PROTHENA CORP PUBLIC LTD CO, 10-Q filed on 5/8/2024
Quarterly Report
v3.24.1.u1
Cover Page - shares
 3 Months Ended
Mar. 31, 2024
May 01, 2024
Cover [Abstract]    
Document Type 10-Q  
Document Quarterly Report true  
Document Period End Date Mar. 31, 2024  
Document Transition Report false  
Entity File Number 001-35676  
Entity Registrant Name PROTHENA CORPORATION PUBLIC LIMITED COMPANY  
Entity Incorporation, State or Country Code L2  
Entity Tax Identification Number 98-1111119  
Entity Address, Address Line One 77 Sir John Rogerson’s Quay, Block C  
Entity Address, Address Line Two Grand Canal Docklands  
Entity Address, City or Town Dublin 2,  
Entity Address, Postal Zip Code D02 VK60,  
Entity Address, Country IE  
Country Region 353  
City Area Code 1  
Local Phone Number 236-2500  
Title of 12(b) Security Ordinary Shares, par value $0.01 per share  
Trading Symbol PRTA  
Security Exchange Name NASDAQ  
Entity Current Reporting Status Yes  
Entity Interactive Data Current Yes  
Entity Filer Category Large Accelerated Filer  
Entity Small Business false  
Entity Emerging Growth Company false  
Entity Shell Company false  
Entity Common Stock, Shares Outstanding   53,771,845
Amendment Flag false  
Document Fiscal Year Focus 2024  
Document Fiscal Period Focus Q1  
Entity Central Index Key 0001559053  
Current Fiscal Year End Date --12-31  
v3.24.1.u1
Condensed Consolidated Balance Sheets - USD ($)
$ in Thousands
Mar. 31, 2024
Dec. 31, 2023
Current assets:    
Cash and cash equivalents $ 546,512 $ 618,830
Accounts receivable 0 5,159
Prepaid expenses and other current assets 18,004 13,941
Restricted cash, current 1,352 1,352
Total current assets 565,868 639,282
Non-current assets:    
Property and equipment, net 3,672 3,836
Operating lease right-of-use assets 12,510 12,162
Deferred tax assets 36,675 33,893
Restricted cash, non-current 860 860
Other non-current assets 3,609 6,349
Total non-current assets 57,326 57,100
Total assets 623,194 696,382
Current liabilities:    
Accounts payable 14,420 25,391
Accrued research and development 17,340 14,724
Lease liability, current 2,372 1,114
Other current liabilities 9,134 15,662
Total current liabilities 43,266 56,891
Non-current liabilities:    
Deferred revenue, non-current 67,405 67,405
Lease liability, non-current 10,124 10,721
Total non-current liabilities 77,529 78,126
Total liabilities 120,795 135,017
Commitments and contingencies (Note 6)
Shareholders’ equity:    
Euro deferred shares, €22 nominal value: Authorized shares — 10,000 at March 31, 2024 and December 31, 2023. Issued and outstanding shares — none at March 31, 2024 and December 31, 2023 0 0
Ordinary shares, $0.01 par value: Authorized shares — 100,000,000 at March 31, 2024 and December 31, 2023. Issued and outstanding shares — 53,720,455 and 53,682,117 at March 31, 2024 and December 31, 2023, respectively 537 537
Additional paid-in capital 1,554,132 1,540,859
Accumulated deficit (1,052,270) (980,031)
Total shareholders’ equity 502,399 561,365
Total liabilities and shareholders’ equity $ 623,194 $ 696,382
v3.24.1.u1
Condensed Consolidated Balance Sheets (Parenthetical)
Mar. 31, 2024
€ / shares
shares
Mar. 31, 2024
$ / shares
shares
Dec. 31, 2023
€ / shares
shares
Dec. 31, 2023
$ / shares
shares
Shareholders’ equity:        
Euro deferred shares, nominal value (in euros per share) | € / shares € 22   € 22  
Euro deferred shares, number of shares authorized (in shares) 10,000 10,000 10,000 10,000
Euro deferred shares, number of issued shares (in shares) 0 0 0 0
Euro deferred shares, number of outstanding shares (in shares) 0 0 0 0
Ordinary shares, par value (in dollars per share) | $ / shares   $ 0.01   $ 0.01
Ordinary shares, number of authorized shares (in shares) 100,000,000 100,000,000 100,000,000 100,000,000
Ordinary shares, number of issued shares (in shares) 53,720,455 53,720,455 53,682,117 53,682,117
Ordinary shares, number of outstanding shares (in shares) 53,720,455 53,720,455 53,682,117 53,682,117
v3.24.1.u1
Condensed Consolidated Statements of Operations - USD ($)
shares in Thousands, $ in Thousands
 3 Months Ended
Mar. 31, 2024
Mar. 31, 2023
Total revenue $ 50 $ 2,169
Operating expenses:    
Research and development 64,114 44,756
General and administrative 17,464 13,738
Total operating expenses 81,578 58,494
Loss from operations (81,528) (56,325)
Other income (expense):    
Interest income 7,165 6,690
Other expense, net (77) (141)
Total other income, net 7,088 6,549
Loss before income taxes (74,440) (49,776)
Benefit from income taxes (2,201) (2,912)
Net loss $ (72,239) $ (46,864)
Basic (in dollars per share) $ (1.34) $ (0.89)
Diluted (in dollars per share) $ (1.34) $ (0.89)
Weighted-average ordinary shares outstanding used in per share calculations- basic (in shares) 53,714 52,501
Weighted-average ordinary shares outstanding used in per share calculations- diluted (in shares) 53,714 52,501
Collaboration revenue    
Total revenue $ 0 $ 2,119
Revenue from license and intellectual property    
Total revenue $ 50 $ 50
v3.24.1.u1
Condensed Consolidated Statements of Cash Flows - USD ($)
$ in Thousands
 3 Months Ended
Mar. 31, 2024
Mar. 31, 2023
Operating activities    
Net loss $ (72,239) $ (46,864)
Adjustments to reconcile net loss to cash used in operating activities:    
Depreciation 215 201
Share-based compensation 12,383 8,790
Deferred income taxes (2,782) (3,229)
Reduction in the carrying amount of right-of-use assets 672 1,558
Changes in operating assets and liabilities:    
Accounts receivable 5,159 0
Prepaid and other assets (1,639) (5,935)
Accounts payable, accruals and other liabilities (14,455) 1,728
Deferred revenue 0 (2,119)
Operating lease liabilities (365) (1,588)
Net cash used in operating activities (73,051) (47,458)
Investing activities    
Purchases of property and equipment (103) (48)
Net cash used in investing activities (103) (48)
Financing activities    
Proceeds from issuance of ordinary shares upon exercise of stock options 890 2,602
Net cash provided by financing activities 836 23,284
Net decrease in cash, cash equivalents and restricted cash (72,318) (24,222)
Cash, cash equivalents and restricted cash, beginning of the year 621,042 712,618
Cash, cash equivalents and restricted cash, end of the period 548,724 688,396
Supplemental disclosures of cash flow information    
Cash paid for income taxes 20 0
Supplemental disclosures of non-cash investing and financing activities    
Acquisition of property and equipment included in accounts payable and accrued liabilities 184 345
Cash and cash equivalents 546,512 686,184
Restricted cash, current 1,352 0
Restricted cash, non-current 860 2,212
Total cash, cash equivalents and restricted cash, end of the period 548,724 688,396
Public Offering    
Financing activities    
Proceeds from issuance of ordinary shares in public offering, net 0 20,722
Supplemental disclosures of non-cash investing and financing activities    
Offering costs included in accounts payable and accrued liabilities 0 35
At-The-Market Offering    
Financing activities    
Proceeds from issuance of ordinary shares in at-the market offering, net (54) (40)
Supplemental disclosures of non-cash investing and financing activities    
Offering costs included in accounts payable and accrued liabilities $ 0 $ 2
v3.24.1.u1
Condensed Consolidated Statements of Shareholders' Equity - USD ($)
$ in Thousands
Total
Public Offering
Ordinary Shares
Ordinary Shares
Public Offering
Additional Paid-in Capital
Additional Paid-in Capital
Public Offering
Accumulated Deficit
Beginning balance (in shares) at Dec. 31, 2022     52,103,608        
Beginning balance at Dec. 31, 2022 $ 622,042   $ 521   $ 1,454,524   $ (833,003)
Share-based compensation 8,790       8,790    
Issuance of ordinary shares upon exercise of stock options (in shares)     179,474        
Issuance of ordinary shares upon exercise of stock options 2,540   $ 2   2,538    
Issuance of ordinary shares (in shares)       395,096      
Issuance of ordinary shares, net of issuance costs   $ 20,901   $ 4   $ 20,897  
Net income (loss) (46,864)           (46,864)
Ending balance (in shares) at Mar. 31, 2023     52,678,178        
Ending balance at Mar. 31, 2023 607,409   $ 527   1,486,749   (879,867)
Stock Issuance Costs   $ (1,400)          
Beginning balance (in shares) at Dec. 31, 2023     53,682,117        
Beginning balance at Dec. 31, 2023 561,365   $ 537   1,540,859   (980,031)
Share-based compensation $ 12,383       12,383    
Issuance of ordinary shares upon exercise of stock options (in shares) 38,338   38,338        
Issuance of ordinary shares upon exercise of stock options $ 890   $ 0   890    
Net income (loss) (72,239)           (72,239)
Ending balance (in shares) at Mar. 31, 2024     53,720,455        
Ending balance at Mar. 31, 2024 $ 502,399   $ 537   $ 1,554,132   $ (1,052,270)
v3.24.1.u1
Condensed Consolidated Statements of Shareholders' Equity (Parenthetical)
$ in Millions
 3 Months Ended
Mar. 31, 2023
USD ($)
Public Offering  
Stock Issuance Costs $ (1.4)
v3.24.1.u1
Organization
 3 Months Ended
Mar. 31, 2024
Organization, Consolidation and Presentation of Financial Statements [Abstract]  
Organization Organization
Description of Business

Prothena Corporation plc (“Prothena” or the “Company”) is a late-stage clinical biotechnology company with expertise in protein dysregulation and a pipeline of investigational therapeutics with the potential to change the course of devastating neurodegenerative and rare peripheral amyloid diseases.

Fueled by its deep scientific expertise built over decades of research, the Company is advancing a pipeline of therapeutic candidates for a number of indications and novel targets for which its ability to integrate scientific insights around neurological dysfunction and the biology of misfolded proteins can be leveraged. The Company’s wholly-owned programs include birtamimab for the potential treatment of AL amyloidosis, and a portfolio of programs for the potential treatment of Alzheimer’s disease including PRX012, which targets amyloid beta (Aβ), and PRX123, a novel dual Aβ-tau vaccine. The Company’s partnered programs include prasinezumab, in collaboration with Roche for the potential treatment of Parkinson’s disease and other related synucleinopathies, and programs that target tau (BMS-986446, formerly PRX005), TDP-43, and an undisclosed target (PRX019) in collaboration with Bristol Myers Squibb (BMS) for the potential treatment of Alzheimer’s disease, amyotrophic lateral sclerosis (ALS), and other neurodegenerative diseases, respectively. The Company is also entitled to certain potential milestone payments pursuant to the Company’s share purchase agreement with Novo Nordisk pertaining to the Company’s ATTR amyloidosis business (including NNC6019, formerly PRX004).
The Company was formed on September 26, 2012, under the laws of Ireland and re-registered as an Irish public limited company on October 25, 2012. The Company's ordinary shares began trading on The Nasdaq Global Market under the symbol “PRTA” on December 21, 2012, and currently trade on The Nasdaq Global Select Market.
Liquidity and Business Risks
As of March 31, 2024, the Company had an accumulated deficit of $1.1 billion and cash and cash equivalents of $546.5 million.
Based on the Company's business plans, management believes that the Company’s cash and cash equivalents at March 31, 2024, are sufficient to meet its obligations for at least the next twelve months. To operate beyond such period, or if the Company elects to increase its spending on research and development programs significantly above current long-term plans or enters into potential licenses and or other acquisitions of complementary technologies, products or companies, the Company may need additional capital. The Company expects to continue to finance future cash needs that exceed its cash from operating activities primarily through its current cash and cash equivalents, payments pursuant to its agreements with Roche, BMS, and Novo Nordisk, and, to the extent necessary, through proceeds from public or private equity or debt financings, loans and other collaborative agreements with corporate partners or other arrangements.
v3.24.1.u1
Summary of Significant Accounting Policies
 3 Months Ended
Mar. 31, 2024
Accounting Policies [Abstract]  
Summary of Significant Accounting Policies Summary of Significant Accounting Policies
Basis of Preparation and Presentation of Financial Information
These accompanying Condensed Consolidated Financial Statements have been prepared in accordance with the accounting principles generally accepted in the U.S. (“GAAP”) and with the instructions for Form 10-Q and Regulation S-X statements. Accordingly, they do not include all of the information and notes required for complete financial statements. These Condensed Consolidated Financial Statements should be read in conjunction with the Consolidated Financial Statements and Notes thereto contained in the Company’s Annual Report on Form 10-K filed with the U.S. Securities and Exchange Commission (the “SEC”) on February 22, 2024 (the “2023 Form 10-K”). These Unaudited Interim Condensed Consolidated Financial Statements are presented in U.S. dollars, which is the functional currency of the Company and its consolidated subsidiaries. These Condensed Consolidated Financial Statements include the accounts of the Company and its consolidated subsidiaries. All intercompany balances and transactions have been eliminated in consolidation.

Unaudited Interim Financial Information
The accompanying Condensed Consolidated Financial Statements and related disclosures are unaudited, have been prepared on the same basis as the annual consolidated financial statements and, in the opinion of management, reflect all adjustments, which include only normal recurring adjustments, necessary for a fair presentation of the results of operations for
the periods presented. The year-end condensed consolidated balance sheet data was derived from audited financial statements, however certain information and footnote disclosures normally included in financial statements prepared in accordance with GAAP have been condensed or omitted. The condensed consolidated results of operations for any interim period are not necessarily indicative of the results to be expected for the full year or for any other future year or interim period.
Use of Estimates
The preparation of the Condensed Consolidated Financial Statements in conformity with U.S. GAAP requires the Company to make judgments, estimates and assumptions that affect the reported amounts of assets, liabilities, revenues and expenses, and related disclosures. On an ongoing basis, management evaluates its estimates, including critical accounting policies or estimates related to revenue recognition and research and development expenses. The Company bases its estimates on historical experience and on various other market specific and other relevant assumptions that management believes to be reasonable under the circumstances, the results of which form the basis for making judgments about the carrying values of assets and liabilities that are not readily apparent from other sources. Because of the uncertainties inherent in such estimates, actual results may differ materially from these estimates.
Significant Accounting Policies
There were no significant changes to the accounting policies during the three months ended March 31, 2024, from the significant accounting policies described in Note 2 of the Notes to Consolidated Financial Statements in the 2023 Form 10-K.
Concentration of Risks and Other Risks and Uncertainties
Financial instruments that potentially subject the Company to concentration of credit risk consist of cash and cash equivalents and accounts receivable. The Company places its cash equivalents with high credit quality financial institutions and, by policy, limits the amount of credit exposure with any one financial institution. Deposits held with banks have exceeded, and will continue to exceed, federally insured limits. The Company is exposed to credit risk in the event of a default by the financial institutions holding its cash and cash equivalents. The Company has not experienced any losses on its deposits of cash and cash equivalents and its credit risk exposure is up to the extent recorded on the Company's Condensed Consolidated Balance Sheet.
The Company’s business is primarily conducted in U.S. dollars except for its agreements with contract manufacturers for drug supplies which are primarily denominated in Euros. The Company recorded a loss on foreign currency exchange rate differences of approximately $77,000 and $141,000 during the three months ended March 31, 2024 and 2023, respectively. If the Company increases its business activities that require the use of foreign currencies, it may be exposed to losses if the Euro and other such currencies continue to strengthen against the U.S. dollar.
As of March 31, 2024, and December 31, 2023, approximately $3.7 million and $3.8 million, respectively, of the Company’s property and equipment, net were held in the U.S. and a nominal amount were in Ireland.
The Company is subject to a number of risks similar to other late-stage clinical biotechnology companies, including, but not limited to, the need to obtain adequate additional funding, possible failure of current or future preclinical testing or clinical trials, its reliance on third parties to conduct its clinical trials, the need to obtain regulatory and marketing approvals for its drug candidates, competitors developing new technological innovations, the need to successfully commercialize and gain market acceptance of the Company’s drug candidates, its right to develop and commercialize its drug candidates pursuant to the terms and conditions of the licenses granted to the Company, protection of proprietary technology, and the need to secure and maintain adequate clinical trial management, manufacturing, packaging, labeling, storage, testing, and distribution arrangements with third parties. The Company also relies on third-party consultants to assist in managing these third parties and assist with its clinical trial operations and manufacturing. If the Company does not successfully commercialize or partner any of its drug candidates, it will be unable to generate product revenue or achieve profitability. Further, the Company is also subject to broad market risks and uncertainties resulting from recent events, such as inflation, rising interest rates, and recession risks, as well as supply chain and labor shortages.
Segment
The Company operates in one segment. The Company’s chief operating decision maker (the “CODM”), its Chief Executive Officer, manages the Company’s operations and evaluates the Company’s financial performance on a consolidated basis for purposes of allocating resources.
Recent Accounting Pronouncements

On March 6, 2024, the SEC issued final rule, “The Enhancement and Standardization of Climate-Related Disclosures for Investors”, which requires registrants to disclose material climate-related risks, including descriptions of board oversight and
risk management activities, the material impacts of these risks on a registrants strategy, business model and outlook and any material climate-related targets or goals. The rule requires these climate-related information to be disclosed in registration statements and annual reports. Registrants will also need to quantify certain effects of severe weather events and other natural conditions in a note to their audited financial statements. In addition, accelerated and large accelerated filers will need to disclose Scope 1 and Scope 2 greenhouse gas (GHG) emissions, if material, which will be subject to third-party assurance. The Company will be required to comply with the rule in fiscal year beginning January 1, 2025 for all disclosures other than the compliance with quantitative and qualitative disclosure requirements of material expenditures and material impacts on financial estimates that directly result from (1) activities to mitigate or adapt to the climate-related risks, (2) targets or goals and (3) transition plans will be required beginning fiscal year 2026. The Company’s other compliance dates are the following: 1) Scope 1 and Scope 2 GHG emissions - fiscal year beginning January 1, 2026; Limited assurance - fiscal year beginning January 1, 2029; Reasonable assurance - fiscal year beginning January 1, 2033; and Electronic tagging - fiscal year beginning January 1, 2026. The Company is currently evaluating the impact of the new standard on its consolidated financial statements and related disclosures. On April 4, 2024, the Securities and Exchange Commission (SEC) voluntarily stayed implementation of its recently adopted Climate Disclosure Rules.

On November 27, 2023, the FASB issued Accounting Standards Update 2023-07 ("ASU 2023-07"), Segment Reporting- Improvements to Reportable Segment Disclosures, which requires public entities to provide disclosures on significant segment expenses that are regularly provided to the CODM and included within each reported measure of segment profit or loss and other segment items on an annual and interim basis. The guidance also requires public entities to provide all disclosures about reportable segment’s profit or loss and assets in interim periods that are currently required annually. Public entities with a single reportable segment have to provide all disclosures required by Accounting Standards Codification (ASC) 280, Segment Reporting including the significant segment expense disclosures. The guidance is applied retrospectively to all periods presented in financial statements and is effective for fiscal years beginning after December 15, 2023, and for interim periods beginning after December 15, 2024. Early adoption is permitted. The Company is currently evaluating the impact of adopting the update on the Company's disclosures.

In December 2023, the FASB issued ASU 2023-09, Improvements to Income Tax Disclosures, which requires public business entities to disclose a tabular reconciliation using both percentages and amounts, broken out into specific categories with certain reconciling items at or above 5% of the expected tax further broken out by nature and/or jurisdiction. The guidance also requires all entities to disclose income taxes paid, net of refunds, disaggregated by federal (national), state and foreign taxes for annual periods and to disaggregate the information by jurisdiction based on a quantitative threshold. All entities are required to apply the guidance prospectively, with the option to apply it retrospectively. The guidance is effective for the Company’s fiscal year beginning January 1, 2025. Early adoption is permitted. The Company is currently evaluating the impact of the new standard on its income tax disclosures.
v3.24.1.u1
Fair Value Measurements
 3 Months Ended
Mar. 31, 2024
Fair Value Disclosures [Abstract]  
Fair Value Measurements Fair Value Measurements
The Company measures certain financial assets and liabilities at fair value on a recurring basis, including cash equivalents. Fair value is an exit price, representing the amount that would be received to sell an asset or paid to transfer a liability in an orderly transaction between market participants. As such, fair value is a market-based measurement that should be determined based on assumptions that market participants would use in pricing an asset or a liability. A three-tier fair value hierarchy is established as a basis for considering such assumptions and for inputs used in the valuation methodologies in measuring fair value:
Level 1 —    inputs are quoted prices (unadjusted) for identical assets or liabilities in active markets.
Level 2 —    inputs are other than quoted prices included in Level 1 that are observable for the asset or liability, either directly or indirectly.
Level 3 —    inputs are unobservable inputs that are supported by little or no market activities, which would require the Company to develop its own assumptions.
The fair value hierarchy also requires an entity to maximize the use of observable inputs and minimize the use of unobservable inputs when measuring fair value. The carrying amounts of certain financial instruments, such as cash equivalents, prepaid expenses and other current assets, accounts receivable, accounts payable and accrued liabilities, approximate fair value due to their short-term nature.
Based on the fair value hierarchy, the Company classifies its cash equivalents within Level 1. This is because the Company values its cash equivalents using quoted market prices. The Company’s Level 1 securities consisted of $522.8 million and $589.9 million in money market funds included in cash and cash equivalents at March 31, 2024, and December 31, 2023, respectively.
v3.24.1.u1
Composition of Certain Balance Sheet Items
 3 Months Ended
Mar. 31, 2024
Composition of Certain Balance Sheet Items [Abstract]  
Composition of Certain Balance Sheet Items Composition of Certain Balance Sheet Items
Prepaid Expenses and Other Current Assets
March 31,December 31,
20242023
Prepaid R&D expenses$14,034 $10,998 
Prepaid G&A expenses2,933 803 
Other1,037 2,140 
Prepaid and other current assets$18,004 $13,941 

Property and Equipment, net

Property and equipment, net consisted of the following (in thousands):
March 31,December 31,
20242023
Machinery and equipment$9,110 $9,019 
Purchased computer software2,192 2,232 
11,302 11,251 
Less: accumulated depreciation and amortization(7,630)(7,415)
Property and equipment, net$3,672 $3,836 

Depreciation expense was $0.2 million for the three months ended March 31, 2024, compared to $0.2 million for the three months ended March 31, 2023, respectively.
Other Current Liabilities
Other current liabilities consisted of the following (in thousands):
March 31,December 31,
20242023
Payroll and related expenses$6,847 $13,245 
Professional services323 288 
Other1,964 2,129 
Other current liabilities$9,134 $15,662 
v3.24.1.u1
Net Income (Loss) Per Ordinary Share
 3 Months Ended
Mar. 31, 2024
Earnings Per Share [Abstract]  
Net Income (Loss) Per Ordinary Share Net Income (Loss) Per Ordinary Share
Net income (loss) per ordinary share was determined as follows (in thousands, except per share amounts):
Three Months Ended 
March 31,
20242023
Numerator:
Net loss
$(72,239)$(46,864)
Denominator:
Weighted-average ordinary shares outstanding used in per share calculations - basic53,714 52,501 
Weighted-average ordinary shares outstanding used in per share calculations - diluted53,714 52,501 
Net income (loss) per share:
Basic net income (loss) per ordinary share
$(1.34)$(0.89)
Diluted net income (loss) per ordinary share
$(1.34)$(0.89)
Potentially issuable ordinary shares were not used in computing diluted net loss per ordinary share as their effect would be anti-dilutive due to the loss recorded during the three months ended March 31, 2024 and 2023, and therefore diluted net loss per share is equal to basic net loss per share.
The equivalent ordinary shares not included in diluted net income (loss) per share because their effect would be anti-dilutive are as follows (in thousands):
 Three Months Ended 
March 31,
20242023
Stock options to purchase ordinary shares11,751 10,471 
Restricted Stock Units (RSU)25 23 
Total11,776 10,494 
v3.24.1.u1
Commitment and Contingencies
 3 Months Ended
Mar. 31, 2024
Commitments and Contingencies Disclosure [Abstract]  
Commitment and Contingencies Commitments and Contingencies
Lease Commitments
As of March 31, 2024, the Company currently has three leases relating to its facilities in Brisbane, California, and Dublin, Ireland.

South San Francisco Facility
The Company had a noncancelable operating sublease (the “SSF Lease”) covering 128,751 square feet of office and laboratory space in South San Francisco, California, U.S. (the “SSF Facility”), which expired on December 31, 2023.

Total operating lease cost was nil and $1.6 million for the three months ended March 31, 2024 and 2023, respectively. Total cash paid against the operating lease liability was nil and $1.6 million for the three months ended March 31, 2024 and 2023, respectively. The Company obtained a standby letter of credit which could be drawn down by the sublandlord in the event the Company fails to fully and faithfully perform all of its obligations under the SSF Lease and to compensate the sublandlord for all losses and damages the sublandlord may suffer as a result of the occurrence of any default on the part of Company not cured within the applicable cure period. This standby letter of credit is collateralized by a certificate of deposit of the same amount which is classified as restricted cash. As of March 31, 2024, none of the remaining standby letter of credit amount of $1.4 million included in restricted cash, current was used. The remaining balance was released to the Company in May 2024.

Sub-Sublease of South San Francisco Facility

The Company had a Sub-Sublease Agreement (the “Sub-Sublease”) with Assembly Biosciences, Inc. covering approximately 46,641 square feet of office and laboratory space of the SSF Facility. The Sub-Sublease expired on December 15, 2023, in connection with the expiration of the SSF Lease. The Sub-Sublease was considered an operating lease under ASC 842. For the three months ended March 31, 2024 and 2023, the Company recorded nil and $0.7 million, respectively, of sub-lease rental income as an offset to its operating expenses.

Dublin
In June 2021, the Company entered into a lease agreement for office space in Dublin, Ireland, which commenced in August 2021 and had an initial term of one year. In April 2023, the Company renewed the lease for another one year term with a termination date of July 2024. In addition, the Company entered into a lease agreement for additional office space in Dublin, Ireland, which commenced in August 2023 and has an initial term of one year. Both of these leases have an automatic renewal clause, pursuant to which the agreement will be extended automatically for successive periods equal to the current term, unless the agreement is cancelled by the Company.

Brisbane Facility
On October 28, 2022, the Company entered into a noncancelable operating sublease (the "Brisbane Sublease") to sublease approximately 31,157 square feet of office and laboratory space located in Brisbane, California (the “Brisbane Facility”) with Arcus Biosciences, Inc., (the "Sublandlord"). The Brisbane Sublease became effective on October 28, 2022. The Brisbane Sublease provides that the Company's obligation to pay rent commenced on July 1, 2023, which is subject to abatement for the first six months following such date, with the exception of the seventh rent payment that was due upon execution of the Brisbane Sublease. The Company is obligated to make lease payments totaling approximately $14.9 million over the lease term,
which expires on September 30, 2028, unless terminated earlier. The Brisbane Sublease further provides that the Company is obligated to pay to the Sublandlord certain costs, including taxes and operating expenses. The Company has the option to extend the sublease by providing written notice at least nine months prior to the expiration of the sublease term. As of March 31, 2024, the Brisbane Sublease has a remaining lease term of 4.50 years.

The Brisbane Sublease is considered an operating lease and the accounting lease commencement date was on July 31, 2023 when the Company gained control over of the Brisbane Facility. The Company recorded a right-of-use asset of approximately $11.4 million and lease liability of approximately $3.6 million relating to the Brisbane Sublease on the lease commencement date. The discount rate used to determine the lease liability was 5.76%. The initial measurement of the right-of-use asset for the Brisbane Sublease includes the tenant improvement added by the Company wherein the lessor was deemed the accounting owner.

The Company was entitled to an improvement allowance of up to $9.3 million, to be used for costs incurred by the Company to construct certain improvements to the Brisbane Facility and to prepare for the Company's occupancy of the Brisbane Facility. As of March 31, 2024, all of the $9.3 million improvement allowance has been received from the Sublandlord and the Company is obligated to fund construction costs incurred in excess of the improvement allowance.

Total operating lease cost for the Brisbane Sublease was $0.8 million and nil for the three months ended March 31, 2024. Total cash paid against the operating lease liability was $0.5 million for the three months ended March 31, 2024.
In conjunction with the Brisbane Sublease, the Company obtained a standby letter of credit in the initial amount of $0.9 million, which may be drawn down by the Sublandlord in the event the Company fails to fully and faithfully perform all of its obligations under the Brisbane Sublease and to compensate the Sublandlord for all losses and damages the Sublandlord may suffer as a result of the occurrence of any default on the part of the Company not cured within the applicable cure period. As of March 31, 2024, none of the standby letter of credit amount of $0.9 million has been used.

Future minimum payments under the above-described noncancelable operating leases, including a reconciliation to the lease liabilities recognized in the Condensed Consolidated Balance Sheets as of March 31, 2024, are as follows (in thousands):

Year Ended December 31,Operating Leases
2024 (9 months)
2,295 
20253,051 
20263,158 
20273,269 
20282,523 
Thereafter— 
Total $14,296 
Less: Present value adjustment(1,800)
Lease liability$12,496 

Indemnity Obligations
The Company has entered into indemnification agreements with its current and former directors and officers and certain key employees. These agreements contain provisions that may require the Company, among other things, to indemnify such persons against certain liabilities that may arise because of their status or service and advance their expenses incurred as a result of any indemnifiable proceedings brought against them. The obligations of the Company pursuant to the indemnification agreements continue during such time as the indemnified person serves the Company and continues thereafter until such time as a claim can be brought. The maximum potential amount of future payments the Company could be required to make under these indemnification agreements is unlimited; however, the Company has a director and officer liability insurance policy that limits its exposure and enables the Company to recover a portion of any future amounts paid. As a result of its insurance policy coverage, the Company believes the estimated fair value of these indemnification agreements is minimal. Accordingly, the Company had no liabilities recorded for these agreements as of March 31, 2024, and 2023.
Other Commitments
In the normal course of business, the Company enters into various firm purchase commitments primarily related to research and development activities. As of March 31, 2024, the Company had non-cancelable purchase commitments to
suppliers for $11.4 million of which $6.7 million is included in current liabilities, and contractual obligations under license agreements of $0.3 million of which nil is included in current liabilities. The following is a summary of the Company's non-cancelable purchase commitments and contractual obligations as of March 31, 2024 (in thousands):

Total20242025202620272028Thereafter
Purchase Obligations (1)
$11,383 $11,194 $147 $42 $— $— $— 
Contractual obligations under license agreements338 64 64 60 60 45 45 
Total$11,721 $11,258 $211 $102 $60 $45 $45 
________________
(1) Purchase obligations consist of non-cancelable purchase commitments to suppliers and contract research organizations.
v3.24.1.u1
Significant Agreements
 3 Months Ended
Mar. 31, 2024
Collaborative Agreement [Abstract]  
Significant Agreements Significant Agreements
Roche License Agreement
In December 2013, the Company through its wholly owned subsidiary Prothena Biosciences Limited and Prothena Biosciences Inc entered into a License, Development, and Commercialization Agreement (the “License Agreement”) with F. Hoffmann-La Roche Ltd. and Hoffmann-La Roche Inc. (together, “Roche”) to develop and commercialize certain antibodies that target α-synuclein, including prasinezumab, which are referred to collectively as “Licensed Products.” Upon the effectiveness of the License Agreement in January 2014, the Company granted to Roche an exclusive, worldwide license to develop, make, have made, use, sell, offer to sell, import and export the Licensed Products. The Company retained certain rights to conduct development of the Licensed Products and an option to co-promote prasinezumab in the U.S. During the term of the License Agreement, the Company and Roche will work exclusively with each other to research and develop antibody products targeting alpha-synuclein (or α-synuclein) potentially including incorporation of Roche’s proprietary Brain Shuttle™ technology to potentially increase delivery of therapeutic antibodies to the brain. The License Agreement provided for Roche making an upfront payment to the Company of $30.0 million, which was received in February 2014; making a clinical milestone payment of $15.0 million upon initiation of the Phase 1 clinical trial for prasinezumab, which was received in May 2014; making a clinical milestone payment of $30.0 million upon dosing of the first patient in the Phase 2 clinical trial for prasinezumab, which was achieved in June 2017; and making a clinical milestone payment of $60.0 million upon dosing of the first patient in the global Phase 2b PADOVA study for prasinezumab, which was achieved in May 2021.
For prasinezumab, Roche is obligated to pay:
•up to $290.0 million upon the achievement of development, regulatory, and various first commercial sales milestones;
•up to $155.0 million upon achievement of U.S. commercial sales milestones;
•up to $175.0 million upon achievement of ex-U.S. commercial sales milestones; and
•tiered, high single-digit to high double-digit royalties in the teens based on U.S. and ex-U.S. annual net sales, subject to certain adjustments, with respect to the applicable Licensed Product.
Roche bore 100% of the cost of conducting the research collaboration under the License Agreement during the research term, which expired December 31, 2017. In May 2021, the Company exercised its rights under the terms of License Agreement to receive potential U.S. commercial sales milestone and royalties, in lieu of a U.S. profit and loss share for prasinezumab in Parkinson’s disease. Thus, in the U.S., through May 28, 2021, the parties shared all development costs, all of which were allocated 70% to Roche and 30% to the Company, for prasinezumab in the Parkinson’s disease indication. If the Company opts in to participate in co-development and co-funding for any other Licensed Products and/or indications, the parties will share all development and commercialization costs, as well as profits, all of which will be allocated 70% to Roche and 30% to the Company.
The Company initiated a Phase 1 clinical trial for prasinezumab in 2014. Following the Phase 1 clinical trial, Roche became primarily responsible for developing, obtaining and maintaining regulatory approval for and commercializing Licensed Products. Roche also became responsible for the clinical and commercial manufacture and supply of Licensed Products.
In addition, the Company has an option under the License Agreement to co-promote prasinezumab in the U.S. in the Parkinson’s disease indication. If the Company exercises such option, it may also elect to co-promote additional Licensed
Products in the U.S. approved for Parkinson’s disease. Outside the U.S., Roche will have responsibility for developing and commercializing the Licensed Products. Roche bears all costs that are specifically related to obtaining or maintaining regulatory approval outside the U.S. and will pay the Company a variable royalty based on annual net sales of the Licensed Products outside the U.S.
The License Agreement continues on a country-by-country basis until the expiration of all payment obligations under the License Agreement. The License Agreement may also be terminated (i) by Roche at will after the first anniversary of the effective date of the License Agreement, either in its entirety or on a Licensed Product-by-Licensed Product basis, upon 90 days’ prior written notice to the Company prior to first commercial sale and 180 days’ prior written notice to Prothena after first commercial sale, (ii) by either party, either in its entirety or on a Licensed Product-by-Licensed Product or region-by-region basis, upon written notice in connection with a material breach uncured 90 days after initial written notice, and (iii) by either party, in its entirety, upon insolvency of the other party. The License Agreement may be terminated by either party on a patent-by-patent and country-by-country basis if the other party challenges a given patent in a given country. The Company’s rights to co-develop Licensed Products under the License Agreement will terminate if the Company commences certain studies for certain types of competitive products. The Company’s rights to co-promote Licensed Products under the License Agreement will terminate if the Company commences a Phase 3 study for such competitive products.
The License Agreement cannot be assigned by either party without the prior written consent of the other party, except to an affiliate of such party or in the event of a merger or acquisition of such party, subject to certain conditions. The License Agreement also includes customary provisions regarding, among other things, confidentiality, intellectual property ownership, patent prosecution, enforcement and defense, representations and warranties, indemnification, insurance, and arbitration and dispute resolution.

Performance Obligations

As of March 31, 2024, and December 31, 2023, there were no remaining performance obligations under License Agreement since the obligations related to research and development activities were only for the Phase 1 clinical trial and the remaining obligations were delivered or performed.

Milestone Accounting

Under the License Agreement, the Company is eligible to receive certain milestone payments upon the achievement of development, regulatory and various first commercial sales milestones. Milestone payments are evaluated under ASC Topic 606. Factors considered in this determination included scientific and regulatory risk that must be overcome to achieve each milestone, the level of effort and investment required to achieve the milestone, and the monetary value attributed to the milestone. Accordingly, the Company estimates payments in the transaction price based on the most likely approach, which considers the single most likely amount in a range of possible amounts related to the achievement of these milestones. Additionally, milestone payments are included in the transaction price only when the Company can conclude it is probable that a significant revenue reversal will not occur in future periods when the milestone is achieved.

The Company excludes the milestone payments and royalties in the initial transaction price calculation because such payments are considered to be variable considerations with constraint. Such milestone payments and royalties will be recognized as revenue once the Company can conclude it is probable that a significant revenue reversal will not occur in future periods.
The clinical and regulatory milestones under the License Agreement after the point at which the Company could opt out are considered to be variable considerations with constraint due to the fact that active participation in the development activities that generate the milestones is not required under the License Agreement, and the Company can opt out of these activities. There are no refunds or claw-back provisions and the milestones are uncertain of occurrence even after the Company has opted out. Based on this determination, these milestones will be recognized when the Company can conclude it is probable that a significant revenue reversal will not occur in future periods.
Collaboration Agreement with Bristol Myers Squibb
Overview

On March 20, 2018, the Company, through its wholly owned subsidiary Prothena Biosciences Limited (“PBL”), entered into a Master Collaboration Agreement (the “Collaboration Agreement”) with Celgene Switzerland LLC (“Celgene”), a subsidiary of Celgene Corporation (which was acquired by Bristol Myers Squibb (“BMS”) in November 2019), pursuant to which Prothena granted to Celgene a right to elect in its sole discretion to exclusively license rights both in the U.S. (the “US
Rights”) and on a global basis (the “Global Rights”), with respect to the Company’s programs to develop and commercialize antibodies targeting tau, TDP-43 and an undisclosed target (the “Collaboration Targets”). For each such program, BMS may exercise its US Rights at the IND filing, and if it so exercises such US Rights would also have a right to expand the license to Global Rights. If BMS exercises its US Rights for a program, then following the first to occur of (a) completion by the Company, in its discretion and at its cost, of Phase 1 clinical trials for such program or (b) the date on which BMS elects to assume responsibility for completing such Phase 1 clinical trials (at its cost), BMS would have decision making authority over development activities and all regulatory, manufacturing and commercialization activities in the U.S.
As discussed below, BMS exercised its US Rights for the tau/BMS-986446 (formerly PRX005) Collaboration Target and on July 30, 2021, PBL entered into a U.S. License Agreement granting BMS the exclusive license to develop, manufacture and commercialize antibody products in the United States targeting tau (the “Tau US License Agreement”). Subsequently, BMS exercised its Global Rights for the tau/BMS-986446 Collaboration Target and on July 5, 2023, PBL entered into a Global License Agreement granting BMS the exclusive license to develop, manufacture and commercialize tau Collaboration Products globally for any and all uses or purposes with respect to any human or animal disease, disorder or condition (the “Tau Global License Agreement”). The Tau Global License Agreement supersedes and replaces the Tau US License Agreement in its entirety.
The Collaboration Agreement provided for Celgene making an upfront payment to the Company of $100.0 million which was received in April 2018, plus future potential license exercise payments and regulatory and commercial milestones for each program under the Collaboration Agreement, as well as royalties on net sales of any resulting marketed products. In connection with the Collaboration Agreement, the Company and Celgene entered into a Share Subscription Agreement on March 20, 2018, under which Celgene subscribed to 1,174,536 of the Company’s ordinary shares for a price of $42.57 per share, for a total of approximately $50.0 million.
BMS US and Global Rights and Licenses

On a program-by-program basis, beginning on the effective date of the Collaboration Agreement and ending on the date that the IND Option term expires for such program (which generally occurs sixty days after the date on which the Company delivers to BMS the first complete data package for an IND that was filed for a lead candidate from the relevant program), BMS may elect in its sole discretion to exercise its US Rights to receive an exclusive license to develop, manufacture and commercialize antibodies targeting the applicable Collaboration Target in the U.S. (the “US License”). If BMS exercises its US Rights for a collaboration program, it is obligated to pay the Company an exercise fee of approximately $80.0 million per program. Thereafter, following the first to occur of (a) completion by the Company, in its discretion and at its cost, of Phase 1 clinical trials for such program or (b) BMS’ election to assume responsibility to complete such Phase 1 clinical trials (at its cost), BMS would have the sole right to develop, manufacture and commercialize antibody products targeting the relevant Collaboration Target for such program (the “Collaboration Products”) in the U.S.

On a program-by-program basis, following completion of a Phase 1 clinical trial for a collaboration program for which BMS has previously exercised its US Rights, BMS may elect in its sole discretion to exercise its Global Rights with respect to such collaboration program to receive a worldwide, exclusive license to develop, manufacture and commercialize antibodies targeting the applicable Collaboration Target (the “Global License”). If BMS exercises its Global Rights, BMS would be obligated to pay the Company an additional exercise fee of $55.0 million for such collaboration program. The Global Rights would then replace the US Rights for that collaboration program, and BMS would have decision making authority over developing, obtaining and maintaining regulatory approval for, manufacturing and commercializing the Collaboration Products worldwide.
After BMS’ exercise of Global Rights for a collaboration program, the Company is eligible to receive up to $562.5 million in regulatory and commercial milestones per program. Following an exercise by BMS of either US Rights or Global Rights for such collaboration program, the Company will also be eligible to receive tiered royalties on net sales of Collaboration Products ranging from high single digit to high teen percentages, on a weighted average basis depending on the achievement of certain net sales thresholds. Such exercise fees, milestones and royalty payments are subject to certain reductions as specified in the Collaboration Agreement, the agreement for US Rights and the agreement for Global Rights.

BMS will continue to pay royalties on a Collaboration Product-by-Collaboration Product and country-by-country basis, until the latest of (i) expiration of certain patents covering the Collaboration Product, (ii) expiration of all regulatory exclusivity for the Collaboration Product, and (iii) an agreed period of time after the first commercial sale of the Collaboration Product in the applicable country (the “Royalty Term”).
Term and Termination

The research term under the Collaboration Agreement continues to May 24, 2024, which BMS may extend for up to two additional 12-month periods by paying an extension fee of $10.0 million per extension period. The term of the Collaboration Agreement continues until the last to occur of the following: (i) expiration of the research term; (ii) expiration of all US Rights terms; and (iii) expiration of all Global Rights terms.

The term of any US License or Global License would continue on a Licensed Product-by-Licensed Product and country-by-country basis until the expiration of all Royalty Terms under such agreement.

The Collaboration Agreement may be terminated (i) by either party on a program-by-program basis if the other party remains in material breach of the Collaboration Agreement following a cure period to remedy the material breach, (ii) by BMS at will on a program-by-program basis or in its entirety, (iii) by either party, in its entirety, upon insolvency of the other party, or (iv) by the Company, in its entirety, if BMS challenges a patent licensed by the Company to BMS under the Collaboration Agreement.

Performance Obligations

The Company assessed the Collaboration Agreement and concluded that it represented a contract with a customer within the scope of ASC 606. Per ASC 606, a performance obligation is defined as a promise to transfer a good or service or a series of distinct goods or services. At inception of the Collaboration Agreement, the Company is not obligated to transfer any US License or Global License to BMS unless BMS exercises its US Rights or Global Rights, respectively, and the Company is not obligated to perform development activities under the development plan during preclinical and Phase 1 clinical trials including the regulatory filing of the IND.
The discovery, preclinical and clinical development activities performed by the Company are to be performed at the Company’s discretion and are not promised goods or services and therefore are not considered performance obligations under ASC 606, unless and until the Company agrees to perform the Phase 1 clinical trials (after the IND option exercise) that are determined to be performance obligations at the time the option is exercised. Per the terms of the Collaboration Agreement, the Company may conduct discovery activities to characterize, identify and generate antibodies to become collaboration candidates that target such Collaboration Target, and thereafter may pre-clinically develop collaboration candidates to identify lead candidates that target such Collaboration Target and file an IND with the U.S. Food and Drug Administration (the “FDA”) for a Phase 1 clinical trial for such lead candidates. In the event the Company agrees to be involved in a Phase 1 clinical trial, the Company will further evaluate whether any such promise represents a performance obligation at the time the option is exercised. If it is concluded that the Company has obligated itself to an additional performance obligation besides the license granted at IND option exercise, then the effects of the changes in the arrangement will be evaluated under the modification guidance of ASC 606.

The Company is not obligated to perform manufacturing activities. Per the terms of the Collaboration Agreement, to the extent that the Company, at its discretion, conducts a program, the Company shall be responsible for the manufacture of collaboration candidates and collaboration products for use in such program, as well as the associated costs. Delivery of manufactured compound (clinical product supply) is not deemed a performance obligation under ASC 606 as the Company is not obligated to transfer supply of collaboration product to BMS unless BMS exercises its right to participate in the Phase 1 development.

Compensation for the Company’s provision of inventory supply, to the extent requested by BMS would be paid to the Company by BMS at a reasonable stand-alone selling price for such supply. Given that (i) there is substantial uncertainty about the development of the programs, (ii) the pricing for the inventory is at its standalone selling price and (iii) the manufacturing services require the entity to transfer additional goods or services that are incremental to the goods and services provided prior to the resolution of the contingency, the Company’s supply of product is not a material right. Therefore, the inventory supply is not considered a performance obligation unless and until, requested by BMS.

In addition to the grant of the US License after BMS exercises its US Rights for a program, BMS is entitled to receive certain ancillary development services from the Company, such as technology transfer assistance, regulatory support, safety data reporting activities and transition supply, if requested by BMS.

In addition to the grant of the Global License after BMS exercises the Global Rights for a program, BMS is entitled to receive certain ancillary development services from the Company, such as ongoing clinical trial support upon request by BMS, transition supply, if requested by BMS, and regulatory support for coordination of pharmacovigilance matters.
The Company evaluated the potential obligations to transfer the US Licenses and Global Licenses and performance of the ancillary development services subsequent to exercise of the US Rights and Global Rights, if the options are exercised by BMS, under ASC 606-10-55-42 and 55-43 to determine whether the US Rights or the Global Rights provided BMS a “material right” and concluded that BMS’ options to exercise its US Rights and Global Rights represented “material rights” to BMS that it would not have received without entering into the Agreement.

At inception of the Collaboration Agreement, there were a total of six options, including US Rights and Global Rights to acquire a US License and a Global License, respectively, and rights to request certain development services (following exercise of the US Rights and Global Rights, respectively) for each of the three programs, with four such options remaining as of March 31, 2024. The deferred revenue balance as of March 31, 2024 of $67.4 million is related to the outstanding US Rights and Global Rights. Per ASC 606, the US Rights and Global Rights are material rights and therefore are performance obligations. The goods and services underlying the options are not accounted for as separate performance obligations, but rather become performance obligations, if and when, an option is exercised.

US License Agreement for the Tau/BMS-986446 Collaboration Target

On July 30, 2021, the Company entered into the Tau US License Agreement. The Tau US License Agreement included an upfront payment of $80.0 million.
The Tau US License Agreement included the following distinct performance obligations: (1) the delivery of the US License for tau/BMS-986446 Collaboration Target (“Tau US License Obligation”); and (2) the Company’s obligation to provide development activities under the development plan during any Phase 1 clinical trials (the “Tau US Development Services Obligation”). Revenue allocated to the Tau US License Obligation is recognized when the Company has satisfied its obligation at a point in time, while the revenue allocated to the Tau US Development Services Obligation are recognized over time using an input-based model.

Global License Agreement for the Tau/BMS-986446 Collaboration Target

On July 5, 2023, the Company entered into the Tau Global License Agreement, which as discussed above supersedes and replaces the Tau US License Agreement in its entirety. The Company received the associated option exercise fee of $55.0 million in August 2023 and it will be eligible to receive regulatory and sales milestones up to $562.5 million upon achievement of certain developmental events, including regulatory approval of a tau Collaboration Product, and on BMS achieving certain annual net sales thresholds in the United States and worldwide. The Company also will be eligible to receive tiered royalties on net sales of tau Collaboration Products, ranging from high single digit to high teen percentages, on a weighted average basis depending on the achievement of certain net sales thresholds.

The Company’s distinct performance obligation under the Tau Global License Agreement was limited to the delivery of the Global License for tau/BMS-986446 Collaboration Target (“Tau Global License Obligation”). Revenue allocated to the Tau Global License Obligation is recognized when the Company has satisfied its obligation at a point in time.

Transaction Price

At inception of the Collaboration Agreement, the Company did not transfer any goods or services to BMS that are material. Accordingly, the Company has concluded that the initial transaction price will be recognized as a contract liability and will be deferred until the Company transfers control of goods or services to BMS (which would be when BMS exercises the US Right or Global Right and receives control of the US License or Global License for at least one of the programs), or when the IND Option term expires if BMS does not exercise the US Right (which is generally sixty days after the date on which the Company delivers to BMS the first complete data package for an IND that was filed for a lead candidate from the relevant program), or when the Phase 1 Option term expires if BMS does not exercise the Global Right (which is generally ninety days after the date on which the Company delivers to BMS the first complete data package for a Phase 1 clinical trial for a lead candidate from the relevant program) or at the termination of the Collaboration Agreement, whichever occurs first. At such point that the Company transfers control of goods or services to BMS, or when the option expires, the Company will recognize revenue as a continuation of the original contract. Under this approach, the Company will treat the consideration allocated to the material right as an addition to the consideration for the goods or services underlying the contract option.

At inception of the Collaboration Agreement, the Company estimated the standalone selling price for each performance obligation (i.e., the US Rights and Global Rights by program). The estimate of standalone selling price for the US Rights and Global Rights by program was based on the adjusted market assessment approach using a discounted cash flow model. The key assumptions used in the discounted cash flow model included the market opportunity for commercialization of each program in
the U.S. or globally depending on the license, the probability of successfully developing and commercializing a given program target, the estimated remaining development costs for the respective program, the estimated time to commercialization of the drug for that program and a discount rate.

The initial transaction price under the Collaboration Agreement, pursuant to ASC 606, was $110.2 million, including the $100.0 million upfront payment and $10.2 million premium on the ordinary shares purchased under the SSA. The Company allocated the initial transaction price across the US Rights and Global Rights for each program in a range of approximately $15-$25 million and $10-$18 million, respectively.

The Company did not include the option fees in the initial transaction price because such fees are contingent on the options to the US Rights and the Global Rights being exercised. Upon the exercise of the US Rights and the Global Rights for a program, the Company will have the obligation to deliver the US License and Global License and provide certain ancillary development services if requested by BMS, subsequent to its exercise of the US Rights and Global Rights, respectively, for such program. The Company will include the option fees in the transaction price at the point in time a material right is exercised and the Company transfers control of the goods and services to BMS. In addition, the Company did not include in the initial transaction price certain clinical and regulatory milestone payments since they relate to licenses for which BMS has not yet exercised its option to obtain and these variable considerations are constrained due to the likelihood of a significant revenue reversal.
Upon entering into the Tau US License Agreement, the Company granted BMS a US License for the tau/BMS-986446 Collaboration Target, which transferred control of such underlying US License to BMS. Following execution of the Tau US License Agreement, BMS paid the Company a $80.0 million option exercise fee. Under the continuation of the original contract method, the Company computed the relative sales price after the Company transferred control of the US License for tau/BMS-986446. The Company used the original allocated consideration for the US Right for tau/BMS-986446 of $24.9 million (computed at the inception of the contract) plus the $80.0 million option exercise fee to arrive at the total transaction price of approximately $104.9 million. This total transaction price was further allocated using the relative sales price method between the Tau US License Obligation and the Tau US Development Services Obligation.

The best estimate of selling price for the US License for tau/BMS-986446 was based on a discounted cash flow model. The key assumptions used in the discounted cash flow model used to determine the best estimate of selling price for the license included the market opportunity for commercialization of tau/BMS-986446, the probability of successfully developing/commercializing BMS-986446, the remaining development costs for tau/BMS-986446, and the estimated time to commercialization of tau/BMS-986446. Based on the relative selling price method, the amount that the Company allocated to the performance obligations is as follows: $77.5 million to the license to be recognized concurrent with the delivery of the license; and $27.5 million as development services to be recognized based on percentage of completion over the service period.

Upon entering into the Tau Global License Agreement, the Company granted BMS a Global License for the tau/BMS-986446 Collaboration Target, which transferred control of such underlying Global License to BMS. Following execution of the Tau Global License Agreement, BMS paid the Company a $55.0 million option exercise fee. Under the continuation of the original contract method, the Company computed the relative sales price after the Company transferred control of the Global License for tau/BMS-986446. The Company used the original allocated consideration for the Global Right for tau/BMS-986446 of $17.9 million (computed at the inception of the contract) plus the $55.0 million option exercise fee to arrive at the total transaction price of approximately $72.9 million. Given that the Company’s distinct performance obligation under the Tau Global License Agreement was limited to the Tau Global License Obligation no further allocation was required.

Significant Payment Terms

The upfront payment of $100.0 million was received in April 2018, while all option fees and milestone payments are due within 30 days after the achievement of the relevant milestone by BMS or receipt by BMS of an invoice for such an amount from the Company.

The Collaboration Agreement does not have a significant financing component since a substantial amount of consideration promised by BMS to the Company is variable and the amount of such variable consideration varies based upon the occurrence or non-occurrence of future events that are not within the control of either BMS or the Company. Variable considerations related to clinical and regulatory milestone payments and option fees are constrained due to the likelihood of a significant revenue reversal.
Revenue and Expense Recognition

For the three months ended March 31, 2024 and 2023, collaboration revenue from BMS was nil and $2.1 million. As of March 31, 2024, the aggregate amount of the transaction price allocated to the performance obligations that are unsatisfied was nil. The Company had nil and $5.2 million accounts receivable from BMS at March 31, 2024, and December 31, 2023, respectively.
Deferred Revenue
The deferred revenue balance at the beginning of the quarter ended March 31, 2024 was $67.4 million. As of March 31, 2024, the deferred revenue balance related to outstanding US Rights and Global Rights remained at $67.4 million, which was long term deferred revenue. The Company concluded that the deferred revenue should be classified as long term because BMS holds an option to extend the term of the Collaboration Agreement, and therefore the Company’s performance obligations were solely at the option of BMS. Until such time that the Company has determined that BMS will not exercise its option to extend the term, the Company will continue to classify the balance as long term deferred revenue.

Milestone and Royalties Accounting

The Company is eligible to receive milestone payments of up to $90.0 million per program upon the achievement of certain specified regulatory milestones and milestone payments of up to $375.0 million per program upon the achievement of certain specified commercial sales milestones under the US License for such program. The Company is also eligible to receive milestone payments of up to $187.5 million per program upon the achievement of certain specified regulatory milestones and milestone payments of up $375.0 million per program upon the achievement of certain specified commercial sale milestones under the Global License for such program. Milestone payments are evaluated under ASC Topic 606. Factors considered in this determination included scientific and regulatory risk that must be overcome to achieve each milestone, the level of effort and investment required to achieve the milestone, and the monetary value attributed to the milestone. Accordingly, the Company estimates payments in the transaction price based on the most likely approach, which considers the single most likely amount in a range of possible amounts related to the achievement of these milestones. Additionally, milestone payments are included in the transaction price only when the Company can conclude it is probable that a significant revenue reversal will not occur in future periods.
The Company excluded the milestone payments and royalties in the initial transaction price because such payments are considered to be variable considerations with constraint. Such milestone payments and royalties will be recognized as revenue at a point in time when the Company can conclude it is probable that a significant revenue reversal will not occur in future periods.

The Company did not achieve any clinical and regulatory milestones under the Collaboration Agreement during the three months ended March 31, 2024 and 2023.
Novo Nordisk Share Purchase Agreement
On July 8, 2021, the Company together with its wholly owned subsidiary, PBL, entered into a definitive share purchase agreement with Novo Nordisk A/S and Novo Nordisk Region Europe A/S (each an unrelated party). Under the terms of such agreement, Novo Nordisk acquired PBL’s wholly-owned subsidiary, Neotope Neuroscience Limited (“NNL”) and gained full worldwide rights to the intellectual property and related rights to the Company’s ATTR amyloidosis business and pipeline. Upon consummation of the transaction, NNL ceased to be a related party of PBL. The aggregate purchase price consisted of an upfront payment of $60.0 million in cash, subject to customary purchase price adjustments.
Should Novo Nordisk achieve certain stages of development or commercialization for products or product candidates containing NNC6019 (formerly PRX004) or a derivative thereof in ATTR amyloidosis, PBL is entitled to receive certain milestone payments based on specified development and commercial milestones. The development and commercialization milestone payments will be discounted if the milestone events are achieved with respect to other indications. Should Novo Nordisk achieve specified thresholds of worldwide, annual net sales of the milestone products, regardless of indication, PBL will also be entitled to receive specified one-time net sales milestone payments. All milestone payments attributable to an achieved milestone will be paid to PBL, subject to Novo Nordisk’s offset right for indemnity claims or unpaid amounts in respect of any purchase price adjustment.
The upfront payment of $60.0 million was accounted for as revenue in 2021. In addition to the upfront payment, Novo Nordisk agreed to pay for certain out of pocket expenses under the Transition Services Agreement, which netted to $0.7 million after closing adjustments related to the sale of the ATTR amyloidosis business and pipeline.
Contingent Consideration/Milestone Accounting
In December 2022, the Company received a $40.0 million development milestone payment related to the continued advancement of NNC6019 in a Phase 2 clinical trial for the treatment of ATTR cardiomyopathy. This amount was accounted for as revenue from license and intellectual property in 2022.
The Company is eligible to receive additional development and sales milestone payments from Novo Nordisk totaling up to $1.13 billion upon achievement of certain specified development and commercial sales milestones under the share purchase agreement.
The Company excluded the milestone payments in the initial transaction price because such payments are considered to be variable considerations with constraint. Such milestone payments will be recognized as revenue at a point in time when the Company can conclude it is probable that a significant revenue reversal will not occur in future periods.
Revenue Recognition
Total revenue recognized related to the transaction during the three months ended March 31, 2024 and 2023, was nil and nil, respectively. The Company had no accounts receivable from Novo Nordisk as of March 31, 2024 and December 31, 2023, respectively.
v3.24.1.u1
Shareholders' Equity
 3 Months Ended
Mar. 31, 2024
Equity [Abstract]  
Shareholders' Equity Shareholders' Equity
Ordinary Shares
As of March 31, 2024, the Company had 100,000,000 ordinary shares authorized for issuance with a par value of $0.01 per ordinary share and 53,720,455 ordinary shares issued and outstanding. Each ordinary share is entitled to one vote and, on a pro rata basis, to dividends when declared and the remaining assets of the Company in the event of a winding up.
Euro Deferred Shares
As of March 31, 2024, the Company had 10,000 Euro Deferred Shares authorized for issuance with a nominal value of €22 per share. No Euro Deferred Shares are outstanding at March 31, 2024. The rights and restrictions attaching to the Euro Deferred Shares rank pari passu with the ordinary shares and are treated as a single class in all respects.

December 2022 Offering

In December 2022, the Company completed an underwritten public offering of an aggregate of 3,250,000 of its ordinary shares at a public offering price of $56.50 per ordinary share. The Company received aggregate net proceeds of approximately $172.4 million, after deducting the underwriting discount and offering costs.

In January 2023, the Company issued an additional 395,096 ordinary shares resulting from the underwriters’ partial exercise of their 30-day option to purchase up to an additional 487,500 ordinary shares of as part of the December 2022 underwritten public offering. The Company received approximately $20.9 million proceeds from the exercise, net of underwriting discount but before deducting any offering costs.

At-the-Market Offerings
In December 2021, the Company entered into an Equity Distribution Agreement (the “December 2021 Distribution Agreement”), pursuant to which the Company could issue and sell, from time to time, the Company's ordinary shares. In connection with entering into the December 2021 Distribution Agreement, on December 23, 2021, the Company filed with the SEC a prospectus supplement relating to the offer, issuance and sale of up to $250.0 million of the Company’s ordinary shares (the “December 2021 Prospectus”) pursuant to the December 2021 Distribution Agreement. The December 2021 Prospectus was no longer effective as of March 23, 2024. As of March 23, 2024, the Company had sold and issued 953,589 ordinary shares pursuant to the December 2021 Distribution Agreement under the December 2021 Prospectus for total gross proceeds of approximately $56.3 million before deducting underwriting discounts, commissions, and other offering expenses payable by the Company of $1.8 million.
In February 2024, the Company amended the Equity Distribution Agreement that it entered into in December 2021 (the “Amended Distribution Agreement”), pursuant to which the Company may issue and sell, from time to time, the Company's ordinary shares. In connection with amending the Amended Distribution Agreement, on February 22, 2024, the Company filed with the SEC a prospectus relating to the offer, issuance, and sale of up to $250.0 million of the Company’s ordinary shares (the “February 2024 Prospectus”) pursuant to the Amended Distribution Agreement. For the three months ended March 31, 2024,
the Company sold and issued no ordinary shares, pursuant to the Amended Distribution Agreement under the February 2024 Prospectus.
The issuance and sale of the Company’s ordinary shares pursuant to the December 2021 Distribution Agreement and Amended the December 2021 Distribution Agreement is deemed an “at-the-market” offering and is registered under the Securities Act of 1933, as amended.
v3.24.1.u1
Share-Based Compensation
 3 Months Ended
Mar. 31, 2024
Share-Based Payment Arrangement [Abstract]  
Share-Based Compensation Share-Based Compensation
Equity Incentive Plans

The Company’s equity incentive plans, the 2018 Long Term Incentive Plan, as amended (the “2018 LTIP”), 2020 Employment Inducement Incentive Plan, as amended (the “2020 EIIP”), and previously, the Amended and Restated 2012 Long Term Incentive Plan (the “2012 LTIP”), reserve ordinary shares for the issuance of stock options, stock appreciation rights, restricted shares, RSUs, performance bonus awards, performance share units awards, dividend equivalents and other share or cash-based awards to eligible individuals. Options granted under each of the 2018 LTIP, 2020 EIIP, and 2012 LTIP expire no later than ten years from the date of grant.
In May 2023, the Company’s shareholders approved an amendment to the 2018 LTIP to increase the number of ordinary shares available for issuance under the 2018 LTIP by 2,000,000 ordinary shares. As of March 31, 2024, the number of ordinary shares authorized under the 2018 LTIP was 14,620,433. Upon adoption of the 2018 LTIP, no new awards are permitted under the 2012 LTIP.

As of March 31, 2024, the number of ordinary shares authorized under the 2020 EIIP was 1,485,000 and 66,250 ordinary shares remained available for future awards under the 2020 EIIP. The Company’s Board of Directors has adopted a series of amendments to increase the ordinary shares available for issuance under the 2020 EIIP and it reserves the right to both amend the 2020 EIIP to increase the number of ordinary shares available and make additional awards to key new hires.

The Company’s option awards generally vest over four years, while RSUs vest over two years. As of March 31, 2024, 1,662,669 ordinary shares remained available for grant under its equity plans.

Share-based Compensation Expense

Share-based compensation expense recorded in these Condensed Consolidated Financial Statements was based on awards granted under the 2012 LTIP, the 2018 LTIP, and the 2020 EIIP. The estimated forfeiture rate as of March 31, 2024 was 7%. Changes in our estimates and assumptions relating to forfeitures may cause us to realize material changes in stock-based compensation expense in the future.

The amount of unearned share-based compensation related to unvested stock options at March 31, 2024, is $115.2 million. The weighted-average period over which this unearned share-based compensation is expected to be recognized is 2.94 years.

The following table summarizes share-based compensation expense for the periods presented (in thousands):

Three Months Ended 
March 31,
20242023
Research and development$5,455 $4,362 
General and administrative6,928 4,428 
Total share-based compensation expense$12,383 $8,790 

The Company recognized tax benefits from share-based awards of $2.1 million and $1.6 million for the three months ended March 31, 2024 and 2023, respectively.
The fair value of the options granted to employees and non-employee directors during the three months ended March 31, 2024 and 2023 was estimated as of the grant date using the Black-Scholes option-pricing model using the key assumptions listed in the following table:
Three Months Ended 
March 31,
20242023
Expected term (in years)4.60
 -
5.514.53
 -
5.40
Expected volatility74.8 % -78.6%76.4 %-89.7%
Risk-free interest rate3.8 % -4.4%3.5 %-4.4%
Expected dividend yield—%—%
Weighted average grant date fair value$19.57$35.37

The fair value of employee stock options is amortized on a straight-line basis over the requisite service period for each award. Each of the inputs discussed above is subjective and generally requires significant management judgment to determine.

The following table summarizes the Company’s stock option activity during the three months ended March 31, 2024:
OptionsWeighted
Average
Exercise
Price		Weighted
Average
Remaining
Contractual
Term (years)		Aggregate
Intrinsic
Value
(in thousands)
Outstanding at December 31, 2023
9,866,337 $29.06 6.60$118,447 
Granted
1,998,950 30.02 
Exercised(38,338)23.24 
Forfeited(65,792)36.36 
Expired(10,375)28.50 
Outstanding at March 31, 2024
11,750,782 $29.20 6.92$42,936 
Vested and expected to vest at March 31, 2024
11,258,566 $28.84 6.82$42,907 
Vested at March 31, 2024
6,909,977 $22.39 5.48$41,926 
The total intrinsic value of options exercised was $0.4 million, and $6.8 million during the three months ended March 31, 2024 and 2023, determined as of the date of exercise.
The following table summarizes the activity and related information for RSUs during the three months ended March 31, 2024:
Number of UnitsWeighted Average
Grant-Date
Fair Value		Weighted
Average
Remaining
Contractual
Term (years)		Aggregate
Intrinsic
Value
(in thousands)
Unvested at December 31, 2023
25,250 $58.01 1.09$918 
Units Granted
— — 
Units Vested— — 
Units Forfeited— — 
Unvested at March 31, 2024
25,250 $58.01 0.84$625 
Unvested and expected to vest at March 31, 2024
23,760 $58.16 0.83$589 
The fair value of RSUs was determined on the date of grant based on the market price of the Company’s ordinary shares as of that date. The fair value of the RSUs is recognized as an expense on a straight-line basis over the vesting period of each RSU. Upon the vesting of the RSUs, a portion of the shares vested are sold by the employee to satisfy employee withholding tax requirements (sell-to-cover). As of March 31, 2024, total compensation cost not yet recognized related to unvested RSUs was $0.8 million, which is expected to be recognized over a weighted-average period of 0.92 years. RSUs settle into ordinary shares upon vesting.
v3.24.1.u1
Income Taxes
 3 Months Ended
Mar. 31, 2024
Income Tax Disclosure [Abstract]  
Income Taxes Income Taxes
The major taxing jurisdictions for the Company are Ireland and the U.S. The Company recorded an income tax benefit of $2.2 million and $2.9 million for the three months ended March 31, 2024 and 2023, respectively. The provision for income
taxes differs from the statutory tax rate of 12.5% applicable to Ireland primarily due to Irish net operating losses for which a tax provision benefit is not recognized, U.S. income taxed at different rates, adjustments to deferred tax assets for the deductibility of stock compensation and capitalization of research and development costs.
The Company has generally computed its interim period provision for (benefit from) income taxes by applying its forecasted effective tax rate to year-to-date earnings. However, due to a significant amount of U.S. permanent differences relative to the amount of U.S. forecasted income used in computing the effective tax rate, the effective tax rate is highly sensitive to minor fluctuations in U.S. forecasted income. As such, the Company has computed the U.S. component of the consolidated provision for (benefit from) income taxes for the three months ended March 31, 2024 using an actual year-to-date tax calculation.
The non-U.S. tax expense continues to be zero due to cumulative historic and year-to-date losses and a full valuation allowance on our deferred tax assets in our non-U.S. jurisdictions.
Deferred income taxes reflect the net tax effect of temporary differences between the carrying amount of assets and liabilities for financial reporting purposes and the amounts used for income tax purposes. The Company's deferred tax assets (“DTA”) are composed primarily of its Irish subsidiaries' net operating loss carryforwards, California net operating loss carryforwards available to reduce future taxable income of the Company's U.S. subsidiaries, federal and California tax credit carryforwards, share-based compensation, capitalized R&D, and other temporary differences. The Company maintains a valuation allowance against certain U.S. federal and state and Irish deferred tax assets. Each reporting period, the Company evaluates the need for a valuation allowance on its deferred tax assets by jurisdiction.
No provision for income tax in Ireland has been recognized on undistributed earnings of the Company’s U.S. subsidiaries as the Company considers the U.S. earnings to be indefinitely reinvested.
v3.24.1.u1
Pay vs Performance Disclosure - USD ($)
$ in Thousands
 3 Months Ended
Mar. 31, 2024
Mar. 31, 2023
Pay vs Performance Disclosure    
Net income (loss) $ (72,239) $ (46,864)
v3.24.1.u1
Insider Trading Arrangements
 3 Months Ended
Mar. 31, 2024
shares
Trading Arrangements, by Individual  
Non-Rule 10b5-1 Arrangement Adopted false
Non-Rule 10b5-1 Arrangement Terminated false
Carol D. Karp [Member]  
Trading Arrangements, by Individual  
Material Terms of Trading Arrangement
On February 26, 2024, Carol D. Karp, Chief Regulatory Officer, adopted a Rule 10b5-1 trading arrangement that was intended to satisfy the affirmative defense of Rule 10b5-1(c) for the sale of up to 105,000 shares of the Company’s ordinary shares until June 3, 2025. However, this plan was terminated on March 29, 2024. On March 29, 2024, Ms. Karp adopted a Rule 10b5-1 trading arrangement that is intended to satisfy the affirmative defense of Rule 10b5-1(c) for the sale of up to 105,000 shares of the Company’s ordinary shares until June 3, 2025.
Tran B. Nguyen [Member]  
Trading Arrangements, by Individual  
Material Terms of Trading Arrangement
On February 26, 2024, Tran B. Nguyen, Chief Strategy Officer and Chief Financial Officer, adopted a Rule 10b5-1 trading arrangement that is intended to satisfy the affirmative defense of Rule 10b5-1(c) for the sale of up to 510,150 shares of the Company’s ordinary shares until May 15, 2025.
Name Tran B. Nguyen
Title Chief Strategy Officer and Chief Financial Officer
Rule 10b5-1 Arrangement Adopted true
Adoption Date February 26, 2024
Arrangement Duration 444 days
Aggregate Available 510,150
Gene G. Kinney [Member]  
Trading Arrangements, by Individual  
Material Terms of Trading Arrangement
On March 13, 2024, Gene G. Kinney, President and Chief Executive Officer, adopted a Rule 10b5-1 trading arrangement that is intended to satisfy the affirmative defense of Rule 10b5-1(c) for the sale of up to 141,599 shares of the Company’s ordinary shares until June 15, 2025.
Name Gene G. Kinney
Title President and Chief Executive Officer
Rule 10b5-1 Arrangement Adopted true
Adoption Date March 13, 2024
Arrangement Duration 459 days
Aggregate Available 141,599
Richard T. Collier [Member]  
Trading Arrangements, by Individual  
Material Terms of Trading Arrangement
On March 21, 2024, Richard T. Collier, director, adopted a Rule 10b5-1 trading arrangement that is intended to satisfy the affirmative defense of Rule 10b5-1(c) for the sale of up to 18,229 shares of the Company’s ordinary shares until May 22, 2025.
Name Richard T. Collier
Title director
Rule 10b5-1 Arrangement Adopted true
Adoption Date March 21, 2024
Arrangement Duration 427 days
Aggregate Available 18,229
Shane M. Cooke [Member]  
Trading Arrangements, by Individual  
Material Terms of Trading Arrangement
On March 21, 2024, Shane M. Cooke, director, adopted a Rule 10b5-1 trading arrangement that is intended to satisfy the affirmative defense of Rule 10b5-1(c) for the sale of up to 18,229 shares of the Company’s ordinary shares until May 22, 2025.
Name Shane M. Cooke
Title director
Rule 10b5-1 Arrangement Adopted true
Adoption Date March 21, 2024
Arrangement Duration 427 days
Aggregate Available 18,229
Hideki Garren [Member]  
Trading Arrangements, by Individual  
Material Terms of Trading Arrangement
On March 21, 2024, Hideki Garren, Chief Medical Officer, adopted a Rule 10b5-1 trading arrangement that is intended to satisfy the affirmative defense of Rule 10b5-1(c) for the sale of up to 90,000 shares of the Company’s ordinary shares until June 30, 2025.
Name Hideki Garren
Title Chief Medical Officer
Rule 10b5-1 Arrangement Adopted true
Adoption Date March 21, 2024
Arrangement Duration 466 days
Aggregate Available 90,000
Lars G. Ekman [Member]  
Trading Arrangements, by Individual  
Material Terms of Trading Arrangement
On March 26, 2024, Lars G. Ekman, director, adopted a Rule 10b5-1 trading arrangement that is intended to satisfy the affirmative defense of Rule 10b5-1(c) for the sale of up to 18,229 shares of the Company’s ordinary shares until May 22, 2025.
Name Lars G. Ekman
Title director
Rule 10b5-1 Arrangement Adopted true
Adoption Date March 26, 2024
Arrangement Duration 422 days
Aggregate Available 18,229
Carol D. Karp February 2024 Plan [Member] | Carol D. Karp [Member]  
Trading Arrangements, by Individual  
Name Carol D. Karp
Title Chief Regulatory Officer
Adoption Date February 26, 2024
Rule 10b5-1 Arrangement Terminated true
Termination Date March 29, 2024
Aggregate Available 105,000
Carol D. Karp March 2024 Plan [Member] | Carol D. Karp [Member]  
Trading Arrangements, by Individual  
Name Carol D. Karp
Title Chief Regulatory Officer
Rule 10b5-1 Arrangement Adopted true
Adoption Date March 29, 2024
Arrangement Duration 431 days
Aggregate Available 105,000
v3.24.1.u1
Summary of Significant Accounting Policies (Policies)
 3 Months Ended
Mar. 31, 2024
Accounting Policies [Abstract]  
Basis of Preparation and Presentation of Financial Information
Basis of Preparation and Presentation of Financial Information
These accompanying Condensed Consolidated Financial Statements have been prepared in accordance with the accounting principles generally accepted in the U.S. (“GAAP”) and with the instructions for Form 10-Q and Regulation S-X statements. Accordingly, they do not include all of the information and notes required for complete financial statements. These Condensed Consolidated Financial Statements should be read in conjunction with the Consolidated Financial Statements and Notes thereto contained in the Company’s Annual Report on Form 10-K filed with the U.S. Securities and Exchange Commission (the “SEC”) on February 22, 2024 (the “2023 Form 10-K”). These Unaudited Interim Condensed Consolidated Financial Statements are presented in U.S. dollars, which is the functional currency of the Company and its consolidated subsidiaries. These Condensed Consolidated Financial Statements include the accounts of the Company and its consolidated subsidiaries. All intercompany balances and transactions have been eliminated in consolidation.

Unaudited Interim Financial Information
The accompanying Condensed Consolidated Financial Statements and related disclosures are unaudited, have been prepared on the same basis as the annual consolidated financial statements and, in the opinion of management, reflect all adjustments, which include only normal recurring adjustments, necessary for a fair presentation of the results of operations for
the periods presented. The year-end condensed consolidated balance sheet data was derived from audited financial statements, however certain information and footnote disclosures normally included in financial statements prepared in accordance with GAAP have been condensed or omitted. The condensed consolidated results of operations for any interim period are not necessarily indicative of the results to be expected for the full year or for any other future year or interim period.
Use of Estimates
Use of Estimates
The preparation of the Condensed Consolidated Financial Statements in conformity with U.S. GAAP requires the Company to make judgments, estimates and assumptions that affect the reported amounts of assets, liabilities, revenues and expenses, and related disclosures. On an ongoing basis, management evaluates its estimates, including critical accounting policies or estimates related to revenue recognition and research and development expenses. The Company bases its estimates on historical experience and on various other market specific and other relevant assumptions that management believes to be reasonable under the circumstances, the results of which form the basis for making judgments about the carrying values of assets and liabilities that are not readily apparent from other sources. Because of the uncertainties inherent in such estimates, actual results may differ materially from these estimates.
Concentration of Risks and Other Risks and Uncertainties
Concentration of Risks and Other Risks and Uncertainties
Financial instruments that potentially subject the Company to concentration of credit risk consist of cash and cash equivalents and accounts receivable. The Company places its cash equivalents with high credit quality financial institutions and, by policy, limits the amount of credit exposure with any one financial institution. Deposits held with banks have exceeded, and will continue to exceed, federally insured limits. The Company is exposed to credit risk in the event of a default by the financial institutions holding its cash and cash equivalents. The Company has not experienced any losses on its deposits of cash and cash equivalents and its credit risk exposure is up to the extent recorded on the Company's Condensed Consolidated Balance Sheet.
The Company’s business is primarily conducted in U.S. dollars except for its agreements with contract manufacturers for drug supplies which are primarily denominated in Euros. The Company recorded a loss on foreign currency exchange rate differences of approximately $77,000 and $141,000 during the three months ended March 31, 2024 and 2023, respectively. If the Company increases its business activities that require the use of foreign currencies, it may be exposed to losses if the Euro and other such currencies continue to strengthen against the U.S. dollar.
As of March 31, 2024, and December 31, 2023, approximately $3.7 million and $3.8 million, respectively, of the Company’s property and equipment, net were held in the U.S. and a nominal amount were in Ireland.
The Company is subject to a number of risks similar to other late-stage clinical biotechnology companies, including, but not limited to, the need to obtain adequate additional funding, possible failure of current or future preclinical testing or clinical trials, its reliance on third parties to conduct its clinical trials, the need to obtain regulatory and marketing approvals for its drug candidates, competitors developing new technological innovations, the need to successfully commercialize and gain market acceptance of the Company’s drug candidates, its right to develop and commercialize its drug candidates pursuant to the terms and conditions of the licenses granted to the Company, protection of proprietary technology, and the need to secure and maintain adequate clinical trial management, manufacturing, packaging, labeling, storage, testing, and distribution arrangements with third parties. The Company also relies on third-party consultants to assist in managing these third parties and assist with its clinical trial operations and manufacturing. If the Company does not successfully commercialize or partner any of its drug candidates, it will be unable to generate product revenue or achieve profitability. Further, the Company is also subject to broad market risks and uncertainties resulting from recent events, such as inflation, rising interest rates, and recession risks, as well as supply chain and labor shortages.
Segment
Segment
The Company operates in one segment. The Company’s chief operating decision maker (the “CODM”), its Chief Executive Officer, manages the Company’s operations and evaluates the Company’s financial performance on a consolidated basis for purposes of allocating resources.
Recent Accounting Pronouncements
Recent Accounting Pronouncements

On March 6, 2024, the SEC issued final rule, “The Enhancement and Standardization of Climate-Related Disclosures for Investors”, which requires registrants to disclose material climate-related risks, including descriptions of board oversight and
risk management activities, the material impacts of these risks on a registrants strategy, business model and outlook and any material climate-related targets or goals. The rule requires these climate-related information to be disclosed in registration statements and annual reports. Registrants will also need to quantify certain effects of severe weather events and other natural conditions in a note to their audited financial statements. In addition, accelerated and large accelerated filers will need to disclose Scope 1 and Scope 2 greenhouse gas (GHG) emissions, if material, which will be subject to third-party assurance. The Company will be required to comply with the rule in fiscal year beginning January 1, 2025 for all disclosures other than the compliance with quantitative and qualitative disclosure requirements of material expenditures and material impacts on financial estimates that directly result from (1) activities to mitigate or adapt to the climate-related risks, (2) targets or goals and (3) transition plans will be required beginning fiscal year 2026. The Company’s other compliance dates are the following: 1) Scope 1 and Scope 2 GHG emissions - fiscal year beginning January 1, 2026; Limited assurance - fiscal year beginning January 1, 2029; Reasonable assurance - fiscal year beginning January 1, 2033; and Electronic tagging - fiscal year beginning January 1, 2026. The Company is currently evaluating the impact of the new standard on its consolidated financial statements and related disclosures. On April 4, 2024, the Securities and Exchange Commission (SEC) voluntarily stayed implementation of its recently adopted Climate Disclosure Rules.

On November 27, 2023, the FASB issued Accounting Standards Update 2023-07 ("ASU 2023-07"), Segment Reporting- Improvements to Reportable Segment Disclosures, which requires public entities to provide disclosures on significant segment expenses that are regularly provided to the CODM and included within each reported measure of segment profit or loss and other segment items on an annual and interim basis. The guidance also requires public entities to provide all disclosures about reportable segment’s profit or loss and assets in interim periods that are currently required annually. Public entities with a single reportable segment have to provide all disclosures required by Accounting Standards Codification (ASC) 280, Segment Reporting including the significant segment expense disclosures. The guidance is applied retrospectively to all periods presented in financial statements and is effective for fiscal years beginning after December 15, 2023, and for interim periods beginning after December 15, 2024. Early adoption is permitted. The Company is currently evaluating the impact of adopting the update on the Company's disclosures.

In December 2023, the FASB issued ASU 2023-09, Improvements to Income Tax Disclosures, which requires public business entities to disclose a tabular reconciliation using both percentages and amounts, broken out into specific categories with certain reconciling items at or above 5% of the expected tax further broken out by nature and/or jurisdiction. The guidance also requires all entities to disclose income taxes paid, net of refunds, disaggregated by federal (national), state and foreign taxes for annual periods and to disaggregate the information by jurisdiction based on a quantitative threshold. All entities are required to apply the guidance prospectively, with the option to apply it retrospectively. The guidance is effective for the Company’s fiscal year beginning January 1, 2025. Early adoption is permitted. The Company is currently evaluating the impact of the new standard on its income tax disclosures.
v3.24.1.u1
Composition of Certain Balance Sheet Items (Tables)
 3 Months Ended
Mar. 31, 2024
Composition of Certain Balance Sheet Items [Abstract]  
Schedule of Prepaid and Other Current Assets
March 31,December 31,
20242023
Prepaid R&D expenses$14,034 $10,998 
Prepaid G&A expenses2,933 803 
Other1,037 2,140 
Prepaid and other current assets$18,004 $13,941 
Schedule of Property and Equipment
Property and equipment, net consisted of the following (in thousands):
March 31,December 31,
20242023
Machinery and equipment$9,110 $9,019 
Purchased computer software2,192 2,232 
11,302 11,251 
Less: accumulated depreciation and amortization(7,630)(7,415)
Property and equipment, net$3,672 $3,836 
Schedule of Other Current Liabilities
Other current liabilities consisted of the following (in thousands):
March 31,December 31,
20242023
Payroll and related expenses$6,847 $13,245 
Professional services323 288 
Other1,964 2,129 
Other current liabilities$9,134 $15,662 
v3.24.1.u1
Net Income (Loss) Per Ordinary Share (Tables)
 3 Months Ended
Mar. 31, 2024
Earnings Per Share [Abstract]  
Calculation of Basic and Diluted Net Income (Loss) Per Ordinary Share
Net income (loss) per ordinary share was determined as follows (in thousands, except per share amounts):
Three Months Ended 
March 31,
20242023
Numerator:
Net loss
$(72,239)$(46,864)
Denominator:
Weighted-average ordinary shares outstanding used in per share calculations - basic53,714 52,501 
Weighted-average ordinary shares outstanding used in per share calculations - diluted53,714 52,501 
Net income (loss) per share:
Basic net income (loss) per ordinary share
$(1.34)$(0.89)
Diluted net income (loss) per ordinary share
$(1.34)$(0.89)
Ordinary Shares Equivalent Not Included in Diluted Net Income (Loss) Per Ordinary Share
The equivalent ordinary shares not included in diluted net income (loss) per share because their effect would be anti-dilutive are as follows (in thousands):
 Three Months Ended 
March 31,
20242023
Stock options to purchase ordinary shares11,751 10,471 
Restricted Stock Units (RSU)25 23 
Total11,776 10,494 
v3.24.1.u1
Commitments and Contingencies (Tables)
 3 Months Ended
Mar. 31, 2024
Commitments and Contingencies Disclosure [Abstract]  
Schedule of lease liability maturity analysis and future minimum rentals to be received
Future minimum payments under the above-described noncancelable operating leases, including a reconciliation to the lease liabilities recognized in the Condensed Consolidated Balance Sheets as of March 31, 2024, are as follows (in thousands):

Year Ended December 31,Operating Leases
2024 (9 months)
2,295 
20253,051 
20263,158 
20273,269 
20282,523 
Thereafter— 
Total $14,296 
Less: Present value adjustment(1,800)
Lease liability$12,496 
Schedule of Contractual Obligations by Fiscal Year Maturity The following is a summary of the Company's non-cancelable purchase commitments and contractual obligations as of March 31, 2024 (in thousands):
Total20242025202620272028Thereafter
Purchase Obligations (1)
$11,383 $11,194 $147 $42 $— $— $— 
Contractual obligations under license agreements338 64 64 60 60 45 45 
Total$11,721 $11,258 $211 $102 $60 $45 $45 
________________
(1) Purchase obligations consist of non-cancelable purchase commitments to suppliers and contract research organizations.
v3.24.1.u1
Share-Based Compensation (Tables)
 3 Months Ended
Mar. 31, 2024
Share-Based Payment Arrangement [Abstract]  
Summary of Share-Based Compensation Expense The following table summarizes share-based compensation expense for the periods presented (in thousands):
Three Months Ended 
March 31,
20242023
Research and development$5,455 $4,362 
General and administrative6,928 4,428 
Total share-based compensation expense$12,383 $8,790 
Fair Value of Options Granted The fair value of the options granted to employees and non-employee directors during the three months ended March 31, 2024 and 2023 was estimated as of the grant date using the Black-Scholes option-pricing model using the key assumptions listed in the following table:
Three Months Ended 
March 31,
20242023
Expected term (in years)4.60
 -
5.514.53
 -
5.40
Expected volatility74.8 % -78.6%76.4 %-89.7%
Risk-free interest rate3.8 % -4.4%3.5 %-4.4%
Expected dividend yield—%—%
Weighted average grant date fair value$19.57$35.37
Summary of Company's Share Option Activity
The following table summarizes the Company’s stock option activity during the three months ended March 31, 2024:
OptionsWeighted
Average
Exercise
Price		Weighted
Average
Remaining
Contractual
Term (years)		Aggregate
Intrinsic
Value
(in thousands)
Outstanding at December 31, 2023
9,866,337 $29.06 6.60$118,447 
Granted
1,998,950 30.02 
Exercised(38,338)23.24 
Forfeited(65,792)36.36 
Expired(10,375)28.50 
Outstanding at March 31, 2024
11,750,782 $29.20 6.92$42,936 
Vested and expected to vest at March 31, 2024
11,258,566 $28.84 6.82$42,907 
Vested at March 31, 2024
6,909,977 $22.39 5.48$41,926 
Share-Based Payment Arrangement, Outstanding Award, Activity, Excluding Option
The following table summarizes the activity and related information for RSUs during the three months ended March 31, 2024:
Number of UnitsWeighted Average
Grant-Date
Fair Value		Weighted
Average
Remaining
Contractual
Term (years)		Aggregate
Intrinsic
Value
(in thousands)
Unvested at December 31, 2023
25,250 $58.01 1.09$918 
Units Granted
— — 
Units Vested— — 
Units Forfeited— — 
Unvested at March 31, 2024
25,250 $58.01 0.84$625 
Unvested and expected to vest at March 31, 2024
23,760 $58.16 0.83$589 
v3.24.1.u1
Organization - Additional Information (Detail) - USD ($)
$ in Thousands
Mar. 31, 2024
Dec. 31, 2023
Mar. 31, 2023
Organization, Consolidation and Presentation of Financial Statements [Abstract]      
Accumulated deficit $ (1,052,270) $ (980,031)  
Cash and cash equivalents $ 546,512 $ 618,830 $ 686,184
v3.24.1.u1
Summary of Significant Accounting Policies - Additional Information (Details)
$ in Thousands
 3 Months Ended
Mar. 31, 2024
USD ($)
segment
Mar. 31, 2023
USD ($)
Dec. 31, 2023
USD ($)
Significant accounting policies [line item]      
Number of operating segments | segment 1    
Loss on foreign currency translation $ (77) $ (141)  
Property and equipment, net 3,672   $ 3,836
UNITED STATES      
Significant accounting policies [line item]      
Property and equipment, net 3,672   3,836
IRELAND      
Significant accounting policies [line item]      
Property and equipment, net $ 0   $ 0
v3.24.1.u1
Fair Value Measurements - Additional Information (Detail) - USD ($)
$ in Millions
Mar. 31, 2024
Dec. 31, 2023
Level 1    
Fair Value Assets and Liabilities Measured on Recurring and Nonrecurring Basis [Line Items]    
Money market funds at carrying value $ 522.8 $ 589.9
v3.24.1.u1
Composition of Certain Balance Sheet Items - Schedule of Property and Equipment (Detail) - USD ($)
$ in Thousands
Mar. 31, 2024
Dec. 31, 2023
Composition of Certain Balance Sheet Items [Abstract]    
Machinery and equipment $ 9,110 $ 9,019
Purchased computer software 2,192 2,232
Property and equipment, gross 11,302 11,251
Less: accumulated depreciation and amortization (7,630) (7,415)
Property and equipment, net $ 3,672 $ 3,836
v3.24.1.u1
Composition of Certain Balance Sheet Items - Additional Information (Detail) - USD ($)
$ in Millions
 3 Months Ended
Mar. 31, 2024
Mar. 31, 2023
Composition of Certain Balance Sheet Items [Abstract]    
Depreciation expense $ 0.2 $ 0.2
v3.24.1.u1
Composition of Certain Balance Sheet Items - Schedule of Other Current Liabilities (Detail) - USD ($)
$ in Thousands
Mar. 31, 2024
Dec. 31, 2023
Composition of Certain Balance Sheet Items [Abstract]    
Payroll and related expenses $ 6,847 $ 13,245
Professional services 323 288
Other 1,964 2,129
Other current liabilities $ 9,134 $ 15,662
v3.24.1.u1
Composition of Certain Balance Sheet Items - Schedule of Prepaid Expenses and Other Current Assets (Details) - USD ($)
$ in Thousands
Mar. 31, 2024
Dec. 31, 2023
Composition of Certain Balance Sheet Items [Abstract]    
Prepaid R&D expenses $ 14,034 $ 10,998
Prepaid G&A expenses 2,933 803
Other 1,037 2,140
Prepaid and other current assets $ 18,004 $ 13,941
v3.24.1.u1
Net Income (Loss) Per Ordinary Share - Calculation of Basic and Diluted Net Income (Loss) Per Share (Detail) - USD ($)
$ / shares in Units, shares in Thousands, $ in Thousands
 3 Months Ended
Mar. 31, 2024
Mar. 31, 2023
Numerator:    
Net income (loss) $ (72,239) $ (46,864)
Denominator:    
Weighted-average ordinary shares outstanding used in per share calculations- basic (in shares) 53,714 52,501
Weighted-average ordinary shares outstanding used in per share calculations- diluted (in shares) 53,714 52,501
Net Income (Loss) Per Share, Basic and Diluted    
Basic (in dollars per share) $ (1.34) $ (0.89)
Diluted (in dollars per share) $ (1.34) $ (0.89)
v3.24.1.u1
Net Income (Loss) Per Ordinary Share - Ordinary Shares Equivalent Not Included in Diluted Net Income (Loss) Per Share (Detail) - shares
shares in Thousands
 3 Months Ended
Mar. 31, 2024
Mar. 31, 2023
Antidilutive Securities Excluded from Computation of Earnings Per Share [Line Items]    
Equivalent ordinary shares not included in diluted net income (loss) per share(in shares) 11,776 10,494
Stock options to purchase ordinary shares    
Antidilutive Securities Excluded from Computation of Earnings Per Share [Line Items]    
Equivalent ordinary shares not included in diluted net income (loss) per share(in shares) 11,751 10,471
Restricted Stock Units (RSU)    
Antidilutive Securities Excluded from Computation of Earnings Per Share [Line Items]    
Equivalent ordinary shares not included in diluted net income (loss) per share(in shares) 25 23
v3.24.1.u1
Commitment and Contingencies - Lease Narrative (Details)
 1 Months Ended 3 Months Ended
Jul. 18, 2018
ft²
Mar. 31, 2016
ft²
Mar. 31, 2024
USD ($)
Mar. 31, 2023
USD ($)
Apr. 19, 2023
Apr. 11, 2023
Aug. 01, 2021
Lease Description [Line Items]              
Operating lease (area) | ft²   128,751          
Operating lease cost     $ 0 $ 1,600,000      
Operating lease, payments     0 1,600,000      
Operating lease, future minimum payments due     14,296,000        
South San Francisco, California              
Lease Description [Line Items]              
Area of sub-sublease rental | ft² 46,641            
Sublease income     0 $ 700,000      
Dublin, Ireland              
Lease Description [Line Items]              
Operating lease, Dublin, term of contract (in years)         1 year 1 year 1 year
Standby Letters of Credit | South San Francisco, CA              
Lease Description [Line Items]              
Line of credit has been used     0        
Restricted cash     $ 1,400,000        
v3.24.1.u1
Commitment and Contingencies - New Brisbane Facility (Details)
 1 Months Ended 3 Months Ended
Oct. 28, 2022
USD ($)
ft²
Mar. 31, 2016
ft²
Mar. 31, 2024
USD ($)
Mar. 31, 2023
USD ($)
Dec. 31, 2023
USD ($)
Jul. 31, 2023
USD ($)
Lease Description [Line Items]            
Operating lease (area) | ft²   128,751        
Operating lease, future minimum payments due     $ 14,296,000      
Operating lease right-of-use assets     12,510,000   $ 12,162,000  
Lease liability     12,496,000      
Operating lease cost     0 $ 1,600,000    
Operating lease, payments     $ 0 1,600,000    
Brisbane, California            
Lease Description [Line Items]            
Operating lease (area) | ft² 31,157          
Operating lease, future minimum payments due $ 14,900,000          
Operating lease, weighted average remaining lease term     4 years 6 months      
Operating lease right-of-use assets           $ 11,400,000
Lease liability           $ 3,600,000
Discount rate, percent           5.76%
Operating lease cost     $ 800,000 $ 0    
Operating lease, payments     500,000      
Operating Leases, Improvement Allowance 9,300,000          
Operating Leases, Proceeds From Tenant Allowance     9,300,000      
Brisbane, California | Standby Letters of Credit            
Lease Description [Line Items]            
Restricted cash $ 900,000          
Line of credit has been used     $ 0      
v3.24.1.u1
Commitment and Contingencies - Schedule of Lease Liability Maturity Analysis- (Details)
$ in Thousands
Mar. 31, 2024
USD ($)
Operating Lease  
2024 (9 months) $ 2,295
2025 3,051
2026 3,158
2027 3,269
2028 2,523
Thereafter 0
Total 14,296
Less: Present value adjustment (1,800)
Lease liability $ 12,496
v3.24.1.u1
Commitment and Contingencies - Commitment Narrative (Details)
$ in Thousands
Mar. 31, 2024
USD ($)
Long-term Purchase Commitment [Line Items]  
Purchase obligation $ 11,383 [1]
Contractual obligations under license agreements 300
Accrued Current Liabilities  
Long-term Purchase Commitment [Line Items]  
Commitment to suppliers included in accrued current liabilities 6,700
Contractual Obligations under License Agreements included in current liabilities $ 0
[1] Purchase obligations consist of non-cancelable purchase commitments to suppliers and contract research organizations.
v3.24.1.u1
Commitment and Contingencies - Contractual Obligations (Details)
$ in Thousands
Mar. 31, 2024
USD ($)
Purchase Obligations  
Total $ 11,383 [1]
2024 11,194 [1]
2025 147 [1]
2026 42 [1]
2027 0 [1]
2028 0 [1]
Thereafter 0 [1]
Contractual obligations under license agreements  
Total 300
Total  
Total 11,721
2024 11,258
2025 211
2026 102
2027 60
2028 45
Thereafter 45
License Agreements [Member]  
Contractual obligations under license agreements  
Total 338
2024 64
2025 64
2026 60
2027 60
2028 45
Thereafter $ 45
[1] Purchase obligations consist of non-cancelable purchase commitments to suppliers and contract research organizations.
v3.24.1.u1
Significant Agreements - Roche License Agreement (Details) - USD ($)
$ in Thousands
 1 Months Ended 3 Months Ended
May 05, 2021
Jun. 30, 2017
May 31, 2014
Feb. 28, 2014
Mar. 31, 2024
Mar. 31, 2023
Dec. 31, 2023
License Agreement [Line Items]              
Accounts receivable         $ 0   $ 5,159
Collaboration revenue         $ 50 $ 2,169  
Collaborative Arrangement              
License Agreement [Line Items]              
Portion of revenue and expenses attributable to company, Percentage         30.00%    
Roche              
License Agreement [Line Items]              
Revenue, Remaining performance obligation, Amount         $ 0   $ 0
Roche | Collaborative Arrangement              
License Agreement [Line Items]              
Collaboration revenue, License, Upfront payment       $ 30,000      
Milestone payment received, Clinical milestone     $ 15,000        
Milestone achievement, Clinical milestone $ 60,000 $ 30,000          
Potential payment upon achievement of development, regulatory and various first commercial sales milestones         290,000    
Potential Payment for U.S. Commercial Sales Milestones         155,000    
Potential payment for achievement of non U.S. commercial sales milestones         $ 175,000    
License agreement, Cost allocation, Percentage         100.00%    
Portion of revenue and expenses attributable to company, Percentage         70.00%    
Collaboration revenue              
License Agreement [Line Items]              
Collaboration revenue         $ 0 $ 2,119  
v3.24.1.u1
Significant Agreements - Bristol Myers Squibb Collaboration Agreement (Details)
 3 Months Ended
Jul. 05, 2023
USD ($)
Jul. 30, 2021
USD ($)
Mar. 20, 2018
USD ($)
agreement_term
$ / shares
shares
Mar. 31, 2024
USD ($)
Mar. 31, 2023
USD ($)
Dec. 31, 2023
USD ($)
Collaborative Arrangement and Arrangement Other than Collaborative [Line Items]            
Collaboration revenue       $ 50,000 $ 2,169,000  
Accounts receivable       0   $ 5,159,000
Deferred revenue, non-current       67,405,000   67,405,000
Collaboration Program, US Rights            
Collaborative Arrangement and Arrangement Other than Collaborative [Line Items]            
Collaboration agreement, potential regulatory milestone payments per program     $ 90,000,000      
Collaboration agreement, potential commercial milestone payments per program     375,000,000      
Collaboration Program, US Rights | Minimum            
Collaborative Arrangement and Arrangement Other than Collaborative [Line Items]            
Collaboration agreement, expected allocation of initial transaction price     15,000,000      
Collaboration Program, US Rights | Maximum            
Collaborative Arrangement and Arrangement Other than Collaborative [Line Items]            
Collaboration agreement, expected allocation of initial transaction price     25,000,000      
Collaboration Program, Global Rights            
Collaborative Arrangement and Arrangement Other than Collaborative [Line Items]            
Collaboration agreement, potential regulatory milestone payments per program     187,500,000      
Collaboration agreement, potential commercial milestone payments per program     375,000,000      
Collaboration Program, Global Rights | Minimum            
Collaborative Arrangement and Arrangement Other than Collaborative [Line Items]            
Collaboration agreement, expected allocation of initial transaction price     10,000,000      
Collaboration Program, Global Rights | Maximum            
Collaborative Arrangement and Arrangement Other than Collaborative [Line Items]            
Collaboration agreement, expected allocation of initial transaction price     18,000,000      
Collaboration revenue            
Collaborative Arrangement and Arrangement Other than Collaborative [Line Items]            
Collaboration revenue       0 2,119,000  
Bristol Myers Squibb            
Collaborative Arrangement and Arrangement Other than Collaborative [Line Items]            
Collaboration agreement, potential regulatory and commercial milestone payments per program     $ 562,500,000      
Collaboration agreement, number of additional 12 month period extension allowed | agreement_term     2      
Collaboration agreement, extension fee per extension period     $ 10,000,000      
Collaboration revenue       0 $ 2,100,000  
Deferred Revenue       67,400,000    
Bristol Myers Squibb | Collaboration Program, US Rights            
Collaborative Arrangement and Arrangement Other than Collaborative [Line Items]            
Collaboration agreement, exercise fee per program     80,000,000      
Bristol Myers Squibb | Collaboration Program, Global Rights            
Collaborative Arrangement and Arrangement Other than Collaborative [Line Items]            
Collaboration agreement, exercise fee per program     55,000,000      
Bristol Myers Squibb | Collaboration Revenue, US License            
Collaborative Arrangement and Arrangement Other than Collaborative [Line Items]            
Allocated consideration to performance obligations   $ 77,500,000        
Bristol Myers Squibb | Collaboration Revenue, US Development Services            
Collaborative Arrangement and Arrangement Other than Collaborative [Line Items]            
Allocated consideration to performance obligations   27,500,000        
Bristol Myers Squibb | Collaboration Program, Global, Tau/ PRX005            
Collaborative Arrangement and Arrangement Other than Collaborative [Line Items]            
Collaboration agreement, potential regulatory and commercial milestone payments per program $ 562,500,000          
Collaboration Agreement, Allocation of Initial Transaction Price 17,900,000          
Collaboration Program, Global Exercise Fee 55,000,000          
Collaboration Agreement, Total Transaction Price, PRX005 Global $ 72,900,000          
Bristol Myers Squibb | Collaboration Program, US, Tau/ PRX005            
Collaborative Arrangement and Arrangement Other than Collaborative [Line Items]            
Collaboration Agreement, Allocation of Initial Transaction Price     24,900,000      
Collaboration Agreement, Total Transaction Price, PRX005 US   104,900,000        
Collaboration Program, PRX005 US License Agreement, Upfront Payment   $ 80,000,000        
BMS (formerly Celgene)            
Collaborative Arrangement and Arrangement Other than Collaborative [Line Items]            
Collaboration agreement, upfront payment     $ 100,000,000      
Collaboration agreement, option fees and milestone payments, payment term     30 days      
BMS (formerly Celgene) | Private Placement            
Collaborative Arrangement and Arrangement Other than Collaborative [Line Items]            
Share subscription agreement, number of ordinary shares issued in transaction (in shares) | shares     1,174,536      
Share subscription agreement, price per share (in dollars per share) | $ / shares     $ 42.57      
Share subscription agreement, consideration received on transaction     $ 50,000,000      
Share subscription agreement, premium received on transaction     10,200,000      
Collaborative Arrangement | Bristol Myers Squibb            
Collaborative Arrangement and Arrangement Other than Collaborative [Line Items]            
Accounts receivable       0   $ 5,200,000
Revenue, Remaining performance obligation, Amount       $ 0    
Collaborative Arrangement | BMS (formerly Celgene)            
Collaborative Arrangement and Arrangement Other than Collaborative [Line Items]            
Collaboration agreement, Initial transaction price     $ 110,200,000      
v3.24.1.u1
Significant Agreements - Novo Nordisk Share Purchase Agreement (Details) - USD ($)
 1 Months Ended 3 Months Ended
Jul. 08, 2021
Dec. 31, 2022
Mar. 31, 2024
Mar. 31, 2023
Dec. 31, 2023
Collaborative Arrangement and Arrangement Other than Collaborative [Line Items]          
Accounts receivable     $ 0   $ 5,159,000
Novo Nordisk          
Collaborative Arrangement and Arrangement Other than Collaborative [Line Items]          
Share Purchase Agreement, Upfront Payment $ 60,000,000        
Share Purchase Agreement, Potential Payment Upon Achievement of Development and Sales Milestones     1,130,000,000    
Revenue from License and Intellectual Property, Share Purchase Agreement     0 $ 0  
Milestone achievement, Clinical milestone   $ 40,000,000      
Accounts Receivable, after Allowance for Credit Loss     $ 0   $ 0
Novo Nordisk | Transition services          
Collaborative Arrangement and Arrangement Other than Collaborative [Line Items]          
Revenue from License and Intellectual Property, Share Purchase Agreement $ 700,000        
v3.24.1.u1
Shareholders' Equity - Additional Information (Details)
 3 Months Ended
Mar. 31, 2024
vote
€ / shares
shares
Mar. 31, 2024
$ / shares
shares
Dec. 31, 2023
€ / shares
shares
Dec. 31, 2023
$ / shares
shares
Equity [Abstract]        
Ordinary shares, number of authorized shares (in shares) 100,000,000 100,000,000 100,000,000 100,000,000
Ordinary shares, par value (in dollars per share) | $ / shares   $ 0.01   $ 0.01
Ordinary shares, number of issued shares (in shares) 53,720,455 53,720,455 53,682,117 53,682,117
Ordinary shares, number of outstanding shares (in shares) 53,720,455 53,720,455 53,682,117 53,682,117
Euro deferred shares, number of shares authorized (in shares) 10,000 10,000 10,000 10,000
Euro deferred shares, nominal value (in euros per share) | € / shares € 22   € 22  
Euro deferred shares, number of outstanding shares (in shares) 0 0 0 0
Number of Votes | vote 1      
v3.24.1.u1
Shareholders' Equity - December 2022 Public Offering - (Details) - Underwritten Public Offering - USD ($)
$ / shares in Units, $ in Millions
Jan. 18, 2023
Dec. 19, 2022
Sale of Ordinary Shares [Line Items]    
Price per share at public offering (in dollars per share)   $ 56.50
Ordinary Shares    
Sale of Ordinary Shares [Line Items]    
Issuance of ordinary shares (in shares) 395,096 3,250,000
Proceeds from issuance of ordinary shares in public offering, net $ 20.9 $ 172.4
Underwritten Public Offering, Maximum Number Of Shares, Underwriters Option to Purchase   487,500
v3.24.1.u1
Shareholders' Equity - At-the-Market Offering (Details) - Ordinary Shares - USD ($)
 3 Months Ended 27 Months Ended
Feb. 22, 2024
Dec. 23, 2021
Mar. 31, 2024
Mar. 31, 2024
December 2021 At-The-Market Offering        
Sale of Ordinary Shares [Line Items]        
Maximum proceeds from sale of ordinary shares   $ 250,000,000    
Issuance of ordinary shares (in shares)       953,589
Stock Issuance Costs       $ 1,800,000
Proceeds from Issuance of Common Stock, Gross       $ 56,300,000
February 2024 Prospectus At-The-Market Offering [Member]        
Sale of Ordinary Shares [Line Items]        
Maximum proceeds from sale of ordinary shares $ 250,000,000      
Issuance of ordinary shares (in shares)     0  
v3.24.1.u1
Share-Based Compensation - Additional Information (Details) - USD ($)
 3 Months Ended
May 16, 2023
Mar. 31, 2024
Mar. 31, 2023
Dec. 31, 2023
Share-based Payment [Line Items]        
Number of shares available for grant (in shares)   1,662,669    
Grant period   10 years    
Options, granted (in shares)   1,998,950    
Options outstanding (in shares)   11,750,782   9,866,337
Weighted average exercise price (in dollars per share)   $ 29.20   $ 29.06
Share-based Payment Arrangement, Nonvested Award, Option, Cost Not yet Recognized, Amount   $ 115,200,000    
Share-based Payment Arrangement, Nonvested Award, Cost Not yet Recognized, Period for Recognition   2 years 11 months 8 days    
Tax benefit recognized from share-based compensation expense   $ 2,100,000 $ 1,600,000  
Share-Based Payment Arrangement, Estimated Forfeiture Rate   7.00%    
Restricted Stock Units (RSU)        
Share-based Payment [Line Items]        
Vesting period (in years)   2 years    
Share-Based Compensation Arrangement by Share-Based Payment Award, Equity Instruments Other than Options, Nonvested, Number   25,250   25,250
Share-based Payment Arrangement, Nonvested Award, Cost Not yet Recognized, Period for Recognition   11 months 1 day    
Share-Based Compensation Arrangement by Share-Based Payment Award, Equity Instruments Other than Options, Nonvested, Weighted Average Grant Date Fair Value   $ 58.01   $ 58.01
Share-Based Payment Arrangement, Nonvested Award, Cost Not yet Recognized, Amount   $ 800,000    
Stock options to purchase ordinary shares        
Share-based Payment [Line Items]        
Vesting period (in years)   4 years    
Intrinsic value of options exercised   $ 400,000 $ 6,800,000  
2018 Long Term Incentive Plan        
Share-based Payment [Line Items]        
Number of additional shares authorized (in shares) 2,000,000      
Authorized shares for issuance (in shares)   14,620,433    
2020 Employment Inducement Incentive Plan        
Share-based Payment [Line Items]        
Authorized shares for issuance (in shares)   1,485,000    
Number of shares available for grant (in shares)   66,250    
v3.24.1.u1
Share-Based Compensation - Summary of Share-Based Compensation Expense (Details) - USD ($)
$ in Thousands
 3 Months Ended
Mar. 31, 2024
Mar. 31, 2023
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]    
Share-based compensation expense $ 12,383 $ 8,790
Research and development    
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]    
Share-based compensation expense 5,455 4,362
General and administrative    
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]    
Share-based compensation expense $ 6,928 $ 4,428
v3.24.1.u1
Share-Based Compensation - Fair Value of Options Granted (Details) - $ / shares
 3 Months Ended
Mar. 31, 2024
Mar. 31, 2023
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]    
Expected dividend yield 0.00% 0.00%
Weighted average fair value (in dollars per share) $ 19.57 $ 35.37
Minimum    
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]    
Expected life (in years) 4 years 7 months 6 days 4 years 6 months 10 days
Expected volatility 74.80% 76.40%
Risk-free interest rate 3.80% 3.50%
Maximum    
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]    
Expected life (in years) 5 years 6 months 3 days 5 years 4 months 24 days
Expected volatility 78.60% 89.70%
Risk-free interest rate 4.40% 4.40%
v3.24.1.u1
Share-based Compensation - Share-based Compensation Plan - Option Activity (Details) - USD ($)
$ / shares in Units, $ in Thousands
 3 Months Ended 12 Months Ended
Mar. 31, 2024
Dec. 31, 2023
Share-Based Payment, Options, Outstanding [Roll Forward]    
Options, outstanding beginning balance (in shares) 9,866,337  
Options, granted (in shares) 1,998,950  
Options, exercised (in shares) (38,338)  
Options, forfeited (in shares) (65,792)  
Options, expired (in shares) (10,375)  
Options, outstanding ending balance (in shares) 11,750,782 9,866,337
Options, vested and expected to vest ending balance (in shares) 11,258,566  
Options, Vested (in shares) 6,909,977  
Share-Based Payment, Options, Outstanding, Weighted Average Exercise Price [Abstract]    
Weighted average exercise price, outstanding beginning balance (in dollars per share) $ 29.06  
Weighted average exercise price, granted (in dollars per share) 30.02  
Weighted average exercise price, exercised (in dollars per share) 23.24  
Weighted average exercise price, forfeited (in dollars per share) 36.36  
Weighted average exercise price, expired (in dollars per share) 28.50  
Weighted average exercise price, outstanding ending balance (in dollars per share) 29.20 $ 29.06
Weighted average exercise price, vested and expected to vest, ending balance (in dollars per share) 28.84  
Weighted Average Exercise Price, vested (in dollars per shares) $ 22.39  
Share-Based Payment, Options, Additional Disclosures [Abstract]    
Weighted average remaining contractual term, outstanding (in years) 6 years 11 months 1 day 6 years 7 months 6 days
Weighted average remaining contractual term, vested and expected to vest (in years) 6 years 9 months 25 days  
Weighted Average Remaining Contractual Term, vested (in years) 5 years 5 months 23 days  
Aggregate intrinsic value, outstanding $ 42,936 $ 118,447
Aggregate intrinsic value, vested and expected to vest, ending balance 42,907  
Aggregate intrinsic value, vested $ 41,926  
v3.24.1.u1
Share-Based Compensation - RSUs Activity (Details) - Restricted Stock Units (RSU) - USD ($)
$ / shares in Units, $ in Thousands
 3 Months Ended 12 Months Ended
Mar. 31, 2024
Dec. 31, 2023
Number of Units    
Restricted stock unit, beginning balance (in shares) 25,250  
Restricted stock units granted in period (in shares) 0  
Restricted stock units vested in period (in shares) 0  
Restricted stock units forfeited in period (in shares) 0  
Restricted stock unit, ending balance (in shares) 25,250 25,250
Restricted stock unit, unvested and expected to vest (in shares) 23,760  
RSU, Weighted Average Grant Date Fair Value    
Restricted stock units beginning balance (in dollars per share) $ 58.01  
Restricted stock units grant-date fair value (in dollars per share) 0  
Restricted stock units vested fair value (in dollars per share) 0  
Restricted stock units forfeited fair value (in dollars per share) 0  
Restricted stock units ending balance (in dollars per share) 58.01 $ 58.01
Restricted stock units, unvested and expected to vest (in dollars per share) $ 58.16  
RSU, Additional Disclosures [Abstract]    
Weighted Average Remaining Contractual Term (years) 10 months 2 days 1 year 1 month 2 days
Weighted average remaining contractual term, unvested and expected to vest (years) 9 months 29 days  
Aggregate Intrinsic Value $ 625 $ 918
Aggregate intrinsic value, invested and expected to vest $ 589  
v3.24.1.u1
Income Taxes - Additional Information (Details) - USD ($)
$ in Thousands
 3 Months Ended
Mar. 31, 2024
Mar. 31, 2023
Income Taxes [Line Items]    
Income tax expense (benefit) $ (2,201) $ (2,912)
Revenue Commissioners, Ireland    
Income Taxes [Line Items]    
Effective income tax rate, percent 12.50%