Bicycle Therapeutics (BCYC) 10-K 11 Mar 21 2020 FY Annual report Financial data

Document and Entity Information

Document and Entity Information - USD ($)	12 Months Ended
	Dec. 31, 2020	Mar. 05, 2021	Jun. 30, 2020
Document Information [Line Items]
Document Type	10-K
Document Period End Date	Dec. 31, 2020
Entity Registrant Name	BICYCLE THERAPEUTICS PLC
Entity Well Known Seasoned Issuer	No
Entity Voluntary Filers	No
Entity Current Reporting Status	Yes
Entity Filer Category	Non-accelerated Filer
Entity Interactive Data Current	Yes
Entity Small Business	true
Entity Emerging Growth Company	true
Entity Shell Company	false
Entity Common Stock, Shares Outstanding		23,090,382
Entity Public Float			$ 189,962,881
Current Fiscal Year End Date	--12-31
Document Fiscal Year Focus	2020
Document Fiscal Period Focus	FY
Entity Central Index Key	0001761612
Amendment Flag	false
Entity Ex Transition Period	true
Ordinary Shares
Document Information [Line Items]
Title of 12(b) Security	Ordinary shares, nominal value £0.01 per share*
None	false
Security Exchange Name	NASDAQ
American Depositary Shares
Document Information [Line Items]
Title of 12(b) Security	American Depositary Shares, each representing one ordinary share, nominal value £0.01 per share
Trading Symbol	BCYC
Security Exchange Name	NASDAQ

Consolidated Balance Sheets

Consolidated Balance Sheets - USD ($) $ in Thousands	Dec. 31, 2020	Dec. 31, 2019
Current assets:
Cash	$ 135,990	$ 92,117
Accounts receivable	5,456	201
Prepaid expenses and other current assets	5,100	4,884
Research and development incentives receivable	9,177	6,944
Total current assets	155,723	104,146
Property and equipment, net	2,317	2,292
Operating lease right-of-use assets	1,290	2,056
Other assets	1,822	1,700
Total assets	161,152	110,194
Current liabilities:
Accounts payable	1,365	1,949
Accrued expenses and other current liabilities	11,629	6,144
Deferred revenue, current portion	10,135	728
Total current liabilities	23,129	8,821
Long-term debt	14,505
Operating lease liabilities	426	1,251
Deferred revenue, net of current portion	25,021	4,929
Other long-term liabilities	2,611	1,995
Total liabilities	65,692	16,996
Commitments and contingencies (Note 13)
Shareholders’ equity:
Ordinary shares, £0.01 nominal value; 31,995,653 shares authorized at December 31, 2020 and December 31, 2019; 21,094,557 and 17,993,701 shares issued and outstanding at December 31, 2020 and December 31, 2019, respectively	266	227
Additional paid-in capital	249,947	195,056
Accumulated other comprehensive loss	(3,193)	(1,535)
Accumulated deficit	(151,560)	(100,550)
Total shareholders’ equity	95,460	93,198
Total liabilities and shareholders’ equity	$ 161,152	$ 110,194

Consolidated Balance Sheets (Pa

Consolidated Balance Sheets (Parenthetical) - £ / shares	Dec. 31, 2020	Dec. 31, 2019
Ordinary shares, nominal value	£ 0.01	£ 0.01
Ordinary shares, shares authorized	31,995,653	31,995,653
Ordinary shares, shares issued	21,094,557	17,993,701
Ordinary shares, shares outstanding	21,094,557	17,993,701

Consolidated Statements of Oper

Consolidated Statements of Operations and Comprehensive Loss - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2020	Dec. 31, 2019	Dec. 31, 2018
Consolidated Statements of Operations and Comprehensive Loss
Collaboration revenues	$ 10,390	$ 13,801	$ 7,136
Operating expenses:
Research and development	33,149	25,540	20,761
General and administrative	29,201	14,560	8,121
Total operating expenses	62,350	40,100	28,882
Loss from operations	(51,960)	(26,299)	(21,746)
Other income (expense):
Interest income	683	814	169
Interest expense	(457)
Other expense, net		(5,377)	(665)
Total other income (expense), net	226	(4,563)	(496)
Net loss before income tax provision	(51,734)	(30,862)	(22,242)
(Benefit from) provision for income taxes	(724)	(254)	(396)
Net loss	(51,010)	(30,608)	(21,846)
Net loss attributable to ordinary shareholders	$ (51,010)	$ (30,608)	$ (21,846)
Net loss per share attributable to ordinary shareholders, basic and diluted	$ (2.66)	$ (2.77)	$ (49.78)
Weighted average ordinary shares outstanding, basic and diluted	19,145,938	11,045,370	438,862
Comprehensives Loss:
Net loss	$ (51,010)	$ (30,608)	$ (21,846)
Other comprehensive income (loss):
Foreign currency translation adjustment	(1,658)	216	(1,820)
Total comprehensive loss	$ (52,668)	$ (30,392)	$ (23,666)

Consolidated Statements of Conv

Consolidated Statements of Convertible Preferred Shares and Shareholders’ Equity (Deficit) - USD ($) $ in Thousands	Series A Convertible Preferred Shares	Series B1 Convertible Preferred Shares	Series B2 Convertible Preferred Shares	Ordinary Shares	Additional Paid-in Capital	Accumulated Other Comprehensive Income (Loss)	Accumulated Deficit	Total
Beginning balance at Dec. 31, 2017	$ 41,820	$ 54,621
Beginning balance (in shares) at Dec. 31, 2017	2,800,001	3,947,198
Increase (decrease) in convertible preferred shares
Issuance of convertible preferred shares			$ 25,756
Issuance of convertible preferred shares (in shares)			1,323,248
Ending balance at Dec. 31, 2018	$ 41,820	$ 54,621	$ 25,756
Ending balance (in shares) at Dec. 31, 2018	2,800,001	3,947,198	1,323,248
Beginning balance at Dec. 31, 2017				$ 5	$ 838	$ 69	$ (48,096)	$ (47,184)
Beginning balance (in shares) at Dec. 31, 2017				368,995
Increase (decrease) in shareholders' equity (deficit)
Issuance of restricted share awards				$ 1	223			224
Issuance of restricted share awards (in shares)				95,644
Issuance of ordinary shares in exchange for surrender of vested share options				$ 4	(4)
Issuance of ordinary shares in exchange for surrender of vested share options (in shares)				340,728
Issuance of ordinary shares upon exercise of share options (in shares)				9,361
Share based compensation expense					800			800
Foreign currency translation adjustment						(1,820)		(1,820)
Net loss							(21,846)	(21,846)
Ending balance at Dec. 31, 2018				$ 10	1,857	(1,751)	(69,942)	(69,826)
Ending balance (in shares) at Dec. 31, 2018				814,728
Increase (decrease) in convertible preferred shares
Issuance of convertible preferred shares			$ 1,583
Issuance of convertible preferred shares (in shares)			80,385
Conversion of convertible preferred shares to ordinary shares	$ (41,820)	$ (54,621)	$ (27,339)
Conversion of convertible preferred shares to ordinary shares (in shares)	(2,800,001)	(3,947,198)	(1,403,633)
Increase (decrease) in shareholders' equity (deficit)
Reclassification of warrant liability to additional paid-in capital and exercise of warrants				$ 9	10,018			10,027
Reclassification of warrant liability to additional paid-in capital and exercise of warrants (in shares)				723,992
Conversion of convertible preferred shares to ordinary shares				$ 146	123,634			123,780
Conversion of convertible preferred shares to ordinary shares (in shares)				11,647,529
Issuance of ADSs in initial public offering, net of underwriting discounts, commissions and offering expenses				$ 59	56,322			56,381
Issuance of ADSs in initial public offering, net of underwriting discounts, commissions and offering expenses (in shares)				4,637,666
Issuance of restricted share awards				$ 2	395			397
Issuance of restricted share awards (in shares)				83,947
Issuance of ordinary shares upon exercise of share options				$ 1	142			143
Issuance of ordinary shares upon exercise of share options (in shares)				85,839
Share based compensation expense					2,688			2,688
Foreign currency translation adjustment						216		216
Net loss							(30,608)	(30,608)
Ending balance at Dec. 31, 2019				$ 227	195,056	(1,535)	(100,550)	$ 93,198
Ending balance (in shares) at Dec. 31, 2019				17,993,701				17,993,701
Increase (decrease) in shareholders' equity (deficit)
Issuance of ordinary shares upon exercise of warrants				$ 1				$ 1
Issuance of ordinary shares upon exercise of warrants (in shares)				92,885
Issuance of ADSs in initial public offering, net of underwriting discounts, commissions and offering expenses				$ 37	48,107			48,144
Issuance of ADSs in initial public offering, net of underwriting discounts, commissions and offering expenses (in shares)				2,928,813
Issuance of ordinary shares upon exercise of share options				$ 1	270			271
Issuance of ordinary shares upon exercise of share options (in shares)				79,158
Share based compensation expense					6,514			6,514
Foreign currency translation adjustment						(1,658)		(1,658)
Net loss							(51,010)	(51,010)
Ending balance at Dec. 31, 2020				$ 266	$ 249,947	$ (3,193)	$ (151,560)	$ 95,460
Ending balance (in shares) at Dec. 31, 2020				21,094,557				21,094,557

Consolidated Statements of Co_2

Consolidated Statements of Convertible Preferred Shares and Shareholders’ Equity (Deficit) (Parenthetical) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2020	Dec. 31, 2019	Dec. 31, 2018
Consolidated Statements of Convertible Preferred Shares and Shareholders’ Equity
Offering expenses	$ 1,900	$ 8,500	$ 327

Consolidated Statements of Cash

Consolidated Statements of Cash Flows - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2020	Dec. 31, 2019	Dec. 31, 2018
Cash flows from operating activities:
Net loss	$ (51,010)	$ (30,608)	$ (21,846)
Adjustments to reconcile net loss to net cash used in operating activities:
Share-based compensation expense	6,514	3,083	1,023
Depreciation and amortization	1,277	960	712
Non-cash interest	78
Change in fair value of warrant liability		5,381	665
Changes in operating assets and liabilities:
Accounts receivable	(2,149)	4,909	(400)
Research and development incentives receivable	(1,786)	(383)	(3,586)
Prepaid expenses and other current assets	(49)	(2,723)	(1,329)
Operating lease right-of-use assets	771	712
Other assets	(122)	(397)	(301)
Accounts payable	(663)	220	(169)
Accrued expenses and other current liabilities	4,832	(852)	2,557
Operating lease liabilities	(621)	(709)
Deferred revenue	24,622	(9,295)	(3,947)
Other long-term liabilities	517	1,089	543
Net cash used in operating activities	(17,789)	(28,613)	(26,078)
Cash used in investing activities:
Purchases of property and equipment	(1,200)	(1,555)	(1,186)
Net cash used in investing activities	(1,200)	(1,555)	(1,186)
Cash flows from financing activities:
Proceeds from the issuance of ADSs, net of issuance costs	48,144	56,957	(576)
Proceeds from the exercise of share options and sale of ordinary shares	271	143	1
Proceeds from the exercise of warrants	1	6
Proceeds from issuance of debt	15,000
Payments of debt issuance costs	(573)
Net cash provided by financing activities	62,843	58,440	25,430
Effect of exchange rate changes on cash	19	465	(2,449)
Net increase (decrease) in cash	43,873	28,737	(4,283)
Cash at beginning of period	92,117	63,380	67,663
Cash at end of period	135,990	92,117	63,380
Supplemental disclosure of cash flow information
Cash paid for interest	378
Cash paid for income taxes	124	117	73
Cash paid for amounts included in the measurement of operating lease liabilities	961	891
Purchases of property and equipment included in accounts payable and accrued expenses	109	76
Advance billings on deferred revenue included in accounts receivable	$ 3,000		5,045
Series B2 convertible preferred financing costs accrued but not paid			249
Debt issuance costs accrued but not paid			1,076
Conversion of convertible preferred shares to ordinary shares upon closing of the initial public offering		123,780
Reclassification of warrant liability to additional paid-in capital		10,021
Series B2 Convertible Preferred Shares
Cash flows from financing activities:
Proceeds from issuance of convertible preferred shares, net of issuance costs		$ 1,334	$ 26,005

Nature of the business and basi

Nature of the business and basis of presentation	12 Months Ended
	Dec. 31, 2020
Nature of business and basis of presentation
Nature of the business and basis of presentation	1. Nature of the business and basis of presentation Bicycle Therapeutics plc (collectively with its subsidiaries, the “Company”) is a clinical‑stage biopharmaceutical company developing a novel class of medicines, which the Company refers to as Bicycles , for diseases that are underserved by existing therapeutics. Bicycles are a unique therapeutic modality combining the pharmacology usually associated with a biologic with the manufacturing and pharmacokinetic properties of a small molecule. The Company’s initial internal programs are focused on oncology indications with high unmet medical need. The Company’s lead product candidate, BT1718, is a Bicycle Toxin Conjugate (“BTC”) that is being developed to target tumors that express Membrane Type 1 matrix metalloproteinase. BT1718 is being investigated for safety, tolerability and efficacy in an ongoing Phase I/IIa clinical trial in collaboration with, and fully funded by, the Centre for Drug Development of Cancer Research UK. The Company is also evaluating BT5528, a second-generation BTC targeting Ephrin type‑A receptor 2 (“EphA2”), in a Company-sponsored Phase I/II clinical trial as a monotherapy and in combination with nivolumab, and BT8009, a second-generation BTC targeting Nectin-4, in a Company-sponsored Phase I/II clinical trial. The Company’s discovery pipeline in oncology includes Bicycle -based systemic immune cell agonists and Bicycle tumor-targeted immune cell agonists (TICAs). Beyond the Company’s wholly-owned oncology portfolio, the Company is collaborating with biopharmaceutical companies and organizations in immuno-oncology, anti-infective, cardiovascular, ophthalmology, dementia and respiratory indications. The accompanying consolidated financial statements include the accounts of Bicycle Therapeutics plc and its wholly owned subsidiaries, BicycleTx Limited, BicycleRD Limited and Bicycle Therapeutics Inc. All intercompany balances and transactions have been eliminated on consolidation. The accompanying consolidated financial statements have been prepared in accordance with accounting principles generally accepted in the United States of America (“GAAP”). Liquidity On May 28, 2019, the Company completed its initial public offering (the “IPO”), pursuant to which it issued and sold 4,333,333 American Depositary Shares (“ADSs”), representing the same number of ordinary shares at a public offering price of $14.00 per ADS. In addition, in June 2019, the Company issued and sold an additional 304,333 ADSs, pursuant to the partial exercise of the underwriters’ option to purchase additional ADSs. The aggregate net proceeds received by the Company from the IPO were $56.4 million, after deducting underwriting discounts and commissions of $4.5 million and offering expenses of $4.0 million. On June 5, 2020, the Company entered into a Sales Agreement (the “Sales Agreement”) with Cantor Fitzgerald & Co. and Oppenheimer & Co. Inc. (the “Sales Agents”) with respect to an at-the-market offering program (“ATM”) pursuant to which the Company may offer and sell through the Sales Agents, from time to time at the Company’s sole discretion, ADSs, each ADS representing one ordinary share. As of December 31, 2020, the Company had issued and sold 2,928,813 ADSs, representing the same number of ordinary shares for gross proceeds of $50.0 million, resulting in net proceeds of $48.1 million after deducting sales commissions and offering expenses of $1.9 million. On September 30, 2020, Bicycle Therapeutics plc and certain of its subsidiaries (together with Bicycle Therapeutics plc, the “Borrowers”) entered into a loan and security agreement (the “Loan Agreement”) with Hercules Capital, Inc. (“Hercules”) as agent, which provided for maximum borrowings of up to $40.0 million in aggregate principal amount, consisting of (i) a term loan of $15.0 million, which was funded on September 30, 2020, (ii) subject to satisfaction of customary conditions, an additional term loan of up to $15.0 million available from September 30, 2020 through March 15, 2021, and (iii) subject to the achievement of certain performance milestones and satisfaction of customary conditions, an additional term loan of $10.0 million available until March 15, 2022. The Company is subject to risks common to companies in the biotechnology industry and in light of the ongoing COVID-19 pandemic, including but not limited to, risks of delays in initiating or continuing research programs and clinical trials, risks of failure of preclinical studies and clinical trials, the need to obtain marketing approval for any drug product candidate that it may identify and develop, the need to successfully commercialize and gain market acceptance of its product candidates, dependence on key personnel and collaboration partners, protection of proprietary technology, compliance with government regulations, development by competitors of technological innovations, and the ability to secure additional capital to fund operations. Product candidates currently under development will require significant additional research and development efforts, including preclinical and clinical testing and regulatory approval prior to commercialization. Even if the Company’s research and development efforts are successful, it is uncertain when, if ever, the Company will realize significant revenue from product sales. The accompanying consolidated financial statements have been prepared on the basis of continuity of operations, realization of assets and the satisfaction of liabilities and commitments in the ordinary course of business. Since inception, the Company has devoted substantially all of its efforts to business planning, research and development, recruiting management and technical staff, and raising capital. The Company has funded its operations with proceeds from the sale of its ordinary shares and ADSs, including in its IPO completed in May 2019 and pursuant to its ATM program, convertible preferred shares (Note 7), and proceeds received from its collaboration arrangements (Note 11), and proceeds from the Loan Agreement with Hercules (Note 6). The Company has incurred recurring losses since inception, including net losses of $51.0 million for the year ended December 31, 2020, $30.6 million for the year ended December 31, 2019 and $21.8 million for the year ended December 31, 2018. As of December 31, 2020, the Company had an accumulated deficit of $151.6 million. The Company expects to continue to generate operating losses in the foreseeable future. As of the issuance date of the annual consolidated financial statements for the year ended December 31, 2020, the Company expects that its cash will be sufficient to fund its operating expenses and capital expenditure requirements through at least twelve months from the issuance date of the annual consolidated financial statements. The Company expects its expenses to increase substantially in connection with ongoing activities, particularly as the Company advances its preclinical activities and clinical trials for its product candidates in development. Accordingly, the Company will need to obtain additional funding in connection with continuing operations. If the Company is unable to raise capital when needed, or on attractive terms, it could be forced to delay, reduce or eliminate its research or drug development programs or any future commercialization efforts. Although management continues to pursue these plans, there is no assurance that the Company will be successful in obtaining sufficient funding on terms acceptable to the Company to fund continuing operations, if at all.

Summary of Significant Accounti

Summary of Significant Accounting Policies	12 Months Ended
	Dec. 31, 2020
Summary of Significant Accounting Policies
Summary of Significant Accounting Policies	2. Summary of Significant Accounting Policies Use of estimates The preparation of consolidated financial statements in conformity with GAAP requires management to make estimates and assumptions that affect the reported amounts of assets and liabilities, the disclosure of contingent assets and liabilities at the date of the consolidated financial statements and the reported amounts of expenses during the reporting periods. Significant estimates and assumptions reflected in these consolidated financial statements include, but are not limited to, the accrual for research and development expenses, revenue recognition, the fair value of ordinary shares and the valuation of the warrant liability prior to the Company’s IPO, share-based compensation expense, and income taxes. The Company bases its estimates on historical experience, known trends and other market‑specific or other relevant factors that it believes to be reasonable under the circumstances. Estimates are periodically reviewed in light of reasonable changes in circumstances, facts and experience. Changes in estimates are recorded in the period in which they become known. Actual results could differ from those estimates or assumptions. Foreign currency and currency translation The functional currency is the currency of the primary economic environment in which an entity’s operations are conducted. On June 1, 2019, Bicycle Therapeutics plc adopted the U.S. dollar as its functional currency. Bicycle Therapeutics plc is a holding company that has no operating activities and its primary functions are to serve as a financing vehicle to fund the operations of the Company’s operating entities, to serve as the listing company needed to access U.S. capital markets, and to hold investments. Therefore, its financing source is the primary indicator of its cash flows and its functional currency. The change in functional currency from the British Pound Sterling is due to a change in the source of Bicycle Therapeutics plc’s financing and cash flows, which following the completion of the IPO is now primarily the U.S. Dollar (“USD”). Historically its financing had been in British Pound Sterling. The functional currency of Bicycle Therapeutics plc’s wholly owned non-U.S. subsidiaries, BicycleTx Limited and BicycleRD Limited, is the British Pound Sterling and the functional currency of its U.S. subsidiary, Bicycle Therapeutics Inc. is the USD. The functional currency of the Company’s subsidiaries is the same as the local currency. Monetary assets and liabilities denominated in currencies other than the functional currency are remeasured into the functional currency at rates of exchange prevailing at the balance sheet dates. Non‑monetary assets and liabilities denominated in foreign currencies are remeasured into the functional currency at the exchange rates prevailing at the date of the transaction. Exchange gains or losses arising from foreign currency transactions are included in the determination of net loss for the respective periods. Adjustments that arise from exchange rate changes on transactions denominated in a currency other than the local currency are included in general and administrative expense in the consolidated statements of operations and comprehensive loss as incurred. The Company recorded foreign exchange gains of $0.6 million, $0.9 million and $0.3 million for the years ended December 31, 2020, 2019 and 2018, respectively. The Company translates the assets and liabilities of BicycleTx Limited and BicycleRD Limited into USD at the exchange rate in effect on the balance sheet date. Revenues and expenses are translated at the average exchange rate in effect during the period. Unrealized translation gains and losses are recorded as a cumulative translation adjustment, which is included in the consolidated statements of convertible preferred shares and shareholders’ equity (deficit) as a component of accumulated other comprehensive loss. Concentrations of credit risk and of significant suppliers Financial instruments that potentially expose the Company to concentrations of credit risk consist primarily of cash and accounts receivable. The Company deposits its cash in financial institutions in amounts that may exceed federally insured limits and has not experienced any losses on such accounts. The Company does not believe it is exposed to any unusual credit risk beyond the normal credit risk associated with commercial banking relationships. Accounts receivable primarily consist of amounts due under the collaboration agreements between BicycleTx Limited and AstraZeneca AB (“AstraZeneca”), between BicycleRD Limited and Oxurion NV (formerly ThromboGenics NV) (“Oxurion”), and pursuant to an evaluation and option agreement with another third party (the “Evaluation and Option Agreement”) (Note 11), for which the Company does not obtain collateral. As of December 31, 2020, the Company’s revenue to date has primarily been generated from the collaboration agreements with Genentech, Inc. (“Genentech”), AstraZeneca, Sanofi (formerly Bioverativ), the Dementia Discovery Fund (“DDF”) and Oxurion. The Company relies, and expects to continue to rely, on a small number of vendors to manufacture supplies and raw materials for its development programs. These programs could be adversely affected by a significant interruption in these manufacturing services or the availability of raw materials. Cash and cash equivalents The Company considers all highly liquid investments with original maturities of three months or less at date of purchase to be cash equivalents. The Company had no cash equivalents at December 31, 2020 and 2019. Accounts receivable The Company makes judgments as to its ability to collect outstanding receivables and provides an allowance for receivables when collection becomes doubtful. Provisions are made based upon a specific review of all significant outstanding invoices and the overall quality and age of those invoices. To date, the Company has not had any write‑offs of bad debt, and the Company did not have an allowance for doubtful accounts as of December 31, 2020 and 2019. Deferred offering costs The Company capitalizes certain legal, professional accounting and other third‑party fees that are directly associated with in‑process equity financings as deferred offering costs until such financings are consummated. After consummation of the equity financing, these costs are recorded in shareholders’ equity (deficit) as a reduction of proceeds generated as a result of the offering. Should an in‑process equity financing be abandoned, the deferred offering costs will be expensed immediately as a charge to operating expenses in the consolidated statements of operations and comprehensive loss. Property and equipment Property and equipment are stated at cost, less accumulated depreciation and amortization. Depreciation and amortization expense is recognized using the straight‑line method over the estimated useful lives of the respective assets as follows: Estimated Useful Life Laboratory equipment 3 to 5 years Leasehold improvements Lesser of lease term or useful life Computer equipment 3 years Furniture and office equipment 5 years Costs for capital assets not yet placed into service are capitalized as construction‑in‑progress and depreciated in accordance with the above guidelines once placed into service. Upon retirement or sale, the cost of assets disposed of and the related accumulated depreciation are removed from the accounts and any resulting gain or loss is included in loss from operations. As of December 31, 2020 and 2019, there have been no significant asset retirements to date. Expenditures for repairs and maintenance are charged to expense as incurred. Impairment of long‑lived assets Long‑lived assets to be held and used are tested for recoverability whenever events or changes in business circumstances indicate that the carrying amount of the assets may not be fully recoverable. Factors that the Company considers in deciding when to perform an impairment review include significant underperformance of the business in relation to expectations, significant negative industry or economic trends and significant changes or planned changes in the use of the assets. If an impairment review is performed to evaluate a long‑lived asset group for recoverability, the Company compares forecasts of undiscounted cash flows expected to result from the use and eventual disposition of the long‑lived asset group to its carrying value. An impairment loss would be recognized when estimated undiscounted future cash flows expected to result from the use of an asset group are less than its carrying amount. The impairment loss would be based on the excess of the carrying value of the impaired asset group over its fair value, determined based on discounted cash flows. To date, the Company has not recorded any impairment losses on long‑lived assets. Fair value measurements Certain assets and liabilities of the Company are carried at fair value under GAAP. Fair value is defined as the exchange price that would be received for an asset or paid to transfer a liability (an exit price) in the principal or most advantageous market for the asset or liability in an orderly transaction between market participants on the measurement date. Valuation techniques used to measure fair value must maximize the use of observable inputs and minimize the use of unobservable inputs. Financial assets and liabilities carried at fair value are to be classified and disclosed in one of the following three levels of the fair value hierarchy, of which the first two are considered observable and the last is considered unobservable: · Level 1 — Quoted prices in active markets for identical assets or liabilities. · Level 2 — Observable inputs (other than Level 1 quoted prices), such as quoted prices in active markets for similar assets or liabilities, quoted prices in markets that are not active for identical or similar assets or liabilities, or other inputs that are observable or can be corroborated by observable market data. · Level 3 — Unobservable inputs that are supported by little or no market activity that are significant to determining the fair value of the assets or liabilities, including pricing models, discounted cash flow methodologies and similar techniques. Prior to the IPO, the Company’s warrant liability was carried at fair value, determined according to the fair value hierarchy described above (Note 3). The carrying values of accounts receivable, research and development incentives receivable, other current assets, accounts payable and accrued expenses and other current liabilities approximate their fair values due to the short‑term nature of these assets and liabilities. At December 31, 2020, the carrying value of the long-term debt approximates its fair value, which was determined using unobservable Level 3 inputs, including quoted interest rates from a lender for borrowings with similar terms. Warrant liability Prior to the IPO, the Company classified warrants to subscribe for Series A convertible preferred shares (“Series A Preferred Shares”) and Series B1 convertible preferred shares (“Series B1 Preferred Shares”) (Note 7) as a liability on its consolidated balance sheets as these warrants to subscribe for Series A Preferred Shares and Series B1 Preferred Shares were free‑standing financial instruments that might have required the Company to transfer assets upon exercise. The warrant liability was initially recorded at fair value upon the date of the warrants’ issuance and was subsequently remeasured to fair value at each reporting date. Changes in the fair value of the warrant liability were recognized as a component of other expense, net in the consolidated statements of operations and comprehensive loss. Upon the closing of the IPO, warrants to subscribe for Series A Preferred Shares and Series B1 Preferred Shares that were not exercised or expired in conjunction with the IPO automatically became warrants to subscribe for ordinary shares, and meet the criteria to be classified as shareholders’ equity (deficit). As such, following the final remeasurement on May 28, 2019, the Company reclassified the carrying value of the warrant liability to additional paid-in-capital in the consolidated balance sheet. Segment and geographic information Operating segments are defined as components of a business for which separate discrete financial information is available for evaluation by the chief operating decision maker in deciding how to allocate resources and assess performance. The Company and its chief operating decision maker, the Company’s Chief Executive Officer, view the Company’s operations and manages its business as a single operating segment, which is developing a unique class of chemically synthesized medicines based on its proprietary constrained peptides. The Company operates in two geographic regions: the United Kingdom and the United States. Leases The Company adopted ASC Topic 842, Leases (ASC 842), using a modified retrospective approach, as of January 1, 2019, with no restatement of prior periods or cumulative adjustment to retained earnings. The Company determines if an arrangement is a lease at inception. Operating leases are included in operating lease right‑of‑use (“ROU”) assets, other current liabilities, and operating lease liabilities in the Company’s consolidated balance sheet. The Company has not entered into any financing leases. ROU assets represent the Company’s right to use and control an underlying asset for the lease term and lease liabilities represent the Company’s obligation to make lease payments arising from the lease. ROU assets and liabilities are recognized at commencement date based on the present value of lease payments over the lease term. As the Company’s leases do not provide an implicit rate, the Company uses its incremental borrowing rate based on the information available at commencement date in determining the present value of lease payments. The ROU asset also includes lease payments made before the lease commencement date and excludes any lease incentives. The Company’s lease terms may include options to extend or terminate the lease when it is reasonably certain that the Company will exercise that option. The components of a lease shall be split into three categories, if applicable: lease components (e.g., land, building, etc.), non‑lease components (e.g., common area maintenance, maintenance, consumables, etc.), and non‑components (e.g., property taxes, insurance, etc.). The fixed and in‑substance fixed contract consideration (including any related to non‑components) must then be allocated based on fair values to the lease components and non‑lease components. The Company’s facilities operating leases may have lease and non‑lease components to which the Company has elected to apply a practical expedient to account for each lease component and related non‑lease component as one single component. The lease component results in a right‑of‑use asset being recorded on the balance sheet. Lease expense for lease payments is recognized on a straight‑line basis over the lease term. Revenue recognition The Company’s revenues are generated primarily through collaborative arrangements and license agreements with pharmaceutical companies. The terms of these arrangements may include (i) performing research and development services using the Company’s bicyclic peptide screening platform with the goal of identifying compounds for further development and commercialization, (ii) options to obtain additional research and development services or licenses for additional targets, or to optimize product candidates, upon the payment of option fees, or (iii) the transfer of intellectual property rights (licenses). The terms of these arrangements typically include payment to the Company of one or more of the following: non‑refundable, upfront license fees; payments for research and development services; fees upon the exercise of options to obtain additional services or licenses; payments based upon the achievement of defined collaboration objectives; future regulatory and sales‑based milestone payments; and royalties on net sales of future products. The Company recognizes revenue in accordance with ASU 2014‑09, Revenue from Contracts with Customers (Topic 606) (“ASC 606”) and all subsequent amendments. This standard applies to all contracts with customers, except for contracts that are within the scope of other standards, such as leases, insurance, collaboration arrangements and financial instruments. Under ASC 606, an entity recognizes revenue when its customer obtains control of promised goods or services, in an amount that reflects the consideration which the entity expects to receive in exchange for those goods or services. To determine revenue recognition for arrangements that the Company determines are within the scope of ASC 606, it performs the following five steps: (i) identify the contract(s) with a customer; (ii) identify the performance obligations in the contract; (iii) determine the transaction price; (iv) allocate the transaction price to the performance obligations in the contract; and (v) recognize revenue when, or as, the Company satisfies the performance obligations. The Company only applies the five‑step model to contracts when it is probable that the entity will collect substantially all of the consideration it is entitled to in exchange for the goods or services it transfers to the customer. As part of the accounting for these arrangements, the Company must make significant judgments, including identifying performance obligations in the contract, estimating the amount of variable consideration to include in the transaction price and allocating the transaction price to each performance obligation. Once a contract is determined to be within the scope of ASC 606, the Company assesses the goods or services promised within the contract and determines those that are performance obligations. Arrangements that include rights to additional goods or services that are exercisable at a customer’s discretion are generally considered options. The Company assesses if these options provide a material right to the customer and if so, they are considered performance obligations. Performance obligations are promised goods or services in a contract to transfer a distinct good or service to the customer. The promised goods or services in the Company’s contracts with customers primarily consist of license rights to the Company’s intellectual property for research and development, research and development services, options to acquire additional research and development services, and options to obtain additional licenses, such as a commercialization license for a potential product candidate. Promised goods or services are considered distinct when: (i) the customer can benefit from the good or service on its own or together with other readily available resources, and (ii) the promised good or service is separately identifiable from other promises in the contract. In assessing whether promised goods or services are distinct, the Company considers factors such as the stage of development of the underlying intellectual property, the capabilities of the customer to develop the intellectual property on their own and whether the required expertise is readily available. In addition, the Company considers whether the collaboration partner can benefit from a promise for its intended purpose without the receipt of the remaining promises, whether the value of the promise is dependent on the unsatisfied promises, whether there are other vendors that could provide the remaining promises, and whether it is separately identifiable from the remaining promises. The Company estimates the transaction price based on the amount of consideration the Company expects to receive for transferring the promised goods or services in the contract. The consideration may include both fixed consideration and variable consideration. At the inception of each arrangement that includes variable consideration, the Company evaluates the amount of the potential payments and the likelihood that the payments will be received. The Company utilizes either the most likely amount method or expected value method to estimate variable consideration to include in the transaction price based on which method better predicts the amount of consideration expected to be received. The amount included in the transaction price is constrained to the amount for which it is probable that a significant reversal of cumulative revenue recognized will not occur. At the end of each subsequent reporting period, the Company re‑evaluates the estimated variable consideration included in the transaction price and any related constraint, and if necessary, adjusts its estimate of the overall transaction price. Any such adjustments are recorded on a cumulative catch‑up basis in the period of adjustment. After the transaction price is determined it is allocated to the identified performance obligations based on the estimated standalone selling price. The Company must develop assumptions that require judgment to determine the standalone selling price for each performance obligation identified in the contract. The Company utilizes key assumptions to determine the standalone selling price, which may include other comparable transactions, pricing considered in negotiating the transaction, probabilities of technical and regulatory success and the estimated costs. Certain variable consideration is allocated specifically to one or more performance obligations in a contract when the terms of the variable consideration relate to the satisfaction of the performance obligation and the resulting amounts allocated to each performance obligation are consistent with the amounts the Company would expect to receive for each performance obligation. The Company then recognizes as revenue in the amount of the transaction price that is allocated to the respective performance obligation when (or as) each performance obligation is satisfied at a point in time or over time, and if over time based on the use of an input method. Licenses of intellectual property: If a license to the Company’s intellectual property is determined to be distinct from the other promises or performance obligations identified in the arrangement, the Company recognizes revenue from non‑refundable, upfront fees allocated to the license when the license is transferred to the customer and the customer is able to use and benefit from the license. For licenses that are combined with other promises, such as research and development services and a research license, the Company utilizes judgment to assess the nature of the combined performance obligation to determine whether the combined performance obligation is satisfied over time or at a point in time and, if over time, the appropriate method of measuring progress for purposes of recognizing revenue. The Company evaluates the measure of progress each reporting period and, if necessary, adjusts the measure of performance and related revenue recognition. The measure of progress, and thereby periods over which revenue should be recognized, are subject to estimates by management and may change over the course of the research and development and licensing agreement. Research and Development Services: The promises under the Company’s collaboration agreements may include research and development services to be performed by the Company on behalf of the partner. Payments or reimbursements resulting from the Company’s research and development efforts are recognized as the services are performed and presented on a gross basis because the Company is the principal for such efforts. Customer Options: The Company evaluates the customer options to obtain additional items (i.e. additional license rights) for material rights, or options to acquire additional goods or services for free or at a discount. Optional future services that reflect their standalone selling prices do not provide the customer with a material right and, therefore, are not considered performance obligations and are accounted for as separate contracts. If optional future services include a material right, they are accounted for as performance obligations. The Company determines an estimated standalone selling price of any material rights for the purpose of allocating the transaction price. The Company considers factors such as the identified discount and the probability that the customer will exercise the option. Amounts allocated to a material right are not recognized as revenue until, at the earliest, the option is exercised or expires. Milestone payments: The Company’s collaboration agreements may include development and regulatory milestones. The Company evaluates whether the milestones are considered probable of being reached and estimates the amount to be included in the transaction price using the most likely amount method. The Company evaluates factors such as the scientific, clinical, regulatory, commercial, and other risks that must be overcome to achieve the particular milestone in making this assessment. If it is probable that a significant revenue reversal would not occur, the associated milestone value is included in the transaction price. Milestone payments that are not within the Company’s control or the licensee’s control, such as regulatory approvals, are not considered probable of being achieved until those approvals are received. At the end of each reporting period, the Company re‑evaluates the probability of achievement of such milestones and any related constraint, and if necessary, adjusts the estimate of the overall transaction price. Any such adjustments are recorded on a cumulative catch‑up basis, which would affect collaboration revenue and net loss in the period of adjustment. Royalties: For sales‑based royalties, including milestone payments based on the level of sales, the Company determines whether the sole or predominant item to which the royalties relate is a license. When the license is the sole or predominant item to which the sales‑based royalty relates, the Company recognizes revenue at the later of: (i) when the related sales occur, or (ii) when the performance obligation to which some or all of the royalty has been allocated has been satisfied (or partially satisfied). To date, the Company has not recognized any sales‑based royalty revenue resulting from the Company’s collaboration agreements. The Company receives payments from customers based on billing schedules established in each contract. Up‑front payments and fees are recorded as deferred revenue upon receipt or when due until the Company performs its obligations under these arrangements. Amounts are recorded as accounts receivable when the Company’s right to consideration is unconditional, such as when the Company has a contractual right to payment per the terms of the contract. For a complete discussion of accounting for collaboration revenues, see Note 11, “Significant Agreements” Government grants From time to time, the Company may enter into arrangements with governmental entities for the purposes of obtaining funding for research and development activities. The Company recognizes government grant funding in the consolidated statements of operations and comprehensive loss as the related expenses being funded are incurred. The Company classifies government grants received under these arrangements as a reduction to the related research and development expense incurred. The Company analyzes each arrangement on a case‑by‑case basis. For the years ended December 31, 2020 and 2019, the Company recognized $0.7 million and $0.6 million, respectively, as a reduction of research and development expense related to government grant arrangements. There were no grant proceeds recognized for the year ended December 31, 2018. Research and development costs Research and development costs are expensed as incurred. Research and development expenses consist of costs incurred in performing research and development activities, including salaries, share‑based compensation and benefits, travel, facilities costs, materials and laboratory supplies, and external costs of outside vendors engaged to conduct preclinical development, clinical development activities, as well as to manufacture clinical trial materials. Facilities costs primarily include the allocation of rent, utilities, and depreciation. Non‑refundable prepayments for goods or services that will be used or rendered for future research and development activities are deferred and capitalized until the related goods are delivered or the related services are performed, or until it is no longer expected that the goods will be delivered, or the services rendered. Research and manufacturing contract costs and accruals The Company has entered into various research and development and manufacturing contracts, including contracts with respect to preclinical studies and clinical trials, with companies both inside and outside of the United States. These agreements are generally cancelable with 90 days or less notice, and related costs are recorded as research and development expenses as incurred. The Company records accruals for estimated ongoing costs. When evaluating the adequacy of the accrued liabilities, the Company analyzes progress of the research and development and manufacturing activities, including the phase or completion of events, invoices received and contracted costs. Significant judgments and estimates are made in determining the accrued balances at the end of any reporting period. Actual results could differ from the Company’s estimates. The Company’s historical accrual estimates have not been materially different from the actual costs. Research and development incentives and receivable The Company, through its subsidiaries in the United Kingdom, receives reimbursements of certain research and development expenditures as part of a United Kingdom government’s research and development tax reliefs program. Under the program, the Company is able to surrender trading losses that arise from qualifying research and development expenses incurred by the Company’s subsidiaries in the United Kingdom for a tax credit of up to 14.5% of the surrenderable losses. Management has assessed the Company’s research and development activities and expenditures to determine which activities and expenditures are likely to be eligible under the research and development incentive program described above. At each period end, management estimates the reimbursement available to the Company based on available information at the time. The Company recognizes income from the research and development incentives when the relevant expenditure has been incurred, the associated conditions have been satisfied and there is reasonable assurance that the reimbursement will be received. The Company records these research and development incentives as a reduction to research and development expenses in the statements of operations and comprehensive loss, as the research and development tax credits are not dependent on us generating future taxable income, the Company’s ongoing tax status, or tax position. The research and development incentives receivable represent an amount due in connection with the above program. The Company recorded a reduction to research and development expense of $9.1 million, $6.7 million and $5.9 million during the years ended December 31, 2020, 2019 and 2018, respectively. Patent costs All patent‑related costs incurred in connection with preparing, filing and prosecuting patent applications are expensed as incurred due to the uncertainty about the recovery of the expenditure. Amounts incurred are classified as general and administrative expenses in the consolidated statements of operations and comprehensive loss. Share‑based compensation The Company measures all equity awards granted to employees and directors based on the fair value on the date of grant. Compensation expense of those awards is recognized over the requisite service period, which is generally the vesting period of the respective award. The Company records the expense for awards with only service‑based vesting conditions using the straight‑line method. The Company accounts for forfeitures as they occur. The Company has granted awards with both a service condition that vest over time and a performance condition that will accelerate vesting upon the achievement of a specified collaboration revenue threshold. For equity awards that contain b

Fair value of financial assets

Fair value of financial assets and liabilities	12 Months Ended
	Dec. 31, 2020
Fair value of financial assets and liabilities
Fair value of financial assets and liabilities	3. Fair value of financial assets and liabilities As of December 31, 2020 and December 31, 2019, there were no assets or liabilities measured at fair value on a recurring basis.

Property and equipment, net

Property and equipment, net	12 Months Ended
	Dec. 31, 2020
Property and equipment, net
Property and equipment, net	4. Property and equipment, net Property and equipment, net consisted of the following (in thousands): December 31, 2020 2019 Laboratory equipment $ 5,583 $ 4,326 Leasehold improvements 383 300 Computer equipment and software 188 229 Furniture and office equipment 195 120 6,349 4,975 Less: Accumulated depreciation and amortization (4,032) (2,683) $ 2,317 $ 2,292 Depreciation expense was $1.3 million, $1.0 million and $0.7 million for the years ended December 31, 2020, 2019 and 2018, respectively.

Accrued expenses and other curr

Accrued expenses and other current liabilities	12 Months Ended
	Dec. 31, 2020
Accrued expenses and other current liabilities
Accrued expenses and other current liabilities	5. Accrued expenses and other current liabilities Accrued expenses and other current liabilities consisted of the following (in thousands): December 31, 2020 2019 Accrued employee compensation and benefits $ 4,390 $ 2,515 Accrued external research and development expenses 4,428 2,055 Accrued professional fees 1,759 867 Current portion of operating lease liabilities 844 640 Other 208 67 $ 11,629 $ 6,144

Long-term debt

Long-term debt	12 Months Ended
	Dec. 31, 2020
Long-term debt
Long-term debt	6. Long-term debt On September 30, 2020 (the “Closing Date”), Bicycle Therapeutics plc and its subsidiaries (the “Borrowers”) entered into the Loan Agreement with Hercules, which provided for aggregate maximum borrowings of up to $40.0 million, consisting of (i) a term loan of $15.0 million, which was funded on the Closing Date, (ii) subject to customary conditions, an additional term loan of up to $15.0 million available from the Closing Date through March 15, 2021, and (iii) subject to the Borrowers achieving certain performance milestones and satisfying customary conditions and available until March 15, 2022, an additional term loan of $10.0 million. Borrowings under the Loan Agreement bear interest at an annual rate equal to the greater of (i) 8.85% or (ii) 5.60% plus the Wall Street Journal prime rate. Payments under the Loan Agreement are interest-only until the first principal payment is due on November 1, 2022 (or if the Borrowers achieve the certain performance milestones, the interest only period is extended with the first principal payment due on May 1, 2023), followed by equal monthly payments of principal and interest through the scheduled maturity date on October 1, 2024 (the “Maturity Date”). At the Borrowers’ option, the Borrowers may prepay all or any portion greater than $5.0 million of the outstanding borrowings, subject to a prepayment premium equal to (i) 2.0% of the principal amount outstanding if the prepayment occurs during the first year following the Closing Date, (ii) 1.5% of the principal amount outstanding if the prepayment occurs during the second year following the Closing Date, and (iii) 1.0% of the principal amount outstanding if the prepayment occurs thereafter but prior to the Maturity Date. The Loan Agreement also provides for an end of term charge (the “End of Term Charge”), payable upon maturity or the repayment of obligations under the Loan Agreement, equal to 5.0% of the principal amount repaid. Borrowings under the Loan Agreement are collateralized by substantially all of the Borrower’s personal property and other assets, other than their intellectual property. Hercules has a perfected first-priority security interest in certain cash accounts. The Loan Agreement contains customary affirmative and restrictive covenants and representations and warranties, including a covenant against the occurrence of a change in control, as defined in the agreement. There are no financial covenants. The Loan Agreement also includes customary events of default, including payment defaults, breaches of covenants following any applicable cure period, cross acceleration to third-party indebtedness, certain events relating to bankruptcy or insolvency, and the occurrence of certain events that could reasonably be expected to have a material adverse effect. Upon the occurrence of an event of default, a default interest rate of an additional 5.0% may be applied to the outstanding principal and interest payments due, and Hercules may declare all outstanding obligations immediately due and payable and take such other actions as set forth in the Loan Agreement. The Company has determined that the risk of subjective acceleration under the material adverse events clause is not probable and therefore has classified the outstanding principal in long-term liabilities based on scheduled principal payments. The Company incurred fees and transaction costs totaling $0.6 million associated with the initial term loan, which are recorded as a reduction to the carrying value of the long-term debt in the consolidated balance sheets. The fees, transaction costs, and the End of Term Charge are amortized to interest expense through the Maturity Date using the effective interest method. The effective interest rate was 12.2% at December 31, 2020. The Company assessed all terms and features of the Loan Agreement in order to identify any potential embedded features that would require bifurcation. As part of this analysis, the Company assessed the economic characteristics and risks of the debt. The Company determined that all features of the Loan Agreement are clearly and closely associated with a debt host and, as such, do not require separate accounting as a derivative liability. Interest expense for the year ended December 31, 2020 related to the Loan Agreement with Hercules was $0.4 million. Long-term debt consisted of the following (in thousands): December 31, 2020 Term loan payable $ 15,000 End of term charge 58 Unamortized debt issuance costs (553) Carrying value of term loan $ 14,505 Future principal payments, including the End of Term Charge, are as follows (in thousands): Year Ending December 31, 2021 $ — 2022 1,148 2023 7,262 2024 7,340 Total $ 15,750 In addition, the Company granted Hercules the right to purchase up to an aggregate of $2.0 million of the Company’s equity securities sold to investors in certain subsequent financing upon the same terms and conditions afforded to such other investors. On October 1, 2020, Hercules purchased 98,100 ADSs, representing the same number of ordinary shares, at a public offering price of $19.05 per ADS ordinary share pursuant to the Sales Agreement, resulting in net proceeds of $1.8 million.

Convertible preferred shares

Convertible preferred shares	12 Months Ended
	Dec. 31, 2020
Convertible preferred shares
Convertible preferred shares	7. Convertible preferred shares Prior to the IPO, the Company issued Series A Preferred Shares, Series B1 Preferred Shares, and Series B2 convertible preferred shares (“Series B2 Preferred Shares”) (collectively the “Preferred Shares”). On December 20, 2018, the Company completed the issuance of 1,323,248 Series B2 Preferred Shares at a price per Series B2 Preferred Share of £15.55, for gross cash proceeds of $26.1 million (the “Series B2 Financing”). On January 3, 2019, the Company completed the issuance of 80,385 Series B2 Preferred Shares at a price per share of £15.55, for gross cash proceeds of $1.6 million. In May 2019, the Company’s board of directors and shareholders approved the reorganization of the Company’s share capital by issuing ordinary shares as bonus shares to each holder of ordinary shares on the basis of 1.429 bonus shares for each ordinary share in issue (having the effect of a one for 1.429 share split (without having an impact on the nominal value of the ordinary shares)), which was effected on May 13, 2019 (the “Share Capital Reorganization”). All issued and outstanding share and per share amounts of ordinary shares and share options included in the accompanying consolidated financial statements have been adjusted to reflect this share split for all periods presented. Upon the closing of the IPO in May 2019, all of the Company’s outstanding convertible preferred shares automatically converted into 11,647,529 ordinary shares on a 1:1.429 basis.

Warrant liability

Warrant liability	12 Months Ended
	Dec. 31, 2020
Warrant liability
Warrant liability	8. Warrant liability In 2017, the Company issued 200,000 warrants to subscribe for Series A Preferred Shares, at £0.01 each. In conjunction with the completion of the IPO, 120,000 warrants to subscribe for Series A Preferred Shares were exercised for 171,480 ordinary shares. The remaining 80,000 warrants, which were exercisable into 114,320 ordinary shares following the completion of the IPO, as adjusted for the impact of the Share Capital Reorganization (Note 7), were exercised in 2019 and 2020. In addition, in 2017, the Company issued a total of 743,287 warrants to subscribe for Series B1 Preferred Shares, with an exercise price of £0.01, in conjunction with the issuance of 3,947,198 Series B1 Preferred Shares. On March 7, 2019, the holders of the warrants to subscribe for Series B1 Preferred Shares agreed that 50% of the warrants would be exercised in conjunction with the IPO and 50% of the warrants would expire. The modification resulted in an incremental change in fair value of $0.1 million, which is included in other expense for the year ended December 31, 2019. On May 28, 2019, in conjunction with the completion of the IPO, all Series B1 Preferred share warrants were exercised for 531,077 ordinary shares, as adjusted for the impact of the Share Capital Reorganization (Note 7). Prior to the completion of the IPO, the warrants to subscribe for Series A and Series B1 Preferred Shares were recorded as a liability and remeasured to fair value at each reporting date. Changes in the fair value of the warrant liability were recognized as other expense, net in the consolidated statements of operations and comprehensive loss. Upon the closing of the IPO on May 28, 2019, warrants that were not exercised in conjunction with the IPO automatically became warrants to subscribe for ordinary shares, and meet the criteria to be classified as shareholders’ equity (deficit). As such, following the final remeasurement on May 28, 2019, the Company reclassified the carrying value of the warrant liability to additional paid-in-capital in the consolidated balance sheet.

Ordinary shares

Ordinary shares	12 Months Ended
	Dec. 31, 2020
Ordinary shares
Ordinary shares	9. Ordinary shares Each holder of ordinary shares is entitled to one vote per ordinary share and to receive dividends when and if such dividends are recommended by the board of directors and declared by the shareholders. Holders of ADSs are not treated as holders of the Company’s ordinary shares, unless they withdraw the ordinary shares underlying their ADSs in accordance with the deposit agreement and applicable laws and regulations. The depositary is the holder of the ordinary shares underlying the ADSs. Holders of ADSs therefore do not have any rights as holders of the Company’s ordinary shares, other than the rights that they have pursuant to the deposit agreement with the depositary. As of December 31, 2020 and 2019, the Company has not declared any dividends. As of December 31, 2020 and 2019, the Company’s authorized capital share consisted of 31,995,653 ordinary shares, with a nominal value of £0.01 per share.

Share-based compensation

Share-based compensation	12 Months Ended
	Dec. 31, 2020
Share-based compensation
Share-based compensation	10. Share‑based compensation Employee incentive pool 2020 Share Option Plan In June 2020, the Company’s shareholders approved the Bicycle Therapeutics plc 2020 Equity Incentive Plan (the “2020 Plan”), under which the Company may grant market value options, market value stock appreciation rights or restricted shares, restricted share units, performance restricted share units and other share-based awards to the Company’s employees. The Company’s non-employee directors and consultants are eligible to receive awards under the 2020 Non-Employee Sub-Plan to the 2020 Plan. All awards under the 2020 Plan, including the 2020 Non-Employee Sub-Plan, will be set forth in award agreements, which will detail the terms and conditions of awards, including any applicable vesting and payment terms, change of control provisions and post-termination exercise limitations. In the event of a change of control of the Company, as defined in the 2020 Plan, any outstanding awards under the 2020 Plan will vest in full immediately prior to such change of control. Share options issued under the 2020 Share Option Plan have a 10 year contractual life, and generally vest over either a three year service period for non-employee directors, or a four year service period with 25% of the award vesting on the first anniversary of the commencement date and the balance thereafter in 36 equal monthly installments for employees and consultants. Certain options granted to the Company’s non-employee directors vest immediately upon grant. The Company initially reserved up to 4,773,557 ordinary shares for future issuance under the 2020 Plan, representing 574,679 new shares, 544,866 shares that remained available for future issuance under the Company’s 2019 Share Option Plan (the “2019 Plan”) immediately prior to the effectiveness of the 2020 Plan and up to 3,654,012 shares subject to options that were granted under the 2019 Plan and that were granted pursuant to option contracts granted prior to the Company’s IPO, in each case that expire, terminate, are forfeited or otherwise not issued from time to time, if any. Additionally, the number of ordinary shares reserved for issuance pursuant to the 2020 Plan will automatically increase on the first day of January of each year, commencing on January 1, 2021, in an amount equal to 5% of the total number of the Company’s ordinary shares outstanding on the last day of the preceding year, or a lesser number of shares determined by the Company’s board of directors. As of December 31, 2020, there were 4,699,470 shares available for issuance and options to purchase 196,550 shares outstanding under the 2020 Plan. The number of shares reserved for issuance under the 2020 Plan was increased by 1,054,727 shares effective January 1, 2021. 2019 Share Option Plan In May 2019, the Company adopted the 2019 Plan, which became effective in conjunction with the IPO. As of December 31, 2020, there were 2,594,277 options to purchase ordinary shares outstanding under the 2019 Plan. In conjunction with the adoption of the 2020 Plan, all shares available for future issuance under the 2019 Plan as of June 29, 2020 became available for issuance under the 2020 Plan and the Company ceased making awards under the 2019 Plan. The 2020 Plan is the successor of the 2019 Plan. Share options previously issued under the 2019 Share Option Plan have a 10 year contractual life, and generally either vest monthly over a three year service period, or over a four‑year service period with 25% of the award vesting on the first anniversary of the commencement date and the balance thereafter in 36 equal monthly installments. Certain awards granted to the Company’s non-employee directors were fully vested on the date of grant. The exercise price of share options issued under the 2019 Share Option Plan is not less than the fair value of ordinary shares as of the date of grant. Pre-IPO Share Options and restricted shares Prior to the IPO, the Company issued share options and ordinary shares, as administered by the board of directors, using standardized share option and share subscription agreements. To the extent such incentives were in the form of share options, the options may have been granted pursuant to a potentially tax-favored Enterprise Management Incentive, or EMI, scheme available to U.K. employees, directors and consultants of the Company. Upon completion of the IPO, shares reserved for future issuance outside of the 2019 Share Option Plan were cancelled. Options granted, as well as restricted shares granted as employee incentives prior to the IPO, typically vest over a four‑year service period with 25% of the award vesting on the first anniversary of the commencement date and the balance thereafter in 36 equal monthly installments and expire no later than 10 years from the date of grant. Certain equity awards were issued in 2017 and 2018 for which 20% of the award vests upon the first anniversary of the vesting start date, 60% vests thereafter in 36 equal monthly installments, and 20% vest upon the earlier of the fourth anniversary of the vesting start date, or the achievement of a specified revenue threshold from the Company’s collaboration arrangements. Options issued to U.K. employees prior to the IPO generally had an exercise price of £0.01 per share. The exercise price for share options granted to U.S. employees, had an exercise price that was not less than the fair value of ordinary shares as determined by the board of directors as of the date of grant. Prior to the IPO, the Company’s board of directors valued the Company’s ordinary shares based on input from management, considering the most recently available valuation of ordinary share performed by an independent third‑party valuation firm as well as additional factors which may have changed since the date of the most recent contemporaneous valuation through the date of grant. Employee Share Purchase Plan (“ESPP”) In May 2019, the Company adopted the 2019 Employee Stock Purchase Plan (the “ESPP”), which became effective in conjunction with the IPO. The Company initially reserved 215,000 ordinary shares for future issuance under this plan. The ESPP provides that the number of shares reserved and available for issuance will automatically increase each January 1, beginning on January 1, 2020 and each January 1 thereafter through January 1, 2029, by the least of (i) 1% of the outstanding number of ordinary shares on the immediately preceding December 31; (ii) 430,000 ordinary shares or (iii) such lesser number of shares as determined by the Compensation Committee. The number of shares reserved under the ESPP is subject to adjustment in the event of a split-up, share dividend or other change in our capitalization. As of December 31, 2020, the total number of shares available for issuance under the ESPP was 394,937 ordinary shares. The number of shares reserved for issuance under the ESPP was increased by 210,945 shares effective January 1, 2021. Once the Company commences offerings under the ESPP, each offering to the employees to purchase shares under the ESPP will begin on each June 1 and December 1 and will end on the following November 30 and May 31, respectively. On each purchase date, which will fall on the last date of each offering period, ESPP participants will purchase ordinary shares at a price per share equal to 85% of the lesser of (1) the fair market value of the shares on the offering date or (2) the fair market value of the shares on the purchase date. The occurrence and duration of offering periods under the ESPP are subject to the determinations of the Company’s compensation committee. As of December 31, 2020, there have been no offering periods to employees under ESPP. Share‑based compensation The Company recorded share‑based compensation expense in the following expense categories of its consolidated statements of operations and comprehensive loss (in thousands): Year Ended December 31, 2020 2019 2018 Research and development expenses $ 2,603 $ 1,286 $ 513 General and administrative expenses 3,911 1,797 510 $ 6,514 $ 3,083 $ 1,023 Share options The following table summarizes the Company’s option activity since December 31, 2019: Weighted Weighted Average Aggregate Number of Average Contractual Intrinsic Shares Exercise Price Term Value (in years) (in thousands) Outstanding as of December 31, 2019 2,634,346 $ 9.57 9.04 $ 6,107 Granted 1,370,984 12.00 — — Exercised (79,158) 3.42 — — Forfeited (189,509) 11.10 — — Outstanding as of December 31, 2020 3,736,663 $ 10.51 8.54 $ 27,553 Vested and expected to vest as of December 31, 2020 3,736,663 $ 10.51 8.54 $ 27,553 Options exercisable as of December 31, 2020 1,518,721 $ 8.81 7.90 $ 13,729 The weighted average grant‑date fair value of share options granted during the years ended December 31, 2020, 2019 and 2018 was $7.87 per share, $6.07 per share and $3.73 per share, respectively. For the years ended December 31, 2020, 2019 and 2018, the Company recorded share‑based compensation expense for share options granted of $6.5 million, $2.7 million and $0.8 million, respectively. Expense for non‑employee consultants for the years ended December 31, 2020, 2019 and 2018, was immaterial. The aggregate intrinsic value of share options is calculated as the difference between the exercise price of the share options and the fair value of the Company’s ordinary shares. The aggregate intrinsic value of share options exercised during the years ended December 31, 2020, 2019 and 2018 was $1.3 million, $0.6 million and $23,000 respectively. During the year ended December 31, 2018, the Company granted share options to purchase 70,875 ordinary shares with performance based vesting, for which 20% of the award vests upon the first anniversary of the vesting start date, 60% vests thereafter in 36 equal monthly installments, and 20% on the earlier of the fourth anniversary of the vesting start date, or the achievement of a specified revenue threshold from the Company’s collaboration arrangements. In May 2018, the Company determined that the performance condition became probable of achievement and recorded a cumulative catch‑up to reflect the expense as if the vesting condition was probable of achievement at the time of the grant of the award. The Company recorded expense of $0.1 million, $0.1 million and $0.7 million, during the years ended December 31, 2020, 2019 and 2018, respectively, related to awards with performance based vesting, which includes the acceleration of vesting expense. The following table presents, on a weighted average basis, the assumptions used in the Black‑Scholes option‑pricing model to determine the fair value of share options granted to employees and directors: The following table presents, on a weighted average basis, the assumptions used in the Black‑Scholes option‑pricing model to determine the fair value of share options granted to employees and directors: The following table presents, on a weighted average basis, the assumptions used in the Black‑Scholes option‑pricing model to determine the fair value of share options granted to employees and directors: Year Ended December 31, 2020 2019 2018 Risk-free interest rate 1.3 % 2.1 % 2.7 % Expected volatility 74.8 % 77.9 % 78.6 % Expected dividend yield — — — Expected term (in years) 5.98 5.86 6.07 As of December 31, 2020, total unrecognized compensation expense related to the unvested employee and director share‑based awards was $13.7 million, which is expected to be recognized over a weighted average period of 2.5 years. Restricted shares Prior to the IPO, the Company granted restricted shares with service‑based vesting conditions. In conjunction with the IPO in May 2019, the board of directors modified the vesting terms to accelerate vesting for all then unvested restricted shares. As a result, the Company recorded $0.2 million of expense upon the modification of the restricted shares during the year ended December 31, 2019. For the years ended December 31, 2020, 2019 and 2018, the Company recorded share-based compensation of zero, $0.4 million, and $0.2 million, respectively, for unvested restricted shares granted. The fair value of employee restricted share awards vested during the years ended December 31, 2020, 2019 and 2018, based on estimated fair values of the ordinary shares underlying the restricted share awards on the day of vesting, was zero, $0.7 million and $0.2 million, respectively. As of December 31, 2020, there was no unrecognized compensation cost related to the unvested employee and director restricted share awards.

Significant Agreements

Significant Agreements	12 Months Ended
	Dec. 31, 2020
Significant Agreements
Significant Agreements	11. Significant Agreements For the years ended December 31, 2020, 2019 and 2018, the Company had collaboration agreements with Genentech, AstraZeneca, Sanofi, Oxurion and DDF. The following table summarizes the revenue recognized in the Company’s consolidated statements of operations and comprehensive loss from these arrangements (in thousands): Year Ended December 31, 2020 2019 2018 Collaboration revenues AstraZeneca $ 2,696 $ 1,683 $ 1,386 Sanofi — 10,724 4,007 Oxurion 2,362 — 1,743 Dementia Discovery Fund 436 394 — Material transfer agreement — 1,000 — Genentech 4,896 — — Total collaboration revenues $ 10,390 $ 13,801 $ 7,136 Genentech Collaboration Agreement On February 21, 2020, the Company entered into a Discovery Collaboration and License Agreement (the “Genentech Collaboration Agreement”) with Genentech. The collaboration is focused on the discovery and development of Bicycle peptides directed to biological targets selected by Genentech and aimed at developing up to four potential development candidates against multiple immuno-oncology targets suitable for Genentech to advance into further development and commercialization. Under the terms of the Genentech Collaboration Agreement, Bicycle received a $30.0 million upfront, non-refundable payment. The initial discovery and optimization activities will focus on utilizing Bicycle’s phage screening technology to identify product candidates aimed at two immuno-oncology targets (“Genentech Collaboration Programs”), which may also include additional discovery and optimization of Bicycles as a targeting elements for each Genentech Collaboration Program (each a “Targeting Arm”). Genentech has the option to nominate up to two additional immuno-oncology targets (each, an “Expansion Option”), which may also include an additional Targeting Arm for each Expansion Option, as additional Genentech Collaboration Programs during a specified period following completion of certain activities under an agreed research plan. If Genentech exercises one or more Expansion Options, Genentech will pay to the Company an expansion fee of $10.0 million per Expansion Option. Genentech also has rights, under certain limited circumstances, to select an alternative target to be the subject of a Genentech Collaboration Program, in some cases subject to payment of an additional target selection fee. If Genentech elects for Bicycle to perform discovery and optimization services for certain Targeting Arms, the Company will be entitled to receive an additional advance payment for the additional research services. Genentech exercised its right to select a Targeting Arm for one of the initial Genentech Collaboration Programs at the inception of the arrangement, which entitled the Company to an additional $1.0 million payment. If a Targeting Arm achieves specified criteria in accordance with the research plan, Genentech will be required to pay a further specified amount in the low single digit millions for each such Targeting Arm as consideration for the additional services to be provided. Bicycle granted to Genentech a non-exclusive research license under Bicycle’s intellectual property solely to enable Genentech to perform any activities under the agreement. The activities under the Genentech Collaboration Agreement are governed by a joint research committee (“JRC”) with representatives from each of the Company and Genentech. The JRC will oversee, review and recommend direction of each Genentech Collaboration Program, achievement of development criteria, and variations of or modifications to the research plans. After the Company performs the initial discovery and optimization activities in accordance with an agreed research plan and achieves specified criteria, Genentech will have the option to have the Company perform initial pre-clinical development and optimization activities in exchange for an additional specified milestone payment in the mid-single digit millions for each Genentech Collaboration Program (the “LSR Go Option”). Upon completion of such initial pre-clinical development and optimization activities for each Genentech Collaboration Program, Genentech will have the option to obtain an exclusive license to exploit any compound developed under such Genentech Collaboration Program in exchange for an additional specified payment in the mid to high single digit millions for each of the initial two Genentech Collaboration Programs and each of the two Expansion Option Genentech Collaboration Programs (the “Dev Go Option”). On a Genentech Collaboration Program by Genentech Collaboration Program basis, if Genentech elects to obtain exclusive development and commercialization rights and pays the applicable LSR Go Option and Dev Go Option fees, Genentech will be required to make milestone payments to the Company upon the achievement of specified development, regulatory, and initial commercialization milestones for products arising from each collaboration program, totaling up to $200.0 million. Specifically, the Company is eligible for additional development milestones totaling up to $65.0 million, as well as regulatory milestones of up to $135.0 million for each collaboration program. In addition, the Company is also eligible to receive up to $200.0 million in sales milestone payments on a Genentech Collaboration Program-by-Genentech Collaboration Program basis. In addition, to the extent any of the product candidates covered by the licenses conveyed to Genentech are commercialized, the Company would be entitled to receive tiered royalty payments on net sales at percentages ranging from the mid-single to low double-digits, subject to certain standard reductions and offsets. Royalties will be payable, on a product by product and country by country basis, until the later of the expiration of specified licensed patents covering such product in such country, or ten years from first commercial sale of such product in such country. Accounting Analysis Upon the execution of the Genentech Collaboration Agreement, the Company has identified the following performance obligations: (i) Research license, and the related research and development and preclinical services through LSR Go for a first Genentech Collaboration Program (Genentech Collaboration Program #1); (ii) Research license, and the related research and development and preclinical services through LSR Go for a second Genentech Collaboration Program with a specified Targeting Arm (Genentech Collaboration Program #2); (iii) Material right associated with an option to a specified Targeting Arm for Genentech Collaboration Program #1; (iv) Two material rights associated with the LSR Go Option for Genentech Collaboration Program #1 and Genentech Collaboration Program #2, which includes research services to be provided through the Dev Go Option and an option to receive an exclusive license; (v) Material rights associated with certain limited substitution rights with respect to a limited number of collaboration targets; (vi) Two material rights related to each Genentech Expansion Option, which upon exercise include the services for an additional immuno-oncology target through the LSR Go Option, an LSR Go Option which includes the services to be provided through the Dev Go Option and an option to receive an exclusive license, limited substitution rights, and an option to select a specified Targeting Arm. The Company concluded that certain substitution rights that require the payment of additional consideration, which approximate the standalone selling price of the underlying services to be provided, do not provide the customer with a material right and therefore, are not considered as performance obligations and are accounted for as separate contracts upon exercise, if ever. The Company’s participation in the joint steering committee was assessed as immaterial in the context of the contract. The Company has concluded that the research license is not distinct from the research and development services as Genentech cannot obtain the benefit of the research license without the Company performing the research and development services. The services incorporate proprietary technology and unique skills and specialized expertise, particularly as it relates to constrained peptide technology that is not available in the marketplace. As a result, for each research program, the research license has been combined with the research and development services into a single performance obligation. In addition, the Company concluded that the Dev Go Option is not distinct or separately exercisable from the LSR Go Option, as the customer cannot benefit from the Dev Go Option unless and until the LSR Go Option is exercised. In assessing whether the various options under the Genentech Collaboration Agreement represent material rights, the Company considered the additional consideration the Company would be entitled to upon the option exercise, the standalone selling price of the underlying goods, services, and additional options. For the material rights identified above the Company concluded that each of the options provided Genentech with a discount that it otherwise would not have received. The total transaction price was initially determined to be $31.0 million, consisting of the $30.0 million upfront fee and the additional $1.0 million for Genentech’s selection of a new Targeting Arm at inception. The Company utilizes the most likely amount method to determine the amount of research and development funding to be received. Additional consideration to be paid to the Company upon the exercise of options by Genentech and subsequent milestones are excluded from the transaction price as they relate to option fees and milestones that can only be achieved subsequent to the exercise of an option. In addition, other variable consideration for development milestones not subject to option exercises was fully constrained, as a result of the uncertainty regarding whether any of the milestones will be achieved. The transaction price was allocated to the performance obligations based on the relative estimated standalone selling prices of each performance obligation. The estimated standalone selling prices for the Genentech Collaboration Programs was based on the nature of the services to be performed and estimates of the associated effort and costs of the services, adjusted for a reasonable profit margin for what would be expected to be realized under similar contracts. The estimated standalone selling price for the material rights was determined based on the fees Genentech would pay to exercise the options, the estimated value of the underlying goods and services, and the probability that Genentech would exercise the option and any underlying options. Based on the relative standalone selling price, the allocation of the transaction price to the separate performance obligations is as follows (in thousands): Allocation of Performance Obligations Transaction Price Genentech Collaboration Program #1 Performance Obligation $ 3,775 Genentech Collaboration Program #2 Performance Obligation 7,550 Specified Targeting Arm Material Right Arm for Genentech Collaboration Program #1 330 Two material rights associated with the LSR Go Option for Collaboration Programs #1 and #2 11,650 Material rights associated with limited substitution rights 1,115 Two material rights for Expansion Options 6,580 $ 31,000 The Company will recognize revenue related to amounts allocated to the Genentech Collaboration Program #1 and #2 Performance Obligations as the underlying services are performed using a proportional performance model over the period of service using input‑based measurements of total full‑time equivalent efforts and external costs incurred to date as a percentage of total full‑time equivalent time and external expected, which best reflects the progress towards satisfaction of the performance obligation. The amount allocated to the material rights is recorded as deferred revenue and the Company will commence revenue recognition upon exercise of or upon expiry of the respective option. The Company anticipates that the Genentech Collaboration Performance Program #1 and #2 obligations will be performed over a period of approximately two years, and the material rights will be exercised or expire within approximately four years from contract execution. During the year ended December 31, 2020, the Company recognized revenue of $4.9 million, and as of December 31, 2020, the Company recorded $27.6 million of deferred revenue in connection with the Genentech Collaboration Agreement. Dementia Discovery Fund Agreement In May 2019, the Company entered into a collaboration with the Dementia Discovery Fund (“DDF”) to use Bicycle technology for the discovery and development of novel therapeutics for dementia (the “DDF Collaboration Agreement”). In October 2019, the collaboration with DDF was expanded to include Oxford University’s Oxford Drug Discovery Institute (ODDI). Under the terms of the DDF Collaboration Agreement, the Company and DDF will collaborate to identify Bicycles that bind to clinically validated dementia targets (the “DDF Research Plan”). The Company is obligated to use commercially reasonable efforts to perform research activities under the DDF Research Plan. DDF shall not be directly engaged in the conduct of any research activities under the arrangement. ODDI will then profile these Bicycles in a range of target-specific and disease-focused assays to determine their therapeutic potential. The activities under the DDF Collaboration Agreement will be governed by a project advisory panel, composed of two representatives from the Company and DDF. The Research Advisory Panel will oversee, review and recommend direction for the Research Plans and variations of or modifications of research plans. The Company received an upfront payment of $1.1 million in May 2019. The Company may receive up to an additional $0.7 million, upon achievement of certain milestones such as the identification of lead Bicycle candidates with a certain affinity, which would be used to fund additional research and development services including lead optimization. Intellectual property created by the collaboration shall be owned by the Company, and background intellectual property improvements shall be owned by the party from whose background intellectual property they exclusively relate. If promising lead compounds are identified, the Company, ODDI and DDF have the option (the “DDF Option”) to establish a jointly owned new company (“NewCo”) to advance the compounds through further development towards commercialization. NewCo will receive a royalty and milestone-bearing assignment and license of intellectual property from the Company for this purpose. The DDF Option is exercisable at any time until 90 days following the completion of the Research Plan and delivery of a final report. If DDF does not elect to exercise the DDF Option during the Option period, then DDF shall have no right in the collaboration intellectual property. NewCo will initially be owned 66% by the Company and 34% by DDF; however, the Company shall not be entitled to exercise more than 50% of the total voting rights related to its ownership interests. After completion of the DDF Option exercise, for a period of two years following the option exercise, NewCo shall have the right to initiate a new research program to develop up to three additional dementia targets, on a target by target basis, and the Company will be entitled to charge NewCo an agreed upon FTE rate for peptide screening and optimization for the active targets. Either party may terminate the DDF Collaboration Agreement upon providing not less than 60 days written notice. A party may terminate the DDF Collaboration Agreement with immediate effect without notice if at any time the other party files for protection under bankruptcy or insolvency laws, makes an arrangement for the benefit of creditors, appoints a receiver, administrator, manager or trustee over its property, proposes a written agreement of composition or extension of its debts, is a party to any dissolution, winding-up or liquidation, or is in material breach that has not been remedied. Accounting Analysis The Company identified a single performance obligation associated with the performance of research and development services under the DDF Research Plan. The Company concluded that the DDF Option is an immaterial obligation at the inception of the arrangement, as it represents a right to acquire shares of NewCo that have de minimis value. The DDF Option also does not contain a material right that otherwise would not have been received. The Company’s participation in the Research Advisory Panel was assessed as immaterial in the context of the contract. In addition, the Company concluded that the option for NewCo to obtain additional peptide screening and optimization services is not an obligation at the inception of the arrangement, as they are optional services and the amount that will be paid for the services do not reflect a discount that the customer would otherwise receive and do not provide the customer with material rights. The total transaction price was initially determined to be $1.1 million, consisting of the upfront payment for research and development funding. The Company may receive additional milestone payments during the DDF Research Plan, as well as for research and development services for additional targets following the exercise of DDF Option. These variable amounts are excluded from the transaction price as they relate to fees that can only be achieved subsequent to the exercise of an option, and therefore are treated as separate contracts. The transaction price was allocated to the single performance obligation of research and development services. The Company will recognize revenue as the underlying services are performed using a proportional performance model, over the period of service using input‑based measurements of total costs, including total full‑time equivalent effort incurred to date as a percentage of total costs expected, which best reflects the progress towards satisfaction of the performance obligation. For both of the years ended December 31, 2020 and 2019, t he Company recognized $0.4 million of revenue. In December 2020, the Company received a payment of $0.5 million upon the achievement of specified scientific criteria. The Company concluded that the payment represents consideration for a single performance obligation to perform lead optimization activities, and will recognize revenue as the underlying services are performed using a proportional performance model, over the period of service using input based measurements of total costs, including total full time equivalent effort incurred to date as a percentage of total costs expected, which best reflects the progress towards satisfaction of the performance obligation. The Company recorded deferred revenue of $0.8 million and $0.7 million for the years ended December 31, 2020 and 2019, respectively, related to its collaboration with DDF. Sanofi Collaboration Agreement (formerly Bioverativ) Summary of Agreement In August 2017, the Company entered into a Collaboration Agreement with Bioverativ Inc., which was acquired by Sanofi in March 2018 (“Sanofi”). Under the collaboration agreement with Sanofi (the “Sanofi Collaboration Agreement”), the Company provided research and development services focused on up to three collaboration programs; (i) Sickle cell disease, (ii) Hemophilia, and (iii) and had an option to a third program that expired unexercised. The Company used its bicyclic peptide screening platform to perform research and development services for the programs and Sanofi had the ability to select a collaboration product for each program and obtain a license to develop and exploit the selected collaboration product for an additional option fee. Sanofi could terminate the Sanofi Collaboration Agreement, entirely or on a program by program, licensed product by licensed product or country by country basis, for convenience upon not less than 30 days prior written notice to the Company. Accounting Analysis The Company identified four performance obligations associated with the Sanofi Collaboration Agreement, consisting of (i) Sickle Cell Research and Related Services, (ii) Hemophilia Research License and Related Services , (iii) a Sickle Cell License Option Material Right, and (iv) a Hemophilia License Option Material Right. The total transaction price consisted of a $10.0 million upfront payment and a non‑refundable research and development funding of $4.2 million. The transaction price was allocated to the performance obligations based on the relative estimated standalone selling prices of each performance obligation. The Company recognized revenue related to amounts allocated to the Sickle Cell and Hemophilia Research License and Related Services obligations as the underlying services were performed using a proportional performance model, over the period of service using input‑based measurements of total full‑time equivalent effort incurred to date as a percentage of total full‑time equivalent time expected, which best reflected the progress towards satisfaction of the performance obligation. The amount allocated to the material rights was recorded as deferred revenue, and the Company commenced revenue recognition when the underlying option was exercised or upon expiry of the option. On March 28, 2019, Sanofi notified the Company that it would not exercise the Sickle Cell License Option. In addition, the collaboration with Sanofi was terminated effective October 23, 2019. As a result, deferred revenue related to amounts allocated to the Sickle Cell License Option Material Right of $5.3 million and the Hemophilia License Option Material Right of $4.7 were recognized during the year ended December 31, 2019. For the years ended December 31, 2020, 2019 and 2018, the Company recognized zero, $10.7 million, and $4.0 million, respectively, of collaboration revenue related to its collaboration with Sanofi. As of December 31, 2020 and 2019, the Company recorded zero deferred revenue related to its collaboration with Sanofi. AstraZeneca Collaboration Agreement Summary of Agreement — 2016 Agreement In November 2016, the Company entered into a Research Collaboration Agreement (the “AstraZeneca Collaboration Agreement”) with AstraZeneca. The collaboration is focused on the research and development of Bicycle peptides that bind to up to six biological targets. After discovery and initial optimization of such Bicycle peptides, AstraZeneca will be responsible for all research and development, including lead optimization and drug candidate selection. AstraZeneca has option rights, at drug candidate selection, which allow it to obtain development and exploitation license rights with regard to such drug candidate. The initial research obligation focuses on two targets within respiratory, cardiovascular and metabolic disease. AstraZeneca also had an option to nominate up to four additional targets at any point up to the second anniversary of the agreement (“Additional Four Target Option”). Under the terms of the AstraZeneca Collaboration Agreement, the Company granted to AstraZeneca, for each research program, a right and license (with the right to sublicense) certain background and platform intellectual property, for the duration of the applicable Research Term, to the extent necessary or useful for AstraZeneca to conduct the activities assigned to it in the applicable research plan, but for no other purpose. AstraZeneca has the option to obtain development and commercialization licenses associated with each designated drug candidate in return for a fee of $8.0 million per drug candidate. In addition, AstraZeneca is required to make certain milestone payments to the Company upon the achievement of specified development, regulatory and commercial milestones. More specifically, for each research program, the Company is eligible to receive up to $29.0 million in development milestone payments and up to $23.0 million in regulatory milestone payments. The Company is also eligible for up to $110.0 million in commercial milestone payments, on a research program by research program basis. AstraZeneca may terminate the AstraZeneca Collaboration Agreement, entirely or on a licensed product by licensed product or country by country basis, for convenience. Accounting Analysis The Company has identified the following performance obligations at the inception of the arrangement: (i) research license and the related research and development services during the Bicycle Research Term for the first target (the “Target One Research License and Related Services”), (ii) research license and the related research and development services during the Bicycle Research Term for the second target (the “Target Two Research License and Related Services”). The Company concluded that the Additional Four Target Option was not a material right, as the option did not provide a discount that AstraZeneca otherwise would not have received. The Company’s participation in the joint steering committee was assessed as immaterial in the context of the contract. The Company concluded that the research license is not distinct from the research and development services during the Bicycle Research Term as AstraZeneca cannot obtain the benefit of the research license without the Company performing the research and development services. The services incorporate proprietary technology and unique skills and specialized expertise, particularly as it relates to constrained peptide technology that is not available in the marketplace. As a result, for each research program, the research license has been combined with the research and development services into a single performance obligation. The total transaction price was initially determined to be $1.2 million, and was raised to $2.0 million when both programs were extended, consisting solely of research and development funding. The Company utilizes the most likely amount method to determine the amount of research and development funding to be received. Additional consideration to be paid to the Company upon the exercise of the license options by AstraZeneca or upon reaching certain milestones is excluded from the transaction price as they relate to option fees and milestones that can only be achieved subsequent to the option exercise or are outside of the initial contact term. The transaction price was allocated to the performance obligations based on the relative estimated standalone selling prices of each performance obligation. The estimated standalone selling prices for the Target One and Target Two Research License and Related Services is primarily based on the nature of the services to be performed and estimates of the associated effort and costs of the services, adjusted for a reasonable profit margin what would be expected to be realized under similar contracts. The transaction price allocated to each performance obligation was initially $0.6 million. The Company recognized revenue related to amounts allocated to the Research License and Related Services as the underlying services were performed using a proportional performance model over the period of service using input‑based measurements of total full‑time equivalent effort incurred to date as a percentage of total full‑time equivalent time expected, which best reflects the progress towards satisfaction of the performance obligation. In October 2020, AstraZeneca terminated the collaboration activities related to the second target. No revenue was recognized upon termination. For the years ended December 31, 2020, 2019 and 2018 the Company recognized zero, $0.2 million, and $1.0 million, respectively, of collaboration revenue related to the Target One and Target Two Research License and Related Services for its Collaboration Agreement with AstraZeneca. As of December 31, 2020 and 2019, the Company recorded zero deferred revenue in connection with the 2016 AstraZeneca Collaboration Agreement. In March 2021, AstraZeneca terminated the collaboration activities related to the first target. May 2018 AstraZeneca Option Exercise — Additional Four Targets Under the AstraZeneca Collaboration Agreement, AstraZeneca was granted an option to nominate up to four additional targets at any point up to the second anniversary of the agreement (“Additional Four Target Option”). In May 2018, AstraZeneca made an irrevocable election to exercise the Additional Four Target Option. As a result, AstraZeneca is entitled to obtain research and development services with respect to Bicycle peptides that bind to up to four additional targets, along with license rights to those selected targets, in exchange for an option fee of $5.0 million. AstraZeneca is obligated to fund two FTEs during the Bicycle Research Term, for each research program, based on an agreed upon FTE reimbursement rate. Payment is made quarterly in advance of services being provided. AstraZeneca has the option to obtain worldwide development and commercialization licenses associated with each designated drug candidate in return for a fee of $8.0 million per drug candidate, upon the selection of such drug candidate, after which AstraZeneca would be required to fund development and commercialization costs, and to pay regulatory and commercial milestone payments and royalties to the Company as for the other products developed under the AstraZeneca Collaboration Agreement. Accounting Analysis Upon the execution of the agreement, the Company has identified the following five performance obligations associated with the AstraZeneca May 2018 Agreement: (i) Research license and the related research and development services during the Bicycle Research Term for the third target (the “Target Three Research License and Related Services”), (ii) Material right associated with the development and exploitation license option for the third target (“Target Three Material Right”), (iii) Material right associated with the research services option, including the underlying development and exploitation license option for the fourth target (“Target Four Material Right”), (iv) Material right associated with the research services option, including the underlying development and exploitation license option for the fifth target (“Target Five Material Right”), and (v) Material right associated with the research services option, including the underlying development and exploitation license option for the sixth target (“Target Six Material Right”). The Company concluded that the fourth, fifth and sixth targets available for selection are options. Upon exercise, AstraZeneca will obtain a research license and the related research and development services and an option to a development and exploitation license. The Company has concluded that the research services option, including the underlying development and exploitation license options related to each respective target results in a material right as the option exercise fee related to the development and exploitation license contains a discount that AstraZeneca would not have otherwise received. The research license and the related research and development services related to the fourth, fifth and sixth targets were not performance obligations at the inception of the arrangement, as they are optional services that will be performed if AstraZeneca selects additional targets and they reflect their standalone selling prices and do not provide the customer with material rights. The Company’s participation in the joint steering committee was assessed as immaterial in the context of the contract. The total transaction price was initially determined to be $5.7 million, consisting of the $5.0 million option exercise fee and research and development funding of an estimated $0.7 million. The research and development funding is being provided based on the costs that are incurred to conduct the research and development services. The Company utilizes the most likely amount method to determine the amount of research and development funding to be received. Additional consideration to be paid to the Company upon the exercise of the license options by AstraZeneca or upon reaching certain milestones are excluded from the transaction price as they relate to option fees and milestones that can only be achieved subsequent to the license option exercise or are outside of the initial contact term. The transaction price was allocated to the performance obligations based on the relative es

Income Taxes

Income Taxes	12 Months Ended
	Dec. 31, 2020
Income Taxes
Income Taxes	12. Income Taxes The components of net loss before tax provision from income taxes are as follows (in thousands): Year Ended December 31, 2020 2019 2018 United Kingdom $ (52,521) $ (31,906) $ (22,229) United States 787 1,044 (13) Total $ (51,734) $ (30,862) $ (22,242) The components of the benefit for income taxes are as follows (in thousands): Year Ended December 31, 2020 2019 2018 Current income tax provision (benefit) Federal $ (24) $ 49 $ (25) State (27) 61 7 Total current income tax provision (benefit) (51) 110 (18) Deferred income tax (benefit) provision Federal (435) (295) (167) State (238) (69) (211) Total deferred income tax (benefit) (673) (364) (378) Total benefit from income taxes $ (724) $ (254) $ (396) A reconciliation of the benefit for income taxes computed at the statutory income tax rate to the benefit for income taxes as reflected in the financial statement is as follows: Year Ended December 31, 2020 2019 2018 Benefit for income taxes at statutory rate 19 % 19 % 19 % (Decreases) increases resulting from: Federal tax credits 0.9 % 1.3 % 1.1 % Change in valuation allowance (15.4) % (8.0) % (7.2) % Net losses surrendered for research credit (6.2) % (5.3) % (3.7) % Preferred share warrants — % (3.3) % (0.6) % Impact of statutory rate change 1.8 % — % — % Other 1.3 % (2.9) % (6.8) % Effective income tax rate 1.4 % 0.8 % 1.8 % Significant components of the Company’s current and deferred tax assets at December 31, 2020 and 2019, were as follows (in thousands): Year Ended December 31, 2020 2019 Deferred tax assets: Operating loss carryforwards $ 13,657 $ 7,082 Research credit carryforwards 1,233 434 Operating lease liability 285 439 Accrued expenses and other 3,050 1,779 Total deferred tax assets 18,225 9,734 Deferred tax liabilities: Operating lease right-of-use asset (270) (422) Depreciation & amortization (311) (326) Total deferred tax liabilities (581) (748) Valuation allowance (16,085) (8,104) Net deferred tax assets $ 1,559 $ 882 During the years ended December 31, 2020, 2019 and 2018, the Company recorded an income tax benefit of $0.7 million, $0.3 million and $0.4 million, respectively. The Company is subject to United Kingdom corporate taxation. Due to the nature of its business, the Company has generated losses since inception and therefore not paid United Kingdom corporation tax. The Company's income tax benefit is mainly the result of deferred tax assets benefited in the United States that do not have a valuation allowance against them because of profits that will be generated by an intercompany service agreement. The Company regularly assesses its ability to realize its deferred tax assets. Assessing the realization of deferred tax assets requires significant judgment. In determining whether its deferred tax assets are more likely than not realizable, the Company evaluated all available positive and negative evidence, and weighed the evidence based on its objectivity. After consideration of the evidence, including the Company's history of cumulative net losses in the U.K., and has concluded that it is more likely than not that the Company will not realize the benefits of its U.K. deferred tax assets and accordingly the Company has provided a valuation allowance for the full amount of the net deferred tax assets in the U.K. The Company has considered the Company's history of cumulative net profits in the United states, estimated future taxable income and concluded that it is more likely than not that the Company will realize the benefits of its United State deferred tax assets and has not provided a valuation allowance against the net deferred tax assets in the United States. The valuation allowance increased in the year ended December 31, 2020 by $8.0 million due to the corresponding increase in UK deferred tax assets, primarily due to operating loss carryforwards generated during the year that were not surrendered for research credit utilization. The Company recorded a valuation allowance against all of its U.K. deferred tax assets as of December 31, 2020 and 2019. The Company intends to continue to maintain a full valuation allowance on its U.K. deferred tax assets until there is sufficient evidence to support the reversal of all or some portion of these allowances. The release of the valuation allowance would result in the recognition of certain deferred tax assets and an increase to the benefit for income taxes for the period the release is recorded. However, the exact timing and amount of the valuation allowance release are subject to change on the basis of the level of profitability that the Company is able to actually achieve. The benefit for income taxes shown on the consolidated statements of operations differs from amounts that would result from applying the statutory tax rates to income before taxes primarily because of certain permanent expenses that were not deductible, U.K., federal and state research and development credits, as well as the application of valuation allowances against the U.K. deferred tax assets. As of December 31, 2020, the Company had $72.0 million of U.K. operating loss carryforwards and $0 of U.S. federal and state net operating loss carryforwards. The U.K. operating loss carryforwards have an indefinite life. As of December 31, 2020, the Company had $0.8 million and $0.4 million of federal and state research and development credit carryforwards, respectively, that expire at various dates through 2040. The Company recognizes, in its consolidated financial statements, the effect of a tax position when it is more likely than not, based on the technical merits, that the position will be sustained upon examination. The Company had no uncertain tax positions during the years ended of December 31, 2020 and 2019. There are no amounts of interest or penalties recognized in the consolidated statements of operations or accrued on the consolidated balance sheet for any period presented. The Company does not expect any material changes in these uncertain tax benefits within the next 12 months. The Company files income tax returns in the United Kingdom, and in the United States for federal income taxes and in the Commonwealth of Massachusetts for state income taxes. In the normal course of business, the Company is subject to examination by tax authorities in these jurisdictions. The 2019 and 2018 tax year remains open to examination the by HM Revenue & Customs. The statute of limitations for assessment with the Internal Revenue Service is generally three years from filing the tax return. As such, all years since 2017 in the U.S. remain open to examination. The Company is currently not under examination by jurisdictions for any tax years.

Commitments and Contingencies

Commitments and Contingencies	12 Months Ended
	Dec. 31, 2020
Commitments and Contingencies
Commitments and Contingencies	13. Commitments and Contingencies Leases In September 2017, Bicycle Therapeutics Inc. entered into a lease agreement for office and laboratory space in Lexington, Massachusetts, which commenced on January 1, 2018 and expires on December 31, 2022. Bicycle Therapeutics Inc. has the option to extend for a successive period which is not included in the lease term as it is not reasonably certain that the option will be exercised. In conjunction with the lease agreement, Bicycle Therapeutics Inc. paid a security deposit of $0.2 million as well as prepaid rent of $0.1 million for the first month of the third, fourth, and fifth year of the lease. The deposit is recorded in other assets in the consolidated balance sheets. The Company has recorded a right‑of‑use asset (inclusive of the impact of prepaid rent) and corresponding lease liability, by calculating the present value of lease payments, discounted at 9%, the incremental borrowing rate, over the lease term. In October 2017, the Company entered into a lease agreement for office and laboratory space in Building 900, Babraham Research Campus, Cambridge, U.K., which expires on December 21, 2021. The annual rent is approximately $0.5 million. The Company has the right to renew the lease for five years commencing December 21, 2021, which is not included in the lease term as it is not reasonably certain that the right will be exercised. Service charges are also payable based on floor area and are estimated to be approximately $0.1 million per year. In conjunction with the 2017 lease agreement, the Company paid a security deposit of $0.6 million, which is recorded in other assets in the consolidated balance sheets. The Company has recorded a right‑of‑use asset and corresponding lease liability, by calculating the present value of lease payments, discounted at 7.75%, the incremental borrowing rate, over the lease term. The Company identified and assessed the following significant assumptions in recognizing the right‑of‑use assets and corresponding lease liabilities: · Expected lease term — The expected lease term includes both contractual lease periods and, when applicable, cancelable option periods when it is reasonably certain that the Company would exercise such options. The Company has not included any option periods in the expected lease term as it is not reasonably certain that the Company will exercise such options. · Incremental borrowing rate — The Company’s lease agreements do not provide an implicit rate. As the Company does not have any external borrowings for comparable terms of its leases, the Company estimated the incremental borrowing rate by comparing interest rates available in the market for similar borrowings and third‑party quotations. · Lease and non‑lease components — In certain cases, the Company is also responsible for certain additional charges for operating costs, including insurance, maintenance, taxes, and other costs incurred, which are billed based on both usage and as a percentage of the Company’s share of total square footage. The amounts paid are considered non‑lease components. The Company has elected the practical expedient which allows the non‑lease components to be combined with the lease components. The payments for other operating costs are considered variable lease cost and are recognized in the period in which the costs are incurred. The components of the Company’s lease expense, which are recorded as a component of research and development expenses and general and administrative expenses in the consolidated statement of operations and comprehensive loss are as follows (in thousands): December 31, December 31, 2020 2019 Operating lease cost $ 896 $ 900 Variable lease cost 662 390 Total lease cost $ 1,558 $ 1,290 Weighted‑average remaining operating lease term (years) 1.6 2.6 Weighted‑average discount rate 8.56 % 8.52 % Also, as previously disclosed in the Company's 2019 Annual Report on Form 10-K and under the previous lease accounting standard, ASC 840, Leases , the Company recorded rent expense of $1.0 million during the year ended December 31, 2018. Future minimum lease payments under non-cancelable operating leases under ASC 842 as of December 31, 2020 are as follows (in thousands): Year Ending December 31, 2021 908 2022 444 2023 — Present value adjustment (82) Total lease liabilities $ 1,270 Less: current lease liabilities (844) Long term lease liabilities $ 426 The Company has entered into various agreements with contract manufacturing organizations to provide clinical trial materials and with vendors for preclinical research studies, synthetic chemistry and other services for operating purposes. These payments are not included in the table of operating lease payments above since the contracts are generally cancelable at any time upon less than 90 days’ prior written notice. The Company is not contractually able to terminate for convenience and avoid any and all future obligations to these vendors. Under such agreements, the Company is contractually obligated to make certain minimum payments to the vendors, with the payments in the event of a termination with less than 90 days’ notice based on the timing of the termination and the exact terms of the agreement. Legal proceedings From time to time, the Company or its subsidiaries may become involved in various legal proceedings and claims, either asserted or unasserted, which arise in the ordinary course of business. In September 2016, the Company’s subsidiary, BicycleRD, filed a complaint in the District Court of the Hague against Pepscan Systems B.V. and its affiliates (“Pepscan”) to contest the right of Pepscan to terminate a non‑exclusive patent license agreement entered into with Pepscan in 2009 (“PLA”). On November 20, 2020, the Company entered into a settlement and license agreement with Pepscan regarding Bicycle’s use of Pepscan’s CLIPS peptide technology. The companies agreed to settle all intellectual property disputes worldwide. Under the terms of the settlement, Bicycle has been granted a license to use CLIPS peptide technology in the development of its product candidates BT1718 and THR-149. Bicycle paid €3 million in November 2020, will pay €1 million on the first anniversary of the date of settlement, and will make additional future milestone payments upon the achievement of development, regulatory and commercial milestones, with an aggregate total value of $92.4 million. The Company recorded $4.7 million of expense related to the settlement and license agreement with Pepscan during the year ended December 31, 2020, and a liability of $1.2 million related to the Pepscan litigation as of December 31, 2020, which is included in current liabilities in the consolidated balance sheet. Founder Royalty arrangements At the time BicycleRD Limited was organized, BicycleRD Limited entered into a royalty agreement with its founders and initial investors (the “Founder Royalty Agreement”). Pursuant to the Founder Royalty Agreement, as amended, the Company will pay a royalty rate in the low single digit percentages on net product sales under the collaborations with Oxurion and AstraZeneca to its founders and initial investors, for a period of 10 years from the first commercial sale on a country by country basis. No royalties have been earned or paid under the royalty arrangements to date. Indemnification obligations In the ordinary course of business, the Company may provide indemnification of varying scope and terms to vendors, lessors, business partners and other parties with respect to certain matters including, but not limited to, losses arising out of breach of such agreements or from intellectual property infringement claims made by third parties. In addition, the Company has indemnification obligations towards members of its board of directors and officers that will require the Company, among other things, to indemnify them against certain liabilities that may arise by reason of their status or service as directors or officers. The maximum potential amount of future payments the Company could be required to make under these indemnification arrangements is, in many cases, unlimited. To date, the Company has not incurred any material costs as a result of such indemnification obligations. The Company is not aware of any claims under indemnification arrangements, and therefore it has not accrued any liabilities related to such obligations in its consolidated financial statements as of December 31, 2020 and 2019.

Net loss per share

Net loss per share	12 Months Ended
	Dec. 31, 2020
Net loss per share
Net loss per share	14. Net loss per share Basic and diluted net loss per share attributable to ordinary shareholders was calculated as follows (in thousands, except share and per share amounts): Year Ended December 31, 2020 2019 2018 Numerator: Net loss attributable to ordinary shareholders $ (51,010) $ (30,608) $ (21,846) Denominator: Weighted average ordinary shares outstanding, basic and diluted 19,145,938 11,045,370 438,862 Net loss per share attributable to ordinary shareholders, basic and diluted $ (2.66) $ (2.77) $ (49.78) The Company’s potentially dilutive securities, which include share options, warrants to subscribe for ordinary shares, and which prior to the completion of the IPO, included convertible preferred shares, warrants to subscribe for Series A and Series B1 Preferred Shares, and unvested restricted shares, have been excluded from the computation of diluted net loss per share as the effect would be to reduce the net loss per share. Therefore, the weighted average number of ordinary shares outstanding used to calculate both basic and diluted net loss per share attributable to ordinary shareholders is the same. The Company excluded the following potentially dilutive ordinary shares, presented based on amounts outstanding at each period end, from the computation of diluted net loss per share attributable to ordinary shareholders for the periods indicated because including them would have had an anti‑dilutive effect: Year Ended December 31, 2020 2019 2018 Convertible preferred shares (as converted to ordinary shares) — — 11,532,659 Warrants to subscribe for ordinary shares (as adjusted to reflect the impact of the share capital reorganization and issuance of bonus shares (Note 7)) (1)(2) — 92,885 1,347,953 Restricted ordinary shares — — 83,947 Options to purchase ordinary shares 3,736,663 2,634,346 863,712 3,736,663 2,727,231 13,828,271 (1) On March 7, 2019, the holders of the Series B1 warrants to subscribe for Series B1 Preferred Shares agreed that 50% of the warrants would be exercised in conjunction with the IPO and 50% of the warrants would expire. (2) At December 31, 2019, 65,000 warrants exercisable into 92,885 ordinary shares were outstanding (Note 8).

Benefit plans

Benefit plans	12 Months Ended
	Dec. 31, 2020
Benefit plans
Benefit plans	15. Benefit plans The Company established a defined‑contribution savings plan under Section 401(k) of the Code (the “401(k) Plan”). The 401(k) Plan covers all U.S. employees and allows participants to defer a portion of their annual compensation on a pre‑tax basis. Matching contributions to the 401(k) Plan may be made at the discretion of the Company’s board of directors. During the years ended December 31, 2020, 2019, and 2018 the Company made contributions totaling $0.2 million, $0.2 million and $0.1 million, respectively, to the 401(k) Plan. The Company provides a pension contribution plan for its employees in the United Kingdom, pursuant to which the Company may make contributions each year (“U.K Plan”). During the years ended December 31, 2020, 2019 and 2018 the Company made contributions totaling $0.5 million, $0.3 million and $0.2 million, respectively, to the U.K. Plan.

Related party transactions

Related party transactions	12 Months Ended
	Dec. 31, 2020
Related party transactions
Related party transactions	16. Related party transactions The Company has entered into Founder Royalty Agreements with its founders and initial investors (Note 13). No royalties have been earned or paid under the Founder Royalty Agreements to date. The Chairman of the Company’s board of directors is associated with Stone Sunny Isles Inc., which provided consultancy services to the Company totaling $0.2 million and $0.1 million during each of the years ended December 31, 2020 and 2019, respectively. The former Chairman of the Company’s board of directors is associated with 10X Capital Inc., which provided consultancy services to the Company totaling $50,000, and $0.2 million during the years ended December 31, 2019 and 2018, respectively.

Geographic information

Geographic information	12 Months Ended
	Dec. 31, 2020
Geographic information
Geographic information	17. Geographic information The Company operates in two geographic regions: the United States and the United Kingdom. Information about the Company’s long‑lived assets held in different geographic regions is presented in the table below (in thousands): December 31, 2020 2019 United States $ 1,708 $ 2,017 United Kingdom 1,899 2,331 $ 3,607 $ 4,348 The Company’s collaboration revenues are attributed to the operations of the Company in the United Kingdom.

Selected Quarterly Financial Da

Selected Quarterly Financial Data (Unaudited)	12 Months Ended
	Dec. 31, 2020
Selected Quarterly Financial Data (Unaudited)
Selected Quarterly Financial Data (Unaudited)	18. Selected Quarterly Financial Data (Unaudited) The following tables contain selected quarterly financial information for 2020 and 2019. The Company believes the following information includes all recurring adjustments necessary for a fair statement of such information (in thousands, except share and per share data): Three Months Ended December 31, September 30, June 30, March 31, 2020 2020 2020 2020 Statements of Operations Data: Collaboration revenues $ 3,848 $ 3,842 $ 1,571 $ 1,129 Total operating expenses (1) 20,907 14,517 14,154 12,772 Total other income (expense), net (429) 72 371 212 Net loss before income tax provision (17,488) (10,603) (12,212) (11,431) Benefit from income taxes (55) (465) (97) (107) Net loss $ (17,433) $ (10,138) $ (12,115) $ (11,324) Net loss per share attributable to ordinary shareholders, basic and diluted $ (0.83) $ (0.52) $ (0.67) $ (0.63) Weighted average ordinary shares outstanding, basic and diluted 21,057,855 19,426,833 18,077,770 17,997,929 Three Months Ended December 31, September 30, June 30, March 31, 2019 2019 2019 2019 Statements of Operations Data: Collaboration revenues (2),(3) $ 5,281 $ 614 $ 1,522 $ 6,384 Total operating expenses 10,045 10,867 9,510 9,678 Total other income (expense), net 220 440 (2,094) (3,129) Net loss before income tax provision (4,544) (9,813) (10,082) (6,423) (Benefit from) provision for income taxes (138) (331) 135 80 Net loss $ (4,406) $ (9,482) $ (10,217) $ (6,503) Net loss per share attributable to ordinary shareholders, basic and diluted $ (0.25) $ (0.53) $ (1.40) $ (7.80) Weighted average ordinary shares outstanding, basic and diluted 17,926,165 17,900,978 7,298,139 834,043 (1) Operating expenses in the fourth quarter of 2020 include $4.7 million of expense related to the settlement and license agreement with Pepscan (Note 13). (2) Collaboration revenues in the fourth quarter of 2019 include $4.7 million recognized upon notification that the collaboration with Sanofi was terminated for amounts allocated to a material right when an option expired (Note 11). (3) Collaboration revenues in the first quarter of 2019 include $5.3 million recognized upon notification that Sanofi would not exercise the Sickle Cell License Option for amounts allocated to a material right when the option expired (Note 11).

Subsequent events

Subsequent events	12 Months Ended
	Dec. 31, 2020
Subsequent events
Subsequent events	19. Subsequent events In January and February 2021, the Company issued and sold 1,958,485 ADSs, representing the same number of ordinary shares, pursuant to its ATM program for gross proceeds of $50.2 million, resulting in net proceeds of $48.7 million after deducting sales commissions and offering expenses of $1.5 million. In March 2021, the Company achieved specified criteria in accordance with the research plan under the Genentech Collaboration agreement, for which Genentech owes the Company a $2.0 million payment. On March 10, 2021 or the Amendment Closing Date, the Borrowers entered into the First Amendment to the Loan and Security Agreement (the “First Amendment to LSA”), with Hercules, in its capacity as administrative agent and collateral agent, and the lenders named in the First Amendment to LSA. The First Amendment to LSA amended certain terms of the Company’s debt facility with Hercules. Pursuant to the First Amendment to LSA, payments on borrowings under the Company’s debt facility with Hercules will be interest-only until the first payment is due on August 1, 2023, which date was extended from November 1, 2022. If the Company achieves certain performance milestones, the interest-only period will be extended, with the first principal payment due on February 1, 2024, which date was extended from May 1, 2023. On the Amendment Closing Date and pursuant to the terms of the First Amendment to LSA, the Company borrowed the additional term loan of $15.0 million that had been available from September 30, 2020 to March 15, 2021.

Summary of Significant Accoun_2

Summary of Significant Accounting Policies (Policies)	12 Months Ended
	Dec. 31, 2020
Summary of Significant Accounting Policies
Use of estimates	Use of estimates The preparation of consolidated financial statements in conformity with GAAP requires management to make estimates and assumptions that affect the reported amounts of assets and liabilities, the disclosure of contingent assets and liabilities at the date of the consolidated financial statements and the reported amounts of expenses during the reporting periods. Significant estimates and assumptions reflected in these consolidated financial statements include, but are not limited to, the accrual for research and development expenses, revenue recognition, the fair value of ordinary shares and the valuation of the warrant liability prior to the Company’s IPO, share-based compensation expense, and income taxes. The Company bases its estimates on historical experience, known trends and other market‑specific or other relevant factors that it believes to be reasonable under the circumstances. Estimates are periodically reviewed in light of reasonable changes in circumstances, facts and experience. Changes in estimates are recorded in the period in which they become known. Actual results could differ from those estimates or assumptions.
Foreign currency and currency translation	Foreign currency and currency translation The functional currency is the currency of the primary economic environment in which an entity’s operations are conducted. On June 1, 2019, Bicycle Therapeutics plc adopted the U.S. dollar as its functional currency. Bicycle Therapeutics plc is a holding company that has no operating activities and its primary functions are to serve as a financing vehicle to fund the operations of the Company’s operating entities, to serve as the listing company needed to access U.S. capital markets, and to hold investments. Therefore, its financing source is the primary indicator of its cash flows and its functional currency. The change in functional currency from the British Pound Sterling is due to a change in the source of Bicycle Therapeutics plc’s financing and cash flows, which following the completion of the IPO is now primarily the U.S. Dollar (“USD”). Historically its financing had been in British Pound Sterling. The functional currency of Bicycle Therapeutics plc’s wholly owned non-U.S. subsidiaries, BicycleTx Limited and BicycleRD Limited, is the British Pound Sterling and the functional currency of its U.S. subsidiary, Bicycle Therapeutics Inc. is the USD. The functional currency of the Company’s subsidiaries is the same as the local currency. Monetary assets and liabilities denominated in currencies other than the functional currency are remeasured into the functional currency at rates of exchange prevailing at the balance sheet dates. Non‑monetary assets and liabilities denominated in foreign currencies are remeasured into the functional currency at the exchange rates prevailing at the date of the transaction. Exchange gains or losses arising from foreign currency transactions are included in the determination of net loss for the respective periods. Adjustments that arise from exchange rate changes on transactions denominated in a currency other than the local currency are included in general and administrative expense in the consolidated statements of operations and comprehensive loss as incurred. The Company recorded foreign exchange gains of $0.6 million, $0.9 million and $0.3 million for the years ended December 31, 2020, 2019 and 2018, respectively. The Company translates the assets and liabilities of BicycleTx Limited and BicycleRD Limited into USD at the exchange rate in effect on the balance sheet date. Revenues and expenses are translated at the average exchange rate in effect during the period. Unrealized translation gains and losses are recorded as a cumulative translation adjustment, which is included in the consolidated statements of convertible preferred shares and shareholders’ equity (deficit) as a component of accumulated other comprehensive loss.
Concentrations of credit risk and of significant suppliers	Concentrations of credit risk and of significant suppliers Financial instruments that potentially expose the Company to concentrations of credit risk consist primarily of cash and accounts receivable. The Company deposits its cash in financial institutions in amounts that may exceed federally insured limits and has not experienced any losses on such accounts. The Company does not believe it is exposed to any unusual credit risk beyond the normal credit risk associated with commercial banking relationships. Accounts receivable primarily consist of amounts due under the collaboration agreements between BicycleTx Limited and AstraZeneca AB (“AstraZeneca”), between BicycleRD Limited and Oxurion NV (formerly ThromboGenics NV) (“Oxurion”), and pursuant to an evaluation and option agreement with another third party (the “Evaluation and Option Agreement”) (Note 11), for which the Company does not obtain collateral. As of December 31, 2020, the Company’s revenue to date has primarily been generated from the collaboration agreements with Genentech, Inc. (“Genentech”), AstraZeneca, Sanofi (formerly Bioverativ), the Dementia Discovery Fund (“DDF”) and Oxurion. The Company relies, and expects to continue to rely, on a small number of vendors to manufacture supplies and raw materials for its development programs. These programs could be adversely affected by a significant interruption in these manufacturing services or the availability of raw materials.
Cash and cash equivalents	Cash and cash equivalents The Company considers all highly liquid investments with original maturities of three months or less at date of purchase to be cash equivalents. The Company had no cash equivalents at December 31, 2020 and 2019.
Accounts receivable	Accounts receivable The Company makes judgments as to its ability to collect outstanding receivables and provides an allowance for receivables when collection becomes doubtful. Provisions are made based upon a specific review of all significant outstanding invoices and the overall quality and age of those invoices. To date, the Company has not had any write‑offs of bad debt, and the Company did not have an allowance for doubtful accounts as of December 31, 2020 and 2019.
Deferred offering costs	Deferred offering costs The Company capitalizes certain legal, professional accounting and other third‑party fees that are directly associated with in‑process equity financings as deferred offering costs until such financings are consummated. After consummation of the equity financing, these costs are recorded in shareholders’ equity (deficit) as a reduction of proceeds generated as a result of the offering. Should an in‑process equity financing be abandoned, the deferred offering costs will be expensed immediately as a charge to operating expenses in the consolidated statements of operations and comprehensive loss.
Property and equipment	Property and equipment Property and equipment are stated at cost, less accumulated depreciation and amortization. Depreciation and amortization expense is recognized using the straight‑line method over the estimated useful lives of the respective assets as follows: Estimated Useful Life Laboratory equipment 3 to 5 years Leasehold improvements Lesser of lease term or useful life Computer equipment 3 years Furniture and office equipment 5 years Costs for capital assets not yet placed into service are capitalized as construction‑in‑progress and depreciated in accordance with the above guidelines once placed into service. Upon retirement or sale, the cost of assets disposed of and the related accumulated depreciation are removed from the accounts and any resulting gain or loss is included in loss from operations. As of December 31, 2020 and 2019, there have been no significant asset retirements to date. Expenditures for repairs and maintenance are charged to expense as incurred.
Impairment of long‑lived assets	Impairment of long‑lived assets Long‑lived assets to be held and used are tested for recoverability whenever events or changes in business circumstances indicate that the carrying amount of the assets may not be fully recoverable. Factors that the Company considers in deciding when to perform an impairment review include significant underperformance of the business in relation to expectations, significant negative industry or economic trends and significant changes or planned changes in the use of the assets. If an impairment review is performed to evaluate a long‑lived asset group for recoverability, the Company compares forecasts of undiscounted cash flows expected to result from the use and eventual disposition of the long‑lived asset group to its carrying value. An impairment loss would be recognized when estimated undiscounted future cash flows expected to result from the use of an asset group are less than its carrying amount. The impairment loss would be based on the excess of the carrying value of the impaired asset group over its fair value, determined based on discounted cash flows. To date, the Company has not recorded any impairment losses on long‑lived assets.
Fair value measurements	Fair value measurements Certain assets and liabilities of the Company are carried at fair value under GAAP. Fair value is defined as the exchange price that would be received for an asset or paid to transfer a liability (an exit price) in the principal or most advantageous market for the asset or liability in an orderly transaction between market participants on the measurement date. Valuation techniques used to measure fair value must maximize the use of observable inputs and minimize the use of unobservable inputs. Financial assets and liabilities carried at fair value are to be classified and disclosed in one of the following three levels of the fair value hierarchy, of which the first two are considered observable and the last is considered unobservable: · Level 1 — Quoted prices in active markets for identical assets or liabilities. · Level 2 — Observable inputs (other than Level 1 quoted prices), such as quoted prices in active markets for similar assets or liabilities, quoted prices in markets that are not active for identical or similar assets or liabilities, or other inputs that are observable or can be corroborated by observable market data. · Level 3 — Unobservable inputs that are supported by little or no market activity that are significant to determining the fair value of the assets or liabilities, including pricing models, discounted cash flow methodologies and similar techniques. Prior to the IPO, the Company’s warrant liability was carried at fair value, determined according to the fair value hierarchy described above (Note 3). The carrying values of accounts receivable, research and development incentives receivable, other current assets, accounts payable and accrued expenses and other current liabilities approximate their fair values due to the short‑term nature of these assets and liabilities. At December 31, 2020, the carrying value of the long-term debt approximates its fair value, which was determined using unobservable Level 3 inputs, including quoted interest rates from a lender for borrowings with similar terms.
Warrant liability	Warrant liability Prior to the IPO, the Company classified warrants to subscribe for Series A convertible preferred shares (“Series A Preferred Shares”) and Series B1 convertible preferred shares (“Series B1 Preferred Shares”) (Note 7) as a liability on its consolidated balance sheets as these warrants to subscribe for Series A Preferred Shares and Series B1 Preferred Shares were free‑standing financial instruments that might have required the Company to transfer assets upon exercise. The warrant liability was initially recorded at fair value upon the date of the warrants’ issuance and was subsequently remeasured to fair value at each reporting date. Changes in the fair value of the warrant liability were recognized as a component of other expense, net in the consolidated statements of operations and comprehensive loss. Upon the closing of the IPO, warrants to subscribe for Series A Preferred Shares and Series B1 Preferred Shares that were not exercised or expired in conjunction with the IPO automatically became warrants to subscribe for ordinary shares, and meet the criteria to be classified as shareholders’ equity (deficit). As such, following the final remeasurement on May 28, 2019, the Company reclassified the carrying value of the warrant liability to additional paid-in-capital in the consolidated balance sheet.
Segment and geographic information	Segment and geographic information Operating segments are defined as components of a business for which separate discrete financial information is available for evaluation by the chief operating decision maker in deciding how to allocate resources and assess performance. The Company and its chief operating decision maker, the Company’s Chief Executive Officer, view the Company’s operations and manages its business as a single operating segment, which is developing a unique class of chemically synthesized medicines based on its proprietary constrained peptides. The Company operates in two geographic regions: the United Kingdom and the United States.
Leases	Leases The Company adopted ASC Topic 842, Leases (ASC 842), using a modified retrospective approach, as of January 1, 2019, with no restatement of prior periods or cumulative adjustment to retained earnings. The Company determines if an arrangement is a lease at inception. Operating leases are included in operating lease right‑of‑use (“ROU”) assets, other current liabilities, and operating lease liabilities in the Company’s consolidated balance sheet. The Company has not entered into any financing leases. ROU assets represent the Company’s right to use and control an underlying asset for the lease term and lease liabilities represent the Company’s obligation to make lease payments arising from the lease. ROU assets and liabilities are recognized at commencement date based on the present value of lease payments over the lease term. As the Company’s leases do not provide an implicit rate, the Company uses its incremental borrowing rate based on the information available at commencement date in determining the present value of lease payments. The ROU asset also includes lease payments made before the lease commencement date and excludes any lease incentives. The Company’s lease terms may include options to extend or terminate the lease when it is reasonably certain that the Company will exercise that option. The components of a lease shall be split into three categories, if applicable: lease components (e.g., land, building, etc.), non‑lease components (e.g., common area maintenance, maintenance, consumables, etc.), and non‑components (e.g., property taxes, insurance, etc.). The fixed and in‑substance fixed contract consideration (including any related to non‑components) must then be allocated based on fair values to the lease components and non‑lease components. The Company’s facilities operating leases may have lease and non‑lease components to which the Company has elected to apply a practical expedient to account for each lease component and related non‑lease component as one single component. The lease component results in a right‑of‑use asset being recorded on the balance sheet. Lease expense for lease payments is recognized on a straight‑line basis over the lease term.
Revenue recognition	Revenue recognition The Company’s revenues are generated primarily through collaborative arrangements and license agreements with pharmaceutical companies. The terms of these arrangements may include (i) performing research and development services using the Company’s bicyclic peptide screening platform with the goal of identifying compounds for further development and commercialization, (ii) options to obtain additional research and development services or licenses for additional targets, or to optimize product candidates, upon the payment of option fees, or (iii) the transfer of intellectual property rights (licenses). The terms of these arrangements typically include payment to the Company of one or more of the following: non‑refundable, upfront license fees; payments for research and development services; fees upon the exercise of options to obtain additional services or licenses; payments based upon the achievement of defined collaboration objectives; future regulatory and sales‑based milestone payments; and royalties on net sales of future products. The Company recognizes revenue in accordance with ASU 2014‑09, Revenue from Contracts with Customers (Topic 606) (“ASC 606”) and all subsequent amendments. This standard applies to all contracts with customers, except for contracts that are within the scope of other standards, such as leases, insurance, collaboration arrangements and financial instruments. Under ASC 606, an entity recognizes revenue when its customer obtains control of promised goods or services, in an amount that reflects the consideration which the entity expects to receive in exchange for those goods or services. To determine revenue recognition for arrangements that the Company determines are within the scope of ASC 606, it performs the following five steps: (i) identify the contract(s) with a customer; (ii) identify the performance obligations in the contract; (iii) determine the transaction price; (iv) allocate the transaction price to the performance obligations in the contract; and (v) recognize revenue when, or as, the Company satisfies the performance obligations. The Company only applies the five‑step model to contracts when it is probable that the entity will collect substantially all of the consideration it is entitled to in exchange for the goods or services it transfers to the customer. As part of the accounting for these arrangements, the Company must make significant judgments, including identifying performance obligations in the contract, estimating the amount of variable consideration to include in the transaction price and allocating the transaction price to each performance obligation. Once a contract is determined to be within the scope of ASC 606, the Company assesses the goods or services promised within the contract and determines those that are performance obligations. Arrangements that include rights to additional goods or services that are exercisable at a customer’s discretion are generally considered options. The Company assesses if these options provide a material right to the customer and if so, they are considered performance obligations. Performance obligations are promised goods or services in a contract to transfer a distinct good or service to the customer. The promised goods or services in the Company’s contracts with customers primarily consist of license rights to the Company’s intellectual property for research and development, research and development services, options to acquire additional research and development services, and options to obtain additional licenses, such as a commercialization license for a potential product candidate. Promised goods or services are considered distinct when: (i) the customer can benefit from the good or service on its own or together with other readily available resources, and (ii) the promised good or service is separately identifiable from other promises in the contract. In assessing whether promised goods or services are distinct, the Company considers factors such as the stage of development of the underlying intellectual property, the capabilities of the customer to develop the intellectual property on their own and whether the required expertise is readily available. In addition, the Company considers whether the collaboration partner can benefit from a promise for its intended purpose without the receipt of the remaining promises, whether the value of the promise is dependent on the unsatisfied promises, whether there are other vendors that could provide the remaining promises, and whether it is separately identifiable from the remaining promises. The Company estimates the transaction price based on the amount of consideration the Company expects to receive for transferring the promised goods or services in the contract. The consideration may include both fixed consideration and variable consideration. At the inception of each arrangement that includes variable consideration, the Company evaluates the amount of the potential payments and the likelihood that the payments will be received. The Company utilizes either the most likely amount method or expected value method to estimate variable consideration to include in the transaction price based on which method better predicts the amount of consideration expected to be received. The amount included in the transaction price is constrained to the amount for which it is probable that a significant reversal of cumulative revenue recognized will not occur. At the end of each subsequent reporting period, the Company re‑evaluates the estimated variable consideration included in the transaction price and any related constraint, and if necessary, adjusts its estimate of the overall transaction price. Any such adjustments are recorded on a cumulative catch‑up basis in the period of adjustment. After the transaction price is determined it is allocated to the identified performance obligations based on the estimated standalone selling price. The Company must develop assumptions that require judgment to determine the standalone selling price for each performance obligation identified in the contract. The Company utilizes key assumptions to determine the standalone selling price, which may include other comparable transactions, pricing considered in negotiating the transaction, probabilities of technical and regulatory success and the estimated costs. Certain variable consideration is allocated specifically to one or more performance obligations in a contract when the terms of the variable consideration relate to the satisfaction of the performance obligation and the resulting amounts allocated to each performance obligation are consistent with the amounts the Company would expect to receive for each performance obligation. The Company then recognizes as revenue in the amount of the transaction price that is allocated to the respective performance obligation when (or as) each performance obligation is satisfied at a point in time or over time, and if over time based on the use of an input method. Licenses of intellectual property: If a license to the Company’s intellectual property is determined to be distinct from the other promises or performance obligations identified in the arrangement, the Company recognizes revenue from non‑refundable, upfront fees allocated to the license when the license is transferred to the customer and the customer is able to use and benefit from the license. For licenses that are combined with other promises, such as research and development services and a research license, the Company utilizes judgment to assess the nature of the combined performance obligation to determine whether the combined performance obligation is satisfied over time or at a point in time and, if over time, the appropriate method of measuring progress for purposes of recognizing revenue. The Company evaluates the measure of progress each reporting period and, if necessary, adjusts the measure of performance and related revenue recognition. The measure of progress, and thereby periods over which revenue should be recognized, are subject to estimates by management and may change over the course of the research and development and licensing agreement. Research and Development Services: The promises under the Company’s collaboration agreements may include research and development services to be performed by the Company on behalf of the partner. Payments or reimbursements resulting from the Company’s research and development efforts are recognized as the services are performed and presented on a gross basis because the Company is the principal for such efforts. Customer Options: The Company evaluates the customer options to obtain additional items (i.e. additional license rights) for material rights, or options to acquire additional goods or services for free or at a discount. Optional future services that reflect their standalone selling prices do not provide the customer with a material right and, therefore, are not considered performance obligations and are accounted for as separate contracts. If optional future services include a material right, they are accounted for as performance obligations. The Company determines an estimated standalone selling price of any material rights for the purpose of allocating the transaction price. The Company considers factors such as the identified discount and the probability that the customer will exercise the option. Amounts allocated to a material right are not recognized as revenue until, at the earliest, the option is exercised or expires. Milestone payments: The Company’s collaboration agreements may include development and regulatory milestones. The Company evaluates whether the milestones are considered probable of being reached and estimates the amount to be included in the transaction price using the most likely amount method. The Company evaluates factors such as the scientific, clinical, regulatory, commercial, and other risks that must be overcome to achieve the particular milestone in making this assessment. If it is probable that a significant revenue reversal would not occur, the associated milestone value is included in the transaction price. Milestone payments that are not within the Company’s control or the licensee’s control, such as regulatory approvals, are not considered probable of being achieved until those approvals are received. At the end of each reporting period, the Company re‑evaluates the probability of achievement of such milestones and any related constraint, and if necessary, adjusts the estimate of the overall transaction price. Any such adjustments are recorded on a cumulative catch‑up basis, which would affect collaboration revenue and net loss in the period of adjustment. Royalties: For sales‑based royalties, including milestone payments based on the level of sales, the Company determines whether the sole or predominant item to which the royalties relate is a license. When the license is the sole or predominant item to which the sales‑based royalty relates, the Company recognizes revenue at the later of: (i) when the related sales occur, or (ii) when the performance obligation to which some or all of the royalty has been allocated has been satisfied (or partially satisfied). To date, the Company has not recognized any sales‑based royalty revenue resulting from the Company’s collaboration agreements. The Company receives payments from customers based on billing schedules established in each contract. Up‑front payments and fees are recorded as deferred revenue upon receipt or when due until the Company performs its obligations under these arrangements. Amounts are recorded as accounts receivable when the Company’s right to consideration is unconditional, such as when the Company has a contractual right to payment per the terms of the contract. For a complete discussion of accounting for collaboration revenues, see Note 11, “Significant Agreements”
Government grants	Government grants From time to time, the Company may enter into arrangements with governmental entities for the purposes of obtaining funding for research and development activities. The Company recognizes government grant funding in the consolidated statements of operations and comprehensive loss as the related expenses being funded are incurred. The Company classifies government grants received under these arrangements as a reduction to the related research and development expense incurred. The Company analyzes each arrangement on a case‑by‑case basis. For the years ended December 31, 2020 and 2019, the Company recognized $0.7 million and $0.6 million, respectively, as a reduction of research and development expense related to government grant arrangements. There were no grant proceeds recognized for the year ended December 31, 2018.
Research and development costs	Research and development costs Research and development costs are expensed as incurred. Research and development expenses consist of costs incurred in performing research and development activities, including salaries, share‑based compensation and benefits, travel, facilities costs, materials and laboratory supplies, and external costs of outside vendors engaged to conduct preclinical development, clinical development activities, as well as to manufacture clinical trial materials. Facilities costs primarily include the allocation of rent, utilities, and depreciation. Non‑refundable prepayments for goods or services that will be used or rendered for future research and development activities are deferred and capitalized until the related goods are delivered or the related services are performed, or until it is no longer expected that the goods will be delivered, or the services rendered.
Research and manufacturing contract costs and accruals	Research and manufacturing contract costs and accruals The Company has entered into various research and development and manufacturing contracts, including contracts with respect to preclinical studies and clinical trials, with companies both inside and outside of the United States. These agreements are generally cancelable with 90 days or less notice, and related costs are recorded as research and development expenses as incurred. The Company records accruals for estimated ongoing costs. When evaluating the adequacy of the accrued liabilities, the Company analyzes progress of the research and development and manufacturing activities, including the phase or completion of events, invoices received and contracted costs. Significant judgments and estimates are made in determining the accrued balances at the end of any reporting period. Actual results could differ from the Company’s estimates. The Company’s historical accrual estimates have not been materially different from the actual costs.
Research and development incentives and receivable	Research and development incentives and receivable The Company, through its subsidiaries in the United Kingdom, receives reimbursements of certain research and development expenditures as part of a United Kingdom government’s research and development tax reliefs program. Under the program, the Company is able to surrender trading losses that arise from qualifying research and development expenses incurred by the Company’s subsidiaries in the United Kingdom for a tax credit of up to 14.5% of the surrenderable losses. Management has assessed the Company’s research and development activities and expenditures to determine which activities and expenditures are likely to be eligible under the research and development incentive program described above. At each period end, management estimates the reimbursement available to the Company based on available information at the time. The Company recognizes income from the research and development incentives when the relevant expenditure has been incurred, the associated conditions have been satisfied and there is reasonable assurance that the reimbursement will be received. The Company records these research and development incentives as a reduction to research and development expenses in the statements of operations and comprehensive loss, as the research and development tax credits are not dependent on us generating future taxable income, the Company’s ongoing tax status, or tax position. The research and development incentives receivable represent an amount due in connection with the above program. The Company recorded a reduction to research and development expense of $9.1 million, $6.7 million and $5.9 million during the years ended December 31, 2020, 2019 and 2018, respectively.
Patent costs	Patent costs All patent‑related costs incurred in connection with preparing, filing and prosecuting patent applications are expensed as incurred due to the uncertainty about the recovery of the expenditure. Amounts incurred are classified as general and administrative expenses in the consolidated statements of operations and comprehensive loss.
Share‑based compensation	Share‑based compensation The Company measures all equity awards granted to employees and directors based on the fair value on the date of grant. Compensation expense of those awards is recognized over the requisite service period, which is generally the vesting period of the respective award. The Company records the expense for awards with only service‑based vesting conditions using the straight‑line method. The Company accounts for forfeitures as they occur. The Company has granted awards with both a service condition that vest over time and a performance condition that will accelerate vesting upon the achievement of a specified collaboration revenue threshold. For equity awards that contain both performance and service conditions, the Company recognizes share‑based compensation expense using an accelerated attribution model over the requisite service period when the achievement of a performance‑based milestone is probable based on the relative satisfaction of the performance condition as of the reporting date. For share‑based awards granted to non‑employee consultants, the measurement date for non-employee awards is the date of grant. The compensation expense is then recognized over the requisite service period, which is the vesting period of the respective award, without subsequent changes in the fair value of the award. The fair value of each restricted ordinary share award is based on the fair value of the Company’s ordinary shares, less any applicable purchase price. The fair value of each share option is estimated using the Black‑Scholes option‑pricing model, which requires inputs based on certain subjective assumptions, including the fair value of ordinary shares, the expected share price volatility, the expected term of the award, the risk‑free interest rate, and expected dividends. Prior to the IPO, the Company utilized significant estimates and assumptions in determining the fair value of its common stock. Given the absence of an active market for the Company’s ordinary shares, the board of directors determined the estimated fair value of the Company’s equity instruments based on input from management which utilized the most recently available independent third‑party valuation, and considering a number of objective and subjective factors, including external market conditions affecting the biotechnology industry sector. The third party valuation reports performed utilized various valuation methodologies in accordance with the framework of the American Institute of Certified Public Accountants’ Technical Practice Aid, Valuation of Privately‑Held Company Equity Securities Issued as Compensation , to estimate the fair value of its ordinary shares. Each valuation methodology includes estimates and assumptions that require judgment. These estimates and assumptions include a number of objective and subjective factors in determining the value of the Company’s ordinary shares at each grant date, including the following: (1) prices paid for the Company’s convertible preferred shares, which the Company had sold to outside investors in arm’s‑length transactions, and the rights, preferences, and privileges of the Company’s convertible preferred shares and ordinary shares; (2) the Company’s stage of development; (3) the fact that the grants of share‑based awards involved illiquid securities in a private company; and (4) the likelihood of achieving a liquidity event for the ordinary shares underlying the share‑based awards, such as an IPO or sale of the Company, given prevailing market conditions. Expected volatility is calculated based on reported volatility data for a representative group of publicly traded companies for which historical information was available. The historical volatility is calculated based on a period of time commensurate with the assumption used for the expected term. The risk‑free interest rate is based on the U.S. Treasury yield curve in effect at the time of grant commensurate with the expected term assumption. The Company uses the simplified method, under which the expected term is presumed to be the midpoint between the vesting date and the end of the contractual term. The Company utilizes this method due to the lack of historical exercise data and the plain nature of its share‑based awards. The Company uses the remaining contractual term for the expected life of non‑employee awards. The expected dividend yield is assumed to be zero as the Company has never paid dividends and has no current plans to pay any dividends on ordinary shares. The Company classifies share‑based compensation expense in its consolidated statements of operations and comprehensive loss in the same manner in which the award recipient’s payroll costs are classified or in which the award recipient’s service payments are classified.
Comprehensive loss	Comprehensive loss Comprehensive loss includes net loss as well as other changes in shareholders’ equity (deficit) that result from transactions and economic events other than those with shareholders. The Company records unrealized gains and losses related to foreign currency translation as a component of other comprehensive loss in the consolidated statements of operations and comprehensive loss.
Contingencies	Contingencies Liabilities for loss contingencies arising from claims, assessments, litigation, fines, penalties and other sources are recorded when it is probable that a liability has been incurred and the amount can be reasonably estimated. At each reporting date, the Company evaluates whether or not a potential loss amount or a potential loss range is probable and reasonably estimable under the provisions of the authoritative guidelines that address accounting for contingencies. The Company expenses costs as incurred in relation to such legal proceedings as general and administrative expense within the consolidated statements of operations and comprehensive loss.
Income taxes	Income taxes The Company accounts for income taxes using the asset and liability method, which requires the recognition of deferred tax assets and liabilities for the expected future tax consequences of events that have been recognized in the consolidated financial statements or in the Company’s tax returns. Deferred tax assets and liabilities are determined on the basis of the differences between the consolidated financial statements and tax basis of assets and liabilities using enacted tax rates in effect for the year in which the differences are expected to reverse. Changes in deferred tax assets and liabilities are recorded in the provision for income taxes. The Company assesses the likelihood that its deferred tax assets will be recovered from future taxable income and, to the extent it believes, based upon the weight of available evidence, that it is more likely than not that all or a portion of the deferred tax assets will not be realized, a valuation allowance is established through a charge to income tax expense. Potential for recovery of deferred tax assets is evaluated by estimating the future taxable profits expected and considering prudent and feasible tax planning strategies. The Company accounts for uncertainty in income taxes recognized in the consolidated financial statements by applying a two‑step process to determine the amount of tax benefit to be recognized. First, the tax position must be evaluated to determine the likelihood that it will be sustained upon external examination by the taxing authorities. If the tax position is deemed more‑likely‑than‑not to be sustained, the tax position is then assessed to determine the amount of benefit to recognize in the consolidated financial statements. The amount of the benefit that may be recognized is the largest amount that will more likely than not be realized upon ultimate settlement. The provision for income taxes includes the effects of any resulting tax reserves, or unrecognized tax benefits, that are considered appropriate as well as the related net interest and penalties.
Net loss per share	Net loss per share The Company follows the two‑class method when computing net loss per share as the Company has issued shares that meet the definition of participating securities. The two‑class method determines net loss per share for each class of ordinary and preferred securities according to dividends declared or accumulated and participation rights in undistributed earnings. The two‑class method requires income available to ordinary shareholders for the period to be allocated between ordinary and preferred securities based upon their respective rights to receive dividends as if all income for the period had been distributed. Basic net loss per share attributable to ordinary shareholders is computed by dividing the net loss attributable to ordinary shareholders by the weighted average number of ordinary shares outstanding for the period. Diluted net loss attributable to ordinary shareholders is computed by adjusting net loss attributable to ordinary shareholders to reallocate undistributed earnings based on the potential impact of dilutive securities. Diluted net loss per share attributable to ordinary shareholders is computed by dividing the diluted net loss attributable to ordinary shareholders by the weighted average number of ordinary shares outstanding for the period, including potential dilutive ordinary shares assuming the dilutive effect of ordinary share equivalents. Prior to the Company’s IPO, convertible preferred shares contractually entitled the holders of such shares to participate in dividends but contractually do not require the holders of such shares to participate in losses of the Company. Accordingly, in periods in which the Company reported a net loss, such losses were not allocated to such preferred securities. In periods in which the Company reported a net loss attributable to ordinary shareholders, diluted net loss per share attributable to ordinary shareholders is the same as basic net loss per share attributable to ordinary shareholders, since dilutive ordinary shares are not assumed to have been issued if their effect is anti‑dilutive.
Recently adopted accounting pronouncements	Recently Issued Accounting Pronouncements In June 2016, the FASB issued ASU No. 2016-13, Measurement of Credit Losses on Financial Instruments (“ASU 2016-13”). ASU 2016-13 will change how companies account for credit losses for most financial assets and certain other instruments. For trade receivables, loans and held-to-maturity debt securities, companies will be required to recognize an allowance for credit losses rather than reducing the carrying value of the asset. In November 2019, the FASB issued ASU No. 2019-10, Financial Instruments — Credit Losses (Topic 326), Derivatives and Hedging (Topic 815), and Leases (Topic 842): Effective Dates to amend the effective date of ASU 2016-13, for entities eligible to be “smaller reporting companies,” as defined by the SEC, to be effective for fiscal years beginning after December 15, 2022, including interim periods within those fiscal years. Early adoption is permitted. The Company has not elected to early adopt ASU No. 2016-13. The Company is currently evaluating the potential impact that the adoption of ASU 2016-13 will have on the Company’s financial position and results of operations. In 2019, the FASB issued ASU No. 2019-12, Income Taxes (Topic 740): Simplifying the Accounting for Income Taxes (“ASU 2019-12”). ASU 2019-12 simplifies the accounting for income taxes and will be effective beginning after December 15, 2020. The Company is currently evaluating the impact of ASU 2019-12 in the consolidated financial statements.

Summary of Significant Accoun_3

Summary of Significant Accounting Policies (Tables)	12 Months Ended
	Dec. 31, 2020
Summary of Significant Accounting Policies
Schedule of estimated useful lives of property and equipment	Estimated Useful Life Laboratory equipment 3 to 5 years Leasehold improvements Lesser of lease term or useful life Computer equipment 3 years Furniture and office equipment 5 years

Property and equipment, net (Ta

Property and equipment, net (Tables)	12 Months Ended
	Dec. 31, 2020
Property and equipment, net
Schedule of property and equipment, net	Property and equipment, net consisted of the following (in thousands): December 31, 2020 2019 Laboratory equipment $ 5,583 $ 4,326 Leasehold improvements 383 300 Computer equipment and software 188 229 Furniture and office equipment 195 120 6,349 4,975 Less: Accumulated depreciation and amortization (4,032) (2,683) $ 2,317 $ 2,292

Accrued expenses and other cu_2

Accrued expenses and other current liabilities (Tables)	12 Months Ended
	Dec. 31, 2020
Accrued expenses and other current liabilities
Schedule of accrued expenses and other current liabilities	Accrued expenses and other current liabilities consisted of the following (in thousands): December 31, 2020 2019 Accrued employee compensation and benefits $ 4,390 $ 2,515 Accrued external research and development expenses 4,428 2,055 Accrued professional fees 1,759 867 Current portion of operating lease liabilities 844 640 Other 208 67 $ 11,629 $ 6,144

Long-term debt (Tables)

Long-term debt (Tables)	12 Months Ended
	Dec. 31, 2020
Long-term debt
Schedule of long term debt instruments	December 31, 2020 Term loan payable $ 15,000 End of term charge 58 Unamortized debt issuance costs (553) Carrying value of term loan $ 14,505
Schedule of maturities of long term debt	Future principal payments, including the End of Term Charge, are as follows (in thousands): Year Ending December 31, 2021 $ — 2022 1,148 2023 7,262 2024 7,340 Total $ 15,750

Share-based compensation (Table

Share-based compensation (Tables)	12 Months Ended
	Dec. 31, 2020
Share-based compensation
Schedule of share based compensation expense	The Company recorded share‑based compensation expense in the following expense categories of its consolidated statements of operations and comprehensive loss (in thousands): Year Ended December 31, 2020 2019 2018 Research and development expenses $ 2,603 $ 1,286 $ 513 General and administrative expenses 3,911 1,797 510 $ 6,514 $ 3,083 $ 1,023
Schedule of share option activity	Weighted Weighted Average Aggregate Number of Average Contractual Intrinsic Shares Exercise Price Term Value (in years) (in thousands) Outstanding as of December 31, 2019 2,634,346 $ 9.57 9.04 $ 6,107 Granted 1,370,984 12.00 — — Exercised (79,158) 3.42 — — Forfeited (189,509) 11.10 — — Outstanding as of December 31, 2020 3,736,663 $ 10.51 8.54 $ 27,553 Vested and expected to vest as of December 31, 2020 3,736,663 $ 10.51 8.54 $ 27,553 Options exercisable as of December 31, 2020 1,518,721 $ 8.81 7.90 $ 13,729
Schedule of assumptions used to determine the fair value of share options granted	The following table presents, on a weighted average basis, the assumptions used in the Black‑Scholes option‑pricing model to determine the fair value of share options granted to employees and directors: The following table presents, on a weighted average basis, the assumptions used in the Black‑Scholes option‑pricing model to determine the fair value of share options granted to employees and directors: Year Ended December 31, 2020 2019 2018 Risk-free interest rate 1.3 % 2.1 % 2.7 % Expected volatility 74.8 % 77.9 % 78.6 % Expected dividend yield — — — Expected term (in years) 5.98 5.86 6.07

Significant Agreements (Tables)

Significant Agreements (Tables)	12 Months Ended
	Dec. 31, 2020
Significant agreements.
Summary of revenue recognized from collaboration arrangements	The following table summarizes the revenue recognized in the Company’s consolidated statements of operations and comprehensive loss from these arrangements (in thousands): Year Ended December 31, 2020 2019 2018 Collaboration revenues AstraZeneca $ 2,696 $ 1,683 $ 1,386 Sanofi — 10,724 4,007 Oxurion 2,362 — 1,743 Dementia Discovery Fund 436 394 — Material transfer agreement — 1,000 — Genentech 4,896 — — Total collaboration revenues $ 10,390 $ 13,801 $ 7,136
Summary of changes in the balances of the Company’s contract assets and liabilities	Beginning Balance Impact of Ending Balance January 1, Exchange December 31, 2020 Additions Deductions Rates 2020 Contract assets $ — $ — $ — $ — $ — Contract liabilities: Deferred revenue AstraZeneca collaboration deferred revenue 4,913 585 (2,696) 954 3,756 DDF collaboration deferred revenue 744 500 (436) 13 821 Genentech collaboration deferred revenue — 31,000 (4,896) 1,475 27,579 Evaluation and Option Agreement deferred revenue — 3,000 — — 3,000 Total deferred revenue $ 5,657 $ 35,085 $ (8,028) $ 2,442 $ 35,156 Beginning Balance Impact of Ending Balance January 1, Exchange December 30, 2019 Additions Deductions Rates 2019 Contract assets $ — $ 149 $ (149) $ — $ — Contract liabilities: Deferred revenue AstraZeneca collaboration deferred revenue 4,727 58 (35) 163 4,913 Sanofi collaboration deferred revenue 9,908 — (9,984) 76 — DDF collaboration deferred revenue — 1,114 (394) 24 744 Total deferred revenue $ 14,635 $ 1,172 $ (10,413) $ 263 $ 5,657
Summary of recognition of revenues as a result of changes in contract asset and contract liability balances	During the years ended December 31, 2020, 2019 and 2018, the Company recognized the following revenues as a result of changes in the contract asset and the contract liability balances in the respective periods (in thousands): Year Ended December 31, 2020 2019 2018 Revenue recognized in the period from: Revenue recognized based on proportional performance $ (6,326) $ (429) $ (4,472) Revenue recognized based on expiration of material rights (1,702) (9,984) — Total $ (8,028) $ (10,413) $ (4,472)
AstraZeneca
Significant agreements.
Summary of allocation of transaction price to separate performance obligations	Based on the relative standalone selling price, the allocation of the transaction price to the separate performance obligations was as follows (in thousands): Allocation of Performance Obligations Transaction Price Target Three Research License and Related Services $ 650 Target 3 Material Right 1,504 Target 4 Material Right 1,204 Target 5 Material Right 1,165 Target 6 Material Right 1,127 $ 5,650
Genentech
Significant agreements.
Summary of allocation of transaction price to separate performance obligations	Based on the relative standalone selling price, the allocation of the transaction price to the separate performance obligations is as follows (in thousands): Allocation of Performance Obligations Transaction Price Genentech Collaboration Program #1 Performance Obligation $ 3,775 Genentech Collaboration Program #2 Performance Obligation 7,550 Specified Targeting Arm Material Right Arm for Genentech Collaboration Program #1 330 Two material rights associated with the LSR Go Option for Collaboration Programs #1 and #2 11,650 Material rights associated with limited substitution rights 1,115 Two material rights for Expansion Options 6,580 $ 31,000

Income Taxes (Tables)

Income Taxes (Tables)	12 Months Ended
	Dec. 31, 2020
Income Taxes
Schedule of components of net loss before tax provision from income taxes	The components of net loss before tax provision from income taxes are as follows (in thousands): Year Ended December 31, 2020 2019 2018 United Kingdom $ (52,521) $ (31,906) $ (22,229) United States 787 1,044 (13) Total $ (51,734) $ (30,862) $ (22,242)
Schedule of components of the benefit for income taxes	The components of the benefit for income taxes are as follows (in thousands): Year Ended December 31, 2020 2019 2018 Current income tax provision (benefit) Federal $ (24) $ 49 $ (25) State (27) 61 7 Total current income tax provision (benefit) (51) 110 (18) Deferred income tax (benefit) provision Federal (435) (295) (167) State (238) (69) (211) Total deferred income tax (benefit) (673) (364) (378) Total benefit from income taxes $ (724) $ (254) $ (396)
Schedule of reconciliation of the provision (benefit) for income taxes	Year Ended December 31, 2020 2019 2018 Benefit for income taxes at statutory rate 19 % 19 % 19 % (Decreases) increases resulting from: Federal tax credits 0.9 % 1.3 % 1.1 % Change in valuation allowance (15.4) % (8.0) % (7.2) % Net losses surrendered for research credit (6.2) % (5.3) % (3.7) % Preferred share warrants — % (3.3) % (0.6) % Impact of statutory rate change 1.8 % — % — % Other 1.3 % (2.9) % (6.8) % Effective income tax rate 1.4 % 0.8 % 1.8 %
Schedule of significant components of the Company’s current and deferred tax assets	Significant components of the Company’s current and deferred tax assets at December 31, 2020 and 2019, were as follows (in thousands): Year Ended December 31, 2020 2019 Deferred tax assets: Operating loss carryforwards $ 13,657 $ 7,082 Research credit carryforwards 1,233 434 Operating lease liability 285 439 Accrued expenses and other 3,050 1,779 Total deferred tax assets 18,225 9,734 Deferred tax liabilities: Operating lease right-of-use asset (270) (422) Depreciation & amortization (311) (326) Total deferred tax liabilities (581) (748) Valuation allowance (16,085) (8,104) Net deferred tax assets $ 1,559 $ 882

Commitments and Contingencies (

Commitments and Contingencies (Tables)	12 Months Ended
	Dec. 31, 2020
Commitments and Contingencies
Schedule of components of lease expense	The components of the Company’s lease expense, which are recorded as a component of research and development expenses and general and administrative expenses in the consolidated statement of operations and comprehensive loss are as follows (in thousands): December 31, December 31, 2020 2019 Operating lease cost $ 896 $ 900 Variable lease cost 662 390 Total lease cost $ 1,558 $ 1,290 Weighted‑average remaining operating lease term (years) 1.6 2.6 Weighted‑average discount rate 8.56 % 8.52 %
Schedule of maturities of operating leases	December 31, December 31, 2020 2019 Operating lease cost $ 896 $ 900 Variable lease cost 662 390 Total lease cost $ 1,558 $ 1,290 Weighted‑average remaining operating lease term (years) 1.6 2.6 Weighted‑average discount rate 8.56 % 8.52 % Also, as previously disclosed in the Company's 2019 Annual Report on Form 10-K and under the previous lease accounting standard, ASC 840, Leases , the Company recorded rent expense of $1.0 million during the year ended December 31, 2018. Future minimum lease payments under non-cancelable operating leases under ASC 842 as of December 31, 2020 are as follows (in thousands): Year Ending December 31, 2021 908 2022 444 2023 — Present value adjustment (82) Total lease liabilities $ 1,270 Less: current lease liabilities (844) Long term lease liabilities $ 426

Net loss per share (Tables)

Net loss per share (Tables)	12 Months Ended
	Dec. 31, 2020
Net loss per share
Schedule of basic and diluted net loss attributable to ordinary shareholders	Basic and diluted net loss per share attributable to ordinary shareholders was calculated as follows (in thousands, except share and per share amounts): Year Ended December 31, 2020 2019 2018 Numerator: Net loss attributable to ordinary shareholders $ (51,010) $ (30,608) $ (21,846) Denominator: Weighted average ordinary shares outstanding, basic and diluted 19,145,938 11,045,370 438,862 Net loss per share attributable to ordinary shareholders, basic and diluted $ (2.66) $ (2.77) $ (49.78)
Schedule of antidilutive securities excluded from computation of net loss per share attributable to ordinary shareholders	Year Ended December 31, 2020 2019 2018 Convertible preferred shares (as converted to ordinary shares) — — 11,532,659 Warrants to subscribe for ordinary shares (as adjusted to reflect the impact of the share capital reorganization and issuance of bonus shares (Note 7)) (1)(2) — 92,885 1,347,953 Restricted ordinary shares — — 83,947 Options to purchase ordinary shares 3,736,663 2,634,346 863,712 3,736,663 2,727,231 13,828,271 (1) On March 7, 2019, the holders of the Series B1 warrants to subscribe for Series B1 Preferred Shares agreed that 50% of the warrants would be exercised in conjunction with the IPO and 50% of the warrants would expire. (2) At December 31, 2019, 65,000 warrants exercisable into 92,885 ordinary shares were outstanding (Note 8).

Geographic information (Tables)

Geographic information (Tables)	12 Months Ended
	Dec. 31, 2020
Geographic information
Schedule of long-lived assets, including operating lease right-of-use assets, held in different geographic regions	Information about the Company’s long‑lived assets held in different geographic regions is presented in the table below (in thousands): December 31, 2020 2019 United States $ 1,708 $ 2,017 United Kingdom 1,899 2,331 $ 3,607 $ 4,348

Selected Quarterly Financial _2

Selected Quarterly Financial Data (Unaudited) (Tables)	12 Months Ended
	Dec. 31, 2020
Selected Quarterly Financial Data (Unaudited)
Schedule of selected quarterly financial information	18. Selected Quarterly Financial Data (Unaudited) The following tables contain selected quarterly financial information for 2020 and 2019. The Company believes the following information includes all recurring adjustments necessary for a fair statement of such information (in thousands, except share and per share data): Three Months Ended December 31, September 30, June 30, March 31, 2020 2020 2020 2020 Statements of Operations Data: Collaboration revenues $ 3,848 $ 3,842 $ 1,571 $ 1,129 Total operating expenses (1) 20,907 14,517 14,154 12,772 Total other income (expense), net (429) 72 371 212 Net loss before income tax provision (17,488) (10,603) (12,212) (11,431) Benefit from income taxes (55) (465) (97) (107) Net loss $ (17,433) $ (10,138) $ (12,115) $ (11,324) Net loss per share attributable to ordinary shareholders, basic and diluted $ (0.83) $ (0.52) $ (0.67) $ (0.63) Weighted average ordinary shares outstanding, basic and diluted 21,057,855 19,426,833 18,077,770 17,997,929 Three Months Ended December 31, September 30, June 30, March 31, 2019 2019 2019 2019 Statements of Operations Data: Collaboration revenues (2),(3) $ 5,281 $ 614 $ 1,522 $ 6,384 Total operating expenses 10,045 10,867 9,510 9,678 Total other income (expense), net 220 440 (2,094) (3,129) Net loss before income tax provision (4,544) (9,813) (10,082) (6,423) (Benefit from) provision for income taxes (138) (331) 135 80 Net loss $ (4,406) $ (9,482) $ (10,217) $ (6,503) Net loss per share attributable to ordinary shareholders, basic and diluted $ (0.25) $ (0.53) $ (1.40) $ (7.80) Weighted average ordinary shares outstanding, basic and diluted 17,926,165 17,900,978 7,298,139 834,043 (1) Operating expenses in the fourth quarter of 2020 include $4.7 million of expense related to the settlement and license agreement with Pepscan (Note 13). (2) Collaboration revenues in the fourth quarter of 2019 include $4.7 million recognized upon notification that the collaboration with Sanofi was terminated for amounts allocated to a material right when an option expired (Note 11). Collaboration revenues in the first quarter of 2019 include $5.3 million recognized upon notification that Sanofi would not exercise the Sickle Cell License Option for amounts allocated to a material right when the option expired (Note 11)

Nature of the business and ba_2

Nature of the business and basis of presentation - Initial public offering (Details) - USD ($) $ / shares in Units, $ in Thousands	May 28, 2019	Jun. 30, 2019	Dec. 31, 2020	Dec. 31, 2019	Dec. 31, 2018
Share capital reorganization and share split
Offering expenses			$ 1,900	$ 8,500	$ 327
Ordinary Shares
Share capital reorganization and share split
Shares issued (in shares)			2,928,813	4,637,666
IPO
Share capital reorganization and share split
Shares issued (in shares)	4,333,333
Share issue price	$ 14
Proceeds from IPO, net			$ 56,400
Underwriting discounts and commissions			4,500
Offering expenses			$ 4,000
Over allotment option
Share capital reorganization and share split
Shares issued (in shares)		304,333
Shares sold (in shares)		304,333
At the market offering
Share capital reorganization and share split
Shares issued (in shares)			2,928,813
Offering expenses			$ 1,900

Nature of the business and ba_3

Nature of the business and basis of presentation- Liquidity (Details) - USD ($) $ in Thousands	3 Months Ended								12 Months Ended
	Dec. 31, 2020	Sep. 30, 2020	Jun. 30, 2020	Mar. 31, 2020	Dec. 31, 2019	Sep. 30, 2019	Jun. 30, 2019	Mar. 31, 2019	Dec. 31, 2020	Dec. 31, 2019	Dec. 31, 2018
Offering expenses									$ 1,900	$ 8,500	$ 327
Net loss	$ 17,433	$ 10,138	$ 12,115	$ 11,324	$ 4,406	$ 9,482	$ 10,217	$ 6,503	51,010	30,608	$ 21,846
Accumulated deficit	$ 151,560				$ 100,550				$ 151,560	$ 100,550
At the market offering
Shares issued (in shares)									2,928,813
Gross proceeds before discounts and commissions									$ 50,000
Net proceeds									48,100
Offering expenses									$ 1,900
Loan and Security Agreement | Term Loan
Maximum borrowing		40,000
Loan and Security Agreement | Initial Term Loan
Term loan		15,000
Loan and Security Agreement | Additional Term Loan One
Term loan		15,000
Loan and Security Agreement | Additional Term Loan Two
Term loan		$ 10,000

Summary of significant accoun_4

Summary of significant accounting policies - Foreign currency and currency translation (Details) - USD ($) $ in Millions	12 Months Ended
	Dec. 31, 2020	Dec. 31, 2019	Dec. 31, 2018
Summary of Significant Accounting Policies
Foreign exchange gains	$ 0.6	$ 0.9	$ 0.3

Summary of Significant Accoun_5

Summary of Significant Accounting Policies - Cash and cash equivalents (Details) - USD ($)	Dec. 31, 2020	Dec. 31, 2019
Summary of Significant Accounting Policies
Cash and Cash Equivalents, at Carrying Value	$ 0	$ 0

Summary of Significant Accoun_6

Summary of Significant Accounting Policies - Property and equipment (Details)	12 Months Ended
	Dec. 31, 2020
Computer equipment and software
Property and equipment
Estimated Useful Life	3 years
Furniture and office equipment
Property and equipment
Estimated Useful Life	5 years
Minimum | Laboratory equipment
Property and equipment
Estimated Useful Life	3 years
Maximum | Laboratory equipment
Property and equipment
Estimated Useful Life	5 years

Summary of Significant Accoun_7

Summary of Significant Accounting Policies - Government grants (Details) - USD ($) $ in Millions	12 Months Ended
	Dec. 31, 2020	Dec. 31, 2019	Dec. 31, 2018
Summary of Significant Accounting Policies
Proceeds from government grants			$ 0
Reduction of research and development	$ 0.7	$ 0.6

Summary of Significant Accoun_8

Summary of Significant Accounting Policies - Research and development incentives and receivable (Details) - USD ($) $ in Millions	12 Months Ended
	Dec. 31, 2020	Dec. 31, 2019	Dec. 31, 2018
Research and development incentives and receivable
Maximum percentage of surrenderable losses	14.50%
Reduction of research and development	$ 9.1	$ 6.7	$ 5.9

Summary of Significant Accoun_9

Summary of Significant Accounting Policies - Share based compensation (Details)	12 Months Ended
	Dec. 31, 2020
Summary of Significant Accounting Policies
Expected dividend yield	0.00%

Fair value of financial asset_2

Fair value of financial assets and liabilities - Financial assets and liabilities measured at fair value (Details) - Recurring - USD ($) $ in Thousands	Dec. 31, 2020	Dec. 31, 2019
Fair value of financial assets and liabilities
Assets at fair value	$ 0	$ 0
Liabilities at fair value	$ 0	$ 0

Property and equipment, net (De

Property and equipment, net (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2020	Dec. 31, 2019	Dec. 31, 2018
Property and equipment, net
Property and equipment, gross	$ 6,349	$ 4,975
Less: Accumulated depreciation and amortization	(4,032)	(2,683)
Property and equipment, net	2,317	2,292
Depreciation expense	1,300	1,000	$ 700
Laboratory equipment
Property and equipment, net
Property and equipment, gross	5,583	4,326
Leasehold improvements
Property and equipment, net
Property and equipment, gross	383	300
Computer equipment and software
Property and equipment, net
Property and equipment, gross	188	229
Furniture and office equipment
Property and equipment, net
Property and equipment, gross	$ 195	$ 120

Accrued expenses and other cu_3

Accrued expenses and other current liabilities (Details) - USD ($) $ in Thousands	Dec. 31, 2020	Dec. 31, 2019
Accrued expenses and other current liabilities
Accrued employee compensation and benefits	$ 4,390	$ 2,515
Accrued external research and development expenses	4,428	2,055
Accrued professional fees	1,759	867
Current portion of operating lease liabilities	844	640
Other	208	67
Accrued expenses and other current liabilities	$ 11,629	$ 6,144

Long-term debt (Details)

Long-term debt (Details) - USD ($) $ in Millions	12 Months Ended
	Dec. 31, 2020	Sep. 30, 2020
Debt Instrument [Line Items]
Borrowing option to prepay subject to minimum debt outstanding	$ 5
End term charge rate	5.00%
Additional interest rate event of default	5.00%
Prepayment occurs in first year
Debt Instrument [Line Items]
Prepayment rate	2.00%
Prepayment occurs in second year
Debt Instrument [Line Items]
Prepayment rate	1.50%
Prepayment occurs after year two
Debt Instrument [Line Items]
Prepayment rate	1.00%
Prime Rate
Debt Instrument [Line Items]
Debt instrument stated percentage	8.85%
Basis spread variable rate	5.60%
Initial Term Loan
Debt Instrument [Line Items]
Fees and transaction costs	$ 0.6
Debt instrument effective percentage	12.20%
Interest expense	$ 0.4
Loan and Security Agreement | Term Loan
Debt Instrument [Line Items]
Maximum borrowing		$ 40
Loan and Security Agreement | Initial Term Loan
Debt Instrument [Line Items]
Term loan		15
Loan and Security Agreement | Additional Term Loan One
Debt Instrument [Line Items]
Term loan		15
Loan and Security Agreement | Additional Term Loan Two
Debt Instrument [Line Items]
Term loan		$ 10

Long-term debt - Debt (Details)

Long-term debt - Debt (Details) $ in Thousands	Dec. 31, 2020USD ($)
Long-term debt
Term loan payable	$ 15,000
End of term charge	58
Unamortized debt issuance costs	(553)
Carrying value of term loan	$ 14,505

Long-term debt - Future Princip

Long-term debt - Future Principal Payments (Details) $ in Thousands	Dec. 31, 2020USD ($)
Long-term debt
2022	$ 1,148
2023	7,262
2024	7,340
Total	$ 15,750

Long-term debt - Additional Inf

Long-term debt - Additional Information (Details) - USD ($) $ / shares in Units, $ in Thousands	Oct. 01, 2020	Dec. 31, 2020	Dec. 31, 2019
Shares issued		$ 48,144	$ 56,381
Hercules
Shares issued		$ 2,000
At the market offering
Shares issued (in shares)		2,928,813
Net proceeds		$ 48,100
At the market offering | Hercules | Sales Agreement
Shares issued (in shares)	98,100
Share issue price	$ 19.05
Net proceeds	$ 1,800

Convertible preferred shares (D

Convertible preferred shares (Details) $ / shares in Units, $ in Millions	May 28, 2019$ / sharesshares	Jan. 03, 2019USD ($)shares	Dec. 20, 2018USD ($)shares	May 31, 2019	Dec. 31, 2020shares	Dec. 31, 2019shares	Jan. 03, 2019£ / shares	Dec. 20, 2018£ / shares
Convertible preferred shares
Number of bonus shares for each ordinary share				1.429
IPO
Convertible preferred shares
Issuance of ADSs in initial public offering, net of underwriting discounts, commissions and offering expenses (in shares)	4,333,333
Share issue price | $ / shares	$ 14
Ordinary Shares
Convertible preferred shares
Issuance of ADSs in initial public offering, net of underwriting discounts, commissions and offering expenses (in shares)					2,928,813	4,637,666
Conversion of convertible preferred shares to ordinary shares (in shares)						11,647,529
Ordinary Shares | IPO
Convertible preferred shares
Conversion of convertible preferred shares to ordinary shares (in shares)	11,647,529
Conversion ratio	1.429
Series B2 Convertible Preferred Shares
Convertible preferred shares
Issuance of ADSs in initial public offering, net of underwriting discounts, commissions and offering expenses (in shares)		80,385	1,323,248
Share issue price | £ / shares							£ 15.55	£ 15.55
Gross proceeds from issues of shares | $		$ 1.6	$ 26.1

Warrant liability - Warrants in

Warrant liability - Warrants information (Details) $ in Thousands	May 28, 2019shares	Mar. 07, 2019	May 31, 2017£ / sharesshares	Dec. 31, 2019USD ($)	Dec. 31, 2018USD ($)	Dec. 31, 2017£ / sharesshares
Warrants information
Number of shares issued for warrant exercise						171,480
Remaining warrants exercisable						80,000
Number of shares into which remaining warrants is exercisable						114,320
Change in fair value of warrant liability recorded as other expense | $				$ 5,381	$ 665
Other expenses
Warrants information
Change in fair value of warrant liability recorded as other expense | $				$ 100
Series A Preferred Shares
Warrants information
Numbers of warrants issued			200,000
Exercise price of warrants | £ / shares			£ 0.01
Number of warrants exercised						120,000
Series B1 Preferred Shares
Warrants information
Numbers of warrants issued						743,287
Exercise price of warrants | £ / shares						£ 0.01
Number of shares issued for warrant exercise	531,077
Shares issued (in shares)						3,947,198
Percentage of warrants exercisable in conjunction with the IPO		50.00%
Percentage of warrants to expire in conjunction with the IPO		50.00%

Ordinary shares (Details)

Ordinary shares (Details)	12 Months Ended
	Dec. 31, 2020item£ / sharesshares	Dec. 31, 2019£ / sharesshares
Ordinary shares
Vote per ordinary share | item	1
Ordinary shares, shares authorized | shares	31,995,653	31,995,653
Ordinary shares, nominal value | £ / shares	£ 0.01	£ 0.01

Share-based compensation (Detai

Share-based compensation (Details)	Jan. 01, 2020shares	Jun. 30, 2020shares	May 31, 2019shares	Dec. 31, 2020$ / sharesshares	Dec. 31, 2018	Dec. 31, 2017	Jan. 01, 2021shares	Dec. 31, 2019$ / sharesshares	May 27, 2019£ / shares
Subsequent events
Share-based compensation.
Number of ordinary shares reserved for issuance							210,945
Stock option
Share-based compensation.
Shares outstanding		3,654,012		3,736,663				2,634,346
Exercise price | $ / shares				$ 10.51				$ 9.57
Employee Share Purchase Plan
Share-based compensation.
Percentage of annual increase in reserves on total number of ordinary shares outstanding			1.00%
Increase in number of ordinary shares reserved for issuance	394,937
Number of ordinary shares reserved for issuance			215,000
Number of shares available for issuance			430,000
Percentage of ordinary shares at a price per share equal to the fair market value on offering date or purchase date			85.00%
2020 Plan
Share-based compensation.
Number of shares reserved for issuance		4,773,557		4,699,470
Shares issued (in shares)		574,679
Shares outstanding				196,550
Percentage of annual increase in reserves on total number of ordinary shares outstanding		5.00%
2020 Plan | Stock option
Share-based compensation.
Contractual life		10 years
Increase in number of ordinary shares reserved for issuance				1,054,727
2020 Plan | Stock option | Non-employee Director
Share-based compensation.
Vesting period		3 years
2020 Plan | Stock option | First anniversary
Share-based compensation.
Vesting Percentage		25.00%
2020 Plan | Stock option | 36 equal monthly installments
Share-based compensation.
Number of equal monthly installments for vesting remaining awards		36 months
2020 Plan | Stock option | Employee
Share-based compensation.
Vesting period		4 years
2019 Plan
Share-based compensation.
Number of shares reserved for issuance		544,866
2019 Plan | Stock option
Share-based compensation.
Shares outstanding				2,594,277
Pre-IPO Share Options and restricted shares | Stock option
Share-based compensation.
Contractual life				10 years
Vesting period				4 years
Pre-IPO Share Options and restricted shares | Stock option | First anniversary
Share-based compensation.
Vesting Percentage				25.00%
Pre-IPO Share Options and restricted shares | Stock option | 36 equal monthly installments
Share-based compensation.
Number of equal monthly installments for vesting remaining awards				36 months
Pre-IPO Share Options and restricted shares | Stock option | United Kingdom
Share-based compensation.
Exercise price | £ / shares									£ 0.01
Pre-IPO Share Options and restricted shares | Performance based option | First anniversary
Share-based compensation.
Vesting Percentage					20.00%	20.00%
Pre-IPO Share Options and restricted shares | Performance based option | 36 equal monthly installments
Share-based compensation.
Vesting Percentage					60.00%	60.00%
Number of equal monthly installments for vesting remaining awards					36 months	36 months
Pre-IPO Share Options and restricted shares | Performance based option | Earlier of the fourth anniversary
Share-based compensation.
Vesting Percentage					20.00%	20.00%
Pre-IPO Share Options and restricted shares | Minimum | Stock option
Share-based compensation.
Vesting period				3 years
Pre-IPO Share Options and restricted shares | Maximum | Stock option
Share-based compensation.
Vesting period				4 years

Share-based compensation - Shar

Share-based compensation - Share based compensation expense (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2020	Dec. 31, 2019	Dec. 31, 2018
Share based compensation expense
Total share-based compensation expense	$ 6,514	$ 3,083	$ 1,023
Research and development expenses
Share based compensation expense
Total share-based compensation expense	2,603	1,286	513
General and administrative expenses
Share based compensation expense
Total share-based compensation expense	$ 3,911	$ 1,797	$ 510

Share-based compensation - Sh_2

Share-based compensation - Share options (Details) - USD ($)	1 Months Ended	12 Months Ended
	Jun. 30, 2020	Dec. 31, 2020	Dec. 31, 2019	Dec. 31, 2018
Additional Information
Total share-based compensation expense		$ 6,514,000	$ 3,083,000	$ 1,023,000
Ordinary Shares
Number of Shares
Exercised		(79,158)	(85,839)	(9,361)
Stock option
Number of Shares
Outstanding number of shares at beginning		2,634,346
Granted		1,370,984
Exercised		(79,158)
Forfeited		(189,509)
Outstanding number of shares at end	3,654,012	3,736,663	2,634,346
Number of shares, vested and expected to vest		3,736,663
Number of shares, options exercisable		1,518,721
Weighted Average Exercise Price
Weighted average exercise price at beginning		$ 9.57
Granted		12
Exercised		3.42
Forfeited		11.10
Weighted average exercise price at ending		10.51	$ 9.57
Weighted average exercise price, vested and expected to vest		10.51
Weighted average exercise price, options exercisable		$ 8.81
Weighted Average Contractual Term
Weighted average contractual term, outstanding		8 years 6 months 15 days	9 years 15 days
Weighted average contractual term, vested and expected to vest		8 years 6 months 15 days
Weighted average contractual term ,options exercisable		7 years 10 months 24 days
Aggregate Intrinsic Value
Aggregate intrinsic value outstanding		$ 27,553,000	$ 6,107,000
Granted		$ 7.87	$ 6.07	$ 3.73
Exercised		$ 1,300,000	$ 600,000	$ 23,000
Aggregate intrinsic value, vested and expected to vest		27,553,000
Aggregate intrinsic value, options exercisable		$ 13,729,000
Additional Information
Granted		$ 7.87	$ 6.07	$ 3.73
Total share-based compensation expense		$ 6,500,000	$ 2,700,000	$ 800,000
Exercised		1,300,000	600,000	$ 23,000
Performance based option
Number of Shares
Granted				70,875
Additional Information
Total share-based compensation expense		$ 100,000	$ 100,000	$ 700,000
Performance based option | Ordinary Shares | First anniversary
Additional Information
Vesting Percentage				20.00%
Performance based option | Ordinary Shares | 36 equal monthly installments
Additional Information
Vesting Percentage			60.00%
Number of equal monthly installments for vesting remaining awards				36 months
Performance based option | Ordinary Shares | Earlier of the fourth anniversary
Additional Information
Vesting Percentage				20.00%

Share-based compensation - Assu

Share-based compensation - Assumptions used in the Black Scholes option pricing model to determine the fair value of share options (Details) - USD ($) $ in Millions	12 Months Ended
	Dec. 31, 2020	Dec. 31, 2019	Dec. 31, 2018
Share-based compensation.
Expected dividend yield	0.00%
Stock option | Employees and directors
Share-based compensation.
Risk-free interest rate	1.30%	2.10%	2.70%
Expected volatility	74.80%	77.90%	78.60%
Expected term (in years)	5 years 11 months 23 days	5 years 10 months 10 days	6 years 26 days
Unrecognized compensation expense
Total unrecognized compensation expense related to the unvested employee and director	$ 13.7
Unrecognized compensation cost expected to be recognized over a weighted average period	2 years 6 months

Share-based compensation - Rest

Share-based compensation - Restricted shares (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2020	Dec. 31, 2019	Dec. 31, 2018
Restricted shares
Total share-based compensation expense	$ 6,514	$ 3,083	$ 1,023
Restricted ordinary shares
Restricted shares
Incremental share based compensation expense		200
Total share-based compensation expense	0	400	200
Restricted ordinary shares | Employees and directors
Restricted shares
Unrecognized compensation cost	$ 0
Restricted ordinary shares | Employee
Restricted shares
Fair value of employee restricted share awards vested		$ 700	$ 200

Significant agreements - Collab

Significant agreements - Collaboration revenues (Details) - USD ($) $ in Thousands	3 Months Ended								12 Months Ended
	Dec. 31, 2020	Sep. 30, 2020	Jun. 30, 2020	Mar. 31, 2020	Dec. 31, 2019	Sep. 30, 2019	Jun. 30, 2019	Mar. 31, 2019	Dec. 31, 2020	Dec. 31, 2019	Dec. 31, 2018
Significant agreements.
Collaboration revenues	$ 3,848	$ 3,842	$ 1,571	$ 1,129	$ 5,281	$ 614	$ 1,522	$ 6,384	$ 10,390	$ 13,801	$ 7,136
AstraZeneca
Significant agreements.
Collaboration revenues									2,696	1,683	1,386
Sanofi
Significant agreements.
Collaboration revenues									0	10,724	4,007
Oxurion
Significant agreements.
Collaboration revenues									2,362	0	$ 1,743
Dementia Discovery Fund
Significant agreements.
Collaboration revenues									436	394
Material transfer agreement
Significant agreements.
Collaboration revenues									0	$ 1,000
Genentech
Significant agreements.
Collaboration revenues									$ 4,896

Significant agreements - Genete

Significant agreements - Genetech Collaboration Agreement (Details) $ in Thousands

Feb. 21, 2021USD ($)item

Feb. 21, 2020USD ($)item

Dec. 31, 2020USD ($)

Sep. 30, 2020USD ($)

Jun. 30, 2020USD ($)

Mar. 31, 2020USD ($)

Dec. 31, 2019USD ($)

Sep. 30, 2019USD ($)

Jun. 30, 2019USD ($)

Mar. 31, 2019USD ($)

Dec. 31, 2020USD ($)

Dec. 31, 2019USD ($)

Dec. 31, 2018USD ($)

Mar. 31, 2021USD ($)

Significant agreements.

Collaboration revenues

$ 3,848

$ 3,842

$ 1,571

$ 1,129

$ 5,281

$ 614

$ 1,522

$ 6,384

$ 10,390

$ 13,801

$ 7,136

Deferred revenue

35,156

$ 5,657

$ 35,156

$ 5,657

$ 14,635

Genentech

Significant agreements.

Number of potential development candidates | item

4

Upfront cash payment

$ 30,000

$ 30,000

Number of immuno oncology targets | item

2

Additional number of immuno oncology targets | item

2

Expansion Fee

$ 10,000

Transaction price

31,000

Period over which performance obligations will be performed

2 years

Material rights exercise period

4 years

Collaboration revenues

$ 4,896

Deferred revenue

$ 27,579

$ 27,579

Genentech | Subsequent events

Significant agreements.

Sales milestone payments, receivable

$ 2,000

Genentech | Royalty

Significant agreements.

Number of years over which royalty is payable

10 years

Genentech | Maximum

Significant agreements.

Regulatory, and initial commercialization milestones, payments receivable

200,000

Genentech | Development milestone | Maximum

Significant agreements.

Sales milestone payments, receivable

65,000

Genentech | Regulatory milestone | Maximum

Significant agreements.

Sales milestone payments, receivable

135,000

Genentech | Collaboration Program 1 Performance Obligation

Significant agreements.

Transaction price

3,775

Genentech | Collaboration Program 2 Performance Obligation

Significant agreements.

Transaction price

$ 7,550

Genentech | Specified Targeting Arm Material Right Arm Program One

Significant agreements.

Number of initial collaboration programs exercised | item

1

Sales milestone payments, receivable

$ 1,000

Transaction price

$ 330

Genentech | Two material rights associated with the LSR Go Option for Collaboration Programs One And Two

Significant agreements.

Number of collaboration programs | item

2

Transaction price

$ 11,650

Genentech | Material rights for associated and limited substitution rights

Significant agreements.

Transaction price

$ 1,115

Genentech | Two material rights for Expansion Options

Significant agreements.

Number of expansion option collaboration programs | item

2

Transaction price

$ 6,580

Genentech | Collaboration Program One and Two Performance Obligation | Maximum

Significant agreements.

Sales milestone payments, receivable

$ 200,000

Significant agreements - Dement

Significant agreements - Dementia Discovery Fund Agreement (Details) - USD ($) $ in Thousands	1 Months Ended		3 Months Ended								12 Months Ended
	Dec. 31, 2020	May 31, 2019	Dec. 31, 2020	Sep. 30, 2020	Jun. 30, 2020	Mar. 31, 2020	Dec. 31, 2019	Sep. 30, 2019	Jun. 30, 2019	Mar. 31, 2019	Dec. 31, 2020	Dec. 31, 2019	Dec. 31, 2018
Significant agreements.
Collaboration revenues			$ 3,848	$ 3,842	$ 1,571	$ 1,129	$ 5,281	$ 614	$ 1,522	$ 6,384	$ 10,390	$ 13,801	$ 7,136
Deferred revenue	$ 35,156		35,156				5,657				35,156	5,657	$ 14,635
Dementia Discovery Fund
Significant agreements.
Upfront cash payment		$ 1,100
Potential milestone payments		$ 700
Threshold period for exercising option to establish a jointly-owned new company		90 days
Option to purchase ownership of new entity		34.00%
Threshold period of notice required for termination of agreement		60 days
Transaction price		$ 1,100
Collaboration revenues											436	394
Deferred revenue	821		$ 821				$ 744				$ 821	$ 744
Dementia Discovery Fund | NewCo
Significant agreements.
Option to purchase ownership of new entity		66.00%
Threshold period in which Newco shall have the right to initiate a new research program		2 years
Dementia Discovery Fund | NewCo | Maximum
Significant agreements.
Total voting rights related to ownership interests		50.00%
Specific scientific criteria milestone | Dementia Discovery Fund
Significant agreements.
Milestone payment received	$ 500

Significant agreements - Sanofi

Significant agreements - Sanofi Collaboration Agreement (Details) - USD ($) $ in Thousands	1 Months Ended	3 Months Ended								12 Months Ended
	Aug. 31, 2017	Dec. 31, 2020	Sep. 30, 2020	Jun. 30, 2020	Mar. 31, 2020	Dec. 31, 2019	Sep. 30, 2019	Jun. 30, 2019	Mar. 31, 2019	Dec. 31, 2020	Dec. 31, 2019	Dec. 31, 2018
Significant agreements.
Revenue recognized by non exercising of option										$ 1,702	$ 9,984
Revenue from collaborative arrangement		$ 3,848	$ 3,842	$ 1,571	$ 1,129	$ 5,281	$ 614	$ 1,522	$ 6,384	10,390	13,801	$ 7,136
Deferred revenue		35,156				5,657				35,156	5,657	14,635
Sanofi
Significant agreements.
Upfront cash payment	$ 10,000
Non refundable payment for services during the BV Bicycle Research Term	$ 4,200
Revenue from collaborative arrangement										0	10,724	4,007
Deferred revenue		$ 0				0				$ 0	0	$ 9,908
Sanofi | Sickle Cell Research License and Related Services
Significant agreements.
Revenue recognized by non exercising of option											5,300
Sanofi | Hemophilia Research License and Related Services
Significant agreements.
Revenue recognized by non exercising of option											$ 4,700
Sanofi | Sickle Cell License Option Material Right
Significant agreements.
Revenue recognized by non exercising of option									$ 5,300
Sanofi | Hemophilia License Option Material Right
Significant agreements.
Revenue recognized by non exercising of option						$ 4,700

Significant agreements - AstraZ

Significant agreements - AstraZeneca Collaboration Agreement (Details) $ in Thousands	May 31, 2019employee	May 31, 2018USD ($)	Nov. 30, 2016USD ($)item	Dec. 31, 2020USD ($)	Sep. 30, 2020USD ($)	Jun. 30, 2020USD ($)	Mar. 31, 2020USD ($)	Dec. 31, 2019USD ($)	Sep. 30, 2019USD ($)	Jun. 30, 2019USD ($)	Mar. 31, 2019USD ($)	Dec. 31, 2020USD ($)	Dec. 31, 2019USD ($)	Dec. 31, 2018USD ($)
Significant agreements.
Collaboration revenues				$ 3,848	$ 3,842	$ 1,571	$ 1,129	$ 5,281	$ 614	$ 1,522	$ 6,384	$ 10,390	$ 13,801	$ 7,136
Deferred revenue				35,156				5,657				35,156	5,657	14,635
AstraZeneca
Significant agreements.
Biological Targets | item			6
Transaction price		$ 5,700
Transaction price raised			$ 2,000
Collaboration revenues												2,696	1,683	1,386
Deferred revenue				3,756				4,913				3,756	4,913	4,727
AstraZeneca | Target One
Significant agreements.
Transaction price			600
AstraZeneca | Target Two
Significant agreements.
Transaction price			600
Collaboration revenues												0
AstraZeneca | Target Three Research License and Related Services
Significant agreements.
Collaboration revenues												2,700	1,500	400
AstraZeneca | Development Milestone
Significant agreements.
Transaction price		700
AstraZeneca | Development Milestone | Development milestone
Significant agreements.
Customer option payment			29,000
AstraZeneca | Regulatory Milestone | Regulatory milestone
Significant agreements.
Customer option payment			23,000
AstraZeneca | Commercial milestone | Commercial milestone
Significant agreements.
Customer option payment			$ 110,000
AstraZeneca | 2016 Collaboration Agreement
Significant agreements.
Biological Targets | item			2
Transaction price			$ 1,200
Deferred revenue				0				$ 0				0	0
AstraZeneca | 2016 Collaboration Agreement | Target One and Target Two Research License and Related Services
Significant agreements.
Collaboration revenues												0	$ 200	$ 1,000
AstraZeneca | 2016 Collaboration Agreement | Commercialization license per candidate
Significant agreements.
Customer option payment			$ 8,000
AstraZeneca | May 2018 Option Exercise
Significant agreements.
Biological Targets | item			4
Transaction price				5,650						$ 6,300		5,650
Option fee for development and exploitation rights		5,000
Number of FTE | employee	2
AstraZeneca | May 2018 Option Exercise | Target Three Research License and Related Services
Significant agreements.
Transaction price				650								650
AstraZeneca | May 2018 Option Exercise | Target 3 Material Right
Significant agreements.
Transaction price				1,504								1,504
Deferred revenue				1,500								1,500
AstraZeneca | May 2018 Option Exercise | Target 4 Material Right
Significant agreements.
Transaction price				1,204								1,204
AstraZeneca | May 2018 Option Exercise | Target 5 Material Right
Significant agreements.
Transaction price				1,165								1,165
AstraZeneca | May 2018 Option Exercise | Target 6 Material Right
Significant agreements.
Transaction price				$ 1,127								$ 1,127
AstraZeneca | May 2018 Option Exercise | Commercialization license per candidate
Significant agreements.
Customer option payment		$ 8,000

Significant agreements - Oxurio

Significant agreements - Oxurion Collaboration Agreement (Details) $ in Thousands, € in Millions

3 Months Ended

12 Months Ended

Dec. 31, 2020USD ($)

Sep. 30, 2020USD ($)

Jun. 30, 2020USD ($)

Mar. 31, 2020USD ($)

Dec. 31, 2019USD ($)

Sep. 30, 2019USD ($)

Jun. 30, 2019USD ($)

Mar. 31, 2019USD ($)

Dec. 31, 2020EUR (€)

Dec. 31, 2020USD ($)

Dec. 31, 2019USD ($)

Dec. 31, 2018USD ($)

Significant agreements.

Revenue from collaborative arrangement | $

$ 3,848

$ 3,842

$ 1,571

$ 1,129

$ 5,281

$ 614

$ 1,522

$ 6,384

$ 10,390

$ 13,801

$ 7,136

Oxurion

Significant agreements.

Threshold period of notice required for termination of agreement

90 days

90 days

Revenue recognized | $

$ 2,400

1,200

Revenue from collaborative arrangement | $

$ 2,362

$ 0

$ 1,743

Oxurion | Development milestone

Significant agreements.

Potential milestone payments

€ 8.3

Revenue under contracts with customer from milestone payment

1.8

Oxurion | Regulatory milestone

Significant agreements.

Potential milestone payments

16.5

Oxurion | Granting first regulatory approval or first indication

Significant agreements.

Potential milestone payments

€ 5

Significant agreements - Evalua

Significant agreements - Evaluation and Option Agreement (Details) - USD ($) $ in Thousands	Dec. 31, 2020	Dec. 31, 2020	Sep. 30, 2020	Jun. 30, 2020	Mar. 31, 2020	Dec. 31, 2019	Sep. 30, 2019	Jun. 30, 2019	Mar. 31, 2019	Dec. 31, 2020	Dec. 31, 2019	Dec. 31, 2018
Collaborative Arrangement and Arrangement Other than Collaborative [Line Items]
Collaboration revenues		$ 3,848	$ 3,842	$ 1,571	$ 1,129	$ 5,281	$ 614	$ 1,522	$ 6,384	$ 10,390	$ 13,801	$ 7,136
Deferred revenue	$ 35,156	35,156				$ 5,657				35,156	$ 5,657	$ 14,635
Evaluation and Option Agreement
Collaborative Arrangement and Arrangement Other than Collaborative [Line Items]
Term, Bicycle Research Team (in months)	4 months
Non refundable payment for services during the BV Bicycle Research Term	$ 3,000
Threshold period for receipt of revenue after receipt of the materials and related data package	5 days
Term extension (in years)	2 months
Extension fees receivable	$ 2,000	2,000								2,000
Threshold period of notice required for termination of agreement	30 days
Upfront cash payment	$ 3,000
Collaboration revenues										0
Deferred revenue	3,000	3,000								3,000
Transaction price	$ 3,000	$ 3,000								$ 3,000

Significant agreements - Materi

Significant agreements - Material Transfer Agreement (Details) - USD ($) $ in Thousands

1 Months Ended

3 Months Ended

12 Months Ended

Oct. 31, 2020

Dec. 31, 2020

Sep. 30, 2020

Jun. 30, 2020

Mar. 31, 2020

Dec. 31, 2019

Sep. 30, 2019

Jun. 30, 2019

Mar. 31, 2019

Dec. 31, 2020

Dec. 31, 2019

Dec. 31, 2018

Significant agreements.

Collaboration revenues

$ 3,848

$ 3,842

$ 1,571

$ 1,129

$ 5,281

$ 614

$ 1,522

$ 6,384

$ 10,390

$ 13,801

$ 7,136

Material transfer agreement

Significant agreements.

Upfront cash payment

$ 1,000

Threshold period for receipt of revenue after receipt of the materials and related data package

30 days

Collaboration revenues

$ 0

$ 1,000

Significant agreements - Summar

Significant agreements - Summary of Contract Assets and Liabilities (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2020	Dec. 31, 2019	Dec. 31, 2018
Contract assets
Additions		$ 149
Deductions		(149)
Contract liabilities:
Beginning Balance	$ 5,657	14,635
Additions	35,085	1,172
Deductions	(8,028)	(10,413)	$ (4,472)
Impact of Exchange Rates	2,442	263
Ending Balance	35,156	5,657	14,635
AstraZeneca
Contract liabilities:
Beginning Balance	4,913	4,727
Additions	585	58
Deductions	(2,696)	(35)
Impact of Exchange Rates	954	163
Ending Balance	3,756	4,913	4,727
Sanofi
Contract liabilities:
Beginning Balance	0	9,908
Deductions		(9,984)
Impact of Exchange Rates		76
Ending Balance	0	0	$ 9,908
Dementia Discovery Fund
Contract liabilities:
Beginning Balance	744
Additions	500	1,114
Deductions	(436)	(394)
Impact of Exchange Rates	13	24
Ending Balance	821	$ 744
Genentech
Contract liabilities:
Additions	31,000
Deductions	(4,896)
Impact of Exchange Rates	1,475
Ending Balance	27,579
Evaluation and Option Agreement
Contract liabilities:
Additions	3,000
Ending Balance	$ 3,000

Significant agreements - Deferr

Significant agreements - Deferred revenue (Details) - USD ($) $ in Thousands	Dec. 31, 2020	Dec. 31, 2019	Dec. 31, 2018
Deferred revenue
Deferred revenue	$ 35,156	$ 5,657	$ 14,635
AstraZeneca
Deferred revenue
Deferred revenue	3,756	$ 4,913	$ 4,727
AstraZeneca | Target 3, Target 4, Target 5 and Target 6 Material Rights
Deferred revenue
Deferred revenue	3,500
Material transfer agreement
Deferred revenue
Deferred revenue	$ 19,500

Significant agreements - Revenu

Significant agreements - Revenue recognition due to changes in contract assets and liabilities (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2020	Dec. 31, 2019	Dec. 31, 2018
Significant Agreements
Revenue recognized based on proportional performance	$ (6,326)	$ (429)	$ (4,472)
Revenue recognized based on expiration of material rights	(1,702)	(9,984)
Total	$ 8,028	$ 10,413	$ 4,472

Significant agreements - Cancer

Significant agreements - Cancer Research UK (Details) - USD ($) $ in Millions	Dec. 13, 2016	Dec. 31, 2019	Dec. 31, 2016	Dec. 31, 2020
Research and development arrangement obligation to repay other parties
Contingent future milestones payments under research and development arrangement	$ 50.9	$ 60.3
Other long term liabilities
Research and development arrangement obligation to repay other parties
Liability from research and development		$ 2		$ 2.6
Commercialization license per candidate
Research and development arrangement obligation to repay other parties
Refunding the costs and expenses incurred in case of termination (as a percent)	50.00%
BT1718 | Minimum
Research and development arrangement obligation to repay other parties
Tiered royalties (percentage)			70.00%
BT1718 | Maximum
Research and development arrangement obligation to repay other parties
Tiered royalties (percentage)			90.00%
BT7401 | Minimum
Research and development arrangement obligation to repay other parties
Tiered royalties (percentage)		55.00%
BT7401 | Maximum
Research and development arrangement obligation to repay other parties
Tiered royalties (percentage)		80.00%

Income Taxes (Details)

Income Taxes (Details) - USD ($) $ in Thousands	3 Months Ended								12 Months Ended
	Dec. 31, 2020	Sep. 30, 2020	Jun. 30, 2020	Mar. 31, 2020	Dec. 31, 2019	Sep. 30, 2019	Jun. 30, 2019	Mar. 31, 2019	Dec. 31, 2020	Dec. 31, 2019	Dec. 31, 2018
Income Taxes.
Benefit from income taxes	$ 55	$ 465	$ 97	$ 107	$ 138	$ 331	$ (135)	$ (80)	$ 724	$ 254	$ 396
Increases recorded to income tax provision									8,000
U.K. operating loss carryforwards	72,000								72,000
Federal and state net operating loss carryforwards	0								0
Research credit carryforwards	1,233				434				1,233	434
Uncertain tax positions	0				0				0	0	0
Interest and penalties accrued	0				$ 0				0	$ 0	$ 0
Federal
Income Taxes.
Research credit carryforwards	800								800
State
Income Taxes.
Research credit carryforwards	$ 400								$ 400

Income Taxes - Components of ne

Income Taxes - Components of net loss before tax provision from income taxes (Details) - USD ($) $ in Thousands	3 Months Ended								12 Months Ended
	Dec. 31, 2020	Sep. 30, 2020	Jun. 30, 2020	Mar. 31, 2020	Dec. 31, 2019	Sep. 30, 2019	Jun. 30, 2019	Mar. 31, 2019	Dec. 31, 2020	Dec. 31, 2019	Dec. 31, 2018
Income Taxes
United Kingdom									$ (52,521)	$ (31,906)	$ (22,229)
United States									787	1,044	(13)
Net loss before income tax provision	$ (17,488)	$ (10,603)	$ (12,212)	$ (11,431)	$ (4,544)	$ (9,813)	$ (10,082)	$ (6,423)	$ (51,734)	$ (30,862)	$ (22,242)

Income Taxes - Components of be

Income Taxes - Components of benefit for income taxes (Details) - USD ($) $ in Thousands	3 Months Ended								12 Months Ended
	Dec. 31, 2020	Sep. 30, 2020	Jun. 30, 2020	Mar. 31, 2020	Dec. 31, 2019	Sep. 30, 2019	Jun. 30, 2019	Mar. 31, 2019	Dec. 31, 2020	Dec. 31, 2019	Dec. 31, 2018
Current income tax provision (benefit)
Federal									$ (24)	$ 49	$ (25)
State									(27)	61	7
Total current income tax provision (benefit)									(51)	110	(18)
Deferred income tax (benefit) provision
Federal									(435)	(295)	(167)
State									(238)	(69)	(211)
Total deferred income tax (benefit)									(673)	(364)	(378)
Total benefit from income taxes	$ (55)	$ (465)	$ (97)	$ (107)	$ (138)	$ (331)	$ 135	$ 80	$ (724)	$ (254)	$ (396)

Income Taxes - Reconciliation o

Income Taxes - Reconciliation of provision (benefit) for income taxes (Details)	12 Months Ended
	Dec. 31, 2020	Dec. 31, 2019	Dec. 31, 2018
Income Taxes
Benefit for income taxes at statutory rate	19.00%	19.00%	19.00%
(Decreases) increases resulting from:
Federal tax credits	0.90%	1.30%	1.10%
Change in valuation allowance	(15.40%)	(8.00%)	(7.20%)
Net losses surrendered for research credit	(6.20%)	(5.30%)	(3.70%)
Preferred share warrants		(3.30%)	(0.60%)
Impact of statutory rate change	1.80%
Other	1.30%	(2.90%)	(6.80%)
Effective income tax rate	1.40%	0.80%	1.80%

Income Taxes - Components of th

Income Taxes - Components of the company’s current and deferred tax assets (Details) - USD ($) $ in Thousands	Dec. 31, 2020	Dec. 31, 2019
Deferred tax assets:
Operating loss carryforwards	$ 13,657	$ 7,082
Research credit carryforwards	1,233	434
Operating lease liability	285	439
Accrued expenses and other	3,050	1,779
Total deferred tax assets	18,225	9,734
Deferred tax liabilities:
Operating lease right-of-use asset	(270)	(422)
Depreciation & amortization	(311)	(326)
Total deferred tax liabilities	(581)	(748)
Valuation allowance	16,085	8,104
Net deferred tax assets	$ 1,559	$ 882

Commitments and Contingencies -

Commitments and Contingencies - Leases (Details) - Office and laboratory space in Lexington, Massachusetts $ in Millions	1 Months Ended
	Sep. 30, 2017USD ($)
Leases
Security deposit	$ 0.2
Payment under the lease	$ 0.1
Discounted percentage for present value of lease payments	9.00%

Commitments and Contingencies_2

Commitments and Contingencies - Leases, Office and laboratory space Cambridge (Details) - USD ($) $ in Millions	Dec. 31, 2018	Oct. 31, 2017
Leases
Annual rent	$ 1
Office and laboratory space in Building 900, Babraham Research Campus, Cambridge
Leases
Annual rent		$ 0.5
Renewal term		5 years
Estimated service charges payable		$ 0.1
Security deposit		$ 0.6
Discounted percentage for present value of lease payments		7.75%

Commitments and Contingencies_3

Commitments and Contingencies - Components of lease expense (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2020	Dec. 31, 2019
Commitments and Contingencies
Operating lease cost	$ 896	$ 900
Variable lease cost	662	390
Total lease cost	$ 1,558	$ 1,290
Weighted-average remaining operating lease term (years)	1 year 7 months 6 days	2 years 7 months 6 days
Weighted-average discount rate	8.56%	8.52%

Commitments and Contingencies_4

Commitments and Contingencies - Leases, Maturities of operating leases (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2020	Dec. 31, 2019
Commitments and Contingencies
2021	$ 908
2022	444
Present value adjustment	(82)
Total lease liabilities	1,270
Less: current lease liabilities	$ (844)	$ (640)
Operating Lease, Liability, Current, Statement of Financial Position [Extensible List]	Accrued Liabilities and Other Liabilities, Current	Accrued Liabilities and Other Liabilities, Current
Long term lease liabilities	$ 426	$ 1,251
Maximum days allowed for cancellation of contracts prior written notice	90 days

Commitments and Contingencies_5

Commitments and Contingencies - Legal proceedings (Details) - Settlement And License Agreement With Pepscan € in Millions, $ in Millions	1 Months Ended	3 Months Ended	12 Months Ended
	Nov. 30, 2020EUR (€)	Dec. 31, 2020USD ($)	Dec. 31, 2020USD ($)	Dec. 31, 2020EUR (€)	Dec. 31, 2020USD ($)
Collaborative Arrangement and Arrangement Other than Collaborative [Line Items]
Payments for Legal Settlements | €	€ 3
Settlement payable on first anniversary | €				€ 1
Milestone payments					$ 92.4
Litigation settlement amount		$ 4.7	$ 4.7
Litigation liability					$ 1

Commitments and Contingencies_6

Commitments and Contingencies - Founder Royalty arrangements (Details) - Founders and initial investors - Royalty Agreements $ in Millions	12 Months Ended
	Dec. 31, 2020USD ($)
Founder Royalty arrangements
Period of royalty payments agreed under arrangement	10 years
Royalties earned	$ 0
Royalties paid	$ 0

Net loss per share - Basic and

Net loss per share - Basic and diluted net loss per share (Details) - USD ($) $ / shares in Units, $ in Thousands	3 Months Ended								12 Months Ended
	Dec. 31, 2020	Sep. 30, 2020	Jun. 30, 2020	Mar. 31, 2020	Dec. 31, 2019	Sep. 30, 2019	Jun. 30, 2019	Mar. 31, 2019	Dec. 31, 2020	Dec. 31, 2019	Dec. 31, 2018
Numerator:
Net loss attributable to ordinary shareholders									$ (51,010)	$ (30,608)	$ (21,846)
Denominator:
Weighted average ordinary shares outstanding, basic and diluted	21,057,855	19,426,833	18,077,770	17,997,929	17,926,165	17,900,978	7,298,139	834,043	19,145,938	11,045,370	438,862
Net loss per share attributable to ordinary shareholders, basic and diluted	$ (0.83)	$ (0.52)	$ (0.67)	$ (0.63)	$ (0.25)	$ (0.53)	$ (1.40)	$ (7.80)	$ (2.66)	$ (2.77)	$ (49.78)

Net loss per share per share -

Net loss per share per share - Securities excluded from the diluted per share calculation (Details) - shares	Mar. 07, 2019	Dec. 31, 2020	Dec. 31, 2019	Dec. 31, 2018	Dec. 31, 2017
Antidilutive securities
Antidilutive securities (in shares)		3,736,663	2,727,231	13,828,271
Remaining warrants exercisable					80,000
Convertible preferred shares (as converted to ordinary shares)
Antidilutive securities
Antidilutive securities (in shares)				11,532,659
Warrants to subscribe for convertible preferred shares (as adjusted to reflect the impact of the share capital reorganization and issuance of bonus shares
Antidilutive securities
Antidilutive securities (in shares)			92,885	1,347,953
Percentage of warrants exercise in conjunction with IPO	50.00%
Percentage of warrants expire	50.00%
Remaining warrants exercisable			65,000
Restricted ordinary shares
Antidilutive securities
Antidilutive securities (in shares)				83,947
Options to purchase ordinary shares
Antidilutive securities
Antidilutive securities (in shares)		3,736,663	2,634,346	863,712
Number of ordinary shares for warrants exercise			92,885

Benefit plans (Details)

Benefit plans (Details) - USD ($) $ in Millions	12 Months Ended
	Dec. 31, 2020	Dec. 31, 2019	Dec. 31, 2018
United States | 401(k) Plan
Benefit plans
Contributions made	$ 0.2	$ 0.2	$ 0.1
Foreign Plan | U.K. Plan
Benefit plans
Contributions made	$ 0.5	$ 0.3	$ 0.2

Related party transactions (Det

Related party transactions (Details) - Chairman of Board of Directors - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2020	Dec. 31, 2019	Dec. 31, 2018
Consultancy services with Stone Sunny Isles Inc.
Related party transactions
Amount of transaction	$ 200	$ 100
Consultancy services with 10X Capital Inc.
Related party transactions
Amount of transaction		$ 50,000	$ 200

Geographic information (Details

Geographic information (Details) $ in Thousands	12 Months Ended
	Dec. 31, 2020USD ($)item	Dec. 31, 2019USD ($)
Geographic information
Number of geographic regions | item	2
Long lived assets, including operating lease right of use assets	$ 3,607	$ 4,348
United States
Geographic information
Long lived assets, including operating lease right of use assets	1,708	2,017
United Kingdom
Geographic information
Long lived assets, including operating lease right of use assets	$ 1,899	$ 2,331

Selected Quarterly Financial _3

Selected Quarterly Financial Data (Unaudited) (Details) - USD ($) $ / shares in Units, $ in Thousands	3 Months Ended								12 Months Ended
	Dec. 31, 2020	Sep. 30, 2020	Jun. 30, 2020	Mar. 31, 2020	Dec. 31, 2019	Sep. 30, 2019	Jun. 30, 2019	Mar. 31, 2019	Dec. 31, 2020	Dec. 31, 2019	Dec. 31, 2018
Selected Quarterly Financial Data (Unaudited)
Collaboration revenues	$ 3,848	$ 3,842	$ 1,571	$ 1,129	$ 5,281	$ 614	$ 1,522	$ 6,384	$ 10,390	$ 13,801	$ 7,136
Total operating expenses	20,907	14,517	14,154	12,772	10,045	10,867	9,510	9,678	62,350	40,100	28,882
Total other income (expense), net	(429)	72	371	212	220	440	(2,094)	(3,129)	226	(4,563)	(496)
Net loss before income tax provision	(17,488)	(10,603)	(12,212)	(11,431)	(4,544)	(9,813)	(10,082)	(6,423)	(51,734)	(30,862)	(22,242)
(Benefit from) provision for income taxes	(55)	(465)	(97)	(107)	(138)	(331)	135	80	(724)	(254)	(396)
Net loss	$ (17,433)	$ (10,138)	$ (12,115)	$ (11,324)	$ (4,406)	$ (9,482)	$ (10,217)	$ (6,503)	$ (51,010)	$ (30,608)	$ (21,846)
Net loss per share attributable to ordinary shareholders, basic and diluted	$ (0.83)	$ (0.52)	$ (0.67)	$ (0.63)	$ (0.25)	$ (0.53)	$ (1.40)	$ (7.80)	$ (2.66)	$ (2.77)	$ (49.78)
Weighted average ordinary shares outstanding, basic and diluted	21,057,855	19,426,833	18,077,770	17,997,929	17,926,165	17,900,978	7,298,139	834,043	19,145,938	11,045,370	438,862
Revenue recognized by non exercising of option									$ 1,702	$ 9,984
Sanofi
Selected Quarterly Financial Data (Unaudited)
Collaboration revenues									0	$ 10,724	$ 4,007
Sanofi | Sickle Cell License Option Material Right
Selected Quarterly Financial Data (Unaudited)
Revenue recognized by non exercising of option								$ 5,300
Sanofi | Hemophilia License Option Material Right
Selected Quarterly Financial Data (Unaudited)
Revenue recognized by non exercising of option					$ 4,700
Settlement And License Agreement With Pepscan
Selected Quarterly Financial Data (Unaudited)
Litigation settlement amount	$ 4,700								$ 4,700

Subsequent events (Details)

Subsequent events (Details) - USD ($) $ in Thousands	Oct. 01, 2020	Feb. 28, 2021	Dec. 31, 2020	Dec. 31, 2019	Dec. 31, 2018	Mar. 31, 2021	Mar. 10, 2021
Subsequent events
Offering expenses			$ 1,900	$ 8,500	$ 327
Subsequent events | Hercules | First Amendment To LSA
Subsequent events
Term loan							$ 15,000
Genentech | Subsequent events
Subsequent events
Sales milestone payments, receivable						$ 2,000
At the market offering
Subsequent events
Shares issued (in shares)			2,928,813
Gross proceeds before discounts and commissions			$ 50,000
Net proceeds			48,100
Offering expenses			$ 1,900
At the market offering | Sales Agreement | Hercules
Subsequent events
Shares issued (in shares)	98,100
Net proceeds	$ 1,800
At the market offering | Sales Agreement | Subsequent events
Subsequent events
Shares sold (in shares)		1,958,485
Gross proceeds before discounts and commissions		$ 50,200
Net proceeds		48,700
Offering expenses		$ 1,500