Company: DNLI
Filing Date: 2025-12-09
Form Type: 424B5
Source: 0001628280-25-056085
Chunk: 20

Company: Denali Therapeutics Inc.
Filing Date: 2025-12-09
Form: 424B5
Chunk 20
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 BIIB122/DNL151 (LRRK2 inhibitor) for Parkinson’s disease, DNL628 (OTV:MAPT) for Alzheimer’s disease and DNL952 (ETV:GAA) for Pompe Disease;

• Expansion and acceleration of our TransportVehicle TM (TV) platform, including continued optimization and clinical translation of the OTV and ATV platforms;

• Progression of our earlier-stage pipeline, including continued IND-enabling and early clinical studies for next-generation biotherapeutics enabled by the TV platform; and

• Build-out and scaling of internal process development and GMP clinical manufacturing capabilities, including production of drug substance and drug product to support clinical trials across our portfolio.

We expect to use any remaining net proceeds from this offering for general and administrative expenses, potential future development programs, early-stage research and development, capital expenditures and working capital and other general corporate purposes.

Our expected use of net proceeds from this offering represents our current intentions based upon our present plans and business condition. As of the date of this prospectus supplement, we cannot predict with certainty all of the particular uses for the net proceeds to be received upon the completion of this offering or the amounts that we will actually spend on the uses set forth above. We may also use a portion of the net proceeds to in-license, acquire or invest in complementary businesses, technologies, products or assets. Due to the many variables inherent to drug development at this time, such as the timing of patient enrollment and evolving regulatory requirements, we cannot currently predict the stage of development we expect the net proceeds of this offering to achieve for our clinical studies and product candidates.

The amount and timing of our actual expenditures will depend upon numerous factors, including our commercial activities, the results of our research and development efforts, the timing and success of preclinical studies, our ongoing clinical studies or clinical studies we may commence in the future and the timing of regulatory submissions. As a result, our management will have broad discretion over the use of the net proceeds from this offering.

Pending the use of the net proceeds from this offering, we intend to invest the net proceeds in short to intermediate-term fixed income securities.

<div align='center'>S-15</div>

### DILUTION
If you invest in our common stock or pre-funded warrants in this offering, your ownership interest will be diluted immediately to the extent of the difference between the price per share of our common stock or pre-funded warrant in this offering and the as adjusted net tangible book value per share of our common stock immediately after this offering.

Our historical