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DENALI Denali Therapeutics Reports First Quarter 2021 Financial Results and Business Highlights May 3 , 2021 12:30 PM PDT SOUTH SAN FRANCISCO , Calif . , May 03 , 2021 ( GLOBE NEWSWIRE ) -- Denali Therapeutics Inc. ( NASDAQ : DNLI ) , a biopharmaceutical company developing a broad portfolio of product candidates engineered to cross the blood - brain barrier ( BBB ) for neurodegenerative diseases , today reported financial results for the first quarter ended March 31 , 2021 , and provided business highlights . " Our programs have reached a number of exciting milestones so far this year across our broad portfolio of targeted therapeutics for neurodegenerative diseases , " said Ryan Watts , Ph.D. , Denali's Chief Executive Officer . " We remain focused on advancing our lead clinical programs including DNL310 for Hunter syndrome , DNL151 ( BIIB122 ) in collaboration with Biogen for Parkinson's disease , and DNL343 for amyotrophic lateral sclerosis ( ALS ) . In addition , based on human biomarker proof of concept achieved with DNL310 , we see significant potential in using our Transport Vehicle ( TV ) technology to create new , effective biologic therapeutics previously not possible due to limitations posed by the blood - brain barrier , and we continue to rigorously advance additional TV - enabled programs towards the clinic . " Recent Business Highlights Achieved clinical and regulatory milestones with DNL310 : In February 2021 , Denali reported three - month data from Cohort A ( n = 5 ) in a Phase 1/2 study of DNL310 , Denali's lead TV - enabled brain - penetrant enzyme replacement therapy , in patients with Hunter syndrome ( MPS II ) . The data showed that DNL310 treatment resulted in normalization of glycosaminoglycan ( GAG ) levels in cerebrospinal fluid and a safety and tolerability profile consistent with standard of care enzyme replacement therapy . In March 2021 , Denali announced that the U.S. Food and Drug Administration ( FDA ) granted Fast Track designation to DNL310 for the treatment of patients with Hunter syndrome . Denali plans to report six - month data from Cohort A in mid - 2021 at a medical conference . Met safety and biomarker goals in DNL151 ( BIIB122 ) Phase 1 / 1b studies : In May 2021 , Denali presented results from two studies of its small molecule LRRK2 inhibitor , DNL151 ( BIIB122 ) , a Phase 1 study in healthy volunteers and a Phase 1b study in patients with Parkinson's disease , at the International Association of Parkinsonism and Related Disorders Virtual Congress held on May 1-4 . DNL 151 ( BIIB122 ) was generally well tolerated , and target engagement and pathway engagement biomarker goals were met . Denali and Biogen plan to initiate late - stage clinical development of DNL151 ( BIIB122 ) in patients with Parkinson's disease by year - end 2021 . Met safety and pathway engagement biomarker goals in DNL343 Phase 1 healthy volunteer study : Based on interim data from the ongoing Phase 1 single- and multiple - ascending - dose study of Denali's small molecule EIF2B activator , DNL343 , in healthy volunteers , safety and pathway engagement biomarker goals of the study were met . A maximum tolerated dose was not reached , and an additional multiple dose cohort has been added to the study to further explore the therapeutic window . Based on these data , Denali plans to initiate a Phase 1b study in patients with ALS in the second half of 2021 . DNL758 ( SAR443122 ) advancing into Phase 2 study for cutaneous lupus erythematosus ( CLE ) : In February 2021 , Denali announced its partner Sanofi's decision , upon completion of a Phase 1b study in hospitalized adult patients with severe COVID - 19 lung disease , to cease further development of DNL758 ( SAR443122 ) , a peripherally - restricted small molecule inhibitor of RIPK1 , in COVID - 19 based on the rapidly evolving landscape of treatment and prevention options for COVID - 19 . Although the Phase 1b study did not meet its primary endpoint , DNL758 ( SAR443122 ) was generally well tolerated and did generate positive signals of relevant biological effect . Sanofi plans to commence dosing in a Phase 2 study of DNL758 ( SAR443122 ) in CLE patients in the first half of 2021 . Summary Table of Upcoming 2021 Expected Key Milestones Timing 1H 2021 Mid 2021 2H 2021 2H 2021 Late 2021 Investigational Drug Candidate RIPK1 inhibitor ( DNL758 / SAR443122 ) ETV : IDS ( DNL310 ) EIF2B activator ( DNL343 ) RIPK1 inhibitor | ( DNL788 / SAR443820 ) LRRK2 inhibitor ( DNL151 / BIIB122 ) Therapeutic Area Expected Milestone CLE Hunter syndrome ( MPS II ) ALS , FTD ALS , Alzheimer's disease , MS Parkinson's disease Commence dosing in Phase 2 study in CLE patients ( Sanofi ) 6 - month data from Cohort A of Phase 1/2 study Initiate Phase 1b study in ALS patients Phase 1 data in healthy volunteers ( Sanofi ) Initiate late - stage clinical development in Parkinson's patients