0001714899-23-000049 | 10-K | XBRL Viewer

Balance Sheet Components

12 Months Ended

Dec. 31, 2022

Organization, Consolidation and Presentation of Financial Statements [Abstract]

Property and Equipment, Net

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


	As of December 31,
	2022		2021
Leasehold improvements	$	43,698	$	35,235
Manufacturing and laboratory equipment	34,419		30,114
Computers equipment and purchased software	1,605		1,337
Furniture and fixtures	1,580		1,523
Total property and equipment	81,302		68,209
Less: accumulated depreciation	(37,215)		(29,344)
Total property and equipment, net	$	44,087	$	38,865

Depreciation expense was $10.4 million, $8.6 million and $8.5 million for the years ended December 31, 2022, 2021 and 2020, respectively.

Accrued Expenses and Other Current Liabilities

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


	As of December 31,
	2022		2021
Accrued manufacturing costs	$	22,307	$	9,955
Accrued compensation	17,087		19,013
Accrued clinical costs and other research & development costs	16,297		15,887
Operating lease liability, current	7,318		5,453
Other accrued costs and current liabilities	3,682		2,857
Total accrued expenses and other current liabilities	$	66,691	$	53,165

Marketable Securities (Tables)

12 Months Ended

Dec. 31, 2022

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, 2022
	Amortized Cost		Unrealized Holding Gains		Unrealized Holding Losses		Aggregate Fair Value
Short-term marketable securities:
U.S. government treasuries(1)	$	1,009,733	$	58	$	(6,287)	$	1,003,504
U.S. government agency securities	16,823		38		—		16,861
Corporate debt securities(2)	54,571		—		(356)		54,215
Commercial paper	43,591		—		—		43,591
Total short-term marketable securities	1,124,718		96		(6,643)		1,118,171





Total	$	1,124,718	$	96	$	(6,643)	$	1,118,171

______________________________________________

(1)Unrealized holding losses on 51 securities with an aggregate fair value of $683.4 million.

(2)Unrealized holding losses on 16 securities with an aggregate fair value of $54.2 million.


	December 31, 2021
	Amortized Cost		Unrealized Holding Gains		Unrealized Holding Losses		Aggregate Fair Value
Short-term marketable securities:
U.S. government treasuries(1)	$	450,689	$	—	$	(253)	$	450,436

Corporate debt securities(2)	70,076		1		(68)		70,009
Commercial paper	51,485		—		—		51,485
Total short-term marketable securities	572,250		1		(321)		571,930
Long-term marketable securities:
U.S. government treasuries(3)	411,904		—		(1,757)		410,147
Corporate debt securities(4)	15,373		—		(71)		15,302
Total long-term marketable securities	427,277		—		(1,828)		425,449
Total	$	999,527	$	1	$	(2,149)	$	997,379

__________________________________________________

(1)Unrealized holding losses on 19 securities with an aggregate fair value of $450.4 million.

(2)Unrealized holding losses on 16 securities with an aggregate fair value of $68.5 million.

(3)Unrealized holding losses on 16 securities with an aggregate fair value of $410.1 million.

(4)Unrealized holding losses on 6 securities with an aggregate fair value of $15.3 million.

License Agreements	12 Months Ended
License Agreements	Dec. 31, 2022
Organization, Consolidation and Presentation of Financial Statements [Abstract]
License Agreements	License Agreements Genentech In June 2016, the Company entered into an Exclusive License Agreement with Genentech, Inc. (“Genentech”). This agreement gives the Company access to Genentech’s LRRK2 inhibitor small molecule program for Parkinson's disease. Under the agreement, Genentech granted the Company (i) an exclusive, worldwide, sublicensable license under Genentech’s rights to certain patents and patent applications directed to small molecule compounds which bind to and inhibit LRRK2 and (ii) a non-exclusive, worldwide, sublicensable license to certain related know-how, in each case, to develop and commercialize certain compounds and licensed products incorporating any such compound. 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. These milestones include 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. In the year ended December 31, 2022, the Company paid Genentech a $7.5 million clinical milestone payment triggered upon the commencement of dosing in the global Phase 2b LUMA study to evaluate the efficacy and safety of BIIB122/DNL151 by the Company's collaboration partner Biogen, and a $5.0 million clinical milestone payment triggered upon the commencement of dosing in the global Phase 3 LIGHTHOUSE study to evaluate the efficacy and safety profile of BIIB122/DNL151 by Biogen. Under the terms of the Biogen collaboration agreement, Biogen is responsible for 50% of any payment obligation to Genentech after October 4, 2020, including these clinical milestones, and accordingly $6.3 million of research and development expense under this agreement was recognized in the year ended December 31, 2022 associated with these milestones. No expenses were recognized under the Genentech License Agreement in the years ended December 31, 2021 or 2020. To date, the Company has made payments to Genentech of $25.0 million in the aggregate, including an upfront fee, a technology transfer fee and three clinical milestone payments, with $18.8 million of this recorded as research and development expense as incurred, net of cost sharing reimbursements from Biogen.

Fair Value Measurements

12 Months Ended

Dec. 31, 2022

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, 2022
	Level 1		Level 2		Level 3		Total
Assets:
Cash equivalents:
Money market funds	$	105,340	$	—	$	—	$	105,340
U.S. government treasuries	43,781		—		—		43,781
Commercial paper	—		9,948		—		9,948
Short-term marketable securities:
U.S. government treasuries	1,003,504		—		—		1,003,504
U.S. government agency securities	—		16,861		—		16,861
Corporate debt securities	—		54,215		—		54,215
Commercial paper	—		43,591		—		43,591





Total	$	1,152,625	$	124,615	$	—	$	1,277,240


	December 31, 2021
	Level 1		Level 2		Level 3		Total
Assets:
Cash equivalents
Money market funds	$	265,294	$	—	$	—	$	265,294


Short-term marketable securities:
U.S. government treasuries	450,436		—		—		450,436

Corporate debt securities	—		70,009		—		70,009
Commercial paper	—		51,485		—		51,485
Long-term marketable securities:
U.S. government treasuries	410,147		—		—		410,147

Corporate debt securities	—		15,302		—		15,302

Total	$	1,125,877	$	136,796	$	—	$	1,262,673
Liabilities:
Foreign currency derivative contracts	$	—	$	111	$	—	$	111
Total	$	—	$	111	$	—	$	111

The carrying amounts of cost sharing reimbursements due from and due to related party, prepaid expenses and other current assets, accounts payable and accrued expenses approximate their fair values due to their short-term maturities.

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 has not transferred any assets or liabilities between the fair value measurement levels during the years ended December 31, 2022 or 2021.

- 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.

+ References + Details

Acquisition	12 Months Ended
Acquisition	Dec. 31, 2022
Business Combination and Asset Acquisition [Abstract]
Acquisition	Acquisition In August 2016, the Company entered into a License and Collaboration Agreement (“F-star Collaboration Agreement”) with F-star Gamma Limited (“F-star Gamma”), F-star Biotechnologische Forschungs-und Entwicklungsges M.B.H ("F-star GmbH") and F-star Biotechnology Limited ("F-star Ltd") (collectively, “F-star”) to leverage F-star’s modular antibody technology and the Company’s expertise in the development of therapies for neurodegenerative diseases. Under the F-star Collaboration Agreement, the Company made payments to F-star totaling $11.5 million. In connection with the entry into the F-star Collaboration Agreement, the Company also purchased an option for an upfront option fee of $0.5 million (the “buy-out-option”), to acquire all of the outstanding shares of F-star Gamma pursuant to a pre-negotiated buy-out option agreement (the “Option Agreement”). In May 2018, the Company exercised the Option Agreement and entered into a Share Purchase Agreement (the “Purchase Agreement”) with the shareholders of F-star Gamma and Shareholder Representative Services LLC, pursuant to which the Company acquired all of the outstanding shares of F-star Gamma (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 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 Company made initial exercise payments under the Purchase Agreement and the F-star Gamma License, in the aggregate, of $17.8 million. In addition, the Company is required to make contingent payments, to F-star Ltd and the former shareholders of F-star Gamma, up to a maximum amount following completion of the research phase of the F-star collaboration of $243.0 million in the aggregate upon the achievement of certain defined preclinical, clinical, regulatory and commercial milestones. These include up to $3.0 million in preclinical contingent payments, $30.0 million in clinical contingent payments, $60.0 million in regulatory contingent payments and $150.0 million in commercial contingent payments. Through December 31, 2022, $1.5 million of preclinical contingent payments had been paid to F-star. The Company concluded that the assets acquired and liabilities assumed upon the exercise of the Option Agreement did not meet the accounting definition of a business, and as such, the acquisition was accounted for as an asset purchase. As the transaction was accounted for as an asset purchase rather than a business combination, the Company did not recognize any contingent consideration liability on the acquisition date. To date, the Company has paid consideration of $19.8 million in the aggregate, consisting of up-front and preclinical contingent consideration, all of which was recorded as research and development expense as incurred. There was no contingent consideration expense recognized for the years ended December 31, 2022, 2021, or 2020. Any future contingent consideration is expected to be recognized as incurred in research and development expense on the Consolidated Statements of Operations and Comprehensive Income (Loss). Under the F-star Collaboration Agreement, the Company was responsible for certain research costs incurred by F-star Ltd in conducting activities under an agreed development plan for each Fcab, for up to 24 months after the target Fcab is accepted. In July 2021, a side letter was executed to the Company's agreements with F-star, which confirmed the completion of the research services performed by F-star Ltd that were funded by the Company. The Company has not recognized research and development expense related to the funding of F-star Ltd activities under development plans during the year ended December 31, 2022, but recognized $0.1 million and $1.2 million in research and development expense related to the funding of F-star Ltd activities under development plans during the years ended December 31, 2021 and 2020, respectively.

Income Taxes - Provision for Income Taxes (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2022	Dec. 31, 2021	Dec. 31, 2020
Current:
U.S. Federal	$ 0	$ 0	$ 0
U.S. State	7	(576)	823
Foreign	14	1	0
Total Current	21	(575)	823
Deferred:
U.S. Federal	0	0	0
U.S. State	0	0	0
Foreign	0	0	0
Total deferred	$ 0	$ 0	$ 0

Collaboration Agreements (Tables)

12 Months Ended

Dec. 31, 2022

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,
	2022		2021		2020
Takeda Collaboration Agreement:
Takeda Collaboration Agreement Services(1)	$	51,916	$	19,921	$	27,155
PTV:PGRN Collaboration Agreement	—		5,000		—
ATV:TREM2 Collaboration Agreement	—		5,000		—
Total Takeda Collaboration Revenue	51,916		29,921		27,155
Sanofi Collaboration Agreement:
CNS Program License	40,000		—		—
Peripheral Program License	10,000		15,000		—
Alzheimer's Disease Services(2)	3,398		4		98
Retained Activities	—		—		969
Total Sanofi Collaboration Revenue	53,398		15,004		1,067
Biogen Collaboration Agreement:
LRRK2 Program License	—		—		306,545

Option Research Services(3)	3,149		3,736		892
Total Biogen Collaboration Revenue	3,149		3,736		307,437
Total Collaboration Revenue	$	108,463	$	48,661	$	335,659

_________________________________________________

(1)$27.9 million, $15.9 million, and $19.6 million of revenue for the years ended December 31, 2022, 2021 and 2020 was included in the contract liability balance at the beginning of the year.

(2)Revenue for the years ended December 31, 2022, 2021 and 2020 represent amounts that were included in the contract liability balance at the beginning of the respective year.

(3)Revenue for the years ended December 31, 2022 and 2021 represents amounts that were included in the contract liability balance at the beginning of the year.

Commitments and Contingencies - Narrative (Details)		1 Months Ended	12 Months Ended
Commitments and Contingencies - Narrative (Details)	May 02, 2018 USD ($) ft²	Jul. 31, 2022 USD ($) ft²	Dec. 31, 2022 USD ($)	Dec. 31, 2021 USD ($)	Dec. 31, 2020 USD ($)	Feb. 28, 2023 USD ($)	Oct. 31, 2018 ft²
Loss Contingencies [Line Items]
Operating lease costs			$ 12,200,000	$ 11,200,000	$ 11,100,000
Sublease income			3,900,000	3,800,000	3,600,000
Future undiscounted sublease receipts			3,972,000
Subsequent Event
Loss Contingencies [Line Items]
Future undiscounted sublease receipts						$ 1,100,000
DMSA
Loss Contingencies [Line Items]
Purchase order executed			35,900,000	35,800,000
Costs incurred			28,600,000	17,400,000	10,800,000
Payments for development and manufacturing services			23,900,000	14,900,000	$ 7,300,000
Non-Cancellable Purchase Commitments
Loss Contingencies [Line Items]
Purchase commitments			32,300,000	28,300,000
Other Commitments
Loss Contingencies [Line Items]
Purchase commitments			1,600,000	1,700,000
SLC Facility
Loss Contingencies [Line Items]
Purchase commitments			5,600,000
Excluding DMSA
Loss Contingencies [Line Items]
Purchase commitments			9,600,000	$ 11,500,000
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	$ 4,400,000
Operating Lease, 8 Year Lease Agreement \| Building \| SLC Lease
Loss Contingencies [Line Items]
Lease not yet commenced, undiscounted lease payments		$ 19,500,000
Lease not yet commenced, lease liability			0
Lease not yet commenced, ROU asset			0
Lease not yet commenced, operating lease expense			$ 0
New Premises Sublease Agreement
Loss Contingencies [Line Items]
Rentable square feet \| ft²							36,835
Sublease term							5 years
Operating Lease, 9.3 Year Lease Agreement \| Building \| SLC Lease
Loss Contingencies [Line Items]
Lease not yet commenced, area under lease \| ft²		78,000
Lease not yet commenced, period		9 years 3 months 18 days
Minimum \| Headquarters Lease
Loss Contingencies [Line Items]
Lease renewal notice period	9 months
Maximum \| Headquarters Lease
Loss Contingencies [Line Items]
Lease renewal notice period	12 months
Maximum \| Headquarters Lease \| Landlord Funded Tenant Improvements
Loss Contingencies [Line Items]
Leasehold improvements	$ 25,900,000

Net Income (Loss) and Net Income (Loss) Per Share

12 Months Ended

Dec. 31, 2022

Earnings Per Share [Abstract]

Net Income (Loss) and Net Income (Loss) Per Share

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


	Year Ended December 31,
	2022		2021		2020
Numerator:
Net income (loss)	$	(325,991)	$	(290,581)	$	71,136
Denominator:
Weighted average number of shares outstanding, basic	125,530,703		121,524,795		108,974,137
Dilutive effect of shares issuable under equity incentive plans	—		—		3,728,971
Weighted average number of shares outstanding, diluted	125,530,703		121,524,795		112,703,108
Net income (loss) per share, basic	$	(2.60)	$	(2.39)	$	0.65
Net income (loss) per share, diluted	$	(2.60)	$	(2.39)	$	0.63

Potentially dilutive securities that were not included in the diluted per share calculations because they would be anti-dilutive totaled approximately 18.2 million, 16.5 million, and 4.2 million shares as of December 31, 2022, 2021, and 2020, respectively. These consist primarily of all or certain options issued and outstanding and restricted stock awards subject to future vesting.

Consolidated Statements of Operations and Comprehensive Income (Loss) (Parenthetical) - USD ($) $ in Millions	12 Months Ended
	Dec. 31, 2022	Dec. 31, 2021	Dec. 31, 2020
Income Statement [Abstract]
Collaboration revenue from customers, related party	$ 3.2	$ 3.7	$ 307.4
Expense for cost sharing payments due to a related party	$ 8.2
Offset to research and development expense, related party cost reimbursement		$ 6.5	$ 9.3

- Definition

Amount of revenue, fees and commissions earned from transactions between (a) a parent company and its subsidiaries; (b) subsidiaries of a common parent; (c) an entity and trusts for the benefit of employees, for example, but not limited to, pension and profit-sharing trusts that are managed by or under the trusteeship of the entity's management; (d) an entity and its principal, owners, management, or members of their immediate families; and (e) affiliates.

+ References

Reference 1: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 470
-SubTopic 10
-Section S99
-Paragraph 1B
-Subparagraph (SX 210.13-02(a)(4)(iv))
-URI https://asc.fasb.org/extlink&oid=126975872&loc=SL124442552-122756

Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 946
-SubTopic 220
-Section S99
-Paragraph 1
-Subparagraph (SX 210.6-07.1(c))
-URI https://asc.fasb.org/extlink&oid=120401555&loc=SL114874292-224272

Reference 3: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 470
-SubTopic 10
-Section S99
-Paragraph 1A
-Subparagraph (SX 210.13-01(a)(4)(iii)(B))
-URI https://asc.fasb.org/extlink&oid=126975872&loc=SL124442526-122756

Reference 4: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 470
-SubTopic 10
-Section S99
-Paragraph 1B
-Subparagraph (SX 210.13-02(a)(4)(iii)(C))
-URI https://asc.fasb.org/extlink&oid=126975872&loc=SL124442552-122756

Reference 5: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 470
-SubTopic 10
-Section S99
-Paragraph 1A
-Subparagraph (SX 210.13-01(a)(5))
-URI https://asc.fasb.org/extlink&oid=126975872&loc=SL124442526-122756

Reference 6: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 470
-SubTopic 10
-Section S99
-Paragraph 1B
-Subparagraph (SX 210.13-02(a)(5))
-URI https://asc.fasb.org/extlink&oid=126975872&loc=SL124442552-122756

Reference 7: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 470
-SubTopic 10
-Section S99
-Paragraph 1A
-Subparagraph (SX 210.13-01(a)(4)(iv))
-URI https://asc.fasb.org/extlink&oid=126975872&loc=SL124442526-122756

Reference 8: http://fasb.org/us-gaap/role/ref/legacyRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 220
-SubTopic 10
-Section S99
-Paragraph 2
-Subparagraph (SX 210.5-03.1(e))
-URI https://asc.fasb.org/extlink&oid=126953954&loc=SL114868664-224227

+ Details

Significant Accounting Policies (Tables)

12 Months Ended

Dec. 31, 2022

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
Manufacturing and laboratory equipment						five years
Computer hardware and software						three years
Office furniture and equipment						five years

Balance Sheet Components - Accrued Expenses and Other Current Liabilities (Details) - USD ($) $ in Thousands	Dec. 31, 2022	Dec. 31, 2021
Organization, Consolidation and Presentation of Financial Statements [Abstract]
Accrued manufacturing costs	$ 22,307	$ 9,955
Accrued compensation	17,087	19,013
Accrued clinical costs and other research & development costs	16,297	15,887
Operating lease liability, current	7,318	5,453
Other accrued costs and current liabilities	$ 3,682	$ 2,857
Operating Lease, Liability, Current, Statement of Financial Position [Extensible List]	Total accrued expenses and other current liabilities	Total accrued expenses and other current liabilities
Total accrued expenses and other current liabilities	$ 66,691	$ 53,165

Significant Accounting Policies - Derivatives and Hedging Activities (Details) - Designated as Hedging Instrument € in Millions, £ in Millions	Dec. 31, 2022 contract	Dec. 31, 2021 EUR (€) contract	Dec. 31, 2021 GBP (£) contract
Euros
Derivative [Line Items]
Number of contracts	0	7	7
Aggregate notional amount in foreign currency \| €		€ 0.8
British Pounds
Derivative [Line Items]
Number of contracts	0	8	8
Aggregate notional amount in foreign currency \| £			£ 0.9

Marketable Securities - Narrative (Details) - USD ($)	Dec. 31, 2022	Dec. 31, 2021
Investments, Debt and Equity Securities [Abstract]
Allowance for credit losses	$ 0	$ 0
Effective maturity (less than)	1 year

Collaboration Agreements - Biogen (Details)
$ / shares in Units, $ in Thousands

1 Months Ended

12 Months Ended

27 Months Ended

Sep. 22, 2020

USD ($)

$ / shares

Aug. 05, 2020

USD ($)

program

Oct. 31, 2020

USD ($)

Dec. 31, 2022

USD ($)

milestone

Dec. 31, 2021

USD ($)

Dec. 31, 2020

USD ($)

Dec. 31, 2022

USD ($)

milestone

Oct. 06, 2020

USD ($)

Oct. 05, 2020

Nov. 30, 2018

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

Cost sharing payments due to related party

$ 4,388

$ 0

$ 4,388

Offset to research and development expense, related party cost reimbursement

6,500

$ 9,300

Cost sharing reimbursements due

1,226

Collaborative revenue, revenue from contract with customer

^[1]

105,065

48,657

335,561

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%

Collaborative Arrangement

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

Funded percentage

30.00%

Biogen | Related Party

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

Contract liability

$ 290,500

290,500

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

Common stock, voting interest

10.00%

Fair market value of shares issued

$ 420,100

Closing stock price (usd per share) | $ / shares

$ 35.87

Premium on sale of common stock

$ 44,900

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 (TV) Technology Program, Unnamed Program, Right Of First Negotiation Programs (ROFN)

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

Number of additional programs, if circumstances met | program

Biogen | Provisional Collaboration Agreement | Transport Vehicle (TV)Technology Platform, Preclinical Programs

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

Number of programs | program

Term of agreement, number of business days after 5th anniversary date of the effective date of the agreement

30 days

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

Right of first negotiation (ROFN) term, period of time after effective date of agreement, if circumstances met

7 years

Right of first negotiation (ROFN) term, additional program criteria | program

Number of additional programs, no third party agreement executed, if circumstances met | program

Biogen | Biogen Collaboration Agreement

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

Upfront payment

$ 560,000

Transaction price, change

Cost sharing payments due to related party

$ 4,400

Cost sharing reimbursements due

1,200

Number of milestones achieved | milestone

Biogen | Biogen Collaboration Agreement | Related Party

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

Cost sharing payment due to Biogen

$ 8,200

Offset to research and development expense, related party cost reimbursement

$ 6,500

$ 9,300

Biogen | Biogen Collaboration Agreement | Option Research Services | Related Party

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

Contract liability

$ 1,600

1,600

Performance obligation, period (more than)

one year

Biogen | Biogen Collaboration Agreement | Product

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

Collaborative revenue, revenue from contract with customer

$ 0

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

Development milestone payments

375,000

First commercial sale milestone payments

375,000

Net sales-based milestone payments

$ 375,000

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]

Aggregate option exercise and development milestone payments, to be received

$ 270,000

First commercial sale milestone payments, to be received

325,000

Net sales-based milestone payments, to be received

$ 290,000

Biogen | ROFN and Option Agreement | Material Right For An Option | Related Party

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

Contract liability

$ 288,900

Biogen | Collaborative Arrangement

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

Agreed share of commercial profit (loss) percentage

50.00%

[1]	Includes related-party collaboration revenue from customers of $3.2 million, $3.7 million, and $307.4 million for the years ended December 31, 2022, 2021 and 2020 respectively.

Stock-Based Awards

12 Months Ended

Dec. 31, 2022

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 January 2022, common stock available for issuance under the 2017 Plan was increased by approximately 6.1 million shares as a result of this automatic increase provision. As of December 31, 2022 and 2021, there were approximately 9.9 million and 7.0 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, 2021	13,686,386	$	24.33	6.76	$	333,011
Granted	2,255,840	43.06
Exercised	(720,904)	14.59
Forfeited	(547,605)	41.82
Balance at December 31, 2022	14,673,717	$	27.03	6.24	$	127,865
Vested and expected to vest at December 31, 2022	13,083,022	$	30.24	6.67	$	84,709
Exercisable at December 31, 2022	9,886,659	$	21.71	5.66	$	101,574

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 $12.6 million, $47.9 million, and $43.8 million as of December 31, 2022, 2021 and 2020, respectively. During the years ended December 31, 2022, 2021, and 2020 the weighted-average grant-date fair value of the options vested was $23.96, $11.83, and $11.51 per share, respectively. The weighted-average grant date fair value of all options granted during the years ended December 31, 2022, 2021 and 2020 was $26.00, $41.30, and $15.67 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,
	2022	2021	2020
Expected term (in years)	5.50 - 6.08	5.50 - 6.08	5.50 - 6.08
Volatility	65.1% - 66.3%	61.0% - 63.4%	65.2% - 67.1%
Risk-free interest rate	1.5% - 4.3%	0.5% - 1.3%	0.3% - 1.7%
Dividend yield	—	—	—

Performance and Market Contingent Stock Options Granted to Employees

In August and November 2015, the Board of Directors granted approximately 1.6 million and 0.1 million shares of performance- and market- contingent awards to members of the senior management team, respectively. These awards have an exercise price of $0.68 per share.

These awards have two separate market triggers for vesting based upon either (i) the successful achievement of stepped target closing prices on a national securities exchange for 90 consecutive trading days later than 180 days after the Company’s initial public offering for its common stock, or (ii) stepped target prices for a change in control transaction. The first of these market triggers has been met. In the event the second market trigger is not achieved by the specified timelines, such awards will terminate with respect to that portion of the shares. The expense recognized associated with these performance- and market- contingent awards was $0.3 million of general and administrative expense during the year ended December 31, 2020. There was no expense recognized in the years ended December 31, 2022 and 2021.

The Company used a lattice model with a Monte Carlo simulation to value these stock options. This valuation methodology utilized the estimated fair value of the Company’s common stock on grant date and several key assumptions, including expected volatility of the Company’s stock price based on comparable public companies, risk-free rates of return and expected 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, 2022 is summarized below:


	Number of Units	Weighted-Average Fair Value at Date of Grant per Share




Unvested at December 31, 2021	2,629,980	$	43.97
Granted	1,797,231	37.55
Vested and released	(837,096)	40.30
Forfeited	(259,461)	44.52
Unvested and expected to vest at December 31, 2022	3,330,654	$	41.39

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 the number of RSUs expected to vest. The total intrinsic value of RSUs expected to vest was $92.6 million as of December 31, 2022. During the years ended December 31, 2021 and 2020 the weighted-average grant-date fair value of RSUs granted was $68.30 and $29.31, respectively. The total fair value of RSUs that vested during the years ended December 31, 2022, 2021, and 2020 was $29.4 million, $39.8 million, and $8.7 million, respectively.

Stock-Based Compensation Expense

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


	Year Ended December 31,
	2022		2021		2020
Research and development	$	60,196	$	50,036	$	29,002
General and administrative	39,651		35,211		21,349
Total	$	99,847	$	85,247	$	50,351

As of December 31, 2022, total unamortized stock-based compensation expense was $197.6 million. The weighted-average period over which such stock-based compensation expense will be recognized is approximately 2.5 years.

There was no tax benefit realized related to awards vested or exercised during the years ended December 31, 2022 and 2021. For the year ended December 31, 2020 a tax benefit of $1.0 million was realized related to awards vested or exercised during the period. There is no tax benefit on total stock-based compensation expense for the years ended December 31, 2022, 2021 and 2020 since the company has recorded a full valuation allowance on all deferred tax assets.

Significant Accounting Policies

12 Months Ended

Dec. 31, 2022

Accounting Policies [Abstract]

Significant Accounting Policies

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. 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 Income (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 Income (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, 2022 and 2021, 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 the COVID-19 pandemic, the Russian invasion of Ukraine, inflation, rising interest rates, and recession risks as well as supply chain and labor shortages.

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, 2022 and 2021, the Company had no shares of preferred stock issued or outstanding.

Segments

The Company has one operating segment. The Company’s chief operating decision maker, its Chief Executive Officer, manages the Company’s operations on a consolidated basis for the purposes of allocating resources.

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 $1.5 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.

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, short-term marketable securities, or long-term marketable securities on the Consolidated Balance Sheets, are considered available-for-sale, and 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 Income (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, excluding related parties, net of an allowance for credit losses, if required.

Derivatives and Hedging Activities

The Company has used forward foreign currency exchange contracts to hedge certain operational exposures resulting from potential changes in foreign currency exchange rates. Such exposures resulted from portions of the Company's forecasted cash flows being denominated in currencies other than the U.S. dollar, primarily the Euro and British Pound. The Company measures its derivative instruments at fair value, and accounts for them as either assets or liabilities included within Prepaid expenses and other current assets and Accrued expenses and other current liabilities, respectively, on the Consolidated Balance Sheets. The fair values of forward foreign currency exchange contracts were estimated using current exchange rates and interest rates and took into consideration the current creditworthiness of the counterparties. Derivatives are not designated as cash flow hedges, and as such are adjusted to fair value through interest and other income, net, in the Consolidated Statements of Operations and Comprehensive Income (Loss).

As of December 31, 2021, the Company had 7 Euro and 8 British Pound foreign exchange contracts at aggregate notional foreign currency amounts of €0.8 million and £0.9 million, respectively, to be received upon maturity of the contract. All of the outstanding contracts matured between January and June 2022, and the Company had no outstanding forward foreign currency exchange contracts as of December 31, 2022.

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
Manufacturing and laboratory equipment						five years
Computer hardware and software						three years
Office furniture and equipment						five 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. Right-of-use (“ROU”) assets and operating lease liabilities are recognized for identified operating leases in the Consolidated Balance Sheets. The changes in operating lease ROU assets and operating lease liabilities are presented net within non-cash adjustment to operating lease expense in the Consolidated Statements of Cash Flows.

ROU assets represent the Company’s right to use the underlying asset for the lease term and lease liabilities represent the Company’s obligation to make lease payments arising from the lease. Operating lease ROU assets and liabilities are recognized at the lease commencement date based on the present value of lease payments due over the lease term, with the ROU assets adjusted for lease incentives received. 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.

Leases with an initial term of 12 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 recognizes lease expenses on a straight-line basis over the lease term. 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. This assessment is performed throughout the life of the arrangement based on changes in the responsibilities of all parties in the arrangement. For collaboration arrangements within the scope of ASC 808 that contain multiple elements, the Company first determines which elements of the collaboration are deemed to be within the scope of ASC 808 and those that are more reflective of a vendor-customer relationship and, therefore, within the scope of Topic 606. 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.

The terms of license, option and collaboration agreements entered into typically include payment of one or more of the following: non-refundable, up-front license fees; option exercise fees; development, regulatory and commercial milestone payments; payments for manufacturing supply and research and development services and royalties on net sales of licensed products. Each of these payments results in license, collaboration and other revenue, except for revenues from royalties on net sales of licensed products, which are classified as royalty revenue. The core principle of Topic 606 is to recognize revenue when promised goods or services are transferred to customers in an amount that reflects the consideration that is expected to be received in exchange for those goods or services. 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.

In determining the appropriate amount of revenue to be recognized as the Company fulfills its obligations under each of its agreements, the Company performs the following steps: (i) identification of the promised goods or services in the contract; (ii) determination of whether the promised goods or services are performance obligations including whether they are distinct in the context of the contract; (iii) measurement of the transaction price, including the constraint on variable consideration; (iv) allocation of the transaction price to the performance obligations based on estimated selling prices; and (v) recognition of revenue when (or as) the Company satisfies each performance obligation.

Amounts received prior to satisfying the revenue recognition criteria are recorded as contract liabilities in the Company’s Consolidated Balance Sheets. If the related performance obligation is expected to be satisfied within the next twelve months this will be classified in current liabilities. Amounts recognized as revenue prior to the Company having an unconditional right (other than a right that is conditioned only on the passage of time) to receipt are recorded as contract assets in the Company's Consolidated Balance Sheets. If the Company expects to have an unconditional right to receive the consideration in the next twelve months, this will be classified in current assets. A net contract asset or liability is presented for each contract with a customer.

At contract inception, the Company assesses the goods or services promised in a contract with a customer and identifies those distinct goods and services that represent a performance obligation. A promised good or service may not be identified as a performance obligation if it is immaterial in the context of the contract with the customer, if it is not separately identifiable from other promises in the contract (either because it is not capable of being separated or because it is not separable in the context of the contract), or if the promised good or service does not provide the customer with a material right.

The Company considers the terms of the contract to determine the transaction price. The transaction price is the amount of consideration to which the Company expects to be entitled in exchange for transferring promised goods or services to a customer. The consideration promised in a contract with a customer may include fixed amounts, variable amounts, or both. Variable consideration will only be included in the transaction price when it is not considered constrained, which is when it is probable that a significant reversal in the amount of cumulative revenue recognized will not occur.

If it is determined that multiple performance obligations exist, the transaction price is allocated at the inception of the agreement to all identified performance obligations based on the relative standalone selling prices ("SSP"). The relative SSP for each deliverable is estimated using external sourced evidence if it is available. If external sourced evidence is not available, the Company uses its best estimate of the SSP for the deliverable.

Revenue is recognized when, or as, the Company satisfies a performance obligation by transferring a promised good or service to a customer. 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.

After contract inception, the transaction price is reassessed at every period end and updated for changes such as resolution of uncertain events. Any change in the transaction price is allocated to the performance obligations on the same basis as at contract inception, or to a single performance obligation as applicable.

Management may be required to exercise considerable judgment in estimating revenue to be recognized. Judgment is required in identifying performance obligations, estimating the transaction price, estimating the SSP of identified performance obligations, which may include forecasted revenue, development timelines, reimbursement rates for personnel costs, discount rates and probabilities of technical and regulatory success, and estimating the progress towards satisfaction of performance obligations.

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.

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. We do not need to make significant estimates where costs incurred are supported by invoices or reports of costs incurred are obtained from a vendor that is directly performing the underlying services, such as a consultant or contract manufacturing organization.

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 Company recognizes and measures uncertain tax positions using a two–step approach. The first step is to evaluate the tax position taken or expected to be taken by determining whether the weight of available evidence indicates that it is more likely than not that the tax position will be sustained in an audit, including resolution of any related appeals or litigation processes. The second step is to measure the tax benefit as the largest amount that is more than 50% likely to be realized upon ultimate settlement. Significant judgment is required to evaluate uncertain tax positions. The Company evaluates uncertain tax positions on a regular basis. The evaluations are based on a number of factors, including changes in facts and circumstances, changes in tax law, correspondence with tax authorities during the course of the audit, and effective settlement of audit issues. Previously recognized tax positions that no longer meet the more-likely-than-not threshold are derecognized in the first subsequent financial reporting period in which that threshold is no longer met.

The Company’s policy is to recognize interest and penalties accrued on any unrecognized tax benefits as a component of income tax expense.

Comprehensive Income (Loss)

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

Net Income (Loss) per Share

Basic net income (loss) per share is calculated by dividing the net income (loss) by the weighted-average number of shares of common stock outstanding during the period, without consideration for common stock equivalents.

Diluted net income (loss) per share is computed based on the treasury stock method by dividing net income by the weighted-average number of common shares outstanding during the period plus potentially dilutive common equivalent shares outstanding. However, where there is a net loss per ordinary share, no adjustment is made for potentially issuable ordinary shares since their effect would be anti-dilutive. In this case, diluted net loss per share is equal to basic net loss per share.

Commitments and Contingencies

12 Months Ended

Dec. 31, 2022

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 ten years from the legal commencement date, which was April 1, 2019 when the building was ready for occupancy. For accounting purposes, the lease commencement date was determined to be August 1, 2018, which was the date at which the Company was deemed to have obtained control over the property. The Company has an option to extend the lease term for a period of ten years by giving the landlord written notice of the election to exercise the option at least nine months, but not more than twelve months, prior to the expiration of the Headquarters Lease Amendment lease term. The Company determined that this renewal was not reasonably certain at lease inception.

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 ("SLC Facility") in Salt Lake City, Utah (“SLC Lease”). There was an amendment to the SLC Lease in July 2022, subsequent to which the rentable square feet is approximately 78,000, the contractual term is approximately 9.3 years which will commence upon completion of certain improvements by the landlord and the Company, and future undiscounted lease payments total approximately $19.5 million. For accounting purposes, the SLC lease, as amended, had not commenced as of December 31, 2022 since the landlord had not yet made the underlying asset available for use by the Company, and as such, no lease liability or ROU asset has been recorded on the Consolidated Balance Sheet as of December 31, 2022, and no operating lease expense has been recorded for the year ended December 31, 2022.

Management exercised judgment in applying the requirements of ASC 842, including the determination as to whether certain contracts contain a lease, the type of lease in an arrangement, whether there are separate lease components, the lease consideration, and the commencement date of the lease. Further, there is significant judgment in determining the discount rate to use in estimating the lease right of use ("ROU") asset and lease liability. The discount rate is estimated using the rate implicit in the lease, if known, or alternatively is based on an estimate of our incremental borrowing rate on the date of lease commencement. A change in these assumptions could result in changes in the timing and measurement of rent expense, ROU asset and lease liability or a change in future commitment disclosures. There were no changes to the terms of the Company's existing operating leases recognized under ASC 842 for the year ended December 31, 2022.

Operating lease costs, including variable and short-term lease costs recognized under ASC 842, were $12.2 million, $11.2 million, and $11.1 million for the years ended December 31, 2022, 2021 and 2020, respectively. The following table contains a summary of other information pertaining to the Company’s operating leases for the periods presented (in thousands):


	Year Ended December 31,
		2022			2021			2020

Cash paid for amounts included in measurement of lease liabilities		$	11,189		$	10,336		$	9,737

		As of December 31,
		2022			2021			2020
Weighted average remaining lease term		6.2 years			7.3 years			8.3 years
Weighted average discount rate		8.9		%	9		%	9		%

The following table reconciles the undiscounted lease payments under our operating leases to the operating lease liabilities recorded in the Consolidated Balance Sheet as of December 31, 2022 (in thousands):


Year Ended December 31:
2023	$	12,237
2024	12,122
2025	11,793
2026	12,182
2027	12,584
Thereafter	17,382
Total undiscounted lease payments	78,300
Present value adjustment	(17,950)
Net operating lease liabilities	$	60,350

Sublease

In October 2018, the Company entered into a sublease agreement ("Sublease Agreement") to sublease approximately 36,835 rentable square feet of space in its Headquarters. The Sublease Agreement has a term of five years from the commencement date of April 12, 2019 and provides for the Company to receive monthly base rent amounts escalating over the term of the lease. The Company also passes through a portion of the operating expenses, such as taxes and insurance for the Headquarters to the sublessee, which are treated as variable sublease income. Total sublease income, including rent and variable sublease cost reimbursements, was $3.9 million, $3.8 million and $3.6 million for the years ended December 31, 2022, 2021 and 2020, respectively.

The following table details the future undiscounted cash inflows relating to the Company's Sublease Agreement as of December 31, 2022 (in thousands):


Year Ended December 31:

2023	$	3,096
2024	876

Total undiscounted sublease receipts	$	3,972

In February 2023, the sublease was amended to reduce the rentable square feet, which resulted in a reduction in the total future undiscounted sublease receipts to approximately $1.1 million.

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 Income (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.

As of December 31, 2022 and 2021, the Company had open purchase orders for biological product development and manufacturing costs totaling $35.9 million and $35.8 million, respectively, of which certain amounts are subject to cost sharing with Takeda. The activities under these purchase orders are expected to be completed by November 2029. As of December 31, 2022 and 2021, the Company had total non-cancellable purchase commitments under the DMSA of $32.3 million and $28.3 million, respectively.

During the years ended December 31, 2022, 2021 and 2020, the Company incurred costs of $28.6 million, $17.4 million, and $10.8 million, respectively, and made payments of $23.9 million, $14.9 million, and $7.3 million respectively, for the development and manufacturing services rendered under the DMSA.

In the normal course of business, the Company enters into various firm purchase commitments primarily related to research and development activities. The Company had contractual obligations under development and manufacturing agreements other than the DMSA of $9.6 million and $11.5 million, as of December 31, 2022 and 2021, respectively, with certain amounts subject to cost sharing with Takeda. Further, the Company had other commitments of $1.6 million and $1.7 million as of December 31, 2022 and 2021, respectively, and a purchase commitment related to manufacturing equipment for the SLC Facility of $5.6 million as of December 31, 2022.

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.

Income Taxes - Narrative (Details) - USD ($)	12 Months Ended
Income Taxes - Narrative (Details) - USD ($)	Dec. 31, 2022	Dec. 31, 2021
Operating Loss Carryforwards [Line Items]
Deferred tax asset, research and development TCJA adjustment	$ 61,869,000	$ 0
Valuation allowance against net deferred tax assets (as a percentage)	100.00%	100.00%
Net valuation allowance increase	$ 104,000,000
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	231,900,000
Federal authority \| Research Tax Credit Carryforward
Operating Loss Carryforwards [Line Items]
Tax credit carryforward	42,600,000
Federal authority \| Orphan Drug Tax Credit Carryforward
Operating Loss Carryforwards [Line Items]
Tax credit carryforward	19,700,000
State authority
Operating Loss Carryforwards [Line Items]
Net operating loss carryforward	267,000,000
Tax credit carryforward	$ 31,400,000

Significant Accounting Policies - Property and Equipment, Net (Details)	12 Months Ended
	Dec. 31, 2022
Manufacturing and laboratory equipment
Property, Plant and Equipment [Line Items]
Estimated useful life	5 years
Computer hardware and software
Property, Plant and Equipment [Line Items]
Estimated useful life	3 years
Office furniture and equipment
Property, Plant and Equipment [Line Items]
Estimated useful life	5 years

Marketable Securities - Summary of Available for Sale Securities (Details) $ in Thousands	Dec. 31, 2022 USD ($) security	Dec. 31, 2021 USD ($) security derivative_instrument
Debt Securities, Available-for-sale [Line Items]
Amortized Cost	$ 1,124,718	$ 999,527
Unrealized Holding Gains	96	1
Unrealized Holding Losses	(6,643)	(2,149)
Aggregate Fair Value	1,118,171	997,379
Short-term marketable securities
Debt Securities, Available-for-sale [Line Items]
Amortized Cost	1,124,718	572,250
Unrealized Holding Gains	96	1
Unrealized Holding Losses	(6,643)	(321)
Aggregate Fair Value	$ 1,118,171	571,930
Long-term marketable securities
Debt Securities, Available-for-sale [Line Items]
Amortized Cost		427,277
Unrealized Holding Gains		0
Unrealized Holding Losses		(1,828)
Aggregate Fair Value		$ 425,449
U.S. government treasuries
Debt Securities, Available-for-sale [Line Items]
Number of securities held in unrealized holding loss positions, short-term \| security	51	19
Aggregate fair value, unrealized holding loss position, short-term	$ 683,400	$ 450,400
Number of securities held in unrealized holding loss positions, long-term \| derivative_instrument		16
Aggregate fair value, unrealized holding loss position, long-term		$ 410,100
U.S. government treasuries \| Short-term marketable securities
Debt Securities, Available-for-sale [Line Items]
Amortized Cost	1,009,733	450,689
Unrealized Holding Gains	58	0
Unrealized Holding Losses	(6,287)	(253)
Aggregate Fair Value	1,003,504	450,436
U.S. government treasuries \| Long-term marketable securities
Debt Securities, Available-for-sale [Line Items]
Amortized Cost		411,904
Unrealized Holding Gains		0
Unrealized Holding Losses		(1,757)
Aggregate Fair Value		$ 410,147
U.S. government agency securities \| Short-term marketable securities
Debt Securities, Available-for-sale [Line Items]
Amortized Cost	16,823
Unrealized Holding Gains	38
Unrealized Holding Losses	0
Aggregate Fair Value	$ 16,861
Corporate debt securities
Debt Securities, Available-for-sale [Line Items]
Number of securities held in unrealized holding loss positions, short-term \| security	16	16
Aggregate fair value, unrealized holding loss position, short-term	$ 54,200	$ 68,500
Number of securities held in unrealized holding loss positions, long-term \| security		6
Aggregate fair value, unrealized holding loss position, long-term		$ 15,300
Corporate debt securities \| Short-term marketable securities
Debt Securities, Available-for-sale [Line Items]
Amortized Cost	54,571	70,076
Unrealized Holding Gains	0	1
Unrealized Holding Losses	(356)	(68)
Aggregate Fair Value	54,215	70,009
Corporate debt securities \| Long-term marketable securities
Debt Securities, Available-for-sale [Line Items]
Amortized Cost		15,373
Unrealized Holding Gains		0
Unrealized Holding Losses		(71)
Aggregate Fair Value		15,302
Commercial paper \| Short-term marketable securities
Debt Securities, Available-for-sale [Line Items]
Amortized Cost	43,591	51,485
Unrealized Holding Gains	0	0
Unrealized Holding Losses	0	0
Aggregate Fair Value	$ 43,591	$ 51,485

Income Taxes (Tables)

12 Months Ended

Dec. 31, 2022

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,
	2022		2021		2020
Current:
U.S. Federal	$	—	$	—	$	—
U.S. State	7		(576)		823
Foreign	14		1		—
Total Current	$	21	$	(575)	$	823

Deferred:
U.S. Federal	$	—	$	—	$	—
U.S. State	—		—		—
Foreign	—		—		—
Total deferred	$	—	$	—	$	—

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,
	2022		2021		2020
Taxes at the U.S. statutory tax rate	21.0	%	21.0	%	21.0	%
Effect of Tax Act	—		—		1.1
Change in valuation allowance	(25.1)		(28.2)		(4.0)
Research tax credits	4.9		4.1		(9.2)
Stock-based compensation	(0.5)		3.2		(7.9)

Other	(0.4)		0.1		0.1
Total provision for income taxes	(0.1)	%	0.2	%	1.1	%

Schedule of Deferred Tax Assets and Liabilities

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


	December 31,
	2022		2021
Deferred tax assets:
Net operating loss carryforwards	$	67,492	$	59,285
Tax credit carryforwards	69,562		48,058
Research expense capitalization	61,869		—
Contract liabilities	70,824		75,281
Operating lease liabilities	14,712		15,040
Stock-based compensation	44,473		30,185
Accruals and other	18,381		15,385
Gross deferred tax assets	347,313		243,234
Valuation allowance	(332,580)		(228,586)
Net deferred tax assets	14,733		14,648
Deferred tax liabilities:
Property and equipment	(7,314)		(7,424)
Operating lease right-of-use assets	(7,419)		(7,224)
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,
	2022		2021		2020
Unrecognized tax benefits at January 1	$	13,699	$	8,139	$	5,299
Additions for tax positions taken in a prior year	135		1,042		—
Additions for tax positions taken in the current year	5,537		4,725		3,009
Reductions for tax positions taken in the prior year	—		(207)		(169)
Unrecognized tax benefits at December 31	$	19,371	$	13,699	$	8,139

Stock-Based Awards - Summary of Restricted Stock Activity (Details) - Restricted Stock Units (RSUs) - $ / shares	12 Months Ended
	Dec. 31, 2022	Dec. 31, 2021	Dec. 31, 2020
Number of Units
Beginning balance (in shares)	2,629,980
Granted (in shares)	1,797,231
Vested and released (in shares)	(837,096)
Forfeited (in shares)	(259,461)
Ending balance (in shares)	3,330,654	2,629,980
Expected to vest (in shares)	3,330,654
Weighted-Average Fair Value at Date of Grant per Share
Beginning balance (usd per share)	$ 43.97
Granted (usd per share)	37.55	$ 68.3	$ 29.31
Vested and released (usd per share)	40.30
Forfeited (usd per share)	44.52
Ending balance (usd per share)	41.39	$ 43.97
Expected to vest (usd per share)	$ 41.39

Marketable Securities

12 Months Ended

Dec. 31, 2022

Investments, Debt and Equity Securities [Abstract]

Marketable Securities

All marketable securities were considered available-for-sale at December 31, 2022 and 2021. 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, 2022
	Amortized Cost		Unrealized Holding Gains		Unrealized Holding Losses		Aggregate Fair Value
Short-term marketable securities:
U.S. government treasuries(1)	$	1,009,733	$	58	$	(6,287)	$	1,003,504
U.S. government agency securities	16,823		38		—		16,861
Corporate debt securities(2)	54,571		—		(356)		54,215
Commercial paper	43,591		—		—		43,591
Total short-term marketable securities	1,124,718		96		(6,643)		1,118,171





Total	$	1,124,718	$	96	$	(6,643)	$	1,118,171

______________________________________________

(1)Unrealized holding losses on 51 securities with an aggregate fair value of $683.4 million.

(2)Unrealized holding losses on 16 securities with an aggregate fair value of $54.2 million.


	December 31, 2021
	Amortized Cost		Unrealized Holding Gains		Unrealized Holding Losses		Aggregate Fair Value
Short-term marketable securities:
U.S. government treasuries(1)	$	450,689	$	—	$	(253)	$	450,436

Corporate debt securities(2)	70,076		1		(68)		70,009
Commercial paper	51,485		—		—		51,485
Total short-term marketable securities	572,250		1		(321)		571,930
Long-term marketable securities:
U.S. government treasuries(3)	411,904		—		(1,757)		410,147
Corporate debt securities(4)	15,373		—		(71)		15,302
Total long-term marketable securities	427,277		—		(1,828)		425,449
Total	$	999,527	$	1	$	(2,149)	$	997,379

__________________________________________________

(1)Unrealized holding losses on 19 securities with an aggregate fair value of $450.4 million.

(2)Unrealized holding losses on 16 securities with an aggregate fair value of $68.5 million.

(3)Unrealized holding losses on 16 securities with an aggregate fair value of $410.1 million.

(4)Unrealized holding losses on 6 securities with an aggregate fair value of $15.3 million.

As of December 31, 2022 and 2021, a majority of the Company's marketable securities were in an unrealized loss position. The Company has not recognized an allowance for credit losses as of December 31, 2022 or 2021. 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 these securities are held in U.S. government securities, and the remainder were initially, and continue to be, held with investment grade, high credit quality institutions. All marketable securities with unrealized losses as of each balance sheet date have been in a loss position for less than twelve months or the loss is not material.

As of December 31, 2022 all of the Company’s marketable securities have an effective maturity of less than one year.

Consolidated Statements of Stockholders' Equity - USD ($) $ in Thousands	Total	Common Stock	Additional Paid-in Capital	Accumulated Other Comprehensive Loss	Accumulated Deficit
Beginning balance (in shares) at Dec. 31, 2019		96,189,935
Beginning balance at Dec. 31, 2019	$ 394,890	$ 1,288	$ 818,803	$ 350	$ (425,551)
Increase (Decrease) in Stockholders' Equity [Roll Forward]
Issuance of common stock in follow-on offering, net of issuance costs of 632 (in shares)		9,000,000
Issuance of common stock in follow-on offering, net of issuance costs of $632	193,948	$ 90	193,858
Issuance of common stock in connection with the Biogen Stock Purchase Agreement (in shares)		13,310,243
Issuance of common stock in connection with the Biogen Stock Purchase Agreement	420,146	$ 133	420,013
Issuances under equity incentive plans (in shares)		1,722,058
Issuances under equity incentive plans	20,655	$ 17	20,638
Vesting of restricted stock units (in shares)		309,097
Vesting of restricted stock units	0	$ 3	(3)
Stock-based compensation	50,351		50,351
Net Income (loss)	71,136				71,136
Other comprehensive loss	(595)			(595)
Ending balance (in shares) at Dec. 31, 2020		120,531,333
Ending balance at Dec. 31, 2020	1,150,531	$ 1,531	1,503,660	(245)	(354,415)
Increase (Decrease) in Stockholders' Equity [Roll Forward]
Common stock issuance costs		$ 632
Issuances under equity incentive plans (in shares)		1,117,636
Issuances under equity incentive plans	19,348	$ 11	19,337
Vesting of restricted stock units (in shares)		634,336
Vesting of restricted stock units	0	$ 6	(6)
Stock-based compensation	85,247		85,247
Net Income (loss)	(290,581)				(290,581)
Other comprehensive loss	$ (2,254)			(2,254)
Ending balance (in shares) at Dec. 31, 2021	122,283,305	122,283,305
Ending 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 in follow-on offering, net of issuance costs of 632 (in shares)		11,933,962
Issuance of common stock in follow-on offering, net of issuance costs of $632	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 Income (loss)	(325,991)				(325,991)
Other comprehensive loss	$ (4,387)			(4,387)
Ending balance (in shares) at Dec. 31, 2022	135,965,918	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]
Common stock issuance costs		$ 1,060

Acquisition - Narrative (Details) - USD ($)

1 Months Ended

12 Months Ended

55 Months Ended

77 Months Ended

May 30, 2018

Aug. 24, 2016

Aug. 31, 2016

Dec. 31, 2022

Dec. 31, 2021

Dec. 31, 2020

Dec. 31, 2022

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

Research and development expense

^[1]

$ 358,732,000

$ 265,353,000

$ 212,615,000

Collaborative Arrangement with F-Star and Acquisition of F-Star Gamma

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

Upfront payment

$ 11,500,000

Upfront option fee

$ 500,000

Contingent consideration recognized

$ 0

Total upfront and contingent consideration

$ 19,800,000

Maximum development plan period for research costs

24 months

Research and development expense

$ 0

$ 100,000

$ 1,200,000

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]

Initial option exercise payments

$ 17,800,000

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

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

Contingent payments upon achievement of milestones

3,000,000

$ 1,500,000

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

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

Contingent payments upon achievement of milestones

30,000,000

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 | 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

$ 243,000,000

[1]	Includes expense for cost sharing payments to a related party of $8.2 million for the year ended December 31, 2022 and an offset to expense from related-party cost reimbursements of $6.5 million and $9.3 million for the years ended December 31, 2021 and 2020, respectively.

Consolidated Balance Sheets - USD ($) $ in Thousands	Dec. 31, 2022	Dec. 31, 2021
Current assets:
Cash and cash equivalents	$ 218,044	$ 293,477
Short-term marketable securities	1,118,171	571,930
Cost sharing reimbursements due from related party	0	1,226
Prepaid expenses and other current assets	36,104	30,601
Total current assets	1,372,319	897,234
Long-term marketable securities	0	425,449
Property and equipment, net	44,087	38,865
Operating lease right-of-use assets	30,437	30,743
Other non-current assets	13,399	11,871
Total assets	1,460,242	1,404,162
Current liabilities:
Accounts payable	2,790	4,779
Cost sharing payments due to related party	4,388	0
Accrued expenses and other current liabilities	66,691	53,165
Related party contract liability, current	290,053	292,386
Contract liabilities, current	0	27,915
Total current liabilities	363,922	378,245
Related party contract liability, less current portion	479	1,295
Contract liabilities, less current portion	0	3,398
Operating lease liabilities, less current portion	53,032	58,554
Other non-current liabilities	379	379
Total liabilities	417,812	441,871
Commitments and contingencies (Note 8)
Stockholders’ equity:
Convertible preferred stock, $0.01 par value; 40,000,000 shares authorized as of December 31, 2022 and December 31, 2021; 0 shares issued and outstanding as of December 31, 2022 and December 31, 2021	0	0
Common stock, $0.01 par value; 400,000,000 shares authorized as of December 31, 2022 and December 31, 2021; 135,965,918 and 122,283,305 shares issued and outstanding as of December 31, 2022 and December 31, 2021, respectively	1,686	1,548
Additional paid-in capital	2,018,617	1,608,238
Accumulated other comprehensive loss	(6,886)	(2,499)
Accumulated deficit	(970,987)	(644,996)
Total stockholders’ equity	1,042,430	962,291
Total liabilities and stockholders’ equity	$ 1,460,242	$ 1,404,162

Significant Accounting Policies (Policies)

12 Months Ended

Dec. 31, 2022

Accounting Policies [Abstract]

Organization and Description of Business

Basis of Presentation

Basis of PresentationThese 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

Use of Estimates

Concentration of Credit Risk and Other Risks and Uncertainties

Segments

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

Accounts ReceivableAccounts 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, excluding related parties, net of an allowance for credit losses, if required.

Derivatives and Hedging Activities

Property and Equipment, Net


Asset						Estimated useful life
Leasehold improvements						Shorter of life of asset or lease term
Manufacturing and laboratory equipment						five years
Computer hardware and software						three years
Office furniture and equipment						five years

Impairment of Long-Lived Assets

Leases

Revenue Recognition

License, Option and Collaboration Revenue

Research and Development Expenses

Stock-Based Compensation

Income Taxes

The Company’s policy is to recognize interest and penalties accrued on any unrecognized tax benefits as a component of income tax expense.

Comprehensive Income (Loss)

Net Income (Loss) per Share

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

12 Months Ended

Dec. 31, 2022

Dec. 31, 2021

Dec. 31, 2020

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

Collaborative revenue, revenue from contract with customer

^[1]

$ 105,065

$ 48,657

$ 335,561

Collaborative revenue, excluding revenue from contract with customer

3,398

Total Collaboration Revenue

108,463

48,661

335,659

Takeda Collaboration Agreement

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

Total Collaboration Revenue

51,916

29,921

27,155

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

27,900

15,900

19,600

Takeda Collaboration Agreement | Collaboration Agreement Services

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

Collaborative revenue, revenue from contract with customer

51,916

19,921

27,155

Takeda Collaboration Agreement | Collaborative Arrangement, PTV:PGRN

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

Collaborative revenue, revenue from contract with customer

5,000

Takeda Collaboration Agreement | Collaborative Arrangement, ATV:TREM2

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

Collaborative revenue, revenue from contract with customer

5,000

Sanofi Collaboration Agreement

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

Total Collaboration Revenue

53,398

15,004

1,067

Sanofi Collaboration Agreement | CNS Program License

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

Collaborative revenue, revenue from contract with customer

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

15,000

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

Sanofi Collaboration Agreement | Retained Activities

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

Collaborative revenue, revenue from contract with customer

969

Biogen Collaboration Agreement

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

Total Collaboration Revenue

3,149

3,736

307,437

Biogen Collaboration Agreement | LRRK2 Program License

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

Collaborative revenue, revenue from contract with customer

306,545

Biogen Collaboration Agreement | Option Research Services

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

Collaborative revenue, revenue from contract with customer

$ 3,149

$ 3,736

$ 892

[1]	Includes related-party collaboration revenue from customers of $3.2 million, $3.7 million, and $307.4 million for the years ended December 31, 2022, 2021 and 2020 respectively.

Consolidated Statements of Cash Flows - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2022	Dec. 31, 2021	Dec. 31, 2020
Operating activities
Net income (loss)	$ (325,991)	$ (290,581)	$ 71,136
Adjustments to reconcile net income (loss) to net cash provided by (used in) operating activities:
Depreciation and amortization	10,383	8,593	8,531
Stock-based compensation expense	99,847	85,247	50,351
Net amortization of premiums and (discounts) on marketable securities	(1,637)	8,748	55
Non-cash adjustment to operating lease expense	(3,351)	(2,984)	(2,360)
Other non-cash items	63	0	38
Changes in operating assets and liabilities:
Prepaid expenses and other assets	(2,760)	(12,865)	(10,569)
Accounts payable	2,274	3,705	(1,623)
Accruals and other current liabilities	10,918	4,732	22,106
Contract liabilities	(31,313)	(11,925)	(19,253)
Related party contract liability	(3,149)	(3,737)	297,418
Other non-current liabilities	0	(322)	322
Net cash provided by (used in) operating activities	(244,716)	(211,389)	416,152
Investing activities
Purchases of marketable securities	(1,115,040)	(1,422,938)	(1,285,468)
Purchases of property and equipment	(17,833)	(8,500)	(3,095)
Maturities and sales of marketable securities	991,486	1,409,812	665,357
Net cash used in investing activities	(141,387)	(21,626)	(623,206)
Financing activities
Proceeds from issuance of common stock in connection with Collaboration Agreements	0	0	420,146
Proceeds from public offering of common stock, net of issuance costs	296,215	0	193,948
Proceeds from exercise of awards under equity incentive plans	14,455	19,348	20,655
Net cash provided by financing activities	310,670	19,348	634,749
Net increase (decrease) in cash, cash equivalents and restricted cash	(75,433)	(213,667)	427,695
Cash, cash equivalents and restricted cash at beginning of year	294,977	508,644	80,949
Cash, cash equivalents and restricted cash at end of year	219,544	294,977	508,644
Supplemental disclosures of cash flow information
Cash paid during the year for income taxes	47	210	0
Issuance costs incurred but not yet paid	224	0	0
Property and equipment purchases accrued but not yet paid	$ 1,464	$ 593	$ 67

Stock-Based Awards - Narrative (Details) - USD ($)	1 Months Ended				12 Months Ended
Stock-Based Awards - Narrative (Details) - USD ($)	Dec. 31, 2017	Dec. 31, 2015	Nov. 30, 2015	Aug. 31, 2015	Dec. 31, 2022	Dec. 31, 2021	Dec. 31, 2020	Jan. 31, 2022
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Aggregate intrinsic value of options exercised					$ 12,600,000	$ 47,900,000	$ 43,800,000
Weighted-average grant date fair value of options vested (usd per share)					$ 23.96	$ 11.83	$ 11.51
Weighted-average grant date fair value of options granted (usd per share)					$ 26	$ 41.3	$ 15.67
Dividend yield					0.00%
Stock options granted (in shares)					2,255,840
Exercise price (usd per share)					$ 14.59
Share-based compensation, expense recognized					$ 99,847,000	$ 85,247,000	$ 50,351,000
Unamortized stock- based compensation expense related to unvested stock options					$ 197,600,000
Expected weighted average period					2 years 6 months
Tax benefit realized, related to awards vested or exercised					$ 0	0	1,000,000
Total stock-based compensation expense, tax benefit					0	0	0
General and administrative
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Share-based compensation, expense recognized					39,651,000	35,211,000	21,349,000
Research and development
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Share-based compensation, expense recognized					$ 60,196,000	50,036,000	29,002,000
Performance and Market Contingent Stock Options
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Stock options granted (in shares)			100,000	1,600,000
Exercise price (usd per share)			$ 0.68	$ 0.68
Vesting trigger, number of consecutive trading days					90 days
Vesting trigger, number of days after IPO					180 days
Share-based compensation, expense recognized					$ 0	$ 0
Performance and Market Contingent Stock Options \| General and administrative
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Share-based compensation, expense recognized							$ 300,000
Restricted Stock Units (RSUs)
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Intrinsic value of units expected to vest					$ 92,600,000
Weighted-average grant-date fair value, granted (usd per share)					$ 37.55	$ 68.3	$ 29.31
Fair value of units vested					$ 29,400,000	$ 39,800,000	$ 8,700,000
2017 Equity Incentive Plan
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Number of shares available for grant (in shares)					9,900,000	7,000,000
Number of additional shares allowable under the plan (in shares)	10,000,000							6,100,000
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
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

Cover Page - USD ($) $ in Billions	12 Months Ended
Cover Page - USD ($) $ in Billions	Dec. 31, 2022	Feb. 21, 2023	Jun. 30, 2022
Cover [Abstract]
Document Type	10-K
Document Annual Report	true
Document Period End Date	Dec. 31, 2022
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	866-8548
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
Entity Shell Company	false
Entity Public Float			$ 1.5
Entity Common Stock, Shares Outstanding (in shares)		136,677,646
Documents Incorporated by Reference	Portions of the registrant’s Definitive Proxy Statement relating to the registrant’s 2023 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 2022 fiscal year ended December 31, 2022.
Document Fiscal Year Focus	2022
Amendment Flag	false
Document Fiscal Period Focus	FY
Entity Central Index Key	0001714899

Defined Contribution Plan - Narrative (Details) - USD ($) $ in Millions	12 Months Ended
	Dec. 31, 2022	Dec. 31, 2021	Dec. 31, 2020
Retirement Benefits [Abstract]
Contribution expenses	$ 2.8	$ 2.3	$ 1.9

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

12 Months Ended

Dec. 31, 2022

Dec. 31, 2021

Dec. 31, 2020

Collaboration revenue:

Collaboration revenue from customers

^[1]

$ 105,065

$ 48,657

$ 335,561

Other collaboration revenue

3,398

Total collaboration revenue

108,463

48,661

335,659

Operating expenses:

Research and development

^[2]

358,732

265,353

212,615

General and administrative

90,475

79,059

60,326

Total operating expenses

449,207

344,412

272,941

Income (loss) from operations

(340,744)

(295,751)

62,718

Interest and other income, net

14,774

4,595

9,241

Income (loss) before income taxes

(325,970)

(291,156)

71,959

Income tax benefit (expense)

(21)

575

(823)

Net income (loss)

(325,991)

(290,581)

71,136

Other comprehensive income (loss):

Net unrealized loss on marketable securities, net of tax

(4,387)

(2,254)

(595)

Comprehensive income (loss)

$ (330,378)

$ (292,835)

$ 70,541

Net income (loss) per share:

Basic net income (loss) per share (usd per share)

$ (2.60)

$ (2.39)

$ 0.65

Diluted net income (loss) per share (usd per share)

$ (2.60)

$ (2.39)

$ 0.63

Weighted-average shares used in calculating:

Basic net income (loss) per share (in shares)

125,530,703

121,524,795

108,974,137

Diluted net income (loss) per share (in shares)

125,530,703

121,524,795

112,703,108

[1]	Includes related-party collaboration revenue from customers of $3.2 million, $3.7 million, and $307.4 million for the years ended December 31, 2022, 2021 and 2020 respectively.
[2]	Includes expense for cost sharing payments to a related party of $8.2 million for the year ended December 31, 2022 and an offset to expense from related-party cost reimbursements of $6.5 million and $9.3 million for the years ended December 31, 2021 and 2020, respectively.

Balance Sheet Components - Narrative (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2022	Dec. 31, 2021	Dec. 31, 2020
Organization, Consolidation and Presentation of Financial Statements [Abstract]
Depreciation expense	$ 10,383	$ 8,593	$ 8,531

Fair Value Measurements (Tables)

12 Months Ended

Dec. 31, 2022

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, 2022
	Level 1		Level 2		Level 3		Total
Assets:
Cash equivalents:
Money market funds	$	105,340	$	—	$	—	$	105,340
U.S. government treasuries	43,781		—		—		43,781
Commercial paper	—		9,948		—		9,948
Short-term marketable securities:
U.S. government treasuries	1,003,504		—		—		1,003,504
U.S. government agency securities	—		16,861		—		16,861
Corporate debt securities	—		54,215		—		54,215
Commercial paper	—		43,591		—		43,591





Total	$	1,152,625	$	124,615	$	—	$	1,277,240


	December 31, 2021
	Level 1		Level 2		Level 3		Total
Assets:
Cash equivalents
Money market funds	$	265,294	$	—	$	—	$	265,294


Short-term marketable securities:
U.S. government treasuries	450,436		—		—		450,436

Corporate debt securities	—		70,009		—		70,009
Commercial paper	—		51,485		—		51,485
Long-term marketable securities:
U.S. government treasuries	410,147		—		—		410,147

Corporate debt securities	—		15,302		—		15,302

Total	$	1,125,877	$	136,796	$	—	$	1,262,673
Liabilities:
Foreign currency derivative contracts	$	—	$	111	$	—	$	111
Total	$	—	$	111	$	—	$	111

Stock-Based Awards - Summary of Stock-Based Compensation Expense (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2022	Dec. 31, 2021	Dec. 31, 2020
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Total	$ 99,847	$ 85,247	$ 50,351
Research and development
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Total	60,196	50,036	29,002
General and administrative
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Total	$ 39,651	$ 35,211	$ 21,349

Income Taxes - Schedule of Deferred Tax Assets and Liabilities (Details) - USD ($) $ in Thousands	Dec. 31, 2022	Dec. 31, 2021
Deferred tax assets:
Net operating loss carryforwards	$ 67,492	$ 59,285
Tax credit carryforwards	69,562	48,058
Research expense capitalization	61,869	0
Contract liabilities	70,824	75,281
Operating lease liabilities	14,712	15,040
Stock-based compensation	44,473	30,185
Accruals and other	18,381	15,385
Gross deferred tax assets	347,313	243,234
Valuation allowance	(332,580)	(228,586)
Net deferred tax assets	14,733	14,648
Deferred tax liabilities:
Property and equipment	(7,314)	(7,424)
Operating lease right-of-use assets	(7,419)	(7,224)
Net deferred tax assets	$ 0	$ 0

Net Income (Loss) and Net Income (Loss) Per Share - Calculation of Basic and Diluted Net Loss (Details) - USD ($) $ / shares in Units, $ in Thousands	12 Months Ended
	Dec. 31, 2022	Dec. 31, 2021	Dec. 31, 2020
Numerator:
Net income (loss)	$ (325,991)	$ (290,581)	$ 71,136
Denominator:
Weighted average number of shares outstanding, basic (in shares)	125,530,703	121,524,795	108,974,137
Dilutive effect of outstanding common stock options, ESPP shares issuable, and restricted shares (in shares)	0	0	3,728,971
Weighted average number of shares outstanding, diluted (in shares)	125,530,703	121,524,795	112,703,108
Net income (loss) per share, basic (usd per share)	$ (2.60)	$ (2.39)	$ 0.65
Net income (loss) per share, diluted (usd per share)	$ (2.60)	$ (2.39)	$ 0.63
Total (in shares)	18,200,000	16,500,000	4,200,000

- Definition

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

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+ 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

Income Taxes - Effective Tax Rate Reconciliation (Details)	12 Months Ended
	Dec. 31, 2022	Dec. 31, 2021	Dec. 31, 2020
Income Tax Disclosure [Abstract]
Taxes at the U.S. statutory tax rate	21.00%	21.00%	21.00%
Effect of Tax Act	0.00%	0.00%	1.10%
Change in valuation allowance	(25.10%)	(28.20%)	(4.00%)
Research tax credits	4.90%	4.10%	(9.20%)
Stock-based compensation	(0.50%)	3.20%	(7.90%)
Other	(0.40%)	0.10%	0.10%
Total provision for income taxes	(0.10%)	0.20%	1.10%

Balance Sheet Components - Property and Equipment, Net (Details) - USD ($) $ in Thousands	Dec. 31, 2022	Dec. 31, 2021
Property, Plant and Equipment [Line Items]
Total property and equipment	$ 81,302	$ 68,209
Less: accumulated depreciation	(37,215)	(29,344)
Total property and equipment, net	44,087	38,865
Leasehold improvements
Property, Plant and Equipment [Line Items]
Total property and equipment	43,698	35,235
Manufacturing and laboratory equipment
Property, Plant and Equipment [Line Items]
Total property and equipment	34,419	30,114
Computers equipment and purchased software
Property, Plant and Equipment [Line Items]
Total property and equipment	1,605	1,337
Furniture and fixtures
Property, Plant and Equipment [Line Items]
Total property and equipment	$ 1,580	$ 1,523

Fair Value Measurements - Schedule of Assets and Liabilities (Details) - USD ($) $ in Thousands	Dec. 31, 2022	Dec. 31, 2021
Assets:
Total	$ 1,277,240	$ 1,262,673
Liabilities:
Derivative Liability, Statement of Financial Position [Extensible Enumeration]		Accrued expenses and other current liabilities
Foreign currency derivative contracts		$ 111
Total		111
U.S. government treasuries
Assets:
Short-term marketable securities, fair value	1,003,504	450,436
Long-term marketable securities, fair value		410,147
U.S. government agency securities
Assets:
Short-term marketable securities, fair value	16,861
Corporate debt securities
Assets:
Short-term marketable securities, fair value	54,215	70,009
Long-term marketable securities, fair value		15,302
Commercial paper
Assets:
Short-term marketable securities, fair value	43,591	51,485
Money market funds
Assets:
Cash equivalents	105,340	265,294
U.S. government treasuries
Assets:
Cash equivalents	43,781
Commercial paper
Assets:
Cash equivalents	9,948
Level 1
Assets:
Total	1,152,625	1,125,877
Liabilities:
Foreign currency derivative contracts		0
Total		0
Level 1 \| U.S. government treasuries
Assets:
Short-term marketable securities, fair value	1,003,504	450,436
Long-term marketable securities, fair value		410,147
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	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	105,340	265,294
Level 1 \| U.S. government treasuries
Assets:
Cash equivalents	43,781
Level 1 \| Commercial paper
Assets:
Cash equivalents	0
Level 2
Assets:
Total	124,615	136,796
Liabilities:
Foreign currency derivative contracts		111
Total		111
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	16,861
Level 2 \| Corporate debt securities
Assets:
Short-term marketable securities, fair value	54,215	70,009
Long-term marketable securities, fair value		15,302
Level 2 \| Commercial paper
Assets:
Short-term marketable securities, fair value	43,591	51,485
Level 2 \| Money market funds
Assets:
Cash equivalents	0	0
Level 2 \| U.S. government treasuries
Assets:
Cash equivalents	0
Level 2 \| Commercial paper
Assets:
Cash equivalents	9,948
Level 3
Assets:
Total	0	0
Liabilities:
Foreign currency derivative contracts		0
Total		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	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
Level 3 \| U.S. government treasuries
Assets:
Cash equivalents	0
Level 3 \| Commercial paper
Assets:
Cash equivalents	$ 0

Collaboration Agreements

12 Months Ended

Dec. 31, 2022

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 Transport Vehicle ("TV") technology platform 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 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.

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. 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. Since the shares of common stock owned by Biogen as of December 31, 2022 represent approximately 10% of the voting interest of the Company, Biogen is considered a related party as defined in ASC 850. 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.

On September 22, 2020, the Company closed the sale of the Shares to BIMA pursuant to the Stock Purchase Agreement. The estimated fair market value of the Shares issued to BIMA was $420.1 million, based on the closing stock price of $35.87 on the date of issuance adjusted by a discount for lack of marketability due to certain holding period restrictions, which was valued using an option pricing model. 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 for the Biogen Collaboration Agreement.

ROFN and Option Agreement

Under this agreement, Biogen received an exclusive option to license two preclinical programs enabled by the Company's TV technology platform, which platform aims to improve brain uptake of biotherapeutics, including its ATV-enabled anti-amyloid beta program ("ATV-Abeta program") and a second program utilizing the Company's TV technology for an unnamed target ("TV program"), excluding small molecules, Adeno-associated viruses ("AAV") and oligonucleotides. Biogen’s option may be exercised up to initiation of investigational new drug ("IND")-enabling studies for each program and continues for each program until a specified period of time after delivery of an option data package, or thirty business days after the 5th anniversary of the effective date of the Provisional Biogen Collaboration Agreement, whichever is earlier.

Further, Biogen will have the right of first negotiation ("ROFN") on two additional TV-enabled therapeutics within Alzheimer’s disease, Parkinson’s disease, ALS and MS should the Company decide to seek a collaboration with a third party for such programs, but this does not include any of the Company’s small molecule, AAV or oligonucleotide programs. The ROFN period continues until seven years after the effective date of the Provisional Biogen Collaboration Agreement or the date on which the Company has offered Biogen two ROFN Programs, and for which Biogen has agreed to trigger a ROFN for such program, whichever is earlier. However, if the Company does not execute an agreement with a third party with respect to a particular ROFN Program offered to Biogen within a specified amount of time, Biogen will have one additional right to exercise the ROFN again with respect to such ROFN Program.

Under the ROFN and Option Agreement, with respect to the options granted by the Company to Biogen, if exercised, Biogen is obligated to pay to the Company an aggregate of up to $270.0 million in option exercise and development milestone payments, up to $325.0 million upon first commercial sale, and up to $290.0 million of net sales-based milestone payments, following the achievement of certain prespecified milestone events and if Biogen exercises both of its options. Furthermore, Biogen is obligated to pay to the Company royalties in the mid-single digit to mid-teens percentages, depending on the program for which Biogen exercises its option and upon the achievement of certain sales thresholds.

The Biogen Collaboration Agreement was considered 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 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 transaction price at inception included fixed consideration consisting of the upfront fee of $560.0 million and the $44.9 million premium on the sale of common stock. All potential future milestones and other payments were considered constrained at the inception of the Biogen Collaboration Agreement since the Company could not conclude it was probable that a significant reversal in the amount recognized would not occur. From inception of the Biogen Collaboration Agreement through December 31, 2022, there was no change to the transaction price.

The respective standalone value for each of the performance obligations was determined by applying the SSP method and the transaction price 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 Company used an adjusted market assessment approach to estimate the selling price for the LRRK2 Program license, an expected cost plus margin approach for estimating the Option Research Services and estimated the intrinsic value of the material right for the option, taking into account the likelihood that an option would be exercised. 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 are expected to be delivered over time as the services are performed, with revenue being recognized over time based on costs incurred to perform the services, since the level of costs incurred over time is thought to best reflect the transfer of services to Biogen. Revenue allocated to the material right for an option under the ROFN and Option Agreement is deferred as a contract liability until the option opt in period ends, expiration or ROFN and Option Agreement termination. The LRRK2 Development Activities cost sharing reimbursements or expenses will be recognized over time as earned or incurred, since this is believed to directly correlate to the value of the services performed.

A related party contract liability of $290.5 million was recorded on the Consolidated Balance Sheet as of December 31, 2022. Approximately $288.9 million of this contract liability relates to the revenue allocated to the material right for an option under the ROFN and Option Agreement which is being deferred until resolution of the option, which is expected to be within six months of the balance sheet date, and $1.6 million of this contract liability relates to the portion of the Option Research Services performance obligation yet to be satisfied, with such amount to be recognized over the estimated period of the services, which is expected to be more than one year. The Company recorded $8.2 million of cost sharing payments to Biogen for LRRK2 development activities in research and development expenses in the Consolidated Statements of Operations and Comprehensive Income (Loss) for the year ended December 31, 2022, of which $4.4 million was recorded as cost sharing payments due to related party on the Consolidated Balance Sheet as of December 31, 2022. The Company recorded $6.5 million and $9.3 million of cost sharing reimbursements for LRRK2 Development Activities as an offset to research and development expenses in the Consolidated Statements of Operations and Comprehensive Income (Loss) for the years ended December 31, 2021 and 2020, respectively, of which $1.2 million was recorded as cost sharing reimbursement due from related party on the Consolidated Balance Sheet as of December 31, 2021.

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, 2022, the Company had not achieved any milestones and had not recorded any 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 will be developed and commercialized. The Sanofi Collaboration Agreement became effective in November 2018 at which time Sanofi paid the Company an upfront payment of $125.0 million. Under the Sanofi Collaboration Agreement, the Company is eligible to receive milestone payments from Sanofi up to approximately $1.1 billion upon achievement of certain clinical, regulatory and sales milestone events. Such milestone payments include $215.0 million in clinical milestone payments and $385.0 million in regulatory milestone payments for CNS Products, as defined, that are developed and approved in the United States, by the European Medicines Agency ("EMA") and in Japan for three indications, including Alzheimer's disease. These milestones also 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, by the EMA and Japan for three indications.

The Company will share profits and losses equally with Sanofi for CNS Products sold in the United States and China, and receive variable royalties on net sales for CNS Products sold outside of the United States and China and for Peripheral Products sold worldwide.

The Company and Sanofi will jointly develop CNS Products pursuant to a global development plan. The Company will be responsible, at its own cost, for conducting Phase 1 and Phase 2 trials for CNS Products in Alzheimer’s disease and any activities required to support such clinical trials and specific for Alzheimer’s disease ("Denali CNS Development Activities"). Other than with the Denali CNS Development Activities, Sanofi is responsible, at its cost, for all other Phase 1 and Phase 2 trials for CNS Products, including for ALS and multiple sclerosis. Sanofi will lead the conduct of all Phase 3 and later stage development trials for CNS Products, with Sanofi and the Company funding 70% and 30% of such costs, respectively. Sanofi will also lead the commercialization activities globally for CNS Products, subject to certain options that the Company has to conduct co-commercialization activities with respect to each CNS Product in the United States and China.

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 identified the following distinct performance obligations associated with the Sanofi Collaboration Agreement upon inception: 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").

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 three of the performance obligations identified at inception, but does not meet the definition of a customer for the Alzheimer's Disease Services. Further, Sanofi does not meet the definition of a customer for all Phase 3 and later stage development trials for CNS Products led by Sanofi for which the Company will fund 30% of total costs. 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 Alzheimer's Disease Services, the guidance in ASC 606 should be analogized for the recognition, measurement and reporting of this performance obligation, and for the cost sharing provisions, the Company determined that the guidance in ASC 730, Research and Development should be applied.

The transaction price at inception included upfront fixed consideration of $125.0 million. All potential future milestones and other payments were considered constrained at the inception of the Sanofi Collaboration Agreement since the Company could not conclude it was probable that a significant reversal in the amount recognized would not occur. The transaction price increased by $50.0 million and $15.0 million for the years ended December 31, 2022 and 2021, respectively, related to clinical milestones received, and by $1.0 million for the year ended December 31, 2020 related to costs incurred for Retained Activities that were no longer constrained.

The respective standalone value for each of the performance obligations was determined by applying the SSP method and the transaction price allocated based on the relative SSP method with revenue recognition timing to be determined either by delivery or the provision of services.

The Company used an adjusted market assessment approach to estimate the selling price for the program licenses, and an expected cost plus margin approach for estimating the Alzheimer’s Disease Services and the Retained Activities. The program licenses and existing know-how were delivered on the effective date of the Sanofi Collaboration Agreement. 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 is being recognized over time using the input method, based on costs incurred to perform the services, since the level of costs incurred over time is 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.

A contract liability of $3.4 million was recorded on the Consolidated Balance Sheet as of December 31, 2021, which related to the portion of the Alzheimer's Disease Services performance obligation yet to be satisfied. This performance obligation has been satisfied, and therefore no contract liability remains on the Consolidated Balance Sheet as of December 31, 2022. The Company did not record a receivable associated with the Sanofi Collaboration Agreement on the Consolidated Balance Sheets as of December 31, 2022 or 2021.

In assessing the Sanofi Collaboration Agreement, management is required to exercise considerable judgment in estimating revenue to be recognized. Management applies 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, 2022, the Company has earned milestone payments of $75.0 million, including a $40.0 million milestone triggered in April 2022 upon first patient dosed in a Phase 2 study of SAR443820/DNL788 in individuals with ALS which was received in May 2022, and a $10.0 million milestone triggered in December 2022 upon first patient dosed in a Phase 2 study of SAR443122/DNL758 in individuals with UC which was received in December 2022. A further $25.0 million milestone was earned and received in January 2023 upon commencement of dosing in the Phase 2 study of SAR443820/ DNL788 in patients with MS. The Company has 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 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. The amendment did not have a material impact to the consolidated financial statements. In March 2022, Takeda and the Company agreed to terminate activity on the ATV:Tau program over which Takeda had an option to develop and commercialize jointly with the Company. Subsequent to this decision, total preclinical milestone payments that Takeda may owe was $55.0 million, 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. The fair market value of the common stock sold to Takeda was $94.4 million, resulting in a $15.6 million premium paid to the Company above the fair value of the Company's common stock.

Under the Takeda Collaboration Agreement and unless otherwise agreed jointly between both parties, the Company was responsible, at its cost, for conducting activities relating to pre-IND development of biologic products directed to the three identified targets and enabled by its BBB delivery technology targeting TfR during the applicable research period. The period through which the option could be exercised for each target was until the first biologic product directed to the relevant target was IND-ready or approximately five years after selection of the target, whichever was earlier.

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), then 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 believes that the Takeda Collaboration Agreement is a collaboration arrangement as defined in ASC 808, Collaborative Arrangements. Further, during the research period, the Company believes that the arrangement is a contract with a customer as defined in ASC 606, Revenue From Contracts With Customers. The Takeda Collaboration Agreement and the Stock Purchase Agreement are being accounted for as one arrangement because they were entered into at the same time with interrelated financial terms.

The Company identified performance obligations during the research period consisting of the license, the development options, and joint steering committee ("JSC") participation together with the research services for each collaboration program. The license rights, JSC involvement, option and research services were considered to be a single performance obligation for each program since the research services were highly interrelated with the option and JSC involvement and significantly modify the license. The performance obligations under each of the three programs are separate since the activities and risks under the programs are distinct. The Company determined that all other goods or services which were contingent upon Takeda exercising its option for each program were not performance obligations at the inception of the Takeda Collaboration Agreement.

The transaction price at inception included fixed consideration consisting of the upfront fee of $40.0 million, the $15.6 million premium on the sale of common stock, and the first preclinical milestone payment of $5.0 million. It also included variable consideration of $26.0 million relating to future milestones that were not constrained, and have since all been met and received. The transaction price of the Takeda Collaboration Agreement increased by $24.0 million during the year end December 31, 2022 due to two $12.0 million in preclinical milestones becoming unconstrained and recorded as collaboration revenue from customers. The first milestone was earned in January 2022 upon approval of the TAK-594/DNL593 ("PTV:PGRN") clinical trial application ("CTA"), and the second milestone was earned in June 2022 upon approval of the TAK-920/DNL919 ("ATV:TREM2") CTA. Payments for the PTV:PGRN and ATV:TREM2 milestones were received in February and July 2022, respectively.

Revenue is recognized when, or as, the Company satisfies its performance obligations by transferring the promised services to Takeda. Revenue was recognized over time using the input method, based on costs incurred to perform the research services, since the level of costs incurred over time was thought to best reflect the transfer of services to Takeda. There were no material changes in estimates during the years ended December 31, 2022, 2021, or 2020.

A contract liability of $27.9 million was recorded on the Consolidated Balance Sheet as of December 31, 2021 relating to the remaining Tau program services. As a result of the decision to terminate the ATV:Tau program, the performance obligation related to ATV:Tau was considered fully satisfied, and the contract liability was recognized in its entirety within collaboration revenue from customers in the Consolidated Statements of Operations and Comprehensive Income (Loss) for year ended December 31, 2022. No contract liability remains on the Consolidated Balance Sheet as of December 31, 2022. There was no receivable under the Takeda Collaboration Agreement as of either December 31, 2022 or December 31, 2021. The Company has not recorded any product sales and has no remaining performance obligations under the 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. 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. For each contract, 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 is 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.

The transaction price for each contract at inception included fixed consideration consisting of the option fee of $5.0 million. All potential future milestones and other payments were considered constrained at the inception of the PTV:PGRN and the ATV:TREM2 Collaboration Agreements since the Company could not conclude it was probable that a significant reversal in the amount recognized would not occur. From inception of the PTV:PGRN Collaboration Agreement and the ATV:TREM2 Collaboration Agreement through December 31, 2022, there was no change to the terms of, or the transaction price in either agreement.

Takeda may be obligated to pay the Company up to an aggregate of $280.0 million upon achievement of certain clinical milestone events and up to an aggregate of $200.0 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 per biologic product upon achievement of a certain sales-based milestone, or an aggregate of $150.0 million if one biologic product from each program achieves this milestone.

The entire transaction price 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, with the revenue allocated to this performance obligation recognized during the year ended December 31, 2021. The Development Activities cost sharing reimbursements or expenses will be recognized over time as earned or incurred, since this is believed to directly correlate to the value of the services performed. The Company recorded $11.3 million and $7.7 million of cost sharing reimbursements for PTV:PGRN, and $6.9 million and $6.0 million of cost sharing reimbursements for ATV:TREM2 Development Activities for the years ended December 31, 2022 and 2021, respectively, as offsets to research and development expenses in the Consolidated Statements of Operations and Comprehensive Income (Loss). Cost sharing reimbursements of $8.9 million and $13.7 million are recorded as receivables on the Consolidated Balance Sheets as of December 31, 2022 and 2021, respectively.

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.

As of December 31, 2022, the Company had earned $10.0 million in option fee payments from Takeda under the PTV:PGRN and the ATV:TREM2 Collaboration Agreements, and had not recorded any product sales under either agreement.

Collaboration Revenue

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


	Year Ended December 31,
	2022		2021		2020
Takeda Collaboration Agreement:
Takeda Collaboration Agreement Services(1)	$	51,916	$	19,921	$	27,155
PTV:PGRN Collaboration Agreement	—		5,000		—
ATV:TREM2 Collaboration Agreement	—		5,000		—
Total Takeda Collaboration Revenue	51,916		29,921		27,155
Sanofi Collaboration Agreement:
CNS Program License	40,000		—		—
Peripheral Program License	10,000		15,000		—
Alzheimer's Disease Services(2)	3,398		4		98
Retained Activities	—		—		969
Total Sanofi Collaboration Revenue	53,398		15,004		1,067
Biogen Collaboration Agreement:
LRRK2 Program License	—		—		306,545

Option Research Services(3)	3,149		3,736		892
Total Biogen Collaboration Revenue	3,149		3,736		307,437
Total Collaboration Revenue	$	108,463	$	48,661	$	335,659

_________________________________________________

(1)$27.9 million, $15.9 million, and $19.6 million of revenue for the years ended December 31, 2022, 2021 and 2020 was included in the contract liability balance at the beginning of the year.

(2)Revenue for the years ended December 31, 2022, 2021 and 2020 represent amounts that were included in the contract liability balance at the beginning of the respective year.

(3)Revenue for the years ended December 31, 2022 and 2021 represents amounts that were included in the contract liability balance at the beginning of the year.

Income Taxes - Reconciliation of Unrecognized Tax Benefits (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2022	Dec. 31, 2021	Dec. 31, 2020
Reconciliation of Unrecognized Tax Benefits, Excluding Amounts Pertaining to Examined Tax Returns [Roll Forward]
Unrecognized tax benefits at January 1	$ 13,699	$ 8,139	$ 5,299
Additions for tax positions taken in a prior year	135	1,042	0
Additions for tax positions taken in the current year	5,537	4,725	3,009
Reductions for tax positions taken in the prior year	0	(207)	(169)
Unrecognized tax benefits at December 31	$ 19,371	$ 13,699	$ 8,139

Stock-Based Awards (Tables)

12 Months Ended

Dec. 31, 2022

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, 2021	13,686,386	$	24.33	6.76	$	333,011
Granted	2,255,840	43.06
Exercised	(720,904)	14.59
Forfeited	(547,605)	41.82
Balance at December 31, 2022	14,673,717	$	27.03	6.24	$	127,865
Vested and expected to vest at December 31, 2022	13,083,022	$	30.24	6.67	$	84,709
Exercisable at December 31, 2022	9,886,659	$	21.71	5.66	$	101,574

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,
	2022	2021	2020
Expected term (in years)	5.50 - 6.08	5.50 - 6.08	5.50 - 6.08
Volatility	65.1% - 66.3%	61.0% - 63.4%	65.2% - 67.1%
Risk-free interest rate	1.5% - 4.3%	0.5% - 1.3%	0.3% - 1.7%
Dividend yield	—	—	—

Summary of Restricted Stock Activity

Aggregated information regarding RSUs granted under the Plan for the year ended December 31, 2022 is summarized below:


	Number of Units	Weighted-Average Fair Value at Date of Grant per Share




Unvested at December 31, 2021	2,629,980	$	43.97
Granted	1,797,231	37.55
Vested and released	(837,096)	40.30
Forfeited	(259,461)	44.52
Unvested and expected to vest at December 31, 2022	3,330,654	$	41.39

Summary of Stock-Based Compensation Expense

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


	Year Ended December 31,
	2022		2021		2020
Research and development	$	60,196	$	50,036	$	29,002
General and administrative	39,651		35,211		21,349
Total	$	99,847	$	85,247	$	50,351

Collaboration Agreements - Sanofi (Details)

1 Months Ended

12 Months Ended

51 Months Ended

Jan. 31, 2023

USD ($)

Dec. 31, 2022

USD ($)

Apr. 30, 2022

USD ($)

Nov. 30, 2018

USD ($)

indication

Dec. 31, 2022

USD ($)

Dec. 31, 2021

USD ($)

Dec. 31, 2020

USD ($)

Dec. 31, 2022

USD ($)

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

Collaboration revenue from customers

^[1]

$ 105,065,000

$ 48,657,000

$ 335,561,000

Collaborative Arrangement

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

Funded percentage

30.00%

Sanofi | Collaborative Arrangement

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

Funded percentage

70.00%

Sanofi | Collaborative Arrangement

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

Upfront payment

$ 125,000,000

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

1,100,000,000

Collaboration revenue from customers

75,000,000

Receivable

$ 0

Sanofi | Collaborative Arrangement | CNS Product

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

Clinical milestone payment

215,000,000

Regulatory milestone payment

$ 385,000,000

Number of indications | indication

Sanofi | Collaborative Arrangement | Peripheral Program License

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

Clinical milestone payment

$ 120,000,000

Regulatory milestone payment

175,000,000

Commercial milestone payments

$ 200,000,000

Number of indications | indication

Sanofi | Collaborative Arrangement | Retained Activities

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

Transaction price increase

$ 1,000,000

Sanofi | Collaborative Arrangement | Milestone Triggered

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

Transaction price increase

50,000,000

15,000,000

Sanofi | Collaborative Arrangement | Milestone Triggered | ALS

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

Collaboration revenue from customers

$ 40,000,000

Sanofi | Collaborative Arrangement | Milestone Triggered | UC

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

Collaboration revenue from customers

10,000,000

Sanofi | Collaborative Arrangement | Milestone Triggered | Subsequent Event | MS

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

Collaboration revenue from customers

$ 25,000,000

Sanofi | Collaborative Arrangement | Alzheimer's Disease Services

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

Contract liability

$ 0

$ 3,400,000

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 $3.2 million, $3.7 million, and $307.4 million for the years ended December 31, 2022, 2021 and 2020 respectively.

Stock-Based Awards - Summary of Assumptions Used for Estimating the Fair Value of Stock Options Granted (Details)	12 Months Ended
	Dec. 31, 2022	Dec. 31, 2021	Dec. 31, 2020
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	65.10%	61.00%	65.20%
Volatility, maximum	66.30%	63.40%	67.10%
Risk-free interest rate, minimum	1.50%	0.50%	0.30%
Risk-free interest rate, maximum	4.30%	1.30%	1.70%
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

Consolidated Statements of Stockholders' Equity (Parenthetical) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2022	Dec. 31, 2020
Common Stock
Common stock issuance costs	$ 1,060	$ 632

Commitments and Contingencies (Tables)

12 Months Ended

Dec. 31, 2022

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 operating leases for the periods presented (in thousands):


	Year Ended December 31,
		2022			2021			2020

Cash paid for amounts included in measurement of lease liabilities		$	11,189		$	10,336		$	9,737

		As of December 31,
		2022			2021			2020
Weighted average remaining lease term		6.2 years			7.3 years			8.3 years
Weighted average discount rate		8.9		%	9		%	9		%

Summary of Company's Future Minimum Lease Commitments


Year Ended December 31:
2023	$	12,237
2024	12,122
2025	11,793
2026	12,182
2027	12,584
Thereafter	17,382
Total undiscounted lease payments	78,300
Present value adjustment	(17,950)
Net operating lease liabilities	$	60,350

Summary of Company's Future Minimum Lease Receivables

The following table details the future undiscounted cash inflows relating to the Company's Sublease Agreement as of December 31, 2022 (in thousands):


Year Ended December 31:

2023	$	3,096
2024	876

Total undiscounted sublease receipts	$	3,972

Commitments and Contingencies - Summary of Company's Future Minimum Lease Commitments (Details) $ in Thousands	Dec. 31, 2022 USD ($)
Commitments and Contingencies Disclosure [Abstract]
2023	$ 12,237
2024	12,122
2025	11,793
2026	12,182
2027	12,584
Thereafter	17,382
Total undiscounted lease payments	78,300
Present value adjustment	(17,950)
Net operating lease liabilities	$ 60,350

Significant Accounting Policies - Narrative (Details)	12 Months Ended
Significant Accounting Policies - Narrative (Details)	Dec. 31, 2022 USD ($) segment shares	Dec. 31, 2021 USD ($) shares
Accounting Policies [Abstract]
Off-balance sheet concentrations of credit risk \| $	$ 0	$ 0
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
Number of operating segments \| segment	1
Restricted cash \| $	$ 1,500,000

Defined Contribution Plan	12 Months Ended
Defined Contribution Plan	Dec. 31, 2022
Retirement Benefits [Abstract]
Defined Contribution Plan	Defined Contribution PlanThe 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 $2.8 million, $2.3 million and $1.9 million for the years ended December 31, 2022, 2021, and 2020 respectively.

- Definition

The entire disclosure for retirement benefits.

+ References

Reference 1: http://www.xbrl.org/2003/role/exampleRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 715
-SubTopic 20
-Section 55
-Paragraph 17
-URI https://asc.fasb.org/extlink&oid=123450688&loc=d3e4179-114921

Reference 2: http://www.xbrl.org/2003/role/disclosureRef
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Reference 3: http://www.xbrl.org/2003/role/disclosureRef
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Reference 8: http://www.xbrl.org/2003/role/disclosureRef
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Reference 14: http://www.xbrl.org/2003/role/disclosureRef
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-Name Accounting Standards Codification
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-URI https://asc.fasb.org/extlink&oid=123447040&loc=d3e1928-114920

+ Details

Audit Information	12 Months Ended
Audit Information	Dec. 31, 2022
Audit Information [Abstract]
Auditor Firm ID	42
Auditor Name	Ernst & Young LLP
Auditor Location	San Mateo, California

Net Income (Loss) and Net Income (Loss) Per Share (Tables)

12 Months Ended

Dec. 31, 2022

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 income (loss) per share (in thousands, except share and per share data):


	Year Ended December 31,
	2022		2021		2020
Numerator:
Net income (loss)	$	(325,991)	$	(290,581)	$	71,136
Denominator:
Weighted average number of shares outstanding, basic	125,530,703		121,524,795		108,974,137
Dilutive effect of shares issuable under equity incentive plans	—		—		3,728,971
Weighted average number of shares outstanding, diluted	125,530,703		121,524,795		112,703,108
Net income (loss) per share, basic	$	(2.60)	$	(2.39)	$	0.65
Net income (loss) per share, diluted	$	(2.60)	$	(2.39)	$	0.63

Commitments and Contingencies - Summary of Supplemental Lease Information (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2022	Dec. 31, 2021	Dec. 31, 2020
Commitments and Contingencies Disclosure [Abstract]
Cash paid for amounts included in measurement of lease liabilities	$ 11,189	$ 10,336	$ 9,737
Weighted average remaining lease term	6 years 2 months 12 days	7 years 3 months 18 days	8 years 3 months 18 days
Weighted average discount rate	8.90%	9.00%	9.00%

Income Taxes

12 Months Ended

Dec. 31, 2022

Income Tax Disclosure [Abstract]

Income Taxes

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


	Year Ended December 31,
	2022		2021		2020
Current:
U.S. Federal	$	—	$	—	$	—
U.S. State	7		(576)		823
Foreign	14		1		—
Total Current	$	21	$	(575)	$	823

Deferred:
U.S. Federal	$	—	$	—	$	—
U.S. State	—		—		—
Foreign	—		—		—
Total deferred	$	—	$	—	$	—

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


	Year Ended December 31,
	2022		2021		2020
Taxes at the U.S. statutory tax rate	21.0	%	21.0	%	21.0	%
Effect of Tax Act	—		—		1.1
Change in valuation allowance	(25.1)		(28.2)		(4.0)
Research tax credits	4.9		4.1		(9.2)
Stock-based compensation	(0.5)		3.2		(7.9)

Other	(0.4)		0.1		0.1
Total provision for income taxes	(0.1)	%	0.2	%	1.1	%

Deferred Income Taxes

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


	December 31,
	2022		2021
Deferred tax assets:
Net operating loss carryforwards	$	67,492	$	59,285
Tax credit carryforwards	69,562		48,058
Research expense capitalization	61,869		—
Contract liabilities	70,824		75,281
Operating lease liabilities	14,712		15,040
Stock-based compensation	44,473		30,185
Accruals and other	18,381		15,385
Gross deferred tax assets	347,313		243,234
Valuation allowance	(332,580)		(228,586)
Net deferred tax assets	14,733		14,648
Deferred tax liabilities:
Property and equipment	(7,314)		(7,424)
Operating lease right-of-use assets	(7,419)		(7,224)
Net deferred tax assets	$	—	$	—

In line with the requirements of the 2017 Tax Cuts and Jobs Act, effective January 1, 2022, our research and development expenditures incurred during the year ended December 31, 2022 have been capitalized for federal income tax purposes, to be amortized over periods of 5 and 15 years for costs incurred in the US and outside the US, respectively. This resulted in a gross deferred tax asset of $61.9 million as of December 31, 2022.

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 100% valuation allowance against its net deferred tax assets as of December 31, 2022 and 2021. There was an increase in the net valuation allowance of $104.0 million during the year ended December 31, 2022.

As of December 31, 2022, the Company has federal net operating loss (“NOL”) carryforwards of approximately $231.9 million, which are available to reduce future taxable income, and has federal R&D and orphan drug tax credits of approximately $42.6 million and $19.7 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 2035. The Company also has state NOL carryforwards of approximately $267.0 million, which are available to reduce future taxable income, and has state tax credits of approximately $31.4 million which may be used to offset future tax liabilities. The state NOL will begin to expire in 2035 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,
	2022		2021		2020
Unrecognized tax benefits at January 1	$	13,699	$	8,139	$	5,299
Additions for tax positions taken in a prior year	135		1,042		—
Additions for tax positions taken in the current year	5,537		4,725		3,009
Reductions for tax positions taken in the prior year	—		(207)		(169)
Unrecognized tax benefits at December 31	$	19,371	$	13,699	$	8,139

If recognized, none of the unrecognized tax benefits would reduce the annual effective tax rate for the year ended December 31, 2022. The Company will recognize both accrued interest and penalties related to unrecognized benefits in income tax expense. As of December 31, 2022, 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 taxes. Disclosures may include net deferred tax liability or asset recognized in an enterprise's statement of financial position, net change during the year in the total valuation allowance, approximate tax effect of each type of temporary difference and carryforward that gives rise to a significant portion of deferred tax liabilities and deferred tax assets, utilization of a tax carryback, and tax uncertainties information.

+ References

Reference 1: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 740
-SubTopic 10
-Section 50
-Paragraph 21
-URI https://asc.fasb.org/extlink&oid=121826272&loc=d3e32857-109319

Reference 2: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 740
-SubTopic 10
-Section S99
-Paragraph 2
-Subparagraph (SAB Topic 11.C)
-URI https://asc.fasb.org/extlink&oid=122134291&loc=d3e330215-122817

Reference 3: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 740
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-Paragraph 17
-Subparagraph (b)
-URI https://asc.fasb.org/extlink&oid=121826272&loc=d3e32809-109319

Reference 4: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 740
-SubTopic 10
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-Paragraph 1
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-URI https://asc.fasb.org/extlink&oid=122134291&loc=d3e330036-122817

Reference 5: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
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-Paragraph 14
-URI https://asc.fasb.org/extlink&oid=121826272&loc=d3e32705-109319

Reference 6: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 740
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-Paragraph 1
-URI https://asc.fasb.org/extlink&oid=6424409&loc=d3e44925-109338

Reference 7: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 740
-URI https://asc.fasb.org/topic&trid=2144680

Reference 8: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 740
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-Paragraph 2
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-URI https://asc.fasb.org/extlink&oid=6424122&loc=d3e41874-109331

Reference 9: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 235
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-Paragraph 1
-Subparagraph (SX 210.4-08(h)(2))
-URI https://asc.fasb.org/extlink&oid=120395691&loc=d3e23780-122690

+ Details

License Agreements - Narrative (Details) - USD ($)

1 Months Ended

12 Months Ended

79 Months Ended

Jun. 30, 2016

Dec. 31, 2022

Dec. 31, 2021

Dec. 31, 2020

Dec. 31, 2022

Oct. 05, 2020

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

Research and development expense

^[1]

$ 358,732,000

$ 265,353,000

$ 212,615,000

License Agreement

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

Research and development expense

$ 18,800,000

Genentech | Clinical

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

Milestone payments upon achievement of specified clinical and regulatory milestones

$ 37,500,000

Genentech | Regulatory

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

Milestone payments upon achievement of specified clinical and regulatory milestones

102,500,000

Genentech | Commercial

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

Milestone payments upon achievement of specified clinical and regulatory milestones

175,000,000

Genentech | License Agreement | LUMA Study

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

Clinical milestone payment obligation responsibility

7,500,000

Genentech | License Agreement | LIGHTHOUSE Study

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

Clinical milestone payment obligation responsibility

5,000,000

Genentech | License Agreement | Research and development

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

Aggregate payments

$ 25,000,000

Genentech | Collaborative Arrangement

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

Research and development expense

$ 0

Genentech | Maximum

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

Milestone payments upon achievement of specified clinical and regulatory milestones

$ 315,000,000

Biogen | Collaborative Arrangement

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

Research and development expense

$ 6,300,000

Agreed share of commercial profit (loss) percentage

50.00%

[1]	Includes expense for cost sharing payments to a related party of $8.2 million for the year ended December 31, 2022 and an offset to expense from related-party cost reimbursements of $6.5 million and $9.3 million for the years ended December 31, 2021 and 2020, respectively.

Balance Sheet Components (Tables)

12 Months Ended

Dec. 31, 2022

Organization, Consolidation and Presentation of Financial Statements [Abstract]

Scheduled of Property and Equipment, Net

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


	As of December 31,
	2022		2021
Leasehold improvements	$	43,698	$	35,235
Manufacturing and laboratory equipment	34,419		30,114
Computers equipment and purchased software	1,605		1,337
Furniture and fixtures	1,580		1,523
Total property and equipment	81,302		68,209
Less: accumulated depreciation	(37,215)		(29,344)
Total property and equipment, net	$	44,087	$	38,865

Schedule of Accrued Expenses and Other Current Liabilities

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


	As of December 31,
	2022		2021
Accrued manufacturing costs	$	22,307	$	9,955
Accrued compensation	17,087		19,013
Accrued clinical costs and other research & development costs	16,297		15,887
Operating lease liability, current	7,318		5,453
Other accrued costs and current liabilities	3,682		2,857
Total accrued expenses and other current liabilities	$	66,691	$	53,165

Consolidated Balance Sheets (Parenthetical) - $ / shares	Dec. 31, 2022	Dec. 31, 2021
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)	135,965,918	122,283,305
Common stock, shares outstanding (in shares)	135,965,918	122,283,305

Commitments and Contingencies - Summary of Company's Future Minimum Lease Receivables (Details) $ in Thousands	Dec. 31, 2022 USD ($)
Commitments and Contingencies Disclosure [Abstract]
2023	$ 3,096
2024	876
Total undiscounted sublease receipts	$ 3,972

Collaboration Agreements - Takeda (Details)

1 Months Ended

12 Months Ended

51 Months Ended

Feb. 23, 2018

USD ($)

program

Dec. 31, 2021

USD ($)

contract

Dec. 31, 2022

USD ($)

milestone

Dec. 31, 2021

USD ($)

Dec. 31, 2020

USD ($)

Dec. 31, 2022

USD ($)

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

Collaboration revenue from customers

^[1]

$ 105,065,000

$ 48,657,000

$ 335,561,000

Offset to expense, related party cost reimbursement

6,500,000

$ 9,300,000

Takeda Pharmaceutical Company Limited

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

Offset to expense, related party cost reimbursement

8,900,000

13,700,000

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

$ 55,000,000

Target option period

5 years

Number of performance obligations under the programs | program

Preclinical milestone payment received

$ 5,000,000

Variable consideration relating to future milestones

$ 26,000,000

Transaction price, change

$ 24,000,000

Number of preclinical milestones | milestone

Collaboration revenue from customers

$ 12,000,000

Contract liability

$ 27,900,000

27,900,000

Performance obligation

Receivable

$ 0

Takeda Pharmaceutical Company Limited | Collaborative Arrangement | Product

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

Collaboration revenue from customers

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

Fair market value of common stock

94,400,000

Premium on sale of common stock

15,600,000

Takeda Pharmaceutical Company Limited | Collaborative Arrangement | Maximum

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

Total aggregate payments due upon achievement of certain clinical and regulatory milestone events

280,000,000

Regulatory milestone payment

200,000,000

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

75,000,000

Milestone payments upon achievement of biologic product from each program

150,000,000

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

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

Number of new contracts | contract

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

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

Collaboration revenue from customers

10,000,000

Takeda Pharmaceutical Company Limited | Collaborative Arrangement, PTV:PGRN

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

Transaction price, change

Option fee

5,000,000

Offset to expense, related party cost reimbursement

11,300,000

7,700,000

Takeda Pharmaceutical Company Limited | Collaborative Arrangement, PTV:PGRN | Product

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

Collaboration revenue from customers

Takeda Pharmaceutical Company Limited | Collaborative Arrangement, ATV:TREM2

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

Transaction price, change

Option fee

$ 5,000,000

Offset to expense, related party cost reimbursement

$ 6,900,000

$ 6,000,000

Takeda Pharmaceutical Company Limited | Collaborative Arrangement, ATV:TREM2 | Product

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

Collaboration revenue from customers

$ 0

[1]	Includes related-party collaboration revenue from customers of $3.2 million, $3.7 million, and $307.4 million for the years ended December 31, 2022, 2021 and 2020 respectively.

Stock-Based Awards - Summary of Stock Option Activity (Details) - USD ($) $ / shares in Units, $ in Thousands	12 Months Ended
	Dec. 31, 2022	Dec. 31, 2021
Number of Options
Beginning balance (in shares)	13,686,386
Granted (in shares)	2,255,840
Exercised (in shares)	(720,904)
Forfeited (in shares)	(547,605)
Ending balance (in shares)	14,673,717	13,686,386
Options, vested and expected to vest (in shares)	13,083,022
Options, exercisable (in shares)	9,886,659
Weighted- Average Exercise Price
Beginning balance (usd per share)	$ 24.33
Granted (usd per share)	43.06
Exercised (usd per share)	14.59
Forfeited (usd per share)	41.82
Ending balance (usd per share)	27.03	$ 24.33
Options, vested and expected to vest (in shares)	30.24
Options, exercisable (in shares)	$ 21.71
Stock Option Activity, Additional Disclosures
Weighted- Average remaining contractual life (years)	6 years 2 months 26 days	6 years 9 months 3 days
Weighted-Average remaining contractual life (years), Options vested and expected to vest	6 years 8 months 1 day
Weighted-Average remaining contractual life (years), Options exercisable	5 years 7 months 28 days
Aggregate Intrinsic Value (in thousands)	$ 127,865	$ 333,011
Aggregate Intrinsic Value (in thousands), Options vested and expected to vest	84,709
Aggregate Intrinsic Value (in thousands), Options exercisable	$ 101,574