Company: DNLI
Filing Date: 2025-12-09
Form Type: 424B5
Source: 0001628280-25-056085
Chunk: 55

Company: Denali Therapeutics Inc.
Filing Date: 2025-12-09
Form: 424B5
Chunk 55
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, June 30, 2025 and September 30, 2025, as filed with the SEC on May 6, 2025 , August 11, 2025 , and November 6, 2025 , respectively;

• Current Reports on Form 8-K filed with the SEC on February 27, 2025 , June 3, 2025 , December 4, 2025 , and December 4, 2025 (other than information furnished rather than filed); and

• The description of our common stock contained in our registration statement on Form 8-A , which was filed with the SEC on November 30, 2017, including any amendment or report filed for the purpose of updating such description.

You may request a copy of these filings, at no cost, by contacting us, either orally or in writing, at the following:

<div align='center'>Denali Therapeutics Inc.

161 Oyster Point Blvd.

South San Francisco CA 94080

Phone: (650) 866-8547

S-43</div>

### PROSPECTUS

#### DENALI THERAPEUTICS INC.

#### Common Stock

#### Preferred Stock

#### Debt Securities

#### Warrants

#### Purchase Contracts

#### Units
<div align='center'>________________________________________</div>

We may offer and sell the securities identified above from time to time in one or more offerings. This prospectus provides you with a general description of the securities.

Each time we offer and sell securities, we will provide a supplement to this prospectus that contains specific information about the offering and the amounts, prices and terms of the securities. The supplement may also add, update or change information contained in this prospectus with respect to that offering. You should carefully read this prospectus and the applicable prospectus supplement, together with any documents we incorporated by reference, before you invest in any of our securities.

We may offer and sell the securities described in this prospectus and any prospectus supplement to or through one or more underwriters, dealers and agents, or directly to purchasers, or through a combination of these methods. If any underwriters, dealers or agents are involved in the sale of any of the securities, their names and any applicable purchase price, fee, commission or discount arrangement between or among them will be set forth, or will be calculable from the information set forth, in the applicable prospectus supplement. See the sections of this prospectus entitled "About this Prospectus" and "Plan