July 16, 2019

VIA EDGAR AND HAND DELIVERY

U.S. Securities and Exchange Commission

Division of Corporation Finance

Office of Healthcare & Insurance

100 F Street, N.E.

Washington, DC 20549-3720

Ladies and Gentlemen:

On behalf of our client, Denali Therapeutics Inc. (the “Company”), we submit this letter in response to the comments contained in the letter dated July 2, 2019 (the “Comment Letter”) from the staff (the “Staff”) of the Securities and Exchange Commission relating to the above referenced Form 10-K for the fiscal year ended December 31, 2018 as filed by the Company on March 12, 2019 (the “Form 10-K”). In this letter, we have repeated the comments by the Staff contained in the Comment Letter in bold italics and have followed each comment with the Company’s response in ordinary type.

Confidential Treatment Request

Due to the commercially sensitive nature of information contained in this letter, the Company hereby requests, pursuant to 17 C.F.R. §200.83, that certain portions of this letter be maintained in confidence, not be made part of any public record and not be disclosed to any person. The Company has

Denali Therapeutics Inc. requests that the information contained in this letter, marked by brackets, be treated as confidential information pursuant to 17 C.F.R. §200.83.

U.S. Securities and Exchange Commission

July 16, 2019

Page 2

sent to the Commission a separate copy of this letter, marked to show the portions redacted from the version confidentially submitted via EDGAR and for which the Company is requesting confidential treatment. In accordance with 17 C.F.R. §200.83(d)(1), if any person (including any governmental employee who is not an employee of the Commission) should request access to or an opportunity to inspect this letter, we request that we be immediately notified of any such request, be furnished with a copy of all written materials pertaining to such request (including, but not limited to, the request itself) and be given at least 10 business days’ advance notice of any intended release so that the Company may, if it deems it to be necessary or appropriate, pursue any remedies available to it. In such event, we request that you telephone the undersigned at (650) 493-9300 rather than rely on the U.S. mail for such notice.

Form 10-K for the Fiscal Year Ended December 31, 2018

Notes to the Consolidated Financial Statements

6. Collaboration Agreements

Sanofi, page 156

Response: The following tables outline the amounts of the clinical and regulatory milestones included in the Sanofi Collaboration Agreement with respect to the CNS products, broken down, as applicable, by indication and geographic area:

The following tables outline the amounts of clinical and regulatory milestones included in the Sanofi Collaboration Agreement with respect to peripheral products, broken down, as applicable, by indication and geographic area:

Denali Therapeutics Inc. requests that the information contained in this letter, marked by brackets, be treated as confidential information pursuant to 17 C.F.R. §200.83.

U.S. Securities and Exchange Commission

July 16, 2019

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Takeda, page 158

Response: The following table outlines the amounts of the clinical and regulatory milestones included in the Takeda Collaboration Agreement:

As noted on page 160 of the Form 10-K, the transaction price at inception of the Takeda Collaboration Agreement in February 2018 included fixed consideration consisting of the upfront fee of $40.0 million, the $15.6 million premium on the sale of the Company’s common stock, and the first preclinical milestone payment of $5.0 million. It also included variable consideration of $26.0 million relating to future preclinical milestones that were not constrained. The amount of variable consideration was estimated using the most likely amount method. The remaining $44.0 million of preclinical milestones were considered constrained at the inception of the Takeda Collaboration Agreement since the Company could not conclude it is probable that a significant reversal in the amount recognized will not occur.

There was no change to the transaction price during the year ended December 31, 2018. Preclinical milestones in the aggregate of $10.0 million were met prior to December 31, 2018, such that as of December 31, 2018, $16.0 million of the transaction price represented future preclinical milestones that were not constrained.

The Company identified three performance obligations related to the Takeda Collaboration Agreement: the combined license, the development options, and JSC participation together with the research services for each of Denali’s ATV:BACE1/Tau program, ATV:TREM2 program, and a third identified discovery stage program. $5.7 million of revenue was recorded during the year ended

Denali Therapeutics Inc. requests that the information contained in this letter, marked by brackets, be treated as confidential information pursuant to 17 C.F.R. §200.83.

U.S. Securities and Exchange Commission

July 16, 2019

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December 31, 2018 related to the Takeda Collaboration Agreement, consisting of $[*] related to the ATV:BACE1/Tau program, $[*] related to the ATV:TREM2 program, and $[*] related to the third identified discovery stage program. All three performance obligations were partially satisfied as of December 31, 2018.

* * * * *

Denali Therapeutics Inc. requests that the information contained in this letter, marked by brackets, be treated as confidential information pursuant to 17 C.F.R. §200.83.

U.S. Securities and Exchange Commission

July 16, 2019

Page 5

If you have any questions or comments regarding this letter and the responses set forth above, please direct the questions to me at (650) 493-9300 or tjeffries@wsgr.com.

Steve E. Krognes, Denali Therapeutics Inc.

Jennifer Knapp, Wilson Sonsini Goodrich & Rosati, P.C.

Surita Jolly, Ernst & Young LLP

Denali Therapeutics Inc. requests that the information contained in this letter, marked by brackets, be treated as confidential information pursuant to 17 C.F.R. §200.83.