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.