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Denali Stock Dips as Biogen-Partnered Parkinson's Disease Study Fails
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Key Takeaways
Denali and Biogen will stop BIIB122 development after a phase IIb Parkinson's study miss.
DNLI will continue the BEACON study in Parkinson's patients with pathogenic LRRK2 variants.
Avlayah FDA approval boosted Denali's outlook as pipeline and late-stage programs advance.
Shares of Denali Therapeutics, Inc. (DNLI - Free Report) were down 8% in after-market trading on May 21, after the company and partner Biogen (BIIB - Free Report) announced disappointing top-line results from a mid-stage study evaluating BIIB122 (DNL151) in individuals with early-stage Parkinson’s disease.
The study did not meet its primary or secondary endpoints.
Consequently, Biogen and Denali will discontinue development of BIIB122 in idiopathic Parkinson’s disease.
More on BIIB & DNLI’s Parkinson’s Study
LUMA was a phase IIb, multicenter, randomized, double-blind, placebo-controlled trial evaluating the safety and efficacy of BIIB122 in 648 patients aged 30 to 80 with early-stage Parkinson’s disease. The study was led by Biogen.
Participants received either BIIB122 or placebo for at least 48 weeks and up to 144 weeks. The study enrolled patients both with and without pathogenic LRRK2 variants and was designed to assess whether LRRK2 inhibition could target the underlying biology of Parkinson’s disease.
The study results showed that BIIB122 failed to slow the progression of Parkinson’s disease compared with placebo, missing the primary endpoint of time to confirmed worsening on the modified MDS-UPDRS Part II and III combined score. The study also failed to demonstrate meaningful benefit across secondary endpoints.
However, exploratory biomarker analyses demonstrated more than 90% inhibition of peripheral LRRK2 kinase activity and up to a 30% reduction in phosphorylated Rab10, a CSF biomarker of LRRK2 activity, in a sub-study. BIIB122 maintained expected concentrations in both blood and CSF throughout the trial and was generally well tolerated with an acceptable safety profile.
Following these findings, Biogen and Denali plan to discontinue development of BIIB122 for idiopathic Parkinson’s disease. Nonetheless, Denali will continue independently advancing the phase IIa BEACON study on evaluating the small molecule inhibitor in patients carrying pathogenic LRRK2 variants.
Data from the BEACON study is expected in the first half of 2027. The trial is being led by Denali and funded through a Collaboration and Development Funding Agreement with a third party.
Road Ahead for Denali
In October 2020, the company entered into collaboration agreements with Biogen covering co-development and co-commercialization of its LRRK2 inhibitor program, along with options for select TransportVehicle (TV)-based programs, including an amyloid beta program. The agreements were later amended in August 2023 and July 2024.
The disappointing results for the LUMA study cloud the successful development of this program.
Shares of DNLI have gained 10.6% year to date while the industry’s price movement remained flat.
Image Source: Zacks Investment Research
In late March, Denali secured a major regulatory win with the FDA approval of lead pipeline candidate tividenofusp alfa-eknm, under the brand name Avlayah, for the treatment of Hunter Syndrome (MPS II). The FDA granted accelerated approval to Avlayah, marking the first new treatment option in nearly 20 years for patients with Hunter syndrome, a rare lysosomal storage disorder.
The approval for Avlayah has significantly boosted DNLI’s growth prospects.
Denali is evaluating DNL126 for the treatment of Sanfilippo syndrome type A (MPS IIIA). It is an investigational intravenously administered ETV-enabled SGSH replacement therapy, being developed to target the neurological and systemic manifestations of the disease by delivering the enzyme to both the brain and body.
Per DNLI, the phase I/II MPS IIIA study is ongoing, while start-up activities for a global phase III confirmatory study for this indication are also underway. A regulatory submission with potential accelerated approval is anticipated in 2027.
Denali has also collaborated with other pharma giants like Sanofi (SNY - Free Report) and Takeda (TAK - Free Report) to develop other candidates. Partner Sanofi is developing eclitasertib for moderate to severe ulcerative colitis.
In April 2026, Denali announced that partner Takeda had decided to terminate their collaboration for DNL593 (PTV:PGRN) in frontotemporal dementia associated with GRN mutations (FTD-GRN).
The termination, effective 60 days after notice, will return full rights to the program to Denali. Per DNLI, Takeda’s decision was based on strategic priorities and not on any efficacy or safety issues.
The company’s sound cash position is a positive and underscores its ability to fund ongoing programs.
View the Zacks #1 Rank List
Image: Bigstock
Denali Stock Dips as Biogen-Partnered Parkinson's Disease Study Fails
Key Takeaways
Shares of Denali Therapeutics, Inc. (DNLI - Free Report) were down 8% in after-market trading on May 21, after the company and partner Biogen (BIIB - Free Report) announced disappointing top-line results from a mid-stage study evaluating BIIB122 (DNL151) in individuals with early-stage Parkinson’s disease.
The study did not meet its primary or secondary endpoints.
Consequently, Biogen and Denali will discontinue development of BIIB122 in idiopathic Parkinson’s disease.
More on BIIB & DNLI’s Parkinson’s Study
LUMA was a phase IIb, multicenter, randomized, double-blind, placebo-controlled trial evaluating the safety and efficacy of BIIB122 in 648 patients aged 30 to 80 with early-stage Parkinson’s disease. The study was led by Biogen.
Participants received either BIIB122 or placebo for at least 48 weeks and up to 144 weeks. The study enrolled patients both with and without pathogenic LRRK2 variants and was designed to assess whether LRRK2 inhibition could target the underlying biology of Parkinson’s disease.
The study results showed that BIIB122 failed to slow the progression of Parkinson’s disease compared with placebo, missing the primary endpoint of time to confirmed worsening on the modified MDS-UPDRS Part II and III combined score. The study also failed to demonstrate meaningful benefit across secondary endpoints.
However, exploratory biomarker analyses demonstrated more than 90% inhibition of peripheral LRRK2 kinase activity and up to a 30% reduction in phosphorylated Rab10, a CSF biomarker of LRRK2 activity, in a sub-study. BIIB122 maintained expected concentrations in both blood and CSF throughout the trial and was generally well tolerated with an acceptable safety profile.
Following these findings, Biogen and Denali plan to discontinue development of BIIB122 for idiopathic Parkinson’s disease.
Nonetheless, Denali will continue independently advancing the phase IIa BEACON study on evaluating the small molecule inhibitor in patients carrying pathogenic LRRK2 variants.
Data from the BEACON study is expected in the first half of 2027. The trial is being led by Denali and funded through a Collaboration and Development Funding Agreement with a third party.
Road Ahead for Denali
In October 2020, the company entered into collaboration agreements with Biogen covering co-development and co-commercialization of its LRRK2 inhibitor program, along with options for select TransportVehicle (TV)-based programs, including an amyloid beta program. The agreements were later amended in August 2023 and July 2024.
The disappointing results for the LUMA study cloud the successful development of this program.
Shares of DNLI have gained 10.6% year to date while the industry’s price movement remained flat.
Image Source: Zacks Investment Research
In late March, Denali secured a major regulatory win with the FDA approval of lead pipeline candidate tividenofusp alfa-eknm, under the brand name Avlayah, for the treatment of Hunter Syndrome (MPS II). The FDA granted accelerated approval to Avlayah, marking the first new treatment option in nearly 20 years for patients with Hunter syndrome, a rare lysosomal storage disorder.
The approval for Avlayah has significantly boosted DNLI’s growth prospects.
Denali is evaluating DNL126 for the treatment of Sanfilippo syndrome type A (MPS IIIA). It is an investigational intravenously administered ETV-enabled SGSH replacement therapy, being developed to target the neurological and systemic manifestations of the disease by delivering the enzyme to both the brain and body.
Per DNLI, the phase I/II MPS IIIA study is ongoing, while start-up activities for a global phase III confirmatory study for this indication are also underway. A regulatory submission with potential accelerated approval is anticipated in 2027.
Denali has also collaborated with other pharma giants like Sanofi (SNY - Free Report) and Takeda (TAK - Free Report) to develop other candidates. Partner Sanofi is developing eclitasertib for moderate to severe ulcerative colitis.
In April 2026, Denali announced that partner Takeda had decided to terminate their collaboration for DNL593 (PTV:PGRN) in frontotemporal dementia associated with GRN mutations (FTD-GRN).
The termination, effective 60 days after notice, will return full rights to the program to Denali. Per DNLI, Takeda’s decision was based on strategic priorities and not on any efficacy or safety issues.
The company’s sound cash position is a positive and underscores its ability to fund ongoing programs.
DNLI’s Zacks Rank
Denali currently carries a Zacks Rank #3 (Hold). You can see the complete list of today’s Zacks #1 Rank (Strong Buy) stocks here.