Financial Performance - Denali Therapeutics reported a net loss of $133.0 million for Q1 2025, compared to a net loss of $101.8 million in Q1 2024, reflecting an increase of approximately 30.5% year-over-year[13] - Total research and development expenses for Q1 2025 were $116.2 million, up from $107.0 million in Q1 2024, marking an increase of about 8.6%[14] - General and administrative expenses rose to $29.4 million in Q1 2025, compared to $25.2 million in Q1 2024, an increase of approximately 16.5%[15] - Denali's total operating expenses for Q1 2025 were $145.6 million, compared to $132.3 million in Q1 2024, reflecting an increase of approximately 10%[21] Cash and Assets - Cash, cash equivalents, and marketable securities totaled approximately $1.05 billion as of March 31, 2025[16] Regulatory Developments - Denali completed the Biologics License Application (BLA) submission for tividenofusp alfa for Hunter syndrome, initiating the FDA's 60-day filing review process[3] - The FDA granted Breakthrough Therapy Designation for tividenofusp alfa in January 2025, which is also designated as Fast Track, Orphan Drug, and Rare Pediatric Disease[3] - Denali is conducting the ongoing global Phase 2/3 COMPASS study to support global regulatory approvals for tividenofusp alfa[3] - The company is collaborating with the FDA under the START program for accelerated development of DNL126 for Sanfilippo syndrome Type A[4] Operational Developments - Denali's clinical biomanufacturing facility in Salt Lake City commenced operations, enhancing U.S. manufacturing capabilities and supply chain control[9] Contact Information - Investor Relations contact is Laura Hansen, Ph.D., Vice President, reachable at hansen@dnli.com[23] - Media contact is Rich Allan from FGS Global, reachable at Rich.Allan@fgsglobal.com[23]

Core Insights - Denali Therapeutics has completed the Biologics License Application (BLA) submission for tividenofusp alfa, marking a significant milestone in its development as a late-stage commercial organization focused on treating Hunter syndrome [2][3] - The company is preparing for the commercial launch of tividenofusp alfa, expected in late 2025 or early 2026, which would be the first FDA-approved enzyme replacement therapy designed to cross the blood-brain barrier [2][3] - Denali's clinical pipeline includes ongoing programs for Sanfilippo syndrome Type A and frontotemporal dementia, with collaborations with the FDA and Takeda, respectively [4][5] Financial Performance - For Q1 2025, Denali reported a net loss of $133.0 million, an increase from a net loss of $101.8 million in Q1 2024 [10] - Research and development expenses rose to $116.2 million in Q1 2025 from $107.0 million in Q1 2024, primarily due to increased spending on clinical and preclinical programs [11] - General and administrative expenses increased to $29.4 million in Q1 2025 from $25.2 million in Q1 2024, driven by activities related to the BLA submission for tividenofusp alfa [14] Clinical Program Updates - The BLA submission for tividenofusp alfa is based on data from a Phase 1/2 study involving 47 participants, with the FDA's review process now initiated [3] - Denali is conducting a global Phase 2/3 COMPASS study to support regulatory approvals for tividenofusp alfa [3] - The company is also advancing DNL126 for Sanfilippo syndrome Type A, with ongoing discussions with the FDA for an accelerated development path [4] Corporate Developments - Denali has launched a clinical biomanufacturing facility in Salt Lake City, enhancing its manufacturing capabilities and supply chain control [9] - The company is actively participating in several upcoming investor conferences to engage with stakeholders and present its developments [13]

Core Insights - The Medical sector is experiencing a robust first-quarter earnings season, with several drugmakers reporting results, and large caps like J&J, Merck, and Amgen exceeding earnings and sales estimates [1][2] - Overall, first-quarter earnings for the Medical sector are projected to rise by 40%, with revenues expected to increase by 8.3% [3] Earnings Performance - As of April 30, 45% of Medical sector companies, representing approximately 57.9% of the sector's market capitalization, have reported earnings, with 66.7% beating both earnings and revenue estimates [2] - Year-over-year earnings growth for the sector is reported at 60.5%, while revenues have increased by 7.8% [2] Company Highlights - **Novo Nordisk**: Expected to report earnings of 92 cents per share and revenues of $11.33 billion, with strong sales anticipated from diabetes and obesity care products [6][7] - **Pacira BioSciences**: Projected earnings of 57 cents per share and revenues of $174.96 million, driven by sales of its pain-management product Exparel [8][9] - **Ultragenyx Pharmaceuticals**: Expected to report a loss of $1.54 per share and revenues of $141.99 million, with growth driven by its lead drug Crysvita [10][11] - **Acadia Pharmaceuticals**: Anticipated earnings of 6 cents per share and revenues of $241.74 million, primarily from sales of Nuplazid for Parkinson's disease psychosis [12][13] - **Denali Therapeutics**: Expected loss of 71 cents per share and revenues of $8.3 million, with updates on pipeline programs anticipated during the earnings report [17][18] Earnings Surprise Potential - The Earnings ESP methodology indicates that stocks with a positive Earnings ESP and a Zacks Rank of 1, 2, or 3 have a high chance of delivering earnings surprises, with a success rate of up to 70% [4][5]

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 ...