Denali Therapeutics Inc

Securities Trading Plans of Directors and Executive Officers

Our policy governing transactions in our securities by our directors, officers, and employees permits our officers, directors and employees to enter into trading plans complying with Rule 10b5-1 under the Securities Exchange Act of 1934, as amended. As disclosed in the table below, during the fourth quarter of 2024, certain of our directors adopted a “Rule 10b5-1 trading arrangement”. This plan provides for the sale of our common stock and is intended to satisfy the affirmative defense in Rule 10b5-1(c).

(1)The trading arrangement may expire on an earlier date if and when all transactions under the arrangement are completed.

(2)This amounts represents the maximum total shares that could be sold under the plan, but the amounts may change for executive officers due to the sale of shares to satisfy tax withholding requirements.

No other officers or directors, as defined in Rule 16a-1(f), adopted and/orterminated of a “Rule 10b5-1 trading arrangement” or a “non-Rule 10b5-1 trading arrangement,” as defined in Regulation S-K Item 408, during the fourth quarter ended December 31, 2024.

Entry into a Material Definitive Agreement

On February 24, 2025, Denali and Sanofi executed a side letter terminating the CNS program portion of their Collaboration Agreement dated October 29, 2018. Under the Collaboration Agreement, certain CNS and peripheral RIPK1 small molecule inhibitors (the "CNS Products" and "Peripheral Products," respectively) were to be developed and commercialized. The side letter terminated provisions of the Collaboration Agreement relating to CNS Products, including Sanofi’s obligations to make milestones or other payments to Denali on future development and commercialization of CNS Products, and delineated the parties' ongoing rights and obligations.

Sanofi will continue to develop eclitasertib (SAR443122/DNL758), a Peripheral Product discovered by us, and licensed to Sanofi under the Collaboration Agreement. Sanofi is currently conducting a Phase 2 clinical trialfor eclitasertibin patients with UC, and we remain eligible to receive milestones and tiered royalties on net sales for Peripheral Products sold worldwide.

Entry into a Material Definitive Agreement

In February 2025, after mutual agreement to discontinue preclinical activities on ATV:TREM2, Takeda delivered notice of its election to terminate the ATV:TREM2 program on February 26, 2025, as per the terms of the Takeda Collaboration Agreement dated January 3, 2018. Under the Takeda Collaboration Agreement, Denali had granted Takeda options with respect to the ATV:BACE1/Tau, ATV:TREM2 and PTV:PGRN programs in exchange for an upfront payment of $40.0 million and an additional $110.0 million under a February 2018 share purchase agreement. The Takeda Collaboration Agreement became effective in February 2018, following satisfaction of certain requirements of the Hart-Scott-Rodino Antitrust Improvements Act of 1976.

The ATV:Tau program was substituted for the ATV:BACE1/Tau program via amendment of the Takeda Collaboration Agreement in February 2019, and in March 2022, the parties mutually agreed to terminate activity on the ATV:Tau program. Takeda exercised its option for the PTV:PGRN program in November 2021 and the parties have continuing obligations with respect to this program under the Takeda Collaboration Agreement. We are eligible to receive payments under the Takeda Collaboration Agreement for PTV:PGRN upon the achievement of certain clinical and sales-based milestones or upon achievement of certain regulatory milestones relating to regulatory approval in the United States, certain European countries, and Japan. Further, we and Takeda share equally the development and commercialization costs, and, if applicable, will share the profits, for the PTV:PGRN program.

Takeda exercised its option for the ATV:TREM2 program in December 2021. On February 26, 2025, after mutual agreement to discontinue preclinical activities on ATV:TREM2, we received notice of Takeda's election to terminate the ATV:TREM2 program effective sixty days following the date of the notice from Takeda, or earlier if mutually agreed by the parties. Takeda's notice terminated provisions of the Collaboration Agreement relating to the ATV:TREM2 program, including those related to future milestones, cost or profit sharing.