Financial Performance - For the three months ended March 31, 2023, the company reported a net product revenue of $534,000, a decrease of $4.525 million compared to $5.059 million in the same period of 2022[157]. - Total revenues for the three months ended March 31, 2023, were $1.237 million, down from $5.524 million in the same period of 2022, reflecting a decrease of $4.287 million[157]. - The company incurred a net loss of $17.4 million for the three months ended March 31, 2023, compared to a net loss of $44.3 million for the same period in 2022, representing an improvement of $26.8 million[157]. - Other income increased from a $6.7 million loss in Q1 2022 to an $8.8 million gain in Q1 2023, driven by foreign currency transaction gains[165]. - Net cash used in operating activities for Q1 2023 was $29.5 million, compared to $19.6 million in Q1 2022[173]. Revenue Sources - Collaboration revenue increased by $238,000 to $703,000 for the three months ended March 31, 2023, compared to $465,000 in the same period of 2022[157]. - Collaboration revenue for Q1 2023 was $0.7 million, up from $0.5 million in Q1 2022, reflecting a 40% increase[159]. Expenses - Research and development expenses for the three months ended March 31, 2023, were $15.993 million, down from $28.234 million in the same period of 2022, a decrease of $12.241 million[157]. - Total direct research and development expenses decreased by $8.5 million, or 60%, from $14.1 million in Q1 2022 to $5.6 million in Q1 2023[162]. - Total indirect research and development expenses decreased by $3.7 million, or 26%, from $14.1 million in Q1 2022 to $10.4 million in Q1 2023[163]. - Selling, general, and administrative expenses decreased by $2.2 million, or 16%, from $13.3 million in Q1 2022 to $11.1 million in Q1 2023[164]. - Interest expense increased to $1.0 million in Q1 2023 from $0.7 million in Q1 2022, while interest income rose to $1.0 million from $0.1 million[166]. Cash and Funding - As of March 31, 2023, the company had an accumulated deficit of $918.3 million and cash, cash equivalents, and marketable securities totaling $146.3 million[134]. - The company expects to incur significant expenses and increasing operating losses in the foreseeable future, necessitating substantial additional funding[135]. - In March 2023, the company completed a private placement, raising gross proceeds of $34.0 million by selling 56,666,900 ordinary shares and warrants[138]. - Net cash provided by financing activities in Q1 2023 was $31.5 million, primarily from a private placement financing of $34 million[178]. - The company believes existing cash, cash equivalents, and marketable securities, along with expected proceeds from Libmeldy sales, will fund operating expenses and capital requirements into 2025[180]. - As of March 31, 2023, the company had cash, cash equivalents, marketable securities, and restricted cash totaling $150.5 million[185]. - The company has borrowed $33.0 million under its credit facility, with a carrying value of term loans at $30.1 million as of March 31, 2023[186]. Strategic Plans - The company plans to continue its commercialization efforts for Libmeldy, with a focus on severe neurometabolic diseases and early research programs[136]. - The company aims to grow its sales, marketing, and distribution infrastructure for Libmeldy in Europe and other product candidates[181]. - The company plans to develop in-house manufacturing operations and facilities[181]. - The company is focused on expanding its intellectual property portfolio and complying with public company obligations[181]. Accounting and Compliance - There have been no material changes to the company's critical accounting policies since December 31, 2022[182]. - The company does not currently engage in currency hedging activities but may consider it in the future[189].

Financial Performance - For the year ended December 31, 2022, the company reported a net loss of $150.7 million, with an accumulated deficit of $900.9 million as of the same date[563]. - Total revenues for 2022 were $22.7 million, a significant increase of $21.0 million compared to $1.7 million in 2021[585]. - Product revenue, net, was $20.6 million in 2022, up from $700,000 in 2021, primarily driven by the commercial sale of Libmeldy[586]. - Collaboration revenue increased to $2.0 million in 2022 from $975,000 in 2021, reflecting growth in partnerships[585]. - Collaboration revenue increased from $1.0 million in 2021 to $2.0 million in 2022, reflecting a 100% growth under the collaboration agreement with Pharming[588]. - The company reported a net loss of $150.7 million for the year ended December 31, 2022[601]. Expenses - Research and development expenses for 2022 were $93.8 million, an increase of $6.9 million from $87.0 million in 2021[585]. - Total research and development expenses increased from $86.98 million in 2021 to $93.85 million in 2022, a rise of 8%[590]. - Direct research and development expenses decreased by $1.1 million, or 2%, from $46.6 million in 2021 to $45.5 million in 2022[590]. - Indirect research and development expenses rose by $7.9 million, or 20%, from $40.4 million in 2021 to $48.3 million in 2022[591]. - Selling, general, and administrative expenses decreased from $54.9 million in 2021 to $49.1 million in 2022, a reduction of 11%[592]. - The company expects to incur significant expenses and increasing operating losses for the foreseeable future, necessitating substantial additional funding[564]. Cash Flow and Funding - Net cash used in operating activities was $76.0 million in 2022, compared to $125.1 million in 2021, indicating improved cash flow management[600][601]. - Net cash provided by investing activities was $90.6 million in 2022, primarily from sales and maturities of marketable securities[603]. - The company has $34 million received in March 2023 from a private placement, which will fund operations into 2025[610]. - The company announced a private placement on March 6, 2023, expected to generate up to $68 million, contingent on FDA meeting outcomes and shareholder approval[598]. Product Development and Commercialization - The company plans to continue its commercialization strategy for Libmeldy, focusing on severe neurometabolic diseases and reducing workforce by approximately 30%[565]. - Libmeldy received approval from the European Commission in December 2020, with the first commercial sale occurring in Q1 2022[587]. - The company has transitioned from a clinical development stage to a commercial stage following the approval of Libmeldy in Europe[563]. - Libmeldy product sales began in January 2022, following European Commission approval in December 2020[623]. - The company is actively seeking marketing approvals for its product candidates that successfully complete clinical trials[608]. - The company plans to expand its sales, marketing, and distribution infrastructure for Libmeldy in Europe[608]. - The company is focused on developing additional product candidates and establishing in-house manufacturing operations[614]. Financial Position and Investments - As of December 31, 2022, the company had cash, cash equivalents, marketable securities, and restricted cash totaling $148.0 million[632]. - The company has borrowed $33.0 million under its credit facility, with a carrying value of term loans at $32.7 million[633]. - The credit facility bears a variable interest rate of 5.95% plus LIBOR, which was amended in January 2023 to reference SOFR instead[634]. - The company’s investment portfolio is conservative, focusing on capital preservation with short-term maturities, minimizing the impact of interest rate changes[632]. - The company has not entered into investments for trading or speculative purposes, indicating a risk-averse investment strategy[632]. Currency and Foreign Exchange - The company recorded realized and unrealized foreign currency losses of $24.3 million and $1.2 million for the years ended December 31, 2022, and 2021, respectively[636]. - The company does not currently engage in currency hedging activities but may consider it in the future[638]. - The company’s functional currency is U.S. dollars, as it predominantly raises finance and expends cash in U.S. dollars[635]. - Foreign currency transaction gains and losses are included in other (expense) income in the consolidated statements of operations[636]. - The company may use foreign currency forward and swap contracts in the future to manage currency risks[638].

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, DC 20549 (Exact Name of Registrant as Specified in its Charter) 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 September 30, 2022 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: 001-38722 ORCHARD THERAPEUTICS PLC England and Wales Not Applicable ( Stat ...

(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, 2022 OR ☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, DC 20549 FORM 10-Q For the transition period from to Commission File Number: 001-38722 ORCHARD THERAPEUTICS PLC (Exact Name of Registrant as Specified in its Charter) England and Wales Not Applicable ( State or ...

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 EXCHANGE ACT OF 1934 For the transition period from to Commission File Number: 001-38722 ORCHARD THERAPEUTICS PLC (Exact Name of Registrant as Specified in its Charter) England and Wales Not Applicable ( State or ...

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, 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 001-38722 ORCHARD THERAPEUTICS PLC (Exact name of Registrant as specified in its Charter) England and Wales Not Applicable (State or othe ...

(Mark One) ☒ QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the quarterly period ended September 30, 2021 OR UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, DC 20549 FORM 10-Q ☐ 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: 001-38722 ORCHARD THERAPEUTICS PLC (Exact Name of Registrant as Specified in its Charter) England and Wales Not Applicable ( Stat ...

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 EXCHANGE ACT OF 1934 For the transition period from to Commission File Number: 001-38722 ORCHARD THERAPEUTICS PLC (Exact Name of Registrant as Specified in its Charter) England and Wales Not Applicable ( State or ...

[PART I. FINANCIAL INFORMATION](index=7&type=section&id=PART%20I.%20FINANCIAL%20INFORMATION) This section provides the unaudited condensed consolidated financial statements and management's discussion and analysis for the quarter ended March 31, 2021 [Item 1. Financial Statements (Unaudited)](index=7&type=section&id=Item%201.%20Financial%20Statements%20%28Unaudited%29) This section presents the unaudited condensed consolidated financial statements for Orchard Therapeutics plc for the quarterly period ended March 31, 2021, including balance sheets, statements of operations, cash flows, and shareholders' equity [Condensed Consolidated Balance Sheets](index=7&type=section&id=Condensed%20Consolidated%20Balance%20Sheets) The balance sheet as of March 31, 2021, shows a significant increase in cash, marketable securities, and total shareholders' equity compared to December 31, 2020, primarily due to a private placement financing Condensed Consolidated Balance Sheet Highlights (in thousands) | Account | March 31, 2021 | December 31, 2020 | | :--- | :--- | :--- | | **Assets** | | | | Cash and cash equivalents | $78,883 | $55,135 | | Marketable securities | $219,543 | $136,813 | | Total current assets | $328,423 | $223,535 | | Total assets | $389,113 | $280,937 | | **Liabilities & Equity** | | | | Total current liabilities | $48,485 | $51,561 | | Total liabilities | $93,533 | $102,503 | | Total shareholders' equity | $295,580 | $178,434 | [Condensed Consolidated Statements of Operations and Comprehensive Loss](index=8&type=section&id=Condensed%20Consolidated%20Statements%20of%20Operations%20and%20Comprehensive%20Loss) For the three months ended March 31, 2021, the company reported a net loss of $35.2 million, a reduction from the $50.6 million net loss in the same period of 2020, driven by lower operating expenses Statement of Operations Highlights (in thousands, except per share data) | Metric | Q1 2021 | Q1 2020 | | :--- | :--- | :--- | | Product sales, net | $0 | $0 | | Research and development | $21,035 | $24,836 | | Selling, general and administrative | $14,051 | $20,145 | | Loss from operations | $(35,086) | $(44,981) | | Net loss | $(35,182) | $(50,569) | | Net loss per share, basic and diluted | $(0.31) | $(0.51) | [Condensed Consolidated Statements of Cash Flows](index=9&type=section&id=Condensed%20Consolidated%20Statements%20of%20Cash%20Flows) Net cash used in operating activities was $39.2 million for the first quarter of 2021, while financing activities provided $146.4 million, primarily from a private placement, resulting in a net increase in cash - Net cash used in operating activities decreased to **$39.2 million** in Q1 2021 from **$49.9 million** in Q1 2020[23](index=23&type=chunk) - The company received **$150.0 million** in proceeds from the issuance of ordinary shares in a private placement, resulting in net cash of **$143.7 million** after fees and costs[23](index=23&type=chunk)[31](index=31&type=chunk) - Cash used in investing activities was **$83.5 million**, a significant shift from the **$56.8 million** provided by investing activities in the prior year period, mainly due to a **$130.4 million** purchase of marketable securities[23](index=23&type=chunk)[143](index=143&type=chunk) [Notes to Unaudited Condensed Consolidated Financial Statements](index=11&type=section&id=Notes%20to%20Unaudited%20Condensed%20Consolidated%20Financial%20Statements) The notes detail the company's business, accounting policies, and financial activities, including the European marketing authorization for Libmeldy and a private placement that significantly boosted liquidity - In February 2021, the company completed a private placement, selling ordinary and non-voting ordinary shares for net proceeds of **$143.7 million** after deducting fees and costs[31](index=31&type=chunk) - The company received standard marketing authorization from the European Commission for Libmeldy™ for the treatment of early-onset MLD in December 2020[30](index=30&type=chunk) - As of March 31, 2021, the company had an accumulated deficit of **$640.8 million** but expects its cash, cash equivalents, and marketable securities of **$298.4 million** to be sufficient to fund operations for at least the next twelve months[33](index=33&type=chunk) - The company has a manufacturing agreement with AGC Biologics with total remaining commitments of approximately **$61.0 million** as of March 31, 2021[100](index=100&type=chunk) [Management's Discussion and Analysis of Financial Condition and Results of Operations](index=26&type=section&id=Management's%20Discussion%20and%20Analysis%20of%20Financial%20Condition%20and%20Results%20of%20Operations) Management discusses the company's transition to a commercial-stage entity, highlighting reduced net loss in Q1 2021 due to lower operating expenses and a significant liquidity boost from a private placement [Results of Operations](index=30&type=section&id=Results%20of%20Operations) Comparing Q1 2021 to Q1 2020, total operating expenses decreased by $9.9 million to $35.1 million, driven by reductions in research and development and selling, general, and administrative expenses Comparison of Operating Results (in thousands) | Metric | Q1 2021 | Q1 2020 | Change | | :--- | :--- | :--- | :--- | | Research and development | $21,035 | $24,836 | $(3,801) | | Selling, general and administrative | $14,051 | $20,145 | $(6,094) | | **Total costs and operating expenses** | **$35,086** | **$44,981** | **$(9,895)** | | Net loss | $(35,182) | $(50,569) | $15,387 | - Direct R&D expenses for primary immune deficiency programs declined by **$1.8 million**, mainly due to a **$2.5 million** reduction in costs for OTL-101 following its de-prioritization[131](index=131&type=chunk) - SG&A expenses declined by **$6.1 million**, primarily due to a **$2.7 million** share-based compensation charge and a **$0.7 million** severance charge in Q1 2020 related to the separation of the former CEO, which did not recur[87](index=87&type=chunk)[135](index=135&type=chunk) [Liquidity and Capital Resources](index=32&type=section&id=Liquidity%20and%20Capital%20Resources) As of March 31, 2021, the company had $298.4 million in cash, cash equivalents, and marketable securities, with existing cash expected to fund operations into the first half of 2023 - The company's cash, cash equivalents, and marketable securities totaled **$298.4 million** as of March 31, 2021[108](index=108&type=chunk) - A private placement in February 2021 provided net proceeds of **$143.7 million**[112](index=112&type=chunk)[144](index=144&type=chunk) - The company believes its existing cash will fund operations and capital expenditures into the first half of 2023[147](index=147&type=chunk) - The company has an "at the market offering" agreement to sell up to **$100.0 million** in ADSs, but no shares had been sold under this agreement as of March 31, 2021[138](index=138&type=chunk) [Item 3. Quantitative and Qualitative Disclosures About Market Risk](index=35&type=section&id=Item%203.%20Quantitative%20and%20Qualitative%20Disclosures%20About%20Market%20Risk) The company is exposed to market risks, primarily interest rate sensitivity from its variable-rate debt and foreign currency exchange risk from international operations, without currently using hedging instruments - The company has **$25.0 million** in debt under a credit facility with a variable interest rate of **6% plus LIBOR**, exposing it to interest rate risk[152](index=152&type=chunk) - The company is exposed to foreign currency exchange risk, particularly between the U.S. dollar, pound sterling, and euro, recording a net foreign currency gain of **$1.4 million** in Q1 2021, compared to a loss of **$6.6 million** in Q1 2020[153](index=153&type=chunk) [Item 4. Controls and Procedures](index=35&type=section&id=Item%204.%20Controls%20and%20Procedures) Management concluded that the company's disclosure controls and procedures were effective as of March 31, 2021, with no material changes in internal control over financial reporting during the quarter - The Principal Executive Officer and Principal Financial Officer concluded that as of March 31, 2021, the company's disclosure controls and procedures were effective[157](index=157&type=chunk) - No changes in internal control over financial reporting occurred during the quarter ended March 31, 2021, that have materially affected, or are reasonably likely to materially affect, internal controls[160](index=160&type=chunk) [PART II. OTHER INFORMATION](index=37&type=section&id=PART%20II.%20OTHER%20INFORMATION) This section outlines legal proceedings, various risk factors, and other required disclosures for the company [Item 1. Legal Proceedings](index=37&type=section&id=Item%201.%20Legal%20Proceedings) As of March 31, 2021, the company was not a party to any material legal proceedings, expecting no material adverse effect from ordinary course claims - The company is not currently a party to any material litigation[162](index=162&type=chunk) [Item 1A. Risk Factors](index=37&type=section&id=Item%201A.%20Risk%20Factors) This section details numerous risks that could harm the company's business, financial condition, and prospects, including financial position, development, manufacturing, commercialization, and COVID-19 impacts [Risks related to financial position and need for additional capital](index=37&type=section&id=Risks%20related%20to%20our%20financial%20position%20and%20need%20for%20additional%20capital) The company has a history of net losses and expects to incur losses for the foreseeable future, requiring substantial additional funding to support operations and achieve profitability - The company has incurred net losses since inception and expects to continue incurring them for the foreseeable future, with a net loss of **$35.2 million** for the three months ended March 31, 2021[164](index=164&type=chunk) - Additional funding is necessary and failure to obtain it on acceptable terms may force the company to delay, limit, or terminate product development or other operations[172](index=172&type=chunk) [Risks related to the discovery, development and regulatory approval of our product candidates](index=40&type=section&id=Risks%20related%20to%20the%20discovery,%20development%20and%20regulatory%20approval%20of%20our%20product%20candidates) The novelty of gene therapy makes development time and cost difficult to predict, with risks including insufficient clinical trial data, serious adverse events from administration, and challenges in demonstrating manufacturing comparability - The novelty of gene therapy makes it difficult to predict the time and cost of development and regulatory approval[178](index=178&type=chunk) - The FDA and/or EMA may require additional clinical trials for OTL-200 (MLD) and OTL-103 (WAS) before considering marketing approval, as a single registrational trial may be deemed insufficient[181](index=181&type=chunk) - A patient treated with Strimvelis was diagnosed with lymphoid T-cell leukemia due to insertional oncogenesis, a known risk for gammaretroviral vectors, which could impact perception and regulation of gene therapies[194](index=194&type=chunk) - The company may be unable to demonstrate comparability between drug product manufactured using different cell sources (bone marrow vs. peripheral blood) or formulations (fresh vs. cryopreserved), which could delay or limit regulatory approval[199](index=199&type=chunk)[202](index=202&type=chunk) [Risks related to manufacturing and supply](index=57&type=section&id=Risks%20related%20to%20manufacturing%20and%20supply) The company relies on third-party CDMOs, often single sources, for its complex gene therapies, creating risks of delays, supply interruptions, compliance failures, and challenges in managing the highly complex autologous supply chain - The company relies on third-party manufacturers (CDMOs), which are often single sources of supply, for its complex and difficult-to-manufacture gene therapies[269](index=269&type=chunk) - The autologous ex vivo gene therapy supply chain is highly complex, requiring coordination of patient cell collection, transport to manufacturing, and return of the cryopreserved drug product to the treatment center under strict time and temperature conditions[279](index=279&type=chunk)[280](index=280&type=chunk) - Any microbial contamination, raw material shortages, or failure of key suppliers could result in significant delays in clinical development or commercialization[284](index=284&type=chunk) [Risks related to commercialization](index=66&type=section&id=Risks%20related%20to%20commercialization%20of%20our%20product%20candidates) The company faces significant hurdles in commercializing its products, including building sales capabilities, gaining market acceptance, navigating competition, and securing adequate insurance coverage and reimbursement for high-cost therapies - The company may not be successful in establishing effective sales, marketing, and distribution capabilities for Libmeldy and other future products, which is expensive and time-consuming[318](index=318&type=chunk) - The company faces significant competition from larger pharmaceutical and biotech companies with greater resources, and its lack of issued patents for key products like Libmeldy lowers barriers to entry[323](index=323&type=chunk)[324](index=324&type=chunk) - Failure to obtain and maintain adequate insurance coverage and reimbursement for high-cost gene therapies could severely limit the ability to market and sell products[331](index=331&type=chunk) [Risks related to the impact of COVID-19](index=70&type=section&id=Risks%20related%20to%20the%20impact%20of%20COVID-19) The COVID-19 pandemic has caused and may continue to cause significant disruptions, including delays in clinical trials, diversion of healthcare resources, and interruptions in global shipping, with uncertain full impact on business operations - The COVID-19 pandemic has caused disruptions that may continue to delay clinical trial enrollment, patient follow-up, and regulatory timelines[337](index=337&type=chunk)[339](index=339&type=chunk) - Specific impacts include diversion of healthcare resources, limitations on travel for trial activities, and interruptions in global shipping of clinical materials[340](index=340&type=chunk) [Item 2. Unregistered Sales of Equity Securities and Use of Proceeds](index=103&type=section&id=Item%202.%20Unregistered%20Sales%20of%20Equity%20Securities%20and%20Use%20of%20Proceeds) During the quarter ended March 31, 2021, the company had no sales of unregistered securities other than those detailed in its Current Report on Form 8-K filed on February 9, 2021 - Details regarding unregistered sales of equity securities during the quarter are referenced in the Form 8-K filed on February 9, 2021[508](index=508&type=chunk) [Item 3. Defaults Upon Senior Securities](index=103&type=section&id=Item%203.%20Defaults%20Upon%20Senior%20Securities) Not applicable, as the company reports no defaults upon senior securities [Item 4. Mine Safety Disclosures](index=103&type=section&id=Item%204.%20Mine%20Safety%20Disclosures) Not applicable, as the company has no mine safety disclosures to report [Item 5. Other Information](index=103&type=section&id=Item%205.%20Other%20Information) Not applicable, as the company reports no other information for this item [Item 6. Exhibits](index=104&type=section&id=Item%206.%20Exhibits) This section lists the exhibits filed with the Form 10-Q, including the Securities Purchase Agreement from the February 2021 private placement, certifications, and XBRL data files - The exhibits include the Securities Purchase Agreement dated February 4, 2021, CEO/CFO certifications (Rule 13a-14(a) and Section 906), and Inline XBRL documents[513](index=513&type=chunk)

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 001-38722 ORCHARD THERAPEUTICS PLC (Exact name of Registrant as specified in its Charter) England and Wales Not Applicable (State or othe ...