Protagonist Therapeutics, Inc 10-K

Item 8. Financial Statements and Supplementary Data PROTAGONIST THERAPEUTICS, INC. INDEX TO CONSOLIDATED FINANCIAL STATEMENTS Audited Consolidated Financial Statements Page Report of Independent Registered Public Accounting Firm (PCAOB ID: 42 ) 74 Report of Independent Registered Public Accounting Firm (PCAOB ID: 238 ) 77 Consolidated Balance Sheets 78 Consolidated Statements of Operations 79 Consolidated Statements of Comprehensive Loss 80 Consolidated Statements of Stockholders’ Equity 81 Consolidated Statements of Cash Flows 82 Notes to the Consolidated Financial Statements 83 ​ ​ ​ 73 Table of Contents Report of Independent Registered Public Accounting Firm To the Stockholders and the Board of Directors of Protagonist Therapeutics, Inc. Opinion on the Financial Statements We have audited the accompanying consolidated balance sheets of Protagonist Therapeutics, Inc. (the Company) as of December 31, 2021 and 2020, the related consolidated statements of operations, comprehensive loss, stockholders' equity and cash flows for each of the two years in the period ended December 31, 2021, and the related notes (collectively referred to as the “consolidated financial statements”). In our opinion, the consolidated financial statements present fairly, in all material respects, the financial position of the Company at December 31, 2021 and 2020, and the results of its operations and its cash flows for each of the two years in the period ended December 31, 2021, in conformity with U.S. generally accepted accounting principles. ​ We also have audited, in accordance with the standards of the Public Company Accounting Oversight Board (United States) (PCAOB), the Company's internal control over financial reporting as of December 31, 2021, based on criteria established in Internal Control-Integrated Framework issued by the Committee of Sponsoring Organizations of the Treadway Commission (2013 framework) and our report dated February 28, 2022 expressed an unqualified opinion thereon. Basis for Opinion These financial statements are the responsibility of the Company's management. Our responsibility is to express an opinion on the Company’s financial statements based on our audits. We are a public accounting firm registered with the PCAOB and are required to be independent with respect to the Company in accordance with the U.S. federal securities laws and the applicable rules and regulations of the Securities and Exchange Commission and the PCAOB. ​ We conducted our audits in accordance with the standards of the PCAOB. Those standards require that we plan and perform the audit to obtain reasonable assurance about whether the financial statements are free of material misstatement, whether due to error or fraud. Our audits included performing procedures to assess the risks of material misstatement of the financial statements, whether due to error or fraud, and performing procedures that respond to those risks. Such procedures included examining, on a test basis, evidence regarding the amounts and disclosures in the financial statements. Our audits also included evaluating the accounting principles used and significant estimates made by management, as well as evaluating the overall presentation of the financial statements. We believe that our audits provide a reasonable basis for our opinion. ​ Critical Audit Matters The critical audit matters communicated below are matters arising from the current period audit of the financial statements that were communicated or required to be communicated to the audit committee and that: (1) relate to accounts or disclosures that are material to the financial statements and (2) involved our especially challenging, subjective or complex judgments. The communication of critical audit matters does not alter in any way our opinion on the consolidated financial statements, taken as a whole, and we are not, by communicating the critical audit matters below, providing separate opinions on the critical audit matters or on the accounts or disclosures to which they relate. 74 Table of Contents ​ ​ ​ ​ ​ ​ ​ Accrued clinical and research related expenses Description of the Matter ​ At December 31, 2021, the Company has accrued $27.9 million of clinical and research related expenses. As described in Note 2 to the consolidated financial statements, the Company records estimated costs of research and development activities conducted by third-party service providers, which include the conduct of pre-clinical studies and clinical trials, and contract manufacturing activities, based upon the estimated amount of services provided but not yet invoiced. The Company accrues for these costs based on factors such as estimates of the work completed and in accordance with agreements established with its third-party service providers. Auditing management’s accounting for accrued clinical development cost is especially challenging because the evaluation is dependent on a high volume of data exchanged between third-party service providers, internal clinical personnel, and the Company’s finance department. The accrued amounts are determined based on an evaluation of the unique terms and conditions set forth in each respective agreement. Additionally, due to the duration of clinical trial activities and the timing of invoices received from third parties, the calculation of the accrual for services incurred requires management to determine that they have complete and accurate information from its vendors. ​ How We Addressed the Matter in Our Audit ​ To test accrued clinical development costs, our audit procedures included, among others, testing the accuracy and completeness of the inputs used in management’s analysis to determine costs incurred. We also inspected terms and conditions for selected research and development contracts and change orders and compared these to the cost models management used in tracking progress of service agreements. We met with the Company’s internal clinical personnel to understand the status of significant clinical activities. We evaluated services incurred by third parties by understanding the terms and timeline of significant projects, and evaluating management’s determination of work performed, subjects enrolled, sites activated and costs incurred. Further, we inspected selected invoices received from third parties after the balance sheet date and evaluated whether services performed prior to the balance sheet date had been properly included in costs accrued. ​ ​ ​ ​ ​ ​ Accounting for related party revenue recognition under the Janssen License and Collaboration Agreement Description of the Matter ​ As described in Note 3 to the consolidated financial statements, the Company is party to a License and Collaboration Agreement with Janssen Biotech, Inc. (Janssen), which was amended during 2021. The Company re-evaluates the transaction price for this agreement, including variable consideration, at the end of each reporting period and as uncertain events are resolved or other changes in circumstances occur. The Company and Janssen make quarterly cost sharing payments to one another in amounts necessary to ensure that each party bears its contractual share of the overall shared costs incurred. The Company utilizes a cost-based input method to measure proportional performance and to calculate the corresponding amount of revenue to recognize each reporting period. For the year ended December 31, 2021, the Company recorded $27.4 million of related party revenue under the License and Collaboration Agreement. ​ Auditing the Company’s revenue recognition for the Janssen agreement is complex due to the judgments made by management in the determination of the transaction price and the calculation of the cost-based input method. The determination of the transaction price and the calculation of the cost-based input method involve subjective estimates of future development costs to be incurred by the Company and by Janssen. Changes to these assumptions can have a material effect on the amount and timing of revenue recognized. ​ 75 Table of Contents How We Addressed the Matter in Our Audit ​ Our audit procedures included, among others, evaluating the changes to estimated future development resulting from the 2021 amendment to the agreement. We recomputed revenue recognized and tested the eligibility of research and development costs and appropriateness of FTE costs applied in the determination of the percentage completed under the revenue recognition model. We evaluated the appropriateness of the transaction price based upon estimated payments to be received during the duration of the contract, net of remaining development costs expected to be reimbursed by the Company to Janssen. We met with Company personnel to corroborate our understanding of collaboration developments and activities that have occurred to date. We also tested a sample of cash payments and receipts exchanged between the two parties throughout the year. ​ ​ /s/ Ernst & Young LLP ​ ​ We have served as the Company’s auditor since 2020. Redwood City, California February 28, 2022 ​ 76 Table of Contents ​ ​ Report of Independent Registered Public Accounting Firm To the Board of Directors and Stockholders of Protagonist Therapeutics, Inc. ​ Opinion on the Financial Statements ​ We have audited the consolidated statements of operation, comprehensive loss, changes in stockholders’ equity and cash flows of Protagonist Therapeutics, Inc. and its subsidiaries (the “Company”) for the year ended December 31, 2019, including the related notes (collectively referred to as the “consolidated financial statements”). In our opinion, the consolidated financial statements present fairly, in all material respects, the results of operations and cash flows of the Company for the year ended December 31, 2019 in conformity with accounting principles generally accepted in the United States of America. Basis for Opinion ​ These consolidated financial statements are the responsibility of the Company's management. Our responsibility is to express an opinion on the Company’s consolidated financial statements based on our audit. We are a public accounting firm registered with the Public Company Accounting Oversight Board (United States) (PCAOB) and are required to be independent with respect to the Company in accordance with the U.S. federal securities laws and the applicable rules and regulations of the Securities and Exchange Commission and the PCAOB. We conducted our audits of these consolidated financial statements in accordance with the standards of the PCAOB. Those standards require that we plan and perform the audit to obtain reasonable assurance about whether the consolidated financial statements are free of material misstatement, whether due to error or fraud. Our audit included performing procedures to assess the risks of material misstatement of the consolidated financial statements, whether due to error or fraud, and performing procedures that respond to those risks. Such procedures included examining, on a test basis, evidence regarding the amounts and disclosures in the consolidated financial statements. Our audit also included evaluating the accounting principles used and significant estimates made by management, as well as evaluating the overall presentation of the consolidated financial statements. We believe that our audits provide a reasonable basis for our opinion. ​ /s/ PricewaterhouseCoopers LLP San Jose, California February 28, 2022 ​ We served as the Company's auditor from 2015 to 2019. ​ ​ 77 Table of Contents PR OTAGONIST THERAPEUTICS, INC. Consolidated Balance Sheets (In thousands, except share data) ​ ​ ​ ​ ​ ​ ​ ​ ​ December 31, ​ 2021 2020 Assets ​ ​ ​ ​ ​ ​ Current assets: ​ ​ ​ ​ ​ ​ Cash and cash equivalents ​ $ 123,665 ​ $ 117,358 Marketable securities ​ ​ 203,235 ​ ​ 188,451 Restricted cash - current ​ ​ — ​ ​ 10 Receivable from collaboration partner and contract asset - related party ​ ​ 1,566 ​ ​ 2,426 Research and development tax incentive receivable ​ ​ 2,792 ​ ​ 1,084 Prepaid expenses and other current assets ​ ​ 9,478 ​ ​ 6,277 Total current assets ​ ​ 340,736 ​ ​ 315,606 Marketable securities - noncurrent ​ ​ — ​ ​ 2,000 Property and equipment, net ​ ​ 1,798 ​ ​ 1,462 Restricted cash - noncurrent ​ ​ 225 ​ ​ 450 Operating lease right-of-use asset ​ ​ 4,936 ​ ​ 4,950 Total assets ​ $ 347,695 ​ $ 324,468 Liabilities and Stockholders’ Equity ​ ​ ​ ​ ​ ​ Current liabilities: ​ ​ ​ ​ ​ Accounts payable ​ $ 1,600 ​ $ 3,075 Payable to collaboration partner - related party ​ ​ 899 ​ ​ 2,732 Accrued expenses and other payables ​ ​ 37,716 ​ ​ 18,498 Deferred revenue - related party ​ ​ 1,601 ​ ​ 14,477 Operating lease liability - current ​ ​ 2,200 ​ ​ 1,459 Total current liabilities ​ ​ 44,016 ​ ​ 40,241 Operating lease liability - noncurrent ​ ​ 3,658 ​ ​ 4,500 Other liabilities ​ ​ — ​ ​ 121 Total liabilities ​ ​ 47,674 ​ ​ 44,862 Commitments and contingencies ​ ​ ​ ​ ​ ​ Stockholders’ equity: ​ ​ ​ ​ ​ ​ Preferred stock, $ 0.00001 par value, 10,000,000 shares authorized; no shares issued and outstanding ​ ​ — ​ ​ — Common stock, $ 0.00001 par value, 90,000,000 shares authorized; 47,838,330 and 43,745,465 shares issued and outstanding as of December 31, 2021 and 2020, respectively ​ ​ — ​ ​ — Additional paid-in capital ​ ​ 709,682 ​ ​ 563,389 Accumulated other comprehensive (loss) gain ​ ​ ( 299 ) ​ ​ 28 Accumulated deficit ​ ​ ( 409,362 ) ​ ​ ( 283,811 ) Total stockholders’ equity ​ ​ 300,021 ​ ​ 279,606 Total liabilities and stockholders’ equity ​ $ 347,695 ​ $ 324,468 ​ The accompanying notes are an integral part of these consolidated financial statements. ​ 78 Table of Contents PROTAGONIST THERAPEUTICS, INC. Consolidated Statements of Operations (In thousands, except share and per share data) ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Year Ended December 31, ​ 2021 2020 2019 License and collaboration revenue - related party ​ $ 27,357 ​ $ 28,628 ​ $ 231 Operating expenses: ​ ​ ​ ​ ​ ​ ​ ​ ​ Research and development ​ ​ 126,006 ​ ​ 74,506 ​ ​ 65,003 General and administrative ​ 27,196 ​ 18,638 ​ 15,749 Total operating expenses ​ 153,202 ​ 93,144 ​ 80,752 Loss from operations ​ ( 125,845 ) ​ ( 64,516 ) ​ ( 80,521 ) Interest income ​ 443 ​ ​ 900 ​ 2,813 Interest expense ​ ​ — ​ ​ ( 598 ) ​ ​ ( 169 ) Loss on early repayment of debt ​ ​ — ​ ​ ( 585 ) ​ ​ — Other expense, net ​ ​ ( 149 ) ​ ​ ( 46 ) ​ ​ ( 1 ) Loss before income tax (expense) benefit ​ ​ ( 125,551 ) ​ ​ ( 64,845 ) ​ ​ ( 77,878 ) Income tax (expense) benefit ​ ​ — ​ ​ ( 1,305 ) ​ ​ 691 Net loss ​ $ ( 125,551 ) ​ $ ( 66,150 ) ​ $ ( 77,187 ) Net loss per share, basic and diluted ​ $ ( 2.71 ) ​ $ ( 1.92 ) ​ $ ( 2.98 ) Weighted-average shares used to compute net loss per share, basic and diluted ​ 46,322,910 34,396,446 25,894,024 ​ The accompanying notes are an integral part of these consolidated financial statements. ​ 79 Table of Contents PROTAGONIST THERAPEUTICS, INC. Consolidated Statements of Comprehensive Loss (In thousands) ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Year Ended December 31, ​ 2021 2020 2019 Net loss ​ $ ( 125,551 ) ​ $ ( 66,150 ) ​ $ ( 77,187 ) Other comprehensive loss: ​ ​ ​ ​ ​ ​ ​ (Loss) gain on translation of foreign operations ​ ( 182 ) ​ 266 ​ ( 44 ) Unrealized (loss) gain on marketable securities ​ ( 145 ) ​ ( 17 ) ​ 56 Comprehensive loss ​ $ ( 125,878 ) ​ $ ( 65,901 ) ​ $ ( 77,175 ) ​ The accompanying notes are an integral part of these consolidated financial statements. ​ ​ 80 Table of Contents PROTAGONIST THERAPEUTICS, INC. Consolidated Statements of Stockholders’ Equity (In thousands, except share and per share data) ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Accumulated ​ ​ ​ ​ ​ ​ ​ ​ Additional ​ Other ​ ​ ​ Total ​ ​ Common ​ Paid-In ​ Comprehensive ​ Accumulated ​ Stockholders’ ​ ​ Stock Capital (Loss) Gain Deficit Equity ​ Shares Amount ​ ​ ​ ​ ​ ​ ​ ​ ​ Balance at December 31, 2018 ​ 23,187,219 $ — ​ $ 253,222 $ ( 233 ) ​ $ ( 140,474 ) $ 112,515 Issuance of common stock pursuant to at-the-market offering, net of issuance costs ​ 2,846,641 ​ ​ — ​ ​ 34,492 ​ ​ — ​ ​ — ​ ​ 34,492 Issuance of common stock under equity incentive and employee stock purchase plans ​ 583,792 — ​ 1,779 — ​ — 1,779 Issuance of common stock upon exercise of Exchange Warrants ​ 599,997 ​ ​ — ​ ​ — ​ ​ — ​ ​ — ​ ​ — Stock-based compensation expense ​ — — ​ 8,353 — ​ — 8,353 Other comprehensive gain ​ — — ​ — 12 ​ — 12 Net loss ​ — — ​ — — ​ ( 77,187 ) ( 77,187 ) Balance at December 31, 2019 ​ 27,217,649 — ​ 297,846 ( 221 ) ​ ( 217,661 ) 79,964 Issuance of common stock pursuant to public offerings, net of issuance costs ​ 13,526,189 ​ ​ — ​ ​ 212,974 ​ ​ — ​ ​ — ​ ​ 212,974 Issuance of common stock pursuant to at-the-market offering, net of issuance costs ​ 2,483,719 ​ ​ — ​ ​ 41,871 ​ ​ — ​ ​ — ​ ​ 41,871 Issuance of common stock under equity incentive and employee stock purchase plans ​ 517,908 — ​ 2,799 — ​ — 2,799 Stock-based compensation expense ​ — — ​ 7,899 — ​ — 7,899 Other comprehensive gain ​ — — ​ — 249 ​ — 249 Net loss ​ — — ​ — — ​ ( 66,150 ) ( 66,150 ) Balance at December 31, 2020 ​ 43,745,465 — ​ 563,389 28 ​ ( 283,811 ) 279,606 Issuance of common stock pursuant to public offerings, net of issuance costs ​ 3,503,311 ​ ​ — ​ ​ 123,804 ​ ​ — ​ ​ — ​ ​ 123,804 Issuance of common stock under equity incentive and employee stock purchase plans ​ 596,614 — ​ 6,283 — ​ — 6,283 Shares withheld for net settlement of tax withholding upon vesting of restricted stock units ​ ( 7,060 ) ​ ​ — ​ ​ ( 189 ) ​ ​ — ​ ​ — ​ ​ ( 189 ) Stock-based compensation expense ​ — — ​ 16,395 — ​ — 16,395 Other comprehensive loss ​ — — ​ — ( 327 ) ​ — ( 327 ) Net loss ​ — — ​ — — ​ ( 125,551 ) ( 125,551 ) Balance at December 31, 2021 ​ 47,838,330 $ — ​ $ 709,682 $ ( 299 ) ​ $ ( 409,362 ) $ 300,021 ​ The accompanying notes are an integral part of these consolidated financial statements. ​ ​ 81 Table of Contents PROTAGONIST THERAPEUTICS, INC. Consolidated Statements of Cash Flows (In thousands) ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Year Ended December 31, ​ 2021 2020 2019 Cash Flows from Operating Activities ​ ​ ​ ​ Net loss ​ $ ( 125,551 ) ​ $ ( 66,150 ) ​ $ ( 77,187 ) Adjustments to reconcile net loss to net cash used in operating activities: ​ ​ ​ ​ ​ ​ ​ ​ ​ Stock-based compensation ​ ​ 16,395 ​ ​ 7,899 ​ ​ 8,353 Operating lease right-of-use asset amortization ​ ​ 1,962 ​ ​ 1,775 ​ ​ 1,792 Net amortization of premium (accretion of discount) on marketable securities ​ ​ 1,830 ​ ​ 37 ​ ​ ( 594 ) Depreciation and amortization ​ ​ 813 ​ ​ 948 ​ ​ 732 Change in deferred tax asset ​ ​ — ​ ​ 1,438 ​ ​ ( 775 ) Loss on early repayment of debt ​ ​ — ​ ​ 585 ​ ​ — Gain on disposal of property and equipment ​ ​ — ​ ​ — ​ ​ 8 Changes in operating assets and liabilities: ​ ​ ​ ​ ​ ​ ​ ​ ​ Research and development tax incentive receivable ​ ​ ( 1,775 ) ​ ​ ( 990 ) ​ ​ 1,411 Receivable from collaboration partner - related party ​ ​ 860 ​ ​ 4,329 ​ ​ ( 2,168 ) Prepaid expenses and other assets ​ ​ ( 3,227 ) ​ ​ ( 1,102 ) ​ ​ ( 2,820 ) Accounts payable ​ ​ ( 1,390 ) ​ ​ 309 ​ ​ ( 3,000 ) Payable to collaboration partner - related party ​ ​ ( 1,833 ) ​ ​ 1,471 ​ ​ 201 Accrued expenses and other payables ​ ​ 19,097 ​ ​ 5,840 ​ ​ 1,098 Deferred revenue - related party ​ ​ ( 12,876 ) ​ ​ ( 27,053 ) ​ ​ 33,307 Operating lease liability ​ ​ ( 2,049 ) ​ ​ ( 1,941 ) ​ ​ ( 1,885 ) Other liabilities ​ ​ ( 121 ) ​ ​ 121 ​ ​ — Net cash used in operating activities ​ ​ ( 107,865 ) ​ ​ ( 72,484 ) ​ ​ ( 41,527 ) Cash Flows from Investing Activities ​ ​ ​ ​ ​ ​ ​ ​ ​ Purchase of marketable securities ​ ​ ( 286,589 ) ​ ​ ( 280,027 ) ​ ​ ( 166,936 ) Proceeds from maturities of marketable securities ​ ​ 271,830 ​ ​ 189,533 ​ ​ 114,193 Purchases of property and equipment ​ ​ ( 1,101 ) ​ ​ ( 471 ) ​ ​ ( 967 ) Net cash used in investing activities ​ ​ ( 15,860 ) ​ ​ ( 90,965 ) ​ ​ ( 53,710 ) Cash Flows from Financing Activities ​ ​ ​ ​ ​ ​ ​ ​ ​ Proceeds from public offering of common stock, net of issuance costs ​ ​ 123,829 ​ ​ 213,303 ​ ​ — Proceeds from issuance of common stock upon exercise of stock options and purchases under employee stock purchase plan ​ ​ 6,283 ​ ​ 2,799 ​ ​ 1,779 Tax withholding payments related to net settlement of restricted stock units ​ ​ ( 189 ) ​ ​ — ​ ​ — Proceeds from at-the-market offering, net of issuance costs ​ ​ — ​ ​ 42,062 ​ ​ 34,492 Early repayment of long-term debt ​ ​ — ​ ​ ( 10,524 ) ​ ​ — Issuance costs related to long-term debt ​ ​ — ​ ​ ( 14 ) ​ ​ — Proceeds from issuance of long-term debt, net of issuance costs ​ ​ — ​ ​ — ​ ​ 9,765 Net cash provided by financing activities ​ ​ 129,923 ​ ​ 247,626 ​ ​ 46,036 Effect of exchange rate changes on cash, cash equivalents and restricted cash ​ ​ ( 126 ) ​ ​ 175 ​ ​ ( 26 ) Net increase (decrease) in cash, cash equivalents and restricted cash ​ ​ 6,072 ​ ​ 84,352 ​ ​ ( 49,227 ) Cash, cash equivalents and restricted cash, beginning of period ​ 117,818 ​ 33,466 ​ 82,693 Cash, cash equivalents and restricted cash, end of period ​ $ 123,890 ​ $ 117,818 ​ $ 33,466 Supplemental Disclosure of Cash Flow Information: ​ ​ ​ ​ ​ ​ ​ ​ ​ Cash paid for interest ​ $ — ​ $ 438 ​ $ 70 Supplemental Disclosure of Non-Cash Financing and Investing Information: ​ ​ ​ ​ ​ ​ ​ ​ ​ Purchases of property and equipment in accounts payable and accrued liabilities ​ $ 143 ​ $ 85 ​ $ 100 Issuance costs related to common stock offering included in accrued liabilities and other payables ​ $ 25 ​ $ 205 ​ $ 80 Issuance costs related to at-the-market offering of common stock included in prepaid expenses and other assets at the end of the previous year ​ $ — ​ $ 191 ​ $ — Issuance costs related to common stock offering included in prepaid expenses and other assets at the end of the previous year ​ $ — ​ $ 124 ​ $ — ​ The accompanying notes are an integral part of these consolidated financial statements. ​ ​ 82 Table of Contents PROTAGONIST THERAPEUTICS, INC. Notes to Consolidated Financial Statements Note 1. Organization and Description of Business Protagonist Therapeutics, Inc. (the “Company”) is headquartered in Newark, California. The Company is a biopharmaceutical company with multiple peptide-based investigational new chemical entities in different stages of development, all derived from the Company’s proprietary technology platform. Protagonist Pty Limited (“Protagonist Australia”) is a wholly-owned subsidiary of the Company and is located in Brisbane, Queensland, Australia. Operating segments are components of an enterprise for which separate financial information is available and is evaluated regularly by the Company’s chief operating decision maker in deciding how to allocate resources and assessing performance. The Company operates and manages its business as one operating segment. The Company’s Chief Executive Officer, who is the chief operating decision maker, reviews financial information on an aggregate basis for allocating and evaluating financial performance. Substantially all of the Company’s long-lived assets are maintained in the United States. Liquidity As of December 31, 2021, the Company had cash, cash equivalents and marketable securities of $ 326.9 million. The Company has incurred net losses from operations since inception and has an accumulated deficit of $ 409.4 million as of December 31, 2021. The Company’s ultimate success depends on the outcome of its research and development and collaboration activities. The Company expects to incur additional losses in the future and anticipates the need to raise additional capital to continue to execute its long-range business plan. Since the Company’s initial public offering in August 2016, it has financed its operations primarily through offerings of common stock and payments received under a license and collaboration agreements. Risks and Uncertainties The Company is subject to risks and uncertainties as a result of the ongoing COVID-19 pandemic. The Company is continuing to closely monitor the impact of the COVID-19 pandemic on its business and has taken and continues to take proactive efforts to protect the health and safety of its patients, clinical research staff and employees, and to maintain business continuity. The extent of the impact of the COVID-19 pandemic on the Company's activities remains uncertain and difficult to predict, as the response to the pandemic is ongoing and information continues to evolve. Capital markets and economies worldwide have been negatively impacted by the COVID-19 pandemic and may be further impacted in the future. Such economic disruption could have a material adverse effect on the Company’s business. Policymakers around the globe have responded with fiscal policy actions to support the healthcare industry and economy as a whole. The magnitude and overall effectiveness of these actions remains uncertain. The severity of the impact of the COVID-19 pandemic on the Company's activities will depend on a number of factors, including, but not limited to, the duration and severity of the pandemic, including the severity of any additional periods of increases or spikes in the number of cases in the areas the Company its suppliers and its manufacturers operate and areas where the Company’s clinical trial sites are located; the development and spread of COVID-19 variants, the timing, extent, effectiveness and durability of COVID-19 vaccine programs or other treatments; and new or continuing travel and other restrictions and public health measures, such as social distancing, business closures or disruptions. Accordingly, the extent and severity of the impact on the Company's existing and planned clinical trials, manufacturing, collaboration activities and operations is uncertain and cannot be fully predicted. The Company has experienced delays in its existing and planned clinical trials due to the worldwide impacts of the pandemic. The Company's future results of operations and liquidity could be adversely impacted by further delays in existing and planned clinical trials, continued difficulty in recruiting patients for these clinical trials, delays in manufacturing and collaboration activities, supply chain disruptions, the ongoing impact on its operating activities and employees, and the ongoing impact of any initiatives or programs that the Company may undertake to address financial and operational challenges. As of the date of issuance of 83 Table of Contents these consolidated financial statements, the extent to which the COVID-19 pandemic may materially impact the Company's future financial condition, liquidity or results of operations remains uncertain. Note 2. Summary of Significant Accounting Policies Basis of Presentation and Consolidation The accompanying consolidated financial statements include the accounts of the Company and its wholly owned subsidiary, Protagonist Australia, and have been prepared in conformity with accounting principles generally accepted in the United States of America (“GAAP”). All intercompany balances and transactions have been eliminated upon consolidation. The financial statements of Protagonist Australia use the Australian dollar as the functional currency since the majority of expense transactions occur in such currency. Gains and losses from foreign currency transactions were not material for all periods presented. The re-measurement from Australian dollar to U.S. dollars is outlined below: a. Equity accounts, except for the change in retained earnings during the year, have been translated using historical exchange rates. b. All other Australian dollar denominated assets and liabilities as of December 31, 2021 and 2020 have been translated using the year-end exchange rate. c. The consolidated statements of operations have been translated at the weighted average exchange rates in effect during each year. Foreign currency translation gains and losses are reported as a component of stockholders’ equity in accumulated other comprehensive loss on the consolidated balance sheets. Use of Estimates The preparation of the consolidated financial statements in conformity with GAAP requires management to make estimates, assumptions and judgments that affect the reported amounts of assets and liabilities and disclosure of contingent liabilities as of the date of the consolidated financial statements and the reported amounts of revenues and expenses during the reporting period. On an ongoing basis, management evaluates its estimates, including those related to revenue recognition, accruals for research and development activities, stock-based compensation, income taxes, marketable securities and leases. Estimates related to revenue recognition include actual costs incurred versus total estimated costs of the Company’s deliverables to determine percentage of completion in addition to the application and estimates of potential revenue constraints in the determination of the transaction price under its license and collaboration agreements. Management bases these estimates on historical and anticipated results, trends and various other assumptions that the Company believes are reasonable under the circumstances, including assumptions as to forecasted amounts and future events. Due to the ongoing COVID-19 pandemic, there has been uncertainty and disruption in the global economy and financial markets. The Company has taken into consideration any known COVID-19 impacts in its accounting estimates to date and is not aware of any additional specific events or circumstances that would require any additional updates to its estimates or judgments or a revision of the carrying value of its assets or liabilities as of the date of issuance of this Annual Report on Form 10-K. These estimates may change as new events occur and additional information is obtained. Actual results could differ materially from these estimates under different assumptions or conditions. Concentrations of Credit Risk Financial instruments that potentially subject the Company to a concentration of credit risk consist of cash, cash equivalents and marketable securities. Substantially all of the Company’s cash is held by two financial institutions that 84 Table of Contents management believes are of high credit quality. Such deposits may, at times, exceed federally insured limits. The primary focus of the Company’s investment strategy is to preserve capital and to meet liquidity requirements. The Company’s cash equivalents, and marketable securities are managed by external managers within the guidelines of the Company’s investment policy. The Company’s investment policy addresses the level of credit exposure by limiting concentration in any one corporate issuer and establishing a minimum allowable credit rating. To manage its credit risk exposure, the Company maintains its U.S. portfolio of cash equivalents and marketable securities in fixed income securities denominated and payable in U.S. dollars. Permissible investments of fixed income securities include obligations of the U.S. government and its agencies, money market instruments including commercial paper and negotiable certificates of deposit, and highly rated corporate debt obligations and money market funds, and highly rated supranational and sovereign government securities. Cash Equivalents Cash equivalents that are readily convertible to cash are stated at cost, which approximates fair value. The Company considers all highly liquid investments purchased with an original maturity of three months or less to be cash equivalents. Restricted Cash Restricted cash consists primarily of cash balances held as security in connection with a letter of credit related to the Company’s facility lease entered into in March 2017, as subsequently amended. The letter of credit balance decreased from $ 0.5 million at December 31, 2020 to $ 0.2 million at December 31, 2021 pursuant to the terms of the facility lease. Cash as Reported in Consolidated Statements of Cash Flows Cash as reported in the consolidated statements of cash flows includes the aggregate amounts of cash and cash equivalents and the restricted cash as presented on the consolidated balance sheets. Cash as reported in the consolidated statements of cash flows consisted of (in thousands): ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ December 31, ​ 2021 2020 ​ 2019 Cash and cash equivalents ​ $ 123,665 ​ $ 117,358 ​ $ 33,006 Restricted cash - current ​ — ​ 10 ​ 10 Restricted cash - noncurrent ​ 225 ​ 450 ​ 450 Total cash reported on consolidated statements of cash flows ​ $ 123,890 ​ $ 117,818 ​ $ 33,466 ​ Marketable Securities All marketable securities have been classified as “available-for-sale” and are carried at estimated fair value as determined based upon quoted market prices or pricing models for similar securities. Management determines the appropriate classification of its marketable securities at the time of purchase and reevaluates such designation as of each balance sheet date. Short-term marketable securities have maturities greater than three months but not longer than 365 days as of the balance sheet date. Long-term marketable securities have maturities of 365 days or longer as of the balance sheet date. Unrealized gains and losses are excluded from earnings and are reported as a component of comprehensive loss. Realized gains and losses and declines in fair value judged to be other than temporary, if any, on available-for-sale securities are included in interest income. The cost of securities sold is based on the specific-identification method. Interest on marketable securities is included in interest income. Fair Value of Financial Instruments Fair value accounting is applied to all financial assets and liabilities that are recognized or disclosed at fair value in the consolidated financial statements on a recurring basis (at least annually). The carrying amount of the Company’s financial instruments, including cash equivalents, receivable from collaboration partner, accounts payable, payable to collaboration partner and accrued expenses and other payables approximate fair value due to their short-term maturities. 85 Table of Contents See Note 4. to the Consolidated Financial Statements for additional information regarding the fair value of the Company’s other financial assets and liabilities. Property and Equipment Property and equipment are stated at cost, net of accumulated depreciation. Depreciation is computed using the straight-line method over the estimated useful lives of the assets, ranging from three to five years . Leasehold improvements are amortized over the shorter of the lease term or the estimated useful lives of the assets. Maintenance and repairs are charged to expense as incurred. When assets are retired or otherwise disposed of, the cost and accumulated depreciation are removed from the consolidated balance sheet and any resulting gain or loss is reflected in operations in the period realized. Leases The Company adopted Accounting Standards Codification Topic 842, Leases, (“ASC 842”) effective January 1, 2019. The Company determines if an arrangement is a lease at inception. Pursuant to ASC 842, operating leases are included in operating lease right-of-use (“ROU”) assets, operating lease liabilities, and noncurrent operating lease liabilities on the consolidated balance sheets. Operating lease ROU assets and operating lease liabilities are recognized based on the present value of the future minimum lease payments over the lease term at commencement date. If the Company’s leases do not provide an implicit rate, the Company uses its incremental borrowing rate based on the information available at commencement date in determining the present value of future payments. The operating lease ROU asset also includes any lease payments made and excludes lease incentives and initial direct costs incurred. Lease terms include options to extend or terminate the lease when it is reasonably certain that the Company will exercise that option. Lease expense for minimum lease payments is recognized on a straight-line basis over the lease term. The Company records tenant improvement allowances as a reduction to the ROU asset with the impact of the decrease recognized prospectively over the remaining lease term. The leasehold improvements will be amortized over the shorter of their useful life or the remaining term of the lease. Impairment of Long-Lived Assets The Company reviews long-lived assets, primarily comprised of property, equipment and operating lease ROU assets, for impairment whenever events or changes in circumstances indicate that the carrying amount of an asset may not be recoverable. Recoverability is measured by comparison of the carrying amount to the future net cash flows which the assets are expected to generate. If such assets are considered to be impaired, the impairment to be recognized is measured as the amount by which the carrying amount of the assets exceeds the projected discounted future net cash flows arising from the asset. There have been no such impairments of long-lived assets for any of the periods presented. ​ Comprehensive Loss Comprehensive loss includes net loss as well as other changes in stockholders’ equity that result from transactions and economic events other than those from stockholders. The Company’s foreign currency translation and unrealized gains and losses on available-for-sale securities represent the only components of other comprehensive loss that are excluded from reported net loss and that are presented in the consolidated statements of comprehensive loss. Income Taxes The Company uses the asset and liability method to account for income taxes in accordance with the authoritative guidance for income taxes. Under this method, deferred tax assets and liabilities are determined based on future tax consequences attributable to differences between the financial statement carrying amounts of existing assets and liabilities and their respective tax bases, and tax loss and credit carryforwards. Deferred tax assets and liabilities are measured using enacted tax rates applied to taxable income in the years in which those temporary differences are expected to be recovered or settled. The effect on deferred tax assets and liabilities of a change in tax rates is recognized in the period that includes 86 Table of Contents the enactment date. A valuation allowance is established when necessary to reduce deferred tax assets to the amount expected to be realized. ​ The Company recognizes the effect of income tax positions only if those positions are more likely than not of being sustained. Recognized income tax positions are measured at the largest amount that is greater than a 50% likelihood of being realized. Changes in recognition or measurement are reflected in the period in which the change in judgment occurs. The Company records interest and penalties related to unrecognized tax benefits in income tax expense. To date, there have been no interest or penalties recorded in relation to unrecognized tax benefits. Revenue Recognition Under Accounting Standards Codification Topic 606, Revenue from Contracts with Customers (“ASC 606”), the Company recognizes revenue when its customer obtains control of promised goods or services, in an amount that reflects the consideration which the Company expects to receive in exchange for those goods or services. To determine revenue recognition for arrangements that the Company determines are within the scope of ASC 606, the Company performs the following five steps: (i) identify the contract(s) with a customer; (ii) identify the performance obligations in the contract; (iii) determine the transaction price; (iv) allocate the transaction price to the performance obligations in the contract; and (v) recognize revenue when (or as) the Company satisfies a performance obligation. The Company applies the five-step model to contracts when it is probable that the Company will collect the consideration it is entitled to in exchange for the goods or services it transfers to the customer. At contract inception, the Company assesses the goods or services promised within each contract, determines those that are performance obligations, and assesses whether each promised good or service is distinct. The Company then recognizes as revenue the amount of the transaction price that is allocated to the respective performance obligations when (or as) the performance obligations are satisfied. The Company constrains its estimate of the transaction price up to the amount (the “variable consideration constraint”) that a significant reversal of recognized revenue is not probable. ​ Licenses of intellectual property: If a license to the Company’s intellectual property is determined to be distinct from the other performance obligations identified in an arrangement, the Company recognizes revenue from non-refundable, upfront fees allocated to the license when the license is transferred to the customer and the customer is able to use and benefit from the license. For licenses that are bundled with other promises, the Company utilizes 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, the appropriate method of measuring proportional performance for purposes of recognizing revenue from non-refundable, upfront fees. The Company evaluates the measure of proportional performance each reporting period and, if necessary, adjusts the measure of performance and related revenue recognition. ​ Milestone payments: At the inception of each arrangement or amendment that includes development, regulatory or commercial milestone payments, the Company evaluates whether the milestones are considered probable of being reached and estimates the amount to be included in the transaction price. ASC 606 suggests two alternatives to use when estimating the amount of variable consideration: the expected value method and the most likely amount method. Under the expected value method, an entity considers the sum of probability-weighted amounts in a range of possible consideration amounts. Under the most likely amount method, an entity considers the single most likely amount in a range of possible consideration amounts. Whichever method is used, it should be consistently applied throughout the life of the contract; however, it is not necessary for the Company to use the same approach for all contracts. The Company expects to use the most likely amount method for development and regulatory milestone payments. If it is probable that a significant revenue reversal would not occur, the associated milestone value is included in the transaction price. Milestone payments that are not within the control of the Company or the licensee, such as regulatory approvals, are not considered probable of being achieved until those approvals are received. If there is more than one performance obligation, the transaction price is then allocated to each performance obligation on a relative stand-alone selling price basis. The Company recognizes revenue as or when the performance obligations under the contract are satisfied. At the end of each subsequent reporting period, the Company re-evaluates the probability or achievement of each such milestone and any related constraint, and if necessary, adjusts its estimates of the overall transaction price. Any such adjustments are recorded on a cumulative catch-up basis, which would affect revenues and earnings in the period of adjustment. 87 Table of Contents Any potential milestone payments that the Company determines are not associated with performance obligations as defined under the contract are excluded from the transaction price and are recognized as the triggering event occurs. Royalties: For arrangements that include sales-based royalties, including milestone payments based on the level of sales, and the license is deemed to be the predominant item to which the royalties relate, the Company recognizes 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). 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 the Company performs its obligations under these arrangements. Amounts payable to the Company are recorded as accounts receivable when the Company’s right to consideration is unconditional. Amounts payable to the Company and not yet billed to the collaboration partner are recorded as contract assets. The Company does not assess whether a contract has a significant financing component if the expectation at contract inception is such that the period between payment by the customer and the transfer of the promised goods or services to the customer will be one year or less. Contractual cost sharing payments made to a customer or collaboration partner are accounted for as a reduction to the transaction price if such payments are not related to distinct goods or services received from the customer or collaboration partner. Contracts may be amended to account for changes in contract specifications and requirements. Contract modifications exist when the amendment either creates new, or changes existing, enforceable rights and obligations. When contract modifications create new performance obligations and the increase in consideration approximates the standalone selling price for goods and services related to such new performance obligations as adjusted for specific facts and circumstances of the contract, the modification is considered to be a separate contract. If a contract modification is not accounted for as a separate contract, the Company accounts for the promised goods or services not yet transferred at the date of the contract modification (the remaining promised goods or services) prospectively, as if it were a termination of the existing contract and the creation of a new contract, if the remaining goods or services are distinct from the goods or services transferred on or before the date of the contract modification. The Company accounts for a contract modification as if it were a part of the existing contract if the remaining goods or services are not distinct and, therefore, form part of a single performance obligation that is partially satisfied at the date of the contract modification. In such case the effect that the contract modification has on the transaction price, and on the entity’s measure of progress toward complete satisfaction of the performance obligation, is recognized as an adjustment to revenue (either as an increase in or a reduction of revenue) at the date of the contract modification (the adjustment to revenue is made on a cumulative catch-up basis). The period between when the Company transfers control of promised goods or services and when the Company receives payment is expected to be one year or less, which is consistent with the Company’s historical experience. Upfront payment contract liabilities resulting from the Company’s license and collaboration agreements do not represent a financing component as the payment is not financing the transfer of goods and services, and the technology underlying the licenses granted reflects research and development expenses already incurred by the Company. As such, the Company does not adjust its revenues for the effects of a significant financing component. Research and Development Costs Research and development costs are expensed as incurred, unless there is an alternate future use in other research and development projects or otherwise. Research and development costs include salaries and benefits, stock-based compensation expense, laboratory supplies and facility-related overhead, outside contracted services including clinical trial costs, manufacturing and process development costs for both clinical and pre-clinical materials, research costs, development milestone payments under license and collaboration agreements, and other consulting services. The Company accrues for estimated costs of research and development activities conducted by third-party service providers, which include the conduct of pre-clinical studies and clinical trials and contract manufacturing activities. The Company records the estimated costs of research and development activities based upon the estimated services provided 88 Table of Contents but not yet invoiced and includes these costs in accrued expenses and other payables in the consolidated balance sheets and within research and development expense in the consolidated statements of operations. The Company accrues for these costs based on factors such as estimates of the work completed and in accordance with agreements established with its third-party service providers. As actual costs become known, the Company adjusts its accrued liabilities. The Company has not experienced any material differences between accrued liabilities and actual costs incurred. However, the status and timing of actual services performed, number of patients enrolled, the rate of patient enrollment and number and location of sites activated may vary from the Company’s estimates, resulting in adjustments to expense in future periods. Changes in these estimates that result in material changes to the Company’s accruals could materially affect the Company’s results of operations. The Company has received orphan drug designation from the U.S. Food and Drug Administration (“FDA”) for its clinical asset rusfertide (generic name for PTG-300) for the treatment of polycythemia vera and beta-thalassemia and may qualify for a related 25 % U.S. Federal income tax credit on qualifying clinical study expenditures. Research and Development Tax Incentive The Company is eligible under the AusIndustry research and development tax incentive program to obtain either a refundable cash tax incentive or a taxable credit in the form of a non-cash tax incentive from the Australian Taxation Office (“ATO”). The refundable cash tax incentive is available to the Company on the basis of specific criteria with which the Company must comply. Specifically, the Company must have annual turnover of less than AUD 20.0 million and cannot be controlled by income tax exempt entities. The refundable cash tax incentive is recognized as a reduction to research and development expense when the right to receive has been attained and funds are considered to be collectible. The Company may alternatively be eligible for a taxable credit in the form of a non-cash tax incentive in years when the annual turnover exceeds the limit. The Company evaluates its eligibility under tax incentive programs as of each balance sheet date and makes accrual and related adjustments based on the most current and relevant data available. Small Business Innovation Research (“SBIR”) Grants The Company has received SBIR grants from the National Institutes of Health (“NIH”) in support of its research activities. The Company recognizes a reduction to research and development expenses when expenses related to grants have been incurred and the grant funds become contractually due from NIH. Stock-based Compensation The Company measures its stock-based awards made to its equity plan participants based on the estimated fair values of the awards as of the grant date. For stock option awards, the Company uses the Black-Scholes option-pricing model to estimate fair values. For restricted stock unit awards, the estimated fair value is generally the fair market value of the underlying stock on the grant date. Stock-based compensation expense is recognized over the requisite service period and is based on the value of the portion of stock-based payment awards that is ultimately expected to vest. The Company recognizes forfeitures of stock-based awards as they occur. The Company has granted performance share units (“PSUs”) to certain executives of the Company. Stock-based compensation expense associated with PSUs is based on the fair value of the Company’s common stock on the grant date, which equals the closing price of the Company’s common stock on the grant date. The Company recognizes compensation expense over the vesting periods of the awards that are ultimately expected to vest when the achievement of the related performance obligation becomes probable. If stock-based awards are granted in contemplation of or shortly before a planned release of material nonpublic information, and such information is expected to result in a material increase in the Company’s share price, the Company considers whether an adjustment to the observable market price is required when estimating fair values. 89 Table of Contents Net Loss per Share Basic net loss per share is calculated by dividing the Company’s net loss by the weighted average number of shares of common stock and Exchange Warrants outstanding during the period, without consideration of potentially dilutive securities. In accordance with Accounting Standards Codification Topic 260, Earnings Per Share , the Exchange Warrants are included in the computation of basic net loss per share because the exercise price is negligible, and they are fully vested and exercisable after the original issuance date. Diluted net loss per share is the same as basic net loss per share for all periods presented since the effect of potentially dilutive securities is anti-dilutive given the net loss of the Company in each period. See Note 12. Stockholders' Equity for additional information regarding the Exchange Warrants. Recently Adopted Accounting Pronouncements In December 2019, the FASB issued Accounting Standards Update (“ASU”) No. 2019-12, Income Taxes (Topic 740): Simplifying the Accounting for Income Taxes, which removes certain exceptions and amends certain requirements in the existing income tax guidance to ease accounting requirements. This guidance is effective for fiscal years, and interim periods within those fiscal years, beginning after December 15, 2020 and must be applied on a retrospective basis. The Company adopted this guidance effective January 1, 2021 and there was no impact on its consolidated financial statements and disclosures. Recently Issued Accounting Pronouncements Not Yet Adopted as of December 31, 2021 In June 2016, the FASB issued ASU No. 2016-13, Financial Instruments - Credit Losses (Topic 326) , which is intended to provide financial statement users with more useful information about expected credit losses on financial assets held by a reporting entity at each reporting date. The new standard replaces the existing incurred loss impairment methodology with a methodology that requires consideration of a broader range of reasonable and supportable forward-looking information to estimate all expected credit losses. This guidance was originally effective for fiscal years and interim periods within those years beginning after December 15, 2019, with early adoption permitted for fiscal years and interim periods within those years beginning after December 15, 2018. In November 2019, the FASB issued ASU No. 2019-10, Financial Instruments – Credit Losses (Topic 326), Derivatives and Hedging (Topic 815), and Leases (Topic 842): Effective Dates , which amended the mandatory effective date of ASU No. 2016-13 for smaller reporting companies. Based on the Company’s status as a smaller reporting company as of November 15, 2019, ASU 2016-13 is effective for the Company for fiscal years and interim periods beginning after December 15, 2022. The Company is currently evaluating the impact of this new guidance on its consolidated financial statements and disclosures. ​ Note 3. License and Collaboration Agreement Agreement Terms On July 27, 2021, the Company entered into an amended and restated License and Collaboration Agreement (“Restated Agreement”) with Janssen Biotech, Inc., a Pennsylvania corporation (“Janssen”). The Restated Agreement amends and restates the License and Collaboration Agreement, dated May 26, 2017, by and between the Company and Janssen (as amended by the First Amendment thereto, effective May 7, 2019, the “Original Agreement”). Janssen is a related party to the Company as Johnson & Johnson Innovation - JJDC, Inc., a significant stockholder of the Company, and Janssen are both subsidiaries of Johnson & Johnson. The Original Agreement became effective on July 13, 2017. Upon the effectiveness of the Original Agreement, the Company received a non-refundable, upfront cash payment of $ 50.0 million from Janssen. Upon the effectiveness of the First Amendment, the Company received a $ 25.0 million payment from Janssen in 2019. The Company also received a $ 5.0 million payment triggered by the successful nomination of a second-generation oral Interleukin (“IL”)-23 receptor antagonist development compound (“second-generation compound”) during the first quarter of 2020 and a $ 7.5 million payment triggered by the completion of data collection activities for the first Phase 1 clinical trial of a second-generation compound during the fourth quarter of 2021. The Restated Agreement relates to the development, manufacture and commercialization of oral IL-23 receptor antagonist drug candidates. The candidates nominated for initial development pursuant to the Restated Agreement included PTG-200 (JNJ-67864238), PN-232 (JNJ-75105186) and PN-235 (JNJ-77242113). PTG-200 was an oral IL-23 90 Table of Contents receptor antagonist in that was in Phase 2a development for the treatment of Crohn’s disease (“CD”). During the fourth quarter of 2021, following a pre-specified interim analysis criteria, a portfolio decision was made by Janssen to stop further development of both PTG-200 and PN-232 in favor of advancing PN-235, based on its superior potency and overall pharmacokinetic and pharmacodynamic profile. Janssen is primarily responsible for the conduct of all future trials, including these anticipated Phase 2 trials, and the Company is primarily responsible for the conduct of the second-generation Phase 1 studies. ​ Pursuant to the Restated Agreement, the parties: ● amended development milestones to reflect Janssen’s expected development of collaboration compounds for multiple indications in the IL-23 pathway; ● limited the Company’s further development and related expense obligations under the Restated Agreement to the PTG-200 Phase 2a study, and the Phase 1 studies in PN-232 and PN-235; Janssen is responsible for all other future development and related expenses under the Restated Agreement; and ● concluded the parties’ two-year research collaboration, while enabling Janssen to continue conducting additional research through July 2024 on compounds developed pursuant to the Original Agreement. The Restated Agreement enables Janssen to develop collaboration compounds for multiple indications. Under the Restated Agreement, Janssen is required to use commercially reasonable efforts to develop at least one collaboration compound for at least two indications. The Company’s development cost obligations in the Original Agreement for the period following the effective date of the Original Agreement were as follows: (a) up to $ 20.0 million of costs related to up to three Phase 1 studies of second-generation compounds; (b) up to $ 20.0 million of costs related to Phase 2a and 2b costs for PTG-200 (i.e., 20 % of the first $ 100.0 million in costs); (c) up to $ 25.0 million in costs related to up to two Phase 2 studies evaluating second-generation compounds. The Company’s continuing development expense obligations under the Restated Agreement were as follows: (a) the Company funded 20 % of the costs related to the Phase 2a study evaluating PTG-200 for the treatment of CD (subject to a $ 20.0 million cap); (b) the Company was responsible for 50 % of agreed-upon costs related to the Phase 1 study evaluating PN-235 incurred through January 4, 2021; (c) the Company was responsible for 100 % of agreed-upon costs related to the Phase 1 study evaluating PN-232. Certain of the Company’s previous development expense obligations under the Original Agreement were limited or eliminated as follows: (a) the Company’s previous $ 25.0 million obligation for 20 % of costs related to Phase 2 studies for second-generation products was eliminated; (b) the Company’s previous $ 5.0 million obligation for 50 % of the costs of a potential third Phase 1 study evaluating a second-generation compound was eliminated; and (c) the Company had no obligation to fund any portion of any Phase 2b or other study evaluating PTG-200 beyond the Phase 2a study in CD. One milestone for second-generation Phase 2 development was reduced from $ 50.0 million to $ 25.0 million in the Restated Agreement; otherwise, t he various milestone payment amounts in the Restated Agreement remain substantially the same as in the Original Agreement. To reflect parallel development of multiple indications in the IL-23 pathway, milestone payments under the Restated Agreement generally now correspond to the achievement of specified milestones in: (a) any initial indication (rather than CD, as in the Original Agreement); (b) any second indication (rather than ulcerative colitis (“UC”), as in the Original Agreement); and (c) any third indication. With respect to second-generation compounds, milestone payments for second and third indications could be triggered by any second-generation compound (i.e., not necessarily the second-generation compound that triggered the initial payment for any indication, or the payment for a second indication). In addition, the opt-in payments contemplated by the Original Agreement related to the scope of Janssen’s license rights have been converted into development milestones in the Restated Agreement. 91 Table of Contents Upcoming potential development milestones for second-generation compounds include: ● $ 25.0 million for dosing of the 3rd patient in the first Phase 2 clinical trial for any second-generation compound for any indication; ● $ 10.0 million for dosing of the 3rd patient in the first Phase 2 clinical trial for any second-generation compound for a second indication (i.e., an indication different than the indication which triggered the $ 25.0 million milestone described above); ● $ 50.0 million for dosing of the 3rd patient in a Phase 3 clinical trial for a second-generation compound for any indication; ● $ 15.0 million for dosing of the 3rd patient in a Phase 3 clinical trial for a second-generation compound for a second indication; and ● $ 115.0 million for a Phase 3 clinical trial for a second-generation compound for any indication meeting its primary clinical endpoint. Development milestones for PTG-200 were unchanged under the Restated Amendment, except that milestone achievement is generally no longer indication-specific. Pursuant to the Restated Agreement, the Company remains eligible to receive tiered royalties on net product sales at percentages ranging from mid-single digits to ten percent. The sales milestone payments in the Original Agreement also remain the same in the Restated Agreement. Pursuant to both the Original and Restated Agreements, payments to the Company for research and development services are generally billed and collected as services are performed or assets are delivered, including research activities and Phase 1 and Phase 2 development activities. Janssen bills the Company for its share of the PTG-200 Phase 2a development costs as expenses are incurred by Janssen. Milestone payments are received after the related milestones are achieved. Janssen retains exclusive, worldwide rights to develop and commercialize IL-23 receptor antagonist compounds derived from the research collaboration conducted under the Original Agreement, or Janssen’s further research under the Restated Agreement. Any further research and development will be conducted by Janssen. The Company will have the right to co-detail (for CD and UC indications) up to two of the IL-23 receptor antagonist compounds under the collaboration in the U.S. market. The Restated Agreement remains in effect until the royalty obligations cease following patent and regulatory expiry, unless terminated earlier. Upon a termination of the Restated Agreement, all rights revert back to the Company, and in certain circumstances, if such termination occurs during ongoing clinical trials, Janssen would, if requested, provide certain financial and operational support to the Company for the completion of such trials. Revenue Recognition The Restated Agreement contains a single performance obligation for the development license; Phase 1 development services for PTG-200, PN-232 and PN-235; the Company’s services associated with Phase 2a development for PTG-200 in CD; the initial year of second-generation compound research services; and all other such services that the Company may perform at the request of Janssen to support the development of PTG-200 through Phase 2a and PN-232 and PN-235 through Phase 1. Under the Restated Agreement, development services performed by the Company for PTG-200 beyond Phase 2a and PN-232 and PN-235 beyond Phase 1 are no longer required. The Company determined that the license was not distinct from the revised development services within the context of the agreement because the revised development services did not change the utility of the intellectual property. The 92 Table of Contents Company also concluded that the remaining development services are not distinct from the partially delivered combined promise comprised under the agreement prior to the Restated Agreement of the development license and PTG-200, PN-232 and PN-235 services, including compound supply and other services. Therefore, the Restated Agreement is treated as if it were part of the Original Agreement. The Restated Agreement is accounted for as if it were a modification of services under the Original Agreement by applying a cumulative catch-up adjustment to revenue. As of the effective date of the Restated Agreement, the Company calculated the adjusted cumulative revenue under the Restated Agreement with primary updates to the transaction price, including the release of and update of prior constraints and fewer remaining services to be provided, resulting in a cumulative adjustment that increased revenue by $ 8.0 million. The contract duration is defined as the period in which parties to the contract have present enforceable rights and obligations. For revenue recognition purposes, the Company determined that the duration of the Restated Agreement for the identified single initial performance obligation began on the Original Agreement effective date of July 13, 2017 and ends upon the later of the end of Phase 2a for PTG-200 in CD or the completion of a Phase 1 clinical trial for either PN-232 or PN-235. Final activities related to the PTG-200 Phase 2a trial, PN-235 Phase 1 trial and PN-232 Phase 1 trial are expected to be completed in early 2022. The Company uses the most likely amount method to estimate variable consideration included in the transaction price. Variable consideration after the effective date of the Restated Agreement consisted of future milestone payments and cost sharing payments for agreed upon services offset by development cost reimbursable to Janssen. Cost sharing payments from Janssen relate to the agreed upon services for development activities that the Company performs within the duration of the contract and are included in the transaction price at the Company’s share of estimated budgeted costs for these activities, including primarily internal full-time equivalent effort and third-party contract costs. Cost sharing payments to Janssen relate to agreed upon services for activities that Janssen performs within the duration of the contract are not a distinct service that Janssen transfers to the Company. Therefore, the consideration payable to Janssen is accounted for as a reduction in the transaction price. The transaction price of the initial performance obligation under the Restated Agreement was $ 106.5 million as of December 31, 2021, an increase of $ 7.9 million from the transaction price of $ 98.6 million at December 31, 2020 under the Original Agreement and a decrease of $ 6.4 million from the transaction price of $ 112.9 million at December 31, 2019 under the Original Agreement. In order to determine the transaction price, the Company evaluated all payments to be received during the duration of the contract, net of development costs reimbursement expected to be payable to Janssen. The transaction price as of December 31, 2021 includes $ 87.5 million of nonrefundable payments received to date, $ 17.9 million of reimbursement from Janssen for services performed for IL-23 receptor antagonist compound research costs and other services, and estimated variable consideration consisting of $ 8.2 million of development cost reimbursement receivable from Janssen, partially offset by $ 7.1 million of net cost reimbursement due to Janssen for services performed. The Company evaluated whether the variable component of the transaction price should be constrained to ensure that a significant reversal of revenue recognized on a cumulative basis as of December 31, 2021 is not probable. The Company concluded that the variable consideration constraint is appropriately reflected in the estimated transaction price as of December 31, 2021, and that the achievement of future milestones is subject to additional development and/or regulatory uncertainty and therefore it is not probable at December 31, 2021 that a material reversal of such revenues would not occur. Janssen also opted in for certain additional services to be performed by the Company that are outside the initial performance obligation, revenue is recognized as these services are performed. ​ The Company re-evaluates the transaction price, including variable consideration, at the end of each reporting period and as uncertain events are resolved or other changes in circumstances occur. The Company and Janssen make quarterly cost sharing payments to one another in amounts necessary to ensure that each party bears its contractual share of the overall shared costs incurred. The Company utilizes a cost-based input method to measure proportional performance and to calculate the corresponding amount of revenue to recognize. In applying the cost-based input method of revenue recognition, the Company uses actual costs incurred relative to expected costs to fulfill the combined performance obligation. These costs consist primarily of internal FTE effort and third-party contract costs. Revenue will be recognized based on actual costs incurred as a percentage of total estimated costs as the Company completes its performance obligations. A cost-based input method of revenue recognition requires management to make estimates of costs to complete the Company’s 93 Table of Contents performance obligations. The Company believes this is the best measure of progress because other measures do not reflect how the Company transfers its performance obligation to Janssen. In making such estimates, significant judgment is required to evaluate assumptions related to cost estimates. The cumulative effect of revisions to estimated costs to complete the Company’s performance obligations will be recorded in the period in which changes are identified and amounts can be reasonably estimated. A significant change in these assumptions and estimates could have a material impact on the timing and amount of revenue recognized in future periods. For the year ended December 31, 2021, the Company recognized $ 27.4 million of license and collaboration revenue. This amount included a cumulative catch-up adjustment increasing license and collaboration revenue by $ 8.0 million, and $ 18.6 million of license and collaboration revenue based on proportional performance following the contract modification for the Restated Agreement. In addition, the Company recorded $ 0.8 million of revenue related to additional services provided by the Company under the agreement. For the year ended December 31, 2020, the Company recognized $ 28.6 million of license and collaboration revenue. This amount included a $ 27.1 million of the transaction price based on proportional performance and an update in forecasted amounts for future services remaining to be performed and recognized under the Janssen License and Collaboration Agreement. In addition, the Company recorded $ 1.5 million of revenue for the year ended December 31, 2020 related to additional services provided by the Company under the Janssen License and Collaboration Agreement. For the year ended December 31, 2019, the Company recognized $ 0.2 million of license and collaboration revenue. This amount included a $ 9.4 million cumulative catchup adjustment as a reduction of revenue, offset by $ 8.0 million of license and collaboration revenue recognized following the contract modification for the First Amendment to the agreement and $ 1.6 million of collaboration revenue recognized during the first quarter of 2019 prior to the effectiveness of the First Amendment. No revenue for additional services was recognized for the year ended December 31, 2019. The following table presents changes in the Company’s contract assets and liabilities during the periods presented (in thousands): ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Balance at ​ ​ ​ ​ ​ Balance at ​ ​ Beginning of ​ ​ ​ ​ ​ End of Year Ended December 31, 2021 Period ​ Additions Deductions Period Contract assets: ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Receivable from collaboration partner - related party ​ $ 2,426 ​ $ 14,056 ​ $ ( 14,916 ) ​ $ 1,566 Contract liabilities: ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Deferred revenue - related party ​ $ 14,477 ​ $ 25,141 ​ $ ( 38,017 ) ​ $ 1,601 Payable to collaboration partner - related party ​ $ 2,732 ​ $ 10,225 ​ $ ( 12,058 ) ​ $ 899 ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Balance at ​ ​ ​ ​ ​ ​ ​ Balance at ​ ​ Beginning of ​ ​ ​ ​ ​ End of Year Ended December 31, 2020 Period ​ Additions Deductions Period Contract assets: ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Receivable from collaboration partner - related party ​ $ 5,955 ​ $ 6,221 ​ $ ( 9,750 ) ​ $ 2,426 Contract asset - related party ​ $ 800 ​ $ 342 ​ $ ( 1,142 ) ​ $ — Contract liabilities: ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Deferred revenue - related party ​ $ 41,530 ​ $ 3,963 ​ $ ( 31,016 ) ​ $ 14,477 Payable to collaboration partner - related party ​ $ 1,262 ​ $ 3,800 ​ $ ( 2,330 ) ​ $ 2,732 ​ During the year ended December 31, 2021, the Company recognized revenue of $ 2.8 million from amounts included in the deferred revenue balance at the beginning of the year. During the year ended December 31, 2020, the Company recognized revenue of $ 14.1 million from amounts included in the deferred revenue balance at the beginning of the year. During the year ended December 31, 2019, the Company recognized $ 1.6 million from amounts included in the deferred revenue balance at the beginning of the year. None of the costs to obtain or fulfill the contract were capitalized. 94 Table of Contents Note 4. Fair Value Measurements Financial assets and liabilities are recorded at fair value. The accounting guidance for fair value provides a framework for measuring fair value, clarifies the definition of fair value and expands disclosures regarding fair value measurements. Fair value is defined as the price that would be received to sell an asset or paid to transfer a liability (an exit price) in an orderly transaction between market participants at the reporting date. The accounting guidance establishes a three-tiered hierarchy, which prioritizes the inputs used in the valuation methodologies in measuring fair value as follows: Level 1 —Inputs are unadjusted quoted prices in active markets for identical assets or liabilities at the measurement date. Level 2— Inputs (other than quoted market prices included in Level 1) are either directly or indirectly observable for the asset or liability through correlation with market data at the measurement date and for the duration of the instrument’s anticipated life. Level 3 —Inputs reflect management’s best estimate of what market participants would use in pricing the asset or liability at the measurement date. Consideration is given to the risk inherent in the valuation technique and the risk inherent in the inputs to the model. In determining fair value, the Company utilizes quoted market prices, broker or dealer quotations, or valuation techniques that maximize the use of observable inputs and minimize the use of unobservable inputs to the extent possible and considers counterparty credit risk in its assessment of fair value. The following table presents the fair value of the Company’s financial assets determined using the inputs defined above (in thousands). ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ December 31, 2021 ​ Level 1 Level 2 Level 3 Total Assets: ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Money market funds ​ $ 39,854 ​ $ — ​ $ — $ 39,854 Commercial paper ​ — ​ ​ 157,141 ​ — 157,141 Corporate debt securities ​ ​ — ​ ​ 75,548 ​ ​ — ​ ​ 75,548 U.S. Treasury and agency securities ​ ​ — ​ ​ 40,017 ​ ​ — ​ ​ 40,017 Supranational and sovereign government securities ​ — ​ ​ 6,010 — 6,010 Total financial assets ​ $ 39,854 ​ $ 278,716 $ — $ 318,570 ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ December 31, 2020 ​ Level 1 Level 2 Level 3 Total Assets: ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Money market funds ​ $ 27,481 ​ $ — ​ $ — $ 27,481 Commercial paper ​ — ​ 65,863 ​ — 65,863 Corporate debt securities ​ — ​ 27,590 — 27,590 U.S. Treasury and agency securities ​ — ​ 183,210 — 183,210 Total financial assets ​ $ 27,481 ​ $ 276,663 $ — $ 304,144 ​ The Company’s commercial paper, corporate debt securities U.S. Treasury and agency securities, including U.S. Treasury bills, and supranational and sovereign government securities are classified as Level 2 as they are valued based upon quoted market prices for similar instruments in active markets, quoted prices for identical or similar instruments in markets that are not active and model-based valuation techniques for which all significant inputs are observable in the market or can be corroborated by observable market data for substantially the full term of the assets. ​ ​ 95 Table of Contents Note 5. Cash Equivalents and Marketable Securities Cash equivalents and marketable securities consisted of the following (in thousands): ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ December 31, 2021 ​ ​ Amortized ​ Gross Unrealized ​ ​ Cost Gains Losses Fair Value Money market funds ​ $ 39,854 ​ $ — ​ $ — ​ $ 39,854 Commercial paper ​ 157,157 ​ ​ — ​ ​ ( 16 ) ​ 157,141 Corporate debt securities ​ ​ 75,598 ​ ​ — ​ ​ ( 50 ) ​ ​ 75,548 U.S. Treasury and agency securities ​ ​ 40,093 ​ ​ — ​ ​ ( 76 ) ​ ​ 40,017 Supranational and sovereign government securities ​ 6,011 ​ ​ — ​ ​ ( 1 ) ​ 6,010 Total cash equivalents and marketable securities ​ $ 318,713 ​ $ — $ ( 143 ) ​ $ 318,570 Classified as: ​ ​ ​ ​ ​ ​ ​ ​ ​ Cash equivalents ​ ​ ​ ​ ​ ​ ​ $ 115,335 Marketable securities - current ​ ​ ​ ​ ​ ​ ​ 203,235 Marketable securities - noncurrent ​ ​ ​ ​ ​ ​ ​ — Total cash equivalents and marketable securities ​ ​ ​ ​ ​ ​ ​ $ 318,570 ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ December 31, 2020 ​ ​ Amortized ​ Gross Unrealized ​ ​ Cost Gains Losses Fair Value Money market funds ​ $ 27,481 ​ $ — $ — ​ $ 27,481 Commercial paper ​ 65,866 ​ — ( 3 ) ​ 65,863 Corporate debt securities ​ 27,592 ​ 2 ( 4 ) ​ 27,590 U.S. Treasury and agency securities ​ 183,203 ​ 10 ( 3 ) ​ 183,210 Total cash equivalents and marketable securities ​ $ 304,142 ​ $ 12 $ ( 10 ) ​ $ 304,144 Classified as: ​ ​ ​ ​ ​ ​ ​ ​ ​ Cash equivalents ​ ​ ​ ​ ​ ​ ​ $ 113,693 Marketable securities - current ​ ​ ​ ​ ​ ​ ​ 188,451 Marketable securities - noncurrent ​ ​ ​ ​ ​ ​ ​ 2,000 Total cash equivalents and marketable securities ​ ​ ​ ​ ​ ​ ​ $ 304,144 ​ Marketable securities – current of $ 203.2 million and $ 188.5 million held at December 31, 2021 and 2020, respectively, had contractual maturities of less than one year . Marketable securities – noncurrent of $ 2.0 million held at December 31, 2020 had contractual maturities of at least one year but less than two years . The Company did not hold any marketable securities – noncurrent at December 31, 2021. The Company does not intend to sell its securities that are in an unrealized loss position, and it is not more likely than not that the Company will be required to sell its securities before recovery of their amortized cost basis, which may be at maturity. There were no realized gains or realized losses on marketable securities for the periods presented. Factors considered in determining whether a loss is temporary include the length of time and extent to which the fair value has been less than the amortized cost basis and whether the Company intends to sell the security or whether it is more likely than not that the Company would be required to sell the security before recovery of the amortized cost basis. 96 Table of Contents Note 6. Balance Sheet Components Prepaid Expenses and Other Current Assets Prepaid expenses and other current assets consisted of the following (in thousands): ​ ​ ​ ​ ​ ​ ​ ​ ​ December 31, ​ 2021 2020 Prepaid clinical and research related expenses ​ $ 5,242 ​ $ 3,517 Prepaid insurance ​ ​ 1,746 ​ ​ 1,440 Other prepaid expenses ​ 1,515 ​ 1,009 Other receivable ​ ​ 975 ​ ​ 311 Prepaid expenses and other current assets ​ $ 9,478 ​ $ 6,277 ​ Property and Equipment, Net Property and equipment, net consisted of the following (in thousands): ​ ​ ​ ​ ​ ​ ​ ​ ​ December 31, ​ 2021 2020 Laboratory equipment ​ $ 4,156 ​ $ 3,539 Furniture and computer equipment ​ 1,023 ​ 648 Leasehold improvements ​ 877 ​ 748 Total property and equipment ​ 6,056 ​ 4,935 Less: accumulated depreciation ​ ( 4,258 ) ​ ( 3,473 ) Property and equipment, net ​ $ 1,798 ​ $ 1,462 ​ Depreciation expense for the years ended December 31, 2021, 2020 and 2019, was $ 813,000 , $ 789,000 and $ 703,000 , respectively. As of December 31, 2021, 2020 and 2019, $ 262,000 , $ 46,000 and $ 37,000 , respectively, of property and equipment, net, was located in Australia. The remainder of the Company’s property and equipment, net is located in the United States. Accrued Expenses and Other Payables Accrued expenses and other payables consisted of the following (in thousands): ​ ​ ​ ​ ​ ​ ​ ​ ​ December 31, ​ 2021 ​ 2020 Accrued clinical and research related expenses ​ $ 27,950 ​ $ 11,335 Accrued employee related expenses ​ 7,125 ​ 6,413 Accrued professional service fees ​ ​ 734 ​ ​ 668 Accrued collaboration payments ​ ​ 1,500 ​ ​ — Other ​ 407 ​ 82 Total accrued expenses and other payables ​ $ 37,716 ​ $ 18,498 ​ ​ ​ Note 7. Research Collaboration and License Agreement The Company and Zealand Pharma A/S entered into a collaboration agreement in June 2012. In October 2013, Zealand Pharma abandoned the collaboration, and the collaboration agreement was terminated in 2014. The agreement provides for certain post-termination payment obligations to Zealand with respect to compounds related to the collaboration that meet specified conditions set forth in the collaboration agreement and which the Company elects to further develop following Zealand’s abandonment of the collaboration. The Company has the right, but not the obligation, to further develop and commercialize such compounds. The agreement provides for payments to Zealand for the 97 Table of Contents achievement of certain development, regulatory and sales milestone events that occur prior to a partnering arrangement related to such compounds between the Company and a third party. The Company previously determined that rusfertide is a compound for which the post-termination payments described above are required under the collaboration agreement and has made three development milestone payments for an aggregate amount of $ 1.0 million under the agreement. However, upon reevaluation, the Company concluded in 2019 that rusfertide is not a compound requiring post-termination payments under the agreement and initiated an arbitration proceeding in January 2020. On August 4, 2021, the Company and Zealand agreed to resolve the dispute and entered into an Arbitration Resolution Agreement. See Note 11. Commitments and Contingencies – Legal Proceedings for additional information on the results of arbitration proceedings related to this research and collaboration agreement. Milestone payments to collaboration partners are recorded as research and development expenses in the period that the expense is incurred. For the year ended December 31, 2021, the Company recorded research and development expense of $ 4.0 million under this agreement. No research and development expense was recorded under this agreement for the years ended December 31, 2020 or 2019. Note 8. Government Programs Research and Development Tax Incentive During the years ended December 31, 2021 and 2020, the Company recognized AUD 4.2 million ($ 3.1 million) and AUD 1.4 million ($ 1.0 million), respectively, as a reduction of research and development expenses in connection with the research and development cash tax incentive from the ATO. During the year ended December 31, 2019, the Company recognized AUD 1.9 million ($ 1.3 million) of research and development expenses in connection with the research and development tax incentive from the ATO because the Company determined that it had exceeded the annual turnover limit to claim such amounts following the receipt of certain payments under the Janssen License and Collaboration Agreement. As of December 31, 2021 and 2020, the research and development tax incentive receivable was AUD 3.8 million ($ 2.8 million) and AUD 1.4 million ($ 1.1 million), respectively. Small Business Innovation Research (“SBIR”) Grants In May 2017, the Company was awarded a Phase 2 SBIR grant from the National Institute of Diabetes and Digestive and Kidney Diseases of the NIH in support of research aimed at developing biomarkers that define IL-23R target engagement by orally delivered peptide antagonists and the effects of that engagement of downstream signaling. The total grant award was $ 1.3 million and was originally for the period from May 2017 to April 2019. During the year ended December 31, 2019, the Company requested and received an extension of this grant through April 2020. In September 2018, the Company was awarded a Phase 2 SBIR Grant from the National Heart, Lungs and Blood Institute of the NIH in support of research aimed at developing the Company’s novel hepcidin mimetic rusfertide for the potential treatment of chronic anemia and iron overload in rare blood disorders, including beta-thalassemia. The total grant award was $ 1.5 million and was originally for the period from September 2018 to August 2020. During the year ended December 31, 2020, the Company requested an extension of this grant through July 2021, which was received in February 2021. The Company recognizes a reduction to research and development expenses when expenses related to the grants have been incurred and the grant funds become contractually due from NIH. The Company recorded $ 0.5 million and $ 1.4 million as a reduction of research and development expenses for the years ended December 31, 2020 and 2019, respectively. No such amount was recorded during the year ended December 31, 2021. As of December 31, 2021, the Company has received all grant funds contractually due from NIH for these completed SBIR grants. 98 Table of Contents Note 9. Term Loan Facility On October 30, 2019 (the “Closing Date”), the Company entered into a Credit and Security Agreement, by and among the Company, MidCap Financial Trust, as a lender, Silicon Valley Bank, as a lender, the other lenders party thereto from time to time and MidCap Financial Trust, as administrative agent and collateral agent (“Agent”), (the “Term Loan Credit Agreement”), which provided for a $ 50.0 million term loan facility. The Term Loan Credit Agreement provided for (i) on the Closing Date, $ 10.0 million aggregate principal amount of term loans, (ii) at the Company’s option, until December 31, 2020, an additional $ 20.0 million term loan facility subject to the satisfaction of certain conditions, including clinical milestone achievement, and (iii) at the Company’s option, until September 30, 2021, an additional $ 20.0 million term loan facility subject to the satisfaction of certain conditions, including clinical milestone achievement, (collectively, the “Term Loans”). The Company intended to use any proceeds of the Term Loans for general corporate purposes. The Term Loans were subject to an origination fee of 0.25 % for each funded tranche under the Term Loan Credit Agreement and bore interest at an annual rate based on prime rate plus 2.91 %, subject to a prime rate floor of 4.94 %. The Company would make interest-only payments on the Term Loans for 24 months , followed by 24 months of principal and interest payments. At the Company’s option, the Company could prepay the outstanding principal balance of the Term Loans in whole or in part, subject to a prepayment premium of 3.0 % of any amount prepaid if the prepayment occurred through and including the first anniversary of the closing date, 2.0 % of the amount prepaid if the prepayment occurred after the first anniversary of the closing date through and including the second anniversary of the closing date, and 1.0 % of any amount prepaid after the second anniversary of the closing date and prior to October 1, 2023. An additional fee of 2.85 % of the amount of Term Loans advanced by the Lenders was due upon prepayment or repayment of the Term Loans. The Term Loan Credit Agreement required the Company to maintain cash and cash equivalents of at least 35 % of the outstanding Term Loans at all times and was secured by a perfected security interest in all of the Company's assets except for intellectual property and certain other customary excluded property pursuant to the terms of the Term Loan Credit Agreement. The Term Loan Credit Agreement contained other covenants that limited the Company’s ability and the ability of its subsidiaries to perform certain actions, including obligations to not pay dividends and to maintain unrestricted cash balances above certain threshold, non-occurrence of material adverse change, non-occurrence of change of control and other customary affirmative and negative covenants. The violation of any provision of covenants would result in default for the Company. The Term Loan Credit Agreement included a clause which allowed lenders to accelerate repayment upon the occurrence of certain events of default. In June 2020, the Company prepaid its outstanding $ 10.0 million balance on the term loan as well as $ 0.6 million for related prepayment and exit fees. Accordingly, the company accelerated amortization of $ 0.1 million related to capitalized and unamortized debt issuance costs, which is included as part of the $ 0.6 million loss on early repayment of debt. The Company did not exercise its option to borrow the $ 20.0 million second tranche of Term Loans, which expired on December 31, 2020, and therefore had no outstanding balance as of December 31, 2020 related to the Term Loan Credit Agreement. In September 2021, the Company executed a payoff letter to release all obligations under the Term Loan Credit Agreement, ending the Term Loan Credit Agreement. As a result, the Company had no outstanding balance and no obligations related to the Term Loan Credit Agreement as of December 31, 2021. The Company recognized $ 0.6 million and $ 0.2 million in interest expense related to the Term Loans during the years ended December 31, 2020 and 2019, respectively. No interest expense related to the Term Loans was recognized during the year ended December 31, 2021. The Company accounts for interest on its long-term debt under the effective interest method, with interest expense comprised of contractual interest, amortization of origination fees and other issuance costs, and accretion of final payment fees. Note 10. Leases The Company applies ASC 842 to recognize assets and liabilities for leases with lease terms of more than 12 months on the balance sheet. The Company has elected to account for each separate lease component and non-lease components 99 Table of Contents as one single component for all lease assets. Leases with terms of 12 months or less are not recorded on the balance sheet, and the related lease expenses are recognized on a straight-line basis over the lease term. ​ The Company has one operating lease agreement originally entered into in March 2017 for approximately 42,900 square feet for laboratory and office space located in Newark, California. On July 2, 2021, the Company entered into an amendment (the “Second Amendment”) to its original facility lease agreement for 15,000 square feet of additional office space in Newark, California. The Company commenced operations in the additional space in September 2021. Under the Second Amendment, the Company will pay additional base rent of approximately $ 1.5 million over the lease term, which expires in May 2024. As a result of this amendment, the Company recorded an additional right-of-use-asset and the related liability of $ 1.4 million as of December 31, 2021. ​ The Company provided the landlord with a $ 450,000 letter of credit collateralized by restricted cash as security deposit for the operating lease agreement, which expires in May 2024. The security deposit for the lease was later reduced to $ 225,000 in March 2021. No additional security deposit was required pursuant to the Second Amendment. Under the terms of the lease, as amended, the Company is responsible for its proportional share of operating expenses and tax obligations. ​ Balance sheet information related to operating leases is as follows for the periods presented (in thousands): ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ December 31, Operating Leases: ​ 2021 ​ 2020 Operating lease right-of-use asset ​ $ 4,936 ​ $ 4,950 ​ ​ ​ ​ ​ ​ ​ Operating lease liability - current ​ $ 2,200 ​ $ 1,459 Operating lease liability - noncurrent ​ ​ 3,658 ​ ​ 4,500 Total operating lease liabilities ​ $ 5,858 ​ $ 5,959 ​ ​ ​ ​ ​ ​ ​ Weighted-average remaining lease term (years) ​ ​ 2.4 ​ ​ 3.4 Weighted-average discount rate ​ ​ 10.4 % ​ ​ 11.0 % ​ Other information related to the Company’s operating leases is as follows for the periods presented (in thousands): ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Year Ended December 31, ​ 2021 ​ 2020 ​ 2019 Operating lease cost ​ $ 1,962 ​ $ 1,775 ​ $ 1,792 Less: Sublease income ​ ​ ( 91 ) ​ ​ ( 89 ) ​ ​ ( 64 ) Total lease expense ​ $ 1,871 ​ $ 1,686 ​ $ 1,728 ​ Supplemental cash flow information is as follows for the periods presented (in thousands): ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Year Ended December 31, ​ 2021 ​ 2020 ​ 2019 Operating cash flow used by operating leases ​ $ 2,049 ​ $ 1,941 ​ $ 1,885 New operating lease asset obtained in exchange for operating lease liability ​ $ 1,373 ​ $ — ​ $ — ​ 100 Table of Contents Future lease payments required under lease obligations as of December 31, 2021 are as follows (in thousands): ​ ​ ​ ​ Year Ending December 31: Amount 2022 ​ $ 2,660 2023 ​ ​ 2,744 2024 ​ ​ 1,160 2025 ​ ​ — Thereafter ​ — Total future minimum lease payments ​ ​ 6,564 Less: imputed interest ​ ​ ( 706 ) Present value of lease liabilities ​ $ 5,858 ​ ​ Note 11. Commitments and Contingencies Contract Service Providers In the normal course of business, the Company enters into agreements with contract service providers to assist in the performance of its R&D and clinical and commercial manufacturing activities. Subject to required notice periods and the Company’s obligations under binding purchase orders, the Company can elect to discontinue the work under these agreements at any time. The Company expects to enter into additional clinical development, contract research, clinical and commercial manufacturing, supplier and collaborative research agreements in the future, which may require upfront payments and long-term commitments of capital resources. Indemnification Agreements In the ordinary course of business, the Company enters into agreements that may include indemnification provisions. Pursuant to such agreements, the Company may indemnify, hold harmless and defend an indemnified party for losses suffered or incurred by the indemnified party. Some of the provisions will limit losses to those arising from third-party actions. In some cases, the indemnification will continue after the termination of the agreement. The maximum potential amount of future payments the Company could be required to make under these provisions is not determinable. The Company has also entered into indemnification agreements with its directors and officers that may require the Company to indemnify its directors and officers against liabilities that may arise by reason of their status or service as directors or officers to the fullest extent permitted by California corporate law. The Company carries a directors’ and officers’ insurance policy. To date, the Company has not incurred material costs to defend lawsuits or settle claims related to the indemnification agreements. The Company believes that the fair value of these indemnification agreements is minimal and has not accrued any amounts for the obligations. Legal Proceedings The Company recognizes accruals for legal actions to the extent that it concludes that a loss is both probable and reasonably estimable. The Company accrues for the best estimate of a loss within a range; however, if no estimate in the range is better than any other, it accrues the minimum amount in the range. If the Company determines that a loss is reasonably possible and the loss or range of loss can be estimated, it discloses the possible loss. On January 23, 2020, the Company initiated arbitration proceedings with the International Court of Arbitration of the International Chamber of Commerce against Zealand Pharma A/S (“Zealand”) related to a collaboration agreement the Company and Zealand entered into in 2012 and terminated in 2014. The agreement provides for certain post-termination payment obligations to Zealand with respect to compounds related to the collaboration that the Company elects to further develop and meet specified conditions. ​ On August 4, 2021, the Company and Zealand agreed to resolve the dispute and reached an Arbitration Resolution Agreement. Under the Arbitration Resolution Agreement, (1) the Company is required to make an additional payment of $ 1.5 million to Zealand in August 2022 with respect to rusfertide, (2) all development milestones with respect of 101 Table of Contents rusfertide have been reduced by 50 %, except that the Company agreed to pay in full within two (2) business days after the effective date of the Agreement (and timely paid): (i) a $ 1.0 million milestone for initiation of a Phase 2b clinical trial; and (ii) a $ 1.5 million milestone for initiation of a Phase 3 clinical trial; (3) the royalty rate payable by the Company on net sales of rusfertide has been reduced by 50 %; (4) all sales milestone payments on net sales of rusfertide have been reduced by 50 %; (5) the parties agreed that each party will retain all payments previously made by the other party in connection with the original collaboration agreement; and (6) the parties have released claims related to the original collaboration agreement, the abandonment agreement and the arbitration. In addition to the payments specified in items (1) and (2) above, the Company may also be required to pay Zealand up to $ 2.75 million in future development milestone payments relating to rusfertide. Those payments include up to $ 1.0 million in the aggregate for registrational proposals and up to $ 1.75 million in the aggregate for commercial launch in the three geographic territories specified in the original collaboration agreement. The Company considered the outcome of these arbitration proceedings as being related to research and development project; as such, payments or milestone payments were recorded as research and development expenses. As a result, no accruals related to legal proceedings were recognized as of December 31, 2021. Note 12. Stockholders’ Equity In September 2017, the Company filed a registration statement on Form S-3 with the Securities and Exchange Commission (File No. 333-220314) that was declared effective as of October 5, 2017 and permitted the offering, issuance, and sale by the Company of up to a maximum aggregate offering price of $ 200.0 million of its common stock, preferred stock and certain debt securities (the “2017 Form S-3”). Up to a maximum of $ 50.0 million of the maximum aggregate offering price of $ 200.0 million could be issued and sold pursuant to an at-the-market (“ATM”) financing facility under a sales agreement (the “2017 Sales Agreement”). The 2017 Sales Agreement was terminated in 2019. During the year ended December 31, 2019, prior to the termination of the 2017 Sales Agreement, the Company sold 2,846,641 shares of its common stock for net proceeds of $ 34.5 million, after deducting issuance costs. The 2017 Form S-3 expired in October 2020. In August 2018, the Company entered into a Securities Purchase Agreement with certain accredited investors (each, an “Investor” and, collectively, the “Investors”), pursuant to which the Company sold an aggregate of 2,750,000 shares of its common stock at a price of $ 8.00 per share, for aggregate net proceeds of $ 21.7 million, after deducting offering expenses payable by the Company. In a concurrent private placement, the Company issued the Investors warrants to purchase an aggregate of 2,750,000 shares of its common stock (each, a “Warrant” and, collectively, the “Warrants”). Each Warrant is exercisable from August 8, 2018 through August 8, 2023. Warrants to purchase 1,375,000 shares of the Company’s common stock have an exercise price of $ 10.00 per share and Warrants to purchase 1,375,000 shares of the Company’s common stock have an exercise price of $ 15.00 per share. The exercise price and number of shares of common stock issuable upon the exercise of the Warrants (the “Warrant Shares”) are subject to adjustment in the event of any stock dividends and splits, reverse stock split, recapitalization, reorganization or similar transaction, as described in the Warrants. Under certain circumstances, the Warrants may be exercisable on a “cashless” basis. In connection with the issuance and sale of the common stock and Warrants, the Company granted the Investors certain registration rights with respect to the Warrants and the Warrant Shares. The common stock and warrants are classified as equity in accordance with Accounting Standards Codification Topic 480 , Distinguishing Liabilities from Equity (“ASC 480”) , and the net proceeds from the transaction were recorded as a credit to additional paid-in capital. As of December 31, 2021, none of the Warrants have been exercised. In December 2018, the Company entered into an exchange agreement (the “Exchange Agreement”) with an Investor and its affiliates (the “Exchanging Stockholders”), pursuant to which the Company exchanged an aggregate of 1,000,000 shares of the Company’s common stock, par value $ 0.00001 per share, owned by the Exchanging Stockholders for pre-funded warrants (the “Exchange Warrants”) to purchase an aggregate of 1,000,000 shares of common stock (subject to adjustment in the event of any stock dividends and splits, reverse stock split, recapitalization, reorganization or similar transaction, as described in the Exchange Warrants), with an exercise price of $ 0.00001 per share. The Exchange Warrants will expire ten years from the date of issuance. The Exchange Warrants are exercisable at any time prior to expiration except that the Exchange Warrants cannot be exercised by the Exchanging Stockholders if, after giving effect thereto, the Exchanging Stockholders would beneficially own more than 9.99 % of the Company’s common stock, subject 102 Table of Contents to certain exceptions. In accordance with Accounting Standards Codification Topic 505, Equity , the Company recorded the retirement of the common stock exchanged as a reduction of common stock shares outstanding and a corresponding debit to additional paid-in-capital at the fair value of the Exchange Warrants on the issuance date. The Exchange Warrants are classified as equity in accordance with ASC 480 , and the fair value of the Exchange Warrants was recorded as a credit to additional paid-in capital and is not subject to remeasurement. The Company determined that the fair value of the Exchange Warrants is substantially similar to the fair value of the retired shares on the issuance date due to the negligible exercise price for the Exchange Warrants. During the year ended December 31, 2019, Exchange Warrants to purchase 600,000 shares were net exercised, resulting in the issuance of 599,997 shares of common stock. As of December 31, 2021, 400,000 of the Exchange Warrants remain unexercised. In October 2019, the Company filed a registration statement on Form S-3 (File No. 333-234414) that was declared effective as of November 22, 2019 and permits the offering, issuance, and sale by the Company of up to a maximum aggregate offering price of $ 250.0 million of its common stock, preferred stock, debt securities and warrants (the “2019 Form S-3”). Up to a maximum of $ 75.0 million of the maximum aggregate offering price of $ 250.0 million may be issued and sold pursuant to an ATM financing facility under a sales agreement entered into by the Company on November 27, 2019 (the “2019 Sales Agreement”). In May 2020, the Company completed an underwritten public offering of 7,000,000 shares of common stock at a public offering price of $ 14.00 per share and issued an additional 1,050,000 shares of its common stock at a price of $ 14.00 per share following the underwriters’ exercise of their option to purchase additional shares. Net proceeds, after deducting underwriting commissions and offering costs paid by the Company, were $ 105.3 million. The Company sold 2,483,719 shares of its common stock pursuant to the 2019 Sales Agreement during the year ended December 31, 2020 for net proceeds of $ 41.9 million, after deducting issuance costs. As of December 31, 2021, a total of $ 94.2 million of common stock remained available for sale under the 2019 Form S-3, $ 31.9 million of which remained available for sale under the ATM financing facility. The 2019 Form S-3 expires in October 2022. In December 2020, the Company filed an automatic registration statement on Form S-3ASR and an accompanying prospectus (File No. 333-251254), pursuant to which the Company completed an underwritten public offering of 4,761,904 shares of common stock at a public offering price of $ 21.00 per share and issued an additional 714,285 shares of its common stock at a price of $ 21.00 per share following the underwriters’ exercise of their option to purchase additional shares. Net proceeds, after deducting underwriting commissions and offering costs paid by the Company, were $ 107.6 million. In June 2021, pursuant to the Form S-3ASR (File No. 33-251254), the Company completed an underwritten public offering of 3,046,358 shares of its common stock at a public offering price of $ 37.75 per share and issued an additional 456,953 shares of common stock at a price of $ 37.75 per share following the underwriters’ exercise of their option to purchase additional shares. Net proceeds, after deducting underwriting commissions and offering costs paid by the Company, were $ 123.8 million. The Form S-3ASR expires in December 2023. Note 13. Equity Plans Equity Incentive Plan In May 2007, the Company established the 2007 Stock Option and Incentive Plan (“2007 Plan”) which provided for the granting of stock options to employees and consultants of the Company. Options granted under the 2007 Plan were either incentive stock options (“ISOs”) or nonqualified stock options (“NSOs”). ISOs were granted only to Company employees. NSOs were granted to Company employees, non-employee board directors and consultants. Options under the 2007 Plan have a term of ten years and generally vest over a four-year period. In July 2016, the Company’s board of directors and stockholders approved the 2016 Equity Incentive Plan (“2016 Plan”) to replace the 2007 Plan. Under the 2016 Plan, 1,200,000 shares of the Company’s common stock were initially reserved for the issuance of stock options, restricted stock units and other awards to employees, directors and consultants. Pursuant to the “evergreen” provision contained in the 2016 Plan, the number of shares reserved for issuance under the 2016 Plan automatically increases on January 1 of each year, starting on January 1, 2017 and continuing through (and including) January 1, 2026, by 4 % of the total number of shares of the Company’s capital stock outstanding on December 31 of the preceding fiscal year, or a lesser number of shares determined by the Company’s board of directors. Upon adoption of the 2016 Plan, no additional stock awards were issued under the 2007 Plan. Options granted under the 2007 Plan that were outstanding on the date the 2016 Plan became effective remain subject to the terms of the 2007 Plan. The 103 Table of Contents number of options available for grant under the 2007 Plan was ceased and the number was added to the common stock reserved for issuance under the 2016 Plan. As of December 31, 2021, approximately 564,189 shares of common stock were available for issuance under the 2016 Plan. The 2016 Plan is administered by the board of directors, or a committee appointed by the board of directors, which determines the types of awards to be granted, including the number of shares subject to the awards, the exercise price and the vesting schedule. Options granted under the 2016 Plan expire no later than ten years from the date of grant. The exercise price of each option may not be less than 100 % of the fair market value of the common stock at the date of grant. Options may be granted to stockholders possessing more than 10 % of the total combined voting power of all classes of stocks of the Company at an exercise price at least 110 % of the fair value of the common stock at the date of grant and the options are not exercisable after the expiration of 10 years from the date of grant. Employee stock options generally vest over a period of approximately four years . Non-employee director initial stock options generally vest monthly over a period of approximately three years , and non-employee director annual refresher stock options generally vest over a period of approximately one year . Inducement Plan In May 2018, the Company’s board of directors approved the 2018 Inducement Plan, as subsequently amended. The 2018 Inducement Plan is a non-stockholder approved stock plan, under which it reserved and authorized 750,000 shares of the Company’s common stock in order to award options and restricted stock unit awards to persons that were not previously employees or directors of the Company, or following a bona fide period of non-employment, as an inducement material to such persons entering into employment with the Company, within the meaning of Rule 5635(c)(4) of the Nasdaq Listing Rules. The 2018 Inducement Plan is administered by the board of directors or the Compensation Committee of the board, which determines the types of awards to be granted, including the number of shares subject to the awards, the exercise price and the vesting schedule. Awards granted under the 2018 Inducement Plan expire no later than ten years from the date of grant. As of December 31, 2021, approximately 243,125 shares were available for issuance under the 2018 Inducement Plan. Stock Options Stock option activity under the Company’s equity incentive and inducement plans is set forth below: ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Weighted- ​ Weighted- ​ ​ ​ ​ ​ ​ Average ​ Average ​ ​ ​ ​ ​ ​ Exercise ​ Remaining ​ Aggregate ​ ​ Options ​ Price Per ​ Contractual ​ Intrinsic ​ Outstanding Share Life (years) Value (1) ​ ​ ​ ​ ​ ​ ​ ​ ​ (in millions) Balances at December 31, 2020 4,648,120 $ 11.87 7.61 $ 40.0 Options granted 1,949,940 ​ ​ 29.96 ​ ​ Options exercised ( 474,801 ) ​ ​ 11.34 ​ ​ ​ Options forfeited ​ ( 232,719 ) ​ ​ 17.84 ​ ​ ​ ​ ​ Balances at December 31, 2021 5,890,540 $ 17.66 7.47 ​ $ 102.7 Options exercisable – December 31, 2021 ​ 3,224,575 $ 13.13 6.38 ​ $ 68.1 Options vested and expected to vest – December 31, 2021 ​ 5,890,540 ​ $ 17.66 7.47 ​ $ 102.7 ____________________ (1) The aggregate intrinsic values were calculated as the difference between the exercise price of the options and the closing price of the Company’s common stock on December 31, 2021. The calculation excludes options with an exercise price higher than the closing price of the Company’s common stock on December 31, 2021. ​ The aggregate intrinsic value of options exercised was $ 10.5 million, $ 3.0 million and $ 2.6 million for the years ended December 31, 2021, 2020 and 2019, respectively. 104 Table of Contents During the years ended December 31, 2021, 2020 and 2019, the estimated weighted-average grant-date fair value of common stock underlying options granted was $ 21.94 , $ 7.76 and $ 5.45 per share, respectively. For the years ended December 31, 2021, 2020 and 2019, the aggregate fair value of stock options that vested during the year was $ 11.3 million, $ 7.1 million and $ 7.3 million, respectively. Stock Options Valuation Assumptions The fair value of stock option awards was estimated at the date of grant using a Black-Scholes option-pricing model with the following assumptions: ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Year Ended December 31, ​ ​ 2021 ​ 2020 ​ 2019 Expected term (in years) 5.27 - 6.08 5.27 - 6.08 5.00 - 6.08 Expected volatility 87.4 % - 95.2 % ​ 72.1 % - 87.5 % ​ 61.0 % - 64.8 % Risk-free interest rate 0.11 % - 1.35 % ​ 0.23 % - 1.44 % ​ 1.42 % - 2.58 % Dividend yield — — — ​ In determining the fair value of the options granted, the Company uses the Black-Scholes option-pricing model and assumptions discussed below. Each of these inputs is subjective, and generally requires judgment to determine. ​ Expected Term —The Company’s expected term represents the period that the Company’s options granted are expected to be outstanding and is determined using the simplified method (based on the mid-point between the vesting date and the end of the contractual term). The Company has limited historical exercise information to develop reasonable expectations about future exercise patterns and post-vesting employment termination behavior for its stock option grants. Expected Volatility — Prior to January 1, 2020, the Company’s expected volatility was estimated based on the average volatility for comparable publicly traded biopharmaceutical companies over a period equal to the expected term of the awards. Beginning January 1, 2020, the Company’s expected volatility is based upon a blend of 75 % of the average volatility for comparable publicly traded biopharmaceutical companies and 25 % of the volatility of the Company’s stock price since its initial public offering in August 2016. Beginning January 1, 2021, the Company’s expected volatility is estimated based upon a mix of 50 % of the average volatility for comparable publicly traded biopharmaceutical companies over a period equal to the expected term of the stock option grants and 50 % of the volatility of the Company’s stock price since its initial public offering in August 2016. Risk-Free Interest Rate —The risk-free interest rate is based on the U.S. Treasury zero coupon issues in effect at the time of grant for periods corresponding with the expected term of option. Expected Dividend —The Company has never paid dividends on its common stock and has no plans to pay dividends on its common stock. Therefore, the Company used an expected dividend yield of zero. Restricted Stock Units The Company began issuing restricted stock units under the 2016 Plan during the year ended December 31, 2018. A restricted stock unit is an agreement to issue shares of the Company’s common stock at the time of vesting. Restricted stock unit awards generally vest in four equal installments on approximately the first, second, third and fourth anniversaries of the grant date. Restricted stock unit awards granted to certain executives in 2021 vest 100 % on the third anniversary of the grant date. Restricted stock unit incentive awards granted during 2018 vested in three equal installments at six months intervals over a period of 18 months . 105 Table of Contents Restricted stock unit activity under the Company’s equity incentive plans is set forth below: ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Weighted ​ ​ ​ ​ Average ​ ​ Number of ​ Grant Date ​ Shares Fair Value Unvested RSUs at December 31, 2020 ​ 244,545 ​ $ 9.31 Granted ​ 302,250 ​ ​ 24.40 Vested ​ ( 78,165 ) ​ ​ 10.13 Forfeited ​ ( 62,658 ) ​ ​ 18.65 Unvested RSUs at December 31, 2021 ​ 405,972 ​ $ 20.13 ​ Stock-based compensation expense associated with restricted stock units is based on the fair value of the Company’s common stock on the grant date, which equals the closing market price of the Company’s common stock on the grant date. For restricted stock units, the Company recognizes compensation expense over the vesting period of the awards that are ultimately expected to vest. For the years ended December 31, 2021, 2020 and 2019, the aggregate fair value of restricted stock units that vested during the year was $ 0.8 million, $ 1.2 million and $ 1.8 million, respectively. Performance Stock Units Performance stock unit activity under the Company’s equity incentive plans is set forth below: ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Weighted ​ ​ ​ ​ Average ​ ​ Number of ​ Grant Date ​ Shares Fair Value Unvested PSUs at December 31, 2020 ​ — ​ ​ ​ Granted 110,500 ​ $ 23.57 Vested ​ — ​ ​ — Forfeited ​ ( 5,000 ) ​ ​ 23.57 Unvested PSUs at December 31, 2021 ​ 105,500 ​ $ 23.57 ​ During the first quarter of 2021, the Company granted 110,500 PSUs to certain executives of the Company pursuant to the terms of the 2016 Plan. The grant date fair value of the PSUs was $ 23.57 per share. The terms of the PSUs provide for 100 % of shares to be earned based on the achievement of certain pre-determined performance objectives, subject to the participant’s continued employment. The PSUs will expire five years from the grant date if the performance objectives are not achieved. The PSUs will vest, if at all, upon certification by the Compensation Committee of the Company’s Board of Directors of the actual achievement of the performance objectives, subject to specified change of control exceptions. Stock-based compensation expense associated with PSUs is based on the fair value of the Company’s common stock on the grant date, which equals the closing price of the Company’s common stock on the grant date. The Company recognizes compensation expense over the vesting period of the awards that are ultimately expected to vest when the achievement of the related performance objective becomes probable. The total fair value of outstanding PSUs as of December 31, 2021 was $ 2.5 million. As of December 31, 2021, the achievement of the related performance objective was deemed not probable and, accordingly, no stock-based compensation for the PSUs has been recognized as expense as of December 31, 2021. Employee Stock Purchase Plan In July 2016, the Company’s board of directors and stockholders approved the 2016 Employee Stock Purchase Plan (“2016 ESPP”). The 2016 ESPP is intended to qualify as an employee stock purchase plan under Section 423 of the Internal Revenue Code of 1986, as amended, and is administered by the Company’s board of directors and the Compensation Committee of the board of directors. Under the 2016 ESPP, 150,000 shares of the Company’s common stock were initially reserved for employee purchases of the Company’s common stock. Pursuant to the “evergreen” provision contained in the 2016 ESPP, the number of shares reserved for issuance automatically increases on January 1 of 106 Table of Contents each year, starting on January 1, 2017 and continuing through (and including) January 1, 2026 by the lesser of (i) 1 % of the total number of shares of common stock outstanding on December 31 of the preceding fiscal year (ii) 300,000 shares, or (iii) such other number of shares determined by the board of directors. The 2016 ESPP allows eligible employees to purchase shares of the Company’s common stock at a discount through payroll deductions of up to 15 % of their eligible compensation. At the end of each offering period, eligible employees are able to purchase shares at 85 % of the lower of the fair market value of the Company’s common stock at the beginning of the offering period or at the end of each applicable purchase period. During the year ended December 31, 2021, a total of 43,648 shares were issued under the 2016 ESPP, and 1,013,999 shares remain available for issuance as of December 31, 2021. The fair value of the rights granted under the 2016 ESPP was calculated using the Black-Scholes option-pricing model with the following assumptions: ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Year Ended December 31, ​ ​ 2021 2020 2019 Expected term (in years) ​ 0.50 ​ 0.50 ​ 0.50 Expected volatility ​ 50.9 % - 69.7 % ​ 89.1 % - 120.4 % ​ 58.9 % - 65.3 % Risk-free interest rate ​ 0.06 % ​ 0.12 % - 0.43 % ​ 1.89 % - 2.32 % Dividend yield ​ — ​ — ​ — ​ Stock-Based Compensation Total stock-based compensation expense was as follows (in thousands): ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Year Ended December 31, ​ 2021 2020 2019 Research and development ​ $ 8,996 ​ $ 4,121 ​ $ 4,350 General and administrative ​ 7,399 ​ 3,778 ​ 4,003 Total stock-based compensation expense ​ $ 16,395 ​ $ 7,899 ​ $ 8,353 ​ As of December 31, 2021, total unrecognized stock-based compensation expense was approximately $ 46.3 million, which the Company expects to recognize over a weighted-average period of approximately 2.7 years. Note 14. 401(k) Plan The Company has a retirement and savings plan under Section of 401(k) of Internal Revenue Code (the “401(k) Plan”) covering all U.S. employees. The 401(k) Plan allows employees to make pre- and post-tax contributions up to the maximum allowable amount set by the Internal Revenue Service. The Company may make contributions to this plan at its discretion. For the year ended December 31, 2021, the Company matched 50 % of each employee’s contribution up to a maximum of $ 3,500 , resulting in recognized expense of approximately $ 0.3 million relating to these contributions. No matching contributions were made to the plan by the Company for the years ended December 31, 2020 and 2019. Note 15. Income Taxes No income tax expense was recorded by the Company for the year ended December 31, 2021. The Company recorded income tax expense of $ 1.3 million for the year ended December 31, 2020. During the second quarter of 2020, the Company’s Australia subsidiary sold beneficial rights to discovery intellectual property to its U.S. entity, and the U.S. entity reimbursed the Australia subsidiary for certain direct development costs. Upon completion of the sale, the Company analyzed tax planning strategies and future income and concluded that a full valuation allowance is necessary for its Australia subsidiary. Income tax expense for the year ended December 31, 2020 reflects this sale of intellectual property rights, cost reimbursements and related adjustments to the deferred tax asset, establishing a valuation allowance and certain uncertain tax position liabilities. The Company’s effective income tax rate differed from the Company’s federal statutory rate of 21 %, primarily because its U.S. loss cannot be benefited due to the full valuation position and reduced by foreign taxes. 107 Table of Contents The Company recorded an income tax benefit of $ 0.7 million for the year ended December 31, 2019 primarily due to research and development tax credits and the recognition of deferred tax assets in the Company’s Australia subsidiary. ​ The following table presents domestic and foreign components of net loss before income taxes (in thousands): ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Year Ended December 31, ​ 2021 2020 2019 Domestic ​ $ ( 125,797 ) ​ $ ( 71,073 ) ​ $ ( 72,271 ) Foreign ​ 246 ​ 6,228 ​ ( 5,607 ) Total net loss before taxes ​ $ ( 125,551 ) ​ $ ( 64,845 ) ​ $ ( 77,878 ) ​ The federal, state and foreign components of the income tax expense (benefit) are summarized as follows: ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Year Ended December 31, ​ ​ 2021 ​ 2020 ​ 2019 Current: ​ ​ ​ ​ ​ ​ ​ ​ ​ Federal ​ $ — ​ $ — ​ $ — State ​ ​ — ​ ​ — ​ ​ — Foreign ​ ​ — ​ ​ ( 88 ) ​ ​ 84 Total current tax (benefit) expense ​ ​ — ​ ​ ( 88 ) ​ ​ 84 Deferred: ​ ​ ​ ​ ​ ​ ​ ​ ​ Federal ​ ​ — ​ ​ — ​ ​ — State ​ ​ — ​ ​ — ​ ​ — Foreign ​ ​ — ​ ​ 1,393 ​ ​ ( 775 ) Total deferred tax expense (benefit) ​ ​ — ​ ​ 1,393 ​ ​ ( 775 ) Total income tax expense (benefit) ​ $ — ​ $ 1,305 ​ $ ( 691 ) ​ The effective tax rate of the provision for income taxes differs from the federal statutory rate as follows: ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Year Ended December 31, ​ 2021 2020 2019 Federal statutory income tax rate 21.0 % 21.0 % 21.0 % State taxes, net of federal benefit 1.9 1.9 1.2 Research and development credits ​ 4.3 ​ 6.5 ​ 4.3 ​ Foreign tax rate difference — ( 0.9 ) 0.7 Change in valuation allowance ( 28.0 ) ( 34.3 ) ( 23.8 ) Other 0.8 3.8 ( 2.5 ) (Provision) benefit for income taxes — % ( 2.0 ) % 0.9 % ​ 108 Table of Contents The components of the deferred tax assets are as follows (in thousands): ​ ​ ​ ​ ​ ​ ​ ​ ​ December 31, ​ 2021 2020 Deferred tax assets: ​ ​ ​ ​ ​ Net operating loss carryforwards ​ $ 75,649 ​ $ 50,272 Depreciation and amortization ​ 1,153 ​ 1,237 Accruals/other ​ 5,716 ​ 5,332 Operating lease liability ​ ​ 1,230 ​ ​ 1,252 Research and development and foreign credits ​ 21,197 ​ 14,856 Total deferred tax assets ​ 104,945 ​ 72,949 Deferred tax liabilities: ​ ​ ​ ​ ​ ​ Operating right-of-use asset ​ ​ ( 1,037 ) ​ ​ ( 1,040 ) Total deferred tax liabilities ​ ​ ( 1,037 ) ​ ​ ( 1,040 ) Valuation allowance ​ ( 103,908 ) ​ ( 71,909 ) Net deferred tax assets ​ $ — ​ $ — ​ Realization of the deferred tax assets is dependent upon future taxable income, if any, the amount and timing of which are uncertain. The Company established a valuation allowance to offset U.S. deferred tax assets as of December 31, 2021, 2020 and 2019 due to the uncertainty of realizing future tax benefits from its net operating loss carryforwards and other deferred tax assets. The Company also established a valuation allowance to offset Australian deferred tax assets as of December 31, 2021. The valuation allowance increased by approximately $ 32.0 million, $ 19.4 million and $ 18.5 million during the years ended December 31, 2021, 2020 and 2019, respectively. Federal and state laws impose substantial restrictions on the utilization of net operating loss and tax credit carryforwards in the event of an ownership change for tax purposes, as defined in Section 382 of the Internal Revenue Code. As a result of such ownership changes, the annual limitation may result in the expiration of net operating losses and credits before utilization. The Company performed a Section 382 analysis through December 31, 2021. The Company has experienced ownership changes in the past and in the current year. The ownership changes will not result in a limitation that will materially reduce the total amount of net operating loss carryforwards and credits that can be utilized. Subsequent ownership changes may affect the limitation in future years. At December 31, 2021, the Company had $ 347.7 million of federal net operating loss carryforwards and $ 336.2 million of state net operating loss carryforwards. $ 78.7 million of the federal net operating loss carryforwards will begin to expire in 2033, if not utilized, and the remaining $ 269.0 million have no expiration date. The state net operating loss carryforwards will begin to expire in 2035, if not utilized. At December 31, 2021, the Company also had fully utilized the remaining Australian tax losses of AUD 3.1 million ($ 2.3 million) carryforward. As of December 31, 2021, the Company had $ 19.2 million of federal and $ 7.9 million of state research and development tax credit carryforwards available to reduce future income taxes. The federal research and development tax credits will begin to expire in 2035, if not utilized. The state research and development tax credits have no expiration date. As of December 31, 2021, the Company had AUD 2.9 million ($ 2.1 million) of Australian research and development tax credit carryforwards available to reduce future income taxes. The Australian research and development tax credits have no expiration date. 109 Table of Contents A reconciliation of the beginning and ending amount of unrecognized tax benefits is as follows (in thousands): ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Year Ended December 31, ​ 2021 2020 2019 Balance at beginning of year ​ $ 19,885 ​ $ 16,631 ​ $ 9,466 (Decreases) increases based on tax positions related to prior years ​ — ​ ( 3,799 ) ​ 184 Increases based on tax positions related to current year ​ 13,274 ​ 7,053 ​ 6,981 Balance at end of year ​ $ 33,159 ​ $ 19,885 ​ $ 16,631 ​ At December 31, 2021, the Company had unrecognized tax benefits of $ 33.2 million, which are subject to a valuation allowance and would not affect the effective tax rate if recognized. The Company does not anticipate that the total amounts of unrecognized tax benefits will significantly increase or decrease in the next 12 months. The Company’s policy is to include interest and penalties related to unrecognized tax benefits within the provision for income taxes, as necessary. Management determined that no accrual for interest or penalties was required as of December 31, 2021, 2020 and 2019. The Company files income tax returns in the United States federal jurisdiction, the State of California, the state of Florida, and Australia. The Company is not currently under examination by income tax authorities in federal, state or other jurisdictions. The Company’s tax returns remain open for examination for all years. The Company’s Australia subsidiary had an accumulated deficit at December 31, 2021 and, accordingly, no provision has been provided thereon for any unremitted earnings. ​ The Company has elected to recognize any potential global intangible low-taxed income (“GILTI”) obligation as an expense in the period it is incurred. ​ Note 16. Net Loss per Share As the Company had a net loss for the years ended December 31, 2021, 2020 and 2019, all potential weighted average dilutive common shares were determined to be anti-dilutive. The following table sets forth the computation of basic and diluted net loss per share (in thousands, except share and per share data): ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Year Ended December 31, ​ 2021 2020 2019 Numerator: ​ ​ ​ ​ ​ ​ ​ Net loss ​ $ ( 125,551 ) ​ $ ( 66,150 ) ​ $ ( 77,187 ) Denominator: ​ ​ ​ ​ ​ ​ ​ Weighted-average shares used to compute net loss per common share, basic and diluted ​ 46,322,910 34,396,446 25,894,024 Net loss per share, basic and diluted ​ $ ( 2.71 ) ​ $ ( 1.92 ) ​ $ ( 2.98 ) ​ The following outstanding shares of potentially dilutive securities have been excluded from diluted net loss per share computations for the periods presented because their inclusion would be anti-dilutive: ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ December 31, ​ 2021 2020 2019 Options to purchase common stock ​ 5,890,540 4,648,120 3,681,521 Common stock warrants ​ 2,750,000 ​ 2,750,000 ​ 2,750,000 Restricted stock units ​ 405,972 ​ 244,545 ​ 278,482 Performance stock units ​ 105,500 ​ — ​ — ESPP shares ​ 18,055 ​ 28,445 ​ 40,275 Total 9,170,067 7,671,110 6,750,278 ​ ​ 110 Table of Contents Note 17. Restructuring On May 7, 2020, the Company approved a limited reduction in force plan affecting approximately 12 % of the Company’s employee base and informed the affected employees. The reduction-in-force plan was completed by the end of the second quarter of 2020. Total cash expenditures for the reduction in force plan were $ 0.3 million, substantially all of which were related to employee severance and benefits costs. Note 18. Subsequent Event The Company sold 422,367 shares of its common stock under its ATM financing facility pursuant to the 2019 Sales Agreement during the period from January 1, 2022 through the date of issuance of this Annual Report on Form 10-K. Net proceeds were $ 14.6 million, after deducting issuance costs. As of the date of issuance of this Annual Report on Form 10-K, a total of $ 79.3 million of common stock remained available for sale under the 2019 Form S-3, $ 17.0 million of which remained available for sale under the ATM financing facility. ​ ​ 111 Table of Contents Item 9. Changes in and Disagreements with Accountants on Accounting and Financial Disclosure None.