Denali Therapeut Stock Price, News & Analysis

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.

Denali Therapeutics (DNLI) reported Q3 2024 financial results with a net loss of $107.2 million, compared to $99.4 million in Q3 2023. The company reported no collaboration revenue, down from $1.3 million in the previous year. R&D expenses increased to $98.2 million from $89.7 million, while G&A expenses remained stable at $24.9 million. Cash position stood at $1.28 billion as of September 30, 2024.

Key developments include plans to file for accelerated approval of tividenofusp alfa for MPS II in early 2025, positive preliminary data from DNL126 Phase 1/2 study in MPS IIIA, and the expansion of clinical trials. The company updated its 2024 guidance, projecting a 5-10% increase in cash operating expenses compared to 2023.

Denali Therapeutics (Nasdaq: DNLI) announced a successful meeting with the FDA, paving the way for accelerated approval of tividenofusp alfa (DNL310) for MPS II (Hunter syndrome) treatment. The company plans to submit a biologics license application (BLA) in early 2025 using cerebrospinal fluid heparan sulfate as a surrogate endpoint. New Phase 1/2 data show robust biomarker responses and positive clinical outcomes, including:

• 90% mean reduction in CSF HS at Week 24
• 77% of participants with normal urine GAGs at Week 24
• Significant serum NfL reduction
• Improvements in adaptive behavior, cognitive scores, hearing, liver volume, and growth

The treatment was generally well-tolerated, supporting its development for MPS II.

Denali Therapeutics (DNLI) has published groundbreaking research in Science Translational Medicine, showcasing the potential of their Oligonucleotide Transport Vehicle (OTV) platform. This innovative technology enables broad biodistribution of antisense oligonucleotides (ASOs) in the central nervous system (CNS) and muscle following intravenous administration.

The OTV platform, an extension of Denali's clinically validated Transport Vehicle (TV) technology, addresses a major challenge in oligonucleotide therapeutics: crossing the blood-brain barrier (BBB). Unlike current methods requiring invasive delivery, the OTV allows for uniform distribution throughout the brain via less invasive intravenous administration.

Key findings demonstrate the OTV's ability to provide cumulative and sustained knockdown of target gene expression across multiple CNS regions and cell types, as well as in peripheral muscle tissues. This breakthrough could significantly advance the development of treatments for neurodegenerative and lysosomal storage diseases.

Denali Therapeutics (NASDAQ: DNLI) reported Q2 2024 financial results and business highlights. Key updates include:

1. Completed enrollment of 47 participants in Phase 1/2 study for tividenofusp alfa (DNL310) in MPS II.

2. FDA indicated openness to discussing accelerated approval pathway for tividenofusp alfa.

3. DNL126 selected for FDA's START Pilot Program for rare disease therapeutics.

4. Regained rights to ATV:Abeta program from Biogen for Alzheimer's disease.

5. Net loss of $99.0 million in Q2 2024, compared to net income of $183.4 million in Q2 2023.

6. No collaboration revenue in Q2 2024, down from $294.1 million in Q2 2023.

7. Cash, cash equivalents, and marketable securities of $1.35 billion as of June 30, 2024.

Denali Therapeutics announced that its investigational drug DNL126 has been selected for the FDA's START Pilot Program. This program aims to accelerate the development of therapies for rare diseases. DNL126, designed to cross the blood-brain barrier, targets MPS IIIA (Sanfilippo syndrome type A). The FDA's START initiative will provide Denali with frequent advice and rapid communication with FDA review staff to streamline DNL126's development. Additionally, Denali is conducting a Phase 1/2 study of DNL126 for children with MPS IIIA and anticipates increased engagement will support a marketing application. Denali is also developing tividenofusp alfa (DNL310) for MPS II (Hunter syndrome) and plans to complete a Phase 2/3 study this year.