SECURITIES AND EXCHANGE COMMISSION

WASHINGTON, D.C. 20549

SCHEDULE 13D/A

(Rule 13d-101)

INFORMATION INCLUDED IN STATEMENTS FILED PURSUANT TO RULE 13d-1(a)

AND AMENDMENTS THERETO FILED PURSUANT TO RULE 13d-2(a)

(Amendment No. 5)*

DAY ONE BIOPHARMACEUTICALS, INC.

(Name of Issuer)

Common Stock, par value $0.0001 per share

(Title of Class of Securities)

23954D109

(CUSIP Number)

Canaan XI L.P.

c/o Canaan Partners

285 Riverside Avenue, Suite 250

Westport, Connecticut 06880

(203) 855-0400

(Name, Address and Telephone Number of Person Authorized to Receive Notices and Communications)

October 31, 2022

(Date of Event which Requires Filing of this Statement)

If the filing person has previously filed a statement on Schedule 13G to report the acquisition that is the subject of this Schedule 13D, and is filing this schedule because of §§240.13d 1(e), 240.13d 1(f) or 240.13d 1(g), check the following box.  ☐

Note: Schedules filed in paper format shall include a signed original and five copies of the schedule, including all exhibits. See §240.13d-7 for other parties to whom copies are to be sent.

The information required on the remainder of this cover page shall not be deemed to be “filed” for the purpose of Section 18 of the Securities Exchange Act of 1934 (“Act”) or otherwise subject to the liabilities of that section of the Act but shall be subject to all other provisions of the Act (however, see the Notes).

EXPLANATION.

This Amendment No. 5 to Schedule 13D (“Amendment No. 5”) relates to Common Stock, par value $0.0001 per share (the “Common Stock”), of Day One Biopharmaceuticals, Inc., a Delaware corporation (the “Issuer”), and is being filed on behalf of the Reporting Persons. This Amendment No. 5 amends and supplements Amendment No. 4 previously filed with the SEC (as defined below) on October 19, 2022 (“Amendment No. 4”), Amendment No. 3 previously filed with the SEC (as defined below) on September 22, 2022 (“Amendment No. 3”), Amendment No. 2 previously filed with the SEC (as defined below) on September 19, 2022 (“Amendment No. 2”), Amendment No. 1 previously filed with the SEC (as defined below) on December 22, 2021 (“Amendment No. 1”), and the initial Schedule 13D previously filed with the Securities and Exchange Commission (the “SEC”) by the Reporting Persons on June 10, 2021 (the “Initial Schedule 13D”, together with, Amendment No. 1, Amendment No. 2, Amendment No. 3, Amendment No. 4, and this Amendment No. 5, the “Schedule 13D”). Except as specifically provided herein, this Amendment does not modify any of the information previously reported in the Schedule 13D. The Common Stock is held directly by Canaan XI L.P.

Paragraphs (a), (b) and (c) of this Item 5 are amended and restated as follows:

(a) and (b) As of the date of this Schedule 13D, Canaan XI directly beneficially owns 2,548,403 shares of Common Stock, representing approximately 3.5% of the total outstanding shares of Common Stock based upon 73,461,100 outstanding shares of Common Stock of the Issuer as of August 1, 2022, as reported by the Issuer in its Form 10-Q for the quarter ended June 30, 2022 as filed with the Securities and Exchange Commission on August 4, 2022.

As of the date of this Schedule 13D, Canaan XI GP may be deemed to beneficially own the shares held directly by Canaan XI.

(c) On October 31, 2022, Canaan XI effected a pro rata distribution, for no consideration, of 2,200,000 shares to its partners. Except as reported in this Item 5(c), none of the Reporting Persons have effected any transactions since the most recent filing of Schedule 13D.

(e) On October 31, 2022, the Reporting Persons ceased to be the beneficial owners of more than five percent of the Common Stock of the Issuer.

SIGNATURES

After reasonable inquiry and to the best of its knowledge and belief, the undersigned certifies that the information set forth in this Statement is true, complete and correct.

Dated: November 2, 2022

EXHIBIT INDEX

Exhibit 99.1

Joint Filing Agreement

In accordance with Rule 13d-1(f) under the Securities and Exchange Act of 1934, the persons or entities named below agree to the joint filing on behalf of each of them of a statement on Schedule 13D (including amendments thereto) with respect to the shares of the Issuer and further agree that this joint filing agreement be included as an exhibit to this Schedule 13D. In evidence thereof, the undersigned, being duly authorized, have executed this Joint Filing Agreement as of November 2, 2022.