Denali(DNLI) - 2023 Q4 - Annual Results

Executive Summary & Business Highlights This section summarizes Denali's 2023 achievements, 2024 outlook, pipeline updates, corporate strategy, and financial guidance CEO Statement & 2024 Outlook CEO highlighted 2023 portfolio progress and TV platform validation, with 2024 goals for trial completion and commercial readiness - 2023 achievements include significant progress across the broad therapeutic portfolio and further clinical validation of the BBB-crossing Transport Vehicle (TV) platform[2] - 2024 goals include completing enrollment of late-stage trials in MPS II and ALS, establishing commercial readiness for initial programs, and expanding the TV-enabled portfolio to address large neurodegenerative diseases with enzymes, antibodies, and oligonucleotides[2] Program Updates Denali updated its clinical and preclinical pipeline, detailing late-stage trial progress, new funding, and TV platform advancements Late-stage and Mid-stage Clinical Programs Updates on Denali's late-stage and mid-stage clinical programs for MPS II, ALS, MS, Parkinson's, and UC are presented - Tividenofusp alfa (DNL310) for MPS II (Hunter syndrome): Presented additional interim data from the open-label, single-arm Phase 1/2 study at 2024 WORLDSymposium, showing improvement and stabilization in adaptive behavior, cognition, hearing, and growth trajectory out to 104 weeks. Robust and sustained responses in neuronal health and peripheral activity biomarkers were observed[3][4] - Enrollment continues in the global Phase 2/3 COMPASS study and is expected to be completed in 2024[3] - DNL343 for ALS: Enrollment continues in Regimen G of the Phase 2/3 HEALEY ALS Platform Trial and is expected to be completed in 2024[3] - SAR443820/DNL788 (CNS-penetrant RIPK1 inhibitor) for MS/ALS: The Phase 2 HIMALAYA study in ALS did not meet the primary endpoint of change in ALS Functional Rating Scale-Revised (ALSFRS-R)[3][4] - Sanofi is evaluating SAR443820/DNL788 in another Phase 2 clinical trial in participants with MS, and the outcome of the HIMALAYA study has no impact on the ongoing MS study[3][4] - BIIB122/DNL151 (LRRK2 inhibitor) for Parkinson's disease (PD): Executed a Collaboration and Development Funding Agreement in January 2024 with a third party for a global Phase 2a study, with committed funding of $75.0 million ($12.5 million received in January 2024)[5] - Denali plans to solely operationalize the Phase 2a study to evaluate safety and biomarkers in PD participants with confirmed pathogenic variants of LRRK2[5] - Biogen will continue to conduct the ongoing global Phase 2b LUMA study in early-stage PD; Denali and Biogen will co-commercialize upon regulatory approval[5] - Eclitasertib (SAR443122/DNL758) (Peripheral RIPK1 inhibitor) for Ulcerative Colitis (UC): Sanofi is conducting the Phase 2 trial[5] Early-stage Clinical and Preclinical Programs Updates on Denali's early-stage clinical and preclinical programs for MPS IIIA and FTD-GRN are presented - DNL126 (ETV-enabled SGSH replacement therapy) for MPS IIIA (Sanfilippo syndrome Type A): Initiated dosing in the Phase 1/2 study; biomarker proof of concept and safety data are expected by the end of 2024[6][9] - Preclinical data demonstrated DNL126 improves lysosomal and microglial morphology, neurodegeneration, and cognitive function in adult MPS IIIA mice[6][9] - TAK-594/DNL593 (PTV-enabled progranulin replacement therapy) for FTD-GRN: Part B has been voluntarily paused in the Phase 1/2 study to implement protocol modifications, and is expected to resume this year[6] Transport Vehicle (TV) Platform & Discovery Programs Advancements in Denali's TV platforms, including OTV, ATV:Abeta, and the novel CD98hc-targeting TV platform, are presented - Oligonucleotide Transport Vehicle (OTV) platform: Announced two lead OTV programs in the IND-enabling stage: OTV:MAPT targeting tau for Alzheimer's disease and OTV:SNCA targeting alpha-synuclein for Parkinson's disease[7] - Antibody Transport Vehicle Amyloid beta (ATV:Abeta) program: Licensed by Biogen and is in the IND-enabling stage of development[8][10] - Preclinical data showed superior amyloid plaque binding and reduction compared to a conventional Abeta antibody and the potential to reduce the risk of amyloid-related imaging abnormalities (ARIA)[8][10] - CD98hc-targeting TV platform: Announced as a second TV platform, targeting CD98 heavy chain, an amino acid transporter expressed at the BBB, offering distinct properties from Denali's TfR-targeting TV platform[8] Corporate Updates & Strategic Initiatives Denali completed a $500 million PIPE financing to extend its cash runway and plans to spin out its preclinical small molecule portfolio - PIPE Financing: Entered into a securities purchase agreement for a private investment in public equity (PIPE) financing, issuing 3,244,689 shares of common stock and 26,046,065 pre-funded warrants at $17.07 and $17.06 per share/warrant, respectively[9] - Anticipates gross proceeds of approximately $500 million[9] - Preclinical Small Molecule Portfolio Spin-out: Announced the intention to spin out the company's preclinical small molecule portfolio[11] - Decision based on clinical validation and prioritization of Denali's TV-enabled platforms for brain delivery of large molecules, while maintaining current clinical stage small molecule programs[11] 2024 Financial Guidance & Cash Runway Denali anticipates 2024 operating expenses to be less than or equal to 2023, with PIPE financing extending its cash runway into 2028 - Cash, cash equivalents, and marketable securities were approximately $1.03 billion as of December 31, 2023[12] - For the full year 2024, operating expenses are anticipated to be less than or equal to those in 2023, based on portfolio prioritization[12] - With anticipated proceeds from the PIPE financing, the company's cash runway is expected to extend into 2028[12] Investor Conferences Denali announced participation in several investor conferences in March 2024, including Cowen, Leerink, Jefferies, and Stifel events - Upcoming participation in investor conferences: Cowen 44th Annual Health Care Conference (March 4-6), Leerink Global Biopharma Conference (March 11-13), Jefferies Biotech on the Bay Summit (March 12-13), and Stifel 2023 CNS Days (March 19-20)[15] Financial Performance (Q4 and Full Year 2023) Denali's Q4 and full year 2023 financial performance is reviewed, covering net loss, collaboration revenue, operating expenses, and liquidity Overview of Net Loss Denali reported an increased net loss for Q4 2023 but a significant reduction for full year 2023, driven by higher collaboration revenue Net Loss (in millions) | Metric | Q4 2023 | Q4 2022 | YoY Change (Q4) | FY 2023 | FY 2022 | YoY Change (FY) | | :----------------- | :------ | :------ | :---------------- | :------ | :------ | :---------------- | | Net Loss | $(119.5) | $(98.7) | $(20.8) | $(145.2) | $(326.0) | $180.8 | Collaboration Revenue Q4 2023 collaboration revenue was zero due to milestone timing, while full-year 2023 revenue significantly increased, driven by a Biogen payment Collaboration Revenue (in millions) | Metric | Q4 2023 | Q4 2022 | YoY Change (Q4) | FY 2023 | FY 2022 | YoY Change (FY) | | :------------------- | :------ | :------ | :---------------- | :------ | :------ | :---------------- | | Collaboration Revenue | $0 | $10.3 | $(10.3) | $330.5 | $108.5 | $222.0 | - The Q4 2023 decrease was primarily due to a $10.0 million decrease in revenue earned under the Sanofi Collaboration for a milestone triggered in December 2022[14] - The FY 2023 increase was primarily due to $293.9 million in revenue recognized in April 2023 under the Biogen Collaboration Agreement as a result of Biogen exercising its option to license the ATV:Abeta program, partially offset by decreases from Takeda ($41.9 million) and Sanofi ($28.4 million) due to timing of activities and milestones[14] Operating Expenses Total operating expenses increased in Q4 and full year 2023, driven by higher R&D costs from clinical trial progress and increased headcount, and rising G&A expenses Research and Development Expenses R&D expenses increased in Q4 and full year 2023, primarily due to clinical trial progress, higher headcount, and a shift in net cost sharing Research and Development Expenses (in millions) | Metric | Q4 2023 | Q4 2022 | YoY Change (Q4) | FY 2023 | FY 2022 | YoY Change (FY) | | :----------------------- | :------ | :------ | :---------------- | :------ | :------ | :---------------- | | Research and Development | $107.8 | $92.1 | $15.7 | $423.9 | $358.7 | $65.2 | - Increases were primarily attributable to: increases in ETV:IDS and eIF2B program external expenses reflecting continued clinical trial progress; an increase in personnel-related expenses due to higher headcount; and a shift in net cost sharing from reimbursements to payments[15] - These increases were partially offset by decreases in TV platform and other program external expenses, PTV:PGRN program external expenses, and LRRK2 program external expenses due to timing and transition of activities to Biogen[15] General and Administrative Expenses G&A expenses increased in Q4 and full year 2023, primarily due to higher personnel-related expenses and new facility costs General and Administrative Expenses (in millions) | Metric | Q4 2023 | Q4 2022 | YoY Change (Q4) | FY 2023 | FY 2022 | YoY Change (FY) | | :-------------------------- | :------ | :------ | :---------------- | :------ | :------ | :---------------- | | General and Administrative | $24.8 | $23.5 | $1.3 | $103.4 | $90.5 | $12.9 | - Increases were primarily attributable to an increase in personnel-related expenses, including employee compensation and stock-based compensation expenses, driven by higher headcount and equity award grants. Additionally, there was an increase in facility and other corporate costs associated with the new Salt Lake City manufacturing facility[16] Liquidity and Capital Resources As of December 31, 2023, Denali maintained a strong liquidity position with approximately $1.03 billion in cash, cash equivalents, and marketable securities - Cash, cash equivalents, and marketable securities were approximately $1.03 billion as of December 31, 2023[17] Additional Information Background information on Denali Therapeutics and a cautionary note regarding forward-looking statements are provided About Denali Therapeutics Denali Therapeutics is a biopharmaceutical company developing BBB-crossing product candidates for neurodegenerative and lysosomal storage diseases, focusing on validated targets and biomarker-guided development - Denali Therapeutics is a biopharmaceutical company developing a broad portfolio of product candidates engineered to cross the blood-brain barrier (BBB) for the treatment of neurodegenerative diseases and lysosomal storage diseases[18] - The company's strategy involves rigorously assessing genetically validated targets, engineering delivery across the BBB, and guiding development through biomarkers that demonstrate target and pathway engagement[18] Cautionary Note Regarding Forward-Looking Statements This disclaimer indicates the press release contains forward-looking statements subject to risks and uncertainties, which could cause actual results to differ materially, and Denali does not undertake to update them - The press release contains forward-looking statements subject to risks and uncertainties, and actual results may differ materially from those indicated[20] - Risks include those related to clinical development, regulatory approval, collaborations, manufacturing, intellectual property rights, financing, and the ability to enroll patients or complete trials on expected timelines[20] - Denali does not undertake any obligation to update or revise any forward-looking statements, except as required by law[20] Condensed Consolidated Financial Statements This section presents the unaudited condensed consolidated statements of operations and balance sheets for the specified periods Statements of Operations This section presents the unaudited condensed consolidated statements of operations, detailing collaboration revenue, operating expenses, loss from operations, and net loss for Q4 and full year 2023 and 2022 Condensed Consolidated Statements of Operations (Unaudited, in thousands) | Metric | Three Months Ended Dec 31, 2023 | Three Months Ended Dec 31, 2022 | Twelve Months Ended Dec 31, 2023 | Twelve Months Ended Dec 31, 2022 | | :---------------------------------- | :------------------------------ | :------------------------------ | :------------------------------- | :------------------------------- | | Total collaboration revenue | $— | $10,283 | $330,531 | $108,463 | | Research and development | $107,803 | $92,111 | $423,876 | $358,732 | | General and administrative | $24,769 | $23,516 | $103,354 | $90,475 | | Total operating expenses | $132,572 | $115,627 | $527,230 | $449,207 | | Loss from operations | $(132,572) | $(105,344) | $(196,699) | $(340,744) | | Interest and other income, net | $13,129 | $6,660 | $51,505 | $14,774 | | Net loss | $(119,473) | $(98,678) | $(145,224) | $(325,991) | | Net loss per share, basic and diluted | $(0.86) | $(0.75) | $(1.06) | $(2.60) | Balance Sheets This section provides the unaudited condensed consolidated balance sheets, outlining Denali's assets, liabilities, and stockholders' equity as of December 31, 2023, and 2022 Condensed Consolidated Balance Sheets (Unaudited, in thousands) | Metric | December 31, 2023 | December 31, 2022 | | :-------------------------------------- | :------------------ | :------------------ | | Cash and cash equivalents | $127,106 | $218,044 | | Short-term marketable securities | $907,405 | $1,118,171 | | Total current assets | $1,064,137 | $1,372,319 | | Total assets | $1,153,917 | $1,460,242 | | Total current liabilities | $77,982 | $363,922 | | Total liabilities | $122,963 | $417,812 | | Total stockholders' equity | $1,030,954 | $1,042,430 |