0001714899-25-000066 | 10-K | XBRL Viewer

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Defined Contribution Plan - Narrative (Details) - USD ($) $ in Millions	12 Months Ended
	Dec. 31, 2024	Dec. 31, 2023	Dec. 31, 2022
Retirement Benefits [Abstract]
Contribution expenses	$ 3.0	$ 3.2	$ 2.8

Marketable Securities - Summary of Available for Sale Securities (Details) $ in Thousands	Dec. 31, 2024 USD ($) security	Dec. 31, 2023 USD ($) security
Debt Securities, Available-for-sale [Line Items]
Amortized Cost	$ 1,014,372	$ 906,410
Unrealized Holding Gains	2,595	998
Unrealized Holding Losses	(223)	(3)
Aggregate Fair Value	1,016,744	907,405
Short-term marketable securities
Debt Securities, Available-for-sale [Line Items]
Amortized Cost	655,718
Unrealized Holding Gains	1,680
Unrealized Holding Losses	(27)
Aggregate Fair Value	657,371
Long-term marketable securities
Debt Securities, Available-for-sale [Line Items]
Amortized Cost	358,654
Unrealized Holding Gains	915
Unrealized Holding Losses	(196)
Aggregate Fair Value	359,373
U.S. government treasuries \| Short-term marketable securities
Debt Securities, Available-for-sale [Line Items]
Amortized Cost	627,809	868,174
Unrealized Holding Gains	1,618	998
Unrealized Holding Losses	(27)	0
Aggregate Fair Value	$ 629,400	$ 869,172
Number of securities held in unrealized holding loss positions \| security	3	2
Aggregate fair value, unrealized holding loss position	$ 64,000	$ 7,100
U.S. government treasuries \| Long-term marketable securities
Debt Securities, Available-for-sale [Line Items]
Amortized Cost	334,300
Unrealized Holding Gains	788
Unrealized Holding Losses	(196)
Aggregate Fair Value	$ 334,892
Number of securities held in unrealized holding loss positions \| security	4
Aggregate fair value, unrealized holding loss position	$ 114,000
U.S. government agency securities \| Short-term marketable securities
Debt Securities, Available-for-sale [Line Items]
Amortized Cost		7,089
Unrealized Holding Gains		0
Unrealized Holding Losses		(3)
Aggregate Fair Value		7,086
Corporate debt securities \| Short-term marketable securities
Debt Securities, Available-for-sale [Line Items]
Amortized Cost	21,337
Unrealized Holding Gains	62
Unrealized Holding Losses	0
Aggregate Fair Value	21,399
Corporate debt securities \| Long-term marketable securities
Debt Securities, Available-for-sale [Line Items]
Amortized Cost	24,354
Unrealized Holding Gains	127
Unrealized Holding Losses	0
Aggregate Fair Value	24,481
Commercial paper \| Short-term marketable securities
Debt Securities, Available-for-sale [Line Items]
Amortized Cost	6,572	31,147
Unrealized Holding Gains	0	0
Unrealized Holding Losses	0	0
Aggregate Fair Value	$ 6,572	$ 31,147

Fair Value Measurements - Schedule of Assets and Liabilities (Details) - USD ($) $ in Thousands	Dec. 31, 2024	Dec. 31, 2023
Assets:
Total	$ 1,143,472	$ 1,028,439
U.S. government treasuries
Assets:
Short-term marketable securities, fair value	629,400	869,172
Long-term marketable securities, fair value	334,892
U.S. government agency securities
Assets:
Short-term marketable securities, fair value		7,086
Corporate debt securities
Assets:
Short-term marketable securities, fair value	21,399
Long-term marketable securities, fair value	24,481
Commercial paper
Assets:
Short-term marketable securities, fair value	6,572	31,147
Money market funds
Assets:
Cash equivalents	126,728	121,034
Level 1
Assets:
Total	1,091,020	990,206
Level 1 \| U.S. government treasuries
Assets:
Short-term marketable securities, fair value	629,400	869,172
Long-term marketable securities, fair value	334,892
Level 1 \| U.S. government agency securities
Assets:
Short-term marketable securities, fair value		0
Level 1 \| Corporate debt securities
Assets:
Short-term marketable securities, fair value	0
Long-term marketable securities, fair value	0
Level 1 \| Commercial paper
Assets:
Short-term marketable securities, fair value	0	0
Level 1 \| Money market funds
Assets:
Cash equivalents	126,728	121,034
Level 2
Assets:
Total	52,452	38,233
Level 2 \| U.S. government treasuries
Assets:
Short-term marketable securities, fair value	0	0
Long-term marketable securities, fair value	0
Level 2 \| U.S. government agency securities
Assets:
Short-term marketable securities, fair value		7,086
Level 2 \| Corporate debt securities
Assets:
Short-term marketable securities, fair value	21,399
Long-term marketable securities, fair value	24,481
Level 2 \| Commercial paper
Assets:
Short-term marketable securities, fair value	6,572	31,147
Level 2 \| Money market funds
Assets:
Cash equivalents	0	0
Level 3
Assets:
Total	0	0
Level 3 \| U.S. government treasuries
Assets:
Short-term marketable securities, fair value	0	0
Long-term marketable securities, fair value	0
Level 3 \| U.S. government agency securities
Assets:
Short-term marketable securities, fair value		0
Level 3 \| Corporate debt securities
Assets:
Short-term marketable securities, fair value	0
Long-term marketable securities, fair value	0
Level 3 \| Commercial paper
Assets:
Short-term marketable securities, fair value	0	0
Level 3 \| Money market funds
Assets:
Cash equivalents	$ 0	$ 0

Fair Value Measurements

12 Months Ended

Dec. 31, 2024

Fair Value Disclosures [Abstract]

Fair Value Measurements

Assets and liabilities measured at fair value at each balance sheet date are as follows (in thousands):


	December 31, 2024
	Level 1		Level 2		Level 3		Total
Assets:
Cash equivalents:
Money market funds	$	126,728	$	—	$	—	$	126,728


Short-term marketable securities:
U.S. government treasuries	629,400		—		—		629,400

Corporate debt securities	—		21,399		—		21,399
Commercial paper	—		6,572		—		6,572
Long-term marketable securities:
U.S. government treasuries	334,892		—		—		334,892

Corporate debt securities	—		24,481		—		24,481

Total	$	1,091,020	$	52,452	$	—	$	1,143,472


	December 31, 2023
	Level 1		Level 2		Level 3		Total
Assets:
Cash equivalents
Money market funds	$	121,034	$	—	$	—	$	121,034


Short-term marketable securities:
U.S. government treasuries	869,172		—		—		869,172
U.S. government agency securities	—		7,086		—		7,086

Commercial paper	—		31,147		—		31,147





Total	$	990,206	$	38,233	$	—	$	1,028,439

The Company’s Level 2 securities are valued using third-party pricing sources. The pricing services utilize industry standard valuation models, including both income and market-based approaches, for which all significant inputs are observable, either directly or indirectly.

The Company did not transfer any assets or liabilities between the fair value measurement levels during the years ended December 31, 2024 or 2023.

- Definition

The entire disclosure for the fair value of financial instruments (as defined), including financial assets and financial liabilities (collectively, as defined), and the measurements of those instruments as well as disclosures related to the fair value of non-financial assets and liabilities. Such disclosures about the financial instruments, assets, and liabilities would include: (1) the fair value of the required items together with their carrying amounts (as appropriate); (2) for items for which it is not practicable to estimate fair value, disclosure would include: (a) information pertinent to estimating fair value (including, carrying amount, effective interest rate, and maturity, and (b) the reasons why it is not practicable to estimate fair value; (3) significant concentrations of credit risk including: (a) information about the activity, region, or economic characteristics identifying a concentration, (b) the maximum amount of loss the entity is exposed to based on the gross fair value of the related item, (c) policy for requiring collateral or other security and information as to accessing such collateral or security, and (d) the nature and brief description of such collateral or security; (4) quantitative information about market risks and how such risks are managed; (5) for items measured on both a recurring and nonrecurring basis information regarding the inputs used to develop the fair value measurement; and (6) for items presented in the financial statement for which fair value measurement is elected: (a) information necessary to understand the reasons for the election, (b) discussion of the effect of fair value changes on earnings, (c) a description of [similar groups] items for which the election is made and the relation thereof to the balance sheet, the aggregate carrying value of items included in the balance sheet that are not eligible for the election; (7) all other required (as defined) and desired information.

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+ Details

Consolidated Balance Sheets - USD ($) $ in Thousands	Dec. 31, 2024	Dec. 31, 2023
Current assets:
Cash and cash equivalents	$ 174,960	$ 127,106
Short-term marketable securities	657,371	907,405
Prepaid expenses and other current assets	32,105	29,626
Total current assets	864,436	1,064,137
Long-term marketable securities	359,373	0
Property and equipment, net	55,236	45,589
Finance lease right-of-use asset	47,533	0
Operating lease right-of-use asset	22,861	26,048
Other non-current assets	24,741	18,143
Total assets	1,374,180	1,153,917
Current liabilities:
Accounts payable	11,137	9,483
Accrued expenses and other current liabilities	91,071	68,499
Total current liabilities	102,208	77,982
Operating lease liability, less current portion	36,673	44,981
Finance lease liability, less current portion	5,615	0
Total liabilities	144,496	122,963
Commitments and contingencies (Note 7)
Stockholders’ equity:
Convertible preferred stock, $0.01 par value; 40,000,000 shares authorized as of December 31, 2024 and December 31, 2023; 0 shares issued and outstanding as of December 31, 2024 and December 31, 2023	0	0
Common stock, $0.01 par value; 400,000,000 shares authorized as of December 31, 2024 and December 31, 2023; 144,220,986 and 138,385,498 shares issued and outstanding as of December 31, 2024 and December 31, 2023, respectively	1,768	1,711
Additional paid-in capital	2,764,880	2,144,811
Accumulated other comprehensive income	2,020	643
Accumulated deficit	(1,538,984)	(1,116,211)
Total stockholders’ equity	1,229,684	1,030,954
Total liabilities and stockholders’ equity	$ 1,374,180	$ 1,153,917

Consolidated Statements of Stockholders' Equity - USD ($) $ in Thousands	Total	Common Stock	Additional Paid-in Capital	Accumulated Other Comprehensive Income (Loss)	Accumulated Deficit
Beginning balance (in shares) at Dec. 31, 2021		122,283,305
Beginning balance at Dec. 31, 2021	$ 962,291	$ 1,548	$ 1,608,238	$ (2,499)	$ (644,996)
Increase (Decrease) in Stockholders' Equity [Roll Forward]
Issuance of common stock, net of issuance costs (in shares)		11,933,962
Issuance of common stock, net of issuance costs	296,215	$ 120	296,095
Issuances under equity incentive plans (in shares)		911,555
Issuances under equity incentive plans	14,455	$ 10	14,445
Vesting of restricted stock units (in shares)		837,096
Vesting of restricted stock units	0	$ 8	(8)
Stock-based compensation	99,847		99,847
Net loss	(325,991)				(325,991)
Other comprehensive income (loss)	(4,387)			(4,387)
Ending balance (in shares) at Dec. 31, 2022		135,965,918
Ending balance at Dec. 31, 2022	1,042,430	$ 1,686	2,018,617	(6,886)	(970,987)
Increase (Decrease) in Stockholders' Equity [Roll Forward]
Issuances under equity incentive plans (in shares)		1,232,526
Issuances under equity incentive plans	17,820	$ 12	17,808
Vesting of restricted stock units (in shares)		1,187,054
Vesting of restricted stock units	0	$ 13	(13)
Stock-based compensation	108,399		108,399
Net loss	(145,224)				(145,224)
Other comprehensive income (loss)	$ 7,529			7,529
Ending balance (in shares) at Dec. 31, 2023	138,385,498	138,385,498
Ending balance at Dec. 31, 2023	$ 1,030,954	$ 1,711	2,144,811	643	(1,116,211)
Increase (Decrease) in Stockholders' Equity [Roll Forward]
Issuance of common stock, net of issuance costs (in shares)		3,244,689
Issuance of common stock, net of issuance costs	499,253	$ 32	499,221
Issuances under equity incentive plans (in shares)		1,288,609
Issuances under equity incentive plans	17,389	$ 13	17,376
Vesting of restricted stock units (in shares)		1,302,190
Vesting of restricted stock units	0	$ 12	(12)
Stock-based compensation	103,484		103,484
Net loss	(422,773)				(422,773)
Other comprehensive income (loss)	$ 1,377			1,377
Ending balance (in shares) at Dec. 31, 2024	144,220,986	144,220,986
Ending balance at Dec. 31, 2024	$ 1,229,684	$ 1,768	$ 2,764,880	$ 2,020	$ (1,538,984)

Fair Value Measurements (Tables)

12 Months Ended

Dec. 31, 2024

Fair Value Disclosures [Abstract]

Schedule of Assets and Liabilities Measured at Fair Value

Assets and liabilities measured at fair value at each balance sheet date are as follows (in thousands):


	December 31, 2024
	Level 1		Level 2		Level 3		Total
Assets:
Cash equivalents:
Money market funds	$	126,728	$	—	$	—	$	126,728


Short-term marketable securities:
U.S. government treasuries	629,400		—		—		629,400

Corporate debt securities	—		21,399		—		21,399
Commercial paper	—		6,572		—		6,572
Long-term marketable securities:
U.S. government treasuries	334,892		—		—		334,892

Corporate debt securities	—		24,481		—		24,481

Total	$	1,091,020	$	52,452	$	—	$	1,143,472


	December 31, 2023
	Level 1		Level 2		Level 3		Total
Assets:
Cash equivalents
Money market funds	$	121,034	$	—	$	—	$	121,034


Short-term marketable securities:
U.S. government treasuries	869,172		—		—		869,172
U.S. government agency securities	—		7,086		—		7,086

Commercial paper	—		31,147		—		31,147





Total	$	990,206	$	38,233	$	—	$	1,028,439

Net Loss and Net Loss Per Share - Calculation of Basic and Diluted Net Loss (Details) - USD ($) $ / shares in Units, $ in Thousands	12 Months Ended
	Dec. 31, 2024	Dec. 31, 2023	Dec. 31, 2022
Numerator:
Net loss	$ (422,773)	$ (145,224)	$ (325,991)
Denominator:
Common stock shares outstanding (in shares)	142,626,390	137,370,897	125,530,703
Private placement pre-funded warrants (in shares)	21,847,382	0	0
Weighted average number of shares outstanding, basic (in shares)	164,473,772	137,370,897	125,530,703
Weighted average number of shares outstanding, diluted (in shares)	164,473,772	137,370,897	125,530,703
Net loss per share, basic (usd per share)	$ (2.57)	$ (1.06)	$ (2.60)
Net loss per share, diluted (usd per share)	$ (2.57)	$ (1.06)	$ (2.60)

- Definition

The amount of net income (loss) for the period per each share of common stock or unit outstanding during the reporting period.

+ References

+ Details

- Definition

The amount of net income (loss) for the period available to each share of common stock or common unit outstanding during the reporting period and to each share or unit that would have been outstanding assuming the issuance of common shares or units for all dilutive potential common shares or units outstanding during the reporting period.

+ References

+ Details

- Definition

The portion of profit or loss for the period, net of income taxes, which is attributable to the parent.

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+ Details

Stock-Based Awards

12 Months Ended

Dec. 31, 2024

Share-Based Payment Arrangement [Abstract]

Stock-Based Awards

Equity Incentive Plans

The Company's equity incentive plans, the 2017 Equity Incentive Plan (the “2017 Plan”), and previously, the 2015 Stock Incentive Plan (the “2015 Plan”), reserve shares of common stock for the issuance of stock options, restricted stock and other stock awards, to employees, non-employee directors, and consultants under terms and provisions established by the board of directors and approved by the stockholders. Upon adoption of the 2017 Plan, no new awards or grants are permitted under the 2015 Plan. The 2015 Plan continues to govern restricted stock awards and option awards previously granted thereunder.

Awards granted under the 2017 Plan and 2015 Plan expire no later than ten years from the date of grant. For stock options, the option price shall not be less than 100% of the estimated fair value of the Company's common stock on the day of grant. Options granted typically vest over a four-year period but may be granted with different vesting terms.

The 2017 Plan provides that the number of shares reserved and available for issuance under the 2017 Plan will automatically increase each January 1, beginning on January 1, 2019, by the lesser of (i) 10.0 million shares, (ii) 5% of the outstanding shares on the last day of the immediately preceding fiscal year, or (iii) such number of shares determined by the administrator of the 2017 Plan. In 2024, common stock available for issuance under the 2017 Plan was increased by approximately 6.8 million shares as a result of this automatic increase provision. As of December 31, 2024 and 2023, there were approximately 14.3 million and 12.5 million common shares available for the Company to grant under the 2017 Plan, respectively.

Stock Option Activity

The following table summarizes option award activity under the 2017 Plan and the 2015 Plan:


	Number of Options	Weighted- Average Exercise Price		Weighted- Average remaining contractual life (years)	Aggregate Intrinsic Value (in thousands)
Balance at December 31, 2023	16,490,551	$	27.34	5.97	$	61,982
Granted	4,902,211	20.82
Exercised	(968,588)	12.76
Forfeited	(1,764,024)	31.51
Balance at December 31, 2024	18,660,150	$	25.99	5.94	$	48,266
Vested and expected to vest at December 31, 2024	17,850,279	$	27.14	6.19	$	32,311
Exercisable at December 31, 2024	11,650,342	$	28.61	4.84	$	31,781

Aggregate intrinsic value represents the difference between the fair value of the Company's common stock and the exercise price of outstanding options. The total intrinsic value of options exercised was $10.6 million, $12.1 million, and $12.6 million as of December 31, 2024, 2023 and 2022, respectively. During the years ended December 31, 2024, 2023, and 2022 the weighted-average grant-date fair value of the options vested was $23.61, $24.30, and $23.96 per share, respectively. The weighted-average grant date fair value of all options granted during the years ended December 31, 2024, 2023 and 2022 was $12.99, $17.95, and $26.00 per share, respectively.

Stock Options Granted to Employees with Service-Based Vesting

The estimated fair value of stock options granted to employees were calculated using the Black-Scholes option-pricing model, which requires various assumptions, including the fair value of the Company’s common stock, expected term, expected dividend yield, expected volatility, and the risk-free interest rate. The fair value of the Company’s common stock is based on the current market price, unless an adjustment is determined to be required, through discussion with senior management, due to material non-public information known by the Company at the time of grant. The expected volatility of the Company’s stock options is estimated using a combination of average historical stock price volatility of the Company's stock and that of comparable public companies within the biotechnology and pharmaceutical industry that are deemed to be representative of future stock price trends, since the Company does not have sufficient trading history to rely solely on the volatility of its common stock. The Company will continue to apply this process until a sufficient amount of historical information regarding the volatility of its own stock price becomes available. Management considers whether the Company is in possession of material non-public information at the time of grants when making certain estimates, including volatility and the fair value of the Company's common stock. The expected term of stock options represents the period that the Company’s stock-options are expected to be outstanding and is determined using the simplified method (based on the mid-point between the vesting date and the end of the contractual term). The risk-free interest rate is based on the implied yield currently available on U.S. treasury notes with terms approximately equal to the expected life of the option. The expected dividend rate is zero as the Company currently has no history or expectation of declaring cash dividends on the Company’s common stock.

The following assumptions were used in estimating the fair value of grants during the year ended:


	December 31,
	2024	2023	2022
Expected term (in years)	5.50 - 6.08	5.50 - 6.08	5.50 - 6.08
Volatility	64.5% - 66.0%	67.6% - 69.6%	65.1% - 66.3%
Risk-free interest rate	3.7% - 4.5%	3.4% - 4.8%	1.5% - 4.3%
Dividend yield	—	—	—

Restricted Stock Activity

We grant restricted stock units ("RSUs") under the 2017 Plan. The fair value of restricted stock underlying the RSUs is determined based on the closing market price of the Company's common stock on the date of grant.

Aggregated information regarding RSUs granted under the Plan for the year ended December 31, 2024 is summarized below:


	Number of Units	Weighted-Average Fair Value at Date of Grant per Share
Unvested at December 31, 2023	3,635,157	$	35.60
Granted	2,580,174	21.01
Vested and released	(1,302,190)	37.13
Forfeited	(784,627)	28.62
Unvested and expected to vest at December 31, 2024	4,128,514	$	27.33

The aggregate intrinsic value of RSUs is calculated as the closing price per share of the Company's common stock on the last trading day of the fiscal period, multiplied by outstanding RSUs as of December 31, 2024. The total intrinsic value of RSUs expected to vest was $84.1 million as of December 31, 2024. During the years ended December 31, 2023 and 2022 the weighted-average grant-date fair value of RSUs granted was $27.38 and $37.55, respectively. The total fair value of RSUs that vested during the years ended December 31, 2024, 2023, and 2022 was $27.6 million, $31.6 million, and $29.4 million, respectively.

Stock-Based Compensation Expense

The Company’s stock-based compensation expense was as follows (in thousands):


	Year Ended December 31,
	2024		2023		2022
Research and development	$	59,146	$	62,901	$	60,196
General and administrative	43,732		45,201		39,651
Total	$	102,878	$	108,102	$	99,847

As of December 31, 2024, total unamortized stock-based compensation expense was $180.6 million. The weighted-average period over which such stock-based compensation expense will be recognized is approximately 2.4 years.

There was no tax benefit realized related to awards vested or exercised during the years ended December 31, 2024, 2023 and 2022. There is no deferred tax benefit on total stock-based compensation expense for the years ended December 31, 2024, 2023 and 2022 since the company has recorded a full valuation allowance on all deferred tax assets.

Balance Sheet Components - Narrative (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2024	Dec. 31, 2023	Dec. 31, 2022
Property, Plant and Equipment [Line Items]
Depreciation expense	$ 7,795	$ 16,726	$ 10,383
Building \| SLC Lease \| Operating Lease, 9.3 Year Lease Agreement, Terminated
Property, Plant and Equipment [Line Items]
Accelerated depreciation on leasehold improvements in relation to SLC Lease termination		$ 7,900

Significant Accounting Policies (Tables)

12 Months Ended

Dec. 31, 2024

Accounting Policies [Abstract]

Summary of Estimated Useful Life

Depreciation is computed using the straight-line method over the related estimated useful lives as presented in the table below. Significant additions and improvements are capitalized, while repairs and maintenance are charged to expense as incurred.


Asset						Estimated useful life
Leasehold improvements						shorter of life of asset or lease term
Computer equipment and purchased software						three years
Laboratory equipment						five years
Furniture and fixtures						five years
Manufacturing equipment						eight years

Divestiture of Preclinical Small Molecule Programs (Details) $ / shares in Units, ft² in Thousands, $ in Thousands, shares in Millions		1 Months Ended	12 Months Ended
	Mar. 01, 2024 USD ($)	Dec. 31, 2024 USD ($) $ / shares shares	Dec. 31, 2024 USD ($) $ / shares	Dec. 31, 2023 USD ($) $ / shares	Dec. 31, 2022 USD ($)	Mar. 31, 2024 ft² extension_option
Disposal Groups, Including Disposal Of Long-Lived Assets [Line Items]
Equity consideration received in the divestiture of small molecule programs (Note 13)			$ 15,000	$ 0	$ 0
Convertible preferred stock, par value (usd per share) \| $ / shares		$ 0.01	$ 0.01	$ 0.01
Lessor, operating sublease, rentable area \| ft²						12
Lessor, operating sublease, number of options to extend \| extension_option						1
Sublease renewal option term						6 months
Gain from divestiture of small molecule programs			$ 14,537	$ 0	$ 0
Tenvie Therapeutics, Inc
Disposal Groups, Including Disposal Of Long-Lived Assets [Line Items]
Equity consideration received in the divestiture of small molecule programs (Note 13)	$ 15,000
Noncash or part noncash divestiture, milestone payments, to be received		$ 1,200,000	$ 1,200,000
Future royalties, threshold after first commercial sale		10 years	10 years
Gain from divestiture of small molecule programs			$ 14,500
Tenvie Therapeutics, Inc \| Series A Preferred Stock
Disposal Groups, Including Disposal Of Long-Lived Assets [Line Items]
Number of shares converted in simple agreement for future equity (in shares) \| shares		15.0
Convertible preferred stock, par value (usd per share) \| $ / shares		$ 0.0001	$ 0.0001
Fair value of shares converted in simple agreement for future equity		$ 15,000
Fair value of investment		$ 15,000	$ 15,000

Marketable Securities - Narrative (Details) - USD ($)	Dec. 31, 2024	Dec. 31, 2023
Investments, Debt and Equity Securities [Abstract]
Allowance for credit losses	$ 0	$ 0
Effective maturity (less than)	2 years

Income Taxes - Effective Tax Rate Reconciliation (Details)	12 Months Ended
	Dec. 31, 2024	Dec. 31, 2023	Dec. 31, 2022
Income Tax Disclosure [Abstract]
Taxes at the U.S. statutory tax rate	21.00%	21.00%	21.00%
Change in valuation allowance	(25.00%)	(27.30%)	(25.10%)
Research tax credits	5.60%	14.50%	4.90%
Stock-based compensation	(2.10%)	(3.20%)	(0.50%)
Nondeductible acquisition-related costs	0.00%	(3.50%)	0.00%
Impact of IRC 162m	(0.20%)	(0.70%)	0.00%
Other	0.70%	(0.80%)	(0.40%)
Total provision for income taxes	0.00%	0.00%	(0.10%)

Common Stock (Details) - Private Placement - USD ($) $ / shares in Units, $ in Millions	Feb. 29, 2024	Feb. 27, 2024
Class of Warrant or Right [Line Items]
Number of common stock (in shares)		3,244,689
Common stock, price per share sold (usd per share)		$ 17.07
Purchase price	$ 499.3
Stock issuance costs	$ 0.5
Pre-Funded Warrant
Class of Warrant or Right [Line Items]
Common stock, price per share sold (usd per share)		$ 17.06
Number of securities called by warrants (in shares)		26,046,065
Exercise price of warrants (usd per share)		$ 0.01

Balance Sheet Components - Prepaid Expenses and Other Current Assets (Details) - USD ($) $ in Thousands	Dec. 31, 2024	Dec. 31, 2023
Organization, Consolidation and Presentation of Financial Statements [Abstract]
Accounts receivable and other receivables	$ 2,171	$ 3,420
Prepaid clinical research & development costs	6,473	10,178
Prepaid manufacturing and other research & development costs	16,196	12,192
Other prepaid assets and other current assets	7,265	3,836
Prepaid expenses and other current assets	$ 32,105	$ 29,626

Commitments and Contingencies - Summary of Supplemental Lease Information (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2024	Dec. 31, 2023	Dec. 31, 2022
Commitments and Contingencies Disclosure [Abstract]
Operating cash flows from operating lease	$ 11,417	$ 11,345	$ 11,189
Operating lease, weighted-average remaining lease term (in years)	4 years 3 months 18 days	5 years 3 months 18 days	6 years 2 months 12 days
Finance lease, weighted-average remaining lease term (in years)	14 years 3 months 18 days	0 years	0 years
Operating lease, weighted-average discount rate applied	9.00%	9.00%	8.90%
Finance lease, weighted-average discount rate applied	13.70%	0.00%	0.00%

Condensed Consolidated Statements of Cash Flows (Parenthetical) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2024	Dec. 31, 2022
Statement of Cash Flows [Abstract]
Stock issuance costs	$ 480	$ 1,060

Stock-Based Awards - Narrative (Details) - USD ($)		12 Months Ended
Stock-Based Awards - Narrative (Details) - USD ($)	Jan. 01, 2019	Dec. 31, 2024	Dec. 31, 2023	Dec. 31, 2022
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Aggregate intrinsic value of options exercised		$ 10,600,000	$ 12,100,000	$ 12,600,000
Weighted-average grant date fair value of options vested (usd per share)		$ 23.61	$ 24.3	$ 23.96
Weighted-average grant date fair value of options granted (usd per share)		$ 12.99	$ 17.95	$ 26
Dividend yield		0.00%
Unamortized stock- based compensation expense related to unvested stock options		$ 180,600,000
Expected weighted average period		2 years 4 months 24 days
Tax benefit realized, related to awards vested or exercised		$ 0	$ 0	$ 0
Total stock-based compensation expense, tax benefit		0	$ 0	$ 0
Restricted Stock Units (RSUs)
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Intrinsic value of units expected to vest		$ 84,100,000
Weighted-average grant-date fair value, granted (usd per share)		$ 21.01	$ 27.38	$ 37.55
Fair value of units vested		$ 27,600,000	$ 31,600,000	$ 29,400,000
2015 Stock Incentive Plan
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Number of shares available for grant (in shares)		0
2015 Stock Incentive Plan \| Maximum
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Award expiration period		10 years
2015 Stock Incentive Plan \| Minimum
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Percentage of option price of estimated fair value on grant date		100.00%
Award vesting period		4 years
2017 Equity Incentive Plan
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Number of shares available for grant (in shares)		14,300,000	12,500,000
Number of additional shares allowable under the plan (in shares)	10,000,000	6,800,000
Percent of outstanding shares (as a percentage)	5.00%
2017 Equity Incentive Plan \| Maximum
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Award expiration period		10 years
2017 Equity Incentive Plan \| Minimum
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Percentage of option price of estimated fair value on grant date		100.00%
Award vesting period		4 years

Defined Contribution Plan	12 Months Ended
Defined Contribution Plan	Dec. 31, 2024
Retirement Benefits [Abstract]
Defined Contribution Plan	Defined Contribution Plan The Company sponsors a 401(k) retirement savings plan for the benefit of its employees, including Denali's named executive officers, who satisfy certain eligibility requirements. Under the 401(k) plan, eligible employees may elect to defer a portion of their compensation, within the limits prescribed by the Code, on a pre-tax or after-tax (Roth) basis through contributions to the 401(k) plan. The 401(k) plan authorizes employer safe harbor contributions. The Company made contributions to the Plan for eligible participants, and recorded contribution expenses of $3.0 million, $3.2 million and $2.8 million for the years ended December 31, 2024, 2023, and 2022 respectively.

- Definition

The entire disclosure for retirement benefits.

+ References

Reference 1: http://www.xbrl.org/2003/role/disclosureRef
-Topic 715
-SubTopic 70
-Name Accounting Standards Codification
-Section 50
-Paragraph 1
-Publisher FASB
-URI https://asc.fasb.org/1943274/2147480794/715-70-50-1

Reference 2: http://www.xbrl.org/2003/role/exampleRef
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Reference 3: http://www.xbrl.org/2003/role/disclosureRef
-Topic 715
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Reference 4: http://www.xbrl.org/2003/role/disclosureRef
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Reference 5: http://www.xbrl.org/2003/role/disclosureRef
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-URI https://asc.fasb.org/1943274/2147480266/715-60-50-3

+ Details

Consolidated Statements of Operations and Comprehensive Loss (Parenthetical) - USD ($)
$ in Thousands

12 Months Ended

Dec. 31, 2023

Dec. 31, 2022

Collaborative revenue, revenue from contract with customer

^[1]

$ 330,531

$ 105,065

Research and development expense due to cost share payments to related party

^[2]

423,876

358,732

295,500

3,200

Research and development expense due to cost share payments to related party

$ 17,700

$ 8,200

[1]	Includes related-party collaboration revenue from customers of $295.5 million, and $3.2 million for the years ended December 31, 2023 and 2022, respectively.
[2]	Includes expense for cost sharing payments to a related party of $17.7 million and $8.2 million for the years ended December 31, 2023 and 2022, respectively.

- Definition

Amount, excluding tax collected from customer, of revenue from satisfaction of performance obligation by transferring promised good or service to customer. Tax collected from customer is tax assessed by governmental authority that is both imposed on and concurrent with specific revenue-producing transaction, including, but not limited to, sales, use, value added and excise.

+ References

Reference 1: http://www.xbrl.org/2003/role/disclosureRef
-Topic 280
-SubTopic 10
-Name Accounting Standards Codification
-Section 50
-Paragraph 41
-Subparagraph (a)
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+ Details

Segment Information

12 Months Ended

Dec. 31, 2024

Segment Reporting [Abstract]

Segment Information

The Company has one operating segment with the goal to discover, develop and commercialize therapeutics (“Therapeutics”). The Company has not generated any revenue from product sales, and has no marketing or commercial product distribution costs. All revenue to date has been collaboration and license revenue from the Company’s collaboration agreements.

The Company’s chief operating decision maker ("CODM"), its Chief Executive Officer, manages the Company’s operations on a consolidated basis for the purposes of allocating resources.

The CODM, in alignment with the Company's overall corporate strategy and goals, analyses a variety of data to guide segment resource allocation, including program and portfolio scientific data, product market information and projections, probability of regulatory and commercial success, and the competitive environment. The CODM also reviews certain financial results included in the segment Loss from Operations which is reported on the Consolidated Statements of Operations and Comprehensive Loss as total Loss from Operations. The measure of segment assets is reported on the Consolidated Balance Sheets as Total Assets. The accounting policies of the Therapeutics segment are the same as those described in the summary of significant accounting policies.

The following table presents selected financial information with respect to the Company’s single operating segment for the years ended December 31, 2024, 2023 and 2022 (in thousands):


	Therapeutics Segment
	Year Ended December 31,
	2024		2023		2022
Total collaboration revenue	$	—	$	330,531	$	108,463
Expenses
External research and development expenses - TV programs, including cost sharing	138,196		139,064		96,587
External research and development expenses - small molecule programs, including cost sharing	42,623		49,850		44,738
Other research and development expenses	62,715		74,518		73,390
Personnel related research and development expenses	152,906		160,444		144,017
Total research and development expenses	396,440		423,876		358,732
Personnel related general and administrative expenses	73,505		73,668		64,147
Other general and administrative expenses	31,933		29,686		26,328
Total general and administrative expenses	105,438		103,354		90,475
Segment operating expenses	501,878		527,230		449,207
Segment gain from divestiture of small molecule programs	14,537		—		—
Segment loss from operations	(487,341)		(196,699)		(340,744)
Segment interest and other income, net	64,636		51,505		14,774
Segment loss before income taxes	$	(422,705)	$	(145,194)	$	(325,970)

There is no difference between the segment loss before income taxes and total consolidated loss before income taxes for the years ended December 31, 2024, 2023 and 2022.

- Definition

The entire disclosure for reporting segments including data and tables. Reportable segments include those that meet any of the following quantitative thresholds a) it's reported revenue, including sales to external customers and intersegment sales or transfers is 10 percent or more of the combined revenue, internal and external, of all operating segments b) the absolute amount of its reported profit or loss is 10 percent or more of the greater, in absolute amount of 1) the combined reported profit of all operating segments that did not report a loss or 2) the combined reported loss of all operating segments that did report a loss c) its assets are 10 percent or more of the combined assets of all operating segments.

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+ Details

Consolidated Statements of Operations and Comprehensive Loss - USD ($)
$ in Thousands

12 Months Ended

Dec. 31, 2024

Dec. 31, 2023

Dec. 31, 2022

Collaboration revenue:

Collaboration revenue from customers

^[1]

$ 0

$ 330,531

$ 105,065

Other collaboration revenue

3,398

Total collaboration revenue

330,531

108,463

Operating expenses:

Research and development expense

^[2]

396,440

423,876

358,732

General and administrative

105,438

103,354

90,475

Total operating expenses

501,878

527,230

449,207

Gain from divestiture of small molecule programs

14,537

Loss from operations

(487,341)

(196,699)

(340,744)

Interest and other income, net

64,636

51,505

14,774

Loss before income taxes

(422,705)

(145,194)

(325,970)

Income tax expense

(68)

(30)

(21)

Net loss

(422,773)

(145,224)

(325,991)

Other comprehensive income (loss):

Net unrealized gain (loss) on marketable securities, net of tax

1,377

7,529

(4,387)

Comprehensive loss

$ (421,396)

$ (137,695)

$ (330,378)

Net loss per share:

Net loss per share, basic (usd per share)

$ (2.57)

$ (1.06)

$ (2.60)

Net loss per share, diluted (usd per share)

$ (2.57)

$ (1.06)

$ (2.60)

Weighted-average shares used in calculating:

Weighted average number of shares outstanding, basic (in shares)

164,473,772

137,370,897

125,530,703

Weighted average number of shares outstanding, diluted (in shares)

164,473,772

137,370,897

125,530,703

[1]	Includes related-party collaboration revenue from customers of $295.5 million, and $3.2 million for the years ended December 31, 2023 and 2022, respectively.
[2]	Includes expense for cost sharing payments to a related party of $17.7 million and $8.2 million for the years ended December 31, 2023 and 2022, respectively.

Balance Sheet Components

12 Months Ended

Dec. 31, 2024

Organization, Consolidation and Presentation of Financial Statements [Abstract]

Balance Sheet Components

Prepaid Expenses and Other Current Assets

Prepaid expenses and other current assets consists of the following (in thousands):


	As of December 31,
	2024		2023
Accounts receivable and other receivables	$	2,171	$	3,420
Prepaid clinical research & development costs	6,473		10,178
Prepaid manufacturing and other research & development costs	16,196		12,192
Other prepaid assets and other current assets	7,265		3,836
Total prepaid expenses and other current assets	$	32,105	$	29,626

Property and Equipment, Net

Property and equipment, net consists of the following (in thousands):


	As of December 31,
	2024		2023
Leasehold improvements	$	46,905	$	41,238
Laboratory equipment	40,554		36,985
Manufacturing equipment	15,998		9,722
Computer equipment and purchased software	1,841		1,741
Furniture and fixtures	1,980		1,906
Total property and equipment	107,278		91,592
Less: accumulated depreciation	(52,042)		(46,003)
Total property and equipment, net	$	55,236	$	45,589

Depreciation expense was $7.8 million, $16.7 million and $10.4 million for the years ended December 31, 2024, 2023 and 2022, respectively. Depreciation expense for the year ended December 31, 2023 includes $7.9 million of accelerated depreciation on leasehold improvements due to the Company terminating the previous SLC Lease in March 2023.

Accrued Expenses and Other Current Liabilities

Accrued expenses and other current liabilities consists of the following (in thousands):


	As of December 31,
	2024		2023
Accrued compensation	$	24,728	$	21,590
Accrued clinical and other research & development costs	22,822		19,035
Accrued manufacturing costs	12,779		15,462
Operating lease liability, current	8,308		7,260
Finance lease liability, current	3,726		—
Deferred research and development funding liability, current	14,129		—
Other accrued costs and current liabilities	4,579		5,152
Total accrued expenses and other current liabilities	$	91,071	$	68,499

Balance Sheet Components - Accrued Expenses and Other Current Liabilities (Details) - USD ($) $ in Thousands	Dec. 31, 2024	Dec. 31, 2023
Organization, Consolidation and Presentation of Financial Statements [Abstract]
Accrued compensation	$ 24,728	$ 21,590
Accrued clinical and other research & development costs	22,822	19,035
Accrued manufacturing costs	12,779	15,462
Operating lease liability, current	8,308	7,260
Finance lease liability, current	3,726	0
Deferred research and development funding liability, current	14,129	0
Other accrued costs and current liabilities	4,579	5,152
Total accrued expenses and other current liabilities	$ 91,071	$ 68,499
Operating Lease, Liability, Current, Statement of Financial Position [Extensible List]	Total accrued expenses and other current liabilities	Total accrued expenses and other current liabilities
Finance Lease, Liability, Current, Statement of Financial Position [Extensible Enumeration]	Total accrued expenses and other current liabilities	Total accrued expenses and other current liabilities

Stock-Based Awards - Summary of Stock Option Activity (Details) - USD ($) $ / shares in Units, $ in Thousands	12 Months Ended
	Dec. 31, 2024	Dec. 31, 2023
Number of Options
Beginning balance (in shares)	16,490,551
Granted (in shares)	4,902,211
Exercised (in shares)	(968,588)
Forfeited (in shares)	(1,764,024)
Ending balance (in shares)	18,660,150	16,490,551
Options, vested and expected to vest (in shares)	17,850,279
Options, exercisable (in shares)	11,650,342
Weighted- Average Exercise Price
Beginning balance (usd per share)	$ 27.34
Granted (usd per share)	20.82
Exercised (usd per share)	12.76
Forfeited (usd per share)	31.51
Ending balance (usd per share)	25.99	$ 27.34
Options, vested and expected to vest (usd per share)	27.14
Options, exercisable (usd per share)	$ 28.61
Stock Option Activity, Additional Disclosures
Weighted- Average remaining contractual life (years)	5 years 11 months 8 days	5 years 11 months 19 days
Weighted-Average remaining contractual life (years), Options vested and expected to vest	6 years 2 months 8 days
Weighted-Average remaining contractual life (years), Options exercisable	4 years 10 months 2 days
Aggregate Intrinsic Value (in thousands)	$ 48,266	$ 61,982
Aggregate Intrinsic Value (in thousands), Options vested and expected to vest	32,311
Aggregate Intrinsic Value (in thousands), Options exercisable	$ 31,781

Significant Accounting Policies - Cash, Cash Equivalents and Restricted Cash (Details) - USD ($) $ in Millions	Dec. 31, 2024	Dec. 31, 2023
Accounting Policies [Abstract]
Restricted cash	$ 1.6	$ 1.6

Stock-Based Awards - Summary of Restricted Stock Activity (Details) - Restricted Stock Units (RSUs) - $ / shares	12 Months Ended
	Dec. 31, 2024	Dec. 31, 2023	Dec. 31, 2022
Number of Units
Beginning balance (in shares)	3,635,157
Granted (in shares)	2,580,174
Vested and released (in shares)	(1,302,190)
Forfeited (in shares)	(784,627)
Ending balance (in shares)	4,128,514	3,635,157
Expected to vest (in shares)	4,128,514
Weighted-Average Fair Value at Date of Grant per Share
Beginning balance (usd per share)	$ 35.60
Granted (usd per share)	21.01	$ 27.38	$ 37.55
Vested and released (usd per share)	37.13
Forfeited (usd per share)	28.62
Ending balance (usd per share)	27.33	$ 35.60
Expected to vest (usd per share)	$ 27.33

Significant Accounting Policies - Property and Equipment, Net (Details)	Dec. 31, 2024
Computer equipment and purchased software
Property, Plant and Equipment [Line Items]
Estimated useful life	3 years
Laboratory equipment
Property, Plant and Equipment [Line Items]
Estimated useful life	5 years
Furniture and fixtures
Property, Plant and Equipment [Line Items]
Estimated useful life	5 years
Manufacturing equipment
Property, Plant and Equipment [Line Items]
Estimated useful life	8 years

Cover Page - USD ($) $ in Billions	12 Months Ended
Cover Page - USD ($) $ in Billions	Dec. 31, 2024	Feb. 21, 2025	Jun. 28, 2024
Cover [Abstract]
Document Type	10-K
Document Annual Report	true
Document Period End Date	Dec. 31, 2024
Current Fiscal Year End Date	--12-31
Document Transition Report	false
Entity File Number	001-38311
Entity Registrant Name	Denali Therapeutics Inc.
Entity Incorporation, State or Country Code	DE
Entity Tax Identification Number	46-3872213
Entity Address, Address Line One	161 Oyster Point Blvd
Entity Address, City or Town	South San Francisco
Entity Address, State or Province	CA
Entity Address, Postal Zip Code	94080
City Area Code	650
Local Phone Number	866-8547
Title of 12(b) Security	Common Stock, par value $0.01 per share
Trading Symbol	DNLI
Security Exchange Name	NASDAQ
Entity Well-known Seasoned Issuer	Yes
Entity Voluntary Filers	No
Entity Current Reporting Status	Yes
Entity Interactive Data Current	Yes
Entity Filer Category	Large Accelerated Filer
Entity Small Business	false
Entity Emerging Growth Company	false
ICFR Auditor Attestation Flag	true
Document Financial Statement Error Correction [Flag]	false
Entity Shell Company	false
Entity Public Float			$ 1.9
Entity Common Stock, Shares Outstanding		145,215,391
Documents Incorporated by Reference	Portions of the registrant’s Definitive Proxy Statement relating to the registrant’s 2025 Annual Meeting of Stockholders are incorporated by reference into Part III of this Annual Report on Form 10-K where indicated. Such Definitive Proxy Statement will be filed with the Securities and Exchange Commission within 120 days after the end of the registrant’s 2024 fiscal year ended December 31, 2024.
Document Fiscal Year Focus	2024
Amendment Flag	false
Document Fiscal Period Focus	FY
Entity Central Index Key	0001714899

Divestiture of Preclinical Small Molecule Programs	12 Months Ended
Divestiture of Preclinical Small Molecule Programs	Dec. 31, 2024
Disposal Groups, Including Disposal Of Long-Lived Assets [Abstract]
Divestiture of Preclinical Small Molecule Programs	Divestiture of Preclinical Small Molecule Programs On March 1, 2024, the Company divested certain assets, including specified intellectual property, tangible assets, and equipment used to conduct early stage small molecule drug discovery ("Divested Assets") through an Asset Purchase and License Agreement (the "Asset Purchase Agreement") executed with Tenvie. Additionally, certain of the Company’s employees terminated their employment with the Company and became employees of Tenvie. In exchange for the Divested Assets, the Company received equity consideration of $15.0 million in the form of a simple agreement for future equity (“SAFE”). In December 2024, the SAFE converted into 15.0 million shares of Tenvie's Series A Preferred Stock, par value $0.0001 per share, with a fair value of $15.0 million. Under the terms of the Asset Purchase Agreement, the Company is eligible to receive certain market valuation, development and sales based milestone payments up to approximately $1.2 billion in the form of either cash or equity at the election of Tenvie. The Company will also be entitled to receive future royalties on aggregate net sales of certain products, on a product-by-product and country-by-country basis during the periods of time commencing at the time of the first commercial sale of such product in such country, until the later of (i) the expiration of certain related patents, (ii) the expiration of Regulatory Exclusivity, or (iii) ten years after such first commercial sale. In March 2024, Tenvie and the Company also entered into a sublease for approximately 12,000 square feet of office and lab space within the Company's corporate headquarters, and transition and research services agreement ("Service Agreements"). The sublease commenced in May 2024 and continues through September 2025, with one optional six month extension period. The Service Agreements provides access to the Company's equipment and the provision of certain specified administrative and research services to Tenvie for a period concurrent with the sublease term. This divestiture did not meet the criteria for reporting discontinued operations as the sale does not represent a strategic shift in the Company’s business. The Company recognized a gain on divestiture of approximately $14.5 million in the Consolidated Statements of Operations and Comprehensive Loss during the year ended December 31, 2024, representing the difference between the fair value of the consideration received and the carrying amount of the Divested Assets. The Company recorded the investment in the shares of Series A Preferred Stock at $15.0 million which represents the fair value of the shares on the date of issuance. There have been no subsequent observable price changes in orderly transactions for the identical or similar equity securities of Tenvie, and as such, the measurement of this investment remains unchanged, with the $15.0 million included within other non-current assets in the Consolidated Balance Sheet as of December 31, 2024.

Segment Information (Tables)

12 Months Ended

Dec. 31, 2024

Segment Reporting [Abstract]

Schedule of Reconciliation of Segment Loss Before Income Taxes and Total Consolidated Loss Before Income Taxes

The following table presents selected financial information with respect to the Company’s single operating segment for the years ended December 31, 2024, 2023 and 2022 (in thousands):


	Therapeutics Segment
	Year Ended December 31,
	2024		2023		2022
Total collaboration revenue	$	—	$	330,531	$	108,463
Expenses
External research and development expenses - TV programs, including cost sharing	138,196		139,064		96,587
External research and development expenses - small molecule programs, including cost sharing	42,623		49,850		44,738
Other research and development expenses	62,715		74,518		73,390
Personnel related research and development expenses	152,906		160,444		144,017
Total research and development expenses	396,440		423,876		358,732
Personnel related general and administrative expenses	73,505		73,668		64,147
Other general and administrative expenses	31,933		29,686		26,328
Total general and administrative expenses	105,438		103,354		90,475
Segment operating expenses	501,878		527,230		449,207
Segment gain from divestiture of small molecule programs	14,537		—		—
Segment loss from operations	(487,341)		(196,699)		(340,744)
Segment interest and other income, net	64,636		51,505		14,774
Segment loss before income taxes	$	(422,705)	$	(145,194)	$	(325,970)

Commitments and Contingencies - Narrative (Details) $ in Thousands	1 Months Ended	12 Months Ended
	May 31, 2018 USD ($) ft²	Dec. 31, 2024 USD ($)	Dec. 31, 2023 USD ($)	Dec. 31, 2022 USD ($)	Apr. 30, 2023 USD ($) ft²
Loss Contingencies [Line Items]
Finance lease right-of-use asset		$ 47,533	$ 0
Operating lease costs		7,200	8,000	$ 8,000
Variable lease costs		5,100	4,400	4,000
Right-of-use asset amortization for finance lease		1,197	0	0
Finance lease, interest expense		300	0	0
DMSA, Non-Cancellable
Loss Contingencies [Line Items]
Purchase commitments		36,700	37,600
Other than DMSA
Loss Contingencies [Line Items]
Purchase commitments		24,100	34,800
DMSA
Loss Contingencies [Line Items]
Costs incurred		34,100	39,500	28,600
Payments for development and manufacturing services		36,600	37,100	$ 23,900
Other Commitments
Loss Contingencies [Line Items]
Purchase commitments		2,200	1,600
Headquarters Lease
Loss Contingencies [Line Items]
Area under lease \| ft²	148,020
Lease period	10 years
Lease renewal option term	10 years
Headquarters Lease \| Landlord Funded Tenant Improvements
Loss Contingencies [Line Items]
Tenant improvement allowance repayable in rent	$ 4,400
Operating Lease, 9.3 Year Lease Agreement, Terminated \| Building \| SLC Lease
Loss Contingencies [Line Items]
Accelerated depreciation on leasehold improvements in relation to SLC Lease termination			$ (7,900)
Operating Lease, 15 Year Lease Agreement \| Laboratory, Office, and Warehouse \| New SLC Operating Lease
Loss Contingencies [Line Items]
Lease renewal option term					10 years
Lease not yet commenced, area under lease \| ft²					59,336
Lease not yet commenced, period					15 years
Lease not yet commenced, undiscounted lease payments					$ 13,400
Operating Lease, 15 Year Lease Agreement \| Landlord Owned Assets \| New SLC Operating Lease
Loss Contingencies [Line Items]
Finance lease right-of-use asset		$ 41,600
Maximum \| Headquarters Lease \| Landlord Funded Tenant Improvements
Loss Contingencies [Line Items]
Leasehold improvements	$ 25,900

Collaboration Agreements - Biogen (Details)

1 Months Ended

9 Months Ended

12 Months Ended

53 Months Ended

Aug. 05, 2020

USD ($)

Apr. 30, 2023

USD ($)

Oct. 31, 2020

USD ($)

Aug. 31, 2020

USD ($)

program

Sep. 30, 2023

Dec. 31, 2024

USD ($)

Dec. 31, 2023

USD ($)

Dec. 31, 2022

USD ($)

Dec. 31, 2024

USD ($)

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Collaborative revenue, revenue from contract with customer

^[1]

$ 0

$ 330,531,000

$ 105,065,000

LRRK2 Agreement

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Funded percentage

40.00%

LRRK2 Agreement | Biogen

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Funded percentage

60.00%

Biogen | Provisional Collaboration Agreement | Share Purchase Agreement

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Number of common stock (in shares) | shares

13,310,243

Purchase price

$ 465,000,000

Premium on sale of common stock

$ 44,900,000

Common stock, voting interest

10.00%

Biogen | Provisional Collaboration Agreement | Transport Vehicle (TV) Technology Platform, Unnamed Program

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Number of programs | program

Biogen | Provisional Collaboration Agreement | Transport Vehicle Technology Platform, Right Of First Negotiation Programs

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Number of additional programs, if circumstances met | program

Biogen | Biogen Collaboration Agreement

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Upfront payment

$ 560,000,000

Biogen | Biogen Collaboration Agreement | Option Fee Payment

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Collaborative revenue, revenue from contract with customer

$ 5,000,000

Biogen | Biogen Collaboration Agreement | Product

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Collaborative revenue, revenue from contract with customer

Biogen | LRRK2 Agreement

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Milestone payments upon achievement of certain development, first commercial sale, and net sales based milestones

$ 1,125,000,000

Development milestone payments

375,000,000

First commercial sale milestone payments

375,000,000

Net sales-based milestone payments

$ 375,000,000

Biogen | LRRK2 Agreement | United States

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Agreed share of commercial profit (loss) percentage

50.00%

Biogen | LRRK2 Agreement | China

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Agreed share of commercial profit (loss) percentage

40.00%

Biogen | ROFN and Option Agreement

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Collaborative revenue, revenue from contract with customer

$ 288,900,000

Collaborative agreement, transaction price

$ 604,900,000

Biogen | ROFN and Option Agreement | Royalty Payment

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Collaborative revenue, revenue from contract with customer

Biogen | ROFN and Option Agreement | Milestone Triggered

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Collaborative revenue, revenue from contract with customer

$ 0

[1]	Includes related-party collaboration revenue from customers of $295.5 million, and $3.2 million for the years ended December 31, 2023 and 2022, respectively.

Significant Accounting Policies (Policies)

12 Months Ended

Dec. 31, 2024

Accounting Policies [Abstract]

Organization and Description of Business

Denali Therapeutics Inc. ("Denali" or the “Company”) is a biopharmaceutical company, incorporated in Delaware, that discovers and develops therapeutics to defeat neurodegenerative diseases and lysosomal storage diseases. The Company is headquartered in South San Francisco, California.

Basis of Presentation

These consolidated financial statements have been prepared in accordance with accounting principles generally accepted in the United States of America (“U.S. GAAP”) and pursuant to the rules and regulations of the Securities and Exchange Commission (“SEC”).

Principles of Consolidation

These consolidated financial statements include the accounts of the Company and its wholly-owned subsidiaries. All intercompany balances and transactions have been eliminated in consolidation. For the Company and its subsidiaries, the functional currency has been determined to be U.S. dollars. Monetary assets and liabilities denominated in foreign currency are remeasured at period-end exchange rates, non-monetary assets and liabilities denominated in foreign currencies are remeasured at historical rates, and transactions in foreign currencies are remeasured at average exchange rates. Foreign currency gains and losses resulting from remeasurement are recognized in interest and other income, net in the Consolidated Statements of Operations and Comprehensive Loss.

Use of Estimates

The preparation of financial statements in conformity with U.S. GAAP requires the Company to make certain estimates, judgments and assumptions that affect the reported amounts of assets and liabilities and disclosure of contingent assets and liabilities at the date of the consolidated financial statements, as well as the reported amounts of expenses during the reporting period. Actual results could differ from those estimates, and such differences could be material to the Consolidated Balance Sheets and Consolidated Statements of Operations and Comprehensive Loss.

Concentration of Credit Risk and Other Risks and Uncertainties

Financial instruments that potentially subject the Company to significant concentrations of credit risk consist primarily of cash, cash equivalents and marketable securities. Substantially all of the Company’s cash and cash equivalents are deposited in accounts with financial institutions that management believes are of high credit quality. Such deposits have and will continue to exceed federally insured limits. The Company maintains its cash with accredited financial institutions and accordingly, such funds are subject to minimal credit risk.

The Company’s investment policy limits investments to certain types of securities issued by the U.S. government and its agencies, as well as institutions with investment-grade credit ratings and places restrictions on maturities and concentration by type and issuer. The Company is exposed to credit risk in the event of a default by the financial institutions holding its cash, cash equivalents and marketable securities and issuers of marketable securities to the extent recorded on the Consolidated Balance Sheets. As of December 31, 2024 and 2023, the Company had no off-balance sheet concentrations of credit risk.

The Company is subject to a number of risks similar to other clinical-stage biopharmaceutical companies, including, but not limited to, the need to obtain adequate additional funding, possible failure of current or future preclinical testing or clinical trials, its reliance on third parties to conduct its clinical trials, the need to obtain regulatory and marketing approvals for its product candidates, competitors developing new technological innovations, the need to successfully commercialize and gain market acceptance of the Company’s product candidates, its right to develop and commercialize its product candidates pursuant to the terms and conditions of the licenses granted to the Company, protection of proprietary technology, the ability to make milestone, royalty or other payments due under any license or collaboration agreements, and the need to secure and maintain adequate manufacturing arrangements with third parties. If the Company does not successfully commercialize or partner any of its product candidates, it will be unable to generate product revenue or achieve profitability. Further, the company is also subject to broad market risks and uncertainties resulting from recent events, such as bank failures or instability in the financial services sector, global pandemics, war and armed conflicts, inflation, rising interest rates, and recession risks as well as supply chain and labor shortages.

Investments

The Company holds an equity investment in a venture-backed privately held company, Tenvie Therapeutics, Inc. ("Tenvie"). The privately held company is a Variable Interest Entity ("VIE"), but the Company is not the primary beneficiary. The Company does not have the power to direct the activities that most significantly impact the economic performance of the investee. The Company’s maximum exposure to loss from this VIE is limited to the value of the equity investment. The equity investment held by the Company lacks a readily determinable fair value and therefore the securities are measured at cost minus impairment, if any, plus or minus changes resulting from observable price changes in orderly transactions for the identical or similar equity securities of the same issuer. The Company reviews the carrying value of its equity investment for impairment whenever events or changes in business circumstances indicate the carrying amount of such asset may not be fully recoverable. Impairments, if any, are based on the excess of the carrying amount over the recoverable amount of the asset. There were no impairments during the year ended December 31, 2024.

Fair Value of Financial Instruments

Accounting Standards Codification ("ASC") Topic 820, Fair Value Measurement (“ASC 820”), establishes a fair value hierarchy for instruments measured at fair value that distinguishes between assumptions based on market data (observable inputs) and the Company’s own assumptions (unobservable inputs). Observable inputs are inputs that market participants would use in pricing the asset or liability based on market data obtained from sources independent of the Company. Unobservable inputs are inputs that reflect the Company’s assumptions about the inputs that market participants would use in pricing the asset or liability, and are developed based on the best information available in the circumstances.

ASC 820 identifies fair value as the exchange price, or exit price, representing the amount that would be received to sell an asset or paid to transfer a liability in an orderly transaction between market participants. As a basis for considering market participant assumptions in fair value measurements, ASC 820 establishes a three-tier fair value hierarchy that distinguishes between the following:

Level 1 – inputs are quoted prices (unadjusted) in active markets for identical assets or liabilities.

Level 2 – inputs are other than quoted prices included within Level 1 that are observable for the asset or liability, either directly or indirectly.

Level 3 – inputs are unobservable inputs that reflect the Company’s own assumptions about the assumptions market participants would use in pricing the asset or liability. Financial assets and liabilities are classified in their entirety based on the lowest level of input that is significant to the fair value measurement.

To the extent that the valuation is based on models or inputs that are less observable or unobservable in the market, the determination of fair value requires more judgment. Accordingly, the degree of judgment exercised by the Company in determining fair value is greatest for instruments categorized in Level 3.

The carrying amounts reflected in the Consolidated Balance Sheets for cash and cash equivalents, prepaid expenses and other current assets, accounts payable, and accrued liabilities approximate their fair values due to their short-term nature.

Cash, Cash Equivalents and Restricted Cash

The Company considers all highly liquid investments with original maturities of 90 days or less at the date of purchase to be cash and cash equivalents. Cash equivalents are reported at fair value.

Cash, cash equivalents and restricted cash reported within the Consolidated Statements of Cash Flows is composed of cash and cash equivalents reported in the Consolidated Balance Sheets and $1.6 million of restricted cash for the letter of credit for the Company’s headquarters building lease which is included within other non-current assets in the Consolidated Balance Sheets as of December 31, 2024 and 2023.

Marketable Securities

The Company generally invests its excess cash in money market funds and investment grade short to intermediate-term fixed income securities. Such investments are included in cash and cash equivalents, or short-term marketable securities or long-term marketable securities on the Consolidated Balance Sheets, are considered available-for-sale, and are reported at fair value with net unrealized gains and losses included as a component of stockholders’ equity.

The Company classifies investments in securities with remaining maturities of less than one year, or where its intent is to use the investments to fund current operations or to make them available for current operations, as short-term investments. The Company classifies investments in securities with remaining maturities of over one year as long-term investments, unless intended to fund current operations. The amortized cost of debt securities is adjusted for amortization of premiums and accretion of discounts to maturity, which is included in interest and other income, net in the Consolidated Statements of Operations and Comprehensive Loss. Realized gains and losses and declines in value determined to be due to credit losses on marketable securities, if any, are included in interest and other income, net.

The Company periodically evaluates the need for an allowance for credit losses. This evaluation includes consideration of several qualitative and quantitative factors, including whether it has plans to sell the security, whether it is more likely than not it will be required to sell any marketable securities before recovery of its amortized cost basis, and if the entity has the ability and intent to hold the security to maturity, and the portion of any unrealized loss that is the result of a credit loss. Factors considered in making these evaluations include quoted market prices, recent financial results and operating trends, implied values from any recent transactions or offers of investee securities, credit quality of debt instrument issuers, expected cash flows from securities, other publicly available information that may affect the value of the marketable security, duration and severity of the decline in value, and the Company's strategy and intentions for holding the marketable security.

Accounts Receivable

Accounts receivable are included within prepaid expenses and other current assets on the Consolidated Balance Sheets. The accounts receivable balance represents amounts receivable from the Company's collaboration partners net of an allowance for credit losses, if required.

Property and Equipment, Net

Property and equipment are stated at cost, net of accumulated depreciation. Depreciation is computed using the straight-line method over the related estimated useful lives as presented in the table below. Significant additions and improvements are capitalized, while repairs and maintenance are charged to expense as incurred.


Asset						Estimated useful life
Leasehold improvements						shorter of life of asset or lease term
Computer equipment and purchased software						three years
Laboratory equipment						five years
Furniture and fixtures						five years
Manufacturing equipment						eight years

Impairment of Long-Lived Assets

The Company periodically evaluates property and equipment for impairment whenever events or changes in circumstances indicate that a potential impairment may have occurred. If such events or changes in circumstances arise, the Company compares the carrying amount of the long-lived assets to the estimated future undiscounted cash flows expected to be generated by the long-lived assets. If the estimated aggregate undiscounted cash flows are less than the carrying amount of the long-lived assets, an impairment charge, calculated as the amount by which the carrying amount of the assets exceeds the fair value of the assets, is recorded. The fair value of the long-lived assets is determined based on the estimated discounted cash flows expected to be generated from the long-lived assets. The Company has not recorded any material impairment charges during the years presented.

Leases

The Company leases real estate and certain equipment for use in its operations. A determination is made as to whether an arrangement is a lease at inception. The Company recognizes finance and operating lease right-of-use ("ROU") assets, and finance and operating lease liabilities based on the present value of the future minimum lease payments at the commencement date. The Company adjusts ROU assets as needed for any lease incentives it receives and for assets it purchases that are regarded as landlord-owned. When determining the present value of lease payments, the Company uses its incremental borrowing rate on the date of lease commencement, or the rate implicit in the lease, if known. The Company does not assume renewals in its determination of the lease term unless the renewals are deemed by management to be reasonably certain at lease inception.

The Company recognizes amortization of the ROU assets and interest on the lease liabilities for its finance lease. Finance lease ROU assets are amortized on a straight-line basis from the commencement date to the earlier of the end of the useful life of the ROU asset or the end of the lease term. Operating lease expense is recognized on a straight-line basis over the lease term.

Leases with an initial term of twelve months or less are not recorded on the balance sheet, unless they include an option to purchase the underlying asset that the Company is reasonably certain to exercise. The Company has leases with lease and non-lease components, which the Company has elected to account for as a single lease component.

Revenue Recognition

License, Option and Collaboration Revenue

The Company analyzes its collaboration arrangements to assess whether they are within the scope of ASC 808, Collaborative Arrangements (“ASC 808”) to determine whether such arrangements involve joint operating activities performed by parties that are both active participants in the activities and exposed to significant risks and rewards dependent on the commercial success of such activities. For elements of collaboration arrangements that are accounted for pursuant to ASC 808, an appropriate recognition method is determined and applied consistently, generally by analogy to Topic 606. The accounting treatment pursuant to Topic 606 is outlined below.

Each of these Payments received under license, option and collaboration agreements result in license, collaboration and other revenue, except for revenues from royalties on net sales of licensed products, which are classified as royalty revenue. The Company may also receive reimbursement or make payments to a collaboration partner to satisfy cost sharing requirements. These payments are accounted for pursuant to ASC 808 and are recorded as an offset or increase to research and development expenses, respectively.

The Company recognizes revenue as it fulfills its obligations under each of its agreements. An asset is transferred when, or as, the customer obtains control of that asset, which for a service is considered to be as the services are received and used. The Company recognizes revenue over time by measuring the progress toward complete satisfaction of the relevant performance obligation using an appropriate input or output method based on the nature of the service promised to the customer. Amounts received prior to satisfying the revenue recognition criteria are recorded as current or non-current contract liabilities in the Company’s Consolidated Balance Sheets, depending on when the performance obligation is expected to be satisfied.

Research and Development Expenses

Research and development costs are expensed as incurred. Research and development costs consist of salaries and other personnel related expenses, including associated stock–based compensation, consulting fees, lab supplies, and facility costs, as well as fees paid to other entities that conduct certain research, development and manufacturing activities on behalf of the Company. Where the Company shares costs with collaboration partners, such as in the Biogen Collaboration Agreement and the Takeda Collaboration Agreement, research and development expenses may include cost sharing reimbursements from or payments to the collaboration partner, respectively. Where the company has entered into an R&D funding arrangement, payments received will be recorded as a liability, and recognized an offset to research and development expenses as the underlying research and development costs are incurred.

Nonrefundable advance payments for goods and services that will be used or received in future research and development activities are deferred and recognized as expense in the period in which the related goods are delivered or services are performed. There can be judgment involved in measuring the research and development expenses to be recognized in a particular period. In some cases, expense is recorded using an underlying assumption of the progress to completion of specific activities. For example, costs may be recognized based on the passage of time for activities that span reporting periods. If the provision of services is not linear then this assumption could impact the amount of expense recognized. The level of judgment varies based on the nature of the services being performed and the underlying support obtained. For some activities, such as for certain clinical trials, expense is recorded based on information obtained from vendors as an intermediary to those performing the underlying services, such as contract research organizations. These estimates are inherently more judgmental since the quality and availability of the underlying data may vary. The determination of whether an arrangement meets the definition of an R&D funding arrangement under ASC730 requires judgment, including an assessment of the nature of the arrangement, the funding party’s rights and exposure to research and development risks. Further, the timing of recognition of the funding is also subject to the judgments of the underlying research and development costs.

The Company has acquired and may continue to acquire the rights to develop and commercialize new product candidates from third parties. The upfront payments to acquire license, product or rights, as well as any future milestone payments, are immediately recognized as research and development expense provided that there is no alternative future use of the rights in other research and development projects.

Stock-Based Compensation

The Company’s stock-based compensation programs grant awards that have included stock options, restricted stock units, restricted stock awards, and shares issued under its employee stock purchase plan. Grants are awarded to employees, directors, and non-employee service providers.

The Company measures compensation expense for all stock-based awards at the grant date based on the fair value measurement of the award. The expense is recorded on a straight-line basis over the requisite service period, which is generally the vesting period, for the entire award. Expense is adjusted for actual forfeitures of unvested awards as they occur. The Company calculates the fair value measurement of stock options subject solely to service-based vesting requirements using the Black-Scholes valuation model. The Company uses the fair value of its common stock to determine the fair value of restricted stock awards.

Income Taxes

Income taxes are accounted for using the liability method, under which deferred tax assets and liabilities are determined based on the temporary differences between the financial reporting and tax bases of assets and liabilities and consideration is given to net operating losses and tax credit carryforwards. Deferred tax assets and liabilities are measured using the enacted tax rates that are expected to be in effect when the differences are expected to reverse.

The Company assesses the likelihood that deferred tax assets will be recovered from future taxable income, and a valuation allowance is established when necessary to reduce deferred tax assets to the amounts more likely than not expected to be realized.

The calculation of our current provision for income taxes involves the use of estimates, assumptions and judgments while taking into account current tax laws, interpretation of current tax laws and possible outcomes of future tax audits. The Company has established reserves to address potential exposures related to tax positions that could be challenged by tax authorities. Any changes in tax law or interpretation of tax law and the resolutions of potential tax audits could significantly impact the amounts provided for income taxes in our consolidated financial statements.

Comprehensive Loss

Comprehensive loss is composed of net loss and certain changes in stockholders’ equity that are excluded from net loss, primarily unrealized gains or losses on the Company’s marketable securities.

Net Loss Per Share

Basic net loss per share is calculated by dividing the net loss by the weighted-average number of shares of common stock outstanding during the period, without consideration for common stock equivalents. Diluted net loss per share is the same as basic net loss per share, since the effects of potentially dilutive securities are antidilutive given the net loss for each period presented. The weighted-average common shares outstanding as of December 31, 2024 includes pre-funded warrants to purchase shares of common stock that were issued in connection with the February 2024 private placement, as discussed further in Note 8 - "Common Stock".

Recently Issued Accounting Pronouncements

In November 2023, the Financial Accounting Standards Board ("FASB") issued Accounting Standards Update No. 2023-07, Segment Reporting (Topic 280): Improvements to Reportable Segment Disclosures, which is intended to improve reportable segment disclosure requirements primarily through enhanced disclosures about significant segment expenses. The amendments in this Update are effective for all public entities for fiscal years beginning after December 15, 2023, and interim periods within fiscal years beginning after December 15, 2024, with early adoption permitted. The Company adopted this accounting standard update retrospectively on December 31, 2024. Newly required disclosures has been included in Note 14 - "Segment Information".

In December 2023, the FASB issued Accounting Standards Update No. 2023-09, Income Taxes (Topic 740): Improvements to Income Tax Disclosures, which requires that an entity, on an annual basis, disclose additional income tax information, primarily related to the rate reconciliation and income taxes paid. The amendments in this Update are effective to be applied prospectively for annual periods beginning after December 15, 2024, with early adoption permitted. The Company has not early adopted this update, and is currently evaluating the impact of the new standard on its income tax disclosures.

In November 2024, the FASB issued Accounting Standards Update No. 2024-03, Income Statement - Reporting Comprehensive Income - Expense Disaggregation Disclosures (Subtopic 220-40): Disaggregation of Income Statement Expenses, which is intended to improve the disclosures of expenses by providing more detailed information about the types of expenses in commonly presented expense captions. The amendments in this update are effective for annual reporting periods beginning after December 15, 2026, and interim reporting periods beginning after December 15, 2027. Early adoption is permitted. The amendments can be applied either prospectively or retrospectively. The Company has not early adopted this update, and is currently evaluating the impact of this new standard on its consolidated financial statements and related disclosures.

Segments

The Company’s chief operating decision maker ("CODM"), its Chief Executive Officer, manages the Company’s operations on a consolidated basis for the purposes of allocating resources.

Commitments and Contingencies (Tables)

12 Months Ended

Dec. 31, 2024

Commitments and Contingencies Disclosure [Abstract]

Summary of Supplemental Information for Lease Amounts Recognized

The following table contains a summary of other information pertaining to the Company’s leases for the periods presented (in thousands):


	Year Ended December 31,
		2024			2023			2022

Operating cash flows from operating lease		$	11,417		$	11,345		$	11,189

		As of December 31,
		2024			2023			2022
Weighted-average remaining lease term (in years):
Operating lease		4.3 years			5.3 years			6.2 years
Finance lease		14.3 years			—			—
Weighted-average discount rate applied (%):
Operating lease		9.0		%	9.0		%	8.9		%
Finance lease		13.7		%	—		%	—		%

Summary of Company's Future Minimum Lease Commitments

The following table reconciles the undiscounted cash flows for the next five years and total of the remaining years to the operating and finance lease liabilities recorded in the Consolidated Balance Sheet as of December 31, 2024 (in thousands):


Year Ended December 31:	Operating Lease		Finance Lease
2025	$	11,793	$	4,446
2026	12,182		794
2027	12,584		811
2028	13,001		829
2029	4,381		848
Thereafter	—		8,814
Total undiscounted lease payments	53,941		16,542
Less: present value adjustment	(8,960)		—
Less: imputed interest	—		(7,201)
Total future minimum lease payments	$	44,981	$	9,341

Consolidated Statements of Stockholders' Equity (Parenthetical) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2024	Dec. 31, 2022
Statement of Stockholders' Equity [Abstract]
Common stock issuance costs	$ 480	$ 1,060

Collaboration Agreements (Tables)

12 Months Ended

Dec. 31, 2024

Organization, Consolidation and Presentation of Financial Statements [Abstract]

Summary of Collaboration Revenue

Collaboration Revenue

Revenue disaggregated by collaboration agreement and performance obligation is as follows (in thousands):


	Year Ended December 31,
	2024		2023		2022
Takeda Collaboration Agreement:
Takeda Collaboration Agreement Services(1)	$	—	$	—	$	51,916
PTV:PGRN Collaboration Agreement	—		10,000		—

Total Takeda Collaboration Revenue	—		10,000		51,916
Sanofi Collaboration Agreement:
CNS Program License	—		25,000		40,000
Peripheral Program License	—		—		10,000
Alzheimer's Disease Services(2)	—		—		3,398

Total Sanofi Collaboration Revenue	—		25,000		53,398
Biogen Collaboration Agreement:

ATV:Abeta Program License(3)	—		293,912		—
Option Research Services(2)	—		1,619		3,149
Total Biogen Collaboration Revenue	—		295,531		3,149
Total Collaboration Revenue	$	—	$	330,531	$	108,463

_________________________________________________

(1)Revenue of $27.9 million for the year ended December 31, 2022 was included in the contract liability balance at the beginning of the year.

(2)Revenue was included in the contract liability balance at the beginning of the year.

(3)Revenue of $288.9 million for the year ended December 31, 2023 was included in the related-party contract liability balance at the beginning of the period.

Summary Of Cost Sharing Payments And Reimbursements

Cost sharing payments to collaboration partners recorded as expenses in research and development expenses in the Consolidated Statements of Operations and Comprehensive Loss, and cost sharing reimbursements from collaboration partners recorded as an offset to expense in research and development expenses in the Consolidated Statements of Operations and Comprehensive Loss are as follows (in thousands):


	Year Ended December 31,
	2024		2023		2022
Takeda Collaboration Agreement:
PTV:PGRN cost sharing (reimbursements)	$	(4,789)	$	(7,065)	$	(11,276)
ATV:TREM2 cost sharing (reimbursements)	(1,147)		(5,100)		(6,954)
Total Takeda cost sharing (reimbursements)(1)	(5,936)		(12,165)		(18,230)
Biogen Collaboration Agreement: LRRK2 cost sharing payments(2)	16,742		17,678		8,187
Net cost sharing payments (reimbursements)	$	10,806	$	5,513	$	(10,043)

________________________________________________

(1)Cost sharing reimbursements of $1.5 million and $2.7 million were recorded as a receivable within prepaid expenses and other current assets on the Consolidated Balance Sheets as of December 31, 2024 and 2023, respectively.

(2)Cost sharing payments due to Biogen of $2.5 million and $3.2 million were recorded within accounts payable on the Consolidated Balance Sheets as of December 31, 2024 and 2023, respectively.

Commitments and Contingencies

12 Months Ended

Dec. 31, 2024

Commitments and Contingencies Disclosure [Abstract]

Commitments and Contingencies

Lease Obligations

In May 2018, the Company entered into an operating lease for its corporate headquarters in South San Francisco (the "Headquarters Lease"), a 148,020 rentable square feet building in South San Francisco, California (the "Headquarters"). The Headquarters Lease has a contractual term of 10 years which ends on March 31, 2029, after which the Company has an option to extend the lease term for a further ten years. The Company determined that this renewal was not reasonably certain at lease inception. The accounting lease commencement date was determined to be August 1, 2018.

The Headquarters Lease provides for monthly base rent amounts escalating over the term of the lease. In addition, the Headquarters Lease provided a tenant improvement allowance ("TIA") of up to $25.9 million, which was fully utilized, of which $4.4 million will be repaid to the landlord in the form of additional monthly rent. This is recorded as leasehold improvement assets and an offset to the lease ROU asset on the Consolidated Balance Sheets. The Company is also required to pay the operating expenses for the Headquarters, such as taxes and insurance, which are treated as variable lease payments.

In August 2021, the Company entered into an operating lease for laboratory, office and warehouse facilities in Salt Lake City, Utah. In March 2023, the Company terminated this operating lease, which resulted in the recognition of $7.9 million of accelerated depreciation on leasehold improvements during the year ended December 31, 2023. The lease had not commenced for accounting purposes.

In April 2023, the Company entered into a new lease in Salt Lake City (the "SLC Lease") for a 59,336 square foot laboratory, office and warehouse premises with a contractual term of approximately 15 years, and undiscounted lease payments of approximately $13.4 million, which was subsequently amended in October 2023. The Company has the option to extend the lease term for a period of ten years at the end of the lease term. The accounting lease commencement date was determined to be August 1, 2024, the date the Company was deemed to have obtained control over the property, at which time the lease was determined to be a finance lease and the lease liability and ROU asset were recorded on the Consolidated Balance Sheets. Included in the ROU asset as of December 31, 2024 are $41.6 million of assets purchased by the Company, which are considered to be owned by the landlord.

Management exercised judgment in applying the requirements of ASC 842, including the determination as to whether certain contracts contain a lease, lease classification, the lease consideration, and the commencement date of the leases, and for leases identified under the standard, the discount rate used to determine the measurement of the lease liability. The discount rates of the Company's operating and finance leases are an approximation of the Company's incremental borrowing rate and are dependent upon the term and economics of the agreement. To estimate the incremental borrowing rates, management considered observable debt yields of comparable market instruments, as well as benchmarks within the lease agreement that may be indicative of the rate implicit in the lease. There were no changes to the terms of the leases recognized under ASC 842 during the year ended December 31, 2024.

Operating lease costs, including variable lease costs recognized under ASC 842, were $7.2 million for the year ended December 31, 2024 and $8.0 million for each of the years ended December 31, 2023 and 2022. Variable lease costs were $5.1 million, $4.4 million and $4.0 million for the years ended December 31, 2024, 2023 and 2022, respectively. Finance lease costs representing amortization of ROU assets and interest on lease liability were $1.2 million and $0.3 million, respectively, for the year ended December 31, 2024. There were no finance lease costs for the years ended December 31, 2023 and 2022.

The following table contains a summary of other information pertaining to the Company’s leases for the periods presented (in thousands):


	Year Ended December 31,
		2024			2023			2022

Operating cash flows from operating lease		$	11,417		$	11,345		$	11,189

		As of December 31,
		2024			2023			2022
Weighted-average remaining lease term (in years):
Operating lease		4.3 years			5.3 years			6.2 years
Finance lease		14.3 years			—			—
Weighted-average discount rate applied (%):
Operating lease		9.0		%	9.0		%	8.9		%
Finance lease		13.7		%	—		%	—		%


Year Ended December 31:	Operating Lease		Finance Lease
2025	$	11,793	$	4,446
2026	12,182		794
2027	12,584		811
2028	13,001		829
2029	4,381		848
Thereafter	—		8,814
Total undiscounted lease payments	53,941		16,542
Less: present value adjustment	(8,960)		—
Less: imputed interest	—		(7,201)
Total future minimum lease payments	$	44,981	$	9,341

Indemnification

In the ordinary course of business, the Company may provide indemnifications of varying scope and terms to vendors, lessors, business partners, board members, officers, and other parties with respect to certain matters, including, but not limited to, losses arising out of breach of such agreements, services to be provided by the Company, negligence or willful misconduct of the Company, violations of law by the Company, or from intellectual property infringement claims made by third parties. In addition, the Company has entered into indemnification agreements with directors and certain officers and employees that will require the Company, among other things, to indemnify them against certain liabilities that may arise by reason of their status or service as directors, officers or employees. No demands have been made upon the Company to provide indemnification under such agreements, and thus, there are no claims that the Company is aware of that could have a material effect on the Company’s Consolidated Balance Sheets, Consolidated Statements of Operations and Comprehensive Loss, or Consolidated Statements of Cash Flows.

Commitments

Effective September 2017, the Company entered into a Development and Manufacturing Services Agreement as amended (“DMSA”) with Lonza Sales AG (“Lonza”) for the development and manufacture of biologic products. Under the DMSA, the Company will execute purchase orders based on project plans authorizing Lonza to provide development and manufacturing services with respect to certain of the Company's antibody and enzyme products, and will pay for the services provided and batches delivered in accordance with the DMSA and project plan. Unless earlier terminated, the DMSA will expire when all development and manufacturing services are completed, which is not expected to be before November 2029. As of December 31, 2024 and 2023, the Company had total non-cancellable purchase commitments under the DMSA of $36.7 million and $37.6 million, respectively.

During the years ended December 31, 2024, 2023 and 2022, the Company incurred costs of $34.1 million, $39.5 million, and $28.6 million, respectively, and made payments of $36.6 million, $37.1 million, and $23.9 million respectively, for the development and manufacturing services rendered under the DMSA.

In the normal course of business, the Company enters into other firm purchase commitments primarily related to research and development activities. The Company had contractual obligations under certain clinical and manufacturing agreements other than the DMSA of $24.1 million and $34.8 million, as of December 31, 2024 and 2023, respectively, with certain amounts subject to cost sharing with Takeda. Further, the Company had other commitments of $2.2 million and $1.6 million as of both December 31, 2024 and 2023, respectively.

Contingencies

From time to time, the Company may be involved in lawsuits, arbitration, claims, investigations and proceedings consisting of intellectual property, employment and other matters which arise in the ordinary course of business. The Company records accruals for loss contingencies to the extent that the Company concludes that it is probable that a liability has been incurred and the amount of the related loss can be reasonably estimated.

Common Stock	12 Months Ended
Common Stock	Dec. 31, 2024
Equity [Abstract]
Common Stock	Common Stock On February 27, 2024, the Company entered into a securities purchase agreement (the "Purchase Agreement") with certain investors for the private placement of (i) 3,244,689 shares of Denali's common stock at a price of $17.07 per share and (ii) pre-funded warrants to purchase an aggregate of 26,046,065 shares of Denali's common stock (the "Pre-Funded Warrants") at a purchase price of $17.06 per Pre-Funded Warrant, which represents the per share price for the common stock less the $0.01 exercise price. The private placement closed on February 29, 2024, at which time the Company received aggregate net proceeds of approximately $499.3 million, after deducting issuance costs of approximately $0.5 million. The Pre-Funded Warrants were classified as a component of permanent equity in the Company’s consolidated balance sheet as they are freestanding financial instruments that are immediately exercisable, do not embody an obligation for the Company to repurchase its shares and permit the holders to receive a fixed number of shares of common stock upon exercise. All of the Pre-Funded Warrants issued in the private placement were outstanding as of December 31, 2024.

- Definition

The entire disclosure for equity.

+ References

Reference 1: http://www.xbrl.org/2003/role/disclosureRef
-Topic 505
-SubTopic 10
-Name Accounting Standards Codification
-Section 50
-Paragraph 13
-Subparagraph (b)
-Publisher FASB
-URI https://asc.fasb.org/1943274/2147481112/505-10-50-13

Reference 2: http://www.xbrl.org/2003/role/disclosureRef
-Topic 505
-SubTopic 10
-Name Accounting Standards Codification
-Section 50
-Paragraph 13
-Subparagraph (h)
-Publisher FASB
-URI https://asc.fasb.org/1943274/2147481112/505-10-50-13

Reference 3: http://www.xbrl.org/2003/role/disclosureRef
-Topic 505
-SubTopic 10
-Name Accounting Standards Codification
-Section 50
-Paragraph 14
-Subparagraph (b)
-Publisher FASB
-URI https://asc.fasb.org/1943274/2147481112/505-10-50-14

Reference 4: http://www.xbrl.org/2003/role/disclosureRef
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-Section 50
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-Subparagraph (a)
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-URI https://asc.fasb.org/1943274/2147477968/946-235-50-2

Reference 5: http://www.xbrl.org/2003/role/disclosureRef
-Topic 946
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-Name Accounting Standards Codification
-Section 50
-Paragraph 2
-Subparagraph (d)
-Publisher FASB
-URI https://asc.fasb.org/1943274/2147477968/946-235-50-2

Reference 6: http://www.xbrl.org/2003/role/disclosureRef
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-Name Accounting Standards Codification
-Section 50
-Paragraph 6
-Publisher FASB
-URI https://asc.fasb.org/1943274/2147478448/946-505-50-6

Reference 7: http://www.xbrl.org/2003/role/disclosureRef
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-SubTopic 40
-Name Accounting Standards Codification
-Section 50
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-Subparagraph (a)
-Publisher FASB
-URI https://asc.fasb.org/1943274/2147480237/815-40-50-6

Reference 8: http://www.xbrl.org/2003/role/disclosureRef
-Topic 505
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-Name Accounting Standards Codification
-Section S99
-Paragraph 1
-Subparagraph (SX 210.3-04)
-Publisher FASB
-URI https://asc.fasb.org/1943274/2147480008/505-10-S99-1

Reference 9: http://www.xbrl.org/2003/role/disclosureRef
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-Name Accounting Standards Codification
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-Paragraph 1
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Reference 10: http://fasb.org/us-gaap/role/ref/legacyRef
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-Name Accounting Standards Codification
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-URI https://asc.fasb.org/505/tableOfContent

Reference 11: http://www.xbrl.org/2003/role/disclosureRef
-Topic 505
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-Name Accounting Standards Codification
-Section 50
-Paragraph 13
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Reference 12: http://www.xbrl.org/2003/role/disclosureRef
-Topic 505
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-Name Accounting Standards Codification
-Section 50
-Paragraph 13
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-Publisher FASB
-URI https://asc.fasb.org/1943274/2147481112/505-10-50-13

Reference 13: http://www.xbrl.org/2003/role/disclosureRef
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-Subparagraph (i)
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Reference 14: http://www.xbrl.org/2003/role/disclosureRef
-Topic 505
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-Name Accounting Standards Codification
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-Paragraph 14
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Reference 15: http://www.xbrl.org/2003/role/disclosureRef
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Reference 16: http://www.xbrl.org/2003/role/disclosureRef
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Reference 17: http://www.xbrl.org/2003/role/disclosureRef
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Reference 18: http://www.xbrl.org/2003/role/disclosureRef
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Reference 19: http://www.xbrl.org/2003/role/disclosureRef
-Topic 505
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-Name Accounting Standards Codification
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-Publisher FASB
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+ Details

Income Taxes - Narrative (Details)	12 Months Ended
Income Taxes - Narrative (Details)	Dec. 31, 2024 USD ($)
Operating Loss Carryforwards [Line Items]
Net valuation allowance increase	$ 111,900,000
Unrecognized tax benefits that would reduce the annual effective tax rate, if recognized	0
Liability recorded for potential interest or penalties	0
Expected change to unrecognized tax benefit	0
Federal authority
Operating Loss Carryforwards [Line Items]
Net operating loss carryforward	436,600,000
Federal authority \| Research Tax Credit Carryforward
Operating Loss Carryforwards [Line Items]
Tax credit carryforward	64,200,000
Federal authority \| Orphan Drug Tax Credit Carryforward
Operating Loss Carryforwards [Line Items]
Tax credit carryforward	56,900,000
State authority
Operating Loss Carryforwards [Line Items]
Net operating loss carryforward	310,900,000
Tax credit carryforward	$ 44,400,000

Income Taxes - Provision for Income Taxes (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2024	Dec. 31, 2023	Dec. 31, 2022
Current:
U.S. Federal	$ 0	$ 0	$ 0
U.S. State	0	0	7
Foreign	68	30	14
Total Current	68	30	21
Deferred:
U.S. Federal	0	0	0
U.S. State	0	0	0
Foreign	0	0	0
Total deferred	0	0	0
Total provision for income taxes	$ 68	$ 30	$ 21

Income Taxes - Schedule of Deferred Tax Assets and Liabilities (Details) - USD ($) $ in Thousands	Dec. 31, 2024	Dec. 31, 2023
Deferred tax assets:
Net operating loss carryforwards	$ 113,397	$ 89,273
Tax credit carryforwards	124,922	95,808
Research expense capitalization	176,094	119,349
Lease liabilities	11,760	12,663
Stock-based compensation	57,766	53,226
Fixed assets	6,671	0
Accruals and other	13,447	17,453
Gross deferred tax assets	504,057	387,772
Valuation allowance	(487,714)	(375,795)
Net deferred tax assets	16,343	11,977
Deferred tax liabilities:
Property and equipment	0	(5,663)
Lease right-of-use assets	(16,343)	(6,314)
Net deferred tax assets	$ 0	$ 0

Income Taxes

12 Months Ended

Dec. 31, 2024

Income Tax Disclosure [Abstract]

Income Taxes

The provision for income taxes consisted of the following (in thousands):


	Year Ended December 31,
	2024		2023		2022
Current:
U.S. Federal	$	—	$	—	$	—
U.S. State	—		—		7
Foreign	68		30		14
Total Current	$	68	$	30	$	21

Deferred:
U.S. Federal	$	—	$	—	$	—
U.S. State	—		—		—
Foreign	—		—		—
Total deferred	$	—	$	—	$	—
Total provision for income taxes	$	68	$	30	$	21

The reconciliation of federal statutory income tax rate to our effective income tax rate is as follows:


	Year Ended December 31,
	2024		2023		2022
Taxes at the U.S. statutory tax rate	21.0	%	21.0	%	21.0	%

Change in valuation allowance	(25.0)		(27.3)		(25.1)
Research tax credits	5.6		14.5		4.9
Stock-based compensation	(2.1)		(3.2)		(0.5)
Nondeductible acquisition-related costs	—		(3.5)		—


Impact of IRC 162m	(0.2)		(0.7)		—
Other	0.7		(0.8)		(0.4)
Total provision for income taxes	—	%	—	%	(0.1)	%

Deferred Income Taxes

The components of the Company’s net deferred tax assets are as follows (in thousands):


	December 31,
	2024		2023
Deferred tax assets:
Net operating loss carryforwards	$	113,397	$	89,273
Tax credit carryforwards	124,922		95,808
Research expense capitalization	176,094		119,349

Lease liabilities	11,760		12,663
Stock-based compensation	57,766		53,226
Fixed assets	6,671		—
Accruals and other	13,447		17,453
Gross deferred tax assets	504,057		387,772
Valuation allowance	(487,714)		(375,795)
Net deferred tax assets	16,343		11,977
Deferred tax liabilities:
Property and equipment	—		(5,663)
Lease right-of-use assets	(16,343)		(6,314)
Net deferred tax assets	$	—	$	—

Recognition of deferred tax assets is appropriate when realization of such assets is more likely than not. Based upon the weight of available evidence, especially the uncertainties surrounding the realization of deferred tax assets through future taxable income, the Company believes it is not more likely than not that the deferred tax assets will be fully realizable. Accordingly, the Company has provided a full valuation allowance against its net deferred tax assets as of December 31, 2024 and 2023. There was an increase in the net valuation allowance of $111.9 million during the year ended December 31, 2024.

As of December 31, 2024, the Company has federal net operating loss (“NOL”) carryforwards of approximately $436.6 million, which are available to reduce future taxable income, and has federal R&D and orphan drug tax credits of approximately $64.2 million and $56.9 million respectively, both of which may be used to offset future tax liabilities. The federal NOL and federal tax credit carryforwards will begin to expire in 2034. The Company also has state NOL carryforwards of approximately $310.9 million, which are available to reduce future taxable income, and has state tax credits of approximately $44.4 million which may be used to offset future tax liabilities. The state NOL will begin to expire in 2031 and the state tax credit carryforwards will be carried forward indefinitely.

The NOL and tax credit carryforwards are subject to review and possible adjustment by the Internal Revenue Service (“IRS”) and state tax authorities and may become subject to an annual limitation in the event of certain future cumulative changes in the ownership interest of significant stockholders over a three-year period in excess of 50%, as defined under Sections 382 and 383 of the Internal Revenue Code of 1986. This could limit the amount of tax attributes that can be utilized annually to offset future taxable income or tax liabilities. Annual limitations may result in expiration of net operating loss and tax credit carryforwards before some or all of such amounts have been utilized.

The Company follows the provisions of ASC 740, Accounting for Income Taxes, and the accounting guidance related to accounting for uncertainty in income taxes. The Company determines its uncertain tax positions based on a determination of whether and how much of a tax benefit taken by the Company in its tax filings is more likely than not to be sustained upon examination by the relevant income tax authorities.

A reconciliation of the beginning and ending amounts of unrecognized tax benefits is as follows (in thousands):


	December 31,
	2024		2023		2022
Unrecognized tax benefits at January 1	$	26,175	$	19,371	$	13,699
Additions for tax positions taken in a prior year	162		168		135
Additions for tax positions taken in the current year	7,424		6,636		5,537
Reductions for tax positions taken in the prior year	—		—		—
Unrecognized tax benefits at December 31	$	33,761	$	26,175	$	19,371

If recognized, none of the unrecognized tax benefits would reduce the effective tax rate for the year ended December 31, 2024. The Company will recognize both accrued interest and penalties related to unrecognized benefits in income tax expense. As of December 31, 2024, no liability has been recorded for potential interest or penalties. The Company does not expect the unrecognized tax benefits to change significantly over the next 12 months.

Since the Company is in a loss carryforward position, the Company is generally subject to examination by the U.S. federal, state and local income tax authorities for all tax years in which a loss carryforward is available.

- Definition

The entire disclosure for income tax.

+ References

Reference 1: http://www.xbrl.org/2003/role/disclosureRef
-Topic 740
-SubTopic 10
-Name Accounting Standards Codification
-Section 50
-Paragraph 12
-Publisher FASB
-URI https://asc.fasb.org/1943274/2147482685/740-10-50-12

Reference 2: http://www.xbrl.org/2003/role/exampleRef
-Topic 740
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-Name Accounting Standards Codification
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Reference 3: http://www.xbrl.org/2003/role/disclosureRef
-Topic 740
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-Name Accounting Standards Codification
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-Paragraph 12C
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-URI https://asc.fasb.org/1943274/2147482685/740-10-50-12C

Reference 4: http://www.xbrl.org/2003/role/disclosureRef
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-Section 50
-Paragraph 12B
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-URI https://asc.fasb.org/1943274/2147482685/740-10-50-12B

Reference 5: http://www.xbrl.org/2003/role/disclosureRef
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-Name Accounting Standards Codification
-Section 50
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-URI https://asc.fasb.org/1943274/2147477891/740-270-50-1

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Reference 7: http://www.xbrl.org/2003/role/disclosureRef
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Reference 9: http://www.xbrl.org/2003/role/disclosureRef
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Reference 13: http://www.xbrl.org/2003/role/disclosureRef
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-Publisher FASB
-URI https://asc.fasb.org/1943274/2147482603/740-30-50-2

+ Details

Acquisition, License Agreement and Research and Development Funding Collaboration Agreement	12 Months Ended
	Dec. 31, 2024
Business Combination, Asset Acquisition, and Joint Venture Formation [Abstract]
Acquisition, License Agreement and Research and Development Funding Collaboration Agreement	Acquisition, License Agreement and Research and Development Funding Collaboration Agreement Acquisition of F-star Gamma In May 2018, the Company exercised an option to acquire all of the outstanding shares of F-star Gamma Limited ("F-Star Gamma") pursuant to a prenegotiated buy-out option agreement (the "Acquisition"). As a result of the Acquisition, F-star Gamma became a wholly-owned subsidiary of the Company and the Company changed the entity’s name to Denali BBB Holding Limited. In addition, the Company became a direct licensee of certain intellectual property of F-star Biotechnology Limited (“F-Star Ltd”) by way of the Company’s assumption of F-star Gamma’s license agreement with F-star Ltd, dated August 24, 2016, (the “F-star Gamma License”). The transaction was accounted for as an asset acquisition. The Acquisition obligates the Company to make certain contingent payments to former shareholders and under the F-star Gamma license. In 2023, the Company incurred $30.0 million in R&D expenses associated with the achievement of a clinical milestone. There was no contingent consideration expense recognized for the years ended December 31, 2024 or 2022. Under this arrangement, the Company may be required to make additional contingent consideration payments of up to $210.0 million, consisting of up to $60.0 million in regulatory contingent payments and up to $150.0 million in commercial contingent payments. Genentech License Agreement In June 2016, the Company entered into an Exclusive License Agreement with Genentech, Inc. (“Genentech”), giving the Company access to Genentech’s LRRK2 inhibitor small molecule program for Parkinson's disease. The Company may owe Genentech milestone payments upon the achievement of certain development, regulatory, and commercial milestones, up to a maximum of $315.0 million in the aggregate, including up to $37.5 million in clinical milestone payments, $102.5 million in regulatory milestone payments and $175.0 million in commercial milestone payments. In addition, the Company may owe royalties on net sales of licensed products ranging from low to high single-digit percentages. The Company has made a total of $25.0 million in consideration payments under the Genentech agreement, including $12.5 million in the year ended December 31, 2022 related to two clinical milestones. The Company has recognized $18.8 million of research and development expense, net of cost sharing reimbursements from Biogen, including $6.3 million in the year ended December 31, 2022. The Company did not recognize expenses under this agreement in the years ended December 31, 2024 and 2023. Collaboration and Development Funding Agreement On January 29, 2024, the Company entered into a Collaboration and Development Funding Agreement with an unrelated third party, pursuant to which this third party will provide up to $75.0 million of funding and collaborate with the Company to conduct a global Phase 2a study of BIIB122/DNL151 in patients with Parkinson’s disease and confirmed pathogenic variants of LRRK2. Pursuant to this agreement, the Company received payments totaling $25.0 million during the year ended December 31, 2024, with the remainder to be paid upon achievement of operational milestones in the study. After the full $75.0 million in consideration has been paid, the third party will be eligible to receive low single-digit royalties from the Company on annual worldwide net sales of LRRK2 inhibitors for the treatment of Parkinson’s disease. The Company determined that this arrangement is an R&D funding arrangement under ASC 730. As the third party is sharing in the risk associated with research and development activities with the Company, the development funding is recognized as an obligation to perform contractual services. Accordingly, payments received will be recorded as a liability, and recognized by the Company as a reduction to research and development expenses over the estimated Phase 2a study period as the underlying research and development costs are incurred. Under this arrangement, the Company recognized a $10.9 million offset to research and development expenses in the Consolidated Statements of Operations and Comprehensive Loss for the year ended December 31, 2024. The Company recorded a current deferred research and development funding liability of $14.1 million on the Consolidated Balance Sheet as of December 31, 2024.

Collaboration Agreements - Sanofi (Details) - USD ($)

1 Months Ended

12 Months Ended

74 Months Ended

75 Months Ended

Nov. 30, 2018

Dec. 31, 2024

Dec. 31, 2023

Dec. 31, 2022

Dec. 31, 2024

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Collaboration revenue from customers

^[1]

$ 0

$ 330,531,000

$ 105,065,000

Performance obligation

Sanofi | Collaborative Arrangement | CNS Product

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Collaboration revenue from customers

$ 65,000,000

Sanofi | Collaborative Arrangement | Peripheral Program License

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Collaboration revenue from customers

35,000,000

Sanofi | Collaborative Arrangement

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Upfront payment

$ 125,000,000

Collaboration revenue from customers

25,000,000

$ 50,000,000

$ 100,000,000

Performance obligation

Receivable

Sanofi | Collaborative Arrangement | Peripheral Program License

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Milestone payments upon achievement of certain clinical, regulatory and sales milestone events

495,000,000

Clinical milestone payment

120,000,000

Regulatory milestone payment

175,000,000

Commercial milestone payments

$ 200,000,000

Sanofi | Collaborative Arrangement | Alzheimer's Disease Services

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Contract liability

$ 0

Sanofi | Collaborative Arrangement | Product

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Collaboration revenue from customers

$ 0

[1]	Includes related-party collaboration revenue from customers of $295.5 million, and $3.2 million for the years ended December 31, 2023 and 2022, respectively.

Collaboration Agreements - Summary of Cost Sharing Payments and Reimbursements (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2024	Dec. 31, 2023	Dec. 31, 2022
Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]
Net cost sharing payments (reimbursements)	$ 10,806	$ 5,513	$ (10,043)
Accounts payable	11,137	9,483
Takeda Pharmaceutical Company Limited
Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]
Net cost sharing payments (reimbursements)	(5,936)	(12,165)	(18,230)
Takeda Pharmaceutical Company Limited \| PTV:PGRN Collaboration Agreement
Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]
Net cost sharing payments (reimbursements)	(4,789)	(7,065)	(11,276)
Takeda Pharmaceutical Company Limited \| ATV:TREM2 Collaboration Agreement
Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]
Net cost sharing payments (reimbursements)	(1,147)	(5,100)	(6,954)
Takeda Pharmaceutical Company Limited \| Collaborative Arrangement, PTV:PGRN And ATV:TREM2
Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]
Receivable	1,500	2,700
Biogen \| LRRK2 Product
Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]
Cost sharing payments	16,742	17,678	$ 8,187
Biogen \| Biogen Collaboration Agreement
Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]
Accounts payable	$ 2,500	$ 3,200

Marketable Securities

12 Months Ended

Dec. 31, 2024

Investments, Debt and Equity Securities [Abstract]

Marketable Securities

All marketable securities were considered available-for-sale at December 31, 2024 and 2023. On a recurring basis, the Company records its marketable securities at fair value using Level 1 or Level 2 inputs as discussed in Note 2, "Fair Value Measurements". The amortized cost, gross unrealized holding gains or losses, and fair value of the Company’s marketable securities by major security type at each balance sheet date are summarized in the tables below (in thousands):


	December 31, 2024
	Amortized Cost		Unrealized Holding Gains		Unrealized Holding Losses		Aggregate Fair Value
Short-term marketable securities:
U.S. government treasuries(1)	$	627,809	$	1,618	$	(27)	$	629,400

Corporate debt securities	21,337		62		—		21,399
Commercial paper	6,572		—		—		6,572
Total short-term marketable securities	655,718		1,680		(27)		657,371
Long-term marketable securities:
U.S. government treasuries(2)	334,300		788		(196)		334,892

Corporate debt securities	24,354		127		—		24,481
Total long-term marketable securities	358,654		915		(196)		359,373
Total	$	1,014,372	$	2,595	$	(223)	$	1,016,744

______________________________________________

(1)Unrealized holding losses on 3 securities with an aggregate fair value of 64.0 million.

(2)Unrealized holding losses on 4 securities with an aggregate fair value of 114.0 million


	December 31, 2023
	Amortized Cost		Unrealized Holding Gains		Unrealized Holding Losses		Aggregate Fair Value
Short-term marketable securities:
U.S. government treasuries(1)	$	868,174	$	998	$	—	$	869,172
U.S. government agency securities	7,089		—		(3)		7,086

Commercial paper	31,147		—		—		31,147





Total	$	906,410	$	998	$	(3)	$	907,405

__________________________________________________

(1)Unrealized holding losses on 2 securities with an aggregate fair value of $7.1 million.

As of December 31, 2024 and 2023, some of the Company's marketable securities were in an unrealized loss position. The Company had not recognized an allowance for credit losses as of December 31, 2024 or 2023. The Company determined that it had the ability and intent to hold all marketable securities that have been in a continuous loss position until maturity or recovery. Further, a majority of the Company's investments were held in U.S. government securities, and the remainder were held with investment grade, high credit quality institutions. All marketable securities with unrealized losses as of each balance sheet date had been in a loss position for less than twelve months or the loss is not material.

As of December 31, 2024 all of the Company’s marketable securities had an effective maturity of less than two years.

Stock-Based Awards - Summary of Assumptions Used for Estimating the Fair Value of Stock Options Granted (Details)	12 Months Ended
	Dec. 31, 2024	Dec. 31, 2023	Dec. 31, 2022
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Dividend yield	0.00%
Stock Options
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Volatility, minimum	64.50%	67.60%	65.10%
Volatility, maximum	66.00%	69.60%	66.30%
Risk-free interest rate, minimum	3.70%	3.40%	1.50%
Risk-free interest rate, maximum	4.50%	4.80%	4.30%
Dividend yield	0.00%	0.00%	0.00%
Stock Options \| Minimum
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Expected term (in years)	5 years 6 months	5 years 6 months	5 years 6 months
Stock Options \| Maximum
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Expected term (in years)	6 years 29 days	6 years 29 days	6 years 29 days

Pay vs Performance Disclosure - USD ($) $ in Thousands	12 Months Ended
Pay vs Performance Disclosure - USD ($) $ in Thousands	Dec. 31, 2024	Dec. 31, 2023	Dec. 31, 2022
Pay vs Performance Disclosure
Net loss	$ (422,773)	$ (145,224)	$ (325,991)

- Definition

The portion of profit or loss for the period, net of income taxes, which is attributable to the parent.

+ References

+ Details

Stock-Based Awards - Summary of Stock-Based Compensation Expense (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2024	Dec. 31, 2023	Dec. 31, 2022
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Total	$ 102,878	$ 108,102	$ 99,847
Research and development
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Total	59,146	62,901	60,196
General and administrative
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Total	$ 43,732	$ 45,201	$ 39,651

- Definition

Line items represent financial concepts included in a table. These concepts are used to disclose reportable information associated with domain members defined in one or many axes to the table.

+ References

Reference 1: http://www.xbrl.org/2003/role/disclosureRef
-Topic 718
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-Name Accounting Standards Codification
-Section 35
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Reference 2: http://www.xbrl.org/2003/role/disclosureRef
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Reference 9: http://www.xbrl.org/2003/role/disclosureRef
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Reference 12: http://www.xbrl.org/2003/role/disclosureRef
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+ Details

Insider Trading Arrangements

3 Months Ended

12 Months Ended

Dec. 31, 2024

Trading Arrangements, by Individual

Material Terms of Trading Arrangement

Our policy governing transactions in our securities by our directors, officers, and employees permits our officers, directors and employees to enter into trading plans complying with Rule 10b5-1 under the Securities Exchange Act of 1934, as amended. As disclosed in the table below, during the fourth quarter of 2024, certain of our directors adopted a “Rule 10b5-1 trading arrangement”. This plan provides for the sale of our common stock and is intended to satisfy the affirmative defense in Rule 10b5-1(c).

Name

Position

Date of Plan Adoption

Scheduled End Date of Trading Arrangement(1)

Maximum Total Shares of Common Stock to be Sold Under the Plan(2)

Carole Ho, M.D.

Chief Medical Officer

12/11/2024

3/12/2026

373,374

Alexander Schuth, M.D.

Chief Operating and Financial Officer

12/30/2024

3/31/2026

176,026

__________________________________________________

(1)The trading arrangement may expire on an earlier date if and when all transactions under the arrangement are completed.

(2)This amounts represents the maximum total shares that could be sold under the plan, but the amounts may change for executive officers due to the sale of shares to satisfy tax withholding requirements.

Non-Rule 10b5-1 Arrangement Adopted

false

Rule 10b5-1 Arrangement Terminated

false

Non-Rule 10b5-1 Arrangement Terminated

false

Carole Ho, M.D. [Member]

Trading Arrangements, by Individual

Name

Carole Ho, M.D.

Title

Chief Medical Officer

Rule 10b5-1 Arrangement Adopted

true

12/11/2024

3/12/2026

456 days

373,374

Alexander Schuth, M.D. [Member]

Trading Arrangements, by Individual

Name

Alexander Schuth, M.D.

Title

Chief Operating and Financial Officer

Rule 10b5-1 Arrangement Adopted

true

12/30/2024

3/31/2026

456 days

176,026

Significant Accounting Policies - Investments (Details)	12 Months Ended
Significant Accounting Policies - Investments (Details)	Dec. 31, 2024 USD ($)
Accounting Policies [Abstract]
Equity securities without readily determinable fair value, impairment loss, annual amount	$ 0

Significant Accounting Policies - Convertible Preferred Stock (Details) - shares	Dec. 31, 2024	Dec. 31, 2023
Accounting Policies [Abstract]
Convertible preferred stock, shares authorized (in shares)	40,000,000	40,000,000
Convertible preferred stock, shares issued (in shares)	0	0
Convertible preferred stock, shares outstanding (in shares)	0	0

Audit Information	12 Months Ended
Audit Information	Dec. 31, 2024
Audit Information [Abstract]
Auditor Firm ID	42
Auditor Name	Ernst & Young LLP
Auditor Location	San Mateo, California

Balance Sheet Components - Property and Equipment, Net (Details) - USD ($) $ in Thousands	Dec. 31, 2024	Dec. 31, 2023
Property, Plant and Equipment [Line Items]
Total property and equipment	$ 107,278	$ 91,592
Less: accumulated depreciation	(52,042)	(46,003)
Total property and equipment, net	55,236	45,589
Leasehold improvements
Property, Plant and Equipment [Line Items]
Total property and equipment	46,905	41,238
Laboratory equipment
Property, Plant and Equipment [Line Items]
Total property and equipment	40,554	36,985
Manufacturing equipment
Property, Plant and Equipment [Line Items]
Total property and equipment	15,998	9,722
Computer equipment and purchased software
Property, Plant and Equipment [Line Items]
Total property and equipment	1,841	1,741
Furniture and fixtures
Property, Plant and Equipment [Line Items]
Total property and equipment	$ 1,980	$ 1,906

Income Taxes - Reconciliation of Unrecognized Tax Benefits (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2024	Dec. 31, 2023	Dec. 31, 2022
Unrecognized Tax Benefits [Roll Forward]
Unrecognized tax benefits at January 1	$ 26,175	$ 19,371	$ 13,699
Additions for tax positions taken in a prior year	162	168	135
Additions for tax positions taken in the current year	7,424	6,636	5,537
Reductions for tax positions taken in the prior year	0	0	0
Unrecognized tax benefits at December 31	$ 33,761	$ 26,175	$ 19,371

Insider Trading Policies and Procedures	12 Months Ended
Insider Trading Policies and Procedures	Dec. 31, 2024
Insider Trading Policies and Procedures [Line Items]
Insider Trading Policies and Procedures Adopted	true

Collaboration Agreements

12 Months Ended

Dec. 31, 2024

Organization, Consolidation and Presentation of Financial Statements [Abstract]

Collaboration Agreements

Biogen

In August 2020, the Company entered into a binding Provisional Collaboration and License Agreement (“Provisional Biogen Collaboration Agreement”) with Biogen Inc.’s subsidiaries, Biogen MA Inc. (“BIMA”) and Biogen International GmbH (“BIG”) (BIMA and BIG, collectively, “Biogen”) pursuant to which the Company granted Biogen a license to co-develop and co-commercialize Denali’s small molecule LRRK2 inhibitor program (the “LRRK2 Program”), an option in respect of each of (i) the Company’s amyloid beta program utilizing the Company's TransportVehicleTM ("TV") technology to cross the blood-brain barrier ("BBB") and (ii) one other unnamed program also utilizing the Company's TV technology platform (the “Option Programs”), and a right of first negotiation with respect to two additional unnamed programs for indications within Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis ("ALS") and multiple sclerosis ("MS") utilizing the Company's TV technology platform (the “ROFN Programs”), should the Company decide to seek a collaboration with a third party for such programs. The Provisional Biogen Collaboration Agreement was a binding agreement, which became effective on the closing of the Common Stock Purchase Agreement ("SPA"), as described further below. The Provisional Biogen Collaboration Agreement expired in October 2020 upon the execution of a Definitive LRRK2 Collaboration and License Agreement (“LRRK2 Agreement”) with Biogen on October 4, 2020 and a Right of First Negotiation, Option and License Agreement (the “ROFN and Option Agreement”) on October 6, 2020 (collectively, the "Biogen Collaboration Agreement"). Biogen made an upfront payment of $560.0 million upon execution of the Biogen Collaboration Agreement in October 2020, which was included in the transaction price at inception.

In August 2023, the Company and Biogen executed an Amendment (the “Biogen Amendment”) to the LRRK2 Agreement and ROFN and Option Agreement, pursuant to which Biogen waived its option to the second option program and its ROFN rights. In July 2024, Denali and Biogen executed a Side Letter to the ROFN and Option Agreement, pursuant to which, effective as of the date of the Side Letter, Biogen terminated its license to the Company's amyloid beta program utilizing the Company's TV technology platform, and granted Denali rights to data generated during the collaboration. The side letter also effected the immediate termination of the ROFN and Option Agreement; as such, the Company expects to receive no future milestone or royalty payments from Biogen related to the ROFN and Option Agreement.

LRRK2 Agreement

With respect to the LRRK2 Program, Biogen is required to make milestone payments up to approximately $1.125 billion upon achievement of certain development and sales milestone events. Such milestone payments include $375.0 million in development, $375.0 million upon first commercial sale, and $375.0 million in net sales-based milestones. Pursuant to the Biogen Amendment, the schedule of potential LRRK2 Agreement milestones was amended, while maintaining the same total value of milestones that Denali is eligible to receive. The Company will share 50% of the profits and losses with Biogen for LRRK2 Products in the United States, and 40% of such profits and losses in China. The Company will be entitled to receive royalties in the high teens to low twenties percentages on net sales for LRRK2 Products outside of the United States and China.

The Company and Biogen are jointly developing LRRK2 Products pursuant to a clinical development plan set forth within the LRRK2 Agreement. The parties share responsibility and costs for global development of LRRK2 Products pursuant to a mutually agreed development plan and budget ("LRRK2 Development Activities"), with Biogen funding 60% and the Company funding 40% of such costs.

The Company may opt out of development cost sharing worldwide and upon such election, from any further profit-sharing from the LRRK2 Program. The Company also has the right to opt-out of the profit sharing arrangement for the LRRK2 Program or for only those LRRK2 Products that do not penetrate the BBB (“Peripheral LRRK2 Products”), in each of the United States and China. After such an opt out, the Company will no longer be obligated to share in the development and commercialization costs for, or be entitled to share in the applicable revenues from, such LRRK2 Program (or from the Peripheral LRRK2 Products) for such country, as applicable. If the Company chooses to exercise its opt out rights, the Company will be entitled to receive tiered royalties on net sales of the applicable LRRK2 Program in the relevant country (or countries). The royalty rates for the applicable LRRK2 Program will be a percentage in the high teens to low twenties, but may increase to the mid-twenties if the Company has met certain co-funding thresholds or there has been a first commercial sale at the time of the Company's election.

Stock Purchase Agreement

In connection with the Provisional Biogen Collaboration Agreement, the Company entered into a common stock purchase agreement (the "Stock Purchase Agreement") with BIMA on August 5, 2020, pursuant to which the Company sold 13,310,243 shares of common stock (the “Shares”) to BIMA for an aggregate purchase price of $465.0 million. Management determined that it was appropriate to account for the Provisional Biogen Collaboration Agreement and the SPA as one arrangement because they were entered into at the same time with interrelated financial terms. This stock issuance resulted in a $44.9 million premium paid to the Company above the estimated fair value of the Company's common stock, which forms part of the transaction price at inception for the Biogen Collaboration Agreement. The shares of common stock owned by Biogen as of December 31, 2022 and through September 30, 2023, represented approximately 10% of the voting interest of the Company, and as such, Biogen was considered a related party as defined in ASC 850. In the quarter ended December, 2023, the percentage voting interest had declined such that Biogen was no longer considered a related party as defined in ASC 850.

Biogen Collaboration Agreement

In April 2023, Biogen exercised its option to license the Company's ATV:Abeta program and made a $5.0 million option exercise fee payment.

The Biogen Collaboration Agreement was considered to be a contract modification to the Provisional Biogen Collaboration Agreement and was accounted for as a termination of the provisional agreement and commencement of a new contract. The Biogen Amendment was considered to be a continuation of the Biogen Collaboration Agreement.

The Company identified the following distinct performance obligations associated with the Biogen Collaboration Agreement that had not yet been delivered under the original contract: the LRRK2 Program license, the research services for the ATV:Abeta and TV programs (“Option Research Services”) which include option joint steering committee ("JSC") participation, and a material right for an option under the ROFN and Option Agreement. Further, the LRRK2 Development Activities which includes LRRK2 JSC and joint development committee (“JDC”) participation was identified as a unit of account under ASC 808. The LRRK2 Development Activities, JSC and JDC participation are considered to be a single unit of account since the development activities are highly interrelated with the JSC and JDC involvement and these are not distinct in the context of the contract. Further, the same was considered to be true for the option research services and option JSC participation performance obligation.

The Company believes that the Biogen Collaboration Agreement is a collaboration arrangement as defined in ASC 808, Collaborative Arrangements. The Company also believes that Biogen meets the definition of a customer as defined in ASC 606, Revenue From Contracts With Customers for all of the performance obligations identified at inception except for the LRRK2 Development Activities. Since ASC 808 does not address recognition and measurement, the Company looked to other accounting literature for guidance where the performance obligation does not fall under ASC 606, and determined that for the interim LRRK2 development activities subject to cost sharing provisions, the guidance in ASC 730, Research and Development should be applied.

The Company identified the LRRK2 Program license, the research services for the ATV:Abeta and TV programs (“Option Research Services”) and a material right for an option under the ROFN and Option Agreement as distinct performance obligations associated with the Biogen Collaboration Agreement. Further, the LRRK2 Development Activities was identified as a unit of account under ASC 808. The respective standalone value for each of the performance obligations was determined at inception by applying the SSP method and the transaction price of $604.9 million at inception was allocated based on the relative SSP method with revenue recognition timing to be determined either by delivery, resolution of an option, or the provision of services.

The LRRK2 Program license was delivered on or around the effective date of the Biogen Collaboration Agreement and the revenue allocated to this performance obligation was recognized during the year ended December 31, 2020. The Option Research Services were delivered over time as the services are performed, with revenue being recognized over time based on costs incurred to perform the services. As of December 31, 2023, all revenue allocated to the Option Research Services had been recognized. The $288.9 million of revenue allocated to the material right for an option under the ROFN and Option Agreement was initially deferred as a contract liability, and was recognized in full during the year ended December 31, 2023, upon Biogen's ATV:Abeta option exercise, along with the $5.0 million option exercise fee paid upon opt in, which was fully allocated to the material right. The LRRK2 Development Activities cost sharing reimbursements or expenses are being recognized over time as earned or incurred, since this is believed to directly correlate to the value of the services performed.

In assessing the Biogen Collaboration Agreement, management exercised considerable judgment in estimating revenue to be recognized, specifically related to estimating the discount for lack of marketability associated with the stock issuance, determining the separate performance obligations under the Biogen Collaboration Agreement, and estimating the standalone selling price of those performance obligations.

As of December 31, 2024, the Company had earned $5.0 million in option fee payments, but had not recorded milestone revenue or product sales under the Biogen Collaboration Agreement.

Sanofi

In October 2018, the Company entered into a Collaboration and License Agreement ("Sanofi Collaboration Agreement") with Genzyme Corporation, a wholly owned subsidiary of Sanofi S.A. ("Sanofi") pursuant to which certain small molecule CNS and peripheral receptor interacting serine/threonine protein kinase 1 ("RIPK1") inhibitors contributed by Sanofi and by the Company would be developed and commercialized. When the Sanofi Collaboration Agreement became effective in November 2018, Sanofi paid us $125.0 million upfront. Under the Sanofi Collaboration Agreement, Sanofi is required to make milestone payments totaling up to approximately $495.0 million upon achievement of certain clinical, regulatory and sales milestone events for the Peripheral Products. Such milestone payments include $120.0 million in clinical milestone payments, $175.0 million in regulatory milestone payments and $200.0 million in commercial milestone payments for Peripheral Products, as defined, that are developed and approved in the United States, Europe and in Japan for three indications. Sanofi has made payments of $35.0 million for Peripheral Product clinical milestones through December 31, 2024, and payments of $65.0 million for CNS Product clinical milestones through the sale date. On February 24, 2025, Denali and Sanofi executed a side letter terminating Sanofi's license to the CNS Products program including SAR443820/DNL788. Subsequent to this side letter, the Company expects to receive no future milestone or royalty payments from Sanofi related to the CNS Products program. The Company will receive variable royalties on net sales for Peripheral Products sold worldwide, each as further described below.

Sanofi will be responsible, at its cost, for conducting activities relating to the development and commercialization of all Peripheral Products. Denali will be entitled to receive tiered royalties in the low- to mid- teen percentages on net sales of Peripheral Products.

The Company believes that the Sanofi Collaboration Agreement is a collaboration arrangement as defined in ASC 808, Collaborative Arrangements. The Company also believes that Sanofi meets the definition of a customer as defined in ASC 606, Revenue From Contracts With Customers for all of the performance obligations identified at inception except for the Alzheimer's Disease Services. Since ASC 808 does not address recognition and measurement, the Company looked to other accounting literature for guidance where the performance obligation does not fall under ASC 606, and determined that for any future cost sharing, the guidance in ASC 730, Research and Development should be applied.

The Company identified the CNS program license, the Peripheral program license, the Phase 1 and Phase 2 trials for CNS Products for Alzheimer’s disease ("Alzheimer's Disease Services"), and the Phase 1b trial for DNL747 for ALS and associated activities ("Retained Activities") as distinct performance obligations associated with the Sanofi Collaboration Agreement. The respective standalone value for each of the performance obligations was determined at inception by applying the SSP method and the transaction price at inception was allocated based on the relative SSP method with revenue recognition timing to be determined either by delivery or the provision of services.

The program licenses and existing know-how were delivered on the effective date of the Sanofi Collaboration Agreement, and as such upfront revenue allocated to these performance obligations were recognized at this time. Further, clinical milestones are recognized as earned since these relate to the underlying program licenses previously delivered. The Alzheimer’s Disease Services and the Retained Activities were expected to be delivered over time as the services are performed. For the Alzheimer's Disease Services, revenue was recognized over time using the input method, based on costs incurred to perform the services, since the level of costs incurred over time was thought to best reflect the transfer of services to Sanofi. For the Retained Activities, revenue was recognized over time using the output method, based on amounts invoiced to Sanofi, since this is believed to directly correlate to the value of the services performed.

During the years ended December 31, 2023 and 2022, the Company earned clinical milestones of $25.0 million and $50.0 million, respectively. These milestones were recognized in collaboration revenue from customers in the Consolidated Statement of Operations and Comprehensive Loss during for the years ended December 31, 2023 and 2022, respectively, since the associated performance obligation has been satisfied. There were no milestones recognized in collaboration revenue from customers in the Consolidated Statement of Operations and Comprehensive Loss for the year ended December 31, 2024.

The Company has no remaining performance obligations under the Sanofi Collaboration Agreement, and no contract liability remains on the Consolidated Balance Sheets as of December 31, 2024 or 2023. The Company did not record any receivable associated with the Sanofi Collaboration Agreement on the Consolidated Balance Sheets as of December 31, 2024 or 2023.

In assessing the Sanofi Collaboration Agreement, management exercised considerable judgment in estimating revenue to be recognized. Management applied judgment in determining the separate performance obligations, in estimating the selling price, in determining when control was transferred to Sanofi for the licenses, and in estimating total future costs when using the input method.

As of December 31, 2024, the Company had earned milestone payments of $100.0 million and had not recorded any product sales under the Sanofi Collaboration Agreement.

Takeda

Takeda Collaboration Agreement

In January 2018, the Company entered into a Collaboration and Option Agreement ("Takeda Collaboration Agreement") with Takeda Pharmaceutical Company Limited ("Takeda"), pursuant to which the Company granted Takeda an option to develop and commercialize, jointly with the Company, certain biologic products that are enabled by the Company's BBB delivery technology and intended for the treatment of neurodegenerative disorders. The programs subject to the Takeda Collaboration Agreement were the Company’s ATV:BACE1/Tau, ATV:TREM2 and PTV:PGRN programs. The Takeda Collaboration Agreement became effective in February 2018, at which time Takeda paid the Company an upfront payment of $40.0 million. In February 2019, the agreement was amended to replace the ATV:BACE1/Tau program with the ATV:Tau program, and in March 2022, Takeda and the Company agreed to terminate activity on the ATV:Tau program. Subsequent to the ATV:Tau termination, total preclinical milestone payments that Takeda owed under the Takeda Collaboration Agreement was $55.0 million for all three programs, all of which had been earned and received as of December 31, 2022.

Pursuant to the terms of the Takeda Collaboration Agreement, the Company entered into a common stock purchase agreement with Takeda on January 3, 2018, pursuant to which Takeda purchased 4,214,559 shares of the Company’s common stock on February 23, 2018 for an aggregate purchase price of $110.0 million, which included a $15.6 million stock premium.

Subsequent to Takeda exercising its option with respect to a particular target and collaboration program (i.e., the biologic products directed to the target for which Takeda has exercised its option), Takeda has the right to develop and commercialize, jointly with the Company, a specified number of biologic products enabled by its BBB delivery technology that were developed during the research period and which are directed to the relevant target, and the Company grants to Takeda a co-exclusive license under the intellectual property the Company controls related to those biologic products.

The Company did not record any product sales and there are no remaining performance obligations under the initial Takeda Collaboration Agreement. The Takeda Collaboration Agreement was superseded by the PTV:PGRN and ATV:TREM2 Collaboration Agreements subsequent to opt-in for the two programs, recognition of all preclinical milestones, and termination of the ATV:Tau program.

PTV:PGRN and ATV:TREM2 Collaboration Agreements

In November and December 2021, Takeda exercised its options to jointly develop and commercialize the PTV:PGRN and ATV:TREM2 programs, respectively, triggering the option fee of $5.0 million for each program, which formed the transaction price at contract inception for each contract, all of which was allocated to the underlying Technology License in each Collaboration Agreement which was delivered on or around the effective date of the respective Collaboration Agreement. Management determined that the opt-in by Takeda on the PTV:PGRN and ATV:TREM2 programs represent two new contracts with a customer for accounting purposes (the "PTV:PGRN Collaboration Agreement" and the "ATV:TREM2 Collaboration Agreement"), both effective in December 2021 upon payment of the respective option fees. From inception of the PTV:PGRN Collaboration Agreement and the ATV:TREM2 Collaboration Agreement through December 31, 2024, there was no change to the terms of either agreement; In February 2025, after mutual agreement to discontinue preclinical activities on ATV:TREM2, Takeda delivered notice of its election to terminate the ATV:TREM2 program on February 26, 2025, as per the terms of the Takeda Collaboration Agreement. The ATV:TREM2 program termination will become effective 60 days following the notice date.

For each contract, upon option exercise, the Company identified a single performance obligation under ASC 606, and initially one unit of account under ASC 808 associated with each of the PTV:PGRN and ATV:TREM2 Collaboration Agreements. The performance obligation was the delivery of a co-exclusive license under the intellectual property the Company controls related to the PTV:PGRN or ATV:TREM2 program ("PTV:PGRN Technology License" or "ATV;TREM2 Technology License"), and the unit of account is the obligation to share in responsibility and costs for global development of PTV:PGRN or ATV:TREM2 Products pursuant to a mutually agreed upon development plan and budget ("PTV:PGRN Development Activities" or "ATV:TREM2 Development Activities"), which both include JSC involvement. The PTV:PGRN Development Activities and JSC participation, and the ATV:TREM2 Development Activities and JSC participation are each considered to be single units of account since the activities are highly interrelated with the JSC involvement and these are not distinct in the context of the contract.

The Company believes that the PTV:PGRN and ATV:TREM2 Collaboration Agreements are both collaboration arrangements as defined in ASC 808, Collaborative Arrangements. The Company also believes that Takeda meets the definition of a customer as defined in ASC 606, Revenue From Contracts With Customers for the PTV:PGRN Technology License and the ATV:TREM2 Technology License performance obligations delivered in these collaboration agreements, respectively. Since ASC 808 does not address recognition and measurement, the Company looked to other accounting literature for the PTV:PGRN Development Activities and ATV:TREM2 Development Activities units of account, and determined that the guidance in ASC 730, Research and Development should be applied.

Under the PTV:PGRN Collaboration Agreement, Takeda may be obligated to pay the Company up to $140.0 million upon achievement of certain clinical milestone events and up to $100.0 million in regulatory milestone events relating to receipt of regulatory approval in the United States, certain European countries and Japan. Takeda may also be obligated to pay the Company up to $75.0 million upon achievement of a certain sales-based milestone. Further, the Company and Takeda share equally the development and commercialization costs, and, if applicable, the profits, for the PTV:PGRN program. Subsequent to the effective date of the termination of the ATV:TREM2 Collaboration Agreement, there will be no future milestones, cost, or profit sharing related to this agreement.

A $10.0 million milestone was triggered under the PTV:PGRN Collaboration Agreement upon achievement of a specified clinical milestone and recognized in collaboration revenue from customers in the Consolidated Statement of Operations and Comprehensive Loss for the year ended December 31, 2023. No product sales have been recorded under either agreement.

In assessing the Takeda Collaboration Agreement and the PTV:PGRN and the ATV:TREM2 Collaboration Agreements, management was required to exercise considerable judgment in estimating revenue to be recognized. Management applied judgment in determining whether opt-in resulted in a modification to an existing contract or a new contract, in determining the separate performance obligations in the research period, and estimating variable consideration.

Collaboration Revenue

Revenue disaggregated by collaboration agreement and performance obligation is as follows (in thousands):


	Year Ended December 31,
	2024		2023		2022
Takeda Collaboration Agreement:
Takeda Collaboration Agreement Services(1)	$	—	$	—	$	51,916
PTV:PGRN Collaboration Agreement	—		10,000		—

Total Takeda Collaboration Revenue	—		10,000		51,916
Sanofi Collaboration Agreement:
CNS Program License	—		25,000		40,000
Peripheral Program License	—		—		10,000
Alzheimer's Disease Services(2)	—		—		3,398

Total Sanofi Collaboration Revenue	—		25,000		53,398
Biogen Collaboration Agreement:

ATV:Abeta Program License(3)	—		293,912		—
Option Research Services(2)	—		1,619		3,149
Total Biogen Collaboration Revenue	—		295,531		3,149
Total Collaboration Revenue	$	—	$	330,531	$	108,463

_________________________________________________

(1)Revenue of $27.9 million for the year ended December 31, 2022 was included in the contract liability balance at the beginning of the year.

(2)Revenue was included in the contract liability balance at the beginning of the year.

(3)Revenue of $288.9 million for the year ended December 31, 2023 was included in the related-party contract liability balance at the beginning of the period.

Cost Sharing Payments and Reimbursements


	Year Ended December 31,
	2024		2023		2022
Takeda Collaboration Agreement:
PTV:PGRN cost sharing (reimbursements)	$	(4,789)	$	(7,065)	$	(11,276)
ATV:TREM2 cost sharing (reimbursements)	(1,147)		(5,100)		(6,954)
Total Takeda cost sharing (reimbursements)(1)	(5,936)		(12,165)		(18,230)
Biogen Collaboration Agreement: LRRK2 cost sharing payments(2)	16,742		17,678		8,187
Net cost sharing payments (reimbursements)	$	10,806	$	5,513	$	(10,043)

________________________________________________

(2)Cost sharing payments due to Biogen of $2.5 million and $3.2 million were recorded within accounts payable on the Consolidated Balance Sheets as of December 31, 2024 and 2023, respectively.

Significant Accounting Policies

12 Months Ended

Dec. 31, 2024

Accounting Policies [Abstract]

Significant Accounting Policies

Organization and Description of Business

Basis of Presentation

Principles of Consolidation

Use of Estimates

Concentration of Credit Risk and Other Risks and Uncertainties

Convertible Preferred Stock

The Company is authorized to issue 40.0 million shares of preferred stock in one or more series and to fix the powers, designations, preferences and relative participating option or other rights thereof, including dividend rights, conversion rights, voting rights, redemption terms, liquidation preferences and the number of shares constituting any series, without any further vote or action by the Company’s shareholders. As of December 31, 2024 and 2023, the Company had no shares of preferred stock issued or outstanding.

Investments

Fair Value of Financial Instruments

Level 1 – inputs are quoted prices (unadjusted) in active markets for identical assets or liabilities.

Level 2 – inputs are other than quoted prices included within Level 1 that are observable for the asset or liability, either directly or indirectly.

Cash, Cash Equivalents and Restricted Cash

The Company considers all highly liquid investments with original maturities of 90 days or less at the date of purchase to be cash and cash equivalents. Cash equivalents are reported at fair value.

Marketable Securities

Accounts Receivable

Property and Equipment, Net


Asset						Estimated useful life
Leasehold improvements						shorter of life of asset or lease term
Computer equipment and purchased software						three years
Laboratory equipment						five years
Furniture and fixtures						five years
Manufacturing equipment						eight years

Impairment of Long-Lived Assets

Leases

Revenue Recognition

License, Option and Collaboration Revenue

Research and Development Expenses

Stock-Based Compensation

Income Taxes

Comprehensive Loss

Net Loss Per Share

Recently Issued Accounting Pronouncements

Net Loss and Net Loss Per Share

12 Months Ended

Dec. 31, 2024

Earnings Per Share [Abstract]

Net Loss and Net Loss Per Share

The following table sets forth the computation of the basic and diluted net loss per share (in thousands, except share and per share data):


	Year Ended December 31,
	2024		2023		2022
Numerator:
Net loss	$	(422,773)	$	(145,224)	$	(325,991)

Denominator:
Weighted average number of:
Common stock shares outstanding	142,626,390		137,370,897		125,530,703
Private placement pre-funded warrants	21,847,382		—		—
Total	164,473,772		137,370,897		125,530,703


Net loss per share	$	(2.57)	$	(1.06)	$	(2.60)

Since the Company was in a loss position for all periods presented, basic net loss per share is the same as diluted net loss per share for all periods as the inclusion of all potential shares of common stock outstanding would have been anti-dilutive.

Potentially dilutive securities, including all options issued and outstanding, ESPP shares issuable, and restricted shares subject to future vesting, that were not included in the diluted per share calculations for all periods presented because they would be anti-dilutive totaled approximately 23.2 million, 20.5 million, and 18.2 million shares as of December 31, 2024, 2023, and 2022, respectively.

Balance Sheet Components (Tables)

12 Months Ended

Dec. 31, 2024

Organization, Consolidation and Presentation of Financial Statements [Abstract]

Prepaid Expenses and Other Current Assets

Prepaid expenses and other current assets consists of the following (in thousands):


	As of December 31,
	2024		2023
Accounts receivable and other receivables	$	2,171	$	3,420
Prepaid clinical research & development costs	6,473		10,178
Prepaid manufacturing and other research & development costs	16,196		12,192
Other prepaid assets and other current assets	7,265		3,836
Total prepaid expenses and other current assets	$	32,105	$	29,626

Scheduled of Property and Equipment, Net

Property and equipment, net consists of the following (in thousands):


	As of December 31,
	2024		2023
Leasehold improvements	$	46,905	$	41,238
Laboratory equipment	40,554		36,985
Manufacturing equipment	15,998		9,722
Computer equipment and purchased software	1,841		1,741
Furniture and fixtures	1,980		1,906
Total property and equipment	107,278		91,592
Less: accumulated depreciation	(52,042)		(46,003)
Total property and equipment, net	$	55,236	$	45,589

Schedule of Accrued Expenses and Other Current Liabilities

Accrued expenses and other current liabilities consists of the following (in thousands):


	As of December 31,
	2024		2023
Accrued compensation	$	24,728	$	21,590
Accrued clinical and other research & development costs	22,822		19,035
Accrued manufacturing costs	12,779		15,462
Operating lease liability, current	8,308		7,260
Finance lease liability, current	3,726		—
Deferred research and development funding liability, current	14,129		—
Other accrued costs and current liabilities	4,579		5,152
Total accrued expenses and other current liabilities	$	91,071	$	68,499

Commitments and Contingencies - Summary of Company's Future Minimum Lease Commitments (Details) $ in Thousands	Dec. 31, 2024 USD ($)
Operating Lease
2025	$ 11,793
2026	12,182
2027	12,584
2028	13,001
2029	4,381
Thereafter	0
Total undiscounted lease payments	53,941
Less: present value adjustment	(8,960)
Less: imputed interest	0
Total future minimum lease payments	44,981
Finance Lease
2025	4,446
2026	794
2027	811
2028	829
2029	848
Thereafter	8,814
Total undiscounted lease payments	16,542
Less: present value adjustment	0
Less: imputed interest	(7,201)
Total future minimum lease payments	$ 9,341

Collaboration Agreements - Takeda (Details)

1 Months Ended

12 Months Ended

Feb. 26, 2025

Feb. 23, 2018

USD ($)

Dec. 31, 2021

contract

Dec. 31, 2024

USD ($)

program

Dec. 31, 2023

USD ($)

Dec. 31, 2022

USD ($)

program

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Collaboration revenue from customers

^[1]

$ 0

$ 330,531,000

$ 105,065,000

Performance obligation

Takeda Pharmaceutical Company Limited | Collaborative Arrangement

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Upfront payment

$ 40,000,000

Possible preclinical milestone payments (up to)

$ 55,000,000

Number of performance obligations under the programs | program

Number of performance obligations suspended | program

Performance obligation

$ 0

Takeda Pharmaceutical Company Limited | Collaborative Arrangement | Product

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Collaboration revenue from customers

$ 0

Takeda Pharmaceutical Company Limited | Collaborative Arrangement | Share Purchase Agreement

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Number of common stock (in shares) | shares

4,214,559

Purchase price

$ 110,000,000

Premium on sale of common stock

15,600,000

Takeda Pharmaceutical Company Limited | Collaborative Arrangement, PTV:PGRN And ATV:TREM2

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Option fee

5,000,000

Number of new contracts | contract

Takeda Pharmaceutical Company Limited | Collaborative Arrangement, PTV:PGRN And ATV:TREM2 | Subsequent Event

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Notice period for effective termination

60 days

Takeda Pharmaceutical Company Limited | Collaborative Arrangement, PTV:PGRN And ATV:TREM2 | Maximum

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Milestone payments per biologic product upon achievement of a certain sales-based milestone

75,000,000

Takeda Pharmaceutical Company Limited | PTV:PGRN Collaboration Agreement | Milestone Triggered

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Clinical milestone payment

$ 10,000,000

Takeda Pharmaceutical Company Limited | PTV:PGRN Collaboration Agreement | Maximum

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Total aggregate payments due upon achievement of certain clinical milestone events

140,000,000

Regulatory milestone payment

$ 100,000,000

[1]	Includes related-party collaboration revenue from customers of $295.5 million, and $3.2 million for the years ended December 31, 2023 and 2022, respectively.

Marketable Securities (Tables)

12 Months Ended

Dec. 31, 2024

Investments, Debt and Equity Securities [Abstract]

Summary of Available for Sale Securities

The amortized cost, gross unrealized holding gains or losses, and fair value of the Company’s marketable securities by major security type at each balance sheet date are summarized in the tables below (in thousands):


	December 31, 2024
	Amortized Cost		Unrealized Holding Gains		Unrealized Holding Losses		Aggregate Fair Value
Short-term marketable securities:
U.S. government treasuries(1)	$	627,809	$	1,618	$	(27)	$	629,400

Corporate debt securities	21,337		62		—		21,399
Commercial paper	6,572		—		—		6,572
Total short-term marketable securities	655,718		1,680		(27)		657,371
Long-term marketable securities:
U.S. government treasuries(2)	334,300		788		(196)		334,892

Corporate debt securities	24,354		127		—		24,481
Total long-term marketable securities	358,654		915		(196)		359,373
Total	$	1,014,372	$	2,595	$	(223)	$	1,016,744

______________________________________________

(1)Unrealized holding losses on 3 securities with an aggregate fair value of 64.0 million.

(2)Unrealized holding losses on 4 securities with an aggregate fair value of 114.0 million


	December 31, 2023
	Amortized Cost		Unrealized Holding Gains		Unrealized Holding Losses		Aggregate Fair Value
Short-term marketable securities:
U.S. government treasuries(1)	$	868,174	$	998	$	—	$	869,172
U.S. government agency securities	7,089		—		(3)		7,086

Commercial paper	31,147		—		—		31,147





Total	$	906,410	$	998	$	(3)	$	907,405

__________________________________________________

(1)Unrealized holding losses on 2 securities with an aggregate fair value of $7.1 million.

Segment Information (Details)
$ in Thousands

12 Months Ended

Dec. 31, 2024

USD ($)

segment

Dec. 31, 2023

USD ($)

Dec. 31, 2022

USD ($)

Segment Reporting Information [Line Items]

Number of operating segments | segment

Total collaboration revenue

$ 0

$ 330,531

$ 108,463

Expenses

Total research and development expenses

^[1]

396,440

423,876

358,732

Total general and administrative expenses

105,438

103,354

90,475

Total operating expenses

501,878

527,230

449,207

Segment gain from divestiture of small molecule programs

14,537

Loss from operations

(487,341)

(196,699)

(340,744)

Segment interest and other income, net

64,636

51,505

14,774

Loss before income taxes

(422,705)

(145,194)

(325,970)

Therapeutics Segment

Segment Reporting Information [Line Items]

Total collaboration revenue

330,531

108,463

Expenses

Other research and development expenses

62,715

74,518

73,390

152,906

160,444

144,017

Total research and development expenses

396,440

423,876

358,732

73,505

73,668

64,147

Other general and administrative expenses

31,933

29,686

26,328

Total general and administrative expenses

105,438

103,354

90,475

Total operating expenses

501,878

527,230

449,207

Segment gain from divestiture of small molecule programs

14,537

Loss from operations

(487,341)

(196,699)

(340,744)

Segment interest and other income, net

64,636

51,505

14,774

Loss before income taxes

(422,705)

(145,194)

(325,970)

Therapeutics Segment | TV Programs, Including Cost Sharing

Expenses

External research and development expense

138,196

139,064

96,587

Therapeutics Segment | Small Molecule Programs, Including Cost Sharing

Expenses

External research and development expense

$ 42,623

$ 49,850

$ 44,738

[1]	Includes expense for cost sharing payments to a related party of $17.7 million and $8.2 million for the years ended December 31, 2023 and 2022, respectively.

Consolidated Statements of Cash Flows - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2024	Dec. 31, 2023	Dec. 31, 2022
Operating activities
Net loss	$ (422,773)	$ (145,224)	$ (325,991)
Adjustments to reconcile net loss to net cash used in operating activities:
Depreciation and amortization	7,795	16,726	10,383
Stock-based compensation expense	102,878	108,102	99,847
Net accretion of discounts on marketable securities	(35,117)	(43,952)	(1,637)
Non-cash adjustment to operating lease expense	(4,074)	(3,719)	(3,351)
Right-of-use asset amortization for finance lease	1,197	0	0
Non-cash gain from divestiture of small molecule programs	(14,537)	0	0
Other non-cash items	0	2	63
Changes in operating assets and liabilities:
Prepaid expenses and other assets	(2,480)	(4,094)	(2,760)
Other non-current assets	603	0	0
Accounts payable	1,437	2,431	2,274
Accruals and other current liabilities	17,377	2,648	10,918
Contract liabilities	0	0	(31,313)
Related party contract liability	0	(290,532)	(3,149)
Other non-current liabilities	0	(379)	0
Net cash used in operating activities	(347,694)	(357,991)	(244,716)
Investing activities
Maturities of marketable securities	1,157,120	2,075,947	991,486
Purchases of marketable securities	(1,229,964)	(1,813,700)	(1,115,040)
Purchases of property and equipment	(15,912)	(12,939)	(17,833)
Net cash provided by (used in) investing activities	(88,756)	249,308	(141,387)
Financing activities
Proceeds from issuance of common stock and pre-funded warrants, net of issuance costs of $480	499,253	0	0
Proceeds from public offering of common stock, net of issuance costs	0	0	296,215
Proceeds from exercise of awards under equity incentive plans	17,389	17,820	14,455
Payments for finance lease right-of-use asset	(32,338)	0	0
Net cash provided by financing activities	484,304	17,820	310,670
Net increase (decrease) in cash, cash equivalents and restricted cash	47,854	(90,863)	(75,433)
Cash, cash equivalents and restricted cash at beginning of year	128,681	219,544	294,977
Cash, cash equivalents and restricted cash at end of year	176,535	128,681	219,544
Supplemental disclosures of cash flow information
Equity consideration received in the divestiture of small molecule programs (Note 13)	15,000	0	0
Increase in right-of-use asset due to lessor assets	7,051	0	0
Right-of-use asset obtained in exchange for new finance lease liabilities	9,358	0	0
Property and equipment purchases accrued but not yet paid	1,192	553	1,464
Cash paid for finance lease interest	302	0	0
Issuance costs incurred but not yet paid	0	0	224
Cash paid during the year for income taxes	$ 0	$ 3	$ 47

Consolidated Balance Sheets (Parenthetical) - $ / shares	Dec. 31, 2024	Dec. 31, 2023
Statement of Financial Position [Abstract]
Convertible preferred stock, par value (usd per share)	$ 0.01	$ 0.01
Convertible preferred stock, shares authorized (in shares)	40,000,000	40,000,000
Convertible preferred stock, shares issued (in shares)	0	0
Convertible preferred stock, shares outstanding (in shares)	0	0
Common stock, par value (usd per share)	$ 0.01	$ 0.01
Common stock, shares authorized (in shares)	400,000,000	400,000,000
Common stock, shares issued (in shares)	144,220,986	138,385,498
Common stock, shares outstanding (in shares)	144,220,986	138,385,498

Significant Accounting Policies - Concentration of Credit Risk and Other Risks and Uncertainties (Details) - USD ($)	Dec. 31, 2024	Dec. 31, 2023
Accounting Policies [Abstract]
Off-balance sheet concentrations of credit risk	$ 0	$ 0

Net Loss and Net Loss Per Share (Tables)

12 Months Ended

Dec. 31, 2024

Earnings Per Share [Abstract]

Summary of Computation of Basic and Diluted Net Loss Per Share

The following table sets forth the computation of the basic and diluted net loss per share (in thousands, except share and per share data):


	Year Ended December 31,
	2024		2023		2022
Numerator:
Net loss	$	(422,773)	$	(145,224)	$	(325,991)

Denominator:
Weighted average number of:
Common stock shares outstanding	142,626,390		137,370,897		125,530,703
Private placement pre-funded warrants	21,847,382		—		—
Total	164,473,772		137,370,897		125,530,703


Net loss per share	$	(2.57)	$	(1.06)	$	(2.60)

Acquisition, License Agreement and Research and Development Funding Collaboration Agreement - Narrative (Details)

1 Months Ended

12 Months Ended

103 Months Ended

Jan. 29, 2024

USD ($)

Mar. 31, 2023

USD ($)

May 31, 2018

USD ($)

Jun. 30, 2016

USD ($)

Dec. 31, 2024

USD ($)

Dec. 31, 2023

USD ($)

Dec. 31, 2022

USD ($)

payment

Dec. 31, 2024

USD ($)

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Research and development expense

^[1]

$ 396,440,000

$ 423,876,000

$ 358,732,000

Reduction to research and development expense

10,900,000

Deferred research and development funding liability, current

14,100,000

$ 14,100,000

Collaboration And Development Funding Agreement

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Aggregate payments

25,000,000

Collaborative agreement, aggregate consideration amount

$ 75,000,000

Genetech License Agreement

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Research and development expense

18,800,000

Genetech License Agreement | Genentech | Research and development

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Aggregate payments

$ 12,500,000

$ 25,000,000

Number of clinical milestones for which payments were made | payment

Collaborative Arrangement

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Research and development expense

$ 0

Collaborative Arrangement | Biogen Collaboration Agreement

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Research and development expense

$ 6,300,000

Clinical | Genentech

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Milestone payments upon achievement of specified clinical and regulatory milestones

$ 37,500,000

Regulatory | Genentech

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Milestone payments upon achievement of specified clinical and regulatory milestones

102,500,000

Commercial | Genentech

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Milestone payments upon achievement of specified clinical and regulatory milestones

175,000,000

Collaborative Arrangement with F-Star and Acquisition of F-Star Gamma | Contingent Payments Upon Achievement of Specialized Clinical Milestone

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Contingent consideration payment triggered

$ 30,000,000

Contingent consideration amount recognized

$ 0

Exercise of buy-out option | Collaborative Arrangement with F-Star and Acquisition of F-Star Gamma

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Contingent payments upon achievement of milestones

$ 210,000,000

Exercise of buy-out option | Collaborative Arrangement with F-Star and Acquisition of F-Star Gamma | Regulatory

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Contingent payments upon achievement of milestones

60,000,000

Exercise of buy-out option | Collaborative Arrangement with F-Star and Acquisition of F-Star Gamma | Commercial

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Contingent payments upon achievement of milestones

$ 150,000,000

Maximum | Genentech

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Milestone payments upon achievement of specified clinical and regulatory milestones

$ 315,000,000

[1]	Includes expense for cost sharing payments to a related party of $17.7 million and $8.2 million for the years ended December 31, 2023 and 2022, respectively.

Stock-Based Awards (Tables)

12 Months Ended

Dec. 31, 2024

Share-Based Payment Arrangement [Abstract]

Summary of Stock Option Activity

The following table summarizes option award activity under the 2017 Plan and the 2015 Plan:


	Number of Options	Weighted- Average Exercise Price		Weighted- Average remaining contractual life (years)	Aggregate Intrinsic Value (in thousands)
Balance at December 31, 2023	16,490,551	$	27.34	5.97	$	61,982
Granted	4,902,211	20.82
Exercised	(968,588)	12.76
Forfeited	(1,764,024)	31.51
Balance at December 31, 2024	18,660,150	$	25.99	5.94	$	48,266
Vested and expected to vest at December 31, 2024	17,850,279	$	27.14	6.19	$	32,311
Exercisable at December 31, 2024	11,650,342	$	28.61	4.84	$	31,781

Summary of Assumptions Used for Estimating the Fair Value of Stock Granted

The following assumptions were used in estimating the fair value of grants during the year ended:


	December 31,
	2024	2023	2022
Expected term (in years)	5.50 - 6.08	5.50 - 6.08	5.50 - 6.08
Volatility	64.5% - 66.0%	67.6% - 69.6%	65.1% - 66.3%
Risk-free interest rate	3.7% - 4.5%	3.4% - 4.8%	1.5% - 4.3%
Dividend yield	—	—	—

Summary of Restricted Stock Activity

Aggregated information regarding RSUs granted under the Plan for the year ended December 31, 2024 is summarized below:


	Number of Units	Weighted-Average Fair Value at Date of Grant per Share
Unvested at December 31, 2023	3,635,157	$	35.60
Granted	2,580,174	21.01
Vested and released	(1,302,190)	37.13
Forfeited	(784,627)	28.62
Unvested and expected to vest at December 31, 2024	4,128,514	$	27.33

Summary of Stock-Based Compensation Expense

The Company’s stock-based compensation expense was as follows (in thousands):


	Year Ended December 31,
	2024		2023		2022
Research and development	$	59,146	$	62,901	$	60,196
General and administrative	43,732		45,201		39,651
Total	$	102,878	$	108,102	$	99,847

Net Loss and Net Loss Per Share - Narrative (Details) - shares shares in Millions	12 Months Ended
	Dec. 31, 2024	Dec. 31, 2023	Dec. 31, 2022
Earnings Per Share [Abstract]
Total (in shares)	23.2	20.5	18.2

Income Taxes (Tables)

12 Months Ended

Dec. 31, 2024

Income Tax Disclosure [Abstract]

Schedule of Provision for Income Taxes

The provision for income taxes consisted of the following (in thousands):


	Year Ended December 31,
	2024		2023		2022
Current:
U.S. Federal	$	—	$	—	$	—
U.S. State	—		—		7
Foreign	68		30		14
Total Current	$	68	$	30	$	21

Deferred:
U.S. Federal	$	—	$	—	$	—
U.S. State	—		—		—
Foreign	—		—		—
Total deferred	$	—	$	—	$	—
Total provision for income taxes	$	68	$	30	$	21

Schedule of Effective Tax Rate Reconciliation

The reconciliation of federal statutory income tax rate to our effective income tax rate is as follows:


	Year Ended December 31,
	2024		2023		2022
Taxes at the U.S. statutory tax rate	21.0	%	21.0	%	21.0	%

Change in valuation allowance	(25.0)		(27.3)		(25.1)
Research tax credits	5.6		14.5		4.9
Stock-based compensation	(2.1)		(3.2)		(0.5)
Nondeductible acquisition-related costs	—		(3.5)		—


Impact of IRC 162m	(0.2)		(0.7)		—
Other	0.7		(0.8)		(0.4)
Total provision for income taxes	—	%	—	%	(0.1)	%

Schedule of Deferred Tax Assets and Liabilities

The components of the Company’s net deferred tax assets are as follows (in thousands):


	December 31,
	2024		2023
Deferred tax assets:
Net operating loss carryforwards	$	113,397	$	89,273
Tax credit carryforwards	124,922		95,808
Research expense capitalization	176,094		119,349

Lease liabilities	11,760		12,663
Stock-based compensation	57,766		53,226
Fixed assets	6,671		—
Accruals and other	13,447		17,453
Gross deferred tax assets	504,057		387,772
Valuation allowance	(487,714)		(375,795)
Net deferred tax assets	16,343		11,977
Deferred tax liabilities:
Property and equipment	—		(5,663)
Lease right-of-use assets	(16,343)		(6,314)
Net deferred tax assets	$	—	$	—

Schedule of Reconciliation of Unrecognized Tax Benefits

A reconciliation of the beginning and ending amounts of unrecognized tax benefits is as follows (in thousands):


	December 31,
	2024		2023		2022
Unrecognized tax benefits at January 1	$	26,175	$	19,371	$	13,699
Additions for tax positions taken in a prior year	162		168		135
Additions for tax positions taken in the current year	7,424		6,636		5,537
Reductions for tax positions taken in the prior year	—		—		—
Unrecognized tax benefits at December 31	$	33,761	$	26,175	$	19,371

Collaboration Agreements - Summary of Collaboration Revenue (Details) - USD ($)
$ in Thousands

12 Months Ended

Dec. 31, 2024

Dec. 31, 2023

Dec. 31, 2022

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Collaborative revenue, revenue from contract with customer

^[1]

$ 0

$ 330,531

$ 105,065

Collaborative revenue, excluding revenue from contract with customer

3,398

Total collaboration revenue

330,531

108,463

Collaborative revenue, revenue from contract with customer

295,500

3,200

Takeda Collaboration Agreement

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Total collaboration revenue

10,000

51,916

Revenue recognized included in the contract liability balance at the beginning of the year

27,900

Takeda Collaboration Agreement | Collaboration Agreement Services

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Collaborative revenue, revenue from contract with customer

51,916

Takeda Collaboration Agreement | PTV:PGRN Collaboration Agreement

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Collaborative revenue, revenue from contract with customer

10,000

Sanofi Collaboration Agreement

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Total collaboration revenue

25,000

53,398

Sanofi Collaboration Agreement | CNS Program License

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Collaborative revenue, revenue from contract with customer

25,000

40,000

Sanofi Collaboration Agreement | Peripheral Program License

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Collaborative revenue, revenue from contract with customer

10,000

Sanofi Collaboration Agreement | Alzheimer's Disease Services

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Collaborative revenue, excluding revenue from contract with customer

3,398

Biogen Collaboration Agreement

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Total collaboration revenue

295,531

3,149

Biogen Collaboration Agreement | ATV:Abeta Program License

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Collaborative revenue, revenue from contract with customer

293,912

Biogen Collaboration Agreement | ATV:Abeta Program License | Related Party

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Collaborative revenue, revenue from contract with customer

288,900

Biogen Collaboration Agreement | Option Research Services

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Collaborative revenue, revenue from contract with customer

$ 0

$ 1,619

$ 3,149

[1]	Includes related-party collaboration revenue from customers of $295.5 million, and $3.2 million for the years ended December 31, 2023 and 2022, respectively.