Core Viewpoint - Denali Therapeutics (DNLI) has initiated a rolling submission of a biologics license application (BLA) for accelerated approval of tividenofusp alfa for the treatment of Hunter syndrome (MPS II), leading to an 11.8% increase in its shares [1] Company Developments - DNLI is engaged in ongoing collaboration with the FDA's Center for Drug Evaluation and Research (CDER) regarding the BLA data package, including the use of CSF HS as a surrogate endpoint for accelerated approval [2] - The company expects to complete its BLA submission by mid-May 2025 and is preparing for a potential U.S. commercial launch in late 2025 or early 2026 [3] - Tividenofusp alfa has received Fast Track and Breakthrough Therapy designations from the FDA for MPS II, and it holds the Priority Medicines designation in the EU [3] - DNLI has lost 32.6% in share value year-to-date, contrasting with a 1.2% growth in the industry [4] Clinical Trials and Pipeline - Denali is currently enrolling patients in the global phase II/III COMPASS study of tividenofusp alfa to support global regulatory approvals, with an expanded target enrollment for neuronopathic participants to 42 patients [6][7] - The candidate has not yet received approval for therapeutic use by any health authority [7] - Denali is also evaluating DNL126 for the treatment of Sanfilippo syndrome type A (MPS IIIA) in a phase I/II study, which has received Orphan Disease designation and Fast Track status from the FDA [8] - Initial positive phase I/II results for DNL126 have led to productive collaboration with the FDA under the START program to align on a pathway for accelerated development and approval [9]

Core Viewpoint - Denali Therapeutics has initiated a rolling submission of a biologics license application (BLA) for accelerated approval of tividenofusp alfa for Hunter syndrome, with expectations to complete the submission by May 2025 and a potential commercial launch in late 2025 or early 2026 [1][7]. Company Developments - The company is engaged in regular collaboration with the FDA's Center for Drug Evaluation and Research (CDER) regarding the BLA data package, including the use of cerebrospinal fluid heparan sulfate as a surrogate endpoint for accelerated approval [1][2]. - Denali's Chief Medical Officer expressed gratitude for the FDA's support and highlighted the importance of this regulatory milestone for the Hunter syndrome community [2]. - The company is also preparing for the development and approval path for DNL126, a treatment for Sanfilippo syndrome, under the START program with CDER [2][7]. Product Information - Tividenofusp alfa (DNL310) is designed to deliver the iduronate 2-sulfatase enzyme to the brain and body, addressing cognitive, behavioral, and physical symptoms of Hunter syndrome [4]. - The product has received Fast Track and Breakthrough Therapy designations from the FDA, as well as Priority Medicines designation from the European Medicines Agency [4]. - The ongoing Phase 2/3 COMPASS study is enrolling participants to support global approval, comparing tividenofusp alfa with idursulfase [5]. Disease Context - Hunter syndrome (MPS II) is a rare genetic disorder affecting over 2,000 individuals worldwide, primarily males, leading to various physical and cognitive symptoms due to a deficiency of the IDS enzyme [3]. - Current standard treatments only partially address physical symptoms and do not cross the blood-brain barrier, leaving cognitive and behavioral symptoms unmet [3].

Company Overview - Denali Therapeutics Inc. (DNLI) is currently an intriguing investment choice due to solid earnings estimate revision activity and a favorable Zacks Industry Rank [1][3] - The company has seen a positive shift in earnings estimates, indicating a more bullish outlook from analysts [3][4] Industry Analysis - The Medical - Biomedical and Genetics industry has a Zacks Industry Rank of 75 out of more than 250 industries, suggesting it is well-positioned compared to other segments [2] - A rising trend in this industry can positively impact multiple securities, indicating a broad uplift in the sector [2] Earnings Estimates - Current quarter estimates for Denali have improved from a loss of 77 cents per share to a loss of 73 cents per share [4] - Current year estimates have also risen from a loss of $3.03 per share to a loss of $2.90 per share, reflecting a more optimistic outlook [4] - Denali currently holds a Zacks Rank 3 (Hold), which is considered a favorable signal for investors [4]

Denali Therapeutics (DNLI) reported a fourth-quarter 2024 loss of 67 cents per share, narrower than the Zacks Consensus Estimate of a loss of 83 cents. The company reported a loss of 86 cents in the year-ago quarter.The loss per share improved year over year due to a decline in total operating expenses and an increase in the number of shares outstanding.In the absence of a marketed product, the company only recognizes revenues from ongoing collaborations. Denali did not generate collaboration revenues in th ...

Exhibit 1.2 DENALI THERAPEUTICS INC. Common Stock ($0.01 par value) Having an Aggregate Offering Price of up to $400,000,000 Equity Distribution Agreement February 27, 2025 Goldman, Sachs & Co. LLC 200 West Street New York, New York 10282 Leerink Partners LLC 1301 Avenue of the Americas, 5 Floor New York, New York 10019 th Ladies and Gentlemen: Denali Therapeutics Inc., a Delaware corporation (the "Company") confirms its agreement (this "Agreement") with Goldman, Sachs & Co. LLC ("Goldman") and Leerink Part ...

Table of Contents UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 10-K (Mark One) ☒ ANNUAL REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 (Exact name of registrant as specified in its charter) For the fiscal year ended December 31, 2024 OR Delaware 46-3872213 (State or other jurisdiction of incorporation or organization) ☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the transition period from to Comm ...

SOUTH SAN FRANCISCO, Calif., Feb. 27, 2025 (GLOBE NEWSWIRE) -- Denali Therapeutics Inc. (Nasdaq: DNLI) today reported financial results for the fourth quarter and year ended December 31, 2024, and provided business highlights. “In 2024, we made significant strides across our portfolio, particularly with our Enzyme Transport Vehicle (ETV) programs, achieving a path to a potential accelerated approval for our lead program in MPS II,” said Ryan Watts, Ph.D., CEO of Denali. “In 2025, we will continue expanding ...

Denali Therapeutics (DNLI) reported primary analysis data from an early to mid-stage study of its pipeline candidate, tividenofusp alfa (DNL310), in 47 patients with Hunter syndrome (MPS II) over a 24-week treatment period, along with additional long-term follow-up data. DNLI’s wholly-owned program, tividenofusp alfa, is an Enzyme Transport Vehicle-enabled iduronate-2-sulfatase replacement therapy in development for MPS II.Per the additional long-term data readout from the phase I/II study, treatment with t ...

Long-term data demonstrate that robust reductions and normalization in key biomarkers from baseline were maintained over time with continued improvement in hearing, cognition and adaptive behaviorLong-term safety data with median follow-up of two years, and out to more than four years, demonstrate that tividenofusp alfa was generally well tolerated Regulatory submission for accelerated approval is planned for early 2025; U.S. launch preparation is ongoing to deliver tividenofusp alfa to families with MPS II ...

SOUTH SAN FRANCISCO, Calif., Jan. 30, 2025 (GLOBE NEWSWIRE) -- Denali Therapeutics Inc. (NASDAQ:DNLI), today announced upcoming oral (platform) and poster presentations at the 21st Annual WORLDSymposium™, which will be held February 3-7, 2025, in San Diego, California. The oral presentation includes clinical results related to its Hunter syndrome (MPS II) investigational therapeutic, tividenofusp alfa (DNL310). Tividenofusp alfa is enabled by the Denali TransportVehicle™ platform, which is designed to effec ...