0000950170-23-010603 | 10-K | XBRL Viewer | Heron Therapeutics INC DE

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Revenue Recognition - Schedule of Disaggregated Net Product Sales (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2022	Dec. 31, 2021
Product Information [Line Items]
Net product sales	$ 107,672	$ 86,346
CINVANTI
Product Information [Line Items]
Net product sales	87,245	73,507
SUSTOL
Product Information [Line Items]
Net product sales	10,231	9,915
ZYNRELEF
Product Information [Line Items]
Net product sales	$ 10,196	$ 2,924

- Definition

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

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+ Details

Balance Sheet Details

12 Months Ended

Dec. 31, 2022

Organization, Consolidation and Presentation of Financial Statements [Abstract]

Balance Sheet Details

Short-Term Investments

The following is a summary of our short-term investments (in thousands):


	December 31, 2022
	Amortized Cost		Gross Unrealized Gains		Gross Unrealized Losses			Estimated Fair Value
U.S. treasury bills and government agency obligations	$	35,734	$	—	$	(19	)	$	35,715
U.S. commercial paper		5,481		—		—			5,481
Foreign commercial paper		28,292		—		—			28,292
Total	$	69,507	$	—	$	(19	)	$	69,488


	December 31, 2021
	Amortized Cost		Gross Unrealized Gains		Gross Unrealized Losses			Estimated Fair Value
U.S. corporate debt securities	$	15,009	$	—	$	(3	)	$	15,006
Foreign corporate debt securities		10,551		—		(3	)		10,548
U.S. commercial paper		5,998		—		—			5,998
Foreign commercial paper		35,487		—		—			35,487
Total	$	67,045	$	—	$	(6	)	$	67,039

The amortized cost of debt securities is adjusted for amortization of premiums and accretion of discounts to maturity. We regularly monitor and evaluate the realizable value of our marketable securities. We did not recognize any impairment losses for the years ended December 31, 2022 and 2021.

Unrealized gains and losses associated with our investments are reported in accumulated other comprehensive loss. For the years ended December 31, 2022 and 2021, we recorded $13,000 and $263,000, respectively, in net unrealized losses associated with our short-term investments.

Realized gains and losses associated with our investments, if any, are reported in the statements of operations and comprehensive loss. We did not recognize any realized gains or losses during the years ended December 31, 2022 and 2021.

Inventory

Inventory consists of the following (in thousands):


	December 31,
	2022		2021
Raw materials	$	15,137	$	21,193
Work in process		20,723		20,935
Finished goods		18,713		6,254
Total inventory	$	54,573	$	48,382

As of December 31, 2022, total inventory included $30.9 million related to ZYNRELEF, $19.9 million related to CINVANTI, $2.6 million related to SUSTOL and $1.2 million related to APONVIE. As of December 31, 2021, total inventory included $23.6 million related to ZYNRELEF, $23.1 million related to CINVANTI, and $1.7 million related to SUSTOL. Cost of product sales for the year ended December 31, 2022 included charges of $8.9 million, resulting primarily from the write-off of short-dated ZYNRELEF inventory. In addition, cost of product sales for the year ended December 31, 2021 included charges of $3.8 million, resulting from the write-off of short-dated SUSTOL inventory.

Prepaid Expenses and Other Assets

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


	December 31,
	2022		2021
Prepaid expenses	$	21,120	$	27,945
Other receivables		6,197		103
Prepaid insurance		1,947		2,135
Deposits		254		254
Interest receivable		154		245
Total prepaid expenses and other assets	$	29,672	$	30,682

Property and Equipment

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


	December 31,
	2022			2021
Scientific equipment	$	33,318		$	33,403
Leasehold improvements		647			610
Computer equipment and software		1,506			1,497
Furniture, fixtures and office equipment		982			1,467
Property and equipment, gross		36,453			36,977
Less: accumulated depreciation and amortization		(14,293	)		(13,243	)
Property and equipment, net	$	22,160		$	23,734

Depreciation and amortization expense for the years ended December 31, 2022 and 2021 was $2.9 million and $3.0 million, respectively. As of December 31, 2022 and 2021, $5.4 million and $15.9 million of property and equipment, respectively, was in process and not depreciated during the respective years.

Accrued Payroll and Employee Liabilities and Other Accrued Liabilities

Accrued payroll and employee liabilities consist of the following (in thousands):


	December 31,
	2022		2021
Accrued employee salaries and benefits	$	2,134	$	1,784
Accrued bonuses		7,783		9,439
Accrued vacation		3,499		4,040
Total accrued payroll and employee liabilities	$	13,416	$	15,263

Other accrued liabilities consist of the following (in thousands):


	December 31,
	2022		2021
Accrued product sales allowances	$	33,317	$	22,560
Accrued consulting and professional fees		4,236		2,666
Accrued accounts payable		363		70
Other accrued liabilities		636		563
Total other accrued liabilities	$	38,552	$	25,859

Document and Entity Information - USD ($) $ in Millions	12 Months Ended
Document and Entity Information - USD ($) $ in Millions	Dec. 31, 2022	Mar. 14, 2023	Jun. 30, 2022
Document And Entity Information [Line Items]
Document Type	10-K
Amendment Flag	false
Document Period End Date	Dec. 31, 2022
Document Fiscal Year Focus	2022
Document Fiscal Period Focus	FY
Trading Symbol	HRTX
Entity Registrant Name	HERON THERAPEUTICS, INC. /DE/
Entity Central Index Key	0000818033
Current Fiscal Year End Date	--12-31
Entity Current Reporting Status	Yes
Entity Voluntary Filers	No
Entity Filer Category	Non-accelerated Filer
Entity Well-known Seasoned Issuer	No
Entity Common Stock, Shares Outstanding		119,259,315
Entity Small Business	true
Entity Emerging Growth Company	false
ICFR Auditor Attestation Flag	false
Entity Shell Company	false
Entity File Number	001-33221
Entity Tax Identification Number	94-2875566
Entity Address, Address Line One	4242 CAMPUS POINT COURT
Entity Address, Address Line Two	SUITE 200
Entity Address, City or Town	SAN DIEGO
Entity Address, State or Province	CA
Entity Address, Postal Zip Code	92121
City Area Code	858
Local Phone Number	251-4400
Entity Interactive Data Current	Yes
Entity Incorporation, State or Country Code	DE
Document Annual Report	true
Entity Public Float			$ 285.4
Document Transition Report	false
Title of 12(b) Security	Common Stock, par value $0.01 per share
Security Exchange Name	NASDAQ
Auditor Name	WithumSmith+Brown, PC
Auditor Location	San Francisco, California
Auditor Firm ID	100
Documents Incorporated by Reference	Portions of the registrant’s Definitive Proxy Statement related to its 2023 Annual Meeting of Stockholders to be held on or about May 18, 2023 are incorporated by reference into Part III of this Annual Report on Form 10-K. Such Definitive Proxy Statement will be filed with the U.S. Securities and Exchange Commission within 120 days after the end of the fiscal year to which this report relates. Except as expressly incorporated by reference, the registrant’s Definitive Proxy Statement shall not be deemed to be part of this report.

Reorganization

12 Months Ended

Dec. 31, 2022

Reorganizations [Abstract]

Reorganization

In June 2022, we implemented a restructuring plan under which we provided employees one-time severance payments upon termination, continuation of benefits for a specific period of time, outplacement services and certain stock award modifications. The total amount incurred for these activities is $5.4 million, $5.0 million of which is primarily for severance and $0.4 million of which is for non-cash, stock-based compensation expense related to stock award modifications. For the year ended December 31, 2022, we recognized $5.4 million of the total expense, $4.2 million of which was included in research and development expense, $1.0 million of which was included in sales and marketing expense, and $0.2 million of which was included in general and administrative expense. We anticipate that the cash payments due to terminated employees will be substantially completed in the first quarter of 2023. As of December 31, 2022, we have paid $4.1 million of the total cash severance charges.

In October 2021, we implemented a restructuring plan under which we provided employees one-time severance payments upon termination, continued benefits for a specific period of time, outplacement services and certain stock option modifications. The total expense for these activities was $1.4 million, $1.3 million of which was primarily for severance and $0.1 million of which was for non-cash, stock-based compensation expense related to stock option modifications. The total expense was recognized in the fourth quarter of 2021, with $1.2 million included in research and development expense and $0.2 million included in sales and marketing expense. As of December 31, 2022, we have paid $1.3 million of the total cash severance charges.

We have accounted for these expenses in accordance with the FASB ASC Topic 420, Exit or Disposal Cost Obligations.

Stockholders' Equity - Summary of Common Stock Reserved for Future Issuance (Details) - shares	Dec. 31, 2022	Dec. 31, 2021
Stockholders' Equity Note [Abstract]
Stock options outstanding	20,749,349	18,943,937
Restricted stock units outstanding	3,167,000
Stock options available for grant	985,000
Employee Stock Purchase Plan	645,000
Shares of common stock underlying warrants	8,548,000
Shares of common stock underlying convertible notes outstanding (see Note 8)	9,819,000
Total shares reserved for future issuance	43,913,000

Stockholders' Equity

12 Months Ended

Dec. 31, 2022

Equity [Abstract]

Stockholders' Equity

Stockholders’ Equity

2022 Private Placement

On August 8, 2022, we entered into an agreement to sell 16.1 million shares of our common stock in a private placement at a purchase price of $3.10 per share. In addition, as a component of the private placement, we agreed to sell 8.5 million pre-funded warrants to purchase shares of our common stock at a purchase price of $3.0999 per share. The pre-funded warrants have an exercise price of $0.0001 per share. The total net proceeds from the sale of the common stock and pre-funded warrants is $75.1 million (net of $1.4 million in issuance costs). In October 2022, we filed a registration statement with the SEC to register for resale 24.6 million shares of our common stock. The registration statement was declared effective on October 18, 2022.

Public Offering Warrants

In June 2014, as a component of our public offering, we sold 600,000 pre-funded warrants to purchase shares of our common stock. The pre-funded warrants have an exercise price of $0.01 per share and expire on June 30, 2021. During the year ended December 31, 2019, warrant holders exercised 132,130 warrants, which resulted in the issuance of 132,130 shares for net cash proceeds of $1,321. During the year ended December 31, 2020, warrant holders exercised 267,870 warrants, which resulted in the issuance of 267,870 shares for net cash proceeds of $2,679. In April 2021, warrant holders exercised 195,574 warrants using the cashless exercise provision, which resulted in the issuance of 195,461 shares and no cash proceeds. As of December 31, 2021, no warrants from the June 2014 public offering remain outstanding.

Common Stock Reserved for Future Issuance

Shares of our common stock reserved for future issuance as of December 31, 2022 were as follows:


	Number of
	Shares
Stock options outstanding		20,749
Restricted stock units outstanding		3,167
Stock options available for grant		985
Employee Stock Purchase Plan		645
Shares of common stock underlying warrants		8,548
Shares of common stock underlying convertible notes outstanding (see Note 8)		9,819
Total shares reserved for future issuance		43,913

- Definition

The entire disclosure for shareholders' equity comprised of portions attributable to the parent entity and noncontrolling interest, including other comprehensive income. Includes, but is not limited to, balances of common stock, preferred stock, additional paid-in capital, other capital and retained earnings, accumulated balance for each classification of other comprehensive income and amount of comprehensive income.

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+ Details

Balance Sheet Details - Schedule of Inventory (Details) - USD ($) $ in Thousands	Dec. 31, 2022	Dec. 31, 2021
Inventory Disclosure [Abstract]
Raw materials	$ 15,137	$ 21,193
Work in process	20,723	20,935
Finished goods	18,713	6,254
Total inventory	$ 54,573	$ 48,382

Summary of Significant Accounting Policies

12 Months Ended

Dec. 31, 2022

Accounting Policies [Abstract]

Summary of Significant Accounting Policies

Principles of Consolidation

The accompanying consolidated financial statements include the accounts of Heron Therapeutics, Inc. and its wholly-owned subsidiary, Heron Therapeutics B.V., which was organized in the Netherlands in March 2015. Heron Therapeutics B.V. has no operations and no material assets or liabilities, and there have been no significant transactions related to Heron Therapeutics B.V. since its inception.

Use of Estimates

The preparation of financial statements in conformity with accounting principles generally accepted in the U.S. (“GAAP”) requires management to make estimates and assumptions that affect the amounts reported in the financial statements and disclosures made in the accompanying notes to the financial statements. Our significant accounting policies that involve significant judgment and estimates include revenue recognition, investments, inventory and the related reserves, accrued clinical liabilities, income taxes and stock-based compensation. Actual results could differ materially from those estimates.

Cash, Cash Equivalents and Short-term Investments

Cash and cash equivalents consist of cash and highly liquid investments with contractual maturities of three months or less from the original purchase date.

Short-term investments consist of securities with contractual maturities of greater than three months from the original purchase date. Securities with contractual maturities greater than one year are classified as short-term investments on the consolidated balance sheets, as we have the ability, if necessary, to liquidate these securities to meet our liquidity needs in the next 12 months. We have classified our short-term investments as available-for-sale securities in the accompanying consolidated financial statements. Available-for-sale securities are stated at fair market value, with net changes in unrealized gains and losses reported in other comprehensive loss and realized gains and losses included in other expense, net. The cost of securities sold is based on the specific identification method. Interest and dividends on securities classified as available-for-sale are included in interest income.

Fair Value of Financial Instruments

A company may elect to use fair value to measure accounts and loans receivable, available-for-sale and held-to-maturity securities, equity method investments, accounts payable, guarantees and issued debt. Other eligible items include firm commitments for financial instruments that otherwise would not be recognized at inception and non-cash warranty obligations where a warrantor is permitted to pay a third party to provide the warranty goods or services. If the use of fair value is elected, any upfront costs and fees related to the item such as debt issuance costs must be recognized in earnings and cannot be deferred. The fair value election is irrevocable and generally made on an instrument-by-instrument basis, even if a company has similar instruments that it elects not to measure based on fair value. Unrealized gains and losses on existing items for which fair value has been elected are reported as a cumulative adjustment to beginning retained earnings and any changes in fair value are recognized in earnings. We have elected to not apply the fair value option to our financial assets and liabilities.

Financial instruments, including cash and cash equivalents, receivables, inventory, prepaid expenses, other current assets, accounts payable and accrued expenses, are carried at cost, which is considered to be representative of their respective fair values because of the short-term maturity of these instruments. Short-term available-for-sale investments are carried at fair value (see Note 3). Our convertible notes outstanding at December 31, 2022 and 2021 do not have a readily available ascertainable market value, however, the carrying value is considered to approximate its fair value.

Concentration of Credit Risk

Cash, cash equivalents and short-term investments are financial instruments that potentially subject us to concentrations of credit risk. We deposit our cash in financial institutions. At times, such deposits may be in excess of insured limits. We have not experienced any losses in such accounts and believe we are not exposed to significant risk on our cash, cash equivalents and short-term investments.

We may also invest our excess cash in money market funds, U.S. government and agencies, corporate debt securities and commercial paper. We have established guidelines relative to our diversification of our cash investments and their maturities in an effort to maintain safety and liquidity. These guidelines are periodically reviewed and modified to take advantage of trends in yields and interest rates.

CINVANTI, SUSTOL and ZYNRELEF (collectively, our “Products”) are distributed in the U.S. through a limited number of specialty distributors and full line wholesalers (collectively, “Customers”) that resell to healthcare providers and hospitals, the end users of our Products.

The following table includes the percentage of net product sales and accounts receivable balances for our three major Customers, each of which comprised 10% or more of our net product sales:


	Net Product Sales			Accounts Receivable
	Year Ended December 31, 2022			As of December 31, 2022
Customer A		43.5	%		51.6	%
Customer B		36.4	%		32.5	%
Customer C		18.8	%		15.0	%
Total		98.7	%		99.1	%

Accounts Receivable, Net

Accounts receivable are recorded at the invoice amount, net of an allowance for credit losses. The allowance for credit losses reflects accounts receivable balances that are believed to be uncollectible. In estimating the allowance for credit losses, we consider: (1) our historical experience with collections and write-offs; (2) the credit quality of our Customers and any recent or anticipated changes thereto; (3) the outstanding balances and past due amounts from our Customers; and (4) reasonable and supportable forecast of economic conditions expected to exist throughout the contractual term of the receivable.

We offered extended payment terms to our Customers in connection with our product launch of ZYNRELEF in July 2021. In addition, we offered extended payment terms to our Customers in January 2021 when we reinstated the promotion and contracting of SUSTOL. These extended payment terms were offered in anticipation of the timing of reimbursement by government and commercial payers. Effective October 2021, we shortened payment terms to our ZYNRELEF and SUSTOL Customers.

As of December 31, 2022 and 2021, we determined that an allowance for doubtful accounts was not required. For the years ended December 31, 2022 and 2021, we did not have any material write-offs any accounts receivable balances.

Inventory

Inventory is stated at the lower of cost or estimated net realizable value on a first-in, first-out, or FIFO, basis. We periodically analyze our inventory levels and write down inventory that has become obsolete, inventory that has a cost basis in excess of its estimated realizable value and inventory quantities that are in excess of expected sales requirements as cost of product sales. The determination of whether inventory costs will be realizable requires estimates by management. If actual market conditions are less favorable than projected by management, additional write-downs of inventory may be required, which would be recorded as cost of product sales.

Property and Equipment

Property and equipment is stated at cost less accumulated depreciation and amortization. Depreciation is calculated on a straight-line basis over the estimated useful lives of the assets (generally 5 years). Leasehold improvements are stated at cost and amortized on a straight-line basis over the shorter of the estimated useful life of the asset or the lease term.

Impairment of Long-Lived Assets

If indicators of impairment exist, we assess the recoverability of the affected long-lived assets by determining whether the carrying value of such assets can be recovered through undiscounted future operating cash flows. If impairment is indicated, we measure the amount of such impairment by comparing the carrying value of the asset to the fair value of the asset and record the impairment as a reduction in the carrying value of the related asset with a corresponding charge to operating expenses. Estimating the undiscounted future operating cash flows associated with long-lived assets requires judgment and assumptions that could differ materially from actual results.

Leases

We determine if an arrangement is a lease or contains lease components at inception. Operating leases with an initial term greater than 12 months are recorded as lease liabilities with corresponding right-of-use (“ROU”) lease assets on the consolidated balance sheets. ROU lease assets represent our right to use the underlying assets over the lease term, and lease liabilities represent the present value of our obligation to make lease payments arising from the lease. Lease liabilities are recognized at the lease commencement based on the present value of lease payments over the lease term. As most of our leases do not provide an implicit rate, we use our incremental borrowing rate based on the information available at the commencement date in determining the present value of lease payments. We use the implicit rate when readily determinable. The ROU lease assets equal the lease liabilities, less unamortized lease incentives, unamortized initial direct costs and the cumulative difference between rent expense and amounts paid under the lease. The lease term includes any option to extend or terminate the lease when it is reasonably certain that we will exercise that option. Lease expense is recognized on a straight-line basis over the lease term. We have lease agreements with both lease and non-lease components, which are generally accounted for separately.

Revenue Recognition

Revenue is recognized in accordance with the Financial Accounting Standards Board (the “FASB”) ASC Topic 606, Revenue from Contracts with Customers (“Topic 606”). Topic 606 is based on the principle that revenue should be recognized to depict the transfer of promised goods or services to customers in an amount that reflects the consideration to which the entity expects to be entitled in exchange for those goods or services.

Product Sales

Our Products are distributed in the U.S. through a limited number of Customers that resell to healthcare providers and hospitals, the end users of our Products.

Revenue is recognized in an amount that reflects the consideration we expect to receive in exchange for our Products. To determine revenue recognition for contracts with customers within the scope of Topic 606, we perform the following 5 steps: (i) identify the contract(s) with a customer; (ii) identify the performance obligations of the contract(s); (iii) determine the transaction price; (iv) allocate the transaction price to the performance obligations in the contract(s); and (v) recognize revenue when (or as) we satisfy the performance obligations.

Product Sales Allowances

We recognize product sales allowances as a reduction of product sales in the same period the related revenue is recognized. Product sales allowances are based on amounts owed or to be claimed on the related sales. Such variable consideration includes estimates that take into consideration the terms of our agreements with Customers, historical product returns, rebates or discounts taken, the shelf life of the product and specific known market events, such as competitive pricing and new product introductions. If actual future results vary from our estimates, we may need to adjust these estimates, which could have an effect on product sales and earnings in the period of adjustment. Our product sales allowances include:

•

Product Returns—We allow our Customers to return product for credit for up to 12 months after its product expiration date. As such, there may be a significant period of time between the time the product is shipped and the time the credit is issued on returned product.

•

Distributor Fees—We pay distribution service fees to our Customers based on a contractually fixed percentage of the wholesale acquisition cost and fees for data. These fees are paid no later than two months after the quarter in which product was shipped.

•

Group Purchasing Organization (“GPO”) Discounts and Rebates—We offer cash discounts to GPO members. These discounts are taken when the GPO members purchase product from our Customers, who

then charge back to us the discount amount. Additionally, we offer volume and contract-tier rebates to GPO members. Rebates are based on actual purchase levels during the quarterly rebate purchase period.

•

GPO Administrative Fees—We pay administrative fees to GPOs for services and access to data. These fees are based on contracted terms and are paid after the quarter in which the product was purchased by the GPOs’ members.

•

Medicaid Rebates—We participate in Medicaid rebate programs, which provide assistance to certain low-income patients based on each individual state’s guidelines regarding eligibility and services. Under the Medicaid rebate programs, we pay a rebate to each participating state, generally within three months after the quarter in which the product was sold.

We believe our estimated allowance for product returns requires a high degree of judgment and is subject to change based on our experience and certain quantitative and qualitative factors. We believe our estimated allowances for distributor fees, GPO discounts, rebates and administrative fees and Medicaid rebates do not require a high degree of judgment because the amounts are settled within a relatively short period of time.

Our product sales allowances and related accruals are evaluated each reporting period and adjusted when trends or significant events indicate that a change in estimate is appropriate. Changes in product sales allowance estimates could materially affect our results of operations and financial position.

Accrued Clinical Liabilities

We accrue clinical costs based on work performed, which relies on estimates of the progress of the trials and the related expenses incurred. Clinical trial related contracts vary significantly in duration, and may be for a fixed amount, based on the achievement of certain contingent events or deliverables, a variable amount based on actual costs incurred, capped at a certain limit or contain a combination of these elements. Revisions are recorded to research and development expense in the period in which the facts that give rise to the revision become known. Historically, revisions have not resulted in material changes to research and development expense; however, a modification in the protocol of a clinical trial or cancellation of a clinical trial could result in a material charge to our results of operations.

Research and Development Expense

All costs of research and development are expensed in the period incurred. Research and development expense primarily consists of personnel and related costs, stock-based compensation expense, fees paid to outside service providers and consultants, facilities costs and materials used in clinical and preclinical trials and research and development.

Patent Costs

We incur outside legal fees in connection with filing and maintaining our various patent applications. All patent costs are expensed as incurred and are included in general and administrative expense in the consolidated statements of operations and comprehensive loss.

Stock-Based Compensation Expense

We estimate the fair value of stock-based payment awards using the Black-Scholes option pricing model. This fair value is then amortized using the straight-line single-option method of attributing the value of stock-based compensation to expense over the requisite service periods of the awards. The Black-Scholes option pricing model requires the input of complex and subjective assumptions, including each option’s expected life and price volatility of the underlying stock.

As stock-based compensation expense is based on awards ultimately expected to vest, it has been reduced for estimated forfeitures. Forfeitures are estimated at the time of grant and revised, if necessary, in subsequent periods if actual forfeitures differ from those estimates. Forfeitures are estimated based on historical data.

Warrants

We have issued warrants to purchase shares of our common stock in conjunction with certain equity financings or in exchange for services. The terms of the warrants were evaluated to determine the appropriate classification as equity or a liability.

Income Taxes

We recognize the impact of a tax position in our consolidated financial statements if the position is more likely than not to be sustained on examination and on the technical merits of the position. The total amount of unrecognized tax benefits, if recognized, would affect other tax accounts, primarily deferred taxes in future periods, and would not affect our effective tax rate, since we maintain a full valuation allowance against our deferred tax assets (see Note 12). We recognize interest and penalties related to income tax matters in income tax expense.

Comprehensive Loss

Comprehensive loss is defined as the change in equity during a period from transactions and other events and circumstances from non-owner sources. Net changes in unrealized gains and losses on available-for-sale securities are included in other comprehensive loss and represent the difference between our net loss and comprehensive net loss for both periods presented.

Net Loss per Share

Basic net loss per share is calculated by dividing the net loss by the weighted-average number of common shares outstanding for the period, without consideration of common stock equivalents. Diluted net loss per share is computed by dividing the net loss by the weighted-average number of common shares and common stock equivalents outstanding for the period determined using the treasury stock method. For purposes of this calculation, stock options, restricted stock units, warrants and shares of common stock underlying convertible notes are considered to be common stock equivalents and are included in the calculation of diluted net loss per share only when their effect is dilutive.

Because we have incurred a net loss for both periods presented in the consolidated statements of operations and comprehensive loss, the following common stock equivalents were not included in the computation of net loss per share because their effect would be anti-dilutive (in thousands):


	December 31,
	2022		2021
Stock options outstanding		20,749		18,944
Restricted stock units outstanding		3,167		2,803
Warrants outstanding		8,548		—
Shares of common stock underlying convertible notes outstanding		9,819		9,819

Recent Accounting Pronouncements

Adopted in 2022

In August 2020, the FASB issued ASU No. 2020-06, Debt—Debt with Conversion and Other Options (Subtopic 470-20) and Derivatives and Hedging—Contracts in Entity’s Own Equity (Subtopic 815-40): Accounting for Convertible Instruments and Contracts in an Entity’s Own Equity (“ASU 2020-06”). ASU 2020-06 simplifies the accounting for convertible instruments primarily by eliminating the existing cash conversion and beneficial conversion models within Subtopic 470-20, which will result in fewer embedded conversion options being accounted for separately from the debt host. ASU 2020-06 also amends and simplifies the calculation of earnings per share relating to convertible instruments. On January 1, 2022, we adopted the provisions of ASU 2020-06 using the modified retrospective approach, which did not have a material impact on our results of operations, cash flows, financial condition and related disclosures (see Note 8 for further details).

Summary of Significant Accounting Policies (Tables)

12 Months Ended

Dec. 31, 2022

Accounting Policies [Abstract]

Percentage of Net Product Sales and Accounts Receivable Balance

The following table includes the percentage of net product sales and accounts receivable balances for our three major Customers, each of which comprised 10% or more of our net product sales:


	Net Product Sales			Accounts Receivable
	Year Ended December 31, 2022			As of December 31, 2022
Customer A		43.5	%		51.6	%
Customer B		36.4	%		32.5	%
Customer C		18.8	%		15.0	%
Total		98.7	%		99.1	%

Common Stock Equivalents Excluded From Computation of Net Loss Per Share


	December 31,
	2022		2021
Stock options outstanding		20,749		18,944
Restricted stock units outstanding		3,167		2,803
Warrants outstanding		8,548		—
Shares of common stock underlying convertible notes outstanding		9,819		9,819

Consolidated Balance Sheets (Parenthetical) - $ / shares shares in Thousands	Dec. 31, 2022	Dec. 31, 2021
Statement of Financial Position [Abstract]
Preferred stock, par value (in dollars per share)	$ 0.01	$ 0.01
Preferred stock, shares authorized (in shares)	2,500	2,500
Preferred stock, shares issued (in shares)	0	0
Preferred stock, shares outstanding (in shares)	0	0
Common stock, par value (in dollars per share)	$ 0.01	$ 0.01
Common stock, shares authorized (in shares)	150,000	150,000
Common stock, shares issued (in shares)	119,155	102,005
Common stock, shares outstanding (in shares)	119,155	102,005

Equity Incentive Plan - Schedule of Options Exercisable, Vested or Expected to Vest (Details) - $ / shares	Dec. 31, 2022	Dec. 31, 2021
Equity [Abstract]
Options exercisable at end of year	13,650,210	12,243,887
Options vested or expected to vest	20,183,769	18,416,243
Options exercisable at end of year, weighted average exercise price	$ 17.86	$ 19.13
Options vested or expected to vest, weighted average exercise price	$ 14.82	$ 18.77

Balance Sheet Details - Additional Information (Details) - USD ($)	12 Months Ended
	Dec. 31, 2022	Dec. 31, 2021
Debt securities, impairment losses	$ 0	$ 0
Debt securities, available-for-sale, unrealized gain (loss)	(13,000)	(263,000)
Debt securities, available-for-sale, realized gain (loss)	0	0
Inventory	54,573,000	48,382,000
Depreciation and amortization	2,889,000	3,021,000
Construction in Progress, Gross	5,400,000	15,900,000
ZYNRELEF
Inventory	30,900,000	23,600,000
Cost of product sales, charges	8,900,000
SUSTOL
Inventory	2,600,000	1,700,000
Cost of product sales, charges		3,800,000
CINVANTI
Inventory	19,900,000	$ 23,100,000
APONVIE
Inventory	$ 1,200,000

Income Taxes (Tables)

12 Months Ended

Dec. 31, 2022

Income Tax Disclosure [Abstract]

Schedule of Components of Income Tax Expense (Benefit)

The difference between the provision for income taxes and income taxes computed using the effective U.S. federal statutory rate is as follows (in thousands):


	December 31,
	2022			2021
Tax at statutory federal rate	$	(38,225	)	$	(46,343	)
State tax, net of federal benefit		(13,898	)		(8,683	)
Research and development credits		(3,531	)		(4,173	)
Stock-based compensation expense		5,857			4,584
Non-deductible compensation		2,104			1,970
Employee retention credit adjustment		(1,265	)		—
Change in valuation allowance		46,452			51,459
Other		2,506			1,186
Provision for income taxes	$	—		$	—

Schedule of Deferred Tax Assets and Liabilities

Deferred income tax assets and liabilities arising from differences between accounting for financial statement purposes and tax purposes, less valuation allowance at year-end are as follows (in thousands):


	December 31,
	2022			2021
Deferred tax assets:
Net operating loss carryforward	$	313,834		$	294,189
Research and development credits		60,245			55,789
Section 174 capitalized research and development		20,903			—
Stock-based compensation		23,991			23,342
Lease liabilities		2,052			2,564
Other		3,693			3,953
Total gross deferred tax assets		424,718			379,837
Deferred tax liabilities:
Right-of-use lease assets		(1,914	)		(2,420	)
Total gross deferred tax liabilities		(1,914	)		(2,420	)
Valuation allowance		(422,804	)		(377,417	)
Net deferred tax assets	$	—		$	—

Summary of Unrecognized Tax Benefits

A reconciliation of our unrecognized tax benefits is as follows (in thousands):


	Year Ended December 31,
	2022			2021
Balance at beginning of year	$	9,631		$	7,406
Increase (decrease) for tax positions of prior years		(200	)		107
Increase based on tax positions related to current year		1,804			2,118
Balance at end of year	$	11,235		$	9,631

Consolidated Statements of Cash Flows - USD ($)	12 Months Ended
Consolidated Statements of Cash Flows - USD ($)	Dec. 31, 2022	Dec. 31, 2021
Operating activities:
Net loss	$ (182,024,000)	$ (220,683,000)
Adjustments to reconcile net loss to net cash used for operating activities:
Stock-based compensation expense	42,980,000	46,851,000
Depreciation and amortization	2,889,000	3,021,000
Amortization of debt discount		785,000
Amortization of debt issuance costs	202,000	119,000
Amortization of premium (accretion of discount) on short-term investments	(736,000)	332,000
Realized gain on available-for-sale investments	0	0
Impairment of property and equipment	209,000	478,000
Loss on disposal of property and equipment	74,000	822,000
Change in operating assets and liabilities:
Accounts receivable	(16,550,000)	6,351,000
Inventory	(6,191,000)	(6,477,000)
Prepaid expenses and other assets	1,010,000	(8,386,000)
Accounts payable	(578,000)	3,278,000
Accrued clinical and manufacturing liabilities	752,000	(26,246,000)
Accrued payroll and employee liabilities	(1,847,000)	1,666,000
Other accrued liabilities	12,898,000	(5,265,000)
Net cash used in operating activities	(146,912,000)	(203,354,000)
Investing activities:
Purchases of short-term investments	(145,683,000)	(129,221,000)
Maturities and sales of short-term investments	143,957,000	164,940,000
Purchases of property and equipment	(1,825,000)	(3,022,000)
Proceeds from the sale of property and equipment	227,000	32,000
Net cash provided by (used in) investing activities	(3,324,000)	32,729,000
Financing activities:
Net proceeds from sale of common stock	75,145,000
Net proceeds from convertible notes financing		148,963,000
Proceeds from purchases under the Employee Stock Purchase Plan	1,444,000	2,139,000
Proceeds from (payments for) stock issued under the equity incentive plan	(1,530,000)	4,926,000
Net cash provided by financing activities	75,059,000	156,028,000
Net decrease in cash and cash equivalents	(75,177,000)	(14,597,000)
Cash and cash equivalents at beginning of year	90,541,000	105,138,000
Cash and cash equivalents at end of year	15,364,000	90,541,000
Supplemental disclosure of cash flow information:
Interest paid	$ 2,250,000	$ 1,244,000

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 carryforward	$ 313,834	$ 294,189
Research and development credits	60,245	55,789
Section 174 capitalized research and development	20,903
Stock-based compensation	23,991	23,342
Lease liabilities	2,052	2,564
Other	3,693	3,953
Total gross deferred tax assets	424,718	379,837
Deferred Tax Liabilities, Net [Abstract]
Right-of-use lease assets	(1,914)	(2,420)
Total gross deferred tax liabilities	(1,914)	(2,420)
Valuation allowance	$ (422,804)	$ (377,417)

Convertible Notes - Additional Information (Details) - USD ($)	1 Months Ended		12 Months Ended
	May 31, 2021	Apr. 30, 2011	Dec. 31, 2022	Dec. 31, 2021
Debt Instrument [Line Items]
Net proceeds from convertible notes financing				$ 148,963,000
Amortization of debt issuance costs			$ 202,000	119,000
Amortization of debt discount				$ 785,000
Common Stock
Debt Instrument [Line Items]
Initial conversion price/rate	$ 15.276
Issuance of common stock on conversion of notes (in shares)	9,800,000			9,849,000
Notes
Debt Instrument [Line Items]
Convertible debt issuable in connection with private placement	$ 150,000,000.0
Net proceeds from convertible notes financing	$ 149,000,000.0
Debt instrument, interest rate	1.50%
Debt instrument, maturity date	May 26, 2026
Debt instrument, frequency of periodic payment	semi-annually
Debt instrument, date of first required payment	Dec. 15, 2021
Initial conversion price/rate	$ 65.4620
Debt instrument conversion ratio multiple of principal	$ 1,000
Common shares registered for resale in connection with convertible notes	12,400,000
Debt issuance costs incurred			$ 1,000,000.0
Effective interest rate			1.60%
Interest expense			$ 2,500,000
Interest expense, debt, excluding amortization			2,300,000
Amortization of debt issuance costs			200,000
Carrying value of debt			149,300,000
Debt instrument, face amount			150,000,000.0
Debt issuance costs			$ 700,000
Notes \| Redemption Between May 24, 2024 and May 24, 2025
Debt Instrument [Line Items]
Debt instrument, redemption period, stock price exceeds in percentage of conversion price	250.00%
Notes \| Redemption On or After May 24, 2025
Debt Instrument [Line Items]
Debt instrument, redemption period, stock price exceeds in percentage of conversion price	200.00%
Convertible Notes
Debt Instrument [Line Items]
Convertible debt issuable in connection with private placement		$ 4,500,000
Net proceeds from convertible notes financing		$ 4,300,000
Debt instrument, interest rate		6.00%
Debt instrument, maturity date		May 02, 2021
Debt instrument conversion ratio multiple of principal		$ 1,000
Interest expense, debt, excluding amortization				$ 200,000
Carrying value of debt	$ 0
Debt instrument, term		10 years
Amortization of debt discount				$ 800,000
Convertible Notes \| Common Stock
Debt Instrument [Line Items]
Debt instrument, number of shares issued for convertible notes		1,250

Summary of Significant Accounting Policies (Policies)

12 Months Ended

Dec. 31, 2022

Accounting Policies [Abstract]

Principles of Consolidation

Use of Estimates

Cash, Cash Equivalents and Short-term Investments

Cash and cash equivalents consist of cash and highly liquid investments with contractual maturities of three months or less from the original purchase date.

Fair Value of Financial Instruments

Concentration of Credit Risk

The following table includes the percentage of net product sales and accounts receivable balances for our three major Customers, each of which comprised 10% or more of our net product sales:


	Net Product Sales			Accounts Receivable
	Year Ended December 31, 2022			As of December 31, 2022
Customer A		43.5	%		51.6	%
Customer B		36.4	%		32.5	%
Customer C		18.8	%		15.0	%
Total		98.7	%		99.1	%

Accounts Receivable, Net

Inventory

Property and Equipment

Impairment of Long-Lived Assets

Leases

Revenue Recognition

Product Sales

Our Products are distributed in the U.S. through a limited number of Customers that resell to healthcare providers and hospitals, the end users of our Products.

Product Sales Allowances

•

Group Purchasing Organization (“GPO”) Discounts and Rebates—We offer cash discounts to GPO members. These discounts are taken when the GPO members purchase product from our Customers, who

•

Accrued Clinical Liabilities

Research and Development Expense

Patent Costs

Stock-Based Compensation Expense


	December 31,
	2022		2021
Stock options outstanding		20,749		18,944
Restricted stock units outstanding		3,167		2,803
Warrants outstanding		8,548		—
Shares of common stock underlying convertible notes outstanding		9,819		9,819

Recent Accounting Pronouncements

Adopted in 2022

Balance Sheet Details - Schedule of Prepaid Expenses and Other Assets (Details) - USD ($) $ in Thousands	Dec. 31, 2022	Dec. 31, 2021
Prepaid Expense and Other Assets, Current [Abstract]
Prepaid expenses	$ 21,120	$ 27,945
Other receivables	6,197	103
Prepaid insurance	1,947	2,135
Deposits	254	254
Interest receivable	154	245
Total prepaid expenses and other assets	$ 29,672	$ 30,682

Income Taxes - Schedule of Components of Income Tax Expense (Benefit) (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2022	Dec. 31, 2021
Income Tax Disclosure [Abstract]
Tax at statutory federal rate	$ (38,225)	$ (46,343)
State tax, net of federal benefit	(13,898)	(8,683)
Research and development credits	(3,531)	(4,173)
Stock-based compensation expense	5,857	4,584
Non-deductible compensation	2,104	1,970
Employee retention credit adjustment	(1,265)
Change in valuation allowance	46,452	51,459
Other	2,506	1,186
Provision for income taxes	$ 0	$ 0

Organization and Business

12 Months Ended

Dec. 31, 2022

Organization, Consolidation and Presentation of Financial Statements [Abstract]

Organization and Business

We are a commercial-stage biotechnology company focused on improving the lives of patients by developing and commercializing therapeutic innovations that improve medical care. Our advanced science, patented technologies, and innovative approach to drug discovery and development have allowed us to create and commercialize a portfolio of products that aim to advance the standard of care for acute care and oncology patients.

CINVANTI® (aprepitant) injectable emulsion (“CINVANTI”) and SUSTOL® (granisetron) extended-release injection (“SUSTOL”) are both approved in the United States (“U.S.”) for the prevention of chemotherapy-induced nausea and vomiting. ZYNRELEF® (bupivacaine and meloxicam) extended-release solution (“ZYNRELEF”) is approved in the U.S., 31 European countries and Canada for the management of postoperative pain.

In September 2022, APONVIE™ (aprepitant) injectable emulsion (“APONVIE”) was approved in the U.S. for the prevention of postoperative nausea and vomiting and became commercially available in the U.S. in March 2023. We are also developing HTX-034, an investigational agent, our next-generation product candidate for the management of postoperative pain.

In accordance with Accounting Standards Codification (“ASC”) 205-40, Going Concern, we evaluated whether there are conditions and events, considered in the aggregate, that raise substantial doubt about our ability to continue as a going concern within one year after the date that the consolidated financial statements are issued. This evaluation initially does not take into consideration the potential mitigating effect of our plans that have not been fully implemented as of the date the financial statements are issued. When substantial doubt exists under this methodology, we evaluate whether the mitigating effect of its plans sufficiently alleviates substantial doubt about our ability to continue as a going concern. The mitigating effect of our plans, however, is only considered if both (1) it is probable that the plans will be effectively implemented within one year after the date that the financial statements are issued, and (2) it is probable that the plans, when implemented, will mitigate the relevant conditions or events that raise substantial doubt about our ability to continue as a going concern within one year after the date that the financial statements are issued.

We have incurred significant operating losses and negative cash flows from operations. As of December 31, 2022, we had an accumulated deficit of $1.8 billion and cash, cash equivalents and short-term investments of $84.9 million. In addition, our net loss for the year ended December 31, 2022 was $182.0 million. These factors raise substantial doubt regarding our ability to continue as a going concern for a period of one year after the date that the financial statements are issued, however, based on our current operating plan and projections, management believes that the Company’s existing cash, cash equivalents and short-term investments will be sufficient to meet the Company’s anticipated cash requirements for at least one year from the date this Annual Report on Form 10-K is filed with the U.S. Securities and Exchange Commission (“SEC”).

In order to meet our cash requirements, we may be required to obtain additional funds and if we are not able to obtain adequate funds, we may be required to delay, reduce the scope of, or eliminate activities to support our Products and reduce personnel and related costs, which could have a material adverse effect on our business.

Our capital requirements and liquidity for the next twelve months will depend on numerous factors, including but not limited to: the degree of commercial success of our Products; the impact of competitive products; the timing and cost to manufacture our Products; the costs associated with the U.S. commercial launch of ZYNRELEF and APONVIE; the time, cost and outcome involved in seeking a further expanded label for ZYNRELEF in the U.S.; our ability to establish and maintain strategic collaborations or partnerships for research, development, clinical testing, manufacturing and marketing of our Products and product candidates; and general market conditions. Management’s view of our liquidity relies on estimates and assumptions about the market opportunity for the expanded U.S. label of ZYNRELEF, which estimates and assumptions are subject to significant uncertainty.

We may not be able to raise sufficient additional capital when needed on favorable terms, or at all. If we are unable to obtain adequate funds, we may be required to curtail significantly or cease our operations. If we issue

additional equity securities or securities convertible into equity securities to raise funds, our stockholders will suffer dilution of their investment, and such issuance may adversely affect the market price of our common stock.

Any new debt financing we enter into may involve covenants that restrict our operations. These restrictive covenants may include, among other things, limitations on borrowing and specific restrictions on the use of our assets, as well as prohibitions on our ability to create liens, pay dividends, redeem capital stock or make investments. In the event that additional funds are obtained through arrangements with collaborative partners, these arrangements may require us to relinquish rights to some of our technologies, product candidates or Products on terms that are not favorable to us or require us to enter into a collaboration arrangement that we would otherwise seek to develop and commercialize ourselves. If adequate funds are not available, we may default on our indebtedness, which could have a material adverse effect on our business.

Consolidated Statements of Operations and Comprehensive Loss - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2022	Dec. 31, 2021
Revenues:
Net product sales	$ 107,672	$ 86,346
Operating expenses:
Cost of product sales	54,874	46,021
Research and development	107,506	130,821
General and administrative	37,437	40,153
Sales and marketing	82,513	87,179
Total operating expenses	282,330	304,174
Loss from operations	(174,658)	(217,828)
Other expense, net:
Interest income	1,638	433
Interest expense	(2,474)	(2,410)
Other income (expense)	(6,530)	(878)
Total other expense, net	(7,366)	(2,855)
Net loss	(182,024)	(220,683)
Other comprehensive loss:
Unrealized losses on short-term investments	(13)	(263)
Comprehensive loss	$ (182,037)	$ (220,946)
Basic net loss per share	$ (1.67)	$ (2.24)
Shares used in computing basic net loss per share	108,876	98,471
Diluted net loss per share	$ (1.67)	$ (2.24)
Shares used in computing diluted net loss per share	108,876	98,471

Fair Value Measurements

12 Months Ended

Dec. 31, 2022

Fair Value Disclosures [Abstract]

Fair Value Measurements

Fair value is defined as the exchange price that would be received for an asset or paid to transfer a liability (an exit price) in the principal or most advantageous market for the asset or liability in an orderly transaction between market participants on the measurement date. Valuation techniques used to measure fair value must maximize the use of observable inputs and minimize the use of unobservable inputs. The FASB ASC Topic 820, Fair Value Measurements & Disclosures, establishes a fair value hierarchy which prioritizes the inputs used in measuring fair value as follows:

•

Level 1—Observable inputs such as quoted prices in active markets for identical assets or liabilities.

•

Level 2—Inputs other than Level 1 that are observable, either directly or indirectly, such as quoted prices for similar assets or liabilities; quoted prices in markets that are not active; or other inputs that are observable or can be corroborated by observable market data for substantially the full term of the assets or liabilities.

•

Level 3—Unobservable inputs that are supported by little or no market activity and that are significant to the fair value of the assets or liabilities.

We measure cash, cash equivalents and short-term investments at fair value on a recurring basis. The fair values of these such assets were as follows (in thousands):


	Fair Value Measurements at Reporting Date Using
	Balance at December 31, 2022		Quoted Prices in Active Markets for Identical Assets (Level 1)		Significant Other Observable Inputs (Level 2)		Significant Unobservable Inputs (Level 3)
Cash and money market funds	$	13,867	$	13,867	$	—	$	—
U.S. treasury bills and government agency obligations		35,715		35,715		—		—
U.S. corporate debt securities		1,497		—		1,497		—
U.S. commercial paper		5,481		—		5,481		—
Foreign commercial paper		28,292		—		28,292		—
Total	$	84,852	$	49,582	$	35,270	$	—


	Fair Value Measurements at Reporting Date Using
	Balance at December 31, 2021		Quoted Prices in Active Markets for Identical Assets (Level 1)		Significant Other Observable Inputs (Level 2)		Significant Unobservable Inputs (Level 3)
Cash and money market funds	$	86,043	$	86,043	$	—	$	—
U.S. corporate debt securities		15,006		—		15,006		—
Foreign corporate debt securities		10,548		—		10,548		—
U.S. commercial paper		10,496		—		10,496		—
Foreign commercial paper		35,487		—		35,487		—
Total	$	157,580	$	86,043	$	71,537	$	—

We have not transferred any investment securities between the three levels of the fair value hierarchy.

As of December 31, 2022, cash equivalents included $1.5 million of available-for-sale securities with contractual maturities of three months or less and short-term investments included $69.5 million of available-for-sale securities with contractual maturities of three months to one year. As of December 31, 2021, cash equivalents included $4.5 million of available-for-sale securities with contractual maturities of three months or less and short-term investments included $67.0 million of available-for-sale securities with contractual maturities of three months to one year. The money market funds as of December 31, 2022 and 2021 are included in cash and cash equivalents on the consolidated balance sheets.

- 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

Consolidated Balance Sheets - USD ($) $ in Thousands	Dec. 31, 2022	Dec. 31, 2021
Current assets:
Cash and cash equivalents	$ 15,364	$ 90,541
Short-term investments	69,488	67,039
Accounts receivable, net	52,049	35,499
Inventory	54,573	48,382
Prepaid expenses and other current assets	13,961	12,962
Total current assets	205,435	254,423
Property and equipment, net	22,160	23,734
Right-of-use lease assets	7,645	9,829
Other assets	15,711	17,720
Total assets	250,951	305,706
Current liabilities:
Accounts payable	3,225	3,803
Accrued clinical and manufacturing liabilities	24,468	23,716
Accrued payroll and employee liabilities	13,416	15,263
Other accrued liabilities	38,552	25,859
Current lease liabilities	2,694	2,417
Total current liabilities	82,355	71,058
Non-current lease liabilities	5,499	7,996
Non-current convertible notes payable, net	149,284	149,082
Other non-current liabilities	241
Total liabilities	237,379	228,136
Commitments and contingencies (see Note 6)
Stockholders’ equity:
Preferred stock, $0.01 par value: 2,500 shares authorized; no shares issued or outstanding at December 31, 2022 and 2021
Common stock, $0.01 par value: 150,000 shares authorized; 119,155 and 102,005 shares issued and outstanding at December 31, 2022 and 2021, respectively	1,191	1,020
Additional paid-in capital	1,807,855	1,689,987
Accumulated other comprehensive loss	(19)	(6)
Accumulated deficit	(1,795,455)	(1,613,431)
Total stockholders’ equity	13,572	77,570
Total liabilities and stockholders’ equity	$ 250,951	$ 305,706

Revenue Recognition (Tables)

12 Months Ended

Dec. 31, 2022

Revenue from Contract with Customer [Abstract]

Schedule of Disaggregated Net Product Sales

The following table provides disaggregated net product sales (in thousands):


	For the Years Ended December 31,
	2022		2021
CINVANTI net product sales	$	87,245	$	73,507
SUSTOL net product sales		10,231		9,915
ZYNRELEF net product sales		10,196		2,924
Total net product sales	$	107,672	$	86,346

Summary of Activity to Product Returns, Distributor Fees and Discounts, Rebates and Administrative Fees

The following table provides a summary of activity with respect to our product returns, distributor fees and discounts, rebates and administrative fees, which are included in other accrued liabilities on the consolidated balance sheets (in thousands):


							Discounts,
							Rebates and
	Product			Distributor			Administrative
	Returns			Fees			Fees			Total
Balance at December 31, 2021	$	2,579		$	3,466		$	16,515		$	22,560
Provision		1,546			21,153			158,384			181,083
Payments/credits		(789	)		(20,439	)		(149,098	)		(170,326	)
Balance at December 31, 2022	$	3,336		$	4,180		$	25,801		$	33,317

Commitments and Contingencies (Tables)

12 Months Ended

Dec. 31, 2022

Commitments and Contingencies Disclosure [Abstract]

Summary of Future Minimum Lease Payments

Annual future minimum lease payments as of December 31, 2022 are as follows (in thousands):


Year ended December 31:
2023	$	2,969
2024		3,030
2025		3,097
2026		—
2027		—
Thereafter		—
Total future minimum lease payments		9,096
Less: discount		(903	)
Total lease liabilities	$	8,193

Employee Benefit Plan

12 Months Ended

Dec. 31, 2022

Retirement Benefits [Abstract]

Employee Benefit Plan

11.

Employee Benefit Plan

We have a defined contribution 401(k) plan (“Plan”) covering substantially all of our employees. In the past three calendar years, we made matching cash contributions equal to 50% of each participant’s contribution during the Plan year up to a maximum amount equal to the lesser of 3% of each participant’s annual compensation or $9,150 and $8,700 for the years ended December 31, 2022 and 2021, respectively. Such amounts were recorded as expense in the corresponding years. We may also contribute additional discretionary amounts to the Plan as we determine. For the years ended December 31, 2022 and 2021, we contributed $1.4 million and $1.3 million, respectively, to the Plan. No discretionary contributions have been made to the Plan since its inception.

- 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
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Reference 2: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 715
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-Section S99
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Reference 3: http://www.xbrl.org/2003/role/disclosureRef
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-Publisher FASB
-Name Accounting Standards Codification
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Reference 8: http://www.xbrl.org/2003/role/disclosureRef
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Reference 10: http://www.xbrl.org/2003/role/disclosureRef
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Reference 11: http://www.xbrl.org/2003/role/disclosureRef
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Reference 12: http://www.xbrl.org/2003/role/disclosureRef
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-Name Accounting Standards Codification
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+ Details

Reorganization - Additional Information (Details) - USD ($) $ in Millions	1 Months Ended		3 Months Ended	9 Months Ended	12 Months Ended
	Jun. 30, 2022	Oct. 31, 2021	Dec. 31, 2022	Sep. 30, 2022	Dec. 31, 2022
Restructuring charges, total	$ 5.4	$ 1.4
Payments for restructuring charges					$ 5.4
Research and Development Expense
Restructuring charges, total			$ 1.2		4.2
General and Administrative Expense
Restructuring charges, total					0.2
Sales and Marketing Expense
Restructuring charges, total			$ 0.2		1.0
Employee Severance
Restructuring charges, total	5.0	1.3
Employee Severance \| 2022 Restructuring Plan
Payments for restructuring charges					$ 4.1
Employee Severance \| 2021 Restructuring Plan
Payments for restructuring charges				$ 1.3
Accelerated Non-Cash Stock Option Expense
Restructuring charges, total	$ 0.4	$ 0.1

Equity Incentive Plan - Summary of Stock-Based Compensation Expense related to Stock-Based Payment Awards (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2022	Dec. 31, 2021
Share Based Compensation Arrangement By Share Based Payment Award [Line Items]
Stock-based compensation expense	$ 42,980	$ 46,851
Research and Development Expense
Share Based Compensation Arrangement By Share Based Payment Award [Line Items]
Stock-based compensation expense	17,909	19,482
General and Administrative Expense
Share Based Compensation Arrangement By Share Based Payment Award [Line Items]
Stock-based compensation expense	11,688	11,816
Sales and Marketing Expense
Share Based Compensation Arrangement By Share Based Payment Award [Line Items]
Stock-based compensation expense	$ 13,383	$ 15,553

Employee Benefit Plan - Additional Information (Details) - USD ($)	12 Months Ended
	Dec. 31, 2022	Dec. 31, 2021	Dec. 31, 2020
Defined Benefit Plan Disclosure [Line Items]
Defined contribution plan, employer matching contribution, percent of match	50.00%	50.00%	50.00%
Defined contribution plan, maximum annual contributions by employer per employee, amount	$ 9,150	$ 8,700
Defined contribution plan, cost	$ 1,400,000	$ 1,300,000
Maximum
Defined Benefit Plan Disclosure [Line Items]
Defined contribution plan, employer matching contribution, percent of employees' gross pay	3.00%	3.00%	3.00%

Fair Value Measurements (Tables)

12 Months Ended

Dec. 31, 2022

Fair Value Disclosures [Abstract]

Schedule of Fair Value, Assets and Liabilities Measured on Recurring Basis

We measure cash, cash equivalents and short-term investments at fair value on a recurring basis. The fair values of these such assets were as follows (in thousands):


	Fair Value Measurements at Reporting Date Using
	Balance at December 31, 2022		Quoted Prices in Active Markets for Identical Assets (Level 1)		Significant Other Observable Inputs (Level 2)		Significant Unobservable Inputs (Level 3)
Cash and money market funds	$	13,867	$	13,867	$	—	$	—
U.S. treasury bills and government agency obligations		35,715		35,715		—		—
U.S. corporate debt securities		1,497		—		1,497		—
U.S. commercial paper		5,481		—		5,481		—
Foreign commercial paper		28,292		—		28,292		—
Total	$	84,852	$	49,582	$	35,270	$	—


	Fair Value Measurements at Reporting Date Using
	Balance at December 31, 2021		Quoted Prices in Active Markets for Identical Assets (Level 1)		Significant Other Observable Inputs (Level 2)		Significant Unobservable Inputs (Level 3)
Cash and money market funds	$	86,043	$	86,043	$	—	$	—
U.S. corporate debt securities		15,006		—		15,006		—
Foreign corporate debt securities		10,548		—		10,548		—
U.S. commercial paper		10,496		—		10,496		—
Foreign commercial paper		35,487		—		35,487		—
Total	$	157,580	$	86,043	$	71,537	$	—

Balance Sheet Details - Schedule of Property and Equipment, Net (Details) - USD ($) $ in Thousands	Dec. 31, 2022	Dec. 31, 2021
Property Plant And Equipment [Line Items]
Property and equipment, gross	$ 36,453	$ 36,977
Less: accumulated depreciation and amortization	(14,293)	(13,243)
Property and equipment, net	22,160	23,734
Scientific Equipment
Property Plant And Equipment [Line Items]
Property and equipment, gross	33,318	33,403
Leasehold Improvements
Property Plant And Equipment [Line Items]
Property and equipment, gross	647	610
Computer Equipment and Software
Property Plant And Equipment [Line Items]
Property and equipment, gross	1,506	1,497
Furniture, Fixtures and Office Equipment
Property Plant And Equipment [Line Items]
Property and equipment, gross	$ 982	$ 1,467

Equity Incentive Plan - Schedule of Exercise Prices and Weighted-average Remaining Contractual Lives for Options Outstanding (Details)	12 Months Ended
	Dec. 31, 2021 $ / shares shares
Options Outstanding (in shares) \| shares	20,749,349
Weighted- Average Remaining Contractual Life (Year)	6 years 5 months 8 days
Weighted- Average Exercise Price (in dollars per share)	$ 14.61
Options Exercisable (in shares) \| shares	13,650,210
Weighted- Average Exercise Price of Options Exercisable	$ 17.86
Exercise Price Range 1
Options Outstanding (in shares) \| shares	1,440,440
Range of Exercise Prices, Lower Limit (in dollars per share)	$ 2.49
Range of Exercise Prices, Upper Limit (in dollars per share)	$ 2.74
Weighted- Average Remaining Contractual Life (Year)	9 years 10 months 17 days
Weighted- Average Exercise Price (in dollars per share)	$ 2.70
Options Exercisable (in shares) \| shares	2,369
Weighted- Average Exercise Price of Options Exercisable	$ 2.74
Exercise Price Range 2
Options Outstanding (in shares) \| shares	3,483,035
Range of Exercise Prices, Lower Limit (in dollars per share)	$ 2.88
Range of Exercise Prices, Upper Limit (in dollars per share)	$ 3.17
Weighted- Average Remaining Contractual Life (Year)	9 years 3 months 25 days
Weighted- Average Exercise Price (in dollars per share)	$ 3.17
Options Exercisable (in shares) \| shares	764,820
Weighted- Average Exercise Price of Options Exercisable	$ 3.17
Exercise Price Range 3
Options Outstanding (in shares) \| shares	3,758,189
Range of Exercise Prices, Lower Limit (in dollars per share)	$ 3.30
Range of Exercise Prices, Upper Limit (in dollars per share)	$ 13.00
Weighted- Average Remaining Contractual Life (Year)	4 years 5 months 4 days
Weighted- Average Exercise Price (in dollars per share)	$ 9.84
Options Exercisable (in shares) \| shares	2,922,363
Weighted- Average Exercise Price of Options Exercisable	$ 9.94
Exercise Price Range 4
Options Outstanding (in shares) \| shares	3,484,856
Range of Exercise Prices, Lower Limit (in dollars per share)	$ 13.05
Range of Exercise Prices, Upper Limit (in dollars per share)	$ 15.72
Weighted- Average Remaining Contractual Life (Year)	6 years 9 months 29 days
Weighted- Average Exercise Price (in dollars per share)	$ 15.33
Options Exercisable (in shares) \| shares	2,166,837
Weighted- Average Exercise Price of Options Exercisable	$ 15.20
Exercise Price Range 5
Options Outstanding (in shares) \| shares	3,346,234
Range of Exercise Prices, Lower Limit (in dollars per share)	$ 15.75
Range of Exercise Prices, Upper Limit (in dollars per share)	$ 23.90
Weighted- Average Remaining Contractual Life (Year)	4 years 8 months 19 days
Weighted- Average Exercise Price (in dollars per share)	$ 17.93
Options Exercisable (in shares) \| shares	3,154,236
Weighted- Average Exercise Price of Options Exercisable	$ 17.91
Exercise Price Range 6
Options Outstanding (in shares) \| shares	5,236,595
Range of Exercise Prices, Lower Limit (in dollars per share)	$ 24.40
Range of Exercise Prices, Upper Limit (in dollars per share)	$ 39.00
Weighted- Average Remaining Contractual Life (Year)	5 years 10 months 6 days
Weighted- Average Exercise Price (in dollars per share)	$ 26.32
Options Exercisable (in shares) \| shares	4,639,585
Weighted- Average Exercise Price of Options Exercisable	$ 26.49

Equity Incentive Plans

12 Months Ended

Dec. 31, 2022

Equity [Abstract]

Equity Incentive Plans

10.

Equity Incentive Plans

Employee Stock Purchase Plan

In 1997, our stockholders approved our Employee Stock Purchase Plan (“ESPP”) at which time a maximum of 10,000 shares of common stock were available for issuance. In December 2007, May 2009, June 2011, May 2014, May 2015, June 2016, June 2017, June 2019, June 2021 and May 2022, our stockholders authorized increases in the number of shares reserved for issuance under the ESPP by 5,000, 10,000, 25,000, 25,000, 100,000, 100,000, 200,000, 300,000, 200,000 and 850,000 shares, respectively, for a total of 1,825,000 shares reserved at December 31, 2022. Under the terms of the ESPP, employees can elect to have up to a maximum of 10% of their base earnings withheld to purchase shares of our common stock. The purchase price of the stock is 85% of the lower of the closing prices for our common stock on either: (i) the first trading day in the enrollment period, as defined in the ESPP, in which the purchase is made, or (ii) the purchase date. The length of the enrollment period is 6 months. Enrollment dates are the first business day of May and November. Under the ESPP, we issued 406,421 and 175,228 shares in 2022 and 2021, respectively. The weighted-average exercise price per share of the purchase rights exercised during 2022 and 2021 was $3.55 and $12.21, respectively. As of December 31, 2022, 1,180,399 shares of common stock have been issued under the ESPP and 644,601 shares of common stock are available for future issuance.

Stock Option Plans

We currently have one stock option plan from which we can grant options and restricted stock awards to employees, officers, directors and consultants. In December 2007, the stockholders approved our 2007 Amended and Restated Equity Incentive Plan (“2007 Plan”) at which time a maximum of 150,000 shares of common stock were available for grant. In May 2010, June 2011, May 2014, May 2015, June 2016, June 2017, June 2019, June 2021 and May 2022, our stockholders approved amendments to our 2007 Plan to increase the maximum number of shares of common stock available for grant by 100,000, 4,500,000, 1,750,000, 4,300,000, 3,000,000, 5,000,000, 7,000,000, 2,000,000 and 2,900,000 shares of common stock, respectively, resulting in an aggregate of 30,700,000 shares of common stock authorized for issuance as of December 31, 2022. At December 31, 2022, there were 985,119 shares available for future grant under the 2007 Plan. Any shares that are issuable on exercise of options granted that expire, are cancelled or that we receive pursuant to a net exercise of options are available for future grant and issuance.

In 2014 and 2013, we granted options to certain employees outside of our stockholder approved stock option plans. All options to purchase our common stock were granted with an exercise price that equals fair market value of the underlying common stock on the grant dates and expire no later than 10 years from the date of grant. The options are exercisable in accordance with vesting schedules that generally provide for them to be fully vested and exercisable 4 years after the date of grant, provided, however, that we have also issued stock options awards that are subject to performance vesting requirements. All stock option grants issued outside of our stockholder approved plans have been registered on Form S-8 with the SEC.

In 2020, we began granting restricted stock units (“RSUs”) to employees and non-employee directors pursuant to the 2007 Plan. We satisfy such grants through the issuance of new shares upon vesting.

The following table summarizes the stock option plan activity:


	Outstanding Options
				Weighted-
				Average
	Number of			Exercise
	Shares			Price
Balance at December 31, 2021		18,943,937		$	18.71
Granted		5,296,547		$	3.11
Exercised		—		$	-
Cancelled		(3,491,135	)	$	19.40
Balance at December 31, 2022		20,749,349		$	14.61



	Outstanding RSUs
				Weighted-
				Average
	Number of			Grant Date
	Shares			Fair Value
Balance at December 31, 2021		2,803,193		$	11.51
Granted		1,831,508		$	2.73
Released		(899,966	)	$	11.45
Forfeited		(567,338	)	$	11.47
Balance at December 31, 2022		3,167,397		$	6.46

For the year ended December 31, 2022, equity awards cancelled (included in options outstanding) consisted of 1,227,682 options forfeited with a weighted-average exercise price of $15.57 and 2,263,453 options expired with a weighted-average exercise price of $21.47.

As of December 31, 2022, options exercisable have a weighted-average remaining contractual term of 6.4 years. There were no option exercises during the year ended December 31, 2022. The total intrinsic value of stock option exercises, which is the difference between the exercise price and closing price of our common stock on the date of exercise, during the year ended December 31, 2021 was $0.7 million. As of December 31, 2022, there were no options outstanding and exercisable that were in-the-money. As of December 31, 2021, the total intrinsic value of options outstanding and exercisable was $1.7 million.


	Years Ended December 31,
	2022				2021
			Weighted-				Weighted-
			Average				Average
			Exercise				Exercise
	Options		Price		Options		Price
Exercisable at end of year		13,650,210	$	17.86		12,243,887	$	19.13
Options vested or expected to vest		20,183,769	$	14.82		18,416,243	$	18.77

Exercise prices and weighted-average remaining contractual lives for the options outstanding as of December 31, 2022 were:


									Weighted-
			Weighted-						Average
			Average		Weighted-				Exercise
			Remaining		Average				Price of
Outstanding		Range of	Contractual		Exercise		Options		Options
Options		Exercise Prices	Life (in years)		Price		Exercisable		Exercisable
	1,440,440	$2.49–$2.74		9.88	$	2.70		2,369	$	2.74
	3,483,035	$2.88–$3.17		9.32		3.17		764,820		3.17
	3,758,189	$3.30–$13.00		4.43		9.84		2,922,363		9.94
	3,484,856	$13.05–$15.72		6.83		15.33		2,166,837		15.20
	3,346,234	$15.75–$23.90		4.72		17.93		3,154,236		17.91
	5,236,595	$24.40–$39.00		5.85		26.32		4,639,585		26.49
	20,749,349			6.44		14.61		13,650,210		17.86

On December 31, 2022, we had reserved 23,916,746 shares of common stock for future issuance on exercise of outstanding options and vesting of outstanding restricted stock units granted under the 2007 Plan, as well as the non-plan grants.

Stock-Based Compensation

The following table summarizes stock-based compensation expense related to stock-based payment awards pursuant to our equity compensation arrangements (in thousands):


	December 31,
	2022		2021
Research and development	$	17,909	$	19,482
General and administrative		11,688		11,816
Sales and marketing		13,383		15,553
Total stock-based compensation expense	$	42,980	$	46,851

As of December 31, 2022, there was $51.9 million of total unrecognized compensation cost related to non-vested, stock-based payment awards granted under all of our equity compensation plans and all non-plan option grants. Total unrecognized compensation cost will be adjusted for future changes in estimated forfeitures. We expect to recognize this compensation cost over a weighted-average period of 1.9 years.

The fair value of RSUs is estimated based on the closing market price of our common stock on the date of the grant. RSUs generally vest quarterly over a four-year period.

We estimated the fair value of each option grant and ESPP purchase right on the date of grant using the Black-Scholes option pricing model with the following weighted-average assumptions:

Options:


	December 31,
	2022			2021
Risk-free interest rate		3.3	%		1.1	%
Dividend yield		—	%		—	%
Volatility		62.0	%		62.6	%
Expected life (years)		6			6

ESPP:


	December 31,
	2022			2021
Risk-free interest rate		3.2	%		0.1	%
Dividend yield		—	%		—	%
Volatility		83.8	%		46.9	%
Expected life (months)		6			6

The weighted-average fair value of options granted was $1.71 and $7.10 for the years ended December 31, 2022 and 2021, respectively.

The weighted-average fair value of shares purchased through the ESPP was $1.65 and $3.64 for the years ended December 31, 2022 and 2021, respectively.

The risk-free interest rate assumption is based on observed interest rates on U.S. Treasury debt securities with maturities close to the expected term of our employee and director stock options and ESPP purchases.

The dividend yield assumption is based on our history and expectation of dividend payouts. We have never paid dividends on our common stock, and we do not anticipate paying dividends in the foreseeable future.

We used our historical stock price to estimate volatility.

The expected life of employee and director stock options represents the average of the contractual term of the options and the weighted-average vesting period, as permitted under the simplified method. We have elected to use the simplified method, as we do not have enough historical exercise experience to provide a reasonable basis on which to estimate the expected term. The expected life for the ESPP purchase rights is 6 months, which represents the length of each purchase period.

Convertible Notes

12 Months Ended

Dec. 31, 2022

Debt Disclosure [Abstract]

Convertible Notes

Senior Unsecured Convertible Notes

In May 2021, we entered into a note purchase agreement with funds affiliated with Baker Bros. Advisors LP for a private placement of $150.0 million in Senior Unsecured Convertible Notes (“Notes”). We received a total of $149.0 million, net of issuance costs, from the issuance of these Notes.

The Notes were issued at par. The Notes bear interest at a rate of 1.5% per annum, payable in cash semi-annually in arrears on June 15th and December 15th of each year, beginning on December 15, 2021. The Notes mature on May 26, 2026, unless earlier converted, redeemed or repurchased.

The Notes will be subject to redemption at our option, between May 24, 2024 and May 24, 2025, but only if the last reported sale price per share of our common stock exceeds 250% of the conversion price for a specified period of time, or on or after May 24, 2025 if the last reported sale price per share of our common stock exceeds 200% of the conversion price for a specified period of time. The redemption price will be equal to the principal amount of the Notes to be redeemed, plus accrued and unpaid interest.

Upon conversion, we will settle the Notes in shares of our common stock. The initial conversion rate for the Notes is 65.4620 shares per $1,000 principal amount of the Notes (equivalent to an initial conversion price of $15.276 per share of common stock).

If a holder of the Notes converts upon a make-whole fundamental change or company redemption, the holder may be eligible to receive a make-whole premium through an increase to the conversion rate.

In May 2021, we filed a registration statement with the SEC to register for resale 12.4 million shares of our common stock underlying the Notes, including the maximum number of shares of common stock issuable under the make-whole premium.

The Notes were accounted for in accordance with ASC Subtopic 470-20, Debt with Conversion and Other Options (“ASC 470-20”) and ASC Subtopic 815-40, Contracts in Entity’s Own Equity (“ASC 815-40”). Under ASC 815-40, to qualify for equity classification (or non-bifurcation, if embedded), the instrument (or embedded feature) must be both (1) indexed to the issuer’s stock and (2) meet the requirements of the equity classification guidance. Based upon our analysis, it was determined that the Notes do contain embedded features indexed to our own stock, but do not meet the requirements for bifurcation, and therefore do not need to be separately accounted for as an equity component. Since the embedded conversion feature meets the equity scope exception from derivative accounting, and, also since the embedded conversion option does not need to be separately accounted for as an equity component under ASC 470-20, the proceeds received from the issuance of the Notes were recorded as a liability on the consolidated balance sheets.

We incurred issuance costs related to the Notes of $1.0 million, which we recorded as debt issuance costs and are included as a reduction to the Notes on the consolidated balance sheets. The debt issuance costs are being amortized to interest expense using the effective interest rate method over the term of the Notes, resulting in an effective interest rate of 1.6%. For the year ended December 31, 2022, interest expense related to the Notes was $2.5 million, which included $2.3 million related to the stated interest rate and $0.2 million related to the amortization of debt issuance costs. As of December 31, 2022, the carrying value of the Notes was $149.3 million, which is comprised of the $150.0 million principal amount of the Notes outstanding, less debt issuance costs of $0.7 million.

Senior Secured Convertible Notes

In April 2011, we entered into a securities purchase agreement for a private placement of up to $4.5 million in Senior Secured Convertible Notes (“Convertible Notes”) with certain investors, including Tang Capital Partners, LP. We received a total of $4.3 million, net of issuance costs, from the issuance of these Convertible Notes. The Convertible Notes bore interest at 6% per annum, payable quarterly in cash or in additional principal amount of Convertible Notes, at the election of the purchasers. The Convertible Notes matured on May 2, 2021.

The Convertible Notes contained an embedded conversion feature that was in-the-money on the issuance dates. Based on an effective fixed conversion rate of 1,250 shares for every $1,000 of principal and accrued interest due under the Convertible Notes, the total conversion benefit at issuance exceeded the loan proceeds. Therefore, a debt discount was recorded in an amount equal to the face value of the Convertible Notes on the issuance dates, and we amortized the resultant debt discount over the respective 10-year term of the Convertible Notes which ended in May 2021. For the year ended December 31, 2021 interest expense relating to the stated rate was $0.2 million and interest expense relating to the amortization of the debt discount was $0.8 million.

In May 2021, holders of the Convertible Notes exercised their right to convert the outstanding principal and accrued interest into shares, which resulted in the issuance of 9.8 million shares of common stock. Upon issuance of these shares, there were no remaining obligations under the Convertible Notes.

- Definition

The entire disclosure for information about short-term and long-term debt arrangements, which includes amounts of borrowings under each line of credit, note payable, commercial paper issue, bonds indenture, debenture issue, own-share lending arrangements and any other contractual agreement to repay funds, and about the underlying arrangements, rationale for a classification as long-term, including repayment terms, interest rates, collateral provided, restrictions on use of assets and activities, whether or not in compliance with debt covenants, and other matters important to users of the financial statements, such as the effects of refinancing and noncompliance with debt covenants.

+ References

Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 470
-URI https://asc.fasb.org/topic&trid=2208564

Reference 2: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 470
-SubTopic 20
-Section 50
-Paragraph 1B
-Subparagraph (h)
-URI https://asc.fasb.org/extlink&oid=123466505&loc=SL123495323-112611

Reference 3: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 470
-SubTopic 20
-Section 50
-Paragraph 1C
-Subparagraph (c)
-URI https://asc.fasb.org/extlink&oid=123466505&loc=SL123495334-112611

Reference 4: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 470
-SubTopic 20
-Section 50
-Paragraph 1I
-Subparagraph (a)
-URI https://asc.fasb.org/extlink&oid=123466505&loc=SL123495371-112611

Reference 5: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 470
-SubTopic 20
-Section 50
-Paragraph 1I
-Subparagraph (d)
-URI https://asc.fasb.org/extlink&oid=123466505&loc=SL123495371-112611

Reference 6: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 235
-SubTopic 10
-Section S99
-Paragraph 1
-Subparagraph (SX 210.4-08(c))
-URI https://asc.fasb.org/extlink&oid=120395691&loc=d3e23780-122690

Reference 7: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 470
-SubTopic 20
-Section 50
-Paragraph 1B
-Subparagraph (g)
-URI https://asc.fasb.org/extlink&oid=123466505&loc=SL123495323-112611

Reference 8: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 470
-SubTopic 20
-Section 50
-Paragraph 1C
-Subparagraph (b)
-URI https://asc.fasb.org/extlink&oid=123466505&loc=SL123495334-112611

Reference 9: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 470
-SubTopic 20
-Section 50
-Paragraph 1C
-Subparagraph (a)
-URI https://asc.fasb.org/extlink&oid=123466505&loc=SL123495334-112611

Reference 10: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 470
-SubTopic 20
-Section 50
-Paragraph 1E
-Subparagraph (b)
-URI https://asc.fasb.org/extlink&oid=123466505&loc=SL123495348-112611

Reference 11: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 470
-SubTopic 20
-Section 50
-Paragraph 1B
-URI https://asc.fasb.org/extlink&oid=123466505&loc=SL123495323-112611

Reference 12: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 470
-SubTopic 20
-Section 50
-Paragraph 1I
-Subparagraph (b)
-URI https://asc.fasb.org/extlink&oid=123466505&loc=SL123495371-112611

Reference 13: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 470
-SubTopic 20
-Section 50
-Paragraph 1B
-Subparagraph (i)
-URI https://asc.fasb.org/extlink&oid=123466505&loc=SL123495323-112611

+ Details

Equity Incentive Plans (Tables)

12 Months Ended

Dec. 31, 2022

Equity [Abstract]

Summary of Stock Option Plan Activity

The following table summarizes the stock option plan activity:


	Outstanding Options
				Weighted-
				Average
	Number of			Exercise
	Shares			Price
Balance at December 31, 2021		18,943,937		$	18.71
Granted		5,296,547		$	3.11
Exercised		—		$	-
Cancelled		(3,491,135	)	$	19.40
Balance at December 31, 2022		20,749,349		$	14.61



	Outstanding RSUs
				Weighted-
				Average
	Number of			Grant Date
	Shares			Fair Value
Balance at December 31, 2021		2,803,193		$	11.51
Granted		1,831,508		$	2.73
Released		(899,966	)	$	11.45
Forfeited		(567,338	)	$	11.47
Balance at December 31, 2022		3,167,397		$	6.46

Schedule of Options Exercisable, Vested or Expected to Vest


	Years Ended December 31,
	2022				2021
			Weighted-				Weighted-
			Average				Average
			Exercise				Exercise
	Options		Price		Options		Price
Exercisable at end of year		13,650,210	$	17.86		12,243,887	$	19.13
Options vested or expected to vest		20,183,769	$	14.82		18,416,243	$	18.77

Schedule of Exercise Prices and Weighted-average Remaining Contractual Lives for Options Outstanding

Exercise prices and weighted-average remaining contractual lives for the options outstanding as of December 31, 2022 were:


									Weighted-
			Weighted-						Average
			Average		Weighted-				Exercise
			Remaining		Average				Price of
Outstanding		Range of	Contractual		Exercise		Options		Options
Options		Exercise Prices	Life (in years)		Price		Exercisable		Exercisable
	1,440,440	$2.49–$2.74		9.88	$	2.70		2,369	$	2.74
	3,483,035	$2.88–$3.17		9.32		3.17		764,820		3.17
	3,758,189	$3.30–$13.00		4.43		9.84		2,922,363		9.94
	3,484,856	$13.05–$15.72		6.83		15.33		2,166,837		15.20
	3,346,234	$15.75–$23.90		4.72		17.93		3,154,236		17.91
	5,236,595	$24.40–$39.00		5.85		26.32		4,639,585		26.49
	20,749,349			6.44		14.61		13,650,210		17.86

Summary of Stock-Based Compensation Expense related to Stock-Based Payment Awards

The following table summarizes stock-based compensation expense related to stock-based payment awards pursuant to our equity compensation arrangements (in thousands):


	December 31,
	2022		2021
Research and development	$	17,909	$	19,482
General and administrative		11,688		11,816
Sales and marketing		13,383		15,553
Total stock-based compensation expense	$	42,980	$	46,851

Summary of Fair Value of Option Grant and ESPP Purchase Right on Grant Date Using Black-Scholes Option Pricing Model

We estimated the fair value of each option grant and ESPP purchase right on the date of grant using the Black-Scholes option pricing model with the following weighted-average assumptions:

Options:


	December 31,
	2022			2021
Risk-free interest rate		3.3	%		1.1	%
Dividend yield		—	%		—	%
Volatility		62.0	%		62.6	%
Expected life (years)		6			6

ESPP:


	December 31,
	2022			2021
Risk-free interest rate		3.2	%		0.1	%
Dividend yield		—	%		—	%
Volatility		83.8	%		46.9	%
Expected life (months)		6			6

Summary of Significant Accounting Policies - Common Stock Equivalents Excluded From Computation of Net Loss Per Share (Details) - shares shares in Thousands	12 Months Ended
	Dec. 31, 2022	Dec. 31, 2021
Share-based Payment Arrangement, Option
Antidilutive Securities Excluded From Computation Of Earnings Per Share [Line Items]
Shares excluded (in shares)	20,749	18,944
Restricted Stock Units
Antidilutive Securities Excluded From Computation Of Earnings Per Share [Line Items]
Shares excluded (in shares)	3,167	2,803
Warrant
Antidilutive Securities Excluded From Computation Of Earnings Per Share [Line Items]
Shares excluded (in shares)	8,548
Convertible Debt Securities
Antidilutive Securities Excluded From Computation Of Earnings Per Share [Line Items]
Shares excluded (in shares)	9,819	9,819

Balance Sheet Details - Summary of Short -Term Investments (Details) - USD ($) $ in Thousands	Dec. 31, 2022	Dec. 31, 2021
Schedule Of Available For Sale Securities [Line Items]
Available-for-sale securities, amortized cost	$ 69,507	$ 67,045
Available-for-sale securities, gross unrealized losses	(19)	(6)
Available-for-sale securities	69,488	67,039
U.S. Treasury Bills and Government Agency Obligations
Schedule Of Available For Sale Securities [Line Items]
Available-for-sale securities, amortized cost	35,734
Available-for-sale securities, gross unrealized losses	(19)
Available-for-sale securities	35,715
U.S. Corporate Debt Securities
Schedule Of Available For Sale Securities [Line Items]
Available-for-sale securities, amortized cost		15,009
Available-for-sale securities, gross unrealized losses		(3)
Available-for-sale securities		15,006
Foreign Corporate Debt Securities
Schedule Of Available For Sale Securities [Line Items]
Available-for-sale securities, amortized cost		10,551
Available-for-sale securities, gross unrealized losses		(3)
Available-for-sale securities		10,548
U.S. Commercial Paper
Schedule Of Available For Sale Securities [Line Items]
Available-for-sale securities, amortized cost	5,481	5,998
Available-for-sale securities	5,481	5,998
Foreign Commercial Paper
Schedule Of Available For Sale Securities [Line Items]
Available-for-sale securities, amortized cost	28,292	35,487
Available-for-sale securities	$ 28,292	$ 35,487

Commitments and Contingencies

12 Months Ended

Dec. 31, 2022

Commitments and Contingencies Disclosure [Abstract]

Commitments and Contingencies

Leases

As of December 31, 2022, we had an operating lease for 52,148 square feet of laboratory and office space in San Diego, California, with a lease term that expires on December 31, 2025. In October 2021, we entered into a sublease agreement to sublet 23,873 square feet of laboratory and office space. The space was delivered to the subtenant in March 2022. As a result of the sublease agreement, our one 5-year option to renew the lease on expiration applies only with respect to our remaining 28,275 square feet of laboratory and office space. During the year ended December 31, 2022, we paid $2.9 million for our operating lease.

Annual future minimum lease payments as of December 31, 2022 are as follows (in thousands):


Year ended December 31:
2023	$	2,969
2024		3,030
2025		3,097
2026		—
2027		—
Thereafter		—
Total future minimum lease payments		9,096
Less: discount		(903	)
Total lease liabilities	$	8,193

Rent expense under all operating leases totaled $2.8 million and $3.7 million for the years ended December 31, 2022 and 2021, respectively.

Development Agreements

We enter into agreements with clinical sites and clinical research organizations for the conduct of our clinical trials and contract manufacturing organizations for the manufacture and supply of preclinical, clinical and commercial materials and drug product. We make payments to these clinical sites and clinical research organizations based in part on the number of eligible patients enrolled and the length of their participation in the clinical trials. In some of our agreements with contract manufacturing organizations, we are required to meet minimum purchase obligations. Under certain of these agreements, we may be subject to penalties in the event that we prematurely terminate these agreements. At this time, due to the variability associated with clinical site agreements, contract research organization agreements and contract manufacturing agreements, we are unable to estimate with certainty the future costs we will incur. We intend to use our current financial resources to fund our obligations under these commitments.

Purchase Obligations

At December 31, 2022, purchase obligations primarily consisted of non-cancellable commitments with third-party manufacturers in connection with the manufacturing of our commercial products. Total purchase obligations of $103.7 million were not included in our consolidated financial statements for the year ended December 31, 2022, with $38.7 million due in one year and $65.0 million due within two to three years.

Balance Sheet Details - Schedule of Accrued Liabilities (Details) - USD ($) $ in Thousands	Dec. 31, 2022	Dec. 31, 2021
Accrued payroll and employee liabilities
Accrued employee salaries and benefits	$ 2,134	$ 1,784
Accrued bonuses	7,783	9,439
Accrued vacation	3,499	4,040
Total accrued payroll and employee liabilities	13,416	15,263
Other accrued liabilities
Accrued product sales allowances	33,317	22,560
Accrued consulting and professional fees	4,236	2,666
Accrued accounts payable	363	70
Other accrued liabilities	636	563
Total other accrued liabilities	$ 38,552	$ 25,859

Income Taxes - Summary of Unrecognized Tax Benefits (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2022	Dec. 31, 2021
Income Tax Disclosure [Abstract]
Balance at beginning of year	$ 9,631	$ 7,406
Increase (decrease) for tax positions of prior years	200	107
Increase based on tax positions related to current year	1,804	2,118
Balance at end of year	$ 11,235	$ 9,631

Balance Sheet Details (Tables)

12 Months Ended

Dec. 31, 2022

Organization, Consolidation and Presentation of Financial Statements [Abstract]

Summary of Short-Term Investments

The following is a summary of our short-term investments (in thousands):


	December 31, 2022
	Amortized Cost		Gross Unrealized Gains		Gross Unrealized Losses			Estimated Fair Value
U.S. treasury bills and government agency obligations	$	35,734	$	—	$	(19	)	$	35,715
U.S. commercial paper		5,481		—		—			5,481
Foreign commercial paper		28,292		—		—			28,292
Total	$	69,507	$	—	$	(19	)	$	69,488


	December 31, 2021
	Amortized Cost		Gross Unrealized Gains		Gross Unrealized Losses			Estimated Fair Value
U.S. corporate debt securities	$	15,009	$	—	$	(3	)	$	15,006
Foreign corporate debt securities		10,551		—		(3	)		10,548
U.S. commercial paper		5,998		—		—			5,998
Foreign commercial paper		35,487		—		—			35,487
Total	$	67,045	$	—	$	(6	)	$	67,039

Schedule of Inventory

Inventory consists of the following (in thousands):


	December 31,
	2022		2021
Raw materials	$	15,137	$	21,193
Work in process		20,723		20,935
Finished goods		18,713		6,254
Total inventory	$	54,573	$	48,382

Schedule of Prepaid Expenses and Other Assets

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


	December 31,
	2022		2021
Prepaid expenses	$	21,120	$	27,945
Other receivables		6,197		103
Prepaid insurance		1,947		2,135
Deposits		254		254
Interest receivable		154		245
Total prepaid expenses and other assets	$	29,672	$	30,682

Schedule of Property and Equipment, Net

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


	December 31,
	2022			2021
Scientific equipment	$	33,318		$	33,403
Leasehold improvements		647			610
Computer equipment and software		1,506			1,497
Furniture, fixtures and office equipment		982			1,467
Property and equipment, gross		36,453			36,977
Less: accumulated depreciation and amortization		(14,293	)		(13,243	)
Property and equipment, net	$	22,160		$	23,734

Schedule of Accrued Liabilities

Accrued payroll and employee liabilities consist of the following (in thousands):


	December 31,
	2022		2021
Accrued employee salaries and benefits	$	2,134	$	1,784
Accrued bonuses		7,783		9,439
Accrued vacation		3,499		4,040
Total accrued payroll and employee liabilities	$	13,416	$	15,263

Other accrued liabilities consist of the following (in thousands):


	December 31,
	2022		2021
Accrued product sales allowances	$	33,317	$	22,560
Accrued consulting and professional fees		4,236		2,666
Accrued accounts payable		363		70
Other accrued liabilities		636		563
Total other accrued liabilities	$	38,552	$	25,859

Stockholders' Equity - Additional Information (Details) - USD ($)			1 Months Ended		12 Months Ended
	Oct. 18, 2022	Aug. 08, 2022	Apr. 30, 2021	Jun. 30, 2014	Dec. 31, 2022	Dec. 31, 2021	Dec. 31, 2020	Dec. 31, 2019
Class Of Stock [Line Items]
Common shares registered for resale	24,600,000
Proceeds from issuance of common stock					$ 75,145,000
Private Placement
Class Of Stock [Line Items]
Shares of common stock sold		16,100,000
Purchase price per share		$ 3.10
Stock issuance cost		$ 1,400,000
Proceeds from issuance of common stock and pre-funded warrants		$ 75,100,000
Pre-funded Warrants
Class Of Stock [Line Items]
Purchase price per share		$ 3.0999
Class of warrant or right, number of securities called by warrants or rights		8,500,000		600,000
Class of warrant or right, exercise price of warrants or rights		$ 0.0001		$ 0.01
Class of warrant or right, expiration date				Jun. 30, 2021
Class of warrant or right, exercised during period			195,574				267,870	132,130
Proceeds from issuance of warrants			$ 0				$ 2,679,000	$ 1,321,000
Class of warrant or right, outstanding						0
Common Stock
Class Of Stock [Line Items]
Issuance of common stock on exercise of warrants (in shares)						195,000
Common Stock \| Private Placement
Class Of Stock [Line Items]
Shares of common stock sold					16,129,000
Common Stock \| Pre-funded Warrants
Class Of Stock [Line Items]
Issuance of common stock on exercise of warrants (in shares)			195,461				267,870	132,130

Fair Value Measurements - Schedule of Financial Assets Measured on a Recurring Basis (Details) - USD ($) $ in Thousands	Dec. 31, 2022	Dec. 31, 2021
Fair Value Assets And Liabilities Measured On Recurring And Nonrecurring Basis [Line Items]
Available-for-sale securities	$ 69,488	$ 67,039
U.S. Treasury Bills and Government Agency Obligations
Fair Value Assets And Liabilities Measured On Recurring And Nonrecurring Basis [Line Items]
Available-for-sale securities	35,715
U.S. Corporate Debt Securities
Fair Value Assets And Liabilities Measured On Recurring And Nonrecurring Basis [Line Items]
Available-for-sale securities		15,006
Foreign Corporate Debt Securities
Fair Value Assets And Liabilities Measured On Recurring And Nonrecurring Basis [Line Items]
Available-for-sale securities		10,548
U.S. Commercial Paper
Fair Value Assets And Liabilities Measured On Recurring And Nonrecurring Basis [Line Items]
Available-for-sale securities	5,481	5,998
Fair Value, Recurring
Fair Value Assets And Liabilities Measured On Recurring And Nonrecurring Basis [Line Items]
Total	84,852	157,580
Fair Value, Recurring \| Foreign Commercial Paper
Fair Value Assets And Liabilities Measured On Recurring And Nonrecurring Basis [Line Items]
Available-for-sale securities	28,292	35,487
Fair Value, Recurring \| U.S. Treasury Bills and Government Agency Obligations
Fair Value Assets And Liabilities Measured On Recurring And Nonrecurring Basis [Line Items]
Available-for-sale securities	35,715
Fair Value, Recurring \| U.S. Corporate Debt Securities
Fair Value Assets And Liabilities Measured On Recurring And Nonrecurring Basis [Line Items]
Available-for-sale securities	1,497	15,006
Fair Value, Recurring \| Foreign Corporate Debt Securities
Fair Value Assets And Liabilities Measured On Recurring And Nonrecurring Basis [Line Items]
Available-for-sale securities		10,548
Fair Value, Recurring \| U.S. Commercial Paper
Fair Value Assets And Liabilities Measured On Recurring And Nonrecurring Basis [Line Items]
Available-for-sale securities	5,481	10,496
Fair Value, Recurring \| Cash and Money Market Funds
Fair Value Assets And Liabilities Measured On Recurring And Nonrecurring Basis [Line Items]
Cash and money market funds	13,867	86,043
Fair Value, Recurring \| Quoted Prices in Active Markets for Identical Assets (Level 1)
Fair Value Assets And Liabilities Measured On Recurring And Nonrecurring Basis [Line Items]
Total	49,582	86,043
Fair Value, Recurring \| Quoted Prices in Active Markets for Identical Assets (Level 1) \| U.S. Treasury Bills and Government Agency Obligations
Fair Value Assets And Liabilities Measured On Recurring And Nonrecurring Basis [Line Items]
Available-for-sale securities	35,715
Fair Value, Recurring \| Quoted Prices in Active Markets for Identical Assets (Level 1) \| Cash and Money Market Funds
Fair Value Assets And Liabilities Measured On Recurring And Nonrecurring Basis [Line Items]
Cash and money market funds	13,867	86,043
Fair Value, Recurring \| Significant Other Observable Inputs (Level 2)
Fair Value Assets And Liabilities Measured On Recurring And Nonrecurring Basis [Line Items]
Total	35,270	71,537
Fair Value, Recurring \| Significant Other Observable Inputs (Level 2) \| Foreign Commercial Paper
Fair Value Assets And Liabilities Measured On Recurring And Nonrecurring Basis [Line Items]
Available-for-sale securities	28,292	35,487
Fair Value, Recurring \| Significant Other Observable Inputs (Level 2) \| U.S. Corporate Debt Securities
Fair Value Assets And Liabilities Measured On Recurring And Nonrecurring Basis [Line Items]
Available-for-sale securities	1,497	15,006
Fair Value, Recurring \| Significant Other Observable Inputs (Level 2) \| Foreign Corporate Debt Securities
Fair Value Assets And Liabilities Measured On Recurring And Nonrecurring Basis [Line Items]
Available-for-sale securities		10,548
Fair Value, Recurring \| Significant Other Observable Inputs (Level 2) \| U.S. Commercial Paper
Fair Value Assets And Liabilities Measured On Recurring And Nonrecurring Basis [Line Items]
Available-for-sale securities	$ 5,481	$ 10,496

Revenue Recognition

12 Months Ended

Dec. 31, 2022

Revenue from Contract with Customer [Abstract]

Revenue Recognition

The following table provides disaggregated net product sales (in thousands):


	For the Years Ended December 31,
	2022		2021
CINVANTI net product sales	$	87,245	$	73,507
SUSTOL net product sales		10,231		9,915
ZYNRELEF net product sales		10,196		2,924
Total net product sales	$	107,672	$	86,346


							Discounts,
							Rebates and
	Product			Distributor			Administrative
	Returns			Fees			Fees			Total
Balance at December 31, 2021	$	2,579		$	3,466		$	16,515		$	22,560
Provision		1,546			21,153			158,384			181,083
Payments/credits		(789	)		(20,439	)		(149,098	)		(170,326	)
Balance at December 31, 2022	$	3,336		$	4,180		$	25,801		$	33,317

- Definition

The entire disclosure of revenue from contract with customer to transfer good or service and to transfer nonfinancial asset. Includes, but is not limited to, disaggregation of revenue, credit loss recognized from contract with customer, judgment and change in judgment related to contract with customer, and asset recognized from cost incurred to obtain or fulfill contract with customer. Excludes insurance and lease contracts.

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+ Details

Organization and Business - Additional Information (Details) $ in Thousands	12 Months Ended
	Dec. 31, 2022 USD ($) Country	Dec. 31, 2021 USD ($)
Business [Line Items]
Accumulated deficit	$ (1,795,455)	$ (1,613,431)
Cash, cash equivalents and short-term investments	84,900
Net loss	$ (182,024)	$ (220,683)
H T X011 \| European Countries and Canada
Business [Line Items]
Number of countries approved the drug \| Country	31

- 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

Summary of Significant Accounting Policies - Additional Information (Details)	12 Months Ended
	Dec. 31, 2022
Accounting Standards Update 2020-06
Product Information [Line Items]
Change in accounting principle, accounting standards update, adoption date	Jan. 01, 2022
Change in accounting principle, accounting standards update, adopted	true
Change in accounting principle, accounting standards update, immaterial effect	true
Leasehold Improvements
Product Information [Line Items]
Estimated useful lives	5 years

- Definition

Indicates (true false) whether accounting standards update was adopted.

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- Definition

Date accounting standards update was adopted, in YYYY-MM-DD format.

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+ Details

Income Taxes

12 Months Ended

Dec. 31, 2022

Income Tax Disclosure [Abstract]

Income Taxes

12.

Income Taxes

For the years ended December 31, 2022 and 2021, we did not record a provision for income taxes due to a full valuation allowance against our deferred tax assets.

The difference between the provision for income taxes and income taxes computed using the effective U.S. federal statutory rate is as follows (in thousands):


	December 31,
	2022			2021
Tax at statutory federal rate	$	(38,225	)	$	(46,343	)
State tax, net of federal benefit		(13,898	)		(8,683	)
Research and development credits		(3,531	)		(4,173	)
Stock-based compensation expense		5,857			4,584
Non-deductible compensation		2,104			1,970
Employee retention credit adjustment		(1,265	)		—
Change in valuation allowance		46,452			51,459
Other		2,506			1,186
Provision for income taxes	$	—		$	—


	December 31,
	2022			2021
Deferred tax assets:
Net operating loss carryforward	$	313,834		$	294,189
Research and development credits		60,245			55,789
Section 174 capitalized research and development		20,903			—
Stock-based compensation		23,991			23,342
Lease liabilities		2,052			2,564
Other		3,693			3,953
Total gross deferred tax assets		424,718			379,837
Deferred tax liabilities:
Right-of-use lease assets		(1,914	)		(2,420	)
Total gross deferred tax liabilities		(1,914	)		(2,420	)
Valuation allowance		(422,804	)		(377,417	)
Net deferred tax assets	$	—		$	—

We have established a valuation allowance to offset net deferred tax assets as of December 31, 2022 and 2021 due to the uncertainty of realizing future tax benefits from such assets.

As of December 31, 2022, we had federal and state net operating loss (“NOL”) carryforwards of $1.3 billion and $891.7 million, respectively. The federal NOL carryforwards consist of $542.7 million generated before January 1, 2018, which will begin to expire in 2023, and $718.2 million that can be carried forward indefinitely, but are subject to the 80% taxable income limitation. The state NOL carryforwards will begin to expire in 2028.

As of December 31, 2022, we had federal and state research and development credit carryforwards of $49.3 million and $22.2 million, respectively. The federal research and development credit carryforwards will begin to expire in 2023. The state research and development credit carryforwards will be carried forward indefinitely.

Internal Revenue Code (“IRC”) Sections 382 and 383 place a limitation on the amount of taxable income that can be offset by NOL and credit carryforwards after a change in control (generally greater than 50% change in ownership within a three-year period) of a loss corporation. Generally, after a change in control, a loss corporation cannot deduct NOL and credit carryforwards in excess of the IRC Sections 382 and 383 limitation. State jurisdictions have similar rules. We have previously performed an analysis of IRC Sections 382 and 383 through 2018 and determined there were ownership changes in 2007, 2011 and 2013. We are currently in the process of updating our IRC Sections 382 and 383 analysis through 2021. The limitation in the federal and state NOL and research and development credit carryforwards that expire unused would reduce the deferred tax assets, which are fully offset by a valuation allowance.

We file U.S. and state income tax returns with varying statutes of limitations. The tax years from 2002 to 2022 remain open to examination due to the carryover of unused NOL carryforwards and tax credits.

A reconciliation of our unrecognized tax benefits is as follows (in thousands):


	Year Ended December 31,
	2022			2021
Balance at beginning of year	$	9,631		$	7,406
Increase (decrease) for tax positions of prior years		(200	)		107
Increase based on tax positions related to current year		1,804			2,118
Balance at end of year	$	11,235		$	9,631

Due to our valuation allowance, the $11.2 million of unrecognized tax benefits would not affect the effective tax rate, if recognized. It is the Company’s practice to recognize interest and penalties related to income tax matters in income tax expense. As of December 31, 2022, we had no accrued interest and penalties related to uncertain tax positions. We do not expect any material changes to the estimated amount of liability associated with our uncertain tax positions within the next 12 months.

On March 27, 2020, the Coronavirus Aid, Relief and Economic Security Act (“CARES Act”) was enacted and signed into law in response to the COVID-19 pandemic. The CARES Act includes changes to the tax provisions that benefits business such as the Employee Retention Credit (“ERC”). The ERC provides an eligible employer with a tax credit that is allowed against certain employment taxes. We qualified for federal government assistance through the ERC provisions for the period between January 1, 2021 and September 30, 2021. We recognize government grants when there is reasonable assurance of compliance with grant conditions and receipt of the credits. As of December 31, 2022, we expect one-time refunds totaling $6.0 million, which are included in the consolidated balance sheets as prepaid expenses and other current assets, as well as in the consolidated statements of operations and comprehensive loss as an offset to the related employee expenses within research and development, general and administrative, and sales and marketing expenses.

Beginning January 1, 2022, the Tax Cuts and Jobs Act (the “Tax Act”) eliminated the option to deduct research and development expenditures in the current year and requires taxpayers to capitalize such expenses pursuant to IRC Section 174. The capitalized expenses are amortized over a 5-year period for domestic expenses and over a 15-year period for foreign expenses. As a result of this provision of the Tax Act, deferred tax assets related to capitalized research expenses increased by $21 million.

- 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.

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+ Details

Summary of Significant Accounting Policies - Percentage of Net Product Sales and Accounts Receivable Balance (Details) - Customer Concentration Risk	12 Months Ended
	Dec. 31, 2022
Revenue Benchmark \| Largest Customer
Product Information [Line Items]
Concentration risk percentage	43.50%
Revenue Benchmark \| Second Largest Customer
Product Information [Line Items]
Concentration risk percentage	36.40%
Revenue Benchmark \| Third Largest Customer
Product Information [Line Items]
Concentration risk percentage	18.80%
Revenue Benchmark \| Total Customer
Product Information [Line Items]
Concentration risk percentage	98.70%
Accounts Receivable \| Largest Customer
Product Information [Line Items]
Concentration risk percentage	51.60%
Accounts Receivable \| Second Largest Customer
Product Information [Line Items]
Concentration risk percentage	32.50%
Accounts Receivable \| Third Largest Customer
Product Information [Line Items]
Concentration risk percentage	15.00%
Accounts Receivable \| Total Customer
Product Information [Line Items]
Concentration risk percentage	99.10%

Consolidated Statements of Stockholders' Equity - USD ($) shares in Thousands, $ in Thousands	Total	Private Placement	Common Stock	Common Stock Private Placement	Additional Paid-In Capital	Additional Paid-In Capital Private Placement	Accumulated Other Comprehensive Income (Loss)	Accumulated Deficit
Balance at Dec. 31, 2020	$ 236,492		$ 913		$ 1,628,070		$ 257	$ (1,392,748)
Balance (in shares) at Dec. 31, 2020			91,310
Conversion benefit included in Convertible Notes issued	230				230
Issuance of common stock under Employee Stock Purchase Plan	2,139		$ 2		2,137
Issuance of common stock under Employee Stock Purchase Plan (in shares)			175
Issuance of common stock under equity incentive plan	4,926		$ 5		4,921
Issuance of common stock under equity incentive plan (in shares)			476
Issuance of common stock on exercise of warrants			$ 2		(2)
Issuance of common stock on exercise of warrants (in shares)			195
Issuance of common stock on conversion of Convertible Notes	7,878		$ 98		7,780
Issuance of common stock on conversion of notes (in shares)			9,849
Stock-based compensation expense	46,851				46,851
Net loss	(220,683)							(220,683)
Net unrealized gain (loss) on short-term investments	(263)						(263)
Comprehensive loss	(220,946)
Balance at Dec. 31, 2021	77,570		$ 1,020		1,689,987		(6)	(1,613,431)
Balance (in shares) at Dec. 31, 2021			102,005
Issuance of common stock under Employee Stock Purchase Plan	1,444		$ 4		1,440
Issuance of common stock under Employee Stock Purchase Plan (in shares)			407
Issuance of common stock under equity incentive plan	(1,530)		$ 6		(1,536)
Issuance of common stock under equity incentive plan (in shares)			614
Issuance of common stock in a private placement		$ 75,145		$ 161		$ 74,984
Issuance of common stock in a private placement (in shares)				16,129
Stock-based compensation expense	42,980				42,980
Net loss	(182,024)							(182,024)
Net unrealized gain (loss) on short-term investments	(13)						(13)
Comprehensive loss	(182,037)
Balance at Dec. 31, 2022	$ 13,572		$ 1,191		$ 1,807,855		$ (19)	$ (1,795,455)
Balance (in shares) at Dec. 31, 2022			119,155

Equity Incentive Plans - Summary of Stock Option Plan Activity (Details)	12 Months Ended
	Dec. 31, 2022 $ / shares shares
Share Based Compensation Arrangement By Share Based Payment Award [Line Items]
Number of shares outstanding	18,943,937
Number of shares granted	5,296,547
Number of shares exercised	0
Number of shares cancelled	(3,491,135)
Number of shares outstanding	20,749,349
Number of shares outstanding, weighted average exercise price \| $ / shares	$ 18.71
Number of shares granted, weighted average exercise price \| $ / shares	3.11
Number of shares cancelled, weighted average exercise price \| $ / shares	19.40
Number of shares outstanding, weighted average exercise price \| $ / shares	$ 14.61
Restricted Stock Units
Share Based Compensation Arrangement By Share Based Payment Award [Line Items]
Number of shares outstanding	2,803,193
Number of shares granted	1,831,508
Number of shares released	(899,966)
Number of shares forfeited	(567,338)
Number of shares outstanding	3,167,397
Number of shares outstanding, weighted average grant date fair value \| $ / shares	$ 11.51
Number of shares granted, weighted average grant date fair value \| $ / shares	2.73
Number of shares released, weighted average grant date fair value \| $ / shares	11.45
Number of shares forfeited, weighted average grant date fair value \| $ / shares	11.47
Number of shares outstanding, weighted average grant date fair value \| $ / shares	$ 6.46

Revenue Recognition - Summary of Activity to Product Returns, Distributor Fees and Discounts, Rebates and Administrative Fees (Details) $ in Thousands	12 Months Ended
	Dec. 31, 2022 USD ($)
Product Information [Line Items]
Balance	$ 22,560
Provision	181,083
Payments/credits	(170,326)
Balance	33,317
Product Returns
Product Information [Line Items]
Balance	2,579
Provision	1,546
Payments/credits	(789)
Balance	3,336
Distributor Fees
Product Information [Line Items]
Balance	3,466
Provision	21,153
Payments/credits	(20,439)
Balance	4,180
Discounts, Rebates and Administrative Fees
Product Information [Line Items]
Balance	16,515
Provision	158,384
Payments/credits	(149,098)
Balance	$ 25,801

Fair Value Measurements - Additional Information (Details) - USD ($)	12 Months Ended
	Dec. 31, 2022	Dec. 31, 2021
Fair Value Disclosures [Abstract]
Financial instruments transferred among fair value hierarchy levels	$ 0
Cash equivalents included of available-for-sale securities	1,500,000	$ 4,500,000
Available for sale securities with contractual maturities of three months to one year.	$ 69,500,000	$ 67,000,000.0

Stockholders' Equity (Tables)

12 Months Ended

Dec. 31, 2022

Equity [Abstract]

Summary of Common Stock Reserved for Future Issuance

Shares of our common stock reserved for future issuance as of December 31, 2022 were as follows:


	Number of
	Shares
Stock options outstanding		20,749
Restricted stock units outstanding		3,167
Stock options available for grant		985
Employee Stock Purchase Plan		645
Shares of common stock underlying warrants		8,548
Shares of common stock underlying convertible notes outstanding (see Note 8)		9,819
Total shares reserved for future issuance		43,913

Equity Incentive Plan - Additional Information (Details) - USD ($) $ / shares in Units, $ in Millions	1 Months Ended											12 Months Ended
	May 31, 2022	Jun. 30, 2021	Jun. 30, 2019	Jun. 30, 2017	Jun. 30, 2016	May 31, 2015	May 31, 2014	Jun. 30, 2011	May 31, 2010	May 31, 2009	Dec. 31, 2007	Dec. 31, 2022	Dec. 31, 2021	Dec. 31, 1997
Class Of Stock [Line Items]
Common stock, shares, issued, total												119,155,000	102,005,000
Common stock, capital shares reserved for future issuance												43,913,000
Share-based compensation arrangement by share-based payment award, number of shares available for grant												985,000
Share-based compensation arrangement by share-based payment award, expiration period												10 years
Share-based compensation arrangement by share-based payment award, award vesting period												4 years
Share-based compensation arrangement by share-based payment award, options, exercisable, weighted average remaining contractual term												6 years 4 months 24 days
Share-based compensation arrangement by share-based payment award, options, exercises in period												0
Share-based compensation arrangement by share-based payment award, options, exercises in period, intrinsic value													$ 0.7
Share-based compensation arrangement by share-based payment award, options, outstanding, intrinsic value												$ 0.0	$ 1.7
Common stock future issuance on exercise of outstanding options and vesting of outstanding restricted stock units granted												23,916,746
Total unrecognized compensation cost related to non-vested, stock-based payment awards												$ 51.9
Total unrecognized compensation cost, expect to recognize over weighted average period												1 year 10 months 24 days
Restricted Stock Units
Class Of Stock [Line Items]
Share-based compensation arrangement by share-based payment award, award vesting period												4 years
Share-based Payment Arrangement, Option
Class Of Stock [Line Items]
Share-based compensation arrangement by share-based payment award, options, forfeitures in period												1,227,682
Share-based compensation arrangements by share-based payment award, options, forfeitures in period, weighted average exercise price												$ 15.57
Share-based compensation arrangement by share-based payment award, options, expirations in period												2,263,453
Share-based compensation arrangements by share-based payment award, options, expirations in period, weighted average exercise price												$ 21.47
Expected life												6 years	6 years
Employee Stock Purchase Plan
Class Of Stock [Line Items]
Share-based compensation arrangement by share-based payment award, number of shares authorized														10,000
Share-based compensation arrangement by share-based payment award, number of additional shares authorized	850,000	200,000	300,000	200,000	100,000	100,000	25,000	25,000		10,000	5,000	1,825,000
Share-based compensation arrangement by share-based payment award maximum employee earnings with held to purchase common stock percent												10.00%
Share-based compensation arrangement by share-based payment award discount on stock price												85.00%
Share-based compensation arrangement by share-based payment award, shares issued in period												406,421	175,228
Share-based compensation arrangements by share-based payment award, options, exercises in period, weighted average exercise price												$ 3.55	$ 12.21
Common stock, shares, issued, total												1,180,399
Common stock, capital shares reserved for future issuance												644,601
Share-based compensation arrangement by share-based payment award, options, grants in period, weighted average grant date fair value												$ 1.71	7.10
Share-based compensation arrangement by share-based payment award, per share weighted-average fair value price of shares purchased												$ 1.65	$ 3.64
Expected life												6 months
Equity Incentive Plan 2007
Class Of Stock [Line Items]
Share-based compensation arrangement by share-based payment award, number of shares authorized											150,000
Share-based compensation arrangement by share-based payment award, number of additional shares authorized	2,900,000	2,000,000	7,000,000	5,000,000	3,000,000	4,300,000	1,750,000	4,500,000	100,000			30,700,000
Share-based compensation arrangement by share-based payment award, number of shares available for grant												985,119

Income Taxes - Additional Information (Details) - USD ($)	12 Months Ended
	Dec. 31, 2022	Dec. 31, 2021	Dec. 31, 2020
Operating Loss Carryforwards [Line Items]
Deferred Tax Assets, Tax Credit Carryforwards, Research	$ 60,245,000	$ 55,789,000
Unrecognized Tax Benefits, Ending Balance	11,235,000	$ 9,631,000	$ 7,406,000
Unrecognized Tax Benefits, Income Tax Penalties and Interest Accrued, Total	$ 0
Tax cuts and jobs act, capitalize expense of amortized period for domestic expenses	5 years
Tax cuts and jobs act, capitalize expense of amortized period for foreign expenses	15 years
Tax cuts and jobs act, increased capitalized research expenses	$ 21,000,000
Employee Retention Credit
Operating Loss Carryforwards [Line Items]
Expected one-time refund amount	6,000,000.0
Domestic Tax Authority
Operating Loss Carryforwards [Line Items]
Operating Loss Carryforwards, Total	1,300,000,000
Expiring Operating Loss Carryforwards	$ 542,700,000
Net operating loss carryforwards expiration year	2023
Indefinite Operating Loss Carryforwards	$ 718,200,000
Taxable income limitation percentage for operating loss carryforward	80.00%
Deferred Tax Assets, Tax Credit Carryforwards, Research	$ 49,300,000
Research and development credit carryforwards expiration year	2023
State and Local Jurisdiction
Operating Loss Carryforwards [Line Items]
Operating Loss Carryforwards, Total	$ 891,700,000
Net operating loss carryforwards expiration year	2028
Deferred Tax Assets, Tax Credit Carryforwards, Research	$ 22,200,000

Equity Incentive Plan - Summary of Fair Value of Option Grant and ESPP Purchase Right on Grant Date Using Black-Scholes Option Pricing Model (Details)	12 Months Ended
	Dec. 31, 2022	Dec. 31, 2021
Share-based Payment Arrangement, Option
Share Based Compensation Arrangement By Share Based Payment Award [Line Items]
Risk-free interest rate	3.30%	1.10%
Dividend yield	0.00%	0.00%
Volatility	62.00%	62.60%
Expected life	6 years	6 years
Employee Stock Purchase Plan
Share Based Compensation Arrangement By Share Based Payment Award [Line Items]
Risk-free interest rate	3.20%	0.10%
Dividend yield	0.00%	0.00%
Volatility	83.80%	46.90%
Expected life	6 months	6 months

Commitments and Contingencies - Summary of Future Minimum Lease Payments (Details) $ in Thousands	Dec. 31, 2022 USD ($)
Commitments and Contingencies Disclosure [Abstract]
2023	$ 2,969
2024	3,030
2025	3,097
Total future minimum lease payments	9,096
Less: discount	(903)
Total lease liabilities	$ 8,193

Commitments and Contingencies - Additional Information (Details) $ in Millions	12 Months Ended
	Dec. 31, 2022 USD ($) ft²	Dec. 31, 2021 USD ($)	Oct. 31, 2021 ft²
Lessee Lease Description [Line Items]
Purchase obligations due in one year	$ 38.7
Purchase obligations due in two to three year	65.0
Operating lease, rent expense	2.8	$ 3.7
Total purchase obligations	$ 103.7
Maximum
Lessee Lease Description [Line Items]
Purchase obligations due period	3 years
Minimum
Lessee Lease Description [Line Items]
Purchase obligations due period	2 years
Sublease Agreement
Lessee Lease Description [Line Items]
Area of real estate property \| ft²			23,873
San Diego, California
Lessee Lease Description [Line Items]
Area of real estate property \| ft²	52,148
Lease expiration date	Dec. 31, 2025
Lessee, operating lease, renewal term	5 years
Remaining area of real estate property \| ft²	28,275		28,275
Lessee, operating lease, existence of option to extend	true
Operating lease cash payments	$ 2.9