Release Details
Denali Therapeutics Reports Third Quarter 2024 Financial Results and Business Highlights
"As leaders in pioneering a new class of therapeutics that cross the blood-brain barrier, we are making significant progress across our Transport Vehicle (TV)-enabled portfolio,” said
Third Quarter 2024 and Recent Program Updates
Late-stage and mid-stage clinical programs
Tividenofusp alfa (DNL310): Enzyme Transport Vehicle (ETV)-enabled, iduronate-2-sulfatase (IDS) replacement therapy in development for MPS II (Hunter syndrome)
- In September, announced the outcome of a successful meeting with the
Center for Drug Evaluation and Research (CDER) of theU.S. Food and Drug Administration (FDA) providing a path to filing a biologics license application (BLA) for accelerated approval and subsequent conversion to full approval for tividenofusp alfa (DNL310) for the treatment of MPS II. Agreement was reached that cerebrospinal fluid heparan sulfate (CSF HS) is reasonably likely to predict clinical benefit and can be used as a surrogate endpoint to support accelerated approval for tividenofusp alfa in MPS II. Denali intends to submit the BLA under the accelerated approval pathway in early 2025. - In September, presented new interim data from the Phase 1/2 study at the
Society for the Study of Inborn Errors of Metabolism (SSIEM 2024), including data from additional study participants (N=37) and longer duration of treatment with tividenofusp alfa (up to Week 129) as well as new analyses on biomarkers and clinical outcomes. - COMPASS, the global Phase 2/3 study, is expected to complete enrollment in 2024.
DNL343: eIF2B activator in development for the treatment of amyotrophic lateral sclerosis (ALS)
- DNL343 is being evaluated in Regimen G (DNL343) of the Phase 2/3 HEALEY ALS Platform Trial conducted by the Sean M. Healey &
AMG Center for ALS atMassachusetts General Hospital (MGH) in collaboration with theNortheast ALS Consortium (NEALS). Enrollment in Regimen G is complete.
- In October, Denali was informed by its strategic partner Sanofi that the K2 Phase 2 study evaluating the safety and efficacy of oditrasertib (
SAR443820 /DNL788) on serum neurofilament light chain levels in participants with multiple sclerosis was discontinued based on not meeting the primary and key secondary endpoints.
BIIB122/DNL151: LRRK2 inhibitor in development for the treatment of Parkinson’s disease (PD)
- Biogen is conducting the ongoing global Phase 2b LUMA study of BIIB122 in participants with early-stage Parkinson’s disease.
- Denali has initiated screening of participants for the global Phase 2a study to evaluate safety and biomarkers associated with BIIB122 in participants with Parkinson’s disease and confirmed pathogenic variants of LRRK2. This study is being funded under the Collaboration and Development Funding Agreement with a third party.
Eclitasertib (
- Sanofi is conducting the ongoing Phase 2 study of
SAR443122 /DNL758 in participants with UC.
Early-stage clinical and preclinical programs
DNL126: ETV-enabled N-sulfoglucosamine sulfohydrolase (SGSH) replacement therapy in development for the treatment of MPS IIIA (Sanfilippo syndrome Type A)
- Denali today announced that preliminary data from up to 25 weeks of dosing in the ongoing open-label Phase 1/2 study in MPS IIIA participants demonstrate a significant reduction in CSF HS levels from baseline, including normalization. The safety profile supports continued development. The most frequent treatment emergent adverse events were infusion related reactions of mild and moderate severity in all participants. There was one serious adverse event considered by the investigator not related to drug. Denali plans to present the data at a future medical meeting.
- Based on the preliminary Phase 1/2 results and a positive regulatory environment, Denali recently expanded the study and continues to assess the development plans including an accelerated approval path.
- DNL126 was selected in
June 2024 for theFDA's Support for clinical Trials Advancing Rare disease Therapeutics (START) program to accelerate the development of rare disease therapeutics, and collaborative engagement has commenced to support progress to a pre-BLA meeting.
TAK-594/DNL593: Protein Transport Vehicle (PTV)-enabled progranulin (PGRN) replacement therapy in development for the treatment of frontotemporal dementia-granulin (FTD-GRN)
- Screening of participants for Cohort B2 in the Phase 1/2 study is ongoing.
Oligonucleotide Transport Vehicle (OTV) platform
- Denali is advancing OTV:MAPT, targeting tau for Alzheimer’s disease, and OTV:SNCA, targeting alpha-synuclein for Parkinson’s disease, in the investigational new drug (IND)-enabling stage of development.
- In August, announced publication of nonclinical data in the
August 14, 2024 issue of Science Translational Medicine (link) demonstrating the ability of the OTV platform to achieve broad biodistribution of antisense oligonucleotides (ASOs) in the central nervous system and skeletal and cardiac muscle following intravenous administration.
Antibody Transport Vehicle Amyloid beta (ATV:Abeta) program
- Denali is working to develop the next generation of anti-amyloid beta therapeutics with ATV:Abeta, which is designed to increase exposure of the therapeutic antibody and achieve broad biodistribution in the brain with the potential for improved efficacy and safety. Preclinical data demonstrated potential for a wider therapeutic window compared to a standard antibody, with superior plaque decoration and reduction and very low rates of amyloid related imaging abnormalities (ARIA). These data are included in a manuscript posted on bioRxiv (link).
- Denali plans to advance a TfR-targeting ATV:Abeta molecule as well as a CD98hc-targeting ATV:Abeta molecule into development for Alzheimer's disease.
Discovery programs
Denali applies its deep scientific expertise in neurodegeneration biology and the BBB to discover and develop medicines and platforms with the focus on programs enabled by the TV technology and targeting neurodegenerative disease, including Alzheimer’s and Parkinson’s, and lysosomal storage diseases.
2024 Guidance on Operating Expenses
Cash, cash equivalents, and marketable securities were approximately
Participation in Upcoming Investor Conferences
UBS Global Healthcare Conference ,November 11-14 - B. Riley Securities’ Next-Gen Tissue Delivery Modalities Virtual Summit,
November 14 - Stifel 2024 Healthcare Conference,
November 18-19 Jefferies London Healthcare Conference ,November 19-21 - 7th Annual
Evercore ISI HealthCONx Conference ,December 3-5
Third Quarter 2024 Financial Results
Net losses were
There was no collaboration revenue for the quarter ended
Total research and development expenses were
General and administrative expenses were
About
Cautionary Note Regarding Forward-Looking Statements
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements expressed or implied in this press release include, but are not limited to, statements regarding expectations regarding Denali’s TV technology platform; statements made by Denali’s Chief Executive Officer; plans, timelines, and expectations regarding DNL310 and the ongoing Phase 2/3 COMPASS and Phase 1/2 studies, the timing and likelihood of accelerated approval, and the timing and availability of program updates; plans and timelines regarding DNL343, including the timing and availability of data from the Phase 2/3 HEALEY ALS Platform Trial; plans, timelines, and expectations of both Denali and Sanofi regarding DNL788; plans, timelines, and expectations regarding DNL151, including with respect to the ongoing LUMA study as well as enrollment and timing of the proposed Phase 2a study in PD patients with LRRK2 mutations; expectations regarding DNL758, including the ongoing Phase 2 study in patients with UC; plans, timelines, and expectations related to DNL126, including the timing and availability of data in the ongoing Phase 1/2 study and the timing and likelihood of regulatory approval; plans, timelines, and expectations of both Denali and Takeda regarding DNL593 and the ongoing Phase 1/2 study; plans, timelines, and expectations regarding the advancement of OTV:MAPT and OTV:SNCA towards clinical development; plans, timelines, and expectations regarding the ATV:Abeta program, including its therapeutic potential and the clinical advancement of ATV:Abeta molecules; plans and expectations for Denali's preclinical programs; Denali's future operating expenses and anticipated cash runway; and Denali's participation in upcoming investor conferences. All drugs currently being developed by Denali are investigational and have not received regulatory approval for any indication. Actual results are subject to risks and uncertainties and may differ materially from those indicated by these forward-looking statements as a result of these risks and uncertainties, including but not limited to, risks related to: any and all risks to Denali’s business and operations caused by adverse economic conditions; risk of the occurrence of any event, change, or other circumstance that could give rise to the termination of Denali’s agreements with Sanofi, Takeda, or Biogen, or any of Denali’s other collaboration agreements; Denali’s transition to a late-stage clinical drug development company; Denali’s and its collaborators’ ability to complete the development and, if approved, commercialization of its product candidates; Denali’s and its collaborators’ ability to enroll patients in its ongoing and future clinical trials; Denali’s reliance on third parties for the manufacture and supply of its product candidates for clinical trials; Denali’s dependence on successful development of its blood-brain barrier platform technology and its programs and product candidates; Denali’s and its collaborators' ability to conduct or complete clinical trials on expected timelines; the risk that preclinical profiles of Denali’s product candidates may not translate in clinical trials; the potential for clinical trials to differ from preclinical, early clinical, preliminary or expected results; the risk of significant adverse events, toxicities or other undesirable side effects; the uncertainty that product candidates will receive regulatory approval necessary to be commercialized; Denali’s ability to continue to create a pipeline of product candidates or develop commercially successful products; developments relating to Denali's competitors and its industry, including competing product candidates and therapies; Denali’s ability to obtain, maintain, or protect intellectual property rights related to its product candidates; implementation of Denali’s strategic plans for its business, product candidates, and blood-brain barrier platform technology; Denali's ability to obtain additional capital to finance its operations, as needed; Denali's ability to accurately forecast future financial results in the current environment; and other risks and uncertainties, including those described in Denali's most recent Annual and Quarterly Reports on Forms 10-K and 10-Q filed with the
Condensed Consolidated Statements of Operations
(Unaudited)
(In thousands, except share and per share amounts)
| Three Months Ended |
Nine Months Ended |
||||||||||||||
| 2024 | 2023 | 2024 | 2023 | ||||||||||||
| Collaboration revenue: | |||||||||||||||
| Collaboration revenue from customers(1) | $ | — | $ | 1,267 | $ | — | $ | 330,531 | |||||||
| Other collaboration revenue | — | — | — | — | |||||||||||
| Total collaboration revenue | — | 1,267 | — | 330,531 | |||||||||||
| Operating expenses: | |||||||||||||||
| Research and development(2) | 98,238 | 89,737 | 296,653 | 316,073 | |||||||||||
| General and administrative | 24,949 | 25,325 | 75,379 | 78,585 | |||||||||||
| Total operating expenses | 123,187 | 115,062 | 372,032 | 394,658 | |||||||||||
| Gain from divestiture of small molecule programs | — | — | 14,537 | — | |||||||||||
| Loss from operations | (123,187 | ) | (113,795 | ) | (357,495 | ) | (64,127 | ) | |||||||
| Interest and other income, net | 15,995 | 14,442 | 49,475 | 38,376 | |||||||||||
| Net loss | $ | (107,192 | ) | $ | (99,353 | ) | $ | (308,020 | ) | $ | (25,751 | ) | |||
| Net loss per share, basic and diluted | $ | (0.63 | ) | $ | (0.72 | ) | $ | (1.89 | ) | $ | (0.19 | ) | |||
| Weighted average number of shares outstanding, basic and diluted | 169,456,988 | 137,644,534 | 162,589,325 | 137,076,199 | |||||||||||
__________________________________________________
(1) Includes related-party collaboration revenue from customers of
(2) Includes expenses for cost sharing payments due to a related party of
Condensed Consolidated Balance Sheets
(Unaudited)
(In thousands)
| Assets | |||||
| Current assets: | |||||
| Cash and cash equivalents | $ | 90,636 | $ | 127,106 | |
| Short-term marketable securities | 745,923 | 907,405 | |||
| Prepaid expenses and other current assets | 32,280 | 29,626 | |||
| Total current assets | 868,839 | 1,064,137 | |||
| Long-term marketable securities | 445,463 | — | |||
| Property and equipment, net | 50,822 | 45,589 | |||
| Operating lease right-of-use asset | 23,717 | 26,048 | |||
| Finance lease right-of-use asset | 38,685 | — | |||
| Other non-current assets | 26,487 | 18,143 | |||
| Total assets | $ | 1,454,013 | $ | 1,153,917 | |
| Liabilities and stockholders' equity | |||||
| Current liabilities: | |||||
| Accounts payable | $ | 9,594 | $ | 9,483 | |
| Accrued clinical and other research & development costs | 23,923 | 19,035 | |||
| Accrued manufacturing costs | 9,568 | 15,462 | |||
| Accrued compensation | 14,874 | 21,590 | |||
| Operating lease liability, current | 8,036 | 7,260 | |||
| Deferred research and development funding liability, current | 16,269 | — | |||
| Other accrued costs and current liabilities | 4,829 | 5,152 | |||
| Total current liabilities | 87,093 | 77,982 | |||
| Operating lease liability, less current portion | 38,850 | 44,981 | |||
| Finance lease liability, less current portion | 5,631 | — | |||
| Deferred research funding and development liability, less current portion | 3,944 | — | |||
| Total liabilities | 135,518 | 122,963 | |||
| Total stockholders' equity | 1,318,495 | 1,030,954 | |||
| Total liabilities and stockholders’ equity | $ | 1,454,013 | $ | 1,153,917 | |
Investor Contact:
Vice President, Investor Relations
hansen@dnli.com
(650) 452-2747
Media Contact:
FGS Global
Rich.Allan@fgsglobal.com
(503) 851-0807
Source: Denali Therapeutics Inc.