Bicycle Therapeutics Investor Presentation May 2023 ...

[PART I - FINANCIAL INFORMATION](index=7&type=section&id=PART%20I%20-%20FINANCIAL%20INFORMATION) This section presents the company's unaudited financial statements and management's analysis of its financial condition and operations [Financial Statements](index=7&type=section&id=Item%201.%20Financial%20Statements) This section presents the unaudited condensed consolidated financial statements for Q1 2023, including balance sheets, statements of operations, cash flows, and detailed notes [Condensed Consolidated Balance Sheets](index=7&type=section&id=Condensed%20Consolidated%20Balance%20Sheets) As of March 31, 2023, total assets increased to $428.8 million, driven by accounts receivable, while total liabilities grew to $185.6 million due to deferred revenue Condensed Consolidated Balance Sheet (Unaudited, in thousands) | Account | March 31, 2023 | December 31, 2022 | | :--- | :--- | :--- | | **Assets** | | | | Cash and cash equivalents | $293,815 | $339,154 | | Accounts receivable | $50,000 | $2,045 | | Total current assets | $381,253 | $369,383 | | **Total assets** | **$428,801** | **$410,609** | | **Liabilities & Equity** | | | | Total current liabilities | $52,995 | $53,342 | | Deferred revenue, non-current | $83,751 | $41,455 | | Total liabilities | $185,638 | $139,826 | | Total shareholders' equity | $243,163 | $270,783 | | **Total liabilities and shareholders' equity** | **$428,801** | **$410,609** | [Condensed Consolidated Statements of Operations and Comprehensive Loss](index=8&type=section&id=Condensed%20Consolidated%20Statements%20of%20Operations%20and%20Comprehensive%20Loss) For Q1 2023, the company reported a net loss of $39.1 million, primarily due to a significant rise in research and development expenses Condensed Consolidated Statements of Operations (Unaudited, in thousands) | Account | Three Months Ended March 31, 2023 | Three Months Ended March 31, 2022 | | :--- | :--- | :--- | | Collaboration revenues | $4,896 | $3,860 | | Research and development | $32,211 | $14,284 | | General and administrative | $14,488 | $16,959 | | Loss from operations | ($41,803) | ($27,383) | | **Net loss** | **($39,064)** | **($27,564)** | | **Net loss per share, basic and diluted** | **($1.30)** | **($0.93)** | [Condensed Consolidated Statements of Cash Flows](index=10&type=section&id=Condensed%20Consolidated%20Statements%20of%20Cash%20Flows) Net cash used in operating activities significantly increased to $46.4 million in Q1 2023, leading to a decrease in cash and cash equivalents to $293.8 million Condensed Consolidated Statements of Cash Flows (Unaudited, in thousands) | Cash Flow Activity | Three Months Ended March 31, 2023 | Three Months Ended March 31, 2022 | | :--- | :--- | :--- | | Net cash used in operating activities | ($46,411) | ($26,400) | | Net cash used in investing activities | ($2,099) | ($4,756) | | Net cash provided by financing activities | $2,718 | $450 | | **Net decrease in cash and cash equivalents** | **($45,339)** | **($31,309)** | | **Cash and cash equivalents at end of period** | **$293,815** | **$407,371** | [Notes to Condensed Consolidated Financial Statements](index=11&type=section&id=Notes%20to%20Condensed%20Consolidated%20Financial%20Statements) The notes provide critical details supporting the financial statements, covering accounting policies, collaboration agreements, debt, liquidity, and future commitments - The company is a clinical-stage biopharmaceutical company developing a novel class of medicines called Bicycles, with key programs including BT5528, BT8009, and BT7480 in oncology[24](index=24&type=chunk) - As of March 31, 2023, the company had cash and cash equivalents of **$293.8 million** and believes this is sufficient to fund operations for at least twelve months from the issuance date of the financial statements[26](index=26&type=chunk)[27](index=27&type=chunk) - On March 27, 2023, the company entered into a collaboration and license agreement with Novartis, which included a nonrefundable upfront payment of **$50.0 million**, received in April 2023. The company is also eligible for up to **$840.0 million** in development and regulatory milestones and up to **$800.0 million** in sales milestones[77](index=77&type=chunk)[80](index=80&type=chunk) - The company has a loan agreement with Hercules for up to **$75.0 million**, with **$30.0 million** drawn as of March 31, 2023. The interest-only period extends to April 1, 2025, with a maturity date of July 1, 2025[50](index=50&type=chunk)[54](index=54&type=chunk) - The company has potential future milestone payment obligations under its arrangements with CRUK and another third party, with an aggregate total value of **$111.2 million** and **$92.4 million**, respectively[171](index=171&type=chunk) [Management's Discussion and Analysis of Financial Condition and Results of Operations](index=63&type=section&id=Item%202.%20Management%27s%20Discussion%20and%20Analysis%20of%20Financial%20Condition%20and%20Results%20of%20Operations) Management discusses the company's business strategy, financial performance, and liquidity, noting increased net loss from R&D and a strong cash position [Overview](index=63&type=section&id=Overview) The company provides an overview of its clinical-stage biopharmaceutical business, focusing on its novel 'Bicycles' platform in oncology, and its funding history - The company is developing a novel class of medicines, referred to as Bicycles, which are synthetic short peptides constrained to form two loops, combining features of biologics and small molecules[187](index=187&type=chunk) - Key clinical programs include BT5528 (EphA2 BTC), BT8009 (Nectin-4 BTC), and BT7480 (Nectin-4/CD137 TICA)[189](index=189&type=chunk) - On January 4, 2023, the FDA granted Fast Track Designation to BT8009 for the treatment of adult patients with previously treated locally advanced or metastatic urothelial cancer[190](index=190&type=chunk)[191](index=191&type=chunk) - From inception through March 31, 2023, the company has received gross proceeds of **$567.2 million** from equity sales, **$137.3 million** from collaboration payments, and **$30.0 million** from debt borrowings. A **$50.0 million** upfront payment from Novartis was received in April 2023[194](index=194&type=chunk) [Results of Operations](index=77&type=section&id=Results%20of%20Operations) This section details Q1 2023 financial performance, noting increased collaboration revenues, a significant surge in R&D expenses, and a decrease in G&A Comparison of Results of Operations (in thousands) | Account | Three Months Ended March 31, 2023 | Three Months Ended March 31, 2022 | Change | | :--- | :--- | :--- | :--- | | Collaboration revenues | $4,896 | $3,860 | $1,036 | | Research and development | $32,211 | $14,284 | $17,927 | | General and administrative | $14,488 | $16,959 | ($2,471) | | **Net loss** | **($39,064)** | **($27,564)** | **($11,500)** | Research and Development Expenses Breakdown (in thousands) | Program | Three Months Ended March 31, 2023 | Three Months Ended March 31, 2022 | Change | | :--- | :--- | :--- | :--- | | BT5528 (EphA2) | $3,193 | $1,402 | $1,791 | | BT8009 (Nectin-4) | $5,369 | $1,214 | $4,155 | | Bicycle TICA | $4,877 | $1,523 | $3,354 | | Other discovery & platform | $8,205 | $4,439 | $3,766 | | Employee & contractor | $10,793 | $5,582 | $5,211 | | **Total R&D Expenses** | **$32,211** | **$14,284** | **$17,927** | [Liquidity and Capital Resources](index=80&type=section&id=Liquidity%20and%20Capital%20Resources) This section details the company's liquidity, including **$293.8 million** in cash, net cash used in operations, and outlines contractual obligations and future capital needs - The company had cash and cash equivalents of **$293.8 million** as of March 31, 2023, and believes this will fund operations for at least 12 months from the filing date[201](index=201&type=chunk)[247](index=247&type=chunk) - Net cash used in operating activities increased to **$46.4 million** in Q1 2023 from **$26.4 million** in Q1 2022, primarily due to a higher net loss and changes in working capital[237](index=237&type=chunk) Material Contractual Obligations as of March 31, 2023 (in thousands) | Obligation Type | Total | Less than 1 year | 1 to 3 years | 3 to 5 years | | :--- | :--- | :--- | :--- | :--- | | Operating lease commitments | $21,665 | $5,893 | $12,689 | $3,083 | | Debt obligations | $37,358 | $2,526 | $34,832 | $0 | | **Total** | **$59,023** | **$8,419** | **$47,521** | **$3,083** | - The company has contingent future milestone payment obligations to CRUK and another third party with aggregate total values of **$111.2 million** and **$92.4 million**, respectively[246](index=246&type=chunk) [Quantitative and Qualitative Disclosure About Market Risk](index=88&type=section&id=Item%203.%20Quantitative%20and%20Qualitative%20Disclosure%20About%20Market%20Risk) The company identifies its main market risks as interest rate sensitivity and foreign currency exchange risk, with a foreign exchange loss of **$0.5 million** in Q1 2023 - The company's primary market risks are interest rate sensitivity and foreign currency exchange risk[258](index=258&type=chunk)[259](index=259&type=chunk) - Exposure to interest rate changes on cash equivalents and **$30.0 million** in debt is not expected to have a material effect on financial results[258](index=258&type=chunk)[259](index=259&type=chunk) - Foreign currency exchange risk arises from operations in both the U.S. (USD) and U.K. (GBP). The company recorded foreign exchange losses of **$0.5 million** for the three months ended March 31, 2023[260](index=260&type=chunk)[262](index=262&type=chunk) [Controls and Procedures](index=90&type=section&id=Item%204.%20Controls%20and%20Procedures) Management concluded that the company's disclosure controls and procedures were effective as of March 31, 2023, with no material changes to internal controls - Management, including the CEO and CFO, concluded that the company's disclosure controls and procedures were effective as of March 31, 2023[264](index=264&type=chunk) - There were no material changes to the company's internal control over financial reporting during the quarter ended March 31, 2023[265](index=265&type=chunk) [PART II - OTHER INFORMATION](index=91&type=section&id=PART%20II%20-%20OTHER%20INFORMATION) This section covers legal proceedings, risk factors, and other miscellaneous information pertinent to the company's operations [Legal Proceedings](index=91&type=section&id=Item%201.%20Legal%20Proceedings) The company states that it is not currently a party to any material legal proceedings - The company is not currently subject to any material legal proceedings[266](index=266&type=chunk) [Risk Factors](index=91&type=section&id=Item%201A.%20Risk%20Factors) This section outlines key risks including financial sustainability, clinical development uncertainties, third-party reliance, IP challenges, and international operational complexities - **Financial Risks:** The company has a history of significant operating losses, an accumulated deficit of **$370.2 million** as of March 31, 2023, and will require substantial additional funding to continue operations[280](index=280&type=chunk)[281](index=281&type=chunk)[290](index=290&type=chunk) - **Development and Regulatory Risks:** Success is substantially dependent on its BTC and TICA programs, which represent a new category of medicine and may face heightened regulatory scrutiny. Clinical trials are long, expensive, and their outcomes are uncertain[307](index=307&type=chunk)[312](index=312&type=chunk)[314](index=314&type=chunk) - **Third-Party Reliance:** The company relies on collaborators (e.g., Cancer Research UK, Novartis, Genentech) for development and commercialization and on third-party CROs and manufacturers, which introduces risks related to performance, supply, and quality control[471](index=471&type=chunk)[482](index=482&type=chunk)[492](index=492&type=chunk) - **Intellectual Property Risks:** The ability to compete depends on obtaining and maintaining patent protection for its technology, which is uncertain. The company may face costly litigation if sued for infringing third-party IP rights[508](index=508&type=chunk)[541](index=541&type=chunk) - **Commercialization Risks:** The company has no marketing or sales infrastructure and faces significant competition from large pharmaceutical companies. Market acceptance and adequate reimbursement for its products, if approved, are uncertain[376](index=376&type=chunk)[392](index=392&type=chunk)[405](index=405&type=chunk) - **International and Tax Risks:** As a U.K.-based company, it is subject to risks from Brexit, foreign currency fluctuations, and complex tax laws, including potential classification as a PFIC or CFC, which could have adverse U.S. tax consequences for shareholders[362](index=362&type=chunk)[470](index=470&type=chunk)[584](index=584&type=chunk) [Unregistered Sales of Equity Securities and Use of Proceeds](index=205&type=section&id=Item%202.%20Unregistered%20Sales%20of%20Equity%20Securities%20and%20Use%20of%20Proceeds) This item is marked as 'Not Applicable' in the report - Not Applicable[618](index=618&type=chunk) [Defaults Upon Senior Securities](index=205&type=section&id=Item%203.%20Defaults%20Upon%20Senior%20Securities) This item is marked as 'Not Applicable' in the report - Not Applicable[618](index=618&type=chunk) [Mine Safety Disclosures](index=205&type=section&id=Item%204.%20Mine%20Safety%20Disclosures) This item is marked as 'Not Applicable' in the report - Not Applicable[618](index=618&type=chunk) [Other Information](index=205&type=section&id=Item%205.%20Other%20Information) This item is marked as 'Not Applicable' in the report - Not Applicable[618](index=618&type=chunk) [Exhibits](index=205&type=section&id=Item%206.%20Exhibits) This section lists the exhibits filed with the quarterly report, including key executive employment agreements and the Novartis collaboration agreement - Lists filed exhibits, including amendments to several executive employment agreements and the Collaboration and Licence Agreement with Novartis Pharma AG, dated March 27, 2023[619](index=619&type=chunk) [Signatures](index=208&type=section&id=SIGNATURES) The report is duly signed on May 4, 2023, by Kevin Lee, Chief Executive Officer, and Lee Kalowski, Chief Financial Officer, on behalf of Bicycle Therapeutics plc - The report was signed by Kevin Lee, Ph.D., MBA (Chief Executive Officer) and Lee Kalowski, MBA (Chief Financial Officer and President) on May 4, 2023[624](index=624&type=chunk)

Bicycle Therapeutics Investor Presentation February 2023 ...

Financial Performance - The company has incurred net losses of $112.7 million, $66.8 million, and $51.0 million for the years ended December 31, 2022, 2021, and 2020, respectively, with an accumulated deficit of $331.1 million as of December 31, 2022[618]. - The net loss for 2022 was $112.7 million, compared to a net loss of $66.8 million in 2021, indicating a worsening financial position[644]. - The company incurred significant operating losses and negative cash flows since inception in 2009, with no revenue generated from product sales[652]. - Net cash used in operating activities for 2022 was $86.1 million, a significant increase from $14.8 million in 2021, attributed to a higher net loss and changes in operating assets and liabilities[653]. - Net cash provided by financing activities was $6.7 million in 2022, a sharp decline from $320.7 million in 2021, primarily due to reduced proceeds from share offerings[657]. Revenue Generation - The company has not generated any revenue from product sales and does not expect to do so for the foreseeable future, relying primarily on collaboration revenues[623]. - Revenue is primarily generated through collaborative arrangements and license agreements, with various payment structures including upfront fees and milestone payments[675]. - The company has not recognized any sales-based royalty revenue from collaboration agreements to date[689]. Collaboration and Partnerships - The company has received $135.2 million in cash payments under collaboration revenue arrangements, including $46.6 million from Ionis and $54.0 million from Genentech[617]. - Collaboration revenues increased by $2.8 million in 2022, primarily due to a $5.1 million increase from the collaboration with Ionis, offset by a $2.1 million decrease from Genentech[647]. - Future milestone payments related to agreements with Cancer Research UK and Pepscan Systems B.V. could total $203.6 million, contingent upon achieving specific development and regulatory milestones[664]. Expenses and Costs - Research and development expenses rose to $81.6 million in 2022, up from $44.9 million in 2021, reflecting the higher costs associated with later-stage clinical trials[644]. - General and administrative expenses increased to $49.5 million in 2022, compared to $32.4 million in 2021, driven by higher personnel costs and public company expenses[644]. - Total operating expenses for 2022 were $131.1 million, a significant increase from $77.3 million in 2021[644]. - The company expects research and development expenses to continue increasing due to an expanded portfolio of product candidates and ongoing clinical trials[628]. - The company expects general and administrative expenses to continue increasing as it expands headcount to support research and development and potential commercialization efforts[635]. Cash and Liquidity - The company had cash and cash equivalents of $339.2 million as of December 31, 2022, which is expected to fund operations for at least 12 months[622]. - As of December 31, 2022, the company had cash and cash equivalents of $339.2 million, expected to fund operating expenses for at least 12 months[665]. - The company anticipates future capital requirements will depend on factors such as drug discovery costs, clinical trial enrollment, and regulatory review outcomes[667]. Economic and Market Conditions - The ongoing COVID-19 pandemic and geopolitical tensions have led to significant disruptions in global financial markets, contributing to a general economic slowdown and high inflation rates[670]. - Rising inflation and interest rates may adversely affect operating results, particularly in clinical trial materials and labor costs, potentially stressing working capital resources[672]. - Economic conditions, including high inflation and geopolitical tensions, may adversely affect the company's financial position and cash flows[672]. Product Development - The company is developing multiple product candidates, including BT5528, BT8009, BT1718, BT7480, and BT7455, with ongoing clinical trials[611]. - The FDA granted Fast Track Designation to BT8009 for the treatment of adult patients with previously treated locally advanced or metastatic urothelial cancer[615]. - The company plans to continue developing product candidates, including BT5528, BT8009, BT7480, and BT1718, and to seek marketing approvals for successful candidates[659]. - The company anticipates significant commercialization expenses if any product candidates receive marketing approval, impacting future cash flows[660]. Financial Obligations - The company has outstanding term loans of $30.0 million under a Loan Agreement with Hercules, with additional loans of up to $45.0 million available until December 31, 2024[658]. - Total contractual obligations as of December 31, 2022, amounted to $54.1 million, including $16.0 million in operating lease commitments and $38.0 million in debt obligations[661].

Financial Performance - The company has incurred net losses of $28.3 million and $82.7 million for the three and nine months ended September 30, 2022, respectively, with an accumulated deficit of $301.1 million[192]. - The net loss for the three months ended September 30, 2022, was $28.35 million, an increase of $13.67 million from a net loss of $14.68 million in the same period of 2021[224]. - Net loss for the nine months ended September 30, 2022, was $82.7 million, compared to a net loss of $48.8 million for the same period in 2021, reflecting an increase of $33.9 million[233]. - The company has not generated any revenue from product sales since inception and expects to continue incurring significant operating losses[239]. Revenue and Collaboration - The company has not generated any revenue from product sales and does not expect to do so for the foreseeable future, relying primarily on collaboration revenues[201]. - Collaboration revenues decreased by $1.3 million to $3.04 million for the three months ended September 30, 2022, compared to $4.33 million in the same period of 2021[225]. - For the nine months ended September 30, 2022, collaboration revenues increased by $3.35 million to $11.28 million compared to $7.93 million in the same period of 2021[233][232]. Expenses and Costs - Research and development expenses increased by $12.24 million to $22.75 million for the three months ended September 30, 2022, compared to $10.51 million in the same period of 2021[224]. - Total operating expenses rose by $14.17 million to $32.80 million for the three months ended September 30, 2022, compared to $18.63 million in the same period of 2021[224]. - General and administrative expenses increased by $15.2 million to $38.8 million for the nine months ended September 30, 2022, compared to $23.6 million in the same period in 2021[237]. - The company anticipates significant increases in expenses and capital requirements as it advances clinical trials and seeks marketing approvals for its product candidates[193]. Cash and Funding - The company has cash and cash equivalents of $361.5 million as of September 30, 2022, which is expected to fund operations for at least 12 months[199]. - The company may need substantial additional funding to support ongoing operations and growth strategies, with potential challenges in raising capital due to global economic conditions[197]. - Net cash used in operating activities for the nine months ended September 30, 2022, was $55.8 million, significantly higher than $4.4 million for the same period in 2021[241]. - Net cash provided by financing activities for the nine months ended September 30, 2022, was $0.8 million, a significant decrease from $130.1 million in 2021[244]. Product Development - The company is developing multiple product candidates, including BT5528, BT8009, BT1718, BT7480, and BT7455, with ongoing clinical trials for BT5528 and BT8009 showing signs of anti-tumor activity[186][189]. - The company has a proprietary phage display screening platform that enables the identification of potential Bicycles for drug development, encoding quadrillions of potential candidates[185]. - The company expects research and development expenses to continue increasing due to an expanded portfolio of product candidates and ongoing clinical trials[206]. Future Outlook and Risks - The ongoing COVID-19 pandemic poses risks that could materially affect operations, research efforts, and clinical trials[207]. - Rising inflation and interest rates may adversely affect operating results and the ability to secure financing on favorable terms[261]. - The ongoing COVID-19 pandemic continues to impact clinical development and supply chain activities, with measures in place to ensure trial continuity[259]. - Economic conditions, including rising interest rates and recession risks, may lead to further volatility in capital markets and negatively affect operations[261]. Agreements and Obligations - The Cancer Research UK Agreement includes potential future milestone payments totaling $50.9 million, along with tiered royalties of 70% to 90% on net revenue depending on development stage[205]. - Future milestone payments related to collaborations with CRUK and Pepscan Systems B.V. could total $203.6 million, contingent upon achieving specific development and regulatory milestones[251][252]. - The company has material contractual obligations totaling $54.7 million, including operating lease commitments of $15.96 million and debt obligations of $38.73 million[249]. Management and Accounting - Management's financial condition analysis is based on estimates that could differ from actual results, potentially impacting reported financial condition[262]. - There have been no significant changes to critical accounting estimates since the 2021 Annual Report, which could materially affect financial results if actual outcomes differ[264].

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]