Denali Therapeutics Inc. DNLI announced disappointing top-line results from an analysis of Regimen G of the phase II/III HEALEY ALS Platform Trial on pipeline candidate DNL343.

The HEALEY platform trial is evaluating eIF2B agonist DNL343 in the treatment of amyotrophic lateral sclerosis (ALS).

DNL343 is a novel small molecule ALS therapeutic candidate that targets eIF2B, a central regulator of the integrated stress response.

Shares of DNLI have lost 6.5% in the past six months compared with the industry’s 6.4% decline.

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DNLI’s ALS Study Fails

A total of 186 participants who were randomized to receive DNL343 treatment were compared to 139 participants randomized to receive placebo in this regimen (n=63) or shared from a concurrently enrolling regimen (n=76).

ALS causes the progressive degeneration of motor neurons, resulting in muscle weakness and atrophy. The most prevalent adult-onset progressive motor neuron disease, ALS affects approximately 30,000 people in the United States and an estimated 500,000 people worldwide.

Results showed that the study did not meet the primary endpoint of efficacy in slowing disease progression as compared with placebo. The primary endpoint was evaluated as a change in disease severity over time as measured by the ALS Functional Rating Scale-Revised (ALSFRS-R) and survival through week 24.

Key secondary endpoints, measuring muscle strength and respiratory function, were also not statistically different between the active and placebo groups at week 24.

DNL343 was found to be well tolerated. Denali will report additional data later in 2025, including neurofilament light (NfL) and other fluid biomarkers, data from pre-specified subgroups, and extended findings from the active treatment extension period.

Denali will evaluate the data before determining the next steps.

DNLI’s Other Pipeline Updates

Denali and partner Sanofi SNY were co-developing SAR443820/DNL788. However, Sanofi informed Denali that the K2 phase II study evaluating the safety and efficacy of oditrasertib (SAR443820/DNL788) on serum neurofilament light chain levels in participants with multiple sclerosis was discontinued. The decision was taken after the study did not meet the primary and key secondary endpoints.

We remind investors that Sanofi had earlier discontinued the development of SAR443820/DNL788 for the treatment of ALS, based on the results of the phase II HIMALAYA study, which did not meet the primary endpoint.

Meanwhile, Denali and partner Sanofi are also developing SAR443122/DNL758 (eclitasertib), a peripheralRIPK1 inhibitor, for the treatment of ulcerative colitis. Sanofi is currently conducting a phase II study on this candidate.

Denali’s wholly owned program, DNL310 or tividenofusp alfa, is an Enzyme Transport Vehicle-enabled iduronate-2-sulfatase (IDS) replacement therapy in development for MPS II (Hunter syndrome).

Denali recently initiated dosing in a global mid-stage study, BEACON, on BIIB122 (DNL151).

BIIB122, an investigational drug leucine-rich repeat kinase 2 (LRRK2) inhibitor, is being evaluated in participants with LRRK2-associated Parkinson’s disease (LRRK2-PD).

The phase IIa study will evaluate safety and biomarkers associated with oral daily dosing of BIIB122 in approximately 50 participants with Parkinson’s disease and LRRK2 pathogenic mutations confirmed by genetic testing.

BIIB122 is also being evaluated in the ongoing global phase IIb LUMA study in participants with early-stage Parkinson’s disease with or without an LRRK2 mutation in collaboration with Biogen BIIB.

The LUMA study is being conducted by Biogen. This study is expected to enroll approximately 640 participants with early-stage Parkinson’s disease, including eligible participants with LRRK2 mutations.

Denali also has multiple early-stage clinical and preclinical programs in its pipeline.

DNLI's Zacks Rank and Stock to Consider

Denali currently carries a Zacks Rank #4 (Sell).

A better-ranked stock in the biotech sector is Immunocore Holdings plc IMCR, which currently sports a Zacks Rank #1 (Strong Buy). You can see the complete list of today’s Zacks #1 Rank stocks here.

In the past 60 days, estimates for Immunocore’s 2024 loss per share have narrowed from $1.18 to 94 cents. Loss per share estimates for 2025 have narrowed from $1.70 to $1.57 during the same time frame.

IMCR’s earnings beat estimates in two of the trailing four quarters and missed the same on the remaining two occasions, the average surprise being 25.57%.

 

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