Table of Contents Securities registered pursuant to Section 12(b) of the Act: Title of each class Trading Symbol(s) Name of each exchange on which registered Ordinary shares, nominal value £0.01 per share* n/a The Nasdaq Stock Market LLC American Depositary Shares, each representing one ordinary share, nominal value £0.01 per share BCYC The Nasdaq Stock Market LLC UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, DC 20549 FORM 10-Q (Mark One) ☒ QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF ...

Table of Contents Title of each class Trading Symbol(s) Name of each exchange on which registered Ordinary shares, nominal value £0.01 per share * n/a The Nasdaq Stock Market LLC BCYC The Nasdaq Stock Market LLC UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, DC 20549 FORM 10-Q (Mark One) ☒ QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the quarterly period ended March 31, 2022 OR ☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES ...

BT8009 Clinical Trial - Key Findings - BT8009 shows promising clinical activity at a 5mg/m2 weekly dose, with potential for a differentiated product profile[20, 54] - At 5mg/m2 weekly, the Overall Response Rate (ORR) is 50% and the disease control rate is 75%, including a 13% complete response in urothelial cancer patients[20, 28, 42, 54] - Responses to BT8009 are durable, with tumor reductions maintained over time[20, 54] - The 7.5mg/m2 weekly dose was not tolerated due to GI and fatigue-related toxicities[20, 54] - BT8009 demonstrates linear pharmacokinetics and a short terminal half-life, as predicted from preclinical data[20, 54] Patient Demographics and Disease History - A total of 37 patients were enrolled in the BT8009 Phase I dose escalation trial[25, 27, 51] - The median age of patients in the trial is 66 years, ranging from 44 to 83 years[25] - 59% of patients are male, and 41% are female[25] - 41% of patients had an ECOG performance status of 0, while 59% had a status of 1[25] - Urothelial cancer represents 49% of the tumor types in the trial, followed by pancreatic cancer at 16%, and lung cancer at 14%[27, 52] Safety Profile - Common adverse events (≥15% incidence) include fatigue (40.5%), nausea (37.8%), diarrhea (32.4%), pyrexia (32.4%), anemia (32.4%), and decreased appetite (32.4%)[44] - Skin toxicity was observed in 19% of patients, with no Grade ≥3 severity[48] - Neuropathy was observed in 24% of patients, with 3% Grade ≥3 severity[48] - Ocular disorders were observed in 3% of patients, with no Grade ≥3 severity[48]

Company Overview - Bicycle Therapeutics is pioneering Bicycles, a novel class of innovative medicines[4] - The company has a cash balance of $438.7 million as of December 31, 2021, which is expected to fund operations into 2024[5,6] - The company has a strong intellectual property portfolio with 122 patent families as of December 31, 2021[5,9] - The company has approximately 119 employees located in Cambridge, UK and Lexington, MA[5] Technology Platform - Bicycles combine the advantages of both small molecules (1.5-2kDa) and antibodies (>150kDa) offering high specificity and complex protein target druggability[10,11] - The Bicycle platform delivers a toolkit of building blocks to create novel medicines, including Monomeric Bicycles, Targeted Drug Conjugates, and Tumor-Targeted immune cell agonists[12,15] - Bicycle Toxin Conjugates (BTCs) preclinical data indicates higher potency and specificity with fewer side effects than Antibody-Drug Conjugates (ADCs)[26] Clinical Programs - BT5528 (EphA2): Phase I dose escalation trial showed preliminary anti-tumor activity in ovarian cancer (1 PR out of 8 patients) and urothelial cancer (2 PRs out of 2 patients)[5,69,70,71] - BT8009 (Nectin-4): Phase I dose escalation trial showed preliminary responses in urothelial cancer patients, with 4 out of 11 patients achieving a partial response (PR)[5,88,91,101] - BT7480 (Nectin-4/CD137): A Bicycle TICA that entered Phase I clinical trials in Q4 2021[5,58,113]

PART I [Business](index=7&type=section&id=Item%201.%20Business) The company develops a novel class of medicines called Bicycles for oncology and other diseases through internal programs and strategic collaborations [Overview and Strategy](index=7&type=section&id=Overview%20and%20Strategy) The company's strategy centers on advancing its lead oncology candidates, expanding its pipeline, and leveraging its platform through strategic collaborations - The company's core technology is 'Bicycles,' a novel therapeutic modality of fully synthetic short peptides constrained to form two loops, which combines the pharmacology of a biologic with the manufacturing and pharmacokinetic properties of a small molecule[10](index=10&type=chunk) - Bicycle's proprietary phage display screening platform can screen quadrillions of potential molecules to identify candidates for its pipeline[11](index=11&type=chunk) - The company's strategy focuses on advancing its three most advanced clinical candidates: **BT5528** (EphA2-targeting BTC), **BT8009** (Nectin-4-targeting BTC), and **BT7480** (Nectin-4/CD137 TICA)[17](index=17&type=chunk) - Bicycle strategically collaborates with other biopharmaceutical companies to expand the application of its platform to disease areas beyond its internal oncology focus, including anti-infective, cardiovascular, ophthalmology, and CNS indications[21](index=21&type=chunk) [Product Pipeline and Technology Platform](index=10&type=section&id=Product%20Pipeline%20and%20Technology%20Platform) The oncology-focused pipeline includes Bicycle Toxin Conjugates (BTCs) and TICAs, with key assets in Phase I/II trials and partnered programs in other indications Key Pipeline Programs (as of Dec 31, 2021) | Program | Target Indication | Stage | Status | | :--- | :--- | :--- | :--- | | **Internal Programs** | | | | | BT5528 | High EphA2 expressing tumors (oncology) | Phase I/II | Ongoing company-sponsored clinical trial | | BT8009 | High Nectin-4 expressing tumors (oncology) | Phase I/II | Ongoing company-sponsored clinical trial | | BT7480 | Immuno-oncology (Nectin-4/CD137 TICA) | Phase I/II | Ongoing company-sponsored clinical trial | | BT7455 | Immuno-oncology (EphA2/CD137 TICA) | Preclinical | IND-enabling activities in process | | **Partnered Programs** | | | | | THR-149 | Ophthalmology (with Oxurion) | Phase II | Ongoing clinical trial | | BT1718 | High MT1-MMP expressing tumors (with CRUK) | Phase I/IIa | Ongoing clinical trial | | BT7401 | Immuno-oncology (multivalent CD137 agonist with CRUK) | Preclinical | CRUK to fund through Phase IIa | - BT5528 (EphA2 BTC): Interim Phase I results showed **preliminary anti-tumor activity** in urothelial and ovarian cancer and the company plans to initiate expansion cohorts at a Phase II dose of 6.5mg/m2 every other week[52](index=52&type=chunk)[53](index=53&type=chunk) - BT8009 (Nectin-4 BTC): Preliminary Phase I results showed **anti-tumor activity** in urothelial cancer patients, including a confirmed complete response, with dose escalation ongoing[57](index=57&type=chunk)[58](index=58&type=chunk) - BT7480 (Nectin-4/CD137 TICA): The first patient was dosed in a Phase I/II trial in November 2021 to evaluate BT7480 as a monotherapy and potentially in combination with nivolumab[75](index=75&type=chunk) [Collaborations](index=28&type=section&id=Collaborations) The company leverages strategic collaborations with partners like Ionis, Genentech, and CRUK to expand its platform's reach and generate revenue - **Ionis**: Entered a collaboration for TfR1 Bicycles for oligonucleotide delivery, receiving a **$31.0 million upfront payment** and an **$11.0 million equity investment**[87](index=87&type=chunk)[92](index=92&type=chunk)[94](index=94&type=chunk) - **Genentech**: A discovery collaboration for immuno-oncology targets includes a **$30.0 million upfront payment** and a **$10.0 million expansion fee**, with potential for over **$1.7 billion in milestones** per program[98](index=98&type=chunk)[99](index=99&type=chunk)[101](index=101&type=chunk) - **Cancer Research UK (CRUK)**: CRUK fully funds and sponsors the clinical trial of BT1718 and the development of BT7401 through Phase IIa[107](index=107&type=chunk)[112](index=112&type=chunk) - **AstraZeneca**: A collaboration focused on respiratory, cardiovascular, and metabolic diseases with two active programs and eligibility for up to **$170.0 million in milestones** per program[117](index=117&type=chunk)[120](index=120&type=chunk)[122](index=122&type=chunk) - **Oxurion**: A collaboration in ophthalmology for THR-149 makes Bicycle eligible for development, regulatory, and commercial milestones, plus tiered royalties[124](index=124&type=chunk) [Intellectual Property](index=40&type=section&id=Intellectual%20Property) The company protects its technology through a robust intellectual property portfolio of patents, trade secrets, and trademarks Patent Portfolio Overview (as of Dec 31, 2021) | Category | Number of Patent Families | | :--- | :--- | | Novel Scaffolds | 4 | | Platform Technology | 15 | | Bicyclic Peptides & Conjugates | 88 | | Methods of Making/Using Conjugates | 15 | - The company owned approximately **88 issued patents** in the U.S. and foreign jurisdictions, with expiration dates ranging from February 2029 to February 2039[135](index=135&type=chunk) - There were approximately **402 patent applications pending** globally, which, if issued, are expected to expire between February 2029 and December 2042[136](index=136&type=chunk) - The company relies on trade secrets to protect the know-how behind its Bicycle platform, using confidentiality agreements and security measures to safeguard this information[137](index=137&type=chunk) [Competition, Manufacturing, and Sales](index=44&type=section&id=Competition%2C%20Manufacturing%2C%20and%20Sales) The company faces intense competition, utilizes a fully outsourced manufacturing model, and currently lacks internal sales and marketing infrastructure - The company faces significant competition from major pharmaceutical and biotech companies, including **Seagen**, which has a marketed Nectin-4 antibody-drug conjugate[139](index=139&type=chunk) - Bicycle operates a **fully outsourced manufacturing model**, contracting with third-party GMP-licensed organizations for all clinical and non-clinical supplies[145](index=145&type=chunk) - The company currently has **no sales and marketing infrastructure** and intends to either build internal capabilities or collaborate with partners to commercialize its products[143](index=143&type=chunk) [Government Regulation](index=46&type=section&id=Government%20Regulation) Operations are subject to extensive government regulation in the U.S. and other jurisdictions, covering the entire product lifecycle from development to commercialization - The company is subject to extensive regulation by the **FDA** in the United States and comparable authorities in other jurisdictions[147](index=147&type=chunk) - The U.S. drug approval process requires submission of an Investigational New Drug (IND) application before clinical trials, followed by a New Drug Application (NDA)[149](index=149&type=chunk)[157](index=157&type=chunk) - The FDA provides expedited programs such as **Fast Track, Breakthrough Therapy, and Priority Review** for drugs addressing serious conditions with unmet medical needs[162](index=162&type=chunk)[163](index=163&type=chunk)[164](index=164&type=chunk) - **Brexit** has materially impacted the regulatory regime in the UK and EU, requiring separate marketing authorizations for Great Britain via the MHRA[232](index=232&type=chunk)[233](index=233&type=chunk) - Sales of approved products will depend on coverage and reimbursement from third-party payors, which are increasingly focused on **cost-containment**[203](index=203&type=chunk) [Human Capital and Corporate Information](index=79&type=section&id=Human%20Capital%20and%20Corporate%20Information) As of year-end 2021, the company had 119 employees and focused on talent retention, diversity, and inclusion - As of December 31, 2021, the company had **119 full-time or part-time employees**, with 88 engaged in R&D and 31 in general and administrative roles[239](index=239&type=chunk) - The company's human capital objectives include recruiting, retaining, and incentivizing employees, with a focus on diversity, equity, and inclusion (DEI), for which a task force was formed in 2021[240](index=240&type=chunk)[243](index=243&type=chunk) - The company was incorporated in England and Wales in 2009 and its principal executive offices are in Cambridge, UK[245](index=245&type=chunk) [Risk Factors](index=81&type=section&id=Item%201A.%20Risk%20Factors) The company faces substantial financial, clinical, regulatory, and operational risks due to its early-stage nature and reliance on a novel technology [Risks Related to Financial Position and Need for Additional Capital](index=85&type=section&id=Risks%20Related%20to%20Financial%20Position%20and%20Need%20for%20Additional%20Capital) The company has a history of significant operating losses, requires substantial additional funding, and faces risks related to its debt covenants - The company has a history of significant operating losses, with **net losses of $66.8 million in 2021** and an accumulated deficit of $218.4 million[254](index=254&type=chunk) - The company will need **substantial additional funding** to continue operations and may be forced to delay, reduce, or eliminate programs if capital cannot be raised[261](index=261&type=chunk)[262](index=262&type=chunk) - The company has a secured term loan facility with Hercules Capital with **$30.0 million outstanding**; failure to comply with covenants could result in default[270](index=270&type=chunk)[273](index=273&type=chunk) [Risks Related to Discovery, Development and Regulatory Approval](index=93&type=section&id=Risks%20Related%20to%20Discovery%2C%20Development%20and%20Regulatory%20Approval) Success depends on early-stage programs using a novel modality, which face high clinical failure rates, regulatory hurdles, and potential side effects - The company is **substantially dependent on the success of its early-stage BTC and TICA programs**, which may not successfully complete clinical trials[275](index=275&type=chunk) - Bicycles represent a new category of medicine and may be subject to **heightened regulatory scrutiny** due to limited regulatory experience with this modality[281](index=281&type=chunk)[282](index=282&type=chunk) - **Difficulties in enrolling patients** in clinical trials, potentially exacerbated by the COVID-19 pandemic, could delay or prevent program advancement[290](index=290&type=chunk)[294](index=294&type=chunk) - Product candidates may cause undesirable side effects; **Grade 3 or higher adverse events** have been observed in trials for BT5528 and BT8009[304](index=304&type=chunk)[305](index=305&type=chunk) - **Brexit** may adversely impact the ability to obtain regulatory approvals in the EU and UK, potentially increasing costs and causing delays[332](index=332&type=chunk)[336](index=336&type=chunk) [Risks Related to Commercialization and Other Regulatory Matters](index=116&type=section&id=Risks%20Related%20to%20Commercialization%20and%20Other%20Regulatory%20Matters) Commercialization risks include uncertain marketing approval, lack of sales infrastructure, competition, and challenges in pricing and reimbursement - The **marketing approval process is expensive, time-consuming, and uncertain**, with no guarantee of approval from the FDA or other authorities[339](index=339&type=chunk)[340](index=340&type=chunk) - The company has **no marketing, sales, or distribution infrastructure** and faces risks in building or outsourcing these capabilities[346](index=346&type=chunk)[347](index=347&type=chunk) - Failure to obtain or maintain **adequate insurance coverage and reimbursement** for products could limit market access and revenue[371](index=371&type=chunk) - The company is subject to federal and state **healthcare fraud and abuse laws**, which could result in substantial penalties if violated[385](index=385&type=chunk)[386](index=386&type=chunk) - Healthcare legislative reforms and increasing governmental scrutiny on **drug pricing** could negatively impact profitability[395](index=395&type=chunk)[404](index=404&type=chunk) [Risks Related to Third Parties, Business Operations, and Intellectual Property](index=141&type=section&id=Risks%20Related%20to%20Third%20Parties%2C%20Business%20Operations%2C%20and%20Intellectual%20Property) The business is exposed to risks from reliance on third parties, international operations, intellectual property protection, and cybersecurity threats - The company **depends on collaborators** like Cancer Research UK, AstraZeneca, and Ionis; failure by these partners to perform could harm future revenue[445](index=445&type=chunk)[446](index=446&type=chunk) - **Reliance on third-party CROs and manufacturers** increases the risk of delays, insufficient supply, and lack of direct control[455](index=455&type=chunk)[463](index=463&type=chunk) - The ability to **obtain and maintain patent protection is critical**; if patents are insufficient or challenged, competitors could commercialize similar products[477](index=477&type=chunk) - The company may be **sued for infringing third-party intellectual property rights**, which could be costly and delay commercialization[509](index=509&type=chunk) - The ongoing **COVID-19 pandemic** could adversely affect business operations, including clinical trials, manufacturing, and access to capital[418](index=418&type=chunk) - **Cyber-attacks or IT system failures** could result in information theft and significant business disruption[529](index=529&type=chunk) [Unresolved Staff Comments](index=197&type=section&id=Item%201B.%20Unresolved%20Staff%20Comments) Not applicable - The company reports no unresolved staff comments[587](index=587&type=chunk) [Properties](index=197&type=section&id=Item%202.%20Properties) The company leases office and laboratory space in Cambridge, UK, and Lexington, Massachusetts - The company leases approximately **58,500 square feet** of office and laboratory space in Cambridge, United Kingdom, under two separate leases[587](index=587&type=chunk) - The company leases an additional **11,000 square feet** of office and laboratory space in Lexington, Massachusetts[587](index=587&type=chunk) [Legal Proceedings](index=197&type=section&id=Item%203.%20Legal%20Proceedings) The company is involved in European patent opposition proceedings and a UK trademark opposition - The company and Oxurion NV are involved in European patent opposition proceedings against Dyax Corp's patents; one patent was revoked, and an appeal hearing for another is scheduled for November 15, 2022[589](index=589&type=chunk)[590](index=590&type=chunk) - The company's UK trademark application for "TICA" was successfully opposed by Immatics Biotechnologies GmbH, preventing its use for most pharmaceutical products in the UK[591](index=591&type=chunk) [Mine Safety Disclosures](index=199&type=section&id=Item%204.%20Mine%20Safety%20Disclosures) Not applicable - The company reports no mine safety disclosures[593](index=593&type=chunk) PART II [Market for Registrant's Common Equity, Related Stockholder Matters and Issuer Purchases of Equity Securities](index=199&type=section&id=Item%205.%20Market%20for%20Registrant's%20Common%20Equity%2C%20Related%20Stockholder%20Matters%20and%20Issuer%20Purchases%20of%20Equity%20Securities) The company's ADSs trade on Nasdaq, and it has not recently sold unregistered securities or repurchased its equity - The company's American Depositary Shares (ADSs) trade on The Nasdaq Global Select Market under the symbol **"BCYC"**[595](index=595&type=chunk) - As of February 24, 2022, there were approximately **63 holders of record** of the company's ordinary shares[596](index=596&type=chunk) [Management's Discussion and Analysis of Financial Condition and Results of Operations](index=200&type=section&id=Item%207.%20Management's%20Discussion%20and%20Analysis%20of%20Financial%20Condition%20and%20Results%20of%20Operations) The company's 2021 net loss increased to $66.8 million due to higher operating expenses, though its cash position was significantly strengthened by financing activities [Results of Operations](index=213&type=section&id=Results%20of%20Operations) The 2021 net loss widened to $66.8 million as increased R&D and G&A expenses outpaced a slight rise in collaboration revenue Consolidated Statements of Operations (in thousands) | | Year Ended December 31, 2021 | Year Ended December 31, 2020 | | :--- | :--- | :--- | | Collaboration revenues | $11,697 | $10,390 | | Research and development | $44,880 | $33,149 | | General and administrative | $32,435 | $29,201 | | **Total operating expenses** | **$77,315** | **$62,350** | | Loss from operations | ($65,618) | ($51,960) | | **Net loss** | **($66,819)** | **($51,010)** | Research and Development Expenses Breakdown (in thousands) | Expense Category | 2021 | 2020 | | :--- | :--- | :--- | | BT8009 (Nectin-4) | $7,656 | $5,037 | | Bicycle TICA programs | $6,008 | $4,208 | | Other discovery and platform | $15,519 | $10,480 | | Employee and contractor related | $17,133 | $11,927 | | Share-based compensation | $4,974 | $2,603 | | Research and development incentives | ($13,993) | ($9,126) | | **Total R&D Expenses** | **$44,880** | **$33,149** | - Collaboration revenues increased by **$1.3 million** year-over-year, primarily due to revenue from the new Ionis collaboration ($4.2 million) and the Genentech collaboration ($0.8 million increase)[643](index=643&type=chunk) - General and administrative expenses increased by **$3.2 million**, driven by higher personnel-related costs and share-based compensation, offset by a decrease in professional fees[646](index=646&type=chunk) [Liquidity and Capital Resources](index=216&type=section&id=Liquidity%20and%20Capital%20Resources) Cash and equivalents increased to $438.7 million at year-end 2021, primarily due to $320.7 million in net cash from financing activities Cash Flow Summary (in thousands) | | Year Ended Dec 31, 2021 | Year Ended Dec 31, 2020 | | :--- | :--- | :--- | | Net cash used in operating activities | ($14,794) | ($17,789) | | Net cash used in investing activities | ($2,030) | ($1,200) | | Net cash provided by financing activities | $320,725 | $62,843 | | **Net increase in cash** | **$302,690** | **$43,873** | - The company's cash and cash equivalents increased to **$438.7 million** at the end of 2021 from $136.0 million at the end of 2020[618](index=618&type=chunk)[742](index=742&type=chunk) - Financing activities in 2021 provided **$320.7 million**, primarily from a **$188.4 million follow-on offering**, **$102.6 million from the ATM program**, and **$15.0 million in borrowings**[654](index=654&type=chunk) - As of December 31, 2021, the company had **$30.0 million in borrowings outstanding** under its loan agreement with Hercules Capital[657](index=657&type=chunk) - Management believes **existing cash will fund operations** and capital expenditures for at least 12 months from the filing date[618](index=618&type=chunk)[665](index=665&type=chunk) [Quantitative and Qualitative Disclosures About Market Risk](index=231&type=section&id=Item%207A.%20Quantitative%20and%20Qualitative%20Disclosures%20About%20Market%20Risk) The company is exposed to market risks, primarily interest rate sensitivity and foreign currency exchange risk - The company's primary market risks are **interest rate sensitivity** and **foreign currency exchange risk**[692](index=692&type=chunk)[694](index=694&type=chunk) - Interest rate risk is present for its **$438.7 million in cash** and its **$30 million in debt**, with the debt having a floor interest rate of 8.85%[692](index=692&type=chunk)[693](index=693&type=chunk) - Foreign currency risk arises from its UK-based subsidiaries, whose functional currency is the British Pound Sterling, while the reporting currency is the U.S. Dollar[694](index=694&type=chunk)[696](index=696&type=chunk) [Financial Statements and Supplementary Data](index=232&type=section&id=Item%208.%20Financial%20Statements%20and%20Supplementary%20Data) This section contains the company's audited consolidated financial statements for the fiscal year ended December 31, 2021 - This section includes the company's consolidated financial statements and the report of the independent registered public accounting firm[697](index=697&type=chunk) Consolidated Balance Sheet Data (in thousands) | | Dec 31, 2021 | Dec 31, 2020 | | :--- | :--- | :--- | | Cash and cash equivalents | $438,680 | $135,990 | | Total assets | $479,792 | $161,152 | | Total liabilities | $133,538 | $65,692 | | Total shareholders' equity | $346,254 | $95,460 | [Changes in and Disagreements with Accountants on Accounting and Financial Disclosure](index=232&type=section&id=Item%209.%20Changes%20in%20and%20Disagreements%20with%20Accountants%20on%20Accounting%20and%20Financial%20Disclosure) None - The company reports no changes in or disagreements with its accountants on accounting and financial disclosure[697](index=697&type=chunk) [Controls and Procedures](index=232&type=section&id=Item%209A.%20Controls%20and%20Procedures) Management concluded that disclosure controls and internal control over financial reporting were effective as of December 31, 2021 - Management concluded that the company's **disclosure controls and procedures were effective** as of December 31, 2021[701](index=701&type=chunk) - Management concluded that the company's **internal control over financial reporting was effective** as of December 31, 2021, based on the COSO framework[703](index=703&type=chunk) - The independent registered public accounting firm, PricewaterhouseCoopers LLP, has audited and issued an **unqualified opinion** on the effectiveness of the company's internal control over financial reporting[704](index=704&type=chunk)[729](index=729&type=chunk) [Other Information](index=235&type=section&id=Item%209B.%20Other%20Information) Not applicable - The company reports no other information under this item[707](index=707&type=chunk) PART III [Directors, Executive Officers and Corporate Governance](index=236&type=section&id=Item%2010.%20Directors%2C%20Executive%20Officers%20and%20Corporate%20Governance) The required information is incorporated by reference from the company's 2022 Proxy Statement - Information regarding directors, executive officers, and corporate governance is incorporated by reference from the company's 2022 Proxy Statement[709](index=709&type=chunk) [Executive Compensation](index=236&type=section&id=Item%2011.%20Executive%20Compensation) The required information is incorporated by reference from the company's 2022 Proxy Statement - Information regarding executive compensation is incorporated by reference from the company's 2022 Proxy Statement[710](index=710&type=chunk) [Security Ownership of Certain Beneficial Owners and Management and Related Stockholder Matters](index=236&type=section&id=Item%2012.%20Security%20Ownership%20of%20Certain%20Beneficial%20Owners%20and%20Management%20and%20Related%20Stockholder%20Matters) The required information is incorporated by reference from the company's 2022 Proxy Statement - Information regarding security ownership and equity compensation plans is incorporated by reference from the company's 2022 Proxy Statement[711](index=711&type=chunk) [Certain Relationships and Related Transactions, and Director Independence](index=236&type=section&id=Item%2013.%20Certain%20Relationships%20and%20Related%20Transactions%2C%20and%20Director%20Independence) The required information is incorporated by reference from the company's 2022 Proxy Statement - Information regarding certain relationships, related transactions, and director independence is incorporated by reference from the company's 2022 Proxy Statement[712](index=712&type=chunk) [Principal Accountant Fees and Services](index=236&type=section&id=Item%2014.%20Principal%20Accountant%20Fees%20and%20Services) The required information is incorporated by reference from the company's 2022 Proxy Statement - Information regarding principal accountant fees and services is incorporated by reference from the company's 2022 Proxy Statement[712](index=712&type=chunk) PART IV [Exhibit and Financial Statement Schedules](index=237&type=section&id=Item%2015.%20Exhibit%20and%20Financial%20Statement%20Schedules) This section lists the financial statements and exhibits filed as part of the Annual Report - This section lists the financial statements and exhibits filed with the Form 10-K[714](index=714&type=chunk) [Form 10-K Summary](index=242&type=section&id=Item%2016.%20Form%2010-K%20Summary) None - The company provides no summary under this item[723](index=723&type=chunk)

[PART I - FINANCIAL INFORMATION](index=10&type=section&id=PART%20I%20-%20FINANCIAL%20INFORMATION) [Item 1. Financial Statements (unaudited)](index=10&type=section&id=Item%201.%20Financial%20Statements%20(unaudited)) For the nine months ended September 30, 2021, Bicycle Therapeutics reported a net loss of $48.8 million, an increase from the $33.6 million loss in the same period of 2020, driven by higher research and development and general administrative expenses. Collaboration revenues grew to $7.9 million from $6.5 million year-over-year. The company's financial position strengthened, with cash increasing to $259.5 million from $136.0 million at year-end 2020, primarily due to significant financing activities, including proceeds from an at-the-market (ATM) offering and a new debt facility. Total assets grew to $281.3 million, and total liabilities increased to $110.5 million, largely from new debt and increased deferred revenue from collaboration agreements Condensed Consolidated Balance Sheet Highlights (Unaudited) | Account | Sep 30, 2021 (in thousands) | Dec 31, 2020 (in thousands) | | :--- | :--- | :--- | | Cash | $259,524 | $135,990 | | Total current assets | $272,872 | $155,723 | | Total assets | $281,333 | $161,152 | | Deferred revenue (current & long-term) | $62,507 | $35,156 | | Total liabilities | $110,510 | $65,692 | | Total shareholders' equity | $170,823 | $95,460 | Condensed Consolidated Statements of Operations Highlights (Unaudited) | Metric | Three Months Ended Sep 30, 2021 (in thousands) | Three Months Ended Sep 30, 2020 (in thousands) | Nine Months Ended Sep 30, 2021 (in thousands) | Nine Months Ended Sep 30, 2020 (in thousands) | | :--- | :--- | :--- | :--- | :--- | | Collaboration revenues | $4,333 | $3,842 | $7,926 | $6,542 | | Research and development | $10,513 | $7,363 | $31,924 | $23,091 | | General and administrative | $8,114 | $7,154 | $23,596 | $18,351 | | Loss from operations | $(14,294) | $(10,675) | $(47,594) | $(34,900) | | Net loss | $(14,678) | $(10,138) | $(48,782) | $(33,577) | | Net loss per share | $(0.59) | $(0.52) | $(2.06) | $(1.81) | Condensed Consolidated Statements of Cash Flows Highlights (Unaudited, Nine Months Ended) | Cash Flow Activity | Sep 30, 2021 (in thousands) | Sep 30, 2020 (in thousands) | | :--- | :--- | :--- | | Net cash used in operating activities | $(4,359) | $(1,172) | | Net cash used in investing activities | $(963) | $(716) | | Net cash provided by financing activities | $130,061 | $61,099 | | Net increase in cash | $123,534 | $57,725 | [Note 1: Nature of the Business and Basis of Presentation](index=16&type=section&id=1.%20Nature%20of%20the%20business%20and%20basis%20of%20presentation) Bicycle Therapeutics is a clinical-stage biopharmaceutical company developing a novel class of medicines called Bicycles, with an initial focus on oncology. The company is advancing several clinical programs: BT5528, BT8009, and BT7480, alongside the Cancer Research UK (CRUK) sponsored trial for BT1718. The company has a history of significant operating losses, with a net loss of $48.8 million for the first nine months of 2021 and an accumulated deficit of $200.3 million. Despite this, management believes existing cash is sufficient to fund operations for at least the next twelve months, supported by recent financing from an at-the-market (ATM) offering and a loan agreement with Hercules Capital - The company's initial internal programs are focused on oncology, with key candidates being **BT5528** (targeting EphA2), **BT8009** (targeting Nectin-4), and **BT7480** (a Bicycle TICA targeting Nectin-4 and agonizing CD137). **BT1718** is being investigated in a trial sponsored and funded by Cancer Research UK[32](index=32&type=chunk) - As of September 30, 2021, the company had raised net proceeds of **$150.7 million** from its at-the-market (ATM) offering program[34](index=34&type=chunk) - The company entered into a loan agreement with Hercules Capital for up to **$40.0 million**, of which **$30.0 million** was drawn as of March 10, 2021[35](index=35&type=chunk)[38](index=38&type=chunk) - The company has incurred recurring losses since inception, including a net loss of **$48.8 million** for the nine months ended September 30, 2021, and had an accumulated deficit of **$200.3 million**. Management expects cash to be sufficient to fund operations for at least twelve months from the report's issuance date[40](index=40&type=chunk) [Note 9: Significant Agreements](index=32&type=section&id=9.%20Significant%20agreements) The company's revenue is derived from collaboration agreements with Ionis, Genentech, DDF, AstraZeneca, and Oxurion. In July 2021, a significant new collaboration was established with Ionis, which included a $31.0 million upfront payment and an $11.0 million equity investment. This new agreement, along with ongoing activities with Genentech, drove an increase in deferred revenue to $62.5 million as of September 30, 2021. Revenue is recognized as performance obligations, such as R&D services and licenses, are satisfied over time Collaboration Revenues (in thousands) | Partner | Nine Months Ended Sep 30, 2021 | Nine Months Ended Sep 30, 2020 | | :--- | :--- | :--- | | Ionis | $2,066 | $— | | Genentech | $4,142 | $3,066 | | AstraZeneca | $1,404 | $944 | | Oxurion | $— | $2,362 | | Dementia Discovery Fund | $314 | $170 | | **Total** | **$7,926** | **$6,542** | - On July 9, 2021, the company entered into a collaboration and license agreement with Ionis, receiving a **$31.0 million** upfront payment and a concurrent **$11.0 million** equity investment. The total transaction price, including a premium on the share purchase and other fees, was determined to be **$38.0 million**[90](index=90&type=chunk)[92](index=92&type=chunk)[100](index=100&type=chunk) - The company's deferred revenue balance increased from **$35.2 million** at the beginning of 2021 to **$62.5 million** as of September 30, 2021, primarily due to additions from the new Ionis collaboration (**$34.4 million**)[150](index=150&type=chunk) - In August 2021, AstraZeneca terminated collaboration activities related to the sixth target under an option agreement, resulting in the recognition of **$1.1 million** in deferred revenue[143](index=143&type=chunk)[145](index=145&type=chunk) [Note 11: Commitments and Contingencies](index=59&type=section&id=11.%20Commitments%20and%20Contingencies) This section details the company's primary commitments, including operating leases for its facilities in the U.S. and U.K., legal proceedings, and royalty arrangements. In June 2021, the company exercised its option to renew its Cambridge, U.K. lease for five years. A significant legal matter with Pepscan was settled in November 2020, resulting in an upfront payment and future milestone obligations. The company also has a contingent liability related to the Cancer Research UK-funded trial for BT1718 - In June 2021, the company exercised its option to renew its Cambridge, U.K. lease for five years, commencing December 12, 2021[171](index=171&type=chunk) - The company settled litigation with Pepscan in November 2020, agreeing to pay **€3.0 million** upfront, **€1.0 million** on the first anniversary, and potential future milestones valued up to **$92.4 million**. A liability of **$1.2 million** related to this was on the balance sheet as of September 30, 2021[174](index=174&type=chunk)[176](index=176&type=chunk) - A liability of **$3.0 million** was recorded as of September 30, 2021, related to costs incurred by Cancer Research UK for the BT1718 clinical trial, which the company may be obligated to repay under certain conditions[158](index=158&type=chunk)[160](index=160&type=chunk) [Item 2. Management's Discussion and Analysis of Financial Condition and Results of Operations](index=67&type=section&id=Item%202.%20Management's%20Discussion%20and%20Analysis%20of%20Financial%20Condition%20and%20Results%20of%20Operations) Management discusses the company's financial performance, highlighting an increase in both collaboration revenues and operating expenses for the third quarter and first nine months of 2021 compared to 2020. The higher expenses were driven by advancing clinical programs, particularly BT8009, and increased headcount. The company's liquidity remains strong, with $259.5 million in cash as of September 30, 2021, which is expected to fund operations for at least the next 12 months. This position was bolstered by proceeds from an ATM offering, debt financing, and the new Ionis collaboration. The impact of COVID-19 on operations has been limited, but remains a monitored risk - The company is a clinical-stage biopharmaceutical firm developing a novel class of medicines called **Bicycles**. Key clinical programs include **BT5528**, **BT8009**, **BT1718**, and **BT7480**, primarily for oncology indications[193](index=193&type=chunk)[195](index=195&type=chunk) Comparison of Results of Operations (in thousands) | Metric | Three Months Ended Sep 30, 2021 | Three Months Ended Sep 30, 2020 | Nine Months Ended Sep 30, 2021 | Nine Months Ended Sep 30, 2020 | | :--- | :--- | :--- | :--- | :--- | | Collaboration Revenues | $4,333 | $3,842 | $7,926 | $6,542 | | R&D Expenses | $10,513 | $7,363 | $31,924 | $23,091 | | G&A Expenses | $8,114 | $7,154 | $23,596 | $18,351 | | Net Loss | $(14,678) | $(10,138) | $(48,782) | $(33,577) | - The increase in R&D expenses for the nine months ended Sep 30, 2021 was primarily due to increased clinical program development for **BT8009**, costs for collaboration agreements, and higher employee-related expenses from increased headcount[250](index=250&type=chunk) - As of September 30, 2021, the company had cash of **$259.5 million** and believes this will fund operating expenses and capital requirements for at least 12 months. This is supported by recent financing activities, including **$102.6 million** net from its ATM program and **$15.0 million** in debt proceeds in 2021[213](index=213&type=chunk)[273](index=273&type=chunk) [Item 3. Quantitative and Qualitative Disclosure About Market Risk](index=100&type=section&id=Item%203.%20Quantitative%20and%20Qualitative%20Disclosure%20About%20Market%20Risk) The company's primary market risks are interest rate sensitivity and foreign currency exchange risk. Interest rate risk stems from its cash holdings and variable-rate debt, though the impact of a 1% rate change is not expected to be material. Foreign currency risk arises from its international operations, with transactions denominated in U.S. dollars, British Pounds Sterling, and Euros. The company does not currently use hedging instruments to mitigate these risks - The company is subject to interest rate risk from its **$259.5 million** in cash and **$30.0 million** in debt with Hercules. The debt has a variable rate component but is currently at its floor of **8.85%**[297](index=297&type=chunk)[298](index=298&type=chunk) - The company has significant foreign currency exchange risk as its UK subsidiaries use the British Pound Sterling (GBP) as their functional currency, while the consolidated statements are presented in U.S. Dollars (USD). Exchange rate fluctuations are recorded in general and administrative expense[299](index=299&type=chunk)[300](index=300&type=chunk) [Item 4. Controls and Procedures](index=102&type=section&id=Item%204.%20Controls%20and%20Procedures) Based on an evaluation as of September 30, 2021, the company's management, including the Chief Executive Officer and Chief Financial Officer, concluded that its disclosure controls and procedures were effective. There were no material changes to the company's internal control over financial reporting during the quarter - Management concluded that the company's disclosure controls and procedures were effective at a reasonable assurance level as of September 30, 2021[304](index=304&type=chunk) - No changes in internal control over financial reporting occurred during the quarter ended September 30, 2021, that have materially affected, or are reasonably likely to materially affect, internal controls[305](index=305&type=chunk) [PART II - OTHER INFORMATION](index=103&type=section&id=PART%20II%20-%20OTHER%20INFORMATION) [Item 1. Legal Proceedings](index=103&type=section&id=Item%201.%20Legal%20Proceedings) The company provides an update on European patent opposition proceedings against Dyax Corp. One of Dyax's patents was revoked, with the decision becoming final in August 2021. An appeal is pending on a second related patent, with a hearing scheduled for November 2022 - In a European patent opposition proceeding, Dyax Corp's European patent **2 374 472** was revoked, and the decision became final on August 17, 2021, as no appeal was filed[310](index=310&type=chunk) - An appeal is ongoing regarding Dyax Corp's European patent **1 854 477**, with a hearing scheduled for November 15, 2022[309](index=309&type=chunk) [Item 1A. Risk Factors](index=104&type=section&id=Item%201A.%20Risk%20Factors) The company details significant risks that could adversely affect its business. Key risks include its history of operating losses and need for future funding; dependence on the success of its novel and early-stage product candidates (BTCs and Bicycle TICAs); reliance on third parties for clinical trials and manufacturing; potential for undesirable side effects in clinical trials; and challenges in obtaining regulatory approval and market acceptance. The company also highlights risks related to intellectual property protection, competition from larger pharmaceutical companies, potential impacts from COVID-19 and Brexit, and the complexities of international operations and regulations - The company has a history of significant operating losses, with an accumulated deficit of **$200.3 million** as of September 30, 2021, and expects to incur increasing losses for the foreseeable future, requiring substantial additional funding[313](index=313&type=chunk)[323](index=323&type=chunk) - The company is substantially dependent on the success of its early-stage product candidates from its **BTC** and **Bicycle TICA** programs, which represent a new category of medicine and may be subject to heightened regulatory scrutiny[335](index=335&type=chunk)[341](index=341&type=chunk) - The company relies on third parties, such as Cancer Research UK, CROs, and CMOs, to conduct clinical trials and manufacture product candidates, which increases risks related to delays, quality control, and supply sufficiency[511](index=511&type=chunk)[518](index=518&type=chunk) - The business faces risks from the ongoing **COVID-19** pandemic, which could disrupt clinical trials, supply chains, and access to capital. Additionally, as a UK-based company, it is subject to risks associated with **Brexit**, including regulatory divergence and potential trade barriers[469](index=469&type=chunk)[391](index=391&type=chunk) - The company faces significant competition and risks related to intellectual property, including the ability to obtain and maintain patent protection and the possibility of costly infringement litigation[417](index=417&type=chunk)[533](index=533&type=chunk)[561](index=561&type=chunk) [Item 2. Unregistered Sales of Equity Securities and Use of Proceeds](index=220&type=section&id=Item%202.%20Unregistered%20Sales%20of%20Equity%20Securities%20and%20Use%20of%20Proceeds) This item is reported as not applicable, indicating no unregistered sales of equity securities occurred during the reporting period - Not Applicable[644](index=644&type=chunk) [Item 3. Defaults Upon Senior Securities](index=220&type=section&id=Item%203.%20Defaults%20Upon%20Senior%20Securities) This item is reported as not applicable, indicating no defaults upon senior securities - Not Applicable[645](index=645&type=chunk) [Item 4. Mine Safety Disclosures](index=220&type=section&id=Item%204.%20Mine%20Safety%20Disclosures) This item is reported as not applicable as it is not relevant to the company's operations - Not Applicable[646](index=646&type=chunk) [Item 5. Other Information](index=220&type=section&id=Item%205.%20Other%20Information) This item is reported as not applicable, indicating no other material information was required to be disclosed - Not Applicable[647](index=647&type=chunk) [Item 6. Exhibits](index=220&type=section&id=Item%206.%20Exhibits) This section lists the exhibits filed with the Form 10-Q. Key documents include the Collaboration and License Agreement with Ionis Pharmaceuticals, Inc., a related Share Purchase Agreement, and certifications by the Principal Executive Officer and Principal Financial Officer - Key exhibits filed include the Collaboration and License Agreement and the Share Purchase Agreement with Ionis Pharmaceuticals, Inc., both dated July 9, 2021[648](index=648&type=chunk) - Standard officer certifications required under the Sarbanes-Oxley Act of 2002 (Sections 302 and 906) are also included as exhibits[648](index=648&type=chunk)

Table of Contents Title of each class Trading Symbol(s) Name of each exchange on which registered Ordinary shares, nominal value £0.01 per share * n/a The Nasdaq Stock Market LLC BCYC The Nasdaq Stock Market LLC UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, DC 20549 FORM 10-Q (Mark One) ☒ QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the quarterly period ended June 30, 2021 OR ☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES E ...

Table of Contents UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, DC 20549 FORM 10-Q (Mark One) ⌧ QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the quarterly period ended March 31, 2021 OR ◻ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the transition period from to Commission File Number: 001-38916 Bicycle Therapeutics plc (Exact Name of Registrant as Specified in its Charter) England and Wales Not App ...

Table of Contents UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 10-K (Mark One) ⌧ ANNUAL REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the fiscal year ended December 31, 2020. OR ◻ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the transition period from to Commission file number 001-38916 BICYCLE THERAPEUTICS PLC (Exact name of registrant as specified in its charter) England and Wales Not Applic ...

[PART I - FINANCIAL INFORMATION](index=5&type=section&id=PART%20I%20-%20FINANCIAL%20INFORMATION) [Item 1. Financial Statements (unaudited)](index=5&type=section&id=Item%201.%20Financial%20Statements%20(unaudited)) This section presents the unaudited condensed consolidated financial statements for Bicycle Therapeutics plc, including the balance sheets, statements of operations and comprehensive loss, statements of convertible preferred shares and shareholders' equity (deficit), and statements of cash flows, along with detailed notes explaining the company's business, accounting policies, and financial instruments [Condensed Consolidated Balance Sheets](index=5&type=section&id=Condensed%20Consolidated%20Balance%20Sheets) The condensed consolidated balance sheets provide a snapshot of the company's financial position as of September 30, 2020, compared to December 31, 2019, showing significant increases in cash, total current assets, and total liabilities | Metric | September 30, 2020 ($ thousands) | December 31, 2019 ($ thousands) | | :----------------------------------- | :------------------------------- | :------------------------------ | | Cash | 149,842 | 92,117 | | Total current assets | 164,158 | 104,146 | | Total assets | 170,059 | 110,194 | | Total current liabilities | 17,047 | 8,821 | | Total liabilities | 60,508 | 16,996 | | Total shareholders' equity | 109,551 | 93,198 | [Condensed Consolidated Statements of Operations and Comprehensive Loss](index=6&type=section&id=Condensed%20Consolidated%20Statements%20of%20Operations%20and%20Comprehensive%20Loss) The condensed consolidated statements of operations and comprehensive loss highlight the company's financial performance for the three and nine months ended September 30, 2020 and 2019, showing increased collaboration revenues but also higher operating expenses, leading to larger net losses | Metric | Three Months Ended Sep 30, 2020 ($ thousands) | Three Months Ended Sep 30, 2019 ($ thousands) | Nine Months Ended Sep 30, 2020 ($ thousands) | Nine Months Ended Sep 30, 2019 ($ thousands) | | :------------------------------------------------ | :-------------------------------------------- | :-------------------------------------------- | :------------------------------------------- | :------------------------------------------- | | Collaboration revenues | 3,842 | 614 | 6,542 | 8,520 | | Research and development expenses | 7,363 | 6,078 | 23,091 | 18,891 | | General and administrative expenses | 7,154 | 4,789 | 18,351 | 11,164 | | Total operating expenses | 14,517 | 10,867 | 41,442 | 30,055 | | Loss from operations | (10,675) | (10,253) | (34,900) | (21,535) | | Net loss | (10,138) | (9,482) | (33,577) | (26,202) | | Net loss per share (basic and diluted) | (0.52) | (0.53) | (1.81) | (3.00) | [Condensed Consolidated Statements of Convertible Preferred Shares and Shareholders' Equity (Deficit)](index=7&type=section&id=Condensed%20Consolidated%20Statements%20of%20Convertible%20Preferred%20Shares%20and%20Shareholders'%20Equity%20(Deficit)) This section details the changes in convertible preferred shares and shareholders' equity (deficit) for the nine months ended September 30, 2020 and 2019, reflecting share issuances, share-based compensation, foreign currency adjustments, and net losses | Metric | Balance at Dec 31, 2019 ($ thousands) | Balance at Sep 30, 2020 ($ thousands) | | :------------------------------------ | :------------------------------------ | :------------------------------------ | | Ordinary Shares (Amount) | 227 | 264 | | Additional Paid-in Capital | 195,056 | 246,391 | | Accumulated Other Comprehensive Loss | (1,535) | (2,977) | | Accumulated Deficit | (100,550) | (134,127) | | Total Shareholders' Equity (Deficit) | 93,198 | 109,551 | - Issuance of ordinary shares upon exercise of share options and warrants contributed to **additional paid-in capital**[9](index=9&type=chunk) - Issuance of ADSs, net of commissions and offering expenses, significantly increased **additional paid-in capital by $46,287 thousand** for the nine months ended September 30, 2020[9](index=9&type=chunk) [Condensed Consolidated Statements of Cash Flows](index=9&type=section&id=Condensed%20Consolidated%20Statements%20of%20Cash%20Flows) The condensed consolidated statements of cash flows present the cash inflows and outflows from operating, investing, and financing activities for the nine months ended September 30, 2020 and 2019, showing a substantial increase in cash from financing activities in 2020 | Metric | Nine Months Ended Sep 30, 2020 ($ thousands) | Nine Months Ended Sep 30, 2019 ($ thousands) | | :------------------------------------ | :------------------------------------------- | :------------------------------------------- | | Net cash used in operating activities | (1,172) | (23,694) | | Net cash used in investing activities | (716) | (1,164) | | Net cash provided by financing activities | 61,099 | 58,318 | | Effect of exchange rate changes on cash | (1,486) | (886) | | Net increase in cash | 57,725 | 32,574 | | Cash at end of period | 149,842 | 95,954 | - **Net cash provided by financing activities in 2020** was primarily driven by **$46.4 million from ATM offerings** and **$15.0 million from debt issuance**[11](index=11&type=chunk) [Notes to Condensed Consolidated Financial Statements](index=10&type=section&id=Notes%20to%20Condensed%20Consolidated%20Financial%20Statements) These notes provide detailed explanations and disclosures supporting the condensed consolidated financial statements, covering the company's business, significant accounting policies, financial instruments, debt, equity, and collaboration agreements [1. Nature of the business and basis of presentation](index=10&type=section&id=1.%20Nature%20of%20the%20business%20and%20basis%20of%20presentation) Bicycle Therapeutics plc is a clinical-stage biopharmaceutical company focused on developing novel Bicycles® for underserved diseases, primarily in oncology. The notes detail the company's structure, GAAP compliance, liquidity, and risks, including the impact of the COVID-19 pandemic - The Company is a clinical-stage biopharmaceutical company developing Bicycles® for diseases underserved by existing therapeutics, with initial internal programs focused on oncology[12](index=12&type=chunk) - Lead product candidates include **BT1718** (targeting MT1-MMP), **BT5528** (targeting EphA2), and **BT8009** (targeting Nectin-4), all in Phase I/II clinical trials[12](index=12&type=chunk) - The company completed an IPO in May 2019, raising **$56.4 million net proceeds**, and an at-the-market (ATM) offering program in 2020, selling **2,830,713 ADSs for $46.3 million net proceeds** as of September 30, 2020[14](index=14&type=chunk) - On September 30, 2020, the company entered into a loan agreement with Hercules Capital, Inc. for up to **$40.0 million**, with **$15.0 million funded** on that date[14](index=14&type=chunk) - The company has incurred recurring losses since inception, with **net losses of $10.1 million and $33.6 million** for the three and nine months ended September 30, 2020, respectively, and an **accumulated deficit of $134.1 million** as of September 30, 2020[15](index=15&type=chunk) - The COVID-19 pandemic has caused limited financial and operational impacts but poses risks of delays in research, clinical trials, and supply chain disruptions[19](index=19&type=chunk) [2. Summary of significant accounting policies](index=10&type=section&id=2.%20Summary%20of%20significant%20accounting%20policies) This section outlines the company's significant accounting policies, including the use of estimates, foreign currency translation, government grants, and recently issued accounting pronouncements, emphasizing the adoption of USD as the functional currency for the parent company - The company adopted the **U.S. dollar (USD) as its functional currency** on June 1, 2019, due to its primary financing source shifting to the U.S. capital markets[21](index=21&type=chunk) - Foreign currency translation adjustments are recorded as a component of accumulated other comprehensive income (loss)[22](index=22&type=chunk) | Metric | Three Months Ended Sep 30, 2020 ($ thousands) | Three Months Ended Sep 30, 2019 ($ thousands) | Nine Months Ended Sep 30, 2020 ($ thousands) | Nine Months Ended Sep 30, 2019 ($ thousands) | | :------------------------------------ | :-------------------------------------------- | :-------------------------------------------- | :------------------------------------------- | :------------------------------------------- | | Foreign exchange loss | (700) | (800) | 700 (gain) | (400) (loss) | | Government grants (reduction of R&D) | 100 | 200 | 300 | 500 | - The company is evaluating the impact of ASU No. 2016-13 (Credit Losses) and ASU No. 2019-12 (Income Taxes) on its financial statements[24](index=24&type=chunk)[25](index=25&type=chunk) [3. Fair value of financial assets and liabilities](index=13&type=section&id=3.%20Fair%20value%20of%20financial%20assets%20and%20liabilities) This note discusses the classification and disclosure of financial assets and liabilities at fair value, noting that most current assets and liabilities approximate fair value due to their short-term nature, and there were no assets or liabilities measured at fair value on a recurring basis as of September 30, 2020, and December 31, 2019 - The carrying values of accounts receivable, R&D incentives receivable, other current assets, accounts payable, and accrued expenses approximate their fair values due to their short-term nature[25](index=25&type=chunk) - The carrying value of long-term debt approximates its fair value as it's based on market interest rates for similar borrowings[25](index=25&type=chunk) - No assets or liabilities were measured at fair value on a recurring basis as of September 30, 2020, and December 31, 2019[25](index=25&type=chunk) [4. Property and equipment, net](index=13&type=section&id=4.%20Property%20and%20equipment,%20net) This section provides a breakdown of property and equipment, net, and associated depreciation expenses, showing a slight decrease in net property and equipment from December 31, 2019, to September 30, 2020 | Category | September 30, 2020 ($ thousands) | December 31, 2019 ($ thousands) | | :------------------------------------ | :------------------------------- | :------------------------------ | | Laboratory equipment | 4,790 | 4,326 | | Leasehold improvements | 371 | 300 | | Computer equipment and software | 185 | 229 | | Furniture and office equipment | 189 | 120 | | Total gross property and equipment | 5,535 | 4,975 | | Less: Accumulated depreciation and amortization | (3,496) | (2,683) | | Property and equipment, net | 2,039 | 2,292 | | Metric | Three Months Ended Sep 30, 2020 ($ thousands) | Three Months Ended Sep 30, 2019 ($ thousands) | Nine Months Ended Sep 30, 2020 ($ thousands) | Nine Months Ended Sep 30, 2019 ($ thousands) | | :----------------------- | :-------------------------------------------- | :-------------------------------------------- | :------------------------------------------- | :------------------------------------------- | | Depreciation expense | 300 | 200 | 900 | 700 | [5. Accrued expenses and other current liabilities](index=15&type=section&id=5.%20Accrued%20expenses%20and%20other%20current%20liabilities) This note provides a detailed breakdown of accrued expenses and other current liabilities, showing an increase from December 31, 2019, to September 30, 2020, primarily driven by accrued external research and development expenses and professional fees | Category | September 30, 2020 ($ thousands) | December 31, 2019 ($ thousands) | | :------------------------------------ | :------------------------------- | :------------------------------ | | Accrued employee compensation and benefits | 2,559 | 2,514 | | Accrued external research and development expenses | 2,742 | 2,055 | | Accrued professional fees | 1,723 | 867 | | Current portion of operating lease liabilities | 684 | 640 | | Other | 90 | 68 | | Total | 7,798 | 6,144 | [6. Long-term debt](index=15&type=section&id=6.%20Long-term%20debt) This note details the company's long-term debt, including a new loan agreement with Hercules Capital, Inc. for up to $40.0 million, with $15.0 million funded on September 30, 2020, and outlines the interest rates, repayment terms, and collateral - On September 30, 2020, the company entered into a loan agreement with Hercules Capital, Inc. for up to **$40.0 million**, with an initial term loan of **$15.0 million funded**[29](index=29&type=chunk) - Borrowings bear interest at the greater of **8.85% or 5.60% plus the Wall Street Journal prime rate**, with an **effective interest rate of 12.1%** at September 30, 2020[29](index=29&type=chunk) - The loan includes interest-only payments until November 1, 2022 (potentially extended to May 1, 2023), followed by principal and interest payments through October 1, 2024[29](index=29&type=chunk) | Metric | September 30, 2020 ($ thousands) | | :------------------------------------ | :------------------------------- | | Term loan payable | 15,000 | | Unamortized debt issuance costs | (573) | | Carrying value of term loan | 14,427 | | Year Ending December 31, | Principal Payments ($ thousands) | | :----------------------- | :------------------------------- | | 2020 | — | | 2021 | — | | 2022 | 1,148 | | 2023 | 7,262 | | 2024 | 7,340 | | Total | 15,750 | [7. Convertible preferred shares](index=16&type=section&id=7.%20Convertible%20preferred%20shares) This note describes the company's history of issuing Series A, B1, and B2 convertible preferred shares, and their automatic conversion into ordinary shares upon the completion of the IPO in May 2019 - The company previously issued Series A, B1, and B2 convertible preferred shares[31](index=31&type=chunk) - Upon the closing of the IPO in May 2019, all outstanding convertible preferred shares automatically converted into **11,647,529 ordinary shares** on a **1:1.429 basis**[33](index=33&type=chunk) [8. Warrant liability](index=17&type=section&id=8.%20Warrant%20liability) This note explains the accounting for warrant liabilities, which were remeasured to fair value at each reporting date prior to the IPO and reclassified to additional paid-in capital upon the IPO's completion, as warrants became exercisable for ordinary shares - Prior to the IPO, warrants to subscribe for Series A and B1 Preferred Shares were recorded as a liability and remeasured to fair value at each reporting date[34](index=34&type=chunk) - Upon the IPO's closing on May 28, 2019, unexercised warrants became warrants to subscribe for ordinary shares and were reclassified to additional paid-in capital[34](index=34&type=chunk) | Metric | Nine Months Ended Sep 30, 2020 ($ thousands) | Nine Months Ended Sep 30, 2019 ($ thousands) | | :------------------------------------ | :------------------------------------------- | :------------------------------------------- | | Other expense related to warrant liability remeasurement | 0 | 5,400 | [9. Ordinary shares](index=17&type=section&id=9.%20Ordinary%20shares) This note outlines the rights of ordinary shareholders, including voting and dividend entitlements, and states the authorized and outstanding share counts as of September 30, 2020, and December 31, 2019 - Each ordinary share holder is entitled to **one vote per share** and to receive dividends when declared[35](index=35&type=chunk) - As of September 30, 2020, the company had **31,995,653 ordinary shares authorized** and **20,935,853 shares issued and outstanding**[35](index=35&type=chunk) - No dividends have been declared as of September 30, 2020[35](index=35&type=chunk) [10. Share-based compensation](index=18&type=section&id=10.%20Share-based%20compensation) This note details the company's share-based compensation plans, including the 2020 and 2019 Share Option Plans, pre-IPO options, and the Employee Share Purchase Plan (ESPP), along with the associated compensation expenses and valuation assumptions - The 2020 Equity Incentive Plan, approved in June 2020, reserved **4,773,557 ordinary shares** for issuance, with automatic annual increases[36](index=36&type=chunk) - Share options generally vest over a **four-year service period** (25% on first anniversary, then monthly) and have a **10-year contractual life**[36](index=36&type=chunk) | Metric | Three Months Ended Sep 30, 2020 ($ thousands) | Three Months Ended Sep 30, 2019 ($ thousands) | Nine Months Ended Sep 30, 2020 ($ thousands) | Nine Months Ended Sep 30, 2019 ($ thousands) | | :------------------------------------ | :-------------------------------------------- | :-------------------------------------------- | :------------------------------------------- | :------------------------------------------- | | Research and development expenses | 668 | 417 | 4,950 | 2,000 | | General and administrative expenses | 842 | 402 | (Included in R&D total) | (Included in R&D total) | | Total share-based compensation expense | 1,510 | 819 | 4,950 | 2,000 | | Metric | Sep 30, 2020 | Dec 31, 2019 | | :------------------------------------ | :----------- | :----------- | | Outstanding share options (Number of Shares) | 3,779,785 | 2,634,346 | | Weighted Average Exercise Price | $10.24 | $9.57 | | Weighted Average Contractual Term (years) | 8.76 | 9.04 | | Aggregate Intrinsic Value ($ thousands) | 33,340 | 6,107 | - Total unrecognized compensation expense for unvested awards was **$14.7 million** as of September 30, 2020, to be recognized over **2.7 years**[48](index=48&type=chunk) [11. Significant agreements](index=21&type=section&id=11.%20Significant%20agreements) This note details the company's collaboration agreements with various biopharmaceutical companies and organizations, outlining the terms, performance obligations, and revenue recognition for each, as well as a summary of contract assets and liabilities | Collaboration Partner | Three Months Ended Sep 30, 2020 ($ thousands) | Three Months Ended Sep 30, 2019 ($ thousands) | Nine Months Ended Sep 30, 2020 ($ thousands) | Nine Months Ended Sep 30, 2019 ($ thousands) | | :-------------------- | :-------------------------------------------- | :-------------------------------------------- | :------------------------------------------- | :------------------------------------------- | | AstraZeneca | 213 | 441 | 944 | 1,229 | | Sanofi | — | — | — | 6,016 | | Oxurion | 2,362 | — | 2,362 | — | | Dementia Discovery Fund | 58 | 173 | 170 | 275 | | Material transfer agreement | — | — | — | 1,000 | | Genentech | 1,209 | — | 3,066 | — | | Total collaboration revenues | 3,842 | 614 | 6,542 | 8,520 | - AstraZeneca collaboration involves research and development of Bicycle peptides for up to six targets, with potential milestone payments up to **$29.0 million (development)**, **$23.0 million (regulatory)**, and **$110.0 million (commercial)** per program, plus tiered mid-single digit royalties[50](index=50&type=chunk) - Sanofi collaboration was terminated effective October 23, 2019; **$5.3 million** allocated to the Sickle Cell License Option Material Right was recognized as revenue in Q2 2019[63](index=63&type=chunk) - Oxurion collaboration recognized **$2.4 million in revenue** during Q3 2020 due to a milestone achieved for the initiation of a Phase II clinical trial of THR-149[68](index=68&type=chunk) - Genentech collaboration, entered February 2020, included a **$30.0 million upfront payment** and potential milestones up to **$200.0 million (development)**, **$135.0 million (regulatory)**, and **$200.0 million (sales)** per program, plus tiered mid-single to low double-digit royalties[76](index=76&type=chunk) | Deferred Revenue Source | Beginning Balance Jan 1, 2020 ($ thousands) | Additions ($ thousands) | Deductions ($ thousands) | Ending Balance Sep 30, 2020 ($ thousands) | | :------------------------------------ | :------------------------------------------ | :---------------------- | :----------------------- | :---------------------------------------- | | AstraZeneca collaboration | 4,913 | 433 | (118) | 5,090 | | DDF collaboration | 744 | — | (178) | 550 | | Genentech collaboration | — | 31,000 | (3,200) | 27,635 | | Total deferred revenue | 5,657 | 31,433 | (3,496) | 33,275 | [12. Income Taxes](index=35&type=section&id=12.%20Income%20Taxes) This note explains the company's income tax benefit, primarily from deferred tax assets in the United States, and its approach to UK corporate taxation, including R&D tax credits and valuation allowances against UK deferred tax assets | Metric | Three Months Ended Sep 30, 2020 ($ thousands) | Three Months Ended Sep 30, 2019 ($ thousands) | Nine Months Ended Sep 30, 2020 ($ thousands) | Nine Months Ended Sep 30, 2019 ($ thousands) | | :------------------------------------ | :-------------------------------------------- | :-------------------------------------------- | :------------------------------------------- | :------------------------------------------- | | Income tax benefit | 465 | 331 | 668 | 116 | - The income tax benefit is mainly from deferred tax assets in the United States due to intercompany service agreements[91](index=91&type=chunk) - A full valuation allowance is maintained against UK deferred tax assets due to a history of cumulative net losses in the UK[93](index=93&type=chunk) - UK R&D tax credits are recorded as a reduction to R&D expense and are fully refundable[137](index=137&type=chunk) [13. Commitments and Contingencies](index=36&type=section&id=13.%20Commitments%20and%20Contingencies) This note details the company's lease commitments for office and laboratory space, legal proceedings, founder royalty arrangements, and indemnification obligations, highlighting the ongoing Pepscan litigation and the associated risks | Year Ending December 31, | Operating Lease Commitments ($ thousands) | | :----------------------- | :---------------------------------------- | | 2020 | 226 | | 2021 | 766 | | 2022 | 444 | | 2023 | — | | Present value adjustment | (107) | | Total lease liabilities | 1,329 | | Less: current lease liabilities | (684) | | Long term lease liabilities | 645 | - The company is involved in litigation with Pepscan Systems B.V. regarding a non-exclusive patent license agreement, with an injunction granted against BicycleRD exploiting licensed patents and know-how[100](index=100&type=chunk) - Founder Royalty Agreement entails **low single-digit royalty payments** on net product sales from Oxurion and AstraZeneca collaborations for **10 years** from first commercial sale[101](index=101&type=chunk) - The company has indemnification obligations to vendors, partners, and directors, with maximum potential amounts often unlimited, but no material costs incurred to date[102](index=102&type=chunk) [14. Net loss per share](index=38&type=section&id=14.%20Net%20loss%20per%20share) This note presents the calculation of basic and diluted net loss per share, indicating that potentially dilutive securities were excluded due to their anti-dilutive effect, resulting in the same weighted average ordinary shares outstanding for both basic and diluted calculations | Metric | Three Months Ended Sep 30, 2020 | Three Months Ended Sep 30, 2019 | Nine Months Ended Sep 30, 2020 | Nine Months Ended Sep 30, 2019 | | :------------------------------------------------ | :------------------------------ | :------------------------------ | :----------------------------- | :----------------------------- | | Net loss attributable to ordinary shareholders ($ thousands) | (10,138) | (9,482) | (33,577) | (26,202) | | Weighted average ordinary shares outstanding | 19,426,833 | 17,900,978 | 18,504,013 | 8,734,943 | | Net loss per share (basic and diluted) | (0.52) | (0.53) | (1.81) | (3.00) | - Potentially dilutive securities (share options, convertible preferred shares, warrants, unvested restricted shares) were excluded from diluted EPS calculation as their effect would be anti-dilutive[103](index=103&type=chunk)[106](index=106&type=chunk) [15. Benefit plans](index=39&type=section&id=15.%20Benefit%20plans) This note describes the company's employee benefit plans, including the 401(k) Plan for U.S. employees and a pension contribution plan for UK employees, detailing the contributions made for the reported periods | Plan | Three Months Ended Sep 30, 2020 ($ thousands) | Three Months Ended Sep 30, 2019 ($ thousands) | Nine Months Ended Sep 30, 2020 ($ thousands) | Nine Months Ended Sep 30, 2019 ($ thousands) | | :-------------------- | :-------------------------------------------- | :-------------------------------------------- | :------------------------------------------- | :------------------------------------------- | | 401(k) Plan | 34 | 26 | 100 | 100 | | U.K. Plan | 100 | 100 | 300 | 200 | [16. Related party transactions](index=39&type=section&id=16.%20Related%20party%20transactions) This note discloses transactions with related parties, including founder royalty arrangements and consultancy services provided by entities associated with board members - The company has Founder Royalty Agreements with its founders and initial investors, but no royalties have been earned or paid to date[109](index=109&type=chunk) | Related Party | Three Months Ended Sep 30, 2020 ($ thousands) | Three Months Ended Sep 30, 2019 ($ thousands) | Nine Months Ended Sep 30, 2020 ($ thousands) | Nine Months Ended Sep 30, 2019 ($ thousands) | | :------------------------------------ | :-------------------------------------------- | :-------------------------------------------- | :------------------------------------------- | :------------------------------------------- | | Stone Sunny Isles, Inc. (Chairman) | 40 | 40 | 100 | 100 | | 10X Capital Inc. (Former Chairman) | 0 | 0 | 0 | 50 | [17. Geographic information](index=40&type=section&id=17.%20Geographic%20information) This note provides geographic information on the company's long-lived assets, indicating operations in the United States and the United Kingdom, with collaboration revenues attributed to UK operations | Geographic Region | September 30, 2020 ($ thousands) | December 31, 2019 ($ thousands) | | :---------------- | :------------------------------- | :------------------------------ | | United States | 1,672 | 2,017 | | United Kingdom | 1,826 | 2,331 | | Total | 3,498 | 4,348 | - All collaboration revenues are attributed to the company's operations in the United Kingdom[111](index=111&type=chunk) [18. Subsequent events](index=40&type=section&id=18.%20Subsequent%20events) This note discloses subsequent events, specifically the completion of the initial $50.0 million at-the-market (ATM) offering and the registration of an additional $75.0 million ATM offering in October 2020 - On October 1, 2020, the company completed the sale of the initial **$50.0 million** under its ATM program, selling **98,100 ADSs for $1.8 million net proceeds**[111](index=111&type=chunk) - On October 2, 2020, the company registered an offer and sale of ADSs for up to an additional **$75.0 million** under the ATM program[111](index=111&type=chunk) [Item 2. Management's Discussion and Analysis of Financial Condition and Results of Operations](index=41&type=section&id=Item%202.%20Management's%20Discussion%20and%20Analysis%20of%20Financial%20Condition%20and%20Results%20of%20Operations) This section provides management's perspective on the company's financial condition and results of operations, discussing its business overview, the impact of COVID-19, financial performance, liquidity, and critical accounting policies. It highlights the company's focus on developing Bicycle® medicines, its significant operating losses, and its need for additional funding [Overview](index=41&type=section&id=Overview) Bicycle Therapeutics plc is a clinical-stage biopharmaceutical company developing Bicycles®, a novel class of synthetic short peptides, for diseases with high unmet medical needs, particularly in oncology, and through collaborations in other therapeutic areas - Bicycle Therapeutics is a clinical-stage biopharmaceutical company developing Bicycles®, novel synthetic short peptides combining biologic pharmacology with small molecule properties[114](index=114&type=chunk) - The company's initial internal programs focus on oncology, with lead candidates **BT1718**, **BT5528**, and **BT8009** in Phase I/II clinical trials[115](index=115&type=chunk) - Collaborations extend beyond oncology to antibacterial, cardiovascular, ophthalmology, dementia, and respiratory indications[114](index=114&type=chunk)[115](index=115&type=chunk) [COVID-19 Business Update](index=42&type=section&id=COVID-19%20Business%20Update) The company has implemented business continuity plans to mitigate the impact of the COVID-19 pandemic, which has caused limited financial and operational disruptions but led to temporary pauses in clinical trial enrollment and potential future impacts on supply chain and financial markets - The company established a cross-functional task force and implemented business continuity plans to address COVID-19 impacts[117](index=117&type=chunk) - Clinical sites for the BT1718 Phase I/IIa trial temporarily paused new patient enrollment in H1 2020 due to COVID-19, but enrollment resumed in Q2 2020[118](index=118&type=chunk) - The company anticipates potential impacts on patient enrollment, study drug supply, trial results reporting, and interactions with regulators due to the ongoing pandemic[118](index=118&type=chunk) [Financial Overview](index=43&type=section&id=Financial%20Overview) Since inception, the company has focused on R&D, incurring significant operating losses and accumulating a deficit of $134.1 million as of September 30, 2020. Operations are financed through equity sales, collaboration payments, and debt, with substantial additional funding expected to be required for future development and potential commercialization - The company has incurred significant operating losses since inception, with a **net loss of $33.6 million** for the nine months ended September 30, 2020, and an **accumulated deficit of $134.1 million**[123](index=123&type=chunk) - Funding has come from **$241.3 million in equity sales**, **$61.9 million from collaboration agreements**, and **$15.0 million from debt**[123](index=123&type=chunk) - Expenses and capital requirements are expected to increase substantially with ongoing clinical trials, preclinical activities, and potential commercialization efforts[123](index=123&type=chunk) [Components of Our Results of Operations](index=44&type=section&id=Components%20of%20Our%20Results%20of%20Operations) This section breaks down the key components of the company's results of operations, including collaboration revenues, research and development expenses, general and administrative expenses, other income/expense, and benefit from income taxes, explaining the factors influencing each [Collaboration Revenues](index=44&type=section&id=Collaboration%20Revenues) Collaboration revenues are the company's primary revenue source, including upfront payments, milestone payments, option exercise payments, and R&D services under agreements with partners like Genentech, AstraZeneca, Sanofi, Oxurion, and DDF, with future fluctuations expected based on payment timing - Collaboration revenue is the primary revenue source, including upfront payments, milestones, option exercise payments, and R&D services[126](index=126&type=chunk) - Future revenue is expected to fluctuate based on the timing and amount of license, research, development, and milestone payments[126](index=126&type=chunk) [Research and Development Expenses](index=45&type=section&id=Research%20and%20Development%20Expenses) Research and development expenses are expensed as incurred and include employee-related costs, third-party contract services, lab supplies, and regulatory compliance. These costs are expected to increase significantly as product candidates advance through clinical development, with UK R&D tax credits offsetting some expenses - R&D expenses include employee costs, third-party contract services (preclinical, clinical, manufacturing), consultants, lab supplies, and regulatory compliance[128](index=128&type=chunk) - UK R&D tax credits and government grant funding are recorded as an offset to R&D expense[128](index=128&type=chunk) - R&D expenses are expected to increase substantially due to expanded product candidate portfolio and progression into later-stage clinical trials[130](index=130&type=chunk) - The successful development of product candidates is highly uncertain, with numerous risks including the impact of COVID-19, clinical trial failures, and regulatory approvals[130](index=130&type=chunk) [General and Administrative Expenses](index=47&type=section&id=General%20and%20Administrative%20Expenses) General and administrative expenses primarily cover salaries, share-based compensation for executive and administrative functions, professional fees, and facility-related costs. These expenses are expected to increase as the company grows and incurs costs associated with being a public company, with foreign currency fluctuations also impacting these costs - G&A expenses include salaries, share-based compensation, professional fees (legal, accounting, consulting), insurance, and facility costs[133](index=133&type=chunk) - Foreign exchange differences from transactions in non-functional currencies are recorded in G&A expense[133](index=133&type=chunk) - G&A expenses are expected to increase with headcount growth and costs associated with public company operations[133](index=133&type=chunk) [Other Income (Expense)](index=47&type=section&id=Other%20Income%20(Expense)) Other income (expense) primarily consists of interest earned on cash and, prior to the IPO, changes in the fair value of warrant liabilities. Interest expense is expected to increase due to the new loan agreement with Hercules - Interest and other income, net, primarily consists of interest earned on cash[134](index=134&type=chunk) - Other expense, net, prior to the IPO, included changes in the fair value of warrant liability; no additional expense is expected from this in future periods[136](index=136&type=chunk) - Interest expense is expected to increase in future periods due to the Loan Agreement with Hercules[134](index=134&type=chunk) [Benefit From Income Taxes](index=48&type=section&id=Benefit%20From%20Income%20Taxes) The company's income tax benefit primarily stems from US operating activities generating taxable income through intercompany service arrangements, while UK R&D tax credits are recorded as a reduction to R&D expenses, and a full valuation allowance is maintained against UK deferred tax assets - Income tax benefit represents the tax impact from US operating activities, which generated taxable income in certain periods[137](index=137&type=chunk) - UK R&D tax credits are recorded as a reduction to R&D expenses and are fully refundable[137](index=137&type=chunk) - The company maintains a full valuation allowance on its UK deferred tax assets due to a history of cumulative net losses in the UK[93](index=93&type=chunk) [Results of Operations](index=48&type=section&id=Results%20of%20Operations) This section provides a comparative analysis of the company's financial results for the three and nine months ended September 30, 2020, versus 2019, detailing changes in collaboration revenues, research and development expenses, general and administrative expenses, and other income/expense [Comparison of the Three Months Ended September 30, 2020 and 2019](index=48&type=section&id=Comparison%20of%20the%20Three%20Months%20Ended%20September%2030,%202020%20and%202019) For the three months ended September 30, 2020, collaboration revenues increased significantly due to a milestone from Oxurion and revenue from Genentech. Operating expenses also rose, driven by increased R&D for clinical programs and higher G&A costs for public company operations, leading to a larger net loss | Metric | 3 Months Ended Sep 30, 2020 ($ thousands) | 3 Months Ended Sep 30, 2019 ($ thousands) | Change ($ thousands) | | :------------------------------------ | :---------------------------------------- | :---------------------------------------- | :------------------- | | Collaboration revenues | 3,842 | 614 | 3,228 | | Research and development | 7,363 | 6,078 | 1,285 | | General and administrative | 7,154 | 4,789 | 2,365 | | Total operating expenses | 14,517 | 10,867 | 3,650 | | Loss from operations | (10,675) | (10,253) | (422) | | Net loss | (10,138) | (9,482) | (656) | - Collaboration revenues increased by **$3.2 million**, primarily due to a **$2.4 million milestone from Oxurion** and **$1.2 million from the Genentech collaboration**[138](index=138&type=chunk) - R&D expenses increased by **$1.3 million**, driven by higher direct program spend for BT5528 and BT8009, increased personnel costs, and share-based compensation, partially offset by decreased unallocated discovery expense[139](index=139&type=chunk) - G&A expenses increased by **$2.4 million**, mainly due to higher professional fees, personnel costs, and share-based compensation to support public company operations[141](index=141&type=chunk) [Comparison of the Nine Months Ended September 30, 2020 and 2019](index=51&type=section&id=Comparison%20of%20the%20Nine%20Months%20Ended%20September%2030,%202020%20and%202019) For the nine months ended September 30, 2020, collaboration revenues decreased due to the termination of the Sanofi agreement and a one-time payment in 2019, despite new revenues from Genentech and Oxurion. Operating expenses significantly increased across R&D and G&A, leading to a larger net loss, while other income (expense) improved due to the absence of warrant liability remeasurement costs from the prior year | Metric | 9 Months Ended Sep 30, 2020 ($ thousands) | 9 Months Ended Sep 30, 2019 ($ thousands) | Change ($ thousands) | | :------------------------------------ | :---------------------------------------- | :---------------------------------------- | :------------------- | | Collaboration revenues | 6,542 | 8,520 | (1,978) | | Research and development | 23,091 | 18,891 | 4,200 | | General and administrative | 18,351 | 11,164 | 7,187 | | Total operating expenses | 41,442 | 30,055 | 11,387 | | Loss from operations | (34,900) | (21,535) | (13,365) | | Net loss | (33,577) | (26,202) | (7,375) | - Collaboration revenues decreased by **$2.0 million**, primarily due to a **$6.0 million decrease from the Sanofi termination** and a **$1.0 million decrease from a 2019 Material Transfer Agreement**, partially offset by **$3.1 million from Genentech** and **$2.4 million from Oxurion**[144](index=144&type=chunk) - R&D expenses increased by **$4.2 million**, driven by a **$2.4 million increase in direct program spend** (clinical and TICA programs) and higher personnel costs, offset by a **$2.2 million decrease in other unallocated discovery expense**[145](index=145&type=chunk) - G&A expenses increased by **$7.2 million**, mainly due to higher professional fees, personnel costs, and share-based compensation to support public company operations[148](index=148&type=chunk) - Other income (expense), net, increased by **$5.4 million**, primarily due to the absence of a **$5.4 million other expense related to warrant liability remeasurement** in 2019[149](index=149&type=chunk) [Liquidity and Capital Resources](index=52&type=section&id=Liquidity%20and%20Capital%20Resources) The company has historically incurred significant operating losses and relies on equity offerings, collaboration payments, and debt financing. As of September 30, 2020, cash was $149.8 million, expected to fund operations for at least 12 months. Substantial additional funding will be required for future development and commercialization, with risks including market disruptions from COVID-19 and potential dilution or restrictive covenants from new financing - The company has incurred significant operating losses and negative cash flows since inception, with no product sales revenue[149](index=149&type=chunk) - Funding sources include **$241.3 million from equity sales**, **$61.9 million from collaboration agreements**, and **$15.0 million from debt**[147](index=147&type=chunk) | Cash Flow Category | 9 Months Ended Sep 30, 2020 ($ thousands) | 9 Months Ended Sep 30, 2019 ($ thousands) | | :------------------------------------ | :---------------------------------------- | :---------------------------------------- | | Net cash used in operating activities | (1,172) | (23,694) | | Net cash used in investing activities | (716) | (1,164) | | Net cash provided by financing activities | 61,099 | 58,318 | | Net increase in cash | 57,725 | 32,574 | | Cash at end of period | 149,842 | 95,954 | - Existing cash of **$149.8 million** as of September 30, 2020, is expected to fund operating expenses and capital expenditure requirements for at least **12 months**[155](index=155&type=chunk) - Future funding requirements are substantial and depend on the progress of product candidates, regulatory approvals, commercialization costs, and intellectual property protection[155](index=155&type=chunk) | Obligation Type | Total ($ thousands) | Less than 1 year ($ thousands) | 1 to 3 years ($ thousands) | 3 to 5 years ($ thousands) | | :-------------------------- | :------------------ | :----------------------------- | :------------------------- | :------------------------- | | Operating lease commitments | 1,436 | 875 | 561 | — | | Debt obligations | 19,891 | 1,239 | 17,194 | 1,458 | | Total | 21,327 | 2,114 | 17,755 | 1,458 | [Critical Accounting Policies and Significant Judgments and Estimates](index=57&type=section&id=Critical%20Accounting%20Policies%20and%20Significant%20Judgments%20and%20Estimates) This section refers to the company's 2019 Annual Report for a detailed discussion of critical accounting policies and significant judgments and estimates, noting no significant changes since then, other than those disclosed in Note 2 of the current report - Critical accounting policies and significant judgments and estimates are consistent with those disclosed in the 2019 Annual Report on Form 10-K, with no significant changes other than those in Note 2[162](index=162&type=chunk) [Off-Balance Sheet Arrangements](index=57&type=section&id=Off-Balance%20Sheet%20Arrangements) The company states that it has not entered into any off-balance sheet arrangements and does not hold any interests in variable interest entities - The company has not entered into any off-balance sheet arrangements[163](index=163&type=chunk) - The company does not have any holdings in variable interest entities[163](index=163&type=chunk) [Emerging Growth Company and Smaller Reporting Company Status](index=57&type=section&id=Emerging%20Growth%20Company%20and%20Smaller%20Reporting%20Company%20Status) The company qualifies as an 'emerging growth company' (EGC) and 'smaller reporting company,' allowing it to take advantage of reduced disclosure requirements, though it has opted out of the extended transition period for new accounting standards - The company is an **'emerging growth company' (EGC)** and will remain so until the earlier of December 31, 2024, or meeting certain revenue/market value thresholds[163](index=163&type=chunk) - The company has irrevocably elected to **'opt out' of the extended transition period** for complying with new or revised financial accounting standards[163](index=163&type=chunk) - As an EGC and smaller reporting company, it can rely on exemptions from certain disclosure requirements, including auditor attestation on internal controls and reduced executive compensation disclosures[163](index=163&type=chunk)[165](index=165&type=chunk) [Item 3. Quantitative and Qualitative Disclosure About Market Risk](index=58&type=section&id=Item%203.%20Quantitative%20and%20Qualitative%20Disclosure%20About%20Market%20Risk) This section discusses the company's exposure to market risks, specifically interest rate sensitivity and foreign currency exchange risk, and its strategies for managing these risks [Interest Rate Sensitivity](index=58&type=section&id=Interest%20Rate%20Sensitivity) The company's exposure to interest rate sensitivity is primarily from its cash holdings and term debt. Due to the conservative nature of its investments, a one percentage point change in interest rates is not expected to materially affect its portfolio's fair value, though debt interest expense would increase - As of September 30, 2020, the company had **$149.8 million in cash**, invested in interest-bearing savings accounts[166](index=166&type=chunk) - An immediate **one percentage point change in interest rates** is not expected to materially affect the fair market value of the investment portfolio[166](index=166&type=chunk) - A **10% increase in interest rates** on the **$15.0 million term debt** outstanding with Hercules would result in approximately **$0.1 million in incremental annualized interest expense**[166](index=166&type=chunk) [Foreign Currency Exchange Risk](index=58&type=section&id=Foreign%20Currency%20Exchange%20Risk) The company is exposed to foreign currency exchange risk due to international operations, particularly fluctuations between the pound sterling, U.S. dollar, and euro. While the parent company's functional currency is USD, its UK subsidiaries use GBP. Exchange gains/losses are recorded in net loss, and translation adjustments in other comprehensive income/loss. The company does not currently hedge currency exposure - The functional currency of Bicycle Therapeutics plc and Bicycle Therapeutics Inc. is USD, while UK subsidiaries (BicycleTx Limited and BicycleRD Limited) use British Pound Sterling[167](index=167&type=chunk) | Metric | 3 Months Ended Sep 30, 2020 ($ thousands) | 3 Months Ended Sep 30, 2019 ($ thousands) | 9 Months Ended Sep 30, 2020 ($ thousands) | 9 Months Ended Sep 30, 2019 ($ thousands) | | :------------------------------------ | :---------------------------------------- | :---------------------------------------- | :---------------------------------------- | :---------------------------------------- | | Foreign exchange loss (gain) | (700) | (800) | 700 (gain) | (400) (loss) | - The company does not currently engage in currency hedging activities[169](index=169&type=chunk) [Item 4. Controls and Procedures](index=59&type=section&id=Item%204.%20Controls%20and%20Procedures) This section confirms the effectiveness of the company's disclosure controls and procedures as of September 30, 2020, and reports no material changes in internal control over financial reporting during the quarter - Management, including the CEO and CFO, concluded that disclosure controls and procedures were **effective at the reasonable assurance level** as of September 30, 2020[169](index=169&type=chunk) - There were no changes in internal control over financial reporting that materially affected, or are reasonably likely to materially affect, internal control over financial reporting during the three months ended September 30, 2020[169](index=169&type=chunk) [PART II - OTHER INFORMATION](index=60&type=section&id=PART%20II%20-%20OTHER%20INFORMATION) [Item 1. Legal Proceedings](index=60&type=section&id=Item%201.%20Legal%20Proceedings) This section details ongoing legal proceedings, primarily focusing on the license litigation with Pepscan Systems B.V. regarding patent rights for BicycleRD's scaffold technology, including appeals, inter partes reviews, and European patent opposition proceedings - BicycleRD is involved in ongoing license litigation with Pepscan Systems B.V. regarding a non-exclusive patent license agreement from 2009[172](index=172&type=chunk) - The Court of Appeal of The Hague ruled in February 2020 that Pepscan was entitled to terminate the license and granted a worldwide injunction against BicycleRD, which BicycleRD has appealed to the Dutch Supreme Court[172](index=172&type=chunk) - BicycleRD filed two petitions for inter partes review (IPR) with the USPTO in September 2020, challenging the validity of Pepscan's U.S. Patents No. 8,742,070 and No. 8,748,105, both expiring in February 2024[171](index=171&type=chunk)[174](index=174&type=chunk) - European Patent Opposition Proceedings are ongoing for foundational and divisional patents related to the company's technology platform, with hearings scheduled or decisions pending[174](index=174&type=chunk) [Item 1A. Risk Factors](index=61&type=section&id=Item%201A.%20Risk%20Factors) This section outlines significant risks associated with investing in the company, covering financial position, product development, regulatory approvals, commercialization, international operations, dependence on third parties, intellectual property, employee matters, and ownership of securities [Risks Related to Our Financial Position and Need for Additional Capital](index=61&type=section&id=Risks%20Related%20to%20Our%20Financial%20Position%20and%20Need%20for%20Additional%20Capital) The company has a history of significant operating losses and an accumulated deficit, requiring substantial additional funding for future development and commercialization. Failure to raise capital could delay or eliminate programs, and existing debt obligations could limit cash flow or lead to acceleration of repayment - The company has incurred recurring losses since inception, with a **$33.6 million net loss** for the nine months ended September 30, 2020, and an **accumulated deficit of $134.1 million**[176](index=176&type=chunk) - Substantial additional funding is required to advance product candidates, seek marketing approvals, establish manufacturing and commercial infrastructure, and operate as a public company[178](index=178&type=chunk)[180](index=180&type=chunk) - Existing cash of **$149.8 million** (as of Sep 30, 2020) is expected to fund operations for at least **12 months**, but this estimate may be wrong[182](index=182&type=chunk) - Failure to comply with covenants or payment obligations under the Hercules term loan facility (**$15.0 million outstanding**) could result in increased interest, accelerated repayment, or other adverse actions[184](index=184&type=chunk) [Risks Related to the Discovery, Development and Regulatory Approval of Our Product Candidates](index=66&type=section&id=Risks%20Related%20to%20the%20Discovery,%20Development%20and%20Regulatory%20Approval%20of%20Our%20Product%20Candidates) The company's success heavily depends on its internal development programs and product candidates, which are in early stages and face high risks of failure in preclinical and clinical trials. Challenges include unpredictable outcomes, difficulties in patient enrollment (exacerbated by COVID-19), potential for unacceptable side effects, and the need for companion diagnostics, all of which could delay or prevent regulatory approval - Future success is heavily dependent on the success of BTC and tumor-targeted immune cell agonist programs, including **BT1718**, **BT5528**, **BT8009**, and **BT7480**[188](index=188&type=chunk) - Preclinical studies and clinical trials are long, expensive, unpredictable, and have a high risk of failure, with potential delays from patient enrollment difficulties (exacerbated by COVID-19)[190](index=190&type=chunk)[192](index=192&type=chunk)[194](index=194&type=chunk) - Unacceptable side effect profiles could lead to suspension or termination of clinical trials or denial of regulatory approval[202](index=202&type=chunk) - Failure to successfully validate, develop, and obtain regulatory approval for companion diagnostics could harm the drug development strategy[200](index=200&type=chunk) [Risks Related to Commercialization of Our Product Candidates and Other Regulatory Compliance Matters](index=72&type=section&id=Risks%20Related%20to%20Commercialization%20of%20Our%20Product%20Candidates%20and%20Other%20Regulatory%20Compliance%20Matters) Commercialization of product candidates faces significant hurdles, including the expensive and uncertain marketing approval process, lack of internal sales infrastructure, limited market opportunities, and challenges in obtaining adequate insurance coverage and reimbursement. The company is also subject to extensive healthcare fraud and abuse laws, and legislative reforms could negatively impact its business - The marketing approval process is lengthy, expensive, and uncertain, potentially leading to delays, rejections, or limited approvals[210](index=210&type=chunk)[212](index=212&type=chunk) - The company lacks internal marketing, sales, and distribution infrastructure, requiring significant investment or reliance on third-party collaborations, which carry inherent risks[212](index=212&type=chunk)[214](index=214&type=chunk) - Market opportunities may be limited to specific patient populations or later-line therapies, potentially hindering profitability[215](index=215&type=chunk) - Failure to obtain or maintain adequate insurance coverage and reimbursement for approved products could limit marketability and revenue generation[223](index=223&type=chunk)[224](index=224&type=chunk) - The company is subject to federal and state healthcare fraud and abuse laws (e.g., Anti-Kickback Statute, False Claims Act, HIPAA), with potential for substantial penalties for non-compliance[227](index=227&type=chunk)[229](index=229&type=chunk) - Healthcare legislative reforms (e.g., ACA, drug pricing initiatives) could negatively impact the business by imposing stricter regulations, cost containment measures, or reduced reimbursement[232](index=232&type=chunk)[234](index=234&type=chunk)[236](index=236&type=chunk) [Risks Related to Our Business and Our International Operations](index=89&type=section&id=Risks%20Related%20to%20Our%20Business%20and%20Our%20International%20Operations) Operating internationally exposes the company to economic, political, and regulatory risks, including the impact of COVID-19, foreign currency fluctuations, and restrictive data protection regulations like GDPR. Brexit also introduces significant uncertainty regarding regulatory approvals, trade, and data transfers between the UK and EU - The COVID-19 pandemic could materially affect operations, clinical trials, and supply chains, with potential for delays, reduced productivity, and negative economic impacts[242](index=242&type=chunk)[244](index=244&type=chunk) - International operations expose the company to risks such as economic weakness, differing regulatory requirements, intellectual property protection challenges, and changes in currency exchange rates[244](index=244&type=chunk) - European data collection is governed by GDPR, which imposes strict requirements on personal data handling and cross-border transfers, with potential for significant fines for non-compliance[246](index=246&type=chunk)[248](index=248&type=chunk)[249](index=249&type=chunk) - Brexit introduces legal, political, and economic uncertainty, potentially impacting regulatory approvals in the EU/UK, increasing costs, and disrupting operations and data transfers[209](index=209&type=chunk)[251](index=251&type=chunk)[253](index=253&type=chunk) - Fluctuations in exchange rates, particularly between GBP, USD, and EUR, may materially affect results of operations and financial condition, as the company does not currently hedge currency exposure[254](index=254&type=chunk) [Risks Related to Our Dependence on Third Parties](index=95&type=section&id=Risks%20Related%20to%20Our%20Dependence%20on%20Third%20Parties) The company heavily relies on third-party collaborators, clinical investigators, and manufacturers for product development and commercialization. Failures by these third parties to perform as expected, conflicts arising from collaborations, or disruptions in manufacturing could significantly delay or impair the company's ability to obtain regulatory approvals, generate revenue, and protect its intellectual property - The company depends on development and commercialization collaborators (e.g., Genentech, AstraZeneca, Oxurion, CRUK) to develop, conduct clinical trials, obtain regulatory approvals, and market product candidates[255](index=255&type=chunk) - Risks include collaborators not performing obligations, delaying trials, abandoning candidates, or developing competing products, which could reduce or eliminate future revenue[257](index=257&type=chunk) - Conflicts with collaborators or licensors, such as the ongoing litigation with Pepscan, could adversely affect the business and intellectual property rights[259](index=259&type=chunk)[260](index=260&type=chunk) - Reliance on third-party CROs and clinical investigators to conduct trials means the company has limited control over their performance, and any failures could delay regulatory approval[262](index=262&type=chunk)[263](index=263&type=chunk) - Outsourcing all manufacturing to third parties increases risks of production delays, insufficient supplies, quality issues, and non-compliance with cGMP requirements[264](index=264&type=chunk)[265](index=265&type=chunk) - Sharing trade secrets with third parties increases the risk of misappropriation or disclosure, potentially impairing the company's competitive position[266](index=266&type=chunk) [Risks Related to Intellectual Property](index=102&type=section&id=Risks%20Related%20to%20Intellectual%20Property) The company's ability to protect its products and candidates relies on patents, trade secrets, and contractual provisions, but these offer limited protection. Challenges include the uncertainty of patent issuance and enforceability, potential infringement claims from third parties, and the difficulty of protecting trade secrets. Failure to maintain intellectual property rights could severely impact the business and competitive position - The company's intellectual property portfolio includes patent families directed to novel scaffolds, platform technology, bicyclic conjugates, and clinical indications[268](index=268&type=chunk) - Patent applications may not issue as patents, or resulting patents may not provide a competitive advantage or sufficient protection against competitors[268](index=268&type=chunk) - Issued patents could be found invalid or unenforceable if challenged in court or administrative proceedings, such as the ongoing Pepscan litigation and European patent oppositions[271](index=271&type=chunk) - Reliance on trade secrets and know-how is risky, as they are difficult to protect and may become known or independently developed by competitors[270](index=270&type=chunk)[273](index=273&type=chunk) - Changes in patent law (e.g., Leahy-Smith America Invents Act) and judicial interpretations could diminish the value of patents and impair protection efforts[277](index=277&type=chunk) - Being sued for infringing third-party intellectual property rights could be costly, time-consuming, and prevent or delay development/commercialization of product candidates[281](index=281&type=chunk)[283](index=283&type=chunk) [Risks Related to Employee Matters and Managing Growth](index=109&type=section&id=Risks%20Related%20to%20Employee%20Matters%20and%20Managing%20Growth) The company's success is highly dependent on its limited number of key employees, consultants, and advisors, and its ability to attract and retain qualified personnel in a competitive industry. Expected organizational expansion and reliance on IT systems also pose risks related to managing growth, potential misconduct, and cyber-attacks - The company has a limited number of **81 full-time or part-time employees** as of September 30, 2020, and relies heavily on key personnel[289](index=289&type=chunk) - Future success depends on the ability to retain key employees, consultants, and advisors, and to attract, retain, and motivate qualified personnel in a competitive industry[292](index=292&type=chunk) - Cyber-attacks or failures in IT systems could result in information theft, data corruption, and significant business disruption, especially with increased remote work due to COVID-19[290](index=290&type=chunk)[292](index=292&type=chunk) - Employees, contractors, and collaborators may engage in misconduct or improper activities, leading to significant liability and reputational harm[293](index=293&type=chunk)[294](index=294&type=chunk) - Expected organizational expansion poses challenges in managing growth, including implementing systems, expanding facilities, and recruiting/training personnel[294](index=294&type=chunk) [Risks Related to Ownership of Our Securities](index=111&type=section&id=Risks%20Related%20to%20Ownership%20of%20Our%20Securities) The market price of the company's ADSs is highly volatile and influenced by numerous factors, including clinical trial results, funding, and market perception. Future sales of securities could dilute existing shareholders, and the company's broad discretion in using cash reserves may not always enhance shareholder value. As an English company, shareholder rights may differ from those in the U.S., and U.S. civil liabilities may not be enforceable. The company's status as an EGC and smaller reporting company allows for reduced disclosures, which may affect investor attractiveness - The market price of ADSs is highly volatile, influenced by clinical trial results, funding, regulatory decisions, competition, and broader market factors, including the COVID-19 pandemic[295](index=295&type=chunk)[297](index=297&type=chunk)[298](index=298&type=chunk) - Future sales of a substantial number of securities by existing shareholders or through equity incentive plans could adversely affect ADS price and dilute shareholders[303](index=303&type=chunk)[305](index=305&type=chunk) - Management has broad discretion in using cash reserves, which may not always improve results or enhance shareholder value[306](index=306&type=chunk) - As an English company, shareholder rights differ from typical U.S. corporations, and U.S. civil liabilities may not be enforceable against the company or its non-U.S. directors/management[307](index=307&type=chunk)[309](index=309&type=chunk)[322](index=322&type=chunk)[324](index=324&type=chunk) - The company's status as an **'emerging growth company'** and **'smaller reporting company'** allows for reduced disclosure requirements, which may make ADSs less attractive to some investors[309](index=309&type=chunk)[310](index=310&type=chunk) [Item 2. Unregistered Sales of Equity Securities and Use of Proceeds](index=116&type=section&id=Item%202.%20Unregistered%20Sales%20of%20Equity%20Securities%20and%20Use%20of%20Proceeds) This section details the use of proceeds from the company's initial public offering (IPO) in May 2019, including the aggregate net proceeds and how they have been utilized to advance product development programs and for general corporate purposes - The company completed its IPO in May 2019, raising approximately **$56.4 million in aggregate net proceeds**[327](index=327&type=chunk) - As of September 30, 2020, approximately **$47.4 million of the net proceeds** have been used to advance BT1718, BT5528, BT8009, BT7480, BT7455, and other discovery development programs, as well as for working capital and general corporate purposes[327](index=327&type=chunk) - The remaining net proceeds from the IPO are invested in interest-bearing cash accounts[327](index=327&type=chunk) [Item 3. Defaults Upon Senior Securities](index=117&type=section&id=Item%203.%20Defaults%20Upon%20Senior%20Securities) This item states that there are no defaults upon senior securities to report - Not Applicable[327](index=327&type=chunk) [Item 4. Mine Safety Disclosures](index=117&type=section&id=Item%204.%20Mine%20Safety%20Disclosures) This item states that there are no mine safety disclosures to report - Not Applicable[327](index=327&type=chunk) [Item 5. Other Information](index=117&type=section&id=Item%205.%20Other%20Information) This item indicates that there is no other information to report - None[327](index=327&type=chunk) [Item 6. Exhibits](index=117&type=section&id=Item%206.%20Exhibits) This section lists the exhibits filed with the Form 10-Q, including articles of association, letter agreements, loan and security agreements, and certifications - Exhibits include Articles of Association, Letter Agreement with Citibank, N.A., Loan and Security Agreement with Hercules Capital, Inc., and certifications of principal executive and financial officers[328](index=328&type=chunk) [SIGNATURES](index=119&type=section&id=SIGNATURES) This section contains the signatures of the company's Chief Executive Officer and Chief Financial Officer, certifying the accuracy of the Form 10-Q - The report is signed by Kevin Lee, Ph.D., MBA, Chief