0001628280-22-004226 | 10-K | XBRL Viewer

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BALANCE SHEETS - USD ($) $ in Thousands	Dec. 31, 2021	Dec. 31, 2020
Current assets:
Cash and cash equivalents	$ 72,428	$ 91,032
Short-term investments	44,261	95,452
Accounts receivable	502	0
Prepaid expenses and other current assets	16,458	8,202
Total current assets	133,649	194,686
Property and equipment, net	2,362	1,936
Long-term investments	0	2,114
Right-of-use assets	12,752	2,274
Other assets	1,150	552
Total assets	149,913	201,562
Current liabilities:
Accounts payable	4,277	5,626
Accrued compensation and benefits	5,422	5,672
Current portion of operating lease liability	3,492	2,117
Loan payable, current portion	32,264	4,167
Deferred revenue	0	4,177
Accrued expenses and other current liabilities	7,366	6,657
Total current liabilities	52,821	28,416
Operating lease liability, net of current portion	9,748	413
Loan payable, net of current portion	0	46,621
Deferred revenue, non-current	4,727	0
Total liabilities	67,296	75,450
Commitments and contingencies
Stockholders’ equity:
Preferred stock, $0.0001 par value; 5,000,000 shares authorized; no shares issued and outstanding as of December 31, 2021 and December 31, 2020, respectively.	0	0
Common stock, $0.0001 par value; 300,000,000 shares authorized; 130,182,535 and 93,599,975 shares issued and outstanding as of December 31, 2021 and December 31, 2020, respectively.	13	9
Additional paid-in capital	795,540	680,872
Accumulated deficit	(712,930)	(554,765)
Accumulated other comprehensive income (loss)	(6)	(4)
Total stockholders’ equity	82,617	126,112
Total liabilities and stockholders’ equity	$ 149,913	$ 201,562

BALANCE SHEETS (Parenthetical) - $ / shares	Dec. 31, 2021	Dec. 31, 2020
Statement of Financial Position [Abstract]
Preferred stock, par value (in dollars per share)	$ 0.0001	$ 0.0001
Preferred stock, shares authorized	5,000,000	5,000,000
Preferred stock, shares issued	0	0
Preferred stock, shares outstanding	0	0
Common stock, par value (in dollars per share)	$ 0.0001	$ 0.0001
Common stock, shares authorized	300,000,000	300,000,000
Common stock, shares issued	130,182,535	93,599,975
Common stock, shares outstanding	130,182,535	93,599,975

STATEMENTS OF OPERATIONS AND COMPREHENSIVE LOSS - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2021	Dec. 31, 2020	Dec. 31, 2019
Revenues:
Total revenues	$ 10,097	$ 7,571	$ 5,281
Operating expenses:
Cost of revenue	1,000	145	600
Research and development	91,140	65,053	71,677
General and administrative	72,303	33,153	24,267
Total operating expenses	164,443	98,351	96,544
Loss from operations	(154,346)	(90,780)	(91,263)
Interest expense	(4,502)	(5,099)	(5,726)
Other income, net	687	1,568	2,352
Loss before provision for income taxes	(158,161)	(94,311)	(94,637)
Provision for income taxes	4	2	303
Net loss	$ (158,165)	$ (94,313)	$ (94,940)
Net loss per common share - basic (in dollars per share)	$ (1.52)	$ (1.05)	$ (1.47)
Net loss per common share - diluted (in dollars per share)	$ (1.52)	$ (1.05)	$ (1.47)
Shares used in computing net loss per share - basic	104,205,645	89,582,138	64,478,066
Shares used in computing net loss per share - diluted	104,205,645	89,582,138	64,478,066
Comprehensive loss:
Net loss	$ (158,165)	$ (94,313)	$ (94,940)
Unrealized (losses) gains on available-for-sale securities	(2)	(24)	58
Comprehensive loss	(158,167)	(94,337)	(94,882)
Collaborative development revenue
Revenues:
Total revenues	4,177	5,364	459
Product supply revenue
Revenues:
Total revenues	907	1,501	322
Licensing revenue
Revenues:
Total revenues	$ 5,013	$ 706	$ 4,500

STATEMENTS OF STOCKHOLDERS' EQUITY - USD ($) $ in Thousands	Total	Underwritten public offering	Private placement	Common Stock	Common Stock Underwritten public offering	Common Stock Private placement	Additional Paid-In Capital	Additional Paid-In Capital Underwritten public offering	Additional Paid-In Capital Private placement	Accumulated Deficit	Accumulated Other Comprehensive (Loss) Income
Balance at Dec. 31, 2018	$ 115,813			$ 6			$ 481,357			$ (365,512)	$ (38)
Balance (in shares) at Dec. 31, 2018				62,516,627
Issuance of common stock under employee stock purchase plan	396						396
Issuance of common stock under employee stock purchase plan (in shares)				160,744
Issuance of common stock for services	312						312
Issuance of common stock for services (in shares)				113,136
Issuance of common stock upon exercise of options	178						178
Issuance of common stock upon exercise of options (in shares)				68,062
Issuance of common stock upon vesting of restricted stock units (in shares)				85,609
Stock-based compensation	9,936						9,936
Unrealized (losses) gains on available-for-sale securities	58										58
Issuance of common stock		$ 134,927	$ 19,975		$ 3			$ 134,924	$ 19,975
Issuance of common stock (in shares)					23,000,000	2,873,563
Net loss	(94,940)									(94,940)
Balance at Dec. 31, 2019	186,655			$ 9			647,078			(460,452)	20
Balance (in shares) at Dec. 31, 2019				88,817,741
Issuance of common stock under employee stock purchase plan	834						834
Issuance of common stock under employee stock purchase plan (in shares)				169,931
Issuance of common stock for services	310						310
Issuance of common stock for services (in shares)				42,403
Issuance of common stock upon exercise of options	1,020						1,020
Issuance of common stock upon exercise of options (in shares)				445,942
Issuance of common stock upon vesting of restricted stock units (in shares)				866,528
Stock-based compensation	10,583						10,583
Unrealized (losses) gains on available-for-sale securities	(24)										(24)
Issuance of common stock	21,047			$ 0			21,047
Issuance of common stock (in shares)				3,257,430
Net loss	(94,313)									(94,313)
Balance at Dec. 31, 2020	126,112			$ 9			680,872			(554,765)	(4)
Balance (in shares) at Dec. 31, 2020				93,599,975
Issuance of common stock under employee stock purchase plan	819						819
Issuance of common stock under employee stock purchase plan (in shares)				386,664
Issuance of common stock for services	190						190
Issuance of common stock for services (in shares)				25,989
Issuance of common stock upon exercise of options	$ 584						584
Issuance of common stock upon exercise of options (in shares)	331,310			331,310
Issuance of common stock upon vesting of restricted stock units (in shares)				167,158
Taxes paid for net share settlement of equity awards	$ (106)						(106)
Stock-based compensation	12,039						12,039
Unrealized (losses) gains on available-for-sale securities	(2)										(2)
Issuance of common stock	101,146			$ 4			101,142
Issuance of common stock (in shares)				35,671,439
Net loss	(158,165)									(158,165)
Balance at Dec. 31, 2021	$ 82,617			$ 13			$ 795,540			$ (712,930)	$ (6)
Balance (in shares) at Dec. 31, 2021				130,182,535

STATEMENTS OF CASH FLOWS - USD ($) $ in Thousands	12 Months Ended
STATEMENTS OF CASH FLOWS - USD ($) $ in Thousands	Dec. 31, 2021	Dec. 31, 2020	Dec. 31, 2019
Operating activities
Net loss	$ (158,165)	$ (94,313)	$ (94,940)
Adjustments to reconcile net loss to net cash used in operating activities:
Depreciation expense	1,441	1,824	2,501
Amortization of deferred financing costs	638	496	670
Amortization of deferred compensation for services	240	313	309
Amortization of (discount) premium on investment securities	488	(92)	(698)
Non-cash lease expense	3,085	2,147	1,839
Stock-based compensation	12,039	10,583	9,936
Change in derivative liabilities	(678)	407	436
Non-cash interest associated with debt discount accretion	283	413	478
Changes in operating assets and liabilities:
Unbilled revenue	0	750	4,250
Accounts receivable	(502)	0	85
Prepaid expenses and other assets	(8,904)	(4,653)	93
Accounts payable	(1,349)	3,439	39
Accrued compensation and benefits	(250)	1,219	1,730
Operating Lease liabilities	(2,853)	(2,604)	(1,892)
Accrued and other liabilities	1,386	(1,000)	(5,861)
Deferred revenue	550	(364)	4,541
Net cash used in operating activities	(152,551)	(81,435)	(76,484)
Investing activities
Proceeds from maturities and redemptions of investments	125,550	119,734	126,369
Purchases of investments	(72,735)	(150,852)	(102,671)
Purchases of property and equipment	(1,867)	(324)	(325)
Net cash provided by (used in) investing activities	50,948	(31,442)	23,373
Financing activities
Proceeds from underwritten public offering, net of issuance costs	0	0	134,927
Proceeds from issuance of common stock upon private placement, net of issuance costs	0	0	19,975
Proceeds from issuance of common stock in At-the-market offering, net of issuance costs	101,146	21,047	0
Proceeds from issuance of common stock under equity incentive and stock purchase plans	1,403	1,854	574
Principal repayments for loan payable	(19,444)	0	0
Payments for loan payable, net of issuance costs	0	(125)	0
Payments for taxes related to net share settlement of equity awards	(106)	0	0
Net cash provided by financing activities	82,999	22,776	155,476
Net (decrease) increase in cash and cash equivalents	(18,604)	(90,101)	102,365
Cash and cash equivalents at beginning of period	91,032	181,133	78,768
Cash and cash equivalents at end of period	72,428	91,032	181,133
Supplementary disclosure of cash flow information:
Cash paid for interest	3,469	4,200	4,920
Cash paid for income taxes	4	1	2
Supplementary disclosure of non-cash activities:
Right-of-use assets obtained in exchange for lease obligations	1,604	450	5,810
Issuance of common stock for services	$ 190	$ 310	$ 312

Organization and Basis of Presentation	12 Months Ended
Organization and Basis of Presentation	Dec. 31, 2021
Organization, Consolidation and Presentation of Financial Statements [Abstract]
Organization and Basis of Presentation	ORGANIZATION AND BASIS OF PRESENTATION Ardelyx, Inc. (the “Company,” “we,” “us” or “our”) is a biopharmaceutical company founded with a mission to discover, develop and commercialize innovative first-in-class medicines that meet significant unmet medical needs. This includes adult patients with irritable bowel syndrome with constipation (“IBS-C”), adult patients with chronic kidney disease (“CKD”) on dialysis suffering from elevated serum phosphorus, or hyperphosphatemia; and adult CKD patients and/or heart failure patients with elevated serum potassium, or hyperkalemia. We operate in one business segment, which is the development and planned commercialization of biopharmaceutical products.

Summary of Significant Accounting Policies	12 Months Ended
Summary of Significant Accounting Policies	Dec. 31, 2021
Accounting Policies [Abstract]
Summary of Significant Accounting Policies	SUMMARY OF SIGNIFICANT ACCOUNTING POLICIES Basis of Presentation The accompanying financial statements have been prepared in accordance with accounting principles generally accepted in the United States of America (“U.S. GAAP”). Prior Period Errors In connection with our review of our financial statements as of and for the six months ended June 30, 2019, we corrected errors related to the accounting for clinical trial accruals that had resulted in an overstatement of research and development expenses during the year ended December 31, 2018. Specifically, management concluded that our research and development expenses recorded during the year ended December 31, 2018 had been overstated by $3.6 million and that our accrued expenses and other current liabilities as of December 31, 2018 had been overstated by the same amount. We analyzed the potential impact of these errors in accordance with the U.S. Securities and Exchange Commission’s (“SEC”) Staff Accounting Bulletin No. 108, Considering the Effects of Prior Year Misstatements when Quantifying Misstatements in Current Year Financial Statements, and concluded that while the errors were significant to our financial statements as of and for the six months ended June 30, 2019, a correction of the errors would not have been material to the full year results for 2019 and 2018 nor affect the trend of financial results. Accordingly, we reduced accrued and other liabilities by $3.6 million and recorded a cumulative adjustment of $3.6 million in the statement of operations and comprehensive loss to reduce research and development expenses in 2019. Use of Estimates The preparation of financial statements in conformity with U.S. GAAP requires management to make estimates and judgments that affect the amounts reported in the financial statements and accompanying notes. On an ongoing basis, management evaluates its estimates, including those related to recognition of revenue, clinical trial accruals, contract manufacturing accruals, fair value of assets and liabilities, income taxes and stock-based compensation. Management bases its estimates on historical experience and on various other market-specific and relevant assumptions that management believes to be reasonable under the circumstances. Actual results could materially differ from those estimates. Liquidity As of December 31, 2021, we had cash and investments of approximately $116.7 million. We have incurred operating losses since inception and our accumulated deficit as of December 31, 2021 is $712.9 million. Our current level of cash and investments alone is not sufficient to meet our plans for the next twelve months following the issuance of these financial statements. These factors raise substantial doubt regarding our ability to continue as a going concern for a period of one year from the issuance of these financial statements. We plan to address our operating cash flow requirements with our current cash and investments, cash generated from the product launch of IBSRELA, our potential receipt of anticipated milestones from our collaboration partners, our ability to access the capital markets, as well as through the implementation of cash preservation activities to reduce or defer discretionary spending. There are no assurances that our efforts to meet our operating cash flow requirements will be successful. If our current cash and investments as well as our plans to meet our operating cash flow requirements are not sufficient to fund necessary expenditures and meet our obligations for at least the next twelve months following the issuance of these financial statements, our liquidity, financial condition and business prospects will be materially affected. These financial statements have been prepared on a going concern basis and do not include any adjustments to the amounts and classification of assets and liabilities that may be necessary in the event that we can no longer continue as a going concern. Cash and Cash Equivalents We consider all highly liquid investments purchased with an original maturity date of 90 days or less on the date of purchase to be cash equivalents. Short-Term Investments Short-term investments consist of debt securities classified as available-for-sale and have maturities greater than 90 days, but less than one year, from the date of acquisition. Short-term investments are carried at fair value based upon quoted market prices. Unrealized gains and losses on available-for-sale securities are included in earnings and are reported as an allowance for credit losses on our Balance Sheets. The cost of available-for-sale securities sold is based on the specific-identification method. Concentration of Credit Risk Financial instruments that potentially subject us to significant concentrations of credit risk consist primarily of cash, cash equivalents, short-term investments and accounts receivable. We are exposed to credit risks in the event of default by the counterparties to the extent of the amount recorded in its balance sheet. Cash, cash equivalents and short-term investments are invested through banks and other financial institutions in the U.S. Foreign Currency We manage our foreign currency exposures with the use of foreign currency purchases. We primarily conduct business in U.S. dollars; however, a portion of our expense and capital activities are transacted in foreign currencies which are subject to exchange rate fluctuations that can affect cash or earnings. We have been in a loss position and therefore our primary objective is to conserve and manage cash. There are generally two methods by which we may manage the cash flow risk of foreign exchange fluctuations when a contract is signed (i) we can purchase the foreign funds, in full or in part, upon the execution of the contract, or (ii) we can obtain the right to purchase such funds, in full or in part, at the execution of the contract, i.e., obtain a forward contract from an appropriate bank, that can be exercised to obtain the currency of interest at a particular point in time. The derivative instruments that we may use to hedge the exposure shall generally not be designated as cash flow hedges, and as a result, changes in their fair value would be recorded in other income (expense), net, in our statements of operations and comprehensive loss. The fair values of forward foreign currency exchange contracts would be estimated using current exchange rates and interest rates and the current creditworthiness of the counterparties is taken into consideration. Property and Equipment Property and equipment are stated at cost, less accumulated depreciation and amortization. Depreciation is computed using the straight-line method over the estimated useful lives of the respective assets, with ranges generally from three to five years. Leasehold improvements are amortized over the lesser of the estimated useful lives or the related remaining lease term. Impairment of Long-Lived Assets The carrying value of long-lived assets, including property and equipment, are reviewed for impairment whenever events or changes in circumstances indicate that the asset may not be recoverable. An impairment loss is recognized when the total of estimated future undiscounted cash flows, expected to result from the use of the asset and its eventual disposition, are less than the asset’s carrying amount. Impairment, if any, would be assessed using discounted cash flows or other appropriate measures of fair value. For the years ending December 31, 2021, 2020 and 2019 we have recognized no impairment losses. Income Taxes We use the asset and liability method of accounting for income taxes. Under this method, deferred tax assets and liabilities are determined based on the differences between the financial reporting and the tax bases of assets and liabilities and are measured using the enacted tax rates and laws that will be in effect when the differences are expected to reverse. A valuation allowance is provided when it is more likely than not that some portion or all of a deferred tax asset will not be realized. Revenue Recognition On January 1, 2018 we adopted the Financial Accounting Standards Board’s (“FASB”) Accounting Standards Update (“ASU”) No. 2014-9, Revenue from Contracts with Customers (Topic 606) and related amendments (“ASC 606”), on a modified retrospective basis, which resulted in an adjustment to the opening accumulated deficit balance on the adoption date. As a result of the adoption of the new standard, on January 1, 2018, we recorded the following: (i) unbilled revenue under current assets of $5.0 million representing a future receivable related to the first milestone under our license agreement with Kyowa Kirin Co., Ltd. (formerly known as Kyowa Hakko Kirin Co., Ltd ("KHK") (“KKC”), which was subsequently achieved by KKC and collected in February 2019, thereby reducing the unbilled revenue balance to zero, (ii) uncharged license fees under current liabilities of $1.0 million representing the corresponding future payable related to AstraZeneca AB ("AstraZeneca") in accordance with our termination agreement with AstraZeneca, which, upon KKC achieving the milestone, was reclassified to accounts payable and subsequently paid to AstraZeneca during the second quarter of 2019, and (iii) a related decrease in accumulated deficit of approximately $4.0 million as the new standard permitted revenue from milestones that possess certain criteria to be recognized earlier and also contained different recognition criteria related to milestones than under the previous accounting standard. We generate revenue primarily from research and collaboration and license agreements with customers. Goods and services in the agreements may include the grant of licenses for the use of our technology, the provision of services associated with the research and development of product candidates, manufacturing services, and participation in joint steering committees. The terms of these arrangements typically include payment to us of one or more of the following: non-refundable, up-front license fees; research, development, regulatory and commercial milestone payments; reimbursement of research and development services; option payments; reimbursement of certain costs; payments for manufacturing supply services; and future royalties on net sales of licensed products. When two or more contracts are entered into with the same customer at or near the same time, we evaluate the contracts to determine whether the contracts should be accounted for as a single arrangement. Contracts are combined and accounted for as a single arrangement if one or more of the following criteria are met: (i) the contracts are negotiated as a package with a single commercial objective; (ii) the amount of consideration to be paid in one contract depends on the price or performance of the other contract; or (iii) the goods or services promised in the contracts (or some goods or services promised in each of the contracts) are a single performance obligation. In determining the appropriate amount of revenue to be recognized as we fulfill our obligations under each of its agreements, management performs the following steps: (i) identification of the promised goods or services in the contract; (ii) determination of whether the promised goods or services are performance obligations including whether they are distinct in the context of the contract; (iii) measurement of the transaction price, including the constraints on variable consideration; (iv) allocation of the transaction price to the performance obligations; and (v) recognition of revenue when (or as) we satisfy each performance obligation. As part of the accounting for contracts with customers, we develop assumptions that require judgment to determine whether promised goods and services represent distinct performance obligations and the standalone selling price for each performance obligation identified in the contract. This evaluation is subjective and requires us to make judgments about the promised goods and services and whether those goods and services are separable from other aspects of the contract. Further, determining the standalone selling price for performance obligations requires significant judgment, and when an observable price of a promised good or service is not readily available, we consider relevant assumptions to estimate the standalone selling price, including, as applicable, market conditions, development timelines, probabilities of technical and regulatory success, reimbursement rates for personnel costs, forecasted revenues, potential limitations to the selling price of the product and discount rates. We apply judgment in determining whether a combined performance obligation is satisfied at a point in time or over time, and, if over time, concluding upon the appropriate method of measuring progress to be applied for purposes of recognizing revenue. We evaluate the measure of progress each reporting period and, as estimates related to the measure of progress change, related revenue recognition is adjusted accordingly. Changes in our estimated measure of progress are accounted for prospectively as a change in accounting estimate. We recognize collaboration revenue by measuring the progress toward complete satisfaction of the performance obligation using an input measure. In order to recognize revenue over the research and development period, we measure actual costs incurred to date compared to the overall total expected costs to satisfy the performance obligation. Revenues are recognized as the program costs are incurred. We will re-evaluate the estimate of expected costs to satisfy the performance obligation each reporting period and make adjustments for any significant changes. Amounts received prior to satisfying the revenue recognition criteria are recorded as contract liabilities in our Balance Sheets. If the related performance obligation is expected to be satisfied within the next twelve months it will be classified in current liabilities. Amounts recognized as revenue prior to receipt are recorded as contract assets in our Balance Sheets. If we expect to have an unconditional right to receive the consideration in the next twelve months, it will be classified in current assets. A net contract asset or liability is presented for each contract with a customer. Milestone Payments: At the inception of each arrangement that includes development milestone payments, we evaluate whether the milestones are considered probable of being reached and estimates the amount to be included in the transaction price using the most likely amount method. Amounts of variable consideration are included in the transaction price to the extent that it is probable that a significant reversal in the amount of cumulative revenue recognized will not occur and when the uncertainty associated with the variable consideration is subsequently resolved. Milestone payments that are not within our control or the control of the licensee, such as regulatory approvals, are not considered probable of being achieved until those approvals are received. The transaction price is then allocated to each performance obligation on a relative standalone selling price basis, for which we recognize revenue as or when the performance obligations under the contract are satisfied. At the end of each subsequent reporting period, we re-evaluate the probability of achievement of such development milestones and any related constraints, and if necessary, adjusts its estimate of the overall transaction price. Any such adjustments are recorded on a cumulative catch-up basis, which would affect earnings in the period of adjustment. Manufacturing supply services: Arrangements that include a promise for future supply of drug substance or drug product for either clinical development or commercial supply at the customer’s discretion are generally considered as options. We assess if these options provide a material right to the licensee and if so, they are accounted for as separate performance obligations. If we are entitled to additional payments when the customer exercises these options, any payments are recorded in product supply revenue when the customer obtains control of the goods, which is upon delivery. Royalties: For arrangements that include sales-based royalties, including milestone payments based on the level of sales, and where the license is deemed to be the predominant item to which the royalties relate, we recognize revenue at the later of (i) when the related sales occur, or (ii) when the performance obligation to which some or all of the royalty has been allocated has been satisfied (or partially satisfied). To date, we have not recognized any royalty revenue resulting from any of its licensing arrangements. Licenses of intellectual property: If a license granted to a customer to use our intellectual property is determined to be distinct from the other performance obligations identified in the arrangement, we recognize revenue from consideration allocated to the license when the license is transferred to the licensee and the licensee is able to use and benefit from the license. For licenses that are bundled with other promises, we apply judgment to assess the nature of the combined performance obligation to determine whether the combined performance obligation is satisfied over time or at a point in time and, if over time, to conclude upon the appropriate method of measuring progress for purposes of recognizing revenue related to consideration allocated to the performance obligation. Options: Customer options, such as options granted to allow a licensee to choose to research, develop and commercialize licensed compounds are evaluated at contract inception in order to determine whether those options provide a material right (i.e., an optional good or service offered for free or at a discount) to the customer. If the customer options represent a material right, the material right is treated as a separate performance obligation at the outset of the arrangement. The Company allocates the transaction price to material rights based on the standalone selling price, and revenue is recognized when or as the future goods or services are transferred or when the option expires. Customer options that are not material rights do not give rise to a separate performance obligation, and as such, the additional consideration that would result from a customer exercising an option in the future is not included in the transaction price for the current contract. Instead, the option is deemed a marketing offer, and additional option fee payments are recognized or being recognized as revenue when the licensee exercises the option. The exercise of an option that does not represent a material right is treated as a separate contract for accounting purposes. Contract modifications: Contract modifications, defined as changes in the scope or price (or both) of a contract that are approved by the parties to the contract, such as a contract amendment, exist when the parties to a contract approve a modification that either creates new or changes existing enforceable rights and obligations of the parties to the contract. Depending on facts and circumstances, we account for a contract modification as one of the following: (i) a separate contract; (ii) a termination of the existing contract and a creation of a new contract; or (iii) a combination of the preceding treatments. A contract modification is accounted for as a separate contract if the scope of the contract increases because of the addition of promised goods or services that are distinct and the price of the contract increases by an amount of consideration that reflects our standalone selling prices of the additional promised goods or services. When a contract modification is not considered a separate contract and the remaining goods or services are distinct from the goods or services transferred on or before the date of the contract modification, we account for the contract modification as a termination of the existing contract and a creation of a new contract. When a contract modification is not considered a separate contract and the remaining goods or services are not distinct, we account for the contract modification as an add-on to the existing contract and as an adjustment to revenue on a cumulative catch-up basis. We receive payments from its licensees as established in each contract. Upfront payments and fees are recorded as deferred revenue upon receipt or when due and may require deferral of revenue recognition to a future period until we perform our obligations under these arrangements. Where applicable, amounts are recorded as accounts receivable or unbilled revenue when our right to consideration is unconditional. We do not assess whether a contract with a customer has a significant financing component if the expectation at contract inception is such that the period between payment by the licensees and the transfer of the promised goods or services to the licensees will be one year or less. Research and Development Costs Research and development costs are charged to expense as incurred and consisted of costs incurred to further our research and development activities and include salaries and related employee benefits, costs associated with clinical trials, costs related to pre-commercialization manufacturing activities such as manufacturing process validation activities and the manufacturing of clinical drug supply, nonclinical research and development activities, regulatory activities, research-related overhead expenses and fees paid to external service providers and contract research and manufacturing organizations that conduct certain research and development activities on our behalf. Accrued Research and Development Expenses We are required to estimate our accrued expenses at the end of each reporting period. This process involves reviewing open contracts and purchase orders, communicating with our personnel to identify services that have been performed on our behalf and estimating the level of service performed and the associated cost incurred for the service when we have not yet been invoiced or otherwise notified of the actual costs. The majority of our service providers submit invoices in arrears for services performed or when contractual milestones are met. We make estimates of our accrued expenses as of each balance sheet date in the financial statements based on facts and circumstances known to us at that time. We periodically confirm the accuracy of our estimates with our service providers and make adjustments if necessary. Examples of estimated accrued research and development expenses include fees paid to: •contract research organizations ("CROs") in connection with clinical studies; •investigative sites in connection with clinical studies; •vendors related to product manufacturing, development and distribution of clinical supplies; and •vendors in connection with preclinical development activities. We record expenses related to clinical studies and manufacturing development activities based on our estimates of the services received and efforts expended pursuant to contracts with multiple CROs and manufacturing vendors that conduct and manage these activities on our behalf. The financial terms of these agreements are subject to negotiation, vary from contract to contract, and may result in uneven payment flows. There may be instances in which payments made to our vendors will exceed the level of services provided and result in a prepayment of the expense. Payments under some of these contracts depend on factors such as the successful enrollment of subjects and the completion of clinical trial milestones. In accruing service fees, we estimate the time period over which services will be performed, enrollment of subjects, number of sites activated and the level of effort to be expended in each period. If the actual timing of the performance of services or the level of effort varies from our estimate, we will adjust the accrued or prepaid expense balance accordingly. Inventory We consider regulatory approval of product candidates to be uncertain, and product manufactured prior to regulatory approval may not be sold unless regulatory approval is obtained. We expense manufacturing costs for product candidates incurred prior to regulatory approval as research and development expenses as manufacturing processes are performed. If and when regulatory approval of a product is obtained and we have plans to commercially launch the approved product, we begin capitalizing manufacturing costs related to the approved product into inventory. Although we received approval of IBSRELA (tenapanor) for the treatment of IBS-C in adults from the Food and Drug Administration (“FDA”) in September 2019, we did not plan to launch IBSRELA commercially at that time and, therefore, continued to expense manufacturing costs of tenapanor, which is also under development for another indication that has not received FDA approval. On November 30, 2021, we made the decision and announced our plans to commercially launch IBSRELA and as a result, in December 2021 we began to capitalize the costs of manufacturing processes associated with IBSRELA as those processes are completed. No manufacturing processes related to IBSRELA were completed in December, resulting in no inventory balance at December 31, 2021. Stock-Based Compensation We recognize compensation expense for all stock-based payment awards made to employees, nonemployees and directors based on estimated fair values. For employee and nonemployee stock options, we determine the grant date fair value of the awards using the Black-Scholes option-pricing model and generally recognizes the fair value as stock-based compensation expense on a straight-line basis over the vesting period of the respective awards. For restricted stock and performance-based restricted stock, to the extent they are probable, the compensation cost for these awards is based on the closing price of our common stock on the date of grant and recognized as compensation expense on a straight-line basis over the requisite service period. Stock-based compensation expense is based on the value of the portion of stock-based payment awards that is ultimately expected to vest. As such, our stock-based compensation is reduced for the estimated forfeitures at the date of grant and revised, if necessary, in subsequent periods if actual forfeitures differ from those estimates. Derivatives and Hedging Activities We account for our derivative instruments as either assets or liabilities on the balance sheet and measure them at fair value. Derivatives are adjusted to fair value through other income (expense), net in the statements of operations and comprehensive loss. Leases We determine if an arrangement is a lease at the inception of the arrangement. Operating leases are included in right-of-use assets, current portion of operating lease liability, and operating lease liability, net of current portion in our balance sheets. Right-of-use assets represent our right to use an underlying asset for the lease term and lease liabilities represent our obligation to make lease payments arising from the lease. Operating lease right-of-use assets and liabilities are recognized at the lease commencement date based on the present value of lease payments over the lease term. In determining the present value of lease payments, we use our incremental borrowing rate based on the information available at the lease commencement date. The operating lease right-of-use assets also include any lease payments made and exclude lease incentives. Our lease terms may include options to extend or terminate the lease when it is reasonably certain that we will exercise any such options. Lease expense is recognized on a straight-line basis over the expected lease term. We have elected not to separate lease and non-lease components, such as common area maintenance charges, and instead it accounts for these as a single lease component. Restructuring We recognize restructuring charges related to reorganization plans that have been committed to by management when liabilities have been incurred. In connection with these activities, we record restructuring charges at fair value for, (a) contractual employee termination benefits when obligations are associated to services already rendered, rights to such benefits have vested, and payment of benefits is probable and can be reasonably estimated, (b) one-time employee termination benefits when management has committed to a plan of termination, the plan identifies the employees and their expected termination dates, the details of termination benefits are complete, it is unlikely changes to the plan will be made or the plan will be withdrawn and communication to such employees has occurred, and (c) contract termination costs when a contract is terminated before the end of its term. One-time employee termination benefits are recognized in their entirety when communication has occurred and future services are not required. If future services are required, the costs are recorded ratably over the remaining period of service. Contract termination costs to be incurred over the remaining contract term without economic benefit are recorded in their entirety when the contract is canceled. Net Loss per Share Basic net loss per common share is calculated by dividing the net loss by the weighted-average number of common shares outstanding during the period, without consideration of potential common shares. Diluted net loss per common share in the periods presented is the same as basic net loss per common share, since the effects of potentially dilutive securities are antidilutive due to the net loss for all periods presented. Recent Accounting Pronouncements New Accounting Pronouncements - Recently Adopted In December 2019, as part of its initiative to reduce complexity in the accounting standards, the Financial Accounting Standards Board (“FASB”) issued Accounting Standards Update (“ASU”) 2019-12, Income Taxes (Topic 740): Simplifying the Accounting for Income Taxes (“ASU 2019-12”), which eliminates certain exceptions related to the approach for intra-period tax allocation, the methodology for calculating income taxes in an interim period and the recognition of deferred tax liabilities for outside basis differences. ASU 2019-12 also clarifies and simplifies other aspects of the accounting for income taxes. The standard is effective for fiscal years, and interim periods within those fiscal years, beginning after December 15, 2020, with early adoption permitted. We early adopted ASU 2019-12 on April 1, 2020 and this adoption had no material impact on our financial position or results of operations. We adopted Accounting Standards Update 2016-13, Financial Instruments - Credit Losses: Measurement of Credit Losses on Financial Instruments ("ASU 2016-13"), as of December 1, 2021 under the modified retrospective approach. ASU 2016-13 requires an entity to measure and recognize expected credit losses for certain financial instruments, including trade receivables, as an allowance that reflects the entity's current estimate of credit losses expected to be incurred. For available-for-sale debt securities with unrealized credit losses, the standard requires allowances to be recorded through net income instead of directly reducing the amortized cost of the investment under the previous other-than-temporary impairment model. The adoption of this standard did not have a material impact on our financial statements or a significant impact on our internal controls. Recent Accounting Pronouncements Not Yet Adopted There were various accounting standards and interpretations issued recently, none of which are expected to a have a material impact on our financial position, operations or cash flows.

Cash and Investments

12 Months Ended

Dec. 31, 2021

Cash and Cash Equivalents [Abstract]

Cash and Investments

CASH AND INVESTMENTS

Securities classified as cash and investments as of December 31, 2021 and 2020 are summarized below (in thousands). Estimated fair value is based on quoted market prices for these investments.


	December 31, 2021
			Gross Unrealized
	Amortized Cost		Gains		Losses		Fair Value
Cash and cash equivalents:
Money market funds	$	71,175	$	—	$	—	$	71,175

Cash	1,253		—		—		1,253
Total cash and cash equivalents	72,428		—		—		72,428
Short-term investments:
Commercial paper	$	31,936	$	1	$	(2)	$	31,935
Corporate bonds	7,025		—		(3)		7,022
Asset-backed securities	5,306		—		(2)		5,304
U.S. treasury notes	—		—		—		—
Total short-term investments	44,267		1		(7)		44,261


Total cash equivalents and investments	$	116,695	$	1	$	(7)	$	116,689


	December 31, 2020
			Gross Unrealized
	Amortized Cost		Gains		Losses		Fair Value
Cash and cash equivalents:
Money market funds	$	88,151	$	—	$	—	$	88,151
Commercial paper	2,100		—		—		2,100

Cash	781		—		—		781
Total cash and cash equivalents	91,032		—		—		91,032
Short-term investments
Commercial paper	$	60,631	$	2	$	(4)	$	60,629
Corporate bonds	24,547		3		(6)		24,544
U.S. government-sponsored agency bonds	9,277		2		—		9,279
U.S. treasury notes	1,000		—		—		1,000
Total short-term investments	95,455		7		(10)		95,452
Long-term investments:
Corporate bonds	$	2,115	$	—	$	(1)	$	2,114
Total cash equivalents and investments	$	188,602	$	7	$	(11)	$	188,598

Cash equivalents consist of money market funds and other debt securities with original maturities of three months or less at the time of purchase, and the carrying amount is a reasonable approximation of fair value. We invest our cash in high quality securities of financial and commercial institutions. These securities are carried at fair value, which is based on readily available market information, with unrealized gains and losses included in accumulated other comprehensive income (loss) within stockholders’ equity on ours balance sheets. We use the specific identification method to determine the amount of realized gains or losses on sales of marketable securities. Realized gains or losses have been insignificant and are included in other income (expense), net, in the statement of operations.

All short-term available-for-sale securities held as of December 31, 2021 and 2020, had contractual maturities of less than one year. The long-term securities held as of December 31, 2020 had contractual maturities greater than one year. Our available-for-sale securities are subject to a periodic impairment review. We consider a debt security to be impaired when its fair value is less than its carrying cost, in which case we would further review the investment to determine whether it is other-than-temporarily impaired. When we evaluate an investment for other-than-temporary impairment, we review factors such as the length of time and extent to which fair value has been below cost basis, the financial condition of the issuer and any changes thereto, intent to sell, and whether it is more likely than not we will be required to sell the investment before the recovery of its cost basis. If an investment is other-than-temporarily impaired, we write it down through the statement of operations to its fair value and establishes that value as a new cost basis for the investment. We did not identify any of its available-for-sale securities as other-than-temporarily impaired in any of the periods presented. As of December 31, 2021 and 2020, no investment was in a continuous unrealized loss position for more than one year and we believe that it is more likely than not that the investments will be held until maturity or a forecasted recovery of fair value.

As of December 31, 2021, the amortized cost and estimated fair value of available-for-sale debt securities by contractual maturity were as follows (in thousands):


	Amortized Cost		Fair Value
Due in one year or less	$	44,267	$	44,261

Fair Value Measurements

12 Months Ended

Dec. 31, 2021

Fair Value Disclosures [Abstract]

Fair Value Measurements

FAIR VALUE MEASUREMENTSFair 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 three-level hierarchy for the inputs to valuation techniques is briefly summarized as follows:

Level 1 – Valuations are based on quoted prices in active markets for identical assets or liabilities and readily accessible by the Company at the reporting date. Examples of assets and liabilities utilizing Level 1 inputs are certain money market funds, U.S. treasuries and trading securities with quoted prices on active markets.

Level 2 – Valuations based on 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. Examples of assets and liabilities utilizing Level 2 inputs are corporate bonds, commercial paper, certificates of deposit and over-the-counter derivatives.

Level 3 – Valuations based on unobservable inputs in which there is little or no market data, which require the Company to develop its own assumptions.

The following table sets forth the fair value of our financial assets and liabilities measured on a recurring basis by level within the fair value hierarchy (in thousands):


	December 31, 2021
	Total Fair Value		Level 1		Level 2		Level 3
Assets:
Money market funds	$	71,175	$	71,175	$	—	$	—
Commercial paper	31,935		—		31,935		—
Corporate bonds	7,022		—		7,022		—
Asset-backed securities	5,304		—		5,304		—

Total	$	115,436	$	71,175	$	44,261	$	—

Liabilities:
Derivative liability for exit fee	$	698	$	—	$	—	$	698
Total	$	698	$	—	$	—	$	698


	December 31, 2020
	Total Fair Value		Level 1		Level 2		Level 3
Assets:
Money market funds	$	88,151	$	88,151	$	—	$	—
Commercial paper	62,729		—		62,729		—
Corporate bonds	26,658		—		26,658		—
U.S. government-sponsored agency bonds	9,279		—		9,279		—
U.S. treasury notes	1,000		—		1,000		—
Total	$	187,817	$	88,151	$	99,666	$	—

Liabilities:
Derivative liability for exit fee	$	1,376	$	—	$	—	$	1,376
Total	$	1,376	$	—	$	—	$	1,376

Where quoted prices are available in an active market, securities are classified as Level 1. We classify money market funds, U.S. treasury securities and U.S. treasury notes as Level 1. When quoted market prices are not available for the specific security, we estimate fair value by using benchmark yields, reported trades, broker/dealer quotes and issuer spreads. We classify corporate bonds, commercial paper, asset-backed securities and foreign currency derivative contracts as Level 2. In certain cases, where there is limited activity or less transparency around inputs to valuation, securities or derivative liabilities such as the 2018 Exit Fee, as defined and discussed in Note 7 - Derivative Liability, are classified as Level 3.

The carrying amounts reflected in the balance sheets for cash equivalents, short-term investments, accounts receivable, prepaid expenses and other current assets, accounts payable and accrued expenses approximate their fair values at both December 31, 2021 and December 31, 2020, due to their short-term nature.

Based on our procedures under the expected credit loss model, including an assessment of unrealized losses in our portfolio, we concluded that any unrealized losses on our marketable securities were not attributable to credit and, therefore, we have not recorded an allowance for credit losses for these securities as of December 31, 2021 and 2020.

Fair Value of Debt

The interest rate of our term loan facility approximates the rate at which we could obtain alternative financing. Therefore, the carrying amount of the term loan facility approximated its fair value at December 31, 2021 and 2020.

- 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

Collaboration and Licensing Agreements

12 Months Ended

Dec. 31, 2021

Collaboration and Licensing Agreements [Abstract]

Collaboration and Licensing Agreements

COLLABORATION AND LICENSING AGREEMENTS

Kyowa Kirin Co., Ltd. (2019 KKC Agreement)

In November 2019, we entered into a research collaboration and option agreement with KKC (the "2019 KKC Agreement”), to undergo research to identify two preclinical study-ready compounds for designation as development compounds, with one compound inhibiting the first undisclosed target (“Program 1”) and a second inhibiting the second undisclosed target (“Program 2”). Pursuant to the 2019 KKC Agreement, upon completion of the research and designation by the research steering committee of one or more development candidates (“DCs”), KKC has the right to execute one or more separate collaborative agreements relating to the development and commercialization of one or both DCs in certain specified territories.

Under the terms of the 2019 KKC Agreement, KKC agreed to pay us a non-refundable, non-creditable upfront fee of $10.0 million, which was payable as follows: the first installment of $5.0 million within 30 days of the Effective Date, and the second installment of $5.0 million on the first anniversary of the effective date, unless the 2019 KKC Agreement was earlier terminated by KKC due to material breach by us. The term of the 2019 KKC Agreement commenced on November 11, 2019 (“the Effective Date”) and ends on the earliest of: (a) two years following the Effective Date, or (b) the nomination of a program DC for both programs, (c) or the nomination of one program DC and the decision by the parties to cease research for the other program, (d) or the decision by the parties to cease research for both programs. We assessed the 2019 KKC Agreement in accordance with ASC 606 and concluded that the contract’s counterparty, KKC, is a customer. Management also considered the modification guidance prescribed in ASC 606 and concluded that the 2019 KKC Agreement should be accounted for as a separate contract from the 2017 KKC Agreement, as defined and discussed below.

We identified various promises in the 2019 KKC Agreement, including the grant of an initial research license, the Program 1 research, the Program 2 research, the right to obtain certain development and commercialization rights with Program 1 in certain territories and the right to obtain development and commercialization rights with Program 2 in certain territories, and participation in a joint steering committee (“the JSC”) and determined that KKC could not benefit from either of the research programs without the research license and participation in the JSC. As such, the combined license, research programs and participation in the JSC were deemed to be the highest level of goods and services that can be deemed distinct for each of the Program 1 research and Program 2 research. We concluded that the options to obtain additional development and commercialization rights that are exercisable by KKC under certain circumstances are not performance obligations of the contract at inception because the option fees reflect the standalone selling price of the options, and therefore, the options are not considered to be material rights.

At the outset of the 2019 KKC Agreement, we determined that the initial transaction price was $10.0 million and that revenue associated with the combined performance obligations should be recognized as services are provided using the input method. Since transfer of control occurs over time, in management’s judgment this input method is the best measure of progress towards satisfying the performance obligations and reflects a faithful depiction of the transfer of goods and services. Revenue will be recognized over the Program 1 and Program 2 research periods. Management will re-evaluate the estimates related to the transaction price at the end of each reporting period and as uncertain events are resolved or other changes in circumstances occur and adjust the timing of revenue recognition as necessary.

During the years ended December 31, 2021 and 2020, we recognized $4.2 million and $5.4 million, respectively, as revenue under the 2019 KKC Agreement in the statement of operations and comprehensive loss. The aggregate amount of the transaction price allocated to our partially unsatisfied performance obligations as of December 31, 2021 and 2020 was zero and $4.2 million, which was presented in the Balance Sheet as deferred revenue for each respective period. As of December 31,

2021, we have no material future obligations under the 2019 KKC Agreement. There were no significant changes in estimates associated with the 2019 KKC Agreement during the twelve months ended December 31, 2021.

2017 KKC Agreement

In November 2017, we entered into an exclusive license agreement with KKC (the "2017 KKC Agreement") for the development, commercialization and distribution of tenapanor in Japan for cardiorenal indications. We granted KKC an exclusive license to develop and commercialize certain sodium hydrogen exchanger 3 ("NHE3") inhibitors, including tenapanor in Japan for the treatment of cardiorenal diseases and conditions, excluding cancer. We retained the rights to tenapanor outside of Japan, and also retained the rights to tenapanor in Japan for indications other than those stated above. Pursuant to the License Agreement, KKC is responsible for all of the development and commercialization costs for tenapanor in treatment of cardiorenal diseases and conditions, excluding cancer in Japan. Under the 2017 KKC Agreement, we are responsible for supplying the tenapanor drug product for KKC’s use in development and during commercialization until KKC has assumed such responsibility. Additionally, we are responsible for supplying the tenapanor drug substance for KKC’s use in development and commercialization throughout the term of the 2017 KKC Agreement, provided that KKC may exercise an option to manufacture the tenapanor drug substance under certain conditions

We assessed these arrangements in accordance with ASC 606 and concluded that the contract counterparty, KKC, is a customer. Under the terms of the 2017 KKC Agreement, we received $30.0 million in up-front license fees which was recognized as revenue when the agreement was executed. Based on our assessment, we identified that the license and the manufacturing supply services were our material performance obligations at the inception of the agreement, and as such each of the performance obligations are distinct. Additionally, on January 1, 2018, we recorded unbilled revenue under current assets of $5.0 million and an increase in uncharged license fees under current liabilities of $1.0 million related to the first milestone under the 2017 KKC Agreement that KKC achieved in February 2019, reflecting revenues and cost of revenue, respectively, that would have been recognized in the fourth quarter 2017 if we had adopted ASC 606 prior to January 1, 2018. On KKC’s achievement of the milestone in February 2019, the balance related to unbilled revenue was adjusted to zero. Correspondingly, the $1.0 million balance related to uncharged license fees that we owed to AstraZeneca was reclassified to accounts payable during the first quarter of 2019, and subsequently paid to AstraZeneca during the second quarter of 2019.

In addition to the up-front license fee received of $30.0 million, we may be entitled to receive up to $55.0 million in total development milestones, of which $10.0 million has been received to date, ¥8.5 billion Japanese yen for commercialization milestones, or approximately $73.9 million at the currency exchange rate on December 31, 2021, as well as reimbursement of cost, plus a reasonable overhead for the supply of product and high-teen royalties on net sales throughout the term of the agreement. The variable consideration related to the remaining development milestone payments has not been included in the transaction price as these were fully constrained at December 31, 2021.

For the years ended December 31, 2021 and 2020, $0.9 million and $1.4 million, respectively, of product supply revenue was recorded for manufacturing supply of tenapanor and other materials to KKC for product development and clinical trials in Japan, in accordance with our agreement with KKC, including $0.5 million accounts receivable as of December 31, 2021

For the years ended December 31, 2021 and 2020, $5.0 million and zero, respectively, of licensing revenue was recorded. The 2021 licensing revenue was recorded upon the initiation of phase 3 clinical studies by KKC in Japan to evaluate tenapanor for hyperphosphatemia.

During the twelve months ended December 31, 2021, we received a $3.2 million prepayment from KKC for the manufacturing of tenapanor drug substance. In addition, we have unbilled prepayments of $1.5 million from KKC for the manufacturing of tenapanor drug product reflected within prepaid and other current assets. Both amounts are reflected within our deferred revenue, non-current on our balance sheet as of December 31, 2021.

Shanghai Fosun Pharmaceutical Industrial Development Co. Ltd. , or Fosun Pharma

In December 2017, we entered into an exclusive license agreement with Fosun Pharma (the "Fosun Agreement") for the development, commercialization and distribution of tenapanor in China for both hyperphosphatemia and IBS-C. We assessed these arrangements in accordance with ASC 606 and concluded that the contract counterparty, Fosun Pharma, is a customer. Under the terms of the Fosun Agreement, we received $12.0 million in up-front license fees which was recognized as revenue when the agreement was executed. Based on our assessment, we identified that the license and the manufacturing supply services were its material performance obligations at the inception of the agreement, and as such each of the performance obligations are distinct.

In addition, we may be entitled to additional development and commercialization milestones of up to $110.0 million, as well as reimbursement of cost plus a reasonable overhead for the supply of product and tiered royalties on net sales ranging from the mid-teens to 20%. The variable consideration related to the remaining development milestone payments has not been included in the transaction price as these were fully constrained at December 31, 2021 and 2020.

For the years ended December 31, 2021 and 2020, no revenue was recorded related to the Fosun Agreement.

Knight Therapeutics, Inc.

In March 2018, we entered into an exclusive license agreement with Knight Therapeutics, Inc., (the "Knight Agreement") for the development, commercialization and distribution of tenapanor in Canada for hyperphosphatemia and IBS-C. We assessed these arrangements in accordance with ASC 606 and concluded that the contract counterparty, Knight, is a customer. Based on our assessment, it identified that the license and the manufacturing supply services were its material performance obligations at the inception of the agreement, and as such each of the performance obligations are distinct.

Under the terms of the agreement, we received a $2.3 million nonrefundable, one-time upfront payment in March 2018 and are eligible to receive additional development and commercialization milestone payments worth up to CAD22.2 million, or $17.4 million at the currency exchange rate on December 31, 2021, reimbursement of supply costs on a schedule specifying cost per tablet, with a reasonable mark up for overhead, as well as tiered royalty rates on net sales ranging from the mid-single digits to the low twenties. The variable consideration related to the remaining development milestone payments has not been included in the transaction price as these were fully constrained at December 31, 2021 and 2020.

For the years ended December 31, 2021 and 2020, $13 thousand and $0.7 million of licensing revenue was recorded, respectively, related to the Knight Agreement. For the years ended December 31, 2021 and 2020, zero and $0.1 million product supply revenue was recorded, respectively, related to the Knight Agreement. Pursuant to the AstraZeneca Termination Agreement, $1.0 million and $0.1 million of cost of revenue was recorded during 2021 and 2020, respectively.

Xuanzhu (HK) Biopharmaceutical Limited, or XuanZhu

In November 2019, we entered into a license agreement with XuanZhu (“the XuanZhu Agreement") for a license to certain specific patent and patent applications. We assessed these arrangements in accordance with ASC 606 and concluded that the contract counterparty, XuanZhu, is a customer. Under the terms of the XuanZhu Agreement, we recognized $1.5 million in license fees when the agreement was executed, of which, $0.8 million was received upfront in November 2019 and achievement for the second $0.8 million payment was determined to be not materially at risk and probable of achievement and it was included in the transaction price as the amount was not probable of revenue reversal. Based on our assessment, we determined that we had one combined performance obligation, which is the license and the specific patent grant.

In addition to the license fee of $1.5 million, we may be entitled to receive milestone payments. The variable consideration related to the remaining milestone payments has not been included in the transaction price as these were fully constrained at December 31, 2021 and 2020.

For the years ended December 31, 2021 and 2020, no license revenue was recorded related to the XuanZhu Agreement.

AstraZeneca

In June 2015, we entered into a termination agreement with AstraZeneca (the "AstraZeneca Termination Agreement") pursuant to which we remain liable to pay AstraZeneca license fees for (i) future royalties at a royalty rate of 10% of net sales of tenapanor or other NHE3 products by us or our licensees, and (ii) 20% of non-royalty revenue received from a licensee of tenapanor or certain other NHE3 inhibitors, up to a maximum of $75.0 million in aggregate for (i) and (ii).

To date in aggregate, we have recognized $11.6 million of the $75.0 million, recorded as cost of revenue, as follows (in thousands):


	Cost of Revenue
	Recognized			Amount Paid
Year 2017	$	9,400	*	$	6,000
Year 2018	466			2,864
Year 2019	600			1,002
Year 2020	145			742
Year 2021	1,000			1,003
Total	$	11,611		$	11,611
Maximum payment per termination agreement				75,000
Remaining potential commitment				$	63,389

* Includes $1.0 million adjustment recorded pursuant to the adoption of ASC 606, as discussed in Note 2.

Deferred Revenue

The following tables present changes in our current and non-current deferred revenue balances during the reporting period. The current deferred revenue balance is attributable entirely to the 2019 KKC Agreement and the non-current deferred revenue balance is attributable entirely to the 2017 KKC Agreement (in thousands):


Deferred revenue - current	2021		2020
Balance at Balance at January 1,	$	4,177	$	4,541

Decreases due to revenue recognized in the period for which cash has been received	(4,177)		(364)

Balance at Balance at December 31,	$	—	$	4,177


Deferred revenue - non-current	2021		2020
Balance at Balance at January 1,	$	—	$	—
Increases due to cash received during the period	3,242		—
Increase due to unbilled prepayments recorded during the period	1,485		—

Balance at Balance at December 31,	$	4,727	$	—

Borrowings

12 Months Ended

Dec. 31, 2021

Debt Disclosure [Abstract]

Borrowings

BORROWINGS

Solar Capital and Western Alliance Bank Loan Agreement

On May 16, 2018, we entered into a loan and security agreement (the "2018 Loan Agreement"), with Solar Capital Ltd. and Western Alliance Bank (the "Lenders”). The 2018 Loan Agreement provides for a $50.0 million term loan facility with a maturity date of November 1, 2022 (the "2018 Term Loan”). The full amount of the 2018 Term Loan was funded on May 16, 2018. We received net proceeds from the loan of approximately $49.3 million, after deducting the closing fee, legal expenses and issuance costs. On October 9, 2020, we and the Lenders entered into an amendment to the 2018 Loan Agreement (“the 2020 Amendment”) to extend the date through which we were permitted to make interest-only payments on the 2018 Term Loan by twelve months to December 1, 2021 subject to the repayment terms noted below.

Borrowings under the 2018 Term Loan bear interest at a floating per annum rate equal to 7.45% plus the one-month London Inter-bank Offered Rate ("LIBOR"). We were permitted to make interest-only payments on the 2018 Term Loan through June 1, 2020, or until we achieved our primary endpoint in the Phase 3 study of tenapanor for the treatment of hyperphosphatemia in end-stage renal disease patients on dialysis prior to June 1, 2020, in which case we would have been permitted to make interest-only payments on the 2018 Term Loan through December 1, 2020. On December 3, 2019, we reported positive topline results for PHREEDOM, a long-term Phase 3 study evaluating the efficacy and safety of tenapanor as monotherapy for the treatment of hyperphosphatemia in adult patients with CKD on dialysis. The Lenders were in agreement that these positive data from the Phase 3 PHREEDOM study achieve the “Phase 3 Endpoint” required by the 2018 Term Loan to extend the interest only period by six months to December 1, 2020. Subsequent to the 2020 Amendment, the interest only period was extended an additional twelve months to December 1, 2021. Accordingly, beginning on December 1, 2021 through

the maturity date, we would have been required to make monthly payments of interest plus repayment of the 2018 Term Loan in consecutive equal monthly installments of principal. If however, either the FDA did not approve our NDA for tenapanor for control of serum phosphorus in adult patients with CKD on dialysis on or before May 31, 2021 or the FDA issued a Complete Response Letter ("CRL") for tenapanor for the control of serum phosphorus in adult CKD on dialysis, then we would begin principal payments on the earlier of June 1, 2021 or the first day of the month immediately following the date that the FDA issued a CRL to us.

In May and July 2021, we and the Lenders entered into additional amendments to the 2018 Loan Agreement (“the 2021 Amendments”) which together extended the period of time that we were permitted to make interest-only payments on the 2018 Term Loan to December 1, 2021; provided that if we had not received FDA approval for our NDA for tenapanor for the control of serum phosphorus in adult patients with CDK on dialysis on or before October 25, 2021, the interest-only period would expire and principal repayments would be required to begin on November 1, 2021. If principal repayments were required to begin prior to December 1, 2021 under the 2021 Amendments, then the first such repayment was required include all payments that would have been due if monthly principal repayment had begun on June 1, 2021. Accordingly, during November 2021, in compliance with the terms of our 2018 Loan Agreement, we paid the first principal repayment on the 2018 Term Loan in the amount of $16.7 million and have paid all other subsequently due principal payments through December 31, 2021.

We paid a closing fee of $0.5 million, upon the closing of the 2018 Term Loan and $0.1 million upon closing of the 2020 Amendment. Under the 2018 Term Loan, we were obligated to pay a final fee equal to 3.95% of the 2018 Term Loan upon the earliest to occur of the maturity date, the acceleration of the 2018 Term Loan, the prepayment or repayment of the 2018 Term Loan or the termination of the 2018 Loan Agreement. Under the 2020 Amendment, the final fee was increased to 4.95% of the 2018 Term Loan. We may voluntarily prepay the outstanding 2018 Term Loan, subject to a prepayment premium of (i) 3% of the principal amount of the 2018 Term Loan if prepaid prior to or on the first anniversary of the Closing Date, (ii) 2% of the principal amount of the 2018 Term Loan if prepaid after the first anniversary of the Closing Date through and including the second anniversary of the Closing Date, or (iii) 1% of the principal amount of the 2018 Term Loan if prepaid after the second anniversary of the Closing Date and prior to the maturity date. The 2018 Term Loan is secured by substantially all of our assets, except for our intellectual property and certain other customary exclusions. Additionally, in connection with the 2018 Term Loan, we entered into the 2018 Exit Fee Agreement, as discussed in Note 7 - Derivative Liability.

The 2018 Loan Agreement contains customary representations and warranties and customary affirmative and negative covenants, including restrictions on payment of dividends for our common stock. As of December 31, 2021, we were in compliance with all of the covenants set forth in the 2018 Loan Agreement.

In addition, the 2018 Loan Agreement contains customary events of default that entitle the Lender to cause our indebtedness under the 2018 Loan Agreement to become immediately due and payable, and to exercise remedies against us and the collateral securing the 2018 Term Loan, including its cash. Upon the occurrence and for the duration of an event of default, an additional default interest rate equal to 4.0% per annum will apply to all obligations owed under the 2018 Loan Agreement. As of December 31, 2021, to our knowledge, there were no facts or circumstances in existence that would give rise to an event of default.

As discussed in Note 18 - Subsequent Events, on February 23, 2022 (the “Closing Date”), we entered into a loan and security agreement (the “2022 Loan Agreement”) with SLR Investment Corp. as collateral agent (the “Agent”), and the lenders listed in the 2022 Loan Agreement (collectively the “2022 Lenders”). The 2022 Loan Agreement provides for a senior secured term loan facility, with $27.5 million (the “Term A Loan”) funded on the Closing Date and an additional $22.5 million that we may borrow on or prior to July 25, 2023; provided that (i) we have received approval by the FDA for our NDA for tenapanor the control of serum phosphorus in chronic kidney disease patients on dialysis by December 31, 2022, and (ii) we have achieved certain product revenue milestone targets described in the 2022 Loan Agreement (the “Term B Loan”, and collectively, the Term A Loan and the Term B Loan, the “2022 Term Loan”). The Term A Loan funds are being used to repay the Term Loan with the Lenders as discussed in Note 6 - Borrowings and to fund our ongoing operations. We had $25.0 million principal from the 2018 Term Loan outstanding as of the Closing Date. We have continued to classify the 2018 Term Loan balance as a current liability as of December 31, 2021 due to the determination of the existence of substantial doubt about our ability to continue operating as a going concern discussed in Note 2 – Summary of Significant Accounting Policies and our assessment that the material adverse change clause under the 2022 Loan Agreement is not within the Company's control. The lender has not invoked the material adverse change clause as of the date of issuance of these financial statements.

As of December 31, 2021, prior to restructuring our debt as discussed in Note 18 - Subsequent Events, our future payment obligations towards the 2018 Term Loan principal and final fee, excluding interest payments and the 2018 Exit Fee were as follows (in thousands):


2022	$	33,031

Total repayment obligations	$	33,031
Less: Unamortized discount and debt issuance costs	(235)
Less: Unaccreted value of final fee	(532)
Loan payable	32,264
Less: Loan payable, current portion	(32,264)
Loan payable, net of current portion	$	—

Subsequent to restructuring the 2018 Term Loan, we will have no debt repayment obligations in 2022 or 2023. We will be required to repay $6.9 million, $9.2 million, $9.2 million, and $2.3 million in Term A Loan principal repayments per year during 2024, 2025, 2026 and 2027, respectively, as well as a final fee in the amount of $1.4 million in 2027.

- 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.

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+ Details

Derivative Liability

12 Months Ended

Dec. 31, 2021

Derivative Instruments and Hedging Activities Disclosure [Abstract]

Derivative Liability

DERIVATIVE LIABILITY

Exit Fee

In May 2018, in connection with entering into the 2018 Loan Agreement, as defined and discussed in Note 6 - Borrowing, we entered into an agreement pursuant to which we agreed to pay $1.5 million in cash (the "2018 Exit Fee") upon any change of control transaction in respect of the Company or if we obtain both (i) FDA approval of tenapanor for the treatment of hyperphosphatemia in adult patients with CKD on dialysis and (ii) FDA approval of tenapanor for the treatment of patients with IBS-C, which was obtained on September 12, 2019 when the FDA approved IBSRELA, a 50 mg, twice daily oral pill for the treatment of IBS-C in adults (the “2018 Exit Fee Agreement”). Notwithstanding the prepayment or termination of the 2018 Term Loan, our obligation to pay the 2018 Exit Fee will expire on May 16, 2028. We concluded that the 2018 Exit Fee is a freestanding derivative which should be accounted for at fair value on a recurring basis. The estimated fair value of the 2018 Exit Fee is recorded as a derivative liability and included in accrued expense and other current liabilities on the accompanying balance sheets.

The fair value of the derivative liability was determined using a discounted cash flow analysis and is classified as a Level 3 measurement within the fair value hierarchy since our valuation utilized significant unobservable inputs. Specifically, the key assumptions included in the calculation of the estimated fair value of the derivative instrument include: i) our estimates of both the probability and timing of a potential $1.5 million payment to Solar Capital Ltd. and Western Alliance Bank as a result of the FDA approvals, and ii) a discount rate which was derived from our estimated cost of debt, adjusted with current LIBOR. Generally, increases or decreases in the probability of occurrence would result in a directionally similar impact in the fair value measurement of the derivative instrument and it is estimated that a 10% increase (decrease), not to exceed 100%, in the probability of occurrence would result in a fair value fluctuation of no more than $0.1 million.

Changes in the fair value of recurring measurements included in Level 3 of the fair value hierarchy are presented as other income (expense), net in our Statements of Operations and were as follows for the years ended December 31, 2021, 2020 and 2019 (in thousands):


	2021		2020		2019
Fair value of exit fee derivative liability at January 1	$	1,376	$	969	$	533
Change in estimated fair value of derivative liability	$	(678)	$	407	$	436
Fair value of exit fee derivative liability at December 31	$	698	$	1,376	$	969

As discussed in Note 18 - Subsequent Events, on February 23, 2022, we entered into an additional exit fee agreement with Solar whereby we agreed to pay an exit fee in the amount 2% of the 2022 Term Loan funded upon the first to occur of a specified exit event or revenue achievement event.

Leases

12 Months Ended

Dec. 31, 2021

Leases [Abstract]

Leases

LEASESWe have recorded right-of-use operating lease assets under three lease agreements. We have evaluated our facility leases and determined that, effective upon the adoption of Topic 842, the leases evaluated are all operating leases. We have performed

an evaluation of our other contracts with suppliers and collaborators in accordance with Topic 842 and have determined that, except for the facility leases described below, none of our contracts contain a lease.

We have recorded a right-of-use operating lease asset located in Fremont, California under a lease agreement entered into in September 2008 that was amended in December 2012 to extend the lease agreement to September 2016. In September 2014, we signed the second amendment to our facility lease agreement to add space and to extend the lease term through September 2019. In May 2016, we signed a third amendment to our facility lease agreement in Fremont, California to add space and to extend the lease term through September 2021 (the “Third Amendment”). During May 2021, we entered into an additional amendment to the lease for our Fremont, California facility that extended the term of the lease to March 2025. The office space consists of 72,500 square feet, which includes 10,716 square feet added in September 2019. We do not have an option to renew the lease at our current Fremont location beyond March 2025.

We have recorded a right-of-use operating lease asset located in Waltham, Massachusetts under a lease agreement entered into in October 2018. The office space consisted of 3,520 square feet with the lease terminating in September 2021. We did not renew the lease at our original Waltham, Massachusetts facility. During April 2021 and May 2021, we recorded right-of-use operating lease assets for a new facility in Waltham, Massachusetts under a lease agreement entered into during December 2020 with lease commencement dates during April and May 2021. The office space consists of 12,864 square feet with the lease terminating in June 2026. We have an option to extend the lease term for one additional five year period. This option to extend the lease term has not been included in the calculation since currently the exercise of the option is uncertain and therefore deemed not probable. We recorded a $1.6 million right-of-use asset and lease liability for the Waltham lease upon commencement of the lease.

We have recorded a right-of-use operating lease asset located in Milwaukee, Wisconsin under a lease agreement entered into in October 2020 with a lease commencement date in November 2020. The office space consists of 4,768 square feet with the lease terminating in February 2026. We have an option to extend the lease term by one additional five-year period. This option to extend the lease term has not been included in the calculation since currently the exercise of the option is uncertain and therefore deemed not probable. We recorded a $0.4 million right-of use asset and lease liability for the Milwaukee lease upon commencement of the lease.

All of our leases are operating leases and each contain customary rent escalation clauses. Certain of the leases have both lease and non-lease components. We have as elected to account for each separate lease component and the non-lease components associated with that lease component as a single lease component for all classes of underlying assets.

The following table provides additional details of the leases presented in the balance sheets (dollars in thousands):


	As of Dec 31,
Facilities	2021			2020
Right-of-use assets	$	12,752		$	2,274

Current portion of lease liabilities	3,492			2,117
Operating lease liability, net of current portion	9,748			413
Total	$	13,240		$	2,530

Weighted-average remaining life (years)	3.40			1.50
Weighted-average discount rate	6.9		%	11.7		%

The lease costs, which are included in operating expenses in our statements of operations, were as follows (in thousands):


	Year Ended December 31,
	2021		2020		2019
Operating lease expense	$	3,671	$	2,608	$	2,592
Cash paid for operating lease	$	3,438	$	3,065	$	2,645

The following table summarizes our undiscounted cash payment obligations for our operating lease liabilities as of December 31, 2021 (in thousands):


Ending December 31,
2022	$	4,292
2023	4,440
2024	4,589
2025	1,321
2026	252
Thereafter	—
Total undiscounted operating lease payments	14,894
Imputed interest expenses	(1,654)
Total operating lease liabilities	13,240
Less: Current portion of operating lease liability	(3,492)
Operating lease liability, net of current portion	$	9,748

Stockholders' Equity	12 Months Ended
Stockholders' Equity	Dec. 31, 2021
Stockholders' Equity Note [Abstract]
Stockholders' Equity	STOCKHOLDERS’ EQUITY In July 2020, we filed a Form S-3 registration statement, which became effective in August 2020, containing (i) a base prospectus for the offering, issuance and sale by us of up to a maximum aggregate offering price of $250.0 million of our common stock, preferred stock, debt securities, warrants and/or units, from time to time in one or more offerings; and (ii) a prospectus supplement for the offering, issuance and sale by us of up to a maximum aggregate offering price of $100.0 million of its common stock that may be issued and sold, from time to time, under an Open Market Sales Agreement with Jefferies LLC, as sales agent, deemed to be “at-the-market offerings” (the "2020 Open Market Sales Agreement"). Pursuant to the 2020 Open Market Sales Agreement, Jefferies, as sales agent, received a commission of up to 3.0% of the gross sales price for shares of common stock sold under the 2020 Open Market Sales Agreement. We sold 8.2 million shares of our common stock between the dates of November 13, 2020 through February 19, 2021, 4.0 million shares between the dates of May 11, 2021 through June 18, 2021, 3.3 million shares between the dates of August 24, 2021 through September 10, 2021 and 7.7 million between the dates of October 21, 2021 through December 31, 2021 for a cumulative total of 23.3 million shares and gross proceeds of $100.0 million at a weighted average sales price of approximately $4.30 per share which resulted in full utilization of the $100.0 million authorized amount under the 2020 Open Market Sales Agreement. In August 2021, we filed an additional prospectus supplement under the Registration Statement for the offering, issuance and sale by us of up to a maximum aggregate offering price of $150.0 million of our common stock that may be issued and sold, from time to time, under an additional sales agreement we entered into with Jefferies (the "2021 Open Market Sales Agreement"), pursuant to which we may, from time to time, sell up to $150.0 million in shares of our common stock through Jefferies. We are not required to sell shares under the 2021 Open Market Sales Agreement. Pursuant to the 2021 Open Market Sales Agreement, Jefferies, as our sales agent, receives a commission of up to 3.0% of the gross sales price for shares of common stock sold under the 2021 Open Market Sales Agreement. As of December 31, 2021 we have sold 15.7 million shares and received gross proceeds of $25.0 million at a weighted average sales price of approximately $1.60 per share under the 2021 Open Market Sales Agreement. On December 9, 2019, we completed an underwritten public offering of 20.0 million shares of common stock at a price of $6.25 per share before underwriting discounts and commissions (the "2019 Offering"). In connection with the 2019 Offering, we entered into an underwriting agreement, or the 2019 Underwriting Agreement, with Citigroup Global Markets Inc., Cowen and Company LLC, SVB Leerink LLC and Piper Jaffray & Co., or collectively the 2019 Underwriters, pursuant to which we granted to the 2019 Underwriters a 30-day option to purchase up to an additional 3.0 million shares of our common stock, or the 2019 Overallotment. We completed the sale of 23.0 million shares, inclusive of the 2019 Overallotment, to the 2019 Underwriters and that sale resulted in the receipt by us of aggregate gross proceeds of approximately $143.8 million, less underwriting discounts, commissions and offering expenses totaling approximately $8.9 million, which resulted in net proceeds of approximately $134.9 million. On November 22, 2019, we and KKC entered into a stock purchase agreement, pursuant to which we sold an aggregate of approximately 2.9 million shares of its common stock at $6.96 per share for net proceeds of approximately $20.0 million, or the Private Placement. The Private Placement closed on November 25, 2019.

- 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

Equity Incentive Plans

12 Months Ended

Dec. 31, 2021

Share-based Payment Arrangement [Abstract]

Equity Incentive Plans

EQUITY INCENTIVE PLANS

2008 Plan

We granted options under its 2008 Stock Incentive Plan (the “2008 Plan”) until June 2014 when it was terminated as to future awards, although it continues to govern the terms of options that remain outstanding under the 2008 Plan. The 2008 Plan provided for the granting of incentive and non-qualified stock options, and stock purchase rights to employees, directors and consultants at the discretion of the Board of Directors. Stock options granted generally vest over a period of four years from the date of grant. In connection with the Board of Directors and stockholders’ approval of the 2014 Plan, all remaining shares available for future award under the 2008 Plan were transferred to 2014 Plan, and the 2008 Plan was terminated.

2014 Plan

The 2014 Equity Incentive Award Plan (the “2014 Plan”) became effective on June 18, 2014. Under the 2014 Plan, 1.4 million shares of common stock were initially reserved for issuance pursuant to a variety of stock-based compensation awards, including stock options, stock appreciation rights ("SARs"), restricted stock awards, service-based restricted stock unit (“RSU”) awards, performance-based restricted stock unit (“PRSU”) awards, deferred stock awards, deferred stock unit awards, dividend equivalent awards, stock payment awards and performance awards. In addition, 35 thousand shares that had been available for future awards under the 2008 Plan as of June 18, 2014, were added to the initial reserve available under the 2014 Plan, bringing the total reserve upon the effective date of the 2014 Plan to 1.5 million shares. The number of shares initially reserved for issuance or transfer pursuant to awards under the 2014 Plan will be increased by (i) the number of shares represented by awards outstanding under 2008 Plan on June 18, 2014, that are either forfeited or lapse unexercised or that are repurchased for the original purchase price thereof, up to a maximum of 1.2 million shares, and (ii) if approved by the Administrator of the 2014 Plan, an annual increase on the first day of each fiscal year ending in 2024 equal to the lesser of (A) four percent (4.0%) of the shares of stock outstanding (on an as converted basis) on the last day of the immediately preceding fiscal year and (B) such smaller number of shares of stock as determined by our board of directors; provided, however, that no more than 10.7 million shares of stock may be issued upon the exercise of incentive stock options.

2016 Plan

In November 2016, our board of directors approved the 2016 Employment Commencement Incentive Plan (the “Inducement Plan”) under which 1.0 million shares were reserved. In January 2021 and 2022, 0.5 million and 2.0 million shares, respectively, were added to the Inducement Plan. As of December 31, 2021, 0.4 million shares of our common stock were subject to inducement grants that were issued pursuant to the Inducement Plan.

Stock Options

The following table summarizes activity under the 2008 Plan and the 2014 Plan, including grants issued to nonemployees, in the year ended December 31, 2021:


	Shares Available for Grant	Options Issued and Outstanding			Weighted Average Remaining Contractual Term	Aggregate Intrinsic Value
		Number of Shares	Weighted-Average Exercise Price per Share
					(in Years)	(in thousands)
Balance at December 31, 2020	1,757,058	9,790,049	$	6.76
Options authorized	4,201,766	—	$	—
Options granted	(3,409,719)	3,409,719	$	6.60
Options exercised	—	(331,310)	$	1.96
Options canceled	2,451,306	(2,451,306)	$	6.17
Issuance of common stock for services	(25,989)	—	—

Balance at December 31, 2021	4,974,422	10,417,152	$	7.00	6.57	$	—
Vested and expected to vest at December 31, 2021		10,417,152	$	7.00	6.57	$	—
Exercisable at December 31, 2021		6,772,289	$	7.39	5.58	$	—

The aggregate intrinsic value represents the difference between the total pre-tax value (i.e., the difference between our stock price and the exercise price) of stock options outstanding as of December 31, 2021, based on our common stock closing

price of $1.10 per share, which would have been received by the option holders had all their in-the-money options been exercised as of that date.

The intrinsic value of options exercised during the years ended December 31, 2021, 2020 and 2019, was $1.7 million, $2.7 million, and $0.4 million, respectively.

The weighted-average grant-date estimated fair value of options granted during the years ended December 31, 2021, 2020 and 2019 was $3.92, $4.82 and $1.79 per share, respectively. The estimated grant date fair value of employee stock options was calculated using the Black-Scholes option-pricing model, based on the following weighted-average assumptions:


	Year Ended December 31,
	2021		2020		2019
Expected term (years)	4.97		6.00		6.00
Expected volatility	77	%	83	%	81	%
Risk-free interest rate	4.69	%	1.07	%	2.42	%
Dividend yield	—	%	—	%	—	%

Expected Term—We have limited historical information to develop reasonable expectations about future exercise patterns and post-vesting employment termination behavior for its stock-option grants. As such, the expected term has been estimated using the simplified method whereby the expected term equals the arithmetic average of the vesting term and the original contractual term of the option. Beginning in 2021, we estimate the expected term of our options based upon historical exercises and post-vesting termination behavior, which has not resulted in a material difference as compared to using the simplified method.

Expected Volatility—Since January 1, 2017, we use the historic volatility of our own stock over the retrospective period corresponding to the expected remaining term of the options, or the period since our shares were first quoted on The Nasdaq Global Market, if that is shorter, to compute our expected stock price volatility.

Risk-Free Interest Rate—The risk-free interest rate assumption is based on the zero-coupon U.S. treasury instruments on the date of grant with a maturity date consistent with the expected term of our stock option grants.

Dividend Yield—To date, we have not declared or paid any cash dividends and does not have any plans to do so in the future. Therefore, we use an expected dividend yield of zero.

Restricted Stock Units

The following table summarizes restricted stock unit activity under the 2014 Plan in the year ended December 31, 2021, and includes restricted stock units with time or service-based vesting and those restricted stock units with performance-based vesting:


	Number of RSUs	Weighted-Average Grant Date Fair Value Per Share
Non-vested restricted stock units at December 31, 2020	158,626	$	5.64
Granted	4,144,051	$	2.71
Vested	(193,147)	$	6.39
Forfeited	(580,848)	$	6.38
Non-vested restricted stock units at December 31, 2021	3,528,682	$	2.04

In July 2018, we granted 0.9 million PRSUs to our employees that vested upon the achievement of certain performance conditions, subject to the employees’ continued service relationship with us through the achievement date. During 2020, we granted an additional 30 thousand PRSUs subject to the same performance conditions. All 0.9 million of these PRSUs vested in September 2020. None of these PRSUs vested during the years ended December 31, 2019 or 2018. We recognized zero and $1.2 million of related expense during the years ended December 31, 2021 and 2020, respectively.

The total estimated fair value of RSUs vested during the years ended December 31, 2021, 2020 and 2019 was $0.8 million, zero and $0.2 million, respectively.

Issuance of Common Stock for Services

During the years ended December 31, 2021, 2020 and 2019, we issued approximately 26 thousand, 42 thousand and 113 thousand shares, respectively, of common stock to members of the board of directors who elected to receive stock in lieu of their cash fees under our Non-Employee Director Compensation Program. The shares issued during the years ended December 31, 2021, 2020 and 2019 were valued at $0.2 million, $0.3 million and $0.3 million for each year, respectively, based on the fair value of the common stock on the date of grant.

Employee Stock Purchase Plan

We adopted the 2014 Employee Stock Purchase Plan (“ESPP”) and initially reserved approximately 0.2 million shares of common stock as of its effective date of June 18, 2014. If approved by the Administrator of the ESPP, on the first day of each calendar year, ending in 2024, the number of shares in the reserve will increase by an amount equal to the lesser of (i) one percent (1.0%) of the shares of common stock outstanding on the last day of the immediately preceding fiscal year and (ii) such number of shares of common stock as determined by the board of directors; provided, however, no more than $2.2 million shares of our common stock may be issued under the ESPP.

The following table summarizes our ESPP activity during the year ended December 31, 2021:


	Shares Available for Grant	Number of Shares Purchased	Average Purchase Price per Share		Gross Proceeds
					(in thousands)
Balance at December 31, 2020	349,647	661,611
Shares purchased	(386,664)	386,664	$	2.12	$	819
Balance at December 31, 2021	898,982	1,048,275

The following table illustrates the weighted-average assumptions for the Black-Scholes option-pricing model used in determining the fair value of ESPP purchase rights granted to our employees:


	Year Ended December 31,
	2021		2020		2019
Expected term (years)	0.50		0.50		0.50
Expected volatility	123	%	79	%	69	%
Risk-free interest rate	0.65	%	0.48	%	2.00	%
Dividend yield	—	%	—	%	—	%

Stock-based Compensation Expense

Total stock-based compensation recognized was as follows (in thousands):


	Year Ended December 31,
	2021		2020		2019
Research and development	$	4,116	$	4,061	$	4,104
General and administrative	7,923		6,522		5,832
Total	$	12,039	$	10,583	$	9,936

At December 31, 2021, the Company had total unrecognized stock-based compensation expense, net of estimated forfeitures, of the following (dollars in thousands):


	December 31, 2021
	Unrecognized Compensation Expense		Average Remaining Vesting Period (Years)
Stock options grant	$	14,506	2.4
RSU grants	$	2,262	0.8
ESPP	$	44	0.1

Restructuring	12 Months Ended
Restructuring	Dec. 31, 2021
Restructuring and Related Activities [Abstract]
Restructuring	RESTRUCTURING On July 29, 2021, our Board of Directors approved, and on August 2, 2021, we began implementing a restructuring plan to better align our workforce and anticipated commercial and development spend with our capital resources and the needs of our business following the receipt of the CRL. Under the restructuring plan, we reduced our workforce by 83 employees (approximately 33%). Impacted employees received cash payments equal to their base pay for a notice period of sixty (60) days and Company funded COBRA premiums through such notice period. Following the conclusion of an End of Review Type A meeting with the FDA, on October 8, 2021, our Board of Directors approved and, on October 12, 2021, we began to implement an additional restructuring plan to further reduce operating costs and better align our workforce with the needs of our business. Under the additional restructuring plan, we planned to reduce our workforce by approximately 100 of our remaining employees (approximately 60%). The impacted employees received notice that their positions would be eliminated during December 2021. On November 30, 2021, we announced plans to launch IBSRELA, our approved treatment for IBS-C in adults. In connection with the planned launch of IBSRELA, which we currently expect to commence in April 2022, we retained 28 of the employees whose positions were originally eliminated as part of the additional restructuring plan, thereby reducing the number of employees terminated as part of the restructuring plan to 72. The additional restructuring plan, which resulted in the elimination of our research organization and significantly altered our commercial sales and marketing organizations, was substantially completed in December 2021. Impacted employees were eligible to receive severance benefits and additional Company funded COBRA premiums, contingent upon an impacted employee’s execution (and non-revocation) of a separation agreement, which included a general release of claims against us. In connection with restructuring, we have incurred restructuring charges of $6.2 million, which were recorded during the twelve months ended December 31, 2021, related to one-time termination notice and severance payments and other employee-related costs. We did not incur any significant contract termination costs pursuant to restructuring. Of the charges, $2.7 million was recorded in research and development expenses, and $3.5 million was recorded in general and administrative expense in the accompanying statements of operations and comprehensive loss. Most of the cash payments related to the reduction in workforce were disbursed during the twelve months ended December 31, 2021. We have reported the remaining estimated restructuring liability of $0.5 million as accrued compensation and benefits in our Balance Sheet as of December 31, 2021. In addition, on October 8, 2021, our Board approved, and management has implemented a retention program consisting of cash payments and grants of RSUs to our employees, including our executives, not impacted by the reduction in force.

Property and Equipment, Net

12 Months Ended

Dec. 31, 2021

Property, Plant and Equipment [Abstract]

Property and Equipment, Net

PROPERTY AND EQUIPMENT, NET

Property and equipment consist of the following (in thousands):


	December 31,
	2021		2020
Laboratory equipment	$	7,474	$	7,268
Office equipment and furniture	2,034		1,133
Leasehold improvements	8,745		7,985
Property and equipment, gross	18,253		16,386
Less: accumulated depreciation	(15,891)		(14,450)
Total property and equipment, net	$	2,362	$	1,936

We recognized depreciation expense in the amount of $1.4 million, $1.8 million, and $2.5 million for the years ended December 31, 2021, 2020 and 2019, respectively.

Accrued Expenses and Other Current Liabilities

12 Months Ended

Dec. 31, 2021

Payables and Accruals [Abstract]

Accrued Expenses and Other Current Liabilities

ACCRUED EXPENSES AND OTHER CURRENT LIABILITIES

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


	December 31,
	2021		2020
Accrued clinical expenses	$	2,522	$	2,197
Accrued contract manufacturing expenses	2,485		1,840
Derivative liability for exit fee	698		1,376
Accrued professional and consulting services	597		243
Accrued sales and marketing expenses	256		593
Accrued interest expense	203		123
Other	605		285
Total accrued expenses and other current liabilities	$	7,366	$	6,657

Income Taxes

12 Months Ended

Dec. 31, 2021

Income Tax Disclosure [Abstract]

Income Taxes

INCOME TAXES

The components of our provision for income taxes for the year ended December 31, 2021, 2020 and 2019, are as follows (in thousands):


	Year Ended December 31,
	2021		2020		2019
Current:
State	$	4	$	2	$	2
Foreign	—		—		301
Total current	4		2		303
Deferred:
Federal	—		—		—
Total deferred	—		—		—
Provision for income taxes	$	4	$	2	$	303

The following is a reconciliation of the statutory federal income tax rate to our effective tax rate:


	Year Ended December 31,
	2021		2020		2019
Change in valuation allowance	(20.0)	%	(22.3)	%	(21.9)	%
Income tax at the federal statutory rate	21.0		21.0		21.0
Tax credits	1.0		1.3		1.6
State taxes, net of federal benefit	0.4		0.7		0.3
Stock based compensation	(1.3)		(0.1)		(0.4)
Executive compensation disallowed under IRC Sec 162(m)	(1.1)		(0.5)		(0.5)
Other	—		(0.1)		(0.4)
Income tax provision	—	%	—	%	(0.3)	%

Deferred income taxes reflect the tax effects of temporary differences between the carrying amounts of assets and liabilities for financial reporting purposes and the amounts used for income tax purposes. Significant components of our deferred tax assets are as follows as of December 31, 2021 and 2020 (in thousands):


	December 31,
	2021		2020
Deferred tax assets:
Amortization and depreciation	$	61,098	$	51,370
Net operating loss carryforwards	74,989		53,436
Tax credits	13,827		11,777
Stock-based compensation	4,054		5,524

Other	3,867		1,804
Gross deferred tax assets	157,835		123,911
Valuation allowance	(155,141)		(123,402)
Deferred tax assets net of valuation allowance	2,694		509
Deferred tax liabilities:
Right-of-use asset	(2,689)		(479)

Other	(5)		(30)
Net deferred tax assets	$	—	$	—

Realization of deferred tax assets is dependent on future taxable income, if any, the timing and the amount of which are uncertain. We assess the available positive and negative evidence to estimate whether sufficient future taxable income will be generated to permit use of the existing deferred tax assets. A significant component of objective negative evidence evaluated was our cumulative loss incurred over the three-year period ended December 31, 2021. Such objective evidence limits the ability to consider other subjective evidence, such as our projections for future growth. On the basis of this evaluation, as of December 31, 2021, December 31, 2020 and December 31, 2019, a full valuation allowance has been recorded against our net deferred tax asset. The amount of the deferred tax asset considered realizable, however, could be adjusted if estimates of future taxable income during the carryforward period are reduced or increased or if objective negative evidence in the form of cumulative losses is no longer present and additional weight is given to subjective evidence such as our projections for growth.

As of December 31, 2021, we had net operating loss carryforwards for federal income tax purposes of approximately $386.3 million, of which approximately $236.1 million can be carried forward indefinitely and the remaining net operating losses expire beginning in 2030, if not utilized. Federal research and development tax credit carryforwards of approximately $16.4 million that expire beginning in 2027, if not utilized, and foreign tax credit carryforwards of approximately $1.2 million that expire in 2027, if not utilized.

In addition, we had net operating loss carryforwards for California income tax purposes of approximately $88.3 million that expire beginning of 2030, if not utilized, and state research and development tax credit carryforwards of approximately $8.4 million which can be carried forward indefinitely. We had approximately $0.1 million of minimum tax credit carryovers for California income tax purposes. The minimum tax credits have no expiration date. We had other state net operating losses of approximately $4.5 million that begin to expire in 2035.

The future utilization of net operating loss and tax credit carryforwards and credits may be subject to an annual limitation, pursuant to Internal Revenue Code Sections 382 and 383, as a result of ownership changes that may have occurred previously or that could occur in the future. Due to the existence of the valuation allowance, limitations under Section 382 and 383 will not impact our effective tax rate.

On March 27, 2020, the Coronavirus Aid, Relief, and Economic Security Act (“CARES Act”) was enacted and signed into law in response to coronavirus disease 2019 (“COVID-19”). The CARES Act, among other things, included several significant provisions that impacted corporate taxpayers’ accounting for income taxes. Prior to the enactment of the CARES Act, the 2017 Tax Cuts and Jobs Act generally eliminated the ability to carryback net operating losses (“NOLs”), and permitted the NOLs arising in tax years beginning after December 31, 2018 to be carried forward indefinitely, limited to 80% of the taxpayer’s income. The CARES Act amended the NOL rules, suspending the 80% limitation on the utilization of NOLs generated after December 31, 2018 and before January 1, 2021. Additionally, the CARES Act allows corporate NOLs arising in taxable years beginning after December 31, 2018 and before January 1, 2021, to be carried back to each of the five taxable years preceding

the taxable year of the loss. Also, the CARES Act allows companies to defer making certain payroll tax payments until future years. With the enactment of the CARES Act, the company does not expect a financial statement impact from income taxes.

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


	December 31,
	2021		2020		2019
Balance at beginning of year	$	23,624	$	24,538	$	23,052
Additions (subtractions) based on tax positions related to prior year	(811)		(1,388)		755
Additions based on tax positions related to current year	1,613		474		731
Balance at end of year	$	24,426	$	23,624	$	24,538

We recognize a tax benefit from an uncertain tax position when it is more likely than not that the position will be sustained upon examination, including resolutions of any related appeals or litigation processes, based on the technical merits. Income tax positions must meet a more likely than not recognition at the effective date to be recognized. None of our unrecognized tax benefits would impact the effective tax rate if recognized, because the benefit would be offset by an increase in the valuation allowance.

We have elected to include interest and penalties as a component of tax expense. During the years ended December 31, 2021, 2020 and 2019, we did not recognize accrued interest and penalties related to unrecognized tax benefits. Although the timing and outcome of an income tax audit is highly uncertain, we do not anticipate that the amount of existing unrecognized tax benefits will significantly change during the next 12 months.

We file income tax returns in the U.S. federal, Alabama, Arizona, California, Colorado, Connecticut, DC, Florida, Georgia, Idaho, Illinois, Indiana, Kansas, Kentucky, Massachusetts, Maryland, Michigan, Missouri, Kansas City (MO), Mississippi, New York & New York MTA, New York City, Nebraska, New Jersey, New Mexico, North Carolina, Cincinnati (OH), Maineville (OH), Oklahoma, Pennsylvania, Tennessee, Texas, Virginia and Wisconsin tax jurisdictions. Due to our net operating loss and tax credit carryforwards, the income tax returns remain open to U.S. federal and state tax examinations. The Company is not currently under examination in any tax jurisdiction.

- Definition

The entire disclosure for income taxes. Disclosures may include net deferred tax liability or asset recognized in an enterprise's statement of financial position, net change during the year in the total valuation allowance, approximate tax effect of each type of temporary difference and carryforward that gives rise to a significant portion of deferred tax liabilities and deferred tax assets, utilization of a tax carryback, and tax uncertainties information.

+ References

Reference 1: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 740
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-Paragraph 21
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Reference 2: http://www.xbrl.org/2003/role/disclosureRef
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-Name Accounting Standards Codification
-Topic 740
-SubTopic 10
-Section S99
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Reference 3: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
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-Subparagraph (b)
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Reference 4: http://www.xbrl.org/2003/role/disclosureRef
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Reference 5: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
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-SubTopic 10
-Section 50
-Paragraph 14
-URI http://asc.fasb.org/extlink&oid=121826272&loc=d3e32705-109319

Reference 6: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 740
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Reference 7: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 740
-URI http://asc.fasb.org/topic&trid=2144680

Reference 8: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 740
-SubTopic 30
-Section 50
-Paragraph 2
-Subparagraph (a)
-URI http://asc.fasb.org/extlink&oid=6424122&loc=d3e41874-109331

Reference 9: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 235
-SubTopic 10
-Section S99
-Paragraph 1
-Subparagraph (SX 210.4-08(h)(2))
-URI http://asc.fasb.org/extlink&oid=120395691&loc=d3e23780-122690

+ Details

Geographic Information and Concentrations

12 Months Ended

Dec. 31, 2021

Risks and Uncertainties [Abstract]

Geographic Information and Concentrations

GEOGRAPHIC INFORMATION AND CONCENTRATIONS

Revenues are attributed to geographical areas based on the domicile of our collaboration partners. Our revenue by geographic areas for the years ended December 31, 2021, 2020 and 2019, are as follows (in thousands):


	Year Ended December 31,
	2021		2020		2019
United States	$	—	$	—	$	—
International:
North America (1)	13		806		—
Asia Pacific (2) (3)	10,084		6,765		5,281
Total revenue	$	10,097	$	7,571	$	5,281

_________________________________

(1)Revenues from North America are comprised of amounts earned from Canada in accordance with the Knight Agreement.

(2)Revenues from Asia Pacific in 2021 and 2020 are comprised of amounts earned from Japan in accordance with the 2017 KKC Agreement and 2019 KKC Agreement.

(3)Revenues from Asia Pacific in 2019 were comprised of $0.8 million from Japan in accordance with the 2017 KKC Agreement and 2019 KKC Agreement, $1.5 million from Hong Kong in accordance with the XuanZhu Agreement and $3.0 million from China in accordance with the Fosun Agreement.

Revenues recorded in the years ended December 31, 2021, 2020 and 2019, were wholly from collaboration partnerships. Collaboration partnerships accounting for more than 10% of total revenues during the years ended December 31, 2021, 2020 and 2019 are as follows:


	Year Ended December 31,
	2021		2020		2019
KKC	100	%	89	%	15	%
Knight	—	%	11	%	—	%
Fosun Pharma	—	%	—	%	57	%
XuanZhu	—	%	—	%	28	%

Historically, we have not experienced credit losses from our accounts receivable. We have not recorded a reserve for credit losses as of December 31, 2021 and 2020.

Net Loss Per Share

12 Months Ended

Dec. 31, 2021

Earnings Per Share [Abstract]

Net Loss Per Share

NET LOSS PER SHARE

Basic net loss per share is calculated by dividing net loss by the weighted-average number of common shares outstanding during the period, less shares subject to repurchase, and excludes any dilutive effects of stock-based awards and warrants. Diluted net loss per common share is computed giving effect to all potential dilutive common shares, including common stock issuable upon exercise of stock options, and unvested restricted common stock and stock units. As we had net losses for the years ended December 31, 2021, 2020 and 2019, all potential common shares were determined to be anti-dilutive.

The following table sets forth the computation of net loss per common share (in thousands, except per share amounts):


	Year Ended December 31,
	2021		2020		2019
Numerator:
Net loss	$	(158,165)	$	(94,313)	$	(94,940)
Denominator:
Weighted average common shares outstanding - basic and diluted	104,205,645		89,582,138		64,478,066
Net loss per share - basic and diluted	$	(1.52)	$	(1.05)	$	(1.47)

For the years ended December 31, 2021, 2020 and 2019, the total numbers of securities that could potentially dilute net income per share in the future that were not considered in the diluted net loss per share calculations because the effect would have been anti-dilutive were as follows:


	Year Ended December 31,
	2021	2020	2019
Options to purchase common stock	11,870,778	9,246,047	7,128,247
Restricted stock units	1,602,384	26,121	—
ESPP shares issuable	206,522	94,466	78,761
Warrants to purchase common stock	—	932,091	2,172,899
Performance-based restricted stock units	—	—	867,506
Total	13,679,684	10,298,725	10,247,413

The number of potential common shares that would have been included in diluted income per share had it not been for the anti-dilutive effect caused by the net loss, computed by converting these securities using the treasury stock method during the years ended December 31, 2021, 2020 and 2019, was approximately 1.1 million, 2.1 million and 1.1 million, respectively.

Commitments and Contingencies	12 Months Ended
Commitments and Contingencies	Dec. 31, 2021
Commitments and Contingencies Disclosure [Abstract]
Commitments and Contingencies	COMMITMENTS AND CONTINGENCIES Guarantees and Indemnifications We indemnify each of our officers and directors for certain events or occurrences, subject to certain limits, while the officer or director is or was serving at our request in such capacity, as permitted under Delaware law and in accordance with our certificate of incorporation and bylaws. The term of the indemnification period lasts as long as an officer or director may be subject to any proceeding arising out of acts or omissions of such officer or director in such capacity. The maximum amount of potential future indemnification is unlimited; however, we currently hold director and officer liability insurance, which allows the transfer of risk associated with our exposure and may enable us to recover a portion of any future amounts paid. We believe that the fair value of these indemnification obligations is minimal. Accordingly, we have not recognized any liabilities relating to these obligations for any period presented. Legal Proceedings and Claims From time to time we may be involved in claims arising in connection with our business. Based on information currently available, management believes that the amount, or range, of reasonably possible losses in connection with any pending actions against us will not be material to our financial condition or cash flows, and no contingent liabilities were accrued as of December 31, 2021 or 2020.

Subsequent Events	12 Months Ended
Subsequent Events	Dec. 31, 2021
Subsequent Events [Abstract]
Subsequent Events	SUBSEQUENT EVENTS On February 23, 2022 (the “Closing Date”), we entered into a loan and security agreement (the “2022 Loan Agreement”) with SLR Investment Corp. as collateral agent (the “Agent”), and the lenders listed in the 2022 Loan Agreement (collectively the “2022 Lenders”). The 2022 Loan Agreement provides for a senior secured term loan facility, with $27.5 million (the “Term A Loan”) funded on the Closing Date and an additional $22.5 million that we may borrow on or prior to July 25, 2023; provided that (i) we have received approval by the FDA for our NDA for the control of serum phosphorus in chronic kidney disease patients on dialysis by December 31, 2022, and (ii) we have achieved certain product revenue milestone targets described in the 2022 Loan Agreement (the “Term B Loan”, and collectively, the Term A Loan and the Term B Loan, the “2022 Term Loan”). The 2022 Term A Loan funds are being used to repay the 2018 Term Loan with the Lenders as discussed in Note 6 - Borrowings and to fund our ongoing operations. We owed $25.0 million in principal payments from the 2018 Term Loan as of the Closing Date. The 2022 Term Loan has a maturity date of March 1, 2027. Borrowings under the 2022 Term Loan bear interest at a floating per annum rate equal to 7.95% plus the greater of (i) one tenth percent (0.10%) and (ii) one-month LIBOR. We are permitted to make interest-only payments on the 2022 Term Loan through March 31, 2024. Accordingly, beginning on April 1, 2024, we will be required to make monthly payments of interest plus repay the 2022 Term Loan in consecutive equal monthly installments of principal. We were obligated to pay $0.2 million, upon the closing of the Term A Loan, and we are obligated to pay $0.1 million on the earliest of (i) the funding date of the Term B Loan, (ii) July 25, 2023, and (iii) the prepayment, refinancing, substitution, or replacement of the Term A Loan on or prior to July 25, 2023. We are obligated to pay a fee equal to 4.95% of the aggregate original principal amount of the 2022 Term Loan funded upon the earliest to occur of the maturity date, the acceleration of the 2022 Term Loan, and the prepayment, refinancing, substitution, or replacement of the 2022 Term Loan. We may voluntarily prepay the outstanding 2022 Term Loan, subject to a prepayment premium of (i) 3% of the principal amount of the 2022 Term Loan if prepaid prior to or on the first anniversary of the Closing Date, (ii) 2% of the principal amount of the 2022 Term Loan if prepaid after the first anniversary of the Closing Date through and including the second anniversary of the Closing Date, or (iii) 1% of the principal amount of the 2022 Term Loan if prepaid after the second anniversary of the Closing Date and prior to the maturity date. The 2022 Term Loan is secured by substantially all of our assets, except for our intellectual property and certain other customary exclusions. Additionally, in connection with the 2022 Term Loan, we entered into an agreement, whereby we agreed to pay an exit fee in the amount 2% of the 2022 Term Loan funded (the “2022 Exit Fee”) upon (i) any change of control transaction or (ii) our achievement of net revenue from the sale of any products equal to or greater than $100.0 million, measured on a six (6) months basis, tested monthly at the end of each month. Notwithstanding the prepayment or termination of the 2022 Term Loan, the 2022 Exit Fee will expire 10 years from the Closing Date. The 2022 Loan Agreement contains customary representations and warranties and customary affirmative and negative covenants, including, among others, requirements as to financial reporting and insurance and restrictions on our ability to dispose of our business or property, to change our line of business, to liquidate or dissolve, to enter into any change in control transaction, to merge or consolidate with any other entity or to acquire all or substantially all the capital stock or property of another entity, to incur additional indebtedness, to incur liens on our property, to pay any dividends or other distributions on capital stock other than dividends payable solely in capital stock or to redeem capital stock. We have agreed to not allow our cash and cash equivalents to be less than the eighty percent (80%) of the outstanding 2022 Term Loan balance for any period in which our net revenue from the sale of any products, calculated on a trailing six (6) month basis and tested monthly, is less than sixty percent (60%) of the outstanding 2022 Term Loan balance. In addition, the 2022 Loan Agreement contains customary events of default that entitle the Agent to cause our indebtedness under the 2022 Loan Agreement to become immediately due and payable, and to exercise remedies against us and the collateral securing the 2022 Term Loan, including our cash. Under the 2022 Loan Agreement, an event of default will occur if, among other things, we fail to make payments under the 2022 Loan Agreement, we breach any of our covenants under the 2022 Loan Agreement, subject to specified cure periods with respect to certain breaches, certain Lenders determine that a material adverse change has occurred, we or our assets become subject to certain legal proceedings, such as bankruptcy proceedings, we are unable to pay our debts as they become due or we default on contracts with third parties which would permit the holder of indebtedness to accelerate the maturity of such indebtedness or that could have a material adverse change on us. Upon the occurrence and for the duration of an event of default, an additional default interest rate equal to 4% per annum will apply to all obligations owed under the 2022 Loan Agreement.

Summary of Significant Accounting Policies (Policies)	12 Months Ended
Summary of Significant Accounting Policies (Policies)	Dec. 31, 2021
Accounting Policies [Abstract]
Basis of Presentation	Basis of Presentation The accompanying financial statements have been prepared in accordance with accounting principles generally accepted in the United States of America (“U.S. GAAP”).
Prior Period Errors	Prior Period Errors In connection with our review of our financial statements as of and for the six months ended June 30, 2019, we corrected errors related to the accounting for clinical trial accruals that had resulted in an overstatement of research and development expenses during the year ended December 31, 2018. Specifically, management concluded that our research and development expenses recorded during the year ended December 31, 2018 had been overstated by $3.6 million and that our accrued expenses and other current liabilities as of December 31, 2018 had been overstated by the same amount. We analyzed the potential impact of these errors in accordance with the U.S. Securities and Exchange Commission’s (“SEC”) Staff Accounting Bulletin No. 108, Considering the Effects of Prior Year Misstatements when Quantifying Misstatements in Current Year Financial Statements, and concluded that while the errors were significant to our financial statements as of and for the six months ended June 30, 2019, a correction of the errors would not have been material to the full year results for 2019 and 2018 nor affect the trend of financial results. Accordingly, we reduced accrued and other liabilities by $3.6 million and recorded a cumulative adjustment of $3.6 million in the statement of operations and comprehensive loss to reduce research and development expenses in 2019.
Use of Estimates	Use of Estimates The preparation of financial statements in conformity with U.S. GAAP requires management to make estimates and judgments that affect the amounts reported in the financial statements and accompanying notes. On an ongoing basis, management evaluates its estimates, including those related to recognition of revenue, clinical trial accruals, contract manufacturing accruals, fair value of assets and liabilities, income taxes and stock-based compensation. Management bases its estimates on historical experience and on various other market-specific and relevant assumptions that management believes to be reasonable under the circumstances. Actual results could materially differ from those estimates.
Cash and Cash Equivalents	Cash and Cash Equivalents We consider all highly liquid investments purchased with an original maturity date of 90 days or less on the date of purchase to be cash equivalents.
Short-Term Investments	Short-Term Investments Short-term investments consist of debt securities classified as available-for-sale and have maturities greater than 90 days, but less than one year, from the date of acquisition. Short-term investments are carried at fair value based upon quoted market prices. Unrealized gains and losses on available-for-sale securities are included in earnings and are reported as an allowance for credit losses on our Balance Sheets. The cost of available-for-sale securities sold is based on the specific-identification method.
Concentration of Credit Risk	Concentration of Credit Risk Financial instruments that potentially subject us to significant concentrations of credit risk consist primarily of cash, cash equivalents, short-term investments and accounts receivable. We are exposed to credit risks in the event of default by the counterparties to the extent of the amount recorded in its balance sheet. Cash, cash equivalents and short-term investments are invested through banks and other financial institutions in the U.S.
Foreign Currency	Foreign Currency We manage our foreign currency exposures with the use of foreign currency purchases. We primarily conduct business in U.S. dollars; however, a portion of our expense and capital activities are transacted in foreign currencies which are subject to exchange rate fluctuations that can affect cash or earnings. We have been in a loss position and therefore our primary objective is to conserve and manage cash. There are generally two methods by which we may manage the cash flow risk of foreign exchange fluctuations when a contract is signed (i) we can purchase the foreign funds, in full or in part, upon the execution of the contract, or (ii) we can obtain the right to purchase such funds, in full or in part, at the execution of the contract, i.e., obtain a forward contract from an appropriate bank, that can be exercised to obtain the currency of interest at a particular point in time. The derivative instruments that we may use to hedge the exposure shall generally not be designated as cash flow hedges, and as a result, changes in their fair value would be recorded in other income (expense), net, in our statements of operations and comprehensive loss. The fair values of forward foreign currency exchange contracts would be estimated using current exchange rates and interest rates and the current creditworthiness of the counterparties is taken into consideration.
Property and Equipment	Property and Equipment Property and equipment are stated at cost, less accumulated depreciation and amortization. Depreciation is computed using the straight-line method over the estimated useful lives of the respective assets, with ranges generally from three to five years. Leasehold improvements are amortized over the lesser of the estimated useful lives or the related remaining lease term.
Impairment of Long-Lived Assets	Impairment of Long-Lived Assets The carrying value of long-lived assets, including property and equipment, are reviewed for impairment whenever events or changes in circumstances indicate that the asset may not be recoverable. An impairment loss is recognized when the total of estimated future undiscounted cash flows, expected to result from the use of the asset and its eventual disposition, are less than the asset’s carrying amount. Impairment, if any, would be assessed using discounted cash flows or other appropriate measures of fair value. For the years ending December 31, 2021, 2020 and 2019 we have recognized no impairment losses.
Income Taxes	Income Taxes We use the asset and liability method of accounting for income taxes. Under this method, deferred tax assets and liabilities are determined based on the differences between the financial reporting and the tax bases of assets and liabilities and are measured using the enacted tax rates and laws that will be in effect when the differences are expected to reverse. A valuation allowance is provided when it is more likely than not that some portion or all of a deferred tax asset will not be realized.
Revenue Recognition	Revenue Recognition On January 1, 2018 we adopted the Financial Accounting Standards Board’s (“FASB”) Accounting Standards Update (“ASU”) No. 2014-9, Revenue from Contracts with Customers (Topic 606) and related amendments (“ASC 606”), on a modified retrospective basis, which resulted in an adjustment to the opening accumulated deficit balance on the adoption date. As a result of the adoption of the new standard, on January 1, 2018, we recorded the following: (i) unbilled revenue under current assets of $5.0 million representing a future receivable related to the first milestone under our license agreement with Kyowa Kirin Co., Ltd. (formerly known as Kyowa Hakko Kirin Co., Ltd ("KHK") (“KKC”), which was subsequently achieved by KKC and collected in February 2019, thereby reducing the unbilled revenue balance to zero, (ii) uncharged license fees under current liabilities of $1.0 million representing the corresponding future payable related to AstraZeneca AB ("AstraZeneca") in accordance with our termination agreement with AstraZeneca, which, upon KKC achieving the milestone, was reclassified to accounts payable and subsequently paid to AstraZeneca during the second quarter of 2019, and (iii) a related decrease in accumulated deficit of approximately $4.0 million as the new standard permitted revenue from milestones that possess certain criteria to be recognized earlier and also contained different recognition criteria related to milestones than under the previous accounting standard. We generate revenue primarily from research and collaboration and license agreements with customers. Goods and services in the agreements may include the grant of licenses for the use of our technology, the provision of services associated with the research and development of product candidates, manufacturing services, and participation in joint steering committees. The terms of these arrangements typically include payment to us of one or more of the following: non-refundable, up-front license fees; research, development, regulatory and commercial milestone payments; reimbursement of research and development services; option payments; reimbursement of certain costs; payments for manufacturing supply services; and future royalties on net sales of licensed products. When two or more contracts are entered into with the same customer at or near the same time, we evaluate the contracts to determine whether the contracts should be accounted for as a single arrangement. Contracts are combined and accounted for as a single arrangement if one or more of the following criteria are met: (i) the contracts are negotiated as a package with a single commercial objective; (ii) the amount of consideration to be paid in one contract depends on the price or performance of the other contract; or (iii) the goods or services promised in the contracts (or some goods or services promised in each of the contracts) are a single performance obligation. In determining the appropriate amount of revenue to be recognized as we fulfill our obligations under each of its agreements, management performs the following steps: (i) identification of the promised goods or services in the contract; (ii) determination of whether the promised goods or services are performance obligations including whether they are distinct in the context of the contract; (iii) measurement of the transaction price, including the constraints on variable consideration; (iv) allocation of the transaction price to the performance obligations; and (v) recognition of revenue when (or as) we satisfy each performance obligation. As part of the accounting for contracts with customers, we develop assumptions that require judgment to determine whether promised goods and services represent distinct performance obligations and the standalone selling price for each performance obligation identified in the contract. This evaluation is subjective and requires us to make judgments about the promised goods and services and whether those goods and services are separable from other aspects of the contract. Further, determining the standalone selling price for performance obligations requires significant judgment, and when an observable price of a promised good or service is not readily available, we consider relevant assumptions to estimate the standalone selling price, including, as applicable, market conditions, development timelines, probabilities of technical and regulatory success, reimbursement rates for personnel costs, forecasted revenues, potential limitations to the selling price of the product and discount rates. We apply judgment in determining whether a combined performance obligation is satisfied at a point in time or over time, and, if over time, concluding upon the appropriate method of measuring progress to be applied for purposes of recognizing revenue. We evaluate the measure of progress each reporting period and, as estimates related to the measure of progress change, related revenue recognition is adjusted accordingly. Changes in our estimated measure of progress are accounted for prospectively as a change in accounting estimate. We recognize collaboration revenue by measuring the progress toward complete satisfaction of the performance obligation using an input measure. In order to recognize revenue over the research and development period, we measure actual costs incurred to date compared to the overall total expected costs to satisfy the performance obligation. Revenues are recognized as the program costs are incurred. We will re-evaluate the estimate of expected costs to satisfy the performance obligation each reporting period and make adjustments for any significant changes. Amounts received prior to satisfying the revenue recognition criteria are recorded as contract liabilities in our Balance Sheets. If the related performance obligation is expected to be satisfied within the next twelve months it will be classified in current liabilities. Amounts recognized as revenue prior to receipt are recorded as contract assets in our Balance Sheets. If we expect to have an unconditional right to receive the consideration in the next twelve months, it will be classified in current assets. A net contract asset or liability is presented for each contract with a customer. Milestone Payments: At the inception of each arrangement that includes development milestone payments, we evaluate whether the milestones are considered probable of being reached and estimates the amount to be included in the transaction price using the most likely amount method. Amounts of variable consideration are included in the transaction price to the extent that it is probable that a significant reversal in the amount of cumulative revenue recognized will not occur and when the uncertainty associated with the variable consideration is subsequently resolved. Milestone payments that are not within our control or the control of the licensee, such as regulatory approvals, are not considered probable of being achieved until those approvals are received. The transaction price is then allocated to each performance obligation on a relative standalone selling price basis, for which we recognize revenue as or when the performance obligations under the contract are satisfied. At the end of each subsequent reporting period, we re-evaluate the probability of achievement of such development milestones and any related constraints, and if necessary, adjusts its estimate of the overall transaction price. Any such adjustments are recorded on a cumulative catch-up basis, which would affect earnings in the period of adjustment. Manufacturing supply services: Arrangements that include a promise for future supply of drug substance or drug product for either clinical development or commercial supply at the customer’s discretion are generally considered as options. We assess if these options provide a material right to the licensee and if so, they are accounted for as separate performance obligations. If we are entitled to additional payments when the customer exercises these options, any payments are recorded in product supply revenue when the customer obtains control of the goods, which is upon delivery. Royalties: For arrangements that include sales-based royalties, including milestone payments based on the level of sales, and where the license is deemed to be the predominant item to which the royalties relate, we recognize revenue at the later of (i) when the related sales occur, or (ii) when the performance obligation to which some or all of the royalty has been allocated has been satisfied (or partially satisfied). To date, we have not recognized any royalty revenue resulting from any of its licensing arrangements. Licenses of intellectual property: If a license granted to a customer to use our intellectual property is determined to be distinct from the other performance obligations identified in the arrangement, we recognize revenue from consideration allocated to the license when the license is transferred to the licensee and the licensee is able to use and benefit from the license. For licenses that are bundled with other promises, we apply judgment to assess the nature of the combined performance obligation to determine whether the combined performance obligation is satisfied over time or at a point in time and, if over time, to conclude upon the appropriate method of measuring progress for purposes of recognizing revenue related to consideration allocated to the performance obligation. Options: Customer options, such as options granted to allow a licensee to choose to research, develop and commercialize licensed compounds are evaluated at contract inception in order to determine whether those options provide a material right (i.e., an optional good or service offered for free or at a discount) to the customer. If the customer options represent a material right, the material right is treated as a separate performance obligation at the outset of the arrangement. The Company allocates the transaction price to material rights based on the standalone selling price, and revenue is recognized when or as the future goods or services are transferred or when the option expires. Customer options that are not material rights do not give rise to a separate performance obligation, and as such, the additional consideration that would result from a customer exercising an option in the future is not included in the transaction price for the current contract. Instead, the option is deemed a marketing offer, and additional option fee payments are recognized or being recognized as revenue when the licensee exercises the option. The exercise of an option that does not represent a material right is treated as a separate contract for accounting purposes. Contract modifications: Contract modifications, defined as changes in the scope or price (or both) of a contract that are approved by the parties to the contract, such as a contract amendment, exist when the parties to a contract approve a modification that either creates new or changes existing enforceable rights and obligations of the parties to the contract. Depending on facts and circumstances, we account for a contract modification as one of the following: (i) a separate contract; (ii) a termination of the existing contract and a creation of a new contract; or (iii) a combination of the preceding treatments. A contract modification is accounted for as a separate contract if the scope of the contract increases because of the addition of promised goods or services that are distinct and the price of the contract increases by an amount of consideration that reflects our standalone selling prices of the additional promised goods or services. When a contract modification is not considered a separate contract and the remaining goods or services are distinct from the goods or services transferred on or before the date of the contract modification, we account for the contract modification as a termination of the existing contract and a creation of a new contract. When a contract modification is not considered a separate contract and the remaining goods or services are not distinct, we account for the contract modification as an add-on to the existing contract and as an adjustment to revenue on a cumulative catch-up basis. We receive payments from its licensees as established in each contract. Upfront payments and fees are recorded as deferred revenue upon receipt or when due and may require deferral of revenue recognition to a future period until we perform our obligations under these arrangements. Where applicable, amounts are recorded as accounts receivable or unbilled revenue when our right to consideration is unconditional. We do not assess whether a contract with a customer has a significant financing component if the expectation at contract inception is such that the period between payment by the licensees and the transfer of the promised goods or services to the licensees will be one year or less.
Research and Development Costs	Research and Development Costs Research and development costs are charged to expense as incurred and consisted of costs incurred to further our research and development activities and include salaries and related employee benefits, costs associated with clinical trials, costs related to pre-commercialization manufacturing activities such as manufacturing process validation activities and the manufacturing of clinical drug supply, nonclinical research and development activities, regulatory activities, research-related overhead expenses and fees paid to external service providers and contract research and manufacturing organizations that conduct certain research and development activities on our behalf.
Accrued Research and Development Expenses	Accrued Research and Development Expenses We are required to estimate our accrued expenses at the end of each reporting period. This process involves reviewing open contracts and purchase orders, communicating with our personnel to identify services that have been performed on our behalf and estimating the level of service performed and the associated cost incurred for the service when we have not yet been invoiced or otherwise notified of the actual costs. The majority of our service providers submit invoices in arrears for services performed or when contractual milestones are met. We make estimates of our accrued expenses as of each balance sheet date in the financial statements based on facts and circumstances known to us at that time. We periodically confirm the accuracy of our estimates with our service providers and make adjustments if necessary. Examples of estimated accrued research and development expenses include fees paid to: •contract research organizations ("CROs") in connection with clinical studies; •investigative sites in connection with clinical studies; •vendors related to product manufacturing, development and distribution of clinical supplies; and •vendors in connection with preclinical development activities. We record expenses related to clinical studies and manufacturing development activities based on our estimates of the services received and efforts expended pursuant to contracts with multiple CROs and manufacturing vendors that conduct and manage these activities on our behalf. The financial terms of these agreements are subject to negotiation, vary from contract to contract, and may result in uneven payment flows. There may be instances in which payments made to our vendors will exceed the level of services provided and result in a prepayment of the expense. Payments under some of these contracts depend on factors such as the successful enrollment of subjects and the completion of clinical trial milestones. In accruing service fees, we estimate the time period over which services will be performed, enrollment of subjects, number of sites activated and the level of effort to be expended in each period. If the actual timing of the performance of services or the level of effort varies from our estimate, we will adjust the accrued or prepaid expense balance accordingly.
Inventory	Inventory We consider regulatory approval of product candidates to be uncertain, and product manufactured prior to regulatory approval may not be sold unless regulatory approval is obtained. We expense manufacturing costs for product candidates incurred prior to regulatory approval as research and development expenses as manufacturing processes are performed. If and when regulatory approval of a product is obtained and we have plans to commercially launch the approved product, we begin capitalizing manufacturing costs related to the approved product into inventory. Although we received approval of IBSRELA (tenapanor) for the treatment of IBS-C in adults from the Food and Drug Administration (“FDA”) in September 2019, we did not plan to launch IBSRELA commercially at that time and, therefore, continued to expense manufacturing costs of tenapanor, which is also under development for another indication that has not received FDA approval. On November 30, 2021, we made the decision and announced our plans to commercially launch IBSRELA and as a result, in December 2021 we began to capitalize the costs of manufacturing processes associated with IBSRELA as those processes are completed. No manufacturing processes related to IBSRELA were completed in December, resulting in no inventory balance at December 31, 2021.
Stock-Based Compensation	Stock-Based Compensation We recognize compensation expense for all stock-based payment awards made to employees, nonemployees and directors based on estimated fair values. For employee and nonemployee stock options, we determine the grant date fair value of the awards using the Black-Scholes option-pricing model and generally recognizes the fair value as stock-based compensation expense on a straight-line basis over the vesting period of the respective awards. For restricted stock and performance-based restricted stock, to the extent they are probable, the compensation cost for these awards is based on the closing price of our common stock on the date of grant and recognized as compensation expense on a straight-line basis over the requisite service period. Stock-based compensation expense is based on the value of the portion of stock-based payment awards that is ultimately expected to vest. As such, our stock-based compensation is reduced for the estimated forfeitures at the date of grant and revised, if necessary, in subsequent periods if actual forfeitures differ from those estimates.
Derivatives and Hedging Activities	Derivatives and Hedging Activities We account for our derivative instruments as either assets or liabilities on the balance sheet and measure them at fair value. Derivatives are adjusted to fair value through other income (expense), net in the statements of operations and comprehensive loss.
Leases	Leases We determine if an arrangement is a lease at the inception of the arrangement. Operating leases are included in right-of-use assets, current portion of operating lease liability, and operating lease liability, net of current portion in our balance sheets. Right-of-use assets represent our right to use an underlying asset for the lease term and lease liabilities represent our obligation to make lease payments arising from the lease. Operating lease right-of-use assets and liabilities are recognized at the lease commencement date based on the present value of lease payments over the lease term. In determining the present value of lease payments, we use our incremental borrowing rate based on the information available at the lease commencement date. The operating lease right-of-use assets also include any lease payments made and exclude lease incentives. Our lease terms may include options to extend or terminate the lease when it is reasonably certain that we will exercise any such options. Lease expense is recognized on a straight-line basis over the expected lease term. We have elected not to separate lease and non-lease components, such as common area maintenance charges, and instead it accounts for these as a single lease component.
Restructuring	Restructuring We recognize restructuring charges related to reorganization plans that have been committed to by management when liabilities have been incurred. In connection with these activities, we record restructuring charges at fair value for, (a) contractual employee termination benefits when obligations are associated to services already rendered, rights to such benefits have vested, and payment of benefits is probable and can be reasonably estimated, (b) one-time employee termination benefits when management has committed to a plan of termination, the plan identifies the employees and their expected termination dates, the details of termination benefits are complete, it is unlikely changes to the plan will be made or the plan will be withdrawn and communication to such employees has occurred, and (c) contract termination costs when a contract is terminated before the end of its term. One-time employee termination benefits are recognized in their entirety when communication has occurred and future services are not required. If future services are required, the costs are recorded ratably over the remaining period of service. Contract termination costs to be incurred over the remaining contract term without economic benefit are recorded in their entirety when the contract is canceled.
Net Loss per Share	Net Loss per Share Basic net loss per common share is calculated by dividing the net loss by the weighted-average number of common shares outstanding during the period, without consideration of potential common shares. Diluted net loss per common share in the periods presented is the same as basic net loss per common share, since the effects of potentially dilutive securities are antidilutive due to the net loss for all periods presented.
Recent Accounting Pronouncements	Recent Accounting Pronouncements New Accounting Pronouncements - Recently Adopted In December 2019, as part of its initiative to reduce complexity in the accounting standards, the Financial Accounting Standards Board (“FASB”) issued Accounting Standards Update (“ASU”) 2019-12, Income Taxes (Topic 740): Simplifying the Accounting for Income Taxes (“ASU 2019-12”), which eliminates certain exceptions related to the approach for intra-period tax allocation, the methodology for calculating income taxes in an interim period and the recognition of deferred tax liabilities for outside basis differences. ASU 2019-12 also clarifies and simplifies other aspects of the accounting for income taxes. The standard is effective for fiscal years, and interim periods within those fiscal years, beginning after December 15, 2020, with early adoption permitted. We early adopted ASU 2019-12 on April 1, 2020 and this adoption had no material impact on our financial position or results of operations. We adopted Accounting Standards Update 2016-13, Financial Instruments - Credit Losses: Measurement of Credit Losses on Financial Instruments ("ASU 2016-13"), as of December 1, 2021 under the modified retrospective approach. ASU 2016-13 requires an entity to measure and recognize expected credit losses for certain financial instruments, including trade receivables, as an allowance that reflects the entity's current estimate of credit losses expected to be incurred. For available-for-sale debt securities with unrealized credit losses, the standard requires allowances to be recorded through net income instead of directly reducing the amortized cost of the investment under the previous other-than-temporary impairment model. The adoption of this standard did not have a material impact on our financial statements or a significant impact on our internal controls. Recent Accounting Pronouncements Not Yet Adopted There were various accounting standards and interpretations issued recently, none of which are expected to a have a material impact on our financial position, operations or cash flows.

Cash and Investments (Tables)

12 Months Ended

Dec. 31, 2021

Cash and Cash Equivalents [Abstract]

Schedule of Securities Classified as Cash and Investments

Securities classified as cash and investments as of December 31, 2021 and 2020 are summarized below (in thousands). Estimated fair value is based on quoted market prices for these investments.


	December 31, 2021
			Gross Unrealized
	Amortized Cost		Gains		Losses		Fair Value
Cash and cash equivalents:
Money market funds	$	71,175	$	—	$	—	$	71,175

Cash	1,253		—		—		1,253
Total cash and cash equivalents	72,428		—		—		72,428
Short-term investments:
Commercial paper	$	31,936	$	1	$	(2)	$	31,935
Corporate bonds	7,025		—		(3)		7,022
Asset-backed securities	5,306		—		(2)		5,304
U.S. treasury notes	—		—		—		—
Total short-term investments	44,267		1		(7)		44,261


Total cash equivalents and investments	$	116,695	$	1	$	(7)	$	116,689


	December 31, 2020
			Gross Unrealized
	Amortized Cost		Gains		Losses		Fair Value
Cash and cash equivalents:
Money market funds	$	88,151	$	—	$	—	$	88,151
Commercial paper	2,100		—		—		2,100

Cash	781		—		—		781
Total cash and cash equivalents	91,032		—		—		91,032
Short-term investments
Commercial paper	$	60,631	$	2	$	(4)	$	60,629
Corporate bonds	24,547		3		(6)		24,544
U.S. government-sponsored agency bonds	9,277		2		—		9,279
U.S. treasury notes	1,000		—		—		1,000
Total short-term investments	95,455		7		(10)		95,452
Long-term investments:
Corporate bonds	$	2,115	$	—	$	(1)	$	2,114
Total cash equivalents and investments	$	188,602	$	7	$	(11)	$	188,598

Schedule of Amortized Cost and Estimated Fair Value of Available-for-Sale Debt Securities by Contractual Maturity

As of December 31, 2021, the amortized cost and estimated fair value of available-for-sale debt securities by contractual maturity were as follows (in thousands):


	Amortized Cost		Fair Value
Due in one year or less	$	44,267	$	44,261

Fair Value Measurements (Tables)

12 Months Ended

Dec. 31, 2021

Fair Value Disclosures [Abstract]

Schedule of Fair Value of Financial Assets and Liabilities Measured on a Recurring Basis

The following table sets forth the fair value of our financial assets and liabilities measured on a recurring basis by level within the fair value hierarchy (in thousands):


	December 31, 2021
	Total Fair Value		Level 1		Level 2		Level 3
Assets:
Money market funds	$	71,175	$	71,175	$	—	$	—
Commercial paper	31,935		—		31,935		—
Corporate bonds	7,022		—		7,022		—
Asset-backed securities	5,304		—		5,304		—

Total	$	115,436	$	71,175	$	44,261	$	—

Liabilities:
Derivative liability for exit fee	$	698	$	—	$	—	$	698
Total	$	698	$	—	$	—	$	698


	December 31, 2020
	Total Fair Value		Level 1		Level 2		Level 3
Assets:
Money market funds	$	88,151	$	88,151	$	—	$	—
Commercial paper	62,729		—		62,729		—
Corporate bonds	26,658		—		26,658		—
U.S. government-sponsored agency bonds	9,279		—		9,279		—
U.S. treasury notes	1,000		—		1,000		—
Total	$	187,817	$	88,151	$	99,666	$	—

Liabilities:
Derivative liability for exit fee	$	1,376	$	—	$	—	$	1,376
Total	$	1,376	$	—	$	—	$	1,376

Collaboration and Licensing Agreements (Tables)

12 Months Ended

Dec. 31, 2021

Collaboration and Licensing Agreements [Abstract]

Schedule of Cost of Revenue Recognized and Paid

To date in aggregate, we have recognized $11.6 million of the $75.0 million, recorded as cost of revenue, as follows (in thousands):


	Cost of Revenue
	Recognized			Amount Paid
Year 2017	$	9,400	*	$	6,000
Year 2018	466			2,864
Year 2019	600			1,002
Year 2020	145			742
Year 2021	1,000			1,003
Total	$	11,611		$	11,611
Maximum payment per termination agreement				75,000
Remaining potential commitment				$	63,389

* Includes $1.0 million adjustment recorded pursuant to the adoption of ASC 606, as discussed in Note 2.

Schedule of Deferred Revenue Balances


Deferred revenue - current	2021		2020
Balance at Balance at January 1,	$	4,177	$	4,541

Decreases due to revenue recognized in the period for which cash has been received	(4,177)		(364)

Balance at Balance at December 31,	$	—	$	4,177


Deferred revenue - non-current	2021		2020
Balance at Balance at January 1,	$	—	$	—
Increases due to cash received during the period	3,242		—
Increase due to unbilled prepayments recorded during the period	1,485		—

Balance at Balance at December 31,	$	4,727	$	—

Borrowings (Tables)

12 Months Ended

Dec. 31, 2021

Debt Disclosure [Abstract]

Schedule of Future Debt Payment Obligations


2022	$	33,031

Total repayment obligations	$	33,031
Less: Unamortized discount and debt issuance costs	(235)
Less: Unaccreted value of final fee	(532)
Loan payable	32,264
Less: Loan payable, current portion	(32,264)
Loan payable, net of current portion	$	—

Derivative Liability (Tables)

12 Months Ended

Dec. 31, 2021

Derivative Instruments and Hedging Activities Disclosure [Abstract]

Schedule of Changes in Fair Value of Derivative Liability


	2021		2020		2019
Fair value of exit fee derivative liability at January 1	$	1,376	$	969	$	533
Change in estimated fair value of derivative liability	$	(678)	$	407	$	436
Fair value of exit fee derivative liability at December 31	$	698	$	1,376	$	969

Leases (Tables)

12 Months Ended

Dec. 31, 2021

Leases [Abstract]

Summary of Additional Details of the Leases

The following table provides additional details of the leases presented in the balance sheets (dollars in thousands):


	As of Dec 31,
Facilities	2021			2020
Right-of-use assets	$	12,752		$	2,274

Current portion of lease liabilities	3,492			2,117
Operating lease liability, net of current portion	9,748			413
Total	$	13,240		$	2,530

Weighted-average remaining life (years)	3.40			1.50
Weighted-average discount rate	6.9		%	11.7		%

Summary of Lease Costs

The lease costs, which are included in operating expenses in our statements of operations, were as follows (in thousands):


	Year Ended December 31,
	2021		2020		2019
Operating lease expense	$	3,671	$	2,608	$	2,592
Cash paid for operating lease	$	3,438	$	3,065	$	2,645

Summary of Undiscounted Cash Payment Obligations for Operating Lease Liabilities

The following table summarizes our undiscounted cash payment obligations for our operating lease liabilities as of December 31, 2021 (in thousands):


Ending December 31,
2022	$	4,292
2023	4,440
2024	4,589
2025	1,321
2026	252
Thereafter	—
Total undiscounted operating lease payments	14,894
Imputed interest expenses	(1,654)
Total operating lease liabilities	13,240
Less: Current portion of operating lease liability	(3,492)
Operating lease liability, net of current portion	$	9,748

Equity Incentive Plans (Tables)

12 Months Ended

Dec. 31, 2021

Share-based Payment Arrangement [Abstract]

Schedule of Stock Option Activity

The following table summarizes activity under the 2008 Plan and the 2014 Plan, including grants issued to nonemployees, in the year ended December 31, 2021:


	Shares Available for Grant	Options Issued and Outstanding			Weighted Average Remaining Contractual Term	Aggregate Intrinsic Value
		Number of Shares	Weighted-Average Exercise Price per Share
					(in Years)	(in thousands)
Balance at December 31, 2020	1,757,058	9,790,049	$	6.76
Options authorized	4,201,766	—	$	—
Options granted	(3,409,719)	3,409,719	$	6.60
Options exercised	—	(331,310)	$	1.96
Options canceled	2,451,306	(2,451,306)	$	6.17
Issuance of common stock for services	(25,989)	—	—

Balance at December 31, 2021	4,974,422	10,417,152	$	7.00	6.57	$	—
Vested and expected to vest at December 31, 2021		10,417,152	$	7.00	6.57	$	—
Exercisable at December 31, 2021		6,772,289	$	7.39	5.58	$	—

Schedule of Valuation Assumptions for Stock Options

The estimated grant date fair value of employee stock options was calculated using the Black-Scholes option-pricing model, based on the following weighted-average assumptions:


	Year Ended December 31,
	2021		2020		2019
Expected term (years)	4.97		6.00		6.00
Expected volatility	77	%	83	%	81	%
Risk-free interest rate	4.69	%	1.07	%	2.42	%
Dividend yield	—	%	—	%	—	%

Schedule of Restricted Stock Units Activity


	Number of RSUs	Weighted-Average Grant Date Fair Value Per Share
Non-vested restricted stock units at December 31, 2020	158,626	$	5.64
Granted	4,144,051	$	2.71
Vested	(193,147)	$	6.39
Forfeited	(580,848)	$	6.38
Non-vested restricted stock units at December 31, 2021	3,528,682	$	2.04

Schedule of Employee Stock Purchase Plan Activity

The following table summarizes our ESPP activity during the year ended December 31, 2021:


	Shares Available for Grant	Number of Shares Purchased	Average Purchase Price per Share		Gross Proceeds
					(in thousands)
Balance at December 31, 2020	349,647	661,611
Shares purchased	(386,664)	386,664	$	2.12	$	819
Balance at December 31, 2021	898,982	1,048,275

Schedule of Valuation Assumptions for Employee Stock Purchase Plan

The following table illustrates the weighted-average assumptions for the Black-Scholes option-pricing model used in determining the fair value of ESPP purchase rights granted to our employees:


	Year Ended December 31,
	2021		2020		2019
Expected term (years)	0.50		0.50		0.50
Expected volatility	123	%	79	%	69	%
Risk-free interest rate	0.65	%	0.48	%	2.00	%
Dividend yield	—	%	—	%	—	%

Schedule of Stock-Based Compensation Recognized

Total stock-based compensation recognized was as follows (in thousands):


	Year Ended December 31,
	2021		2020		2019
Research and development	$	4,116	$	4,061	$	4,104
General and administrative	7,923		6,522		5,832
Total	$	12,039	$	10,583	$	9,936

Schedule of Total Unrecognized Stock-Based Compensation Expense, Net of Estimated Forfeitures

At December 31, 2021, the Company had total unrecognized stock-based compensation expense, net of estimated forfeitures, of the following (dollars in thousands):


	December 31, 2021
	Unrecognized Compensation Expense		Average Remaining Vesting Period (Years)
Stock options grant	$	14,506	2.4
RSU grants	$	2,262	0.8
ESPP	$	44	0.1

Property and Equipment, Net (Tables)

12 Months Ended

Dec. 31, 2021

Property, Plant and Equipment [Abstract]

Schedule of Property and Equipment

Property and equipment consist of the following (in thousands):


	December 31,
	2021		2020
Laboratory equipment	$	7,474	$	7,268
Office equipment and furniture	2,034		1,133
Leasehold improvements	8,745		7,985
Property and equipment, gross	18,253		16,386
Less: accumulated depreciation	(15,891)		(14,450)
Total property and equipment, net	$	2,362	$	1,936

Accrued Expenses and Other Current Liabilities (Tables)

12 Months Ended

Dec. 31, 2021

Payables and Accruals [Abstract]

Schedule of Accrued Expenses and Other Current Liabilities

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


	December 31,
	2021		2020
Accrued clinical expenses	$	2,522	$	2,197
Accrued contract manufacturing expenses	2,485		1,840
Derivative liability for exit fee	698		1,376
Accrued professional and consulting services	597		243
Accrued sales and marketing expenses	256		593
Accrued interest expense	203		123
Other	605		285
Total accrued expenses and other current liabilities	$	7,366	$	6,657

Income Taxes (Tables)

12 Months Ended

Dec. 31, 2021

Income Tax Disclosure [Abstract]

Schedule of Components of Provision for Income Taxes

The components of our provision for income taxes for the year ended December 31, 2021, 2020 and 2019, are as follows (in thousands):


	Year Ended December 31,
	2021		2020		2019
Current:
State	$	4	$	2	$	2
Foreign	—		—		301
Total current	4		2		303
Deferred:
Federal	—		—		—
Total deferred	—		—		—
Provision for income taxes	$	4	$	2	$	303

Schedule of Reconciliation of Effective Tax Rate

The following is a reconciliation of the statutory federal income tax rate to our effective tax rate:


	Year Ended December 31,
	2021		2020		2019
Change in valuation allowance	(20.0)	%	(22.3)	%	(21.9)	%
Income tax at the federal statutory rate	21.0		21.0		21.0
Tax credits	1.0		1.3		1.6
State taxes, net of federal benefit	0.4		0.7		0.3
Stock based compensation	(1.3)		(0.1)		(0.4)
Executive compensation disallowed under IRC Sec 162(m)	(1.1)		(0.5)		(0.5)
Other	—		(0.1)		(0.4)
Income tax provision	—	%	—	%	(0.3)	%

Schedule of Components of Deferred Tax Assets

Significant components of our deferred tax assets are as follows as of December 31, 2021 and 2020 (in thousands):


	December 31,
	2021		2020
Deferred tax assets:
Amortization and depreciation	$	61,098	$	51,370
Net operating loss carryforwards	74,989		53,436
Tax credits	13,827		11,777
Stock-based compensation	4,054		5,524

Other	3,867		1,804
Gross deferred tax assets	157,835		123,911
Valuation allowance	(155,141)		(123,402)
Deferred tax assets net of valuation allowance	2,694		509
Deferred tax liabilities:
Right-of-use asset	(2,689)		(479)

Other	(5)		(30)
Net deferred tax assets	$	—	$	—

Schedule of Reconciliation of Unrecognized Tax Benefits

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


	December 31,
	2021		2020		2019
Balance at beginning of year	$	23,624	$	24,538	$	23,052
Additions (subtractions) based on tax positions related to prior year	(811)		(1,388)		755
Additions based on tax positions related to current year	1,613		474		731
Balance at end of year	$	24,426	$	23,624	$	24,538

Geographic Information and Concentrations (Tables)

12 Months Ended

Dec. 31, 2021

Risks and Uncertainties [Abstract]

Schedule of Revenue by Geographic Areas

evenue by geographic areas for the years ended December 31, 2021, 2020 and 2019, are as follows (in thousands):


	Year Ended December 31,
	2021		2020		2019
United States	$	—	$	—	$	—
International:
North America (1)	13		806		—
Asia Pacific (2) (3)	10,084		6,765		5,281
Total revenue	$	10,097	$	7,571	$	5,281

_________________________________

(1)Revenues from North America are comprised of amounts earned from Canada in accordance with the Knight Agreement.

(2)Revenues from Asia Pacific in 2021 and 2020 are comprised of amounts earned from Japan in accordance with the 2017 KKC Agreement and 2019 KKC Agreement.

Schedule of Collaboration Partnerships

Collaboration partnerships accounting for more than 10% of total revenues during the years ended December 31, 2021, 2020 and 2019 are as follows:


	Year Ended December 31,
	2021		2020		2019
KKC	100	%	89	%	15	%
Knight	—	%	11	%	—	%
Fosun Pharma	—	%	—	%	57	%
XuanZhu	—	%	—	%	28	%

Net Loss Per Share (Tables)

12 Months Ended

Dec. 31, 2021

Earnings Per Share [Abstract]

Schedule of Computation of Net Loss Per Common Share

The following table sets forth the computation of net loss per common share (in thousands, except per share amounts):


	Year Ended December 31,
	2021		2020		2019
Numerator:
Net loss	$	(158,165)	$	(94,313)	$	(94,940)
Denominator:
Weighted average common shares outstanding - basic and diluted	104,205,645		89,582,138		64,478,066
Net loss per share - basic and diluted	$	(1.52)	$	(1.05)	$	(1.47)

Schedule of Anti-Dilutive Securities Not Considered in Diluted Net Loss Per Common Share Calculation


	Year Ended December 31,
	2021	2020	2019
Options to purchase common stock	11,870,778	9,246,047	7,128,247
Restricted stock units	1,602,384	26,121	—
ESPP shares issuable	206,522	94,466	78,761
Warrants to purchase common stock	—	932,091	2,172,899
Performance-based restricted stock units	—	—	867,506
Total	13,679,684	10,298,725	10,247,413

Organization and Basis of Presentation (Details)	12 Months Ended
Organization and Basis of Presentation (Details)	Dec. 31, 2021 segment
Organization, Consolidation and Presentation of Financial Statements [Abstract]
Number of operating segments	1

Summary of Significant Accounting Policies - Prior Period Errors (Details) - USD ($) $ in Thousands		12 Months Ended
	Jan. 01, 2019	Dec. 31, 2021	Dec. 31, 2020	Dec. 31, 2019
Error Corrections and Prior Period Adjustments Restatement [Line Items]
Accrued expenses and other current liabilities		$ (7,366)	$ (6,657)
Research and development		$ (91,140)	$ (65,053)	$ (71,677)
Accounting for clinical trial accruals \| Cumulative adjustment
Error Corrections and Prior Period Adjustments Restatement [Line Items]
Accrued expenses and other current liabilities	$ 3,600
Research and development	$ 3,600

Summary of Significant Accounting Policies - Liquidity (Details) - USD ($) $ in Thousands	Dec. 31, 2021	Dec. 31, 2020
Accounting Policies [Abstract]
Cash and investments	$ 116,689	$ 188,598
Accumulated deficit	$ (712,930)	$ (554,765)

- Definition

The cumulative amount of the reporting entity's undistributed earnings or deficit.

+ References + Details

Summary of Significant Accounting Policies - Narrative (Details) - USD ($)	12 Months Ended
	Dec. 31, 2021	Dec. 31, 2020	Dec. 31, 2019	Feb. 28, 2019	Jan. 01, 2018
Summary of significant accounting policies
Impairment loss of long-lived assets	$ 0	$ 0	$ 0
Accumulated deficit	$ (712,930,000)	$ (554,765,000)
Minimum
Summary of significant accounting policies
Estimated useful lives	3 years
Maximum
Summary of significant accounting policies
Estimated useful lives	5 years
Kyowa Kirin Co. Ltd \| 2017 KKC Agreement
Summary of significant accounting policies
Unbilled revenue				$ 0
ASU 2014-09 \| Adjustments \| 2017 KKC Agreement
Summary of significant accounting policies
Accumulated deficit					$ 4,000,000
ASU 2014-09 \| Adjustments \| Kyowa Kirin Co. Ltd \| 2017 KKC Agreement
Summary of significant accounting policies
Unbilled revenue					5,000,000
ASU 2014-09 \| Adjustments \| AstraZeneca \| 2017 KKC Agreement
Summary of significant accounting policies
Uncharged license fee					$ 1,000,000

Cash and Investments - Securities Classified as Cash and Investments (Details) - USD ($) $ in Thousands	Dec. 31, 2021	Dec. 31, 2020
Cash and cash equivalents:
Cash and cash equivalents	$ 72,428	$ 91,032
Short-term investments:
Short-term investments, Cost	44,267	95,455
Short-term investments, Gross Unrealized Gains	1	7
Short-term investments, Gross Unrealized Losses	(7)	(10)
Short-term investments, Fair Value	44,261	95,452
Long-term investments:
Total cash equivalents and investments, Cost	116,695	188,602
Total cash equivalents and investments, Gross Unrealized Gains	1	7
Total cash equivalents and investments, Gross Unrealized Losses	(7)	(11)
Total cash equivalents and investments, Fair Value	116,689	188,598
Money market funds
Cash and cash equivalents:
Cash and cash equivalents	71,175	88,151
Commercial paper
Cash and cash equivalents:
Cash and cash equivalents		2,100
Cash
Cash and cash equivalents:
Cash and cash equivalents	1,253	781
Commercial paper
Short-term investments:
Short-term investments, Cost	31,936	60,631
Short-term investments, Gross Unrealized Gains	1	2
Short-term investments, Gross Unrealized Losses	(2)	(4)
Short-term investments, Fair Value	31,935	60,629
Corporate bonds
Short-term investments:
Short-term investments, Cost	7,025	24,547
Short-term investments, Gross Unrealized Gains	0	3
Short-term investments, Gross Unrealized Losses	(3)	(6)
Short-term investments, Fair Value	7,022	24,544
Long-term investments:
Long-term investments, Cost		2,115
Long-term investments, Gross Unrealized Gains		0
Long-term investments, Gross Unrealized Losses		(1)
Long-term investments, Fair Value		2,114
Asset-backed securities
Short-term investments:
Short-term investments, Cost	5,306
Short-term investments, Gross Unrealized Gains	0
Short-term investments, Gross Unrealized Losses	(2)
Short-term investments, Fair Value	5,304
U.S. government-sponsored agency bonds
Short-term investments:
Short-term investments, Cost		9,277
Short-term investments, Gross Unrealized Gains		2
Short-term investments, Gross Unrealized Losses		0
Short-term investments, Fair Value		9,279
U.S. treasury notes
Short-term investments:
Short-term investments, Cost	0	1,000
Short-term investments, Gross Unrealized Gains	0	0
Short-term investments, Gross Unrealized Losses	0	0
Short-term investments, Fair Value	$ 0	$ 1,000

Cash and Investments - Narrative (Details)	12 Months Ended
Cash and Investments - Narrative (Details)	Dec. 31, 2021 USD ($) investment	Dec. 31, 2020 USD ($) investment	Dec. 31, 2019 USD ($)
Available-for-Sale Debt Securities
Short-term available-for-sale securities contractual maturities, maximum	1 year
Long-term securities contractual maturities, minimum	1 year
Other-than-temporary impairment \| $	$ 0	$ 0	$ 0
Investment in continuous unrealized loss position for more than one year \| investment	0	0

Cash and Investments - Available-for-Sale Debt Securities by Contractual Maturity (Details) $ in Thousands	Dec. 31, 2021 USD ($)
Amortized Cost
Due in one year or less	$ 44,267
Fair Value
Due in one year or less	$ 44,261

Fair Value Measurements - Financial Assets and Liabilities Measured on a Recurring Basis (Details) - Recurring - USD ($) $ in Thousands	Dec. 31, 2021	Dec. 31, 2020
Assets:
Assets, fair value	$ 115,436	$ 187,817
Liabilities:
Liabilities, fair value	698	1,376
Money market funds
Assets:
Assets, fair value	71,175	88,151
Commercial paper
Assets:
Assets, fair value	31,935	62,729
Corporate bonds
Assets:
Assets, fair value	7,022	26,658
Asset-backed securities
Assets:
Assets, fair value	5,304
U.S. government-sponsored agency bonds
Assets:
Assets, fair value		9,279
U.S. treasury notes
Assets:
Assets, fair value		1,000
Derivative liability for exit fee
Liabilities:
Liabilities, fair value	698	1,376
Level 1
Assets:
Assets, fair value	71,175	88,151
Liabilities:
Liabilities, fair value	0	0
Level 1 \| Money market funds
Assets:
Assets, fair value	71,175	88,151
Level 1 \| Commercial paper
Assets:
Assets, fair value	0	0
Level 1 \| Corporate bonds
Assets:
Assets, fair value	0	0
Level 1 \| Asset-backed securities
Assets:
Assets, fair value	0
Level 1 \| U.S. government-sponsored agency bonds
Assets:
Assets, fair value		0
Level 1 \| U.S. treasury notes
Assets:
Assets, fair value		0
Level 1 \| Derivative liability for exit fee
Liabilities:
Liabilities, fair value	0	0
Level 2
Assets:
Assets, fair value	44,261	99,666
Liabilities:
Liabilities, fair value	0	0
Level 2 \| Money market funds
Assets:
Assets, fair value	0	0
Level 2 \| Commercial paper
Assets:
Assets, fair value	31,935	62,729
Level 2 \| Corporate bonds
Assets:
Assets, fair value	7,022	26,658
Level 2 \| Asset-backed securities
Assets:
Assets, fair value	5,304
Level 2 \| U.S. government-sponsored agency bonds
Assets:
Assets, fair value		9,279
Level 2 \| U.S. treasury notes
Assets:
Assets, fair value		1,000
Level 2 \| Derivative liability for exit fee
Liabilities:
Liabilities, fair value	0	0
Level 3
Assets:
Assets, fair value	0	0
Liabilities:
Liabilities, fair value	698	1,376
Level 3 \| Money market funds
Assets:
Assets, fair value	0	0
Level 3 \| Commercial paper
Assets:
Assets, fair value	0	0
Level 3 \| Corporate bonds
Assets:
Assets, fair value	0	0
Level 3 \| Asset-backed securities
Assets:
Assets, fair value	0
Level 3 \| U.S. government-sponsored agency bonds
Assets:
Assets, fair value		0
Level 3 \| U.S. treasury notes
Assets:
Assets, fair value		0
Level 3 \| Derivative liability for exit fee
Liabilities:
Liabilities, fair value	$ 698	$ 1,376

Fair Value Measurements - Narrative (Details) - USD ($)	Dec. 31, 2021	Dec. 31, 2020
Fair Value Disclosures [Abstract]
Allowance for credit loss on available-for-sale debt securities	$ 0	$ 0

Collaboration and Licensing Agreements - Narrative (Details) $ in Millions, ¥ in Billions	1 Months Ended					3 Months Ended	12 Months Ended						50 Months Ended	79 Months Ended
	Nov. 30, 2019 USD ($) item	Mar. 31, 2018 USD ($)	Dec. 31, 2017 USD ($)	Nov. 30, 2017 USD ($)	Jun. 30, 2015 USD ($)	Mar. 31, 2019 USD ($)	Dec. 31, 2021 USD ($)	Dec. 31, 2021 CAD ($)	Dec. 31, 2020 USD ($)	Dec. 31, 2019 USD ($)	Dec. 31, 2018 USD ($)	Dec. 31, 2017 USD ($)	Dec. 31, 2021 USD ($)	Dec. 31, 2021 USD ($)	Dec. 31, 2021 JPY (¥)	Feb. 28, 2019 USD ($)	Jan. 01, 2018 USD ($)
Collaborative Arrangement and Arrangement Other than Collaborative [Line Items]
Revenue							$ 10,097,000		$ 7,571,000	$ 5,281,000
Accounts receivable							502,000		0				$ 502,000	$ 502,000
Deferred revenue							0		4,177,000				0	0
Cost of revenue							1,000,000		145,000	600,000
AstraZeneca
Collaborative Arrangement and Arrangement Other than Collaborative [Line Items]
Cost of revenue							1,000,000		145,000	600,000	$ 466,000	$ 9,400,000
Maximum potential payment per agreement							75,000,000						75,000,000	75,000,000
Licensing revenue
Collaborative Arrangement and Arrangement Other than Collaborative [Line Items]
Revenue							5,013,000		706,000	4,500,000
Product supply revenue
Collaborative Arrangement and Arrangement Other than Collaborative [Line Items]
Revenue							907,000		1,501,000	322,000
2019 KKC Agreement
Collaborative Arrangement and Arrangement Other than Collaborative [Line Items]
Revenue							4,200,000		5,400,000
Deferred revenue							0		4,177,000	$ 4,541,000			0	0
2019 KKC Agreement \| Kyowa Kirin Co. Ltd
Collaborative Arrangement and Arrangement Other than Collaborative [Line Items]
Upfront license fees	$ 10,000,000
First installment of upfront license fees	$ 5,000,000
Term of payment of license fee, first installment	30 days
Second installment of upfront license fees	$ 5,000,000
Term of agreement	2 years
Initial transaction price	$ 10,000,000
2019 KKC Agreement \| Kyowa Kirin Co. Ltd \| Minimum
Collaborative Arrangement and Arrangement Other than Collaborative [Line Items]
Number of separate collaborative agreements \| item	1
2017 KKC Agreement
Collaborative Arrangement and Arrangement Other than Collaborative [Line Items]
Accounts receivable							500,000						500,000	500,000
Prepayment received							3,200,000
Unbilled prepayments							1,500,000						1,500,000	1,500,000
2017 KKC Agreement \| Kyowa Kirin Co. Ltd
Collaborative Arrangement and Arrangement Other than Collaborative [Line Items]
Upfront license fees				$ 30,000,000
Unbilled revenue																$ 0
Potential development milestones				$ 55,000,000
Potential commercialization milestones							73,900,000						73,900,000	73,900,000	¥ 8.5
2017 KKC Agreement \| AstraZeneca
Collaborative Arrangement and Arrangement Other than Collaborative [Line Items]
Uncharged license fee reclassified to accounts payable						$ 1,000,000
2017 KKC Agreement \| Licensing revenue
Collaborative Arrangement and Arrangement Other than Collaborative [Line Items]
Revenue							5,000,000		0				$ 10,000,000
2017 KKC Agreement \| Product supply revenue
Collaborative Arrangement and Arrangement Other than Collaborative [Line Items]
Revenue							900,000		1,400,000
AstraZeneca Termination Agreement \| AstraZeneca
Collaborative Arrangement and Arrangement Other than Collaborative [Line Items]
Cost of revenue							1,000,000		100,000					$ 11,600,000
Percentage of royalty revenue					10.00%
Percentage of non royalty revenue					20.00%
Maximum potential payment per agreement					$ 75,000,000
Fosun Agreement
Collaborative Arrangement and Arrangement Other than Collaborative [Line Items]
Revenue							0		0
Fosun Agreement \| Fosun Pharma
Collaborative Arrangement and Arrangement Other than Collaborative [Line Items]
Upfront payment received			$ 12,000,000
Potential development and commercialization milestones							$ 110,000,000
Threshold percentage of net sales for tiered royalties							20.00%	20.00%
Knight Agreement \| Knight
Collaborative Arrangement and Arrangement Other than Collaborative [Line Items]
Upfront payment received		$ 2,300,000
Potential development and commercialization milestones							$ 17,400,000	$ 22.2
Knight Agreement \| Licensing revenue
Collaborative Arrangement and Arrangement Other than Collaborative [Line Items]
Revenue							13,000		700,000
Knight Agreement \| Product supply revenue
Collaborative Arrangement and Arrangement Other than Collaborative [Line Items]
Revenue							0		100,000
XuanZhu Agreement \| XuanZhu
Collaborative Arrangement and Arrangement Other than Collaborative [Line Items]
Upfront payment received	$ 800,000
License fee recognized	1,500,000
Second milestone payment	$ 800,000
XuanZhu Agreement \| Licensing revenue
Collaborative Arrangement and Arrangement Other than Collaborative [Line Items]
Revenue							$ 0		$ 0
ASU 2014-09 \| Adjustments \| 2017 KKC Agreement \| Kyowa Kirin Co. Ltd
Collaborative Arrangement and Arrangement Other than Collaborative [Line Items]
Unbilled revenue																	$ 5,000,000
ASU 2014-09 \| Adjustments \| 2017 KKC Agreement \| AstraZeneca
Collaborative Arrangement and Arrangement Other than Collaborative [Line Items]
Uncharged license fee																	$ 1,000,000

Collaboration and Licensing Agreements - Astra Zeneca Revenue Recognized (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2021	Dec. 31, 2020	Dec. 31, 2019	Dec. 31, 2018	Dec. 31, 2017
Collaborative Arrangement and Arrangement Other than Collaborative [Line Items]
Cost of revenue, recognized	$ 1,000	$ 145	$ 600
AstraZeneca
Collaborative Arrangement and Arrangement Other than Collaborative [Line Items]
Cost of revenue, recognized	1,000	145	600	$ 466	$ 9,400
Cost of revenue, amount paid	1,003	$ 742	$ 1,002	$ 2,864	6,000
Cost of revenue, aggregate amount recognized	11,611
Cost of revenue, aggregate amount paid	11,611
Maximum payment per termination agreement	75,000
Remaining potential commitment	$ 63,389
Cost of revenue, adjustment					$ 1,000

- Definition

The aggregate cost of goods produced and sold and services rendered during the reporting period.

+ References

Reference 1: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 470
-SubTopic 10
-Section S99
-Paragraph 1B
-Subparagraph (SX 210.13-02(a)(5))
-URI http://asc.fasb.org/extlink&oid=124359900&loc=SL124442552-122756

Reference 2: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 825
-SubTopic 10
-Section 50
-Paragraph 28
-Subparagraph (f)
-URI http://asc.fasb.org/extlink&oid=123596393&loc=d3e14064-108612

Reference 3: 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(g)(1)(ii))
-URI http://asc.fasb.org/extlink&oid=120395691&loc=d3e23780-122690

Reference 4: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 470
-SubTopic 10
-Section S99
-Paragraph 1A
-Subparagraph (SX 210.13-01(a)(4)(iv))
-URI http://asc.fasb.org/extlink&oid=124359900&loc=SL124442526-122756

Reference 5: http://fasb.org/us-gaap/role/ref/legacyRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 220
-SubTopic 10
-Section S99
-Paragraph 2
-Subparagraph (SX 210.5-03.2)
-URI http://asc.fasb.org/extlink&oid=123367319&loc=SL114868664-224227

Reference 6: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 323
-SubTopic 10
-Section 50
-Paragraph 3
-Subparagraph (c)
-URI http://asc.fasb.org/extlink&oid=114001798&loc=d3e33918-111571

Reference 7: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 470
-SubTopic 10
-Section S99
-Paragraph 1A
-Subparagraph (SX 210.13-01(a)(5))
-URI http://asc.fasb.org/extlink&oid=124359900&loc=SL124442526-122756

Reference 8: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 470
-SubTopic 10
-Section S99
-Paragraph 1B
-Subparagraph (SX 210.13-02(a)(4)(i))
-URI http://asc.fasb.org/extlink&oid=124359900&loc=SL124442552-122756

Reference 9: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 470
-SubTopic 10
-Section S99
-Paragraph 1B
-Subparagraph (SX 210.13-02(a)(4)(iii)(B))
-URI http://asc.fasb.org/extlink&oid=124359900&loc=SL124442552-122756

Reference 10: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 470
-SubTopic 10
-Section S99
-Paragraph 1B
-Subparagraph (SX 210.13-02(a)(4)(iii)(A))
-URI http://asc.fasb.org/extlink&oid=124359900&loc=SL124442552-122756

Reference 11: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 470
-SubTopic 10
-Section S99
-Paragraph 1A
-Subparagraph (SX 210.13-01(a)(4)(i))
-URI http://asc.fasb.org/extlink&oid=124359900&loc=SL124442526-122756

Reference 12: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 470
-SubTopic 10
-Section S99
-Paragraph 1A
-Subparagraph (SX 210.13-01(a)(4)(iii)(A))
-URI http://asc.fasb.org/extlink&oid=124359900&loc=SL124442526-122756

Reference 13: http://www.xbrl.org/2009/role/commonPracticeRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 470
-SubTopic 10
-Section S99
-Paragraph 1A
-Subparagraph (SX 210.13-01(a)(4)(ii))
-URI http://asc.fasb.org/extlink&oid=124359900&loc=SL124442526-122756

Reference 14: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 470
-SubTopic 10
-Section S99
-Paragraph 1B
-Subparagraph (SX 210.13-02(a)(4)(iv))
-URI http://asc.fasb.org/extlink&oid=124359900&loc=SL124442552-122756

+ Details

Collaboration and Licensing Agreements - Deferred Revenue (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2021	Dec. 31, 2020
Deferred revenue - current
Beginning balance	$ 4,177
Ending balance	0	$ 4,177
Deferred revenue - non-current
Beginning balance	0
Ending balance	4,727	0
2019 KKC Agreement
Deferred revenue - current
Beginning balance	4,177	4,541
Decreases due to revenue recognized in the period for which cash has been received	(4,177)	(364)
Ending balance	0	4,177
2017 KKC Agreement
Deferred revenue - non-current
Beginning balance	0	0
Increases due to cash received during the period	3,242	0
Increase due to unbilled prepayments recorded during the period	1,485	0
Ending balance	$ 4,727	$ 0

Borrowings - Narrative (Details) - USD ($)					1 Months Ended	12 Months Ended
Borrowings - Narrative (Details) - USD ($)	Feb. 23, 2022	Oct. 09, 2020	Dec. 03, 2019	May 16, 2018	Nov. 30, 2021	Dec. 31, 2027	Dec. 31, 2026	Dec. 31, 2025	Dec. 31, 2024	Dec. 31, 2021	Dec. 31, 2020	Dec. 31, 2019
Term Loans
Principal repayment										$ 19,444,000	$ 0	$ 0
Principal outstanding										$ 33,031,000
Loan Agreement \| 2018 Term Loan
Term Loans
Term loan amount				$ 50,000,000
Net proceeds from loan				49,300,000
Interest-only payment extension term (in months)		12 months	6 months
Principal repayment					$ 16,700,000
Closing fee		$ 100,000		$ 500,000
Final fee due upon maturity, acceleration, prepayment, or termination (percent)		4.95%		3.95%
Additional default interest rate				4.00%
Loan Agreement \| 2018 Term Loan \| Subsequent event
Term Loans
Principal outstanding	$ 25,000,000
Loan Agreement \| 2018 Term Loan \| LIBOR
Term Loans
Floating per annum rate (percent)				7.45%
Loan Agreement \| 2018 Term Loan \| Prior to first anniversary of closing date
Term Loans
Prepayment premium (as a percent)				3.00%
Loan Agreement \| 2018 Term Loan \| After first anniversary through second anniversary of closing date
Term Loans
Prepayment premium (as a percent)				2.00%
Loan Agreement \| 2018 Term Loan \| After second anniversary to maturity date
Term Loans
Prepayment premium (as a percent)				1.00%
Loan Agreement \| Term Loan A \| Subsequent event
Term Loans
Net proceeds from loan	27,500,000
Loan Agreement \| Term Loan A \| Forecast
Term Loans
Principal repayment						$ 2,300,000	$ 9,200,000	$ 9,200,000	$ 6,900,000
Final fee payment						$ 1,400,000
Loan Agreement \| Term Loan B \| Subsequent event
Term Loans
Remaining funding based on milestone achievement	$ 22,500,000

Borrowings - Future Payment Obligations (Details) - USD ($) $ in Thousands	Dec. 31, 2021	Dec. 31, 2020
Future payment obligations
2022	$ 33,031
Total repayment obligations	33,031
Less: Unamortized discount and debt issuance costs	(235)
Less: Unaccreted value of final fee	(532)
Loan payable	32,264
Less: Loan payable, current portion	(32,264)	$ (4,167)
Loan payable, net of current portion	$ 0	$ 46,621

- Definition

Amount, after unamortized (discount) premium and debt issuance costs, of long-term debt. Includes, but not limited to, notes payable, bonds payable, debentures, mortgage loans and commercial paper. Excludes capital lease obligations.

+ References + Details

Derivative Liability - Narrative (Details) - USD ($) $ in Millions	Feb. 23, 2022	Dec. 31, 2021	May 31, 2018
Exit fee derivative
Derivative [Line Items]
Agreed amount for exit fee upon change of control or regulatory approval		$ 1.5	$ 1.5
Exit fee derivative \| Level 3
Derivative [Line Items]
Fair value analysis, percentage change in probability of occurrence		10.00%
Fair value analysis, effect on fair value based on 10% change in probability of occurrence		$ 0.1
Subsequent event \| 2022 Exit Fee \| Term loan
Derivative [Line Items]
Exit fee (percent)	2.00%

Derivative Liability - Changes in Fair Value (Details) - Exit fee derivative liability - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2021	Dec. 31, 2020	Dec. 31, 2019
Change in Fair Value of Derivative Liability
Fair value of exit fee derivative liability, beginning	$ 1,376	$ 969	$ 533
Change in estimated fair value of derivative liability	(678)	407	436
Fair value of exit fee derivative liability, ending	$ 698	$ 1,376	$ 969

Leases - Narrative (Details) $ in Thousands	1 Months Ended		2 Months Ended	12 Months Ended
Leases - Narrative (Details) $ in Thousands	Nov. 30, 2020 USD ($) ft² renewal_option	Sep. 30, 2019 ft²	May 31, 2021 USD ($) ft² renewal_option	Dec. 31, 2021 USD ($) ft² lease_agreement	Dec. 31, 2020 USD ($)	Dec. 31, 2019 USD ($)	Oct. 31, 2018 ft²
Lessee, Lease, Description [Line Items]
Number of lease agreements \| lease_agreement				3
Right-of-use assets obtained in exchange for lease obligations \| $				$ 1,604	$ 450	$ 5,810
Fremont facility
Lessee, Lease, Description [Line Items]
Office space area (sq ft)				72,500
Office space area added (sq ft)		10,716
Original Waltham facility
Lessee, Lease, Description [Line Items]
Office space area (sq ft)							3,520
Waltham facility
Lessee, Lease, Description [Line Items]
Office space area (sq ft)			12,864
Existence of option to extend			true
Number of options to extend \| renewal_option			1
Term of lease extension			5 years
Right-of-use assets obtained in exchange for lease obligations \| $			$ 1,600
Milwaukee facility
Lessee, Lease, Description [Line Items]
Office space area (sq ft)	4,768
Existence of option to extend	true
Number of options to extend \| renewal_option	1
Term of lease extension	5 years
Right-of-use assets obtained in exchange for lease obligations \| $	$ 400

Leases - Additional Lease Information (Details) - USD ($) $ in Thousands	Dec. 31, 2021	Dec. 31, 2020
Facilities - right-of-use assets and lease liabilities
Right-of-use assets	$ 12,752	$ 2,274
Current portion of lease liabilities	3,492	2,117
Operating lease liability, net of current portion	9,748	413
Total operating lease liabilities	$ 13,240	$ 2,530
Additional details
Weighted-average remaining life (years)	3 years 4 months 24 days	1 year 6 months
Weighted-average discount rate	6.90%	11.70%

Leases - Lease Costs (Details) - USD ($) $ in Thousands	12 Months Ended
Leases - Lease Costs (Details) - USD ($) $ in Thousands	Dec. 31, 2021	Dec. 31, 2020	Dec. 31, 2019
Lease costs
Operating lease expense	$ 3,671	$ 2,608	$ 2,592
Cash paid for operating lease	$ 3,438	$ 3,065	$ 2,645

Leases - Undiscounted Cash Payment Obligations (Details) - USD ($) $ in Thousands	Dec. 31, 2021	Dec. 31, 2020
Undiscounted cash payment obligations
2022	$ 4,292
2023	4,440
2024	4,589
2025	1,321
2026	252
Thereafter	0
Total undiscounted operating lease payments	14,894
Imputed interest expenses	(1,654)
Total operating lease liabilities	13,240	$ 2,530
Current portion of operating lease liability	(3,492)	(2,117)
Operating lease liability, net of current portion	$ 9,748	$ 413

Stockholders' Equity (Details) - USD ($) $ / shares in Units, shares in Thousands			1 Months Ended			2 Months Ended	3 Months Ended	5 Months Ended	12 Months Ended			14 Months Ended
	Dec. 09, 2019	Nov. 22, 2019	Sep. 10, 2021	Jun. 18, 2021	Dec. 31, 2019	Dec. 31, 2021	Feb. 19, 2021	Dec. 31, 2021	Dec. 31, 2021	Dec. 31, 2020	Dec. 31, 2019	Dec. 31, 2021	Aug. 31, 2021	Jul. 31, 2020
Subsidiary, Sale of Stock [Line Items]
Proceeds from issuance of common stock									$ 101,146,000	$ 21,047,000	$ 0
Common stock
Subsidiary, Sale of Stock [Line Items]
Maximum aggregate offering price														$ 250,000,000
2020 Open Market Sales Agreement
Subsidiary, Sale of Stock [Line Items]
Common stock sold and issued (in shares)			3,300	4,000		7,700	8,200					23,300
Weighted-average share price (in dollars per share)												$ 4.30
Offering sales commission (percent)									3.00%
Proceeds from issuance of common stock												$ 100,000,000
2020 Open Market Sales Agreement \| Common stock
Subsidiary, Sale of Stock [Line Items]
Maximum aggregate offering price														$ 100,000,000
2021 Open Market Sales Agreement
Subsidiary, Sale of Stock [Line Items]
Common stock sold and issued (in shares)								15,700
Weighted-average share price (in dollars per share)								$ 1.60
Offering sales commission (percent)								3.00%
Proceeds from issuance of common stock								$ 25,000,000
2021 Open Market Sales Agreement \| Common stock
Subsidiary, Sale of Stock [Line Items]
Maximum aggregate offering price													$ 150,000,000
Underwritten public offering, including underwriter option
Subsidiary, Sale of Stock [Line Items]
Common stock sold and issued (in shares)	23,000
Gross proceeds from sale of stock					$ 143,800,000
Underwriting discounts, commissions, and offering expenses					8,900,000
Proceeds from issuance of common stock					$ 134,900,000
Underwritten public offering
Subsidiary, Sale of Stock [Line Items]
Common stock sold and issued (in shares)	20,000
Share price (in dollars per share)	$ 6.25
Underwriter option
Subsidiary, Sale of Stock [Line Items]
Common stock sold and issued (in shares)	3,000
Underwriter option period	30 days
Private Placement
Subsidiary, Sale of Stock [Line Items]
Common stock sold and issued (in shares)		2,900
Share price (in dollars per share)		$ 6.96
Proceeds from issuance of common stock		$ 20,000,000

Equity Incentive Plans - Narrative (Details) - USD ($) $ / shares in Units, $ in Thousands		1 Months Ended				6 Months Ended	12 Months Ended
	Jun. 18, 2014	Jan. 31, 2022	Jan. 31, 2021	Sep. 30, 2020	Jul. 31, 2018	Jun. 30, 2014	Dec. 31, 2021	Dec. 31, 2020	Dec. 31, 2019	Dec. 31, 2018	Nov. 30, 2016
Equity Incentive Plans
Common stock closing price (in dollars per share)							$ 1.10
Intrinsic value of options exercised							$ 1,700	$ 2,700	$ 400
Weighted-average grant-date estimated fair value of options granted (in dollars per share)							$ 3.92	$ 4.82	$ 1.79
Stock-based compensation							$ 12,039	$ 10,583	$ 9,936
Issuance of common stock for services							$ 190	$ 310	$ 312
2014 Plan
Equity Incentive Plans
Number of shares initially authorized	1,400,000
Common stock reserved for future issuance (in shares)	1,500,000
Number of shares added to initial reserve	35,000
Potential increase to shares reserved for inclusion of forfeited or unexercised options from prior plan	1,200,000
Potential increase in shares reserved as a percentage of shares outstanding	4.00%
Maximum shares to be issued upon exercise of incentive stock options	10,700,000
Inducement Plan
Equity Incentive Plans
Common stock reserved for future issuance (in shares)											1,000,000
Number of shares added to initial reserve			500,000
Share of common stock subject to issued inducement grants							400,000
Inducement Plan \| Subsequent event
Equity Incentive Plans
Number of shares added to initial reserve		2,000,000
ESPP
Equity Incentive Plans
Common stock reserved for future issuance (in shares)	200,000
Potential increase in shares reserved as a percentage of shares outstanding	1.00%
Maximum shares to be issued under ESPP	2,200,000
Stock options \| 2008 Plan
Equity Incentive Plans
Vesting period (in years)						4 years
PRSUs
Equity Incentive Plans
Number of shares granted					900,000			30,000
Number of shares vested				900,000					0	0
Stock-based compensation							$ 0	$ 1,200
RSUs
Equity Incentive Plans
Number of shares granted							4,144,051
Number of shares vested							193,147
Estimated fair value of RSUs vested							$ 800	$ 0	$ 200
Board of directors
Equity Incentive Plans
Issuance of common stock for services (in shares)							26,000	42,000	113,000
Issuance of common stock for services							$ 200	$ 300	$ 300

Equity Incentive Plans - Stock Options (Details) $ / shares in Units, $ in Thousands	12 Months Ended
	Dec. 31, 2021 USD ($) $ / shares shares
Number of Shares
Options issued and outstanding balance, beginning (shares)	9,790,049
Options granted (shares)	3,409,719
Options exercised (shares)	(331,310)
Options canceled (shares)	(2,451,306)
Options issued and outstanding balance, ending (shares)	10,417,152
Options vested and expected to vest (shares)	10,417,152
Options exercisable (shares)	6,772,289
Weighted-Average Exercise Price per Share
Options issued and outstanding balance, beginning (in dollars per share) \| $ / shares	$ 6.76
Options granted (in dollars per share) \| $ / shares	6.60
Options exercised (in dollars per share) \| $ / shares	1.96
Options canceled (in dollars per share) \| $ / shares	6.17
Options issued and outstanding balance, ending (in dollars per share) \| $ / shares	7.00
Options vested and expected to vest (in dollars per share) \| $ / shares	7.00
Options exercisable (in dollars per share) \| $ / shares	$ 7.39
Weighted Average Remaining Contractual Term
Options issued and outstanding (in years)	6 years 6 months 25 days
Options vest and expected to vest (in years)	6 years 6 months 25 days
Options exercisable (in years)	5 years 6 months 29 days
Aggregate Intrinsic Value
Options issued and outstanding \| $	$ 0
Options vested and expected to vest \| $	0
Options exercisable \| $	$ 0
Stock options
Shares Available for Grant
Shares available for grant, beginning (shares)	1,757,058
Shares available for grant, effect of authorized (shares)	4,201,766
Shares available for grant, effect of granted (shares)	(3,409,719)
Shares available for grant, effect of canceled (shares)	2,451,306
Shares available for grant, effect of shares issued for services (shares)	(25,989)
Shares available for grant, ending (shares)	4,974,422

Equity Incentive Plans - Valuation Assumptions for Stock Options (Details) - Stock options	12 Months Ended
	Dec. 31, 2021	Dec. 31, 2020	Dec. 31, 2019
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Expected term (years)	4 years 11 months 19 days	6 years	6 years
Expected volatility	77.00%	83.00%	81.00%
Risk-free interest rate	4.69%	1.07%	2.42%
Dividend yield	0.00%	0.00%	0.00%

Equity Incentive Plans - Restricted Stock Units (Details) - RSUs	12 Months Ended
	Dec. 31, 2021 $ / shares shares
Number of RSUs
Nonvested balance, beginning (shares) \| shares	158,626
Granted (shares) \| shares	4,144,051
Vested (shares) \| shares	(193,147)
Forfeited (shares) \| shares	(580,848)
Nonvested balance, ending (shares) \| shares	3,528,682
Weighted-Average Grant Date Fair Value Per Share
Nonvested balance, beginning (in dollars per share) \| $ / shares	$ 5.64
Granted (in dollars per share) \| $ / shares	2.71
Vested (in dollars per share) \| $ / shares	6.39
Forfeited (in dollars per share) \| $ / shares	6.38
Nonvested balance, ending (in dollars per share) \| $ / shares	$ 2.04

Equity Incentive Plans - Employee Stock Purchase Plan (Details) - ESPP $ / shares in Units, $ in Thousands	12 Months Ended
	Dec. 31, 2021 USD ($) $ / shares shares
Shares Available for Grant
Shares available for grant, beginning (shares)	349,647
Shares purchased (shares)	(386,664)
Shares available for grant, ending (shares)	898,982
Number of Shares Purchased
Purchased, beginning (shares)	661,611
Shares purchased (shares)	(386,664)
Purchased, ending (shares)	1,048,275
Purchase Price per Share (in dollars per share) \| $ / shares	$ 2.12
Gross Proceeds \| $	$ 819

Equity Incentive Plans - Valuation Assumptions for ESPP (Details) - ESPP	12 Months Ended
	Dec. 31, 2021	Dec. 31, 2020	Dec. 31, 2019
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Expected term (years)	6 months	6 months	6 months
Expected volatility	123.00%	79.00%	69.00%
Risk-free interest rate	0.65%	0.48%	2.00%
Dividend yield	0.00%	0.00%	0.00%

Equity Incentive Plans - Stock-Based Compensation (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2021	Dec. 31, 2020	Dec. 31, 2019
Share-based Payment Arrangement, Expensed and Capitalized, Amount [Line Items]
Stock-based compensation	$ 12,039	$ 10,583	$ 9,936
Research and development
Share-based Payment Arrangement, Expensed and Capitalized, Amount [Line Items]
Stock-based compensation	4,116	4,061	4,104
General and administrative
Share-based Payment Arrangement, Expensed and Capitalized, Amount [Line Items]
Stock-based compensation	$ 7,923	$ 6,522	$ 5,832

Equity Incentive Plans - Unrecognized Stock-Based Compensation (Details) $ in Thousands	12 Months Ended
	Dec. 31, 2021 USD ($)
Stock options
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Unrecognized Compensation Expense	$ 14,506
Average Remaining Vesting Period (years)	2 years 4 months 24 days
RSUs
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Unrecognized Compensation Expense	$ 2,262
Average Remaining Vesting Period (years)	9 months 18 days
ESPP
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Unrecognized Compensation Expense	$ 44
Average Remaining Vesting Period (years)	1 month 6 days

Restructuring (Details) - Workforce realignment $ in Millions			3 Months Ended		12 Months Ended
	Nov. 30, 2021 lease_agreement	Oct. 12, 2021 employee	Dec. 31, 2021 USD ($) employee	Sep. 30, 2021 employee	Dec. 31, 2021 USD ($)
Restructuring Cost and Reserve [Line Items]
Reduction in workforce \| employee			72	83
Reduction in workforce (percent)				33.00%
Notice period for impacted employees cash payments and benefits				60 days
Additional planned reduction in workforce \| employee		100
Additional planned reduction in workforce (percent)		60.00%
Previously eliminated positions retained \| lease_agreement	28
Restructuring charges					$ 6.2
Estimated restructuring liability			$ 0.5		0.5
Research and development expenses
Restructuring Cost and Reserve [Line Items]
Restructuring charges					2.7
General and administrative expense
Restructuring Cost and Reserve [Line Items]
Restructuring charges					$ 3.5

Property and Equipment, Net - Balances (Details) - USD ($) $ in Thousands	Dec. 31, 2021	Dec. 31, 2020
Property, Plant and Equipment [Line Items]
Property and equipment, gross	$ 18,253	$ 16,386
Less: accumulated depreciation	(15,891)	(14,450)
Total property and equipment, net	2,362	1,936
Laboratory equipment
Property, Plant and Equipment [Line Items]
Property and equipment, gross	7,474	7,268
Office equipment and furniture
Property, Plant and Equipment [Line Items]
Property and equipment, gross	2,034	1,133
Leasehold improvements
Property, Plant and Equipment [Line Items]
Property and equipment, gross	$ 8,745	$ 7,985

Property and Equipment, Net - Narrative (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2021	Dec. 31, 2020	Dec. 31, 2019
Property, Plant and Equipment [Abstract]
Depreciation expense	$ 1,441	$ 1,824	$ 2,501

Accrued Expenses and Other Current Liabilities (Details) - USD ($) $ in Thousands	Dec. 31, 2021	Dec. 31, 2020
Payables and Accruals [Abstract]
Accrued clinical expenses	$ 2,522	$ 2,197
Accrued contract manufacturing expenses	2,485	1,840
Derivative liability for exit fee	698	1,376
Accrued professional and consulting services	597	243
Accrued sales and marketing expenses	256	593
Accrued interest expense	203	123
Other	605	285
Accrued liabilities and other liabilities	$ 7,366	$ 6,657

Income Taxes - Components of Provision for Income Taxes (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2021	Dec. 31, 2020	Dec. 31, 2019
Current:
State	$ 4	$ 2	$ 2
Foreign	0	0	301
Total current	4	2	303
Deferred:
Federal	0	0	0
Total deferred	0	0	0
Provision for income taxes	$ 4	$ 2	$ 303

- Definition

Amount of current income tax expense (benefit) and deferred income tax expense (benefit) pertaining to continuing operations.

+ References + Details

Income Taxes - Reconciliation of Effective Tax Rate (Details)	12 Months Ended
	Dec. 31, 2021	Dec. 31, 2020	Dec. 31, 2019
Income Tax Disclosure [Abstract]
Change in valuation allowance	(20.00%)	(22.30%)	(21.90%)
Income tax at the federal statutory rate	21.00%	21.00%	21.00%
Tax credits	1.00%	1.30%	1.60%
State taxes, net of federal benefit	0.40%	0.70%	0.30%
Stock based compensation	(1.30%)	(0.10%)	(0.40%)
Executive compensation disallowed under IRC Sec 162(m)	(1.10%)	(0.50%)	(0.50%)
Other	0.00%	(0.10%)	(0.40%)
Income tax provision	0.00%	0.00%	(0.30%)

Income Taxes - Components of Deferred Tax Assets (Details) - USD ($) $ in Thousands	Dec. 31, 2021	Dec. 31, 2020
Deferred tax assets:
Amortization and depreciation	$ 61,098	$ 51,370
Net operating loss carryforwards	74,989	53,436
Tax credits	13,827	11,777
Stock-based compensation	4,054	5,524
Other	3,867	1,804
Gross deferred tax assets	157,835	123,911
Valuation allowance	(155,141)	(123,402)
Deferred tax assets net of valuation allowance	2,694	509
Deferred tax liabilities:
Right-of-use asset	(2,689)	(479)
Other	(5)	(30)
Net deferred tax assets	$ 0	$ 0

Income Taxes - Narrative (Details) $ in Millions	Dec. 31, 2021 USD ($)
Federal
Income Tax Disclosure [Line Items]
Net operating loss carryforwards	$ 386.3
Net operating loss carryforwards, indefinite	236.1
Federal \| Research and development tax credit
Income Tax Disclosure [Line Items]
Tax credit carryforwards	16.4
Foreign
Income Tax Disclosure [Line Items]
Tax credit carryforwards	1.2
State \| California
Income Tax Disclosure [Line Items]
Net operating loss carryforwards	88.3
State \| California \| Research and development tax credit
Income Tax Disclosure [Line Items]
Tax credit carryforwards	8.4
State \| California \| Minimum tax credit carryforwards
Income Tax Disclosure [Line Items]
Tax credit carryforwards	0.1
State \| Other states
Income Tax Disclosure [Line Items]
Net operating loss carryforwards	$ 4.5

Income Taxes - Reconciliation of Unrecognized Tax Benefits (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2021	Dec. 31, 2020	Dec. 31, 2019
Reconciliation of Unrecognized Tax Benefits
Balance at beginning of year	$ 23,624	$ 24,538	$ 23,052
Additions (subtractions) based on tax positions related to prior year	(811)	(1,388)
Additions (subtractions) based on tax positions related to prior year			755
Additions based on tax positions related to current year	1,613	474	731
Balance at end of year	$ 24,426	$ 23,624	$ 24,538

Geographic Information and Concentrations - Revenue by Geographical Area (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2021	Dec. 31, 2020	Dec. 31, 2019
Revenues from External Customers and Long-Lived Assets [Line Items]
Total revenues	$ 10,097	$ 7,571	$ 5,281
United States
Revenues from External Customers and Long-Lived Assets [Line Items]
Total revenues	0	0	0
North America
Revenues from External Customers and Long-Lived Assets [Line Items]
Total revenues	13	806	0
Asia Pacific
Revenues from External Customers and Long-Lived Assets [Line Items]
Total revenues	$ 10,084	$ 6,765	5,281
Japan
Revenues from External Customers and Long-Lived Assets [Line Items]
Total revenues			800
Hong Kong
Revenues from External Customers and Long-Lived Assets [Line Items]
Total revenues			1,500
China
Revenues from External Customers and Long-Lived Assets [Line Items]
Total revenues			$ 3,000

- Definition

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

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Geographic Information and Concentrations - Concentration Risk (Details) - Revenue - Collaboration partnership concentration risk	12 Months Ended
	Dec. 31, 2021	Dec. 31, 2020	Dec. 31, 2019
KKC
Concentration Risk [Line Items]
Concentration risk (percent)	100.00%	89.00%	15.00%
Knight
Concentration Risk [Line Items]
Concentration risk (percent)	0.00%	11.00%	0.00%
Fosun Pharma
Concentration Risk [Line Items]
Concentration risk (percent)	0.00%	0.00%	57.00%
XuanZhu
Concentration Risk [Line Items]
Concentration risk (percent)	0.00%	0.00%	28.00%

Net Loss Per Share - Computation of Net Loss Per Common Share (Details) - USD ($) $ / shares in Units, $ in Thousands	12 Months Ended
	Dec. 31, 2021	Dec. 31, 2020	Dec. 31, 2019
Numerator:
Net loss	$ (158,165)	$ (94,313)	$ (94,940)
Denominator:
Weighted average common shares outstanding - basic	104,205,645	89,582,138	64,478,066
Weighted average common shares outstanding - diluted	104,205,645	89,582,138	64,478,066
Net loss per share - basic (in dollars per share)	$ (1.52)	$ (1.05)	$ (1.47)
Net loss per share - diluted (in dollars per share)	$ (1.52)	$ (1.05)	$ (1.47)

- Definition

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

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

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+ Details

Net Loss Per Share - Anti-Dilutive Securities and Potential Common Shares (Details) - shares	12 Months Ended
	Dec. 31, 2021	Dec. 31, 2020	Dec. 31, 2019
Antidilutive Securities Excluded from Computation of Earnings Per Share [Line Items]
Anti-dilutive securities not included in computation of diluted net loss per share	13,679,684	10,298,725	10,247,413
Potential common shares that would have been included if not for anti-dilutive effect of securities	1,100,000	2,100,000	1,100,000
Options to purchase common stock
Antidilutive Securities Excluded from Computation of Earnings Per Share [Line Items]
Anti-dilutive securities not included in computation of diluted net loss per share	11,870,778	9,246,047	7,128,247
Restricted stock units
Antidilutive Securities Excluded from Computation of Earnings Per Share [Line Items]
Anti-dilutive securities not included in computation of diluted net loss per share	1,602,384	26,121	0
ESPP shares issuable
Antidilutive Securities Excluded from Computation of Earnings Per Share [Line Items]
Anti-dilutive securities not included in computation of diluted net loss per share	206,522	94,466	78,761
Warrants to purchase common stock
Antidilutive Securities Excluded from Computation of Earnings Per Share [Line Items]
Anti-dilutive securities not included in computation of diluted net loss per share	0	932,091	2,172,899
Performance-based restricted stock units
Antidilutive Securities Excluded from Computation of Earnings Per Share [Line Items]
Anti-dilutive securities not included in computation of diluted net loss per share	0	0	867,506

Commitments and Contingencies (Details) - USD ($)	Dec. 31, 2021	Dec. 31, 2020
Commitments and Contingencies Disclosure [Abstract]
Contingent liabilities	$ 0	$ 0

Subsequent Events (Details) - USD ($) $ in Thousands	Feb. 23, 2022	May 16, 2018	Dec. 31, 2021	Oct. 09, 2020
Subsequent Event [Line Items]
Principal outstanding			$ 33,031
2018 Term Loan \| Term loan
Subsequent Event [Line Items]
Proceeds from loan payable, net of issuance costs		$ 49,300
Final fee due upon maturity, acceleration, prepayment, or termination (percent)		3.95%		4.95%
Additional default interest rate		4.00%
2018 Term Loan \| Term loan \| Prior to first anniversary of closing date
Subsequent Event [Line Items]
Prepayment premium (as a percent)		3.00%
2018 Term Loan \| Term loan \| After first anniversary through second anniversary of closing date
Subsequent Event [Line Items]
Prepayment premium (as a percent)		2.00%
2018 Term Loan \| Term loan \| After second anniversary to maturity date
Subsequent Event [Line Items]
Prepayment premium (as a percent)		1.00%
2018 Term Loan \| Term loan \| LIBOR
Subsequent Event [Line Items]
Floating per annum rate (percent)		7.45%
Subsequent event \| 2022 Term Loan \| Term loan
Subsequent Event [Line Items]
Final fee due upon maturity, acceleration, prepayment, or termination (percent)	4.95%
Loan agreement covenant, cash and cash equivalents as percentage of outstanding loan balance, minimum	80.00%
Loan agreement covenant, net product revenue as percentage of outstanding loan balance, minimum	60.00%
Additional default interest rate	4.00%
Subsequent event \| 2022 Term Loan \| Term loan \| Prior to first anniversary of closing date
Subsequent Event [Line Items]
Prepayment premium (as a percent)	3.00%
Subsequent event \| 2022 Term Loan \| Term loan \| After first anniversary through second anniversary of closing date
Subsequent Event [Line Items]
Prepayment premium (as a percent)	2.00%
Subsequent event \| 2022 Term Loan \| Term loan \| After second anniversary to maturity date
Subsequent Event [Line Items]
Prepayment premium (as a percent)	1.00%
Subsequent event \| 2022 Term Loan \| Term loan \| LIBOR
Subsequent Event [Line Items]
Floating per annum rate (percent)	7.95%
Addition to floating per annum rate (percent)	0.10%
Subsequent event \| Term Loan A \| Term loan
Subsequent Event [Line Items]
Proceeds from loan payable, net of issuance costs	$ 27,500
Closing fee	200
Subsequent event \| Term Loan B \| Term loan
Subsequent Event [Line Items]
Remaining funding based on milestone achievement	22,500
Future obligation upon loan funding or other events	100
Subsequent event \| 2018 Term Loan \| Term loan
Subsequent Event [Line Items]
Principal outstanding	$ 25,000
Subsequent event \| 2022 Exit Fee \| Term loan
Subsequent Event [Line Items]
Exit fee (percent)	2.00%
Exit fee, net product revenue threshold	$ 100,000
Exit fee, term (in years)	10 years