Denali Therapeut Stock Price, News & Analysis

Denali Therapeutics (NASDAQ: DNLI) has completed its BLA rolling submission for tividenofusp alfa, targeting Hunter syndrome treatment. The therapy, if approved, would be the first FDA-approved enzyme replacement treatment engineered to cross the blood-brain barrier. The company received Breakthrough Therapy Designation in January 2025 and expects potential commercial launch in late 2025 or early 2026. Key Q1 2025 financials show a net loss of $133.0 million, compared to $101.8 million in Q1 2024. R&D expenses increased to $116.2 million, up from $107.0 million year-over-year. The company maintains a strong cash position of $1.05 billion. Notable developments include the opening of a clinical biomanufacturing facility in Salt Lake City and productive FDA discussions regarding DNL126 for Sanfilippo syndrome Type A. However, their DNL343 program for ALS did not meet its primary endpoint in Phase 2/3 trials.

Denali Therapeutics (NASDAQ: DNLI) has initiated a rolling submission of a biologics license application (BLA) for accelerated approval of tividenofusp alfa to treat Hunter syndrome (MPS II). The submission has been received by the FDA's Center for Drug Evaluation and Research (CDER).

The company reports alignment with CDER on the BLA data package, including using cerebrospinal fluid heparan sulfate as a surrogate endpoint for accelerated approval. Denali expects to complete the BLA submission by first half of May 2025, with potential U.S. commercial launch anticipated in late 2025 or early 2026.

Additionally, Denali continues productive collaboration with CDER through the START program, focusing on an accelerated development and approval path for DNL126, targeting Sanfilippo syndrome treatment.

Denali Therapeutics (NASDAQ: DNLI) reported financial results for Q4 and full year 2024. The company reported net losses of $114.8M for Q4 and $422.8M for full year 2024. Cash position stood at $1.19B as of December 31, 2024.

Key highlights include progress with their Enzyme Transport Vehicle (ETV) programs, particularly tividenofusp alfa for Hunter syndrome, which is on track for BLA submission in early 2025 with potential commercial launch in late 2025 or early 2026. The drug received FDA Breakthrough Therapy designation in January 2025.

The company expects a 10-15% increase in cash operating expenses for 2025 compared to 2024. R&D expenses decreased to $396.4M in 2024 from $423.9M in 2023, while G&A expenses increased slightly to $105.4M from $103.4M, primarily due to preparation for tividenofusp alfa launch.

Denali Therapeutics (NASDAQ: DNLI) announced primary analysis results from its Phase 1/2 study of tividenofusp alfa (DNL310) in 47 Hunter syndrome (MPS II) participants, along with long-term follow-up data. The study demonstrated sustained biomarker normalization and improvements in hearing, cognition, and adaptive behavior.

The treatment was generally well-tolerated over a median follow-up of two years, extending to more than four years. Most treatment-related adverse events were mild or moderate, with serious events occurring in 6.4% of participants. The company plans to submit a biologics license application (BLA) for accelerated approval in early 2025, targeting a potential launch in late 2025 or early 2026.

Key outcomes included normal liver volume after 24 weeks, hearing threshold improvements across all tested frequencies, and skill gains in most participants. The treatment led to significant reductions in central nervous system and peripheral biomarkers of disease, including CSF and urine heparan sulfate, and neurofilament light.

Denali Therapeutics (NASDAQ: DNLI) has announced multiple presentations at the upcoming 21st Annual WORLDSymposium™ in San Diego, February 3-7, 2025. The presentations will focus on their investigational therapeutic tividenofusp alfa (DNL310) for Hunter syndrome (MPS II), which utilizes their proprietary TransportVehicle™ platform technology.

Key presentations include an interim analysis of tividenofusp alfa's efficacy and safety, a targeted literature review on Hunter Syndrome treatment needs, and research on age-dependent reference intervals for various biomarkers. The company will also sponsor a satellite symposium titled 'Voices in Unison' featuring insights from medical experts and patient community perspectives.

The TransportVehicle™ platform is designed to deliver various therapeutic molecules across the blood-brain barrier to all body tissues, including the brain. All presentations are scheduled for February 6, 2025, with the symposium taking place on February 5.

Denali Therapeutics (NASDAQ: DNLI) has announced significant milestones and priorities for 2025. The company received FDA Breakthrough Therapy Designation for tividenofusp alfa for Hunter syndrome (MPS II) and plans to submit a biologics license application (BLA) in early 2025, targeting a commercial launch by late 2025 or early 2026. Denali is also seeking FDA alignment on an accelerated approval pathway for DNL126 for Sanfilippo syndrome Type A (MPS IIIA).

Other key developments include:

• Ongoing Phase 1/2 studies for DNL593 for GRN-related frontotemporal dementia, showing promising dose-dependent increases in CSF progranulin levels.
• Collaboration with Biogen on BIIB122/DNL151 for Parkinson's disease, with the global Phase 2b LUMA study expected to complete enrollment in 2025.
• Further analyses of DNL343 for ALS following the HEALEY ALS platform trial, with additional data expected in late 2025.

Denali plans to advance one to two new programs to the clinic annually over the next three years, focusing on its TransportVehicle™ (TV) platform. Financially, Denali reported approximately $1.28 billion in cash, cash equivalents, and marketable securities as of September 30, 2024, with a cash runway extending into 2028.

Denali Therapeutics (NASDAQ: DNLI) announced that the FDA has granted Breakthrough Therapy Designation for tividenofusp alfa (DNL310) for treating Hunter syndrome (MPS II). This adds to previously received Fast Track, Orphan Drug, and Rare Pediatric Disease designations.

The company plans to submit a Biologics License Application (BLA) in early 2025 under the accelerated approval pathway. The designation was supported by promising results from an open-label Phase 1/2 study showing positive effects on surrogate endpoints and early signs of improved clinical outcomes.

Breakthrough Therapy Designation expedites development and review of therapies for serious conditions, providing more intensive FDA guidance, senior reviewer involvement, and eligibility for rolling and priority review. This designation requires preliminary clinical evidence indicating substantial improvement over existing therapies.

Denali Therapeutics (NASDAQ: DNLI) announced topline results from Regimen G of the Phase 2/3 HEALEY ALS Platform Trial evaluating eIF2B agonist DNL343 for amyotrophic lateral sclerosis (ALS) treatment. The study did not meet its primary endpoint of slowing disease progression compared to placebo, measured by ALS Functional Rating Scale-Revised (ALSFRS-R) and survival through week 24.

The trial involved 186 participants receiving DNL343 treatment compared to 139 participants receiving placebo. Key secondary endpoints measuring muscle strength and respiratory function showed no statistical difference between treatment and placebo groups. While DNL343 was found to be safe and well-tolerated, further analyses including neurofilament light (NfL) and other fluid biomarkers, pre-specified subgroup analyses, and extended findings from the active treatment extension period are expected later in 2025.

Denali Therapeutics (NASDAQ: DNLI) has initiated dosing in the global Phase 2a BEACON study of BIIB122, a LRRK2 inhibitor, for LRRK2-associated Parkinson's disease. The study will evaluate safety and biomarkers in approximately 50 participants with Parkinson's disease and LRRK2 pathogenic mutations.

The trial includes a three-month double-blind treatment period followed by an open-label extension. BIIB122 is also being investigated in the ongoing Phase 2b LUMA study for early-stage Parkinson's disease patients with or without LRRK2 mutation, in collaboration with Biogen.