of the Nasdaq Capital Market. We have agreed to call a meeting of our stockholders as promptly as practicable, but in any event not later than August 31, 2026, to seek such stockholder approval. At that meeting, Celadon, which is our largest stockholder, will be able to vote its pre-transaction shares, and has agreed to vote such shares, in favor of the Issuance Approval. The Issuance Approval requires the affirmative vote of the holders of a majority in voting power of the votes cast on such matter, and abstentions and broker non-votes, if any, will have no effect on the outcome of the vote on this proposal. Therefore, all 25,555,024 shares of our Common Stock, plus any shares of our common stock underlying Notes issued in the future, may become issuable in exchange for the Notes in the future, notwithstanding the limitations provided by the Notes and the rules the Nasdaq Capital Market that currently apply to the Notes.

The resale of the 25,555,024 shares of Common Stock registered by the registration statement of which this prospectus forms a part or any shares underlying Additional Notes in the public market, or the perception that the Selling Securityholders intend to sell such shares, could reduce the market price of our Common Stock.

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USE OF PROCEEDS

We will not receive any of the proceeds from the sale of the Resale Shares covered by this prospectus.

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DILUTION

As of June 30, 2026, the net tangible book value of our Common Stock was approximately $(16.6) million, or $(0.53) per share of Common Stock based on 31,144,754 shares of our Common Stock issued and outstanding. Net tangible book value per share as of a particular date represents our total tangible assets less total liabilities, divided by the number of shares of outstanding Common Stock.

After giving effect to the issuance of 25,555,024 shares of our Common Stock upon exchange of the Notes at an assumed price of $0.63 per share, the pro forma net tangible book value as of June 30, 2026 would have been approximately $(1.4) million or $(0.03) per share. This represents an immediate increase in the net tangible book value of $0.51 per share to existing stockholders and an immediate dilution of $0.65 per share to the investors purchasing shares of our Common Stock in this offering at the assumed price per share.

The following table illustrates the dilution in net tangible book value per share as a result of this offering:

Assuming the Selling Securityholders purchase the remaining Notes under the Amended Purchase Agreement having an aggregate principal amount of $24.0 million, and exchange a total of $40.0 million of Notes for 63,887,558 shares of our Common Stock at an assumed price of $0.63 per share, the pro forma net tangible book value as of June 30, 2026 would have been approximately $21.8 million or $0.23 per share. This represents an immediate increase in the net tangible book value of $0.31 per share to existing stockholders and an immediate dilution of $0.33 per share to the investors purchasing shares of our Common Stock in this offering at the assumed price per share.

For purposes of calculating pro forma, as adjusted net tangible book value, the number of shares of our Common Stock outstanding prior to and after this offering is based on 31,144,754 shares of Common Stock outstanding as of June 30, 2026, assumes the issuance of 25,555,024 shares of our Common Stock in connection with this offering, and excludes, in each case, as of such date:

To the extent that any of the outstanding options are exercised, warrants to purchase shares of Common Stock are exercised or restricted stock units vest, there would be further dilution to investors participating in this offering.

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SELLING SECURITYHOLDERS

This prospectus relates to the reoffer and resale of up to 25,555,024 Resale Shares by the Selling Securityholders from time to time upon the exchange of the Initial Notes. We are registering the Resale Shares in order to permit the Selling Securityholders to offer the Resale Shares for resale from time to time. For additional information regarding the Resale Shares being offered by the Selling Securityholders pursuant to this prospectus, see "Prospectus Summary-2026 Private Placement" above. As a closing condition to the issuance of the Notes under the Amended Purchase Agreement, we entered into the Registration Rights Agreement pursuant to which we agreed to file a registration statement with the SEC registering the resale of the Common Stock underlying the Notes sold to the Selling Securityholders.

When we refer to the "Selling Securityholders" in this prospectus, we mean the persons listed in the table below, and the pledgees, donees, transferees, assignees, successors and others who later come to hold any of the Selling Securityholders' interest in the Resale Shares after the date of this prospectus such that registration rights shall apply to those securities.

The following table is prepared based on information provided to us by the Selling Securityholders. It sets forth the name and address of the Selling Securityholders, the aggregate number of Resale Shares beneficially owned as of the date of this prospectus, and the aggregate number of Resale Shares that the Selling Securityholders may offer pursuant to this prospectus, and the number of Resale Shares beneficially owned by the Selling Securityholders after the sale of the securities offered hereby. We have based percentage ownership after this offering on 31,144,754 shares of common stock outstanding as of June 30, 2026. Unless otherwise described below, to our knowledge, the Selling Securityholders have not held any position or office or had any other material relationship with us or our affiliates during the three years prior to the date of this prospectus. In addition, except as otherwise described below, based on the information provided to us by the Selling Securityholders, the Selling Securityholders are not broker-dealers or affiliates of a broker-dealer.

We cannot advise you as to whether the Selling Securityholders will in fact sell any or all of such Resale Shares. In addition, the Selling Securityholders may sell, transfer or otherwise dispose of, at any time and from time to time, the Resale Shares in transactions exempt from the registration requirements of the Securities Act after the date of this prospectus. For purposes of this table, we have assumed that the Selling Securityholders will have sold all of the securities covered by this prospectus upon the completion of the offering. Any changed or new information given to us by the Selling Securityholders, including regarding the identity of, and the securities held by, each Selling Securityholder, will be set forth in a prospectus supplement or amendments to the registration statement of which this prospectus is a part, if and when necessary.

Please see the section entitled "Plan of Distribution" for further information regarding the Selling Securityholders' method of distributing these securities.

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Relationship with Selling Securityholder

Pursuant to a letter agreement executed with Celadon in December 2024, Celadon had the right to designate certain directors to our Board, subject to the terms and conditions provided in its letter agreement. On December 9, 2024, Donald Tang was appointed as a director of our predecessor's Board of Directors pursuant to the letter agreement with Celadon. On March 7, 2025, Feng Hsiung was appointed as a director of our predecessor's Board of Directors and on July 18, 2025, Bryan Baum was appointed as a director of our predecessor's Board of Directors pursuant to a request by Celadon under terms of the same letter agreement. In connection with our reorganization, we, Celadon and our predecessor entered into an amended and restated letter agreement adding us as a party to the letter agreement, and the same three directors were appointed to our Board. As of the date of this prospectus, Celadon held three of the eight seats on the Board.

We have entered into certain agreements, which have been amended from time to time, with GeneFab, LLC, a Delaware limited liability company, or GeneFab, and Valere Bio, Inc., a Delaware corporation and the parent company of GeneFab, or Valere, which is wholly owned by a company managed by Celadon, for the transfer of certain assets, provision of services (for which we may be reimbursed) and sublease of our premises in California as well as license of our intellectual property rights to conduct manufacturing services. These agreements with GeneFab include a letter agreement whereby GeneFab has the option to purchase certain shares of our common stock, subject to the terms specified therein. This letter agreement relating to the option was assigned to Valere Holdings LLC, an affiliate of GeneFab, and it was terminated in April 2026. In addition, we entered into an economic share agreement in August 2023, pursuant to which we were entitled to receive 10% of the realized gains of GeneFab's parent company, and this agreement was terminated in April 2026. Donald Tang, who is currently a member of our Board, is a manager of Celadon Partners, LLC, which is the sole manager of Celadon.

In December 2024, we sold certain warrants and shares of convertible preferred stock to Celadon, and the shares of Common Stock underlying such securities were registered for resale pursuant to a registration rights agreement.

On April 27, 2026, we entered into a securities purchase agreement with the Lead Investor for the sale of the Notes. On May 20, 2026, we issued and sold the Initial Notes and entered into certain ancillary agreements with or in favor of the Lead Investor. For more information, see the section above titled "Prospectus Summary-2026 Private Placement".

On July 14, 2026, we entered into the Merger Agreement with affiliates of Celadon. For more information, see the section above titled "Prospectus Summary-Merger Agreement".

On August 14, 2026, Midco issued $4.0 million of Notes to the Lead Investor.

On September 1, 2026, the parties to the Purchase Agreement and NSG executed the Amendment to amend the Purchase Agreement.

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On September 3, 2026, Midco issued $2.0 million of Notes to NSG.

On September 3, 2026, the Company entered into the Equity Commitment Letter with an affiliate of Celadon pursuant to which, subject to the terms and conditions therein, such affiliate of Celadon agreed to purchase $2.5 million of shares of the Company's common stock.

Other than these relationships with Celadon and NSG, the Selling Securityholders have not had material relationships with us or any of our predecessors within the past three years, other than as a result of the ownership of shares of Common Stock, the Notes or other securities.

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DESCRIPTION OF SECURITIES

The following description summarizes certain important terms of our capital stock as of the date of this prospectus as specified in our Certificate of Incorporation and our Bylaws. Because the following description is only a summary, it does not contain all the information that may be important to you. For a complete description of the matters set forth in this section titled "Description of Securities," you should refer to the Charter, the Bylaws, the Investor Rights and Lock-up Agreement dated June 8, 2022, by and among us (as successor to Senti Biosciences, Inc.) and the parties listed therein as Investors (the "Investor Rights and Lock-Up Agreement"), and the Registration Rights Agreement dated December 2, 2024 between us (as successor to Senti Biosciences, Inc.) and the parties listed therein, which are included as exhibits to Senti Biosciences, Inc.'s Annual Report on Form 10-K for the year ended December 31, 2025, and to the applicable provisions of the DGCL.

Authorized and Outstanding Stock

The Charter authorizes the issuance of 510,000,000 shares, consisting of 500,000,000 shares of common stock, $0.0001 par value per share, and 10,000,000 shares of undesignated preferred stock, $0.0001 par value per share. As of June 30, 2026, there were 31,144,754 shares of common stock outstanding and no shares of preferred stock outstanding.

Common Stock

The Charter provides the following with respect to the rights, powers, preferences and privileges of our common stock.

Voting Power

Except as otherwise required by law or as otherwise provided in any certificate of designation for any series of preferred stock, the holders of our common stock possess all voting power for the election of the directors and all other matters requiring stockholder action. Holders of our common stock are entitled to one vote per share on matters to be voted on by stockholders.

Dividends

Holders of our common stock will be entitled to receive such dividends, if any, as may be declared from time to time by our board of directors in its discretion out of funds legally available therefor. We have not historically paid any cash dividends on our common stock to date and do not intend to pay cash dividends in the foreseeable future. Any payment of cash dividends in the future will be dependent upon our revenues and earnings, if any, capital requirements and general financial conditions. In no event will any stock dividends or stock splits or combinations of stock be declared or made on our common stock unless our common stock at the time outstanding are treated equally and identically.

Liquidation, Dissolution and Winding Up

In the event of our voluntary or involuntary liquidation, dissolution or winding-up, our net assets will be distributed pro rata to the holders of our common stock, subject to the rights of the holders of the preferred stock, if any.

Preemptive or Other Rights

There are no sinking fund provisions applicable to our common stock.

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Transfer Rights

Subject to applicable law and the transfer restrictions set forth in Article IV of the Bylaws, shares of our common stock and the rights and obligations associated therewith are fully transferable to any transferee.

Preferred Stock

Undesignated Preferred Stock

The Charter provides that shares of preferred stock may be issued from time to time in one or more series. Our board of directors is authorized to fix designations, powers, including voting powers, full or limited, or no voting powers, preferences and the relative, participating, optional or other special rights of the shares of each series of preferred stock and any qualifications, limitations and restrictions thereof. Our board of directors is also able to, without stockholder approval, issue preferred stock with voting and other rights that could adversely affect the voting power and other rights of the holders of our common stock and could have anti-takeover effects. The ability of our board of directors to issue preferred stock without stockholder approval could have the effect of delaying, deferring or preventing a change of control of Senti or the removal of existing management.

Registration Rights

2022 Registration Rights Agreement

We (as successor to Senti Biosciences, Inc.) and certain of our stockholders are party to the Investor Rights and Lock-up Agreement, pursuant to which, among other things, such stockholders were granted certain registration rights with respect to certain shares of securities held by them.

The holders of the Founder Shares (as defined in the Investor Rights and Lock-up Agreement), the holders of the Private Placement Shares (as defined in the Business Combination Agreement) and the Anchor Investors (as defined in the Business Combination Agreement) are entitled to registration rights pursuant to the registration and stockholder rights agreement requiring us to register such securities for resale. The holders of these securities are entitled to make up to three demands, excluding short form demands, that we register such securities. In addition, the holders have certain "piggy-back" registration rights with respect to registration statements filed subsequent to the completion of an initial business combination and rights to require us to register for resale such securities pursuant to Rule 415 under the Securities Act. The registration rights agreement does not contain liquidated damages or other cash settlement provisions resulting from delays in registering our securities. We will bear the expenses incurred in connection with the filing of any such registration statements. Under the Investor Rights and Lock-up Agreement, the Anchor Investors will be entitled to registration rights in respect of these shares. In addition, the PIPE Investors (as defined in the Business Combination Agreement) are entitled to registration rights pursuant to the subscription agreements they entered into with us in connection with the PIPE Investment (as defined in the Business Combination Agreement).

These registration rights are only applicable so long as we do not already have a resale registration statement in effective for these shares. As of the date of this prospectus, we currently have in effect a resale registration statement for the shares included in the Investor Rights and Lock-up Agreement.

Registration Rights Agreement (PIPE Transaction)

We (as successor to Senti Biosciences, Inc.) and the investors, who participated in the private placement transaction in December 2024 (the "PIPE Transaction"), are party to a registration rights agreement, pursuant to which, among other things, we agreed to file, as promptly as reasonably practicable following the closing of the PIPE Transaction, but, in any event, not later than one hundred twenty (120) days thereafter (the "PIPE Filing Date"), a resale registration statement on Form S-3 (or Form S-1 if Form S-3 is not available) providing for the resale by the Selling Securityholders of (i) the shares of common stock issuable upon conversion of the Series A

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Preferred Stock and (ii) the shares of common stock issuable upon the exercise of the Warrants , wherein (i) and (ii) collectively are referred to as the Registrable Shares, and to use commercially reasonable efforts to cause such resale registration statement to be declared effective as soon as practicable but in any event no later than the earlier of (a) the seventy-fifth (75th) calendar day following the PIPE Filing Date of the registration statement if the SEC notifies us that it will "review" the registration statement and (b) the fifth (5th) business day after the date we are notified (orally or in writing, whichever is earlier) by the SEC that the registration statement will not be "reviewed" or will not be subject to further review. We also agreed to take all steps necessary to keep such registration statement effective at all times until all Registrable Shares have been resold, or there remains no Registrable Shares. We have agreed to pay a liquidated damages penalty upon certain failures to meet the deadlines set forth above or to keep the resale registration statement continuously effective, which penalties will not exceed 5% of the aggregate subscription amount.

Registration Rights Agreement (Notes Offering)

In connection with the sale of the Initial Notes on May 20, 2026, we entered into the Registration Rights Agreement with the Lead Investor, pursuant to which, among other things, we agreed to file, as promptly as reasonably practicable following any issuance of the Notes, but, in any event, not later than thirty days thereafter (the "Filing Deadline"), a resale registration statement on Form S-3 (or another appropriate form if Form S-3 is not available) providing for the resale by the Lead Investor of the shares of common stock issuable upon exchange of the Notes, and to use reasonable best efforts to cause any such resale registration statement to be declared effective as soon as practicable but in any event no later than the earlier of (a) the seventy-fifth calendar day following the earlier of the filing date and the Filing Deadline of such registration statement if the SEC notifies us that it will "review" the registration statement and (b) the fifth business day after the date we are notified (orally or in writing, whichever is earlier) by the SEC that such registration statement will not be "reviewed" or will not be subject to further review. We further agreed to use reasonable best efforts to keep any such registration statement effective at all times until the earlier of (i) the date on which the Lead Investor shall have resold all the Registrable Securities covered thereby pursuant to Rule 144 or pursuant to such registration statement, (ii) the date on which the Registrable Securities may be resold by the Lead Investor without registration and without regard to any volume or manner-of-sale limitations by reason of Rule 144, without the requirement for us to be in compliance with the current public information requirement under Rule 144 under the Securities Act or any other rule of similar effect, and (iii) the date on which the Notes are redeemed, repaid or otherwise repurchased. NSG joined this registration rights agreement when the sale of Notes to NSG was closed.

Equity Commitment Letter

The Company also expects to enter into a registration rights agreement in connection with the consummation of the equity investment pursuant to the terms of the Equity Commitment Letter.

Anti-Takeover Provisions

Charter and Bylaws

Among other things, the Charter and Bylaws (as amended from time to time):

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To the fullest extent permitted by the DGCL, our Charter and Bylaws, provide that our board of directors and Officers (as defined in the DGCL) shall not be personally liable to us or our stockholders for monetary damages for breach of their fiduciary duty except for liability (a) for any breach of the director or officer's duty of loyalty to us or our stockholders, (b) for the director or officer's acts or omissions not in good faith or which involve intentional misconduct or a knowing violation of law, (c) for any transaction from which the director or officer derived an improper personal benefit, (d) in the case of directors, under Section 174 of the DGCL or (e) in the case of officers, arising from any claim brought by or in the right of the Company.

Our Bylaws establish advance notice procedures with regard to stockholder proposals relating to the nomination of candidates for election as directors or new business to be brought before meetings of our stockholders. These procedures provide that notice of stockholder proposals must be timely given in writing to our corporate secretary prior to the meeting at which the action is to be taken. Generally, to be timely, notice must be received at our principal executive offices not less than 90 days nor more than 120 days prior to the first anniversary date of the annual meeting for the preceding year. Our Bylaws specify the requirements as to form and content of all stockholders' notices. These requirements may preclude stockholders from bringing matters before the stockholders at an annual or special meeting.

The combination of these provisions make it more difficult for the existing stockholders to replace our board of directors as well as for another party to obtain control of us by replacing our board of directors. Because our board of directors will have the power to retain and discharge its officers, these provisions could also make it more difficult for existing stockholders or another party to effect a change in management. In addition, the authorization of undesignated preferred stock will make it possible for our board of directors to issue preferred stock with voting or other rights or preferences that could impede the success of any attempt to change our control.

These provisions are intended to enhance the likelihood of continued stability in the composition of our board of directors and its policies and to discourage coercive takeover practices and inadequate takeover bids. These provisions are also designed to reduce our vulnerability to hostile takeovers and to discourage certain tactics that may be used in proxy fights. However, such provisions could have the effect of discouraging others from making tender offers for our shares and may have the effect of delaying changes in our control or management. As a consequence, these provisions may also inhibit fluctuations in the market price of our stock.

Certain Anti-Takeover Provisions of Delaware Law

We are subject to the provisions of Section 203 of the DGCL. This statute prevents certain Delaware corporations, under certain circumstances, from engaging in a "business combination" with:

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A "business combination" includes a merger or sale of more than 10% of a corporation's assets. However, the above provisions of Section 203 would not apply if:

These provisions may have the effect of delaying, deferring, or preventing changes in control.

Choice of Forum

Pursuant to our Bylaws, unless we consent in writing to the selection of an alternative forum, the Court of Chancery of the State of Delaware will be the sole and exclusive forum for the following types of actions or proceedings under Delaware statutory or common law: (i) any derivative action or proceeding brought on our behalf; (ii) any action asserting a claim of breach of a fiduciary duty owed by any of our current or former directors, officers or employees to us or our stockholders; (iii) any action asserting a claim arising pursuant to any provision of the DGCL, our Charter or our Bylaws (including their interpretation, validity or enforceability); or (iv) any action asserting a claim governed by the internal affairs doctrine. This exclusive forum provision will not apply to any causes of action arising under the Securities Act or the Exchange Act, or any other claim for which the federal courts have exclusive jurisdiction. Stockholders cannot waive compliance with the Securities Act, the Exchange Act or any other federal securities laws or the rules and regulations thereunder. Unless we consent in writing to the selection of an alternate forum, the United States federal district courts shall be the sole and exclusive forum for resolving any complaint asserting a cause of action arising under the Securities Act. In addition, our Bylaws provide that any person or entity purchasing or otherwise acquiring any interest in shares of our capital stock is deemed to have notice of and consented to these exclusive forum provisions.

The forum selection provisions in our Bylaws may limit our stockholders' ability to litigate disputes with us in a judicial forum that they find favorable for disputes with us or our directors, officers or employees, which may discourage the filing of lawsuits against us and our directors, officers and employees, even though an action, if successful, might benefit our stockholders. In addition, these forum selection provisions may impose additional litigation costs for stockholders who determine to pursue any such lawsuits against us.

Transfer Agent

Continental Stock Transfer & Trust Company is the transfer agent for our common stock.

Trading Symbol and Market

Our common stock is listed on the Nasdaq Capital Market under the symbol "SNTI".

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PLAN OF DISTRIBUTION

The selling stockholders, which as used herein includes the Selling Securityholders and 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 the Selling Securityholders 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:

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.

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 reasonable best 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 pursuant to Rule 144 or pursuant to 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 and (iii) the date on which the Notes are redeemed, repaid or otherwise repurchased.

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LEGAL MATTERS

Gunderson Dettmer Stough Villeneuve Franklin & Hachigian, LLP has passed upon the validity of the Resale Shares offered by this prospectus and certain other legal matters related to this prospectus.

EXPERTS

The consolidated financial statements of Senti Biosciences, Inc. as of December 31, 2025 and 2024, and for each of the years in the two-year period ended December 31, 2025, 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 authority of said firm as experts in accounting and auditing. The audit report covering the December 31, 2025 consolidated financial statements contains an explanatory paragraph that states that the Company has incurred recurring losses and negative cash flows from operations and has an accumulated deficit that raise substantial doubt about the entity's ability to continue as a going concern. The consolidated financial statements do not include any adjustments that might result from the outcome of that uncertainty.

WHERE YOU CAN FIND MORE INFORMATION

This prospectus is part of a registration statement on Form S-3 we filed with the SEC under the Securities Act and does not contain all the information set forth or incorporated by reference in the registration statement. Whenever a reference is made in this prospectus to any of our contracts, agreements or other documents, the reference may not be complete and you should refer to the exhibits that are a part of the registration statement or the exhibits to the reports or other documents incorporated by reference into this prospectus for a copy of such contract, agreement or other document. You may obtain copies of the registration statement and its exhibits via the SEC's EDGAR database.

In addition, we file annual, quarterly and current reports, proxy statements and other information with the SEC. Our SEC filings, including our reports, proxy and information statements and other information, are available to the public on a website maintained by the SEC located at www.sec.gov. We also maintain a website at https://sentibio.com/. Through our website, we make available, free of charge, annual, quarterly and current reports, proxy statements and other information as soon as reasonably practicable after they are electronically filed with, or furnished to, the SEC. The information contained on, or that may be accessed through, our website is not part of, and is not incorporated into, this prospectus. Information contained on our website is not a part of or incorporated by reference into this prospectus and the inclusion of our website and investor relations website addresses in this prospectus is an inactive textual reference only.

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INCORPORATION OF CERTAIN INFORMATION BY REFERENCE

This Registration Statement incorporates by reference important business and financial information about us that is not included in or delivered with this document. The information incorporated by reference is considered to be part of this prospectus, and the SEC allows us to "incorporate by reference" the information we file with it, which means that we can disclose important information to you by referring you to those documents instead of having to repeat the information in this prospectus. Any statement contained in this prospectus or a document incorporated or deemed to be incorporated by reference herein or therein shall be deemed to be modified or superseded for the purposes of this prospectus to the extent that a statement contained herein or in any subsequently filed document which also is or is deemed to be incorporated by reference herein modifies or supersedes that prior statement. The modifying or superseding statement need not state that it has modified or superseded a prior statement or include any other information set forth in the document that it modifies or supersedes. The making of a modifying or superseding statement shall not be deemed an admission for any purposes that the modified or superseded statement, when made, constituted a misrepresentation, an untrue statement of a material fact or an omission to state a material fact that is required to be stated or that is necessary to make a statement not misleading in light of the circumstances in which it was made. Any statement so modified or superseded shall not be considered in its unmodified or superseded form to constitute a part of this prospectus, except as so modified or superseded.

We hereby incorporate by reference into this prospectus the following documents that we have filed with the SEC under the Exchange Act:

All documents that we file pursuant to Sections 13(a), 13(c), 14 and 15(d) of the Exchange Act (other than any such documents or portions thereof that are deemed to have been furnished and not filed in accordance with the rules of the SEC), after the date hereof and prior to the termination of an offering of securities under this prospectus shall be deemed to be incorporated by reference into this prospectus and will automatically update and supersede the information in this prospectus, the applicable prospectus supplement and any previously filed documents.

We will furnish without charge to each person, including any beneficial owner, to whom a prospectus is delivered, upon written or oral request, a copy of any or all of the documents incorporated by reference, including exhibits to these documents. Any such request may be made by writing or calling us at the following address or phone number:

Senti Biosciences Holdings, Inc.

2 Corporate Drive, First Floor

South San Francisco, CA 94080

Telephone: (650) 239-2030

Attention: Investor Relations

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25,555,024 Shares of Common Stock

PROSPECTUS

September 24, 2026

You should rely only on the information contained in this prospectus or any supplement or amendment hereto. We have not authorized anyone to provide you with different information. You should not assume that the information contained in this prospectus or any supplement or amendment hereto is accurate as of any date other than the date of this prospectus or any such supplement or amendment. 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.