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DENALI Denali Therapeutics Reports Second Quarter 2021 Financial Results and Business Highlights August 4 , 2021 8:01 PM PDT SOUTH SAN FRANCISCO , Calif . , Aug. 04 , 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 second quarter ended June 30 , 2021 , and provided business highlights . " We recently announced positive interim data from a Phase 1/2 study of DNL310 in Hunter syndrome , our lead Transport Vehicle ( TV ) -enabled program , showing rapid normalization of key disease - specific biomarkers in cerebrospinal fluid . This was observed even at low dose regimens , which is consistent with robust and efficient crossing of the blood - brain barrier by DNL310 , " said Ryan Watts , Ph.D. , Denali's Chief Executive Officer . " We are also encouraged by early indications that exploratory clinical measures improved in the first cohort of five patients . In parallel with expanding the ongoing Phase 1/2 study , we are now focused on finalizing the design for and commencing a pivotal Phase 2/3 study in the first half of 2022. Furthermore , we are making significant progress in advancing additional TV - enabled programs towards clinical development as well as our broader therapeutic portfolio . We are on track to initiate late - stage clinical development with our LRRK2 inhibitor DNL151 ( BIIB122 ) for Parkinson's disease in collaboration with Biogen by year end and to initiate a Phase 1b study with our EIF2B agonist DNL343 for amyotrophic lateral sclerosis ( ALS ) in the second half of this year . " Recent Business Highlights Reported positive interim data from the Phase 1/2 study of ETV : IDS ( DNL310 ) in patients with Hunter syndrome ( MPS II ) : In July 2021 , Denali announced longer - term safety data and 6 - month biomarker data on DNL310 from Cohort A in a Phase 1/2 study in patients with Hunter syndrome . The data demonstrated durability of effect with CNS impact , improved peripheral activity after switching from standard of care , and a safety profile consistent with standard of care enzyme replacement therapy . Furthermore , initial indications of improved clinical symptoms and function , assessed as exploratory endpoints , were reported by investigators and parents in all five patients enrolled in Cohort A. Denali also shared data from Cohort B , which is designed to inform dose selection ; exploratory biomarker data demonstrated activity of DNL310 across all dose regimens . Based on these data , Denali plans to begin enrolling Cohort C in the Phase 1/2 study to further investigate clinical endpoints and initiate a pivotal Phase 2/3 study of DNL310 in the first half of 2022 . Phase 2 study of DNL758 ( SAR443122 ) for cutaneous lupus erythematosus ( CLE ) initiated by Sanofi : In June 2021 , Denali announced that its partner Sanofi commenced dosing in a Phase 2 study of DNL758 , a peripherally - restricted small molecule inhibitor of RIPK1 , in patients with CLE . Denali and Sanofi entered into a broad collaboration agreement in October 2018 for the global development and commercialization of RIPK1 inhibitors . This includes peripherally restricted molecules such as DNL758 and CNS - penetrant molecules such as DNL788 ( SAR443820 ) , which is being evaluated in a Phase 1 study in healthy volunteers with potential development for neurological indications such as amyotrophic lateral sclerosis , multiple sclerosis and Alzheimer's disease . Under the collaboration agreement , Denali received a milestone payment of $ 15 million from Sanofi in July 2021 related to the initiation of the Phase 2 study with DNL758 . Sanofi is responsible for the development and commercialization and covers all costs of DNL758 . Denali is entitled to receive development , regulatory and sales milestone payments and royalties on product sales . 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 ) , in 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 . DNL151 ( 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 Parkinson's disease by year - end 2021 . Summary Table of Upcoming 2021 Expected Key Milestones Timing 2H 2021 2H 2021 Late 2021 Late 2021 Late 2021 / Early 2022 | Investigational Drug Candidate Therapeutic Area EIF2B activator ( DNL343 ) RIPK1 inhibitor ( DNL788 / SAR443820 ) LRRK2 inhibitor ( DNL151 / BIIB122 ) PTV : PGRN ( DNL593 ) ATV : TREM2 ( DNL919 ) ALS , FTD ALS , Alzheimer's disease , MS Parkinson's disease FTD Alzheimer's disease Expected Milestone Initiate Phase 1b study in ALS patients Phase 1 data in healthy volunteers ( Sanofi ) Initiate late - stage clinical development in Parkinson's patients File IND application or CTA File IND application or CTA