Free Writing Prospectus (Form FWP)

Issuer Free Writing Prospectus dated November 4, 2025

Relating to Preliminary Prospectus Supplement dated November 4, 2025

Filed pursuant to Rule 433

Registration Statement No. 333-272121

Guardant Health Announces Proposed Public Offering of Common Stock

PALO ALTO, Calif. November 4, 2025 - Guardant Health, Inc. ("Guardant Health") (Nasdaq: GH), a leading precision oncology company, today announced the commencement of an underwritten public offering of $250.0 million of shares of Guardant Health's common stock (the "common stock offering"). Guardant Health also intends to grant the underwriters a 30-day option to purchase up to an additional $37.5 million of shares of its common stock at the public offering price, less underwriting discounts and commissions. The common stock offering is subject to market and other conditions, and there can be no assurance as to whether or when the common stock offering may be completed or as to the actual size or terms of the common stock offering.

Goldman Sachs & Co. LLC, Jefferies, Leerink Partners and Guggenheim Securities are acting as joint book-running managers for the common stock offering.

Guardant Health intends to use the net proceeds from the common stock offering, together with the net proceeds from Guardant Health's concurrent convertible notes offering (as defined below), if consummated, for general corporate purposes, which may include, depending on market conditions, repurchasing a portion of Guardant Health's 0% convertible senior notes due 2027 (the "2027 notes"). General corporate purposes may also include the acquisition of complementary products, technologies, intellectual property or businesses; however, Guardant Health currently does not have any agreements or commitments to complete any such transactions. This press release is not an offer to repurchase any 2027 notes and the common stock offering is not contingent upon the repurchase of any 2027 notes. There can be no assurances that Guardant Health will repurchase any 2027 notes.

In a separate press release and concurrently with the common stock offering, Guardant Health also announced today its intent, subject to market and other conditions, to offer $300.0 million aggregate principal amount of its Convertible Senior Notes due 2033 (the "notes") to persons reasonably believed to be qualified institutional buyers pursuant to Rule 144A under the Securities Act of 1933, as amended (the "concurrent convertible notes offering" and, together with the common stock offering, the "offerings"). Guardant Health also intends to grant to the initial purchasers in the concurrent convertible notes offering an option to purchase, within a 13-day period beginning on, and including, the date on which the notes are first issued, up to an additional $45.0 million aggregate principal amount of notes. The completion of the common stock offering is not contingent on the completion of the concurrent convertible notes offering, and the completion of the concurrent convertible notes offering is not contingent on the completion of the common stock offering.

The common stock offering will be made pursuant to a shelf registration statement, including a base prospectus, that was filed with the Securities and Exchange Commission (the "SEC") on May 22, 2023 and became automatically effective upon filing. The common stock offering will be made only by means of a prospectus supplement and the accompanying prospectus.

Before you invest, you should read the prospectus supplement and the accompanying prospectus and the other documents Guardant Health has filed or will file with the SEC for more complete information about Guardant Health and the common stock offering. You may get these documents for free by visiting EDGAR on the SEC's website at www.sec.gov. Alternatively, copies of the preliminary prospectus supplement and the accompanying prospectus may be obtained by contacting Goldman Sachs & Co. LLC, Attention: Prospectus Department, 200 West Street, New York, New York 10282, telephone: (866) 471-2526, or by emailing [email protected]; Jefferies LLC, Attention: Equity Syndicate Prospectus Department, 520 Madison Avenue, New York, New York

10022, telephone: (877) 821-7388, or by emailing [email protected]; Leerink Partners LLC, Attention: Syndicate Department, 53 State Street, 40th Floor, Boston, MA 02109, telephone: (800) 808-7525, ext. 6105, or by emailing [email protected]; or Guggenheim Securities, LLC, Attention: Equity Syndicate Department, 330 Madison Avenue, 8th Floor, New York, NY 10017, telephone: at (212) 518-9544, or by emailing [email protected].

This press release shall not constitute an offer to sell or a solicitation of an offer to buy any of the securities being offered in the offerings, nor shall there be any offer or sale of any securities in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to the registration or qualification under the securities laws of any such state or jurisdiction.

About Guardant Health

Guardant Health is a leading precision oncology company focused on guarding wellness and giving every person more time free from cancer. Founded in 2012, Guardant is transforming patient care and accelerating new cancer therapies by providing critical insights into what drives disease through its advanced blood and tissue tests, real-world data and AI analytics. Guardant tests help improve outcomes across all stages of care, including screening to find cancer early, monitoring for recurrence in early-stage cancer, and treatment selection for patients with advanced cancer.

Forward Looking Statements

This press release contains forward-looking statements within the meaning of federal securities laws, including statements regarding the proposed terms of the offerings, the completion, timing and size of the proposed offerings, the grant to the underwriters in the common stock offering of the option to purchase additional shares, the grant to the initial purchasers in the concurrent convertible notes offering of the option to purchase additional notes and the anticipated use of proceeds from the offerings, including any potential repurchases of the 2027 notes, which involve risks and uncertainties that could cause the actual results to differ materially from the anticipated results and expectations expressed in these forward-looking statements. These statements are based on current expectations, forecasts and assumptions, and actual outcomes and results could differ materially from these statements due to a number of factors. These and additional risks and uncertainties that could affect Guardant Health's financial and operating results and cause actual results to differ materially from those indicated by the forward-looking statements made in this press release include those discussed under the captions "Risk Factors" and "Management's Discussion and Analysis of Financial Condition and Results of Operation" and elsewhere in its Annual Report on Form 10-K for the year ended December 31, 2024, its Quarterly Reports on Form 10-Q for the quarters ended March 31, 2025, June 30, 2025 and September 30, 2025 and in its other reports filed with or furnished to the SEC thereafter. The forward-looking statements in this press release are based on information available to Guardant Health as of the date hereof, and Guardant Health disclaims any obligation to update any forward-looking statements provided to reflect any change in its expectations or any change in events, conditions, or circumstances on which any such statement is based, except as required by law. These forward-looking statements should not be relied upon as representing Guardant Health's views as of any date subsequent to the date of this press release.

Investor Contact:

Zarak Khurshid

[email protected]

Media Contact:

Meaghan Smith

[email protected]

Source: Guardant Health, Inc.