Iovance Biotherapeutics, Inc. (NASDAQ:IOVA) Q1 2022 Results Conference Call May 5, 2022 4:30 PM ET Company Participants Sara Pellegrino - Vice President, Investor and Public Relations Dr. Fred Vogt - Interim President and Chief Executive Officer Dr. Igor Bilinsky - Chief Operating Officer Jim Ziegler - Senior Vice President, Commercial Dr. Friedrich Finckenstein - Chief Medical Officer Dr. Madan Jagasia - Senior Vice President, Medical Affairs Jean-Marc Bellemin - Chief Financial Officer Dr. Raj Puri - Exec ...

[PART I FINANCIAL INFORMATION](index=3&type=section&id=PART%20I%20FINANCIAL%20INFORMATION) Presents unaudited condensed consolidated financial statements and detailed notes for Iovance Biotherapeutics, Inc [Item 1. Condensed Consolidated Financial Statements](index=3&type=section&id=Item%201.%20Condensed%20Consolidated%20Financial%20Statements) Provides unaudited condensed consolidated financial statements and explanatory notes for the reporting period [Condensed Consolidated Balance Sheets](index=3&type=section&id=Condensed%20Consolidated%20Balance%20Sheets) | Metric | March 31, 2022 (in thousands) | December 31, 2021 (in thousands) | | :-------------------------- | :----------------------------- | :------------------------------- | | Cash and cash equivalents | $92,360 | $78,229 | | Short-term investments | $389,829 | $426,181 | | Long-term investments | $27,701 | $91,588 | | Total Assets | $701,251 | $777,333 | | Total Liabilities | $149,259 | $155,674 | | Total Stockholders' Equity | $551,992 | $621,659 | | Accumulated deficit | $(1,264,052) | $(1,172,445) | [Condensed Consolidated Statements of Operations](index=4&type=section&id=Condensed%20Consolidated%20Statements%20of%20Operations) | Metric | Three Months Ended March 31, 2022 (in thousands) | Three Months Ended March 31, 2021 (in thousands) | | :-------------------------- | :--------------------------------------- | :--------------------------------------- | | Research and development | $68,300 | $55,949 | | General and administrative | $23,413 | $19,621 | | Total costs and expenses | $91,713 | $75,570 | | Loss from operations | $(91,713) | $(75,570) | | Net Loss | $(91,607) | $(75,449) | | Net Loss Per Share (Basic and Diluted) | $(0.58) | $(0.51) | [Condensed Consolidated Statements of Comprehensive Loss](index=5&type=section&id=Condensed%20Consolidated%20Statements%20of%20Comprehensive%20Loss) | Metric | Three Months Ended March 31, 2022 (in thousands) | Three Months Ended March 31, 2021 (in thousands) | | :-------------------------- | :--------------------------------------- | :--------------------------------------- | | Net Loss | $(91,607) | $(75,449) | | Unrealized (loss) gain on investments | $(1,742) | $77 | | Comprehensive Loss | $(93,349) | $(75,372) | [Condensed Consolidated Statements of Stockholders' Equity](index=6&type=section&id=Condensed%20Consolidated%20Statements%20of%20Stockholders%27%20Equity) | Metric | March 31, 2022 (in thousands) | December 31, 2021 (in thousands) | | :-------------------------- | :----------------------------- | :------------------------------- | | Total Stockholders' Equity | $551,992 | $621,659 | | Stock-based compensation expense (Q1) | $22,265 | $16,941 | | Net loss (Q1) | $(91,607) | $(75,449) | | Unrealized loss on investments (Q1) | $(1,742) | — | [Condensed Consolidated Statements of Cash Flows](index=7&type=section&id=Condensed%20Consolidated%20Statements%20of%20Cash%20Flows) | Metric | Three Months Ended March 31, 2022 (in thousands) | Three Months Ended March 31, 2021 (in thousands) | | :--------------------------------------- | :--------------------------------------- | :--------------------------------------- | | Net cash used in operating activities | $(73,802) | $(62,391) | | Net cash provided by investing activities | $86,516 | $77,211 | | Net cash provided by financing activities | $1,417 | $50,364 | | Net increase in cash, cash equivalents and restricted cash | $14,131 | $65,184 | [NOTE 1. GENERAL ORGANIZATION, BUSINESS AND LIQUIDITY](index=8&type=section&id=NOTE%201.%20GENERAL%20ORGANIZATION%2C%20BUSINESS%20AND%20LIQUIDITY) - Iovance Biotherapeutics, Inc. is a **clinical-stage biopharmaceutical company** focused on developing **Tumor Infiltrating Lymphocyte (TIL) therapy** to cure cancer[25](index=25&type=chunk) - The company's lead product candidates include **lifileucel** for metastatic melanoma and metastatic cervical cancer, and **LN-145** for metastatic non-small cell lung cancer (NSCLC)[25](index=25&type=chunk) Financial Metrics (in millions) | Metric | Value (in millions) | | :--------------------------------------- | :------------------ | | Net loss for Q1 2022 | $(91.6) | | Cash used in operating activities for Q1 2022 | $(73.8) | | Total cash, cash equivalents, investments, and restricted cash (Mar 31, 2022) | $516.0 | - The company believes it has **sufficient capital** to fund anticipated operating expenses and capital expenditures for at least the **next twelve months**[28](index=28&type=chunk) [NOTE 2. SUMMARY OF SIGNIFICANT ACCOUNTING POLICIES](index=9&type=section&id=NOTE%202.%20SUMMARY%20OF%20SIGNIFICANT%20ACCOUNTING%20POLICIES) - Investments are classified as '**available-for-sale**' and carried at **fair value**, with unrealized gains and losses recorded in accumulated other comprehensive loss[30](index=30&type=chunk) Restricted Cash (in thousands) | Metric | March 31, 2022 (in thousands) | December 31, 2021 (in thousands) | | :-------------------------- | :----------------------------- | :------------------------------- | | Restricted cash | $6,084 | $6,084 | - Potentially dilutive common stock equivalents (stock options, ESPP, restricted stock units, and convertible preferred stock) are **excluded from diluted net loss per share calculation** when their effect would be **anti-dilutive**[34](index=34&type=chunk)[35](index=35&type=chunk) - Research and development costs are **expensed as incurred**, with accruals for third-party activities based on estimates of work completed[45](index=45&type=chunk) [NOTE 3. CASH EQUIVALENTS, INVESTMENTS AND FAIR VALUE MEASUREMENTS](index=13&type=section&id=NOTE%203.%20CASH%20EQUIVALENTS%2C%20INVESTMENTS%20AND%20FAIR%20VALUE%20MEASUREMENTS) Investment Portfolio Fair Value (in thousands) | Investment Type | March 31, 2022 Fair Value (in thousands) | December 31, 2021 Fair Value (in thousands) | | :-------------------------- | :--------------------------------------- | :--------------------------------------- | | U.S. treasury securities | $246,484 | $246,767 | | U.S. government agency securities | $5,046 | $5,097 | | Corporate securities | $34,329 | $35,588 | | Commercial paper | $158,095 | $235,316 | | Money market funds | $45,249 | $56,250 | | Total investments | $489,203 | $579,018 | - All available-for-sale securities held as of March 31, 2022, and December 31, 2021, had contractual maturities of **less than two years**[51](index=51&type=chunk) [NOTE 4. PROPERTY AND EQUIPMENT, NET](index=16&type=section&id=NOTE%204.%20PROPERTY%20AND%20EQUIPMENT%2C%20NET) Property and Equipment, Net (in thousands) | Asset Category | March 31, 2022 (in thousands) | December 31, 2021 (in thousands) | | :-------------------------- | :----------------------------- | :------------------------------- | | Leasehold improvements | $65,767 | $57,817 | | Construction in progress | $23,732 | $35,782 | | Total Property and equipment, net | $102,757 | $100,938 | | Depreciation expense (Q1) | $1,800 | $400 | [NOTE 5. ACCRUED EXPENSES](index=16&type=section&id=NOTE%205.%20ACCRUED%20EXPENSES) Accrued Expenses (in thousands) | Accrued Expense Category | March 31, 2022 (in thousands) | December 31, 2021 (in thousands) | | :-------------------------- | :----------------------------- | :------------------------------- | | Accrued payroll and employee related expenses | $18,204 | $21,513 | | Clinical related | $17,910 | $18,167 | | Manufacturing related | $6,295 | $6,566 | | Total accrued expenses | $48,911 | $56,766 | [NOTE 6. STOCKHOLDERS' EQUITY](index=16&type=section&id=NOTE%206.%20STOCKHOLDERS%27%20EQUITY) - As of March 31, 2022, **157,168,321 shares** of common stock were issued and outstanding[56](index=56&type=chunk) - No sales were made under the 'at the market' offering program during the three months ended March 31, 2022, compared to **$42.9 million in net proceeds** from sales in the same period of 2021[60](index=60&type=chunk) Equity Award Details | Equity Award Type | March 31, 2022 Outstanding | Unrecognized Compensation Expense (in thousands) | | :-------------------------- | :------------------------- | :--------------------------------------- | | Stock options | 14,101,526 | $94,100 | | Restricted stock units (RSUs) and Performance Restricted Stock Units (PRSUs) | 3,095,177 | $37,000 | Stock-Based Compensation Expense (in thousands) | Expense Category | Three Months Ended March 31, 2022 (in thousands) | Three Months Ended March 31, 2021 (in thousands) | | :-------------------------- | :--------------------------------------- | :--------------------------------------- | | Total stock-based compensation expense | $22,265 | $16,941 | [NOTE 7. LICENSES AND AGREEMENTS](index=22&type=section&id=NOTE%207.%20LICENSES%20AND%20AGREEMENTS) - The Cooperative Research and Development Agreement (CRADA) with the NCI was extended by **three years to August 2024**, requiring quarterly payments of **$0.5 million** for research activities[85](index=85&type=chunk)[86](index=86&type=chunk) - An Amended and Restated Patent License Agreement with NIH grants additional **exclusive worldwide patent rights** to cytokine-tethered TIL technology and expands the non-exclusive field of use to all cancers[89](index=89&type=chunk) - The company has an exclusive patent license agreement with NIH for TIL selection technologies, which includes customary royalties based on a percentage of net sales (**mid-single digits**)[90](index=90&type=chunk)[91](index=91&type=chunk) Manufacturing and Gene-Editing Agreements (in thousands) | Agreement | Three Months Ended March 31, 2022 (in thousands) | Three Months Ended March 31, 2021 (in thousands) | | :-------------------------- | :--------------------------------------- | :--------------------------------------- | | WuXi Advanced Therapies, Inc. (manufacturing) | $3,900 | $3,400 | | Cellectis S.A. (gene-editing technology) | $100 | $100 | [NOTE 8. LEASES](index=25&type=section&id=NOTE%208.%20LEASES) Lease Assets and Liabilities (in thousands) | Metric | March 31, 2022 (in thousands) | December 31, 2021 (in thousands) | | :-------------------------- | :----------------------------- | :------------------------------- | | Operating lease right-of-use assets | $73,475 | $68,983 | | Total operating lease liabilities | $78,894 | $70,531 | Lease Costs (in thousands) | Lease Cost Type | Three Months Ended March 31, 2022 (in thousands) | Three Months Ended March 31, 2021 (in thousands) | | :-------------------------- | :--------------------------------------- | :--------------------------------------- | | Operating lease cost | $4,555 | $3,398 | | Variable lease cost | $980 | $710 | | Short-term lease cost | $42 | $36 | | Total lease cost | $5,577 | $4,144 | - The weighted-average remaining lease term as of March 31, 2022, was **14.13 years**, with a weighted-average discount rate of **7.2%**[111](index=111&type=chunk) [NOTE 9. LEGAL PROCEEDINGS](index=28&type=section&id=NOTE%209.%20LEGAL%20PROCEEDINGS) - A derivative lawsuit was filed on **December 11, 2020**, alleging breach of fiduciary duty and unjust enrichment related to excessive non-executive director compensation[112](index=112&type=chunk) - The company is involved in two lawsuits with Solomon Capital, LLC, concerning alleged unpaid funds and shares, with one suit's damages for the Equity Claim limited to **$47,420** by court order[113](index=113&type=chunk)[115](index=115&type=chunk)[116](index=116&type=chunk) - In the Second Solomon Suit, claims against the former CEO and two claims against the company were dismissed by the Court on **January 5, 2022**[117](index=117&type=chunk) - The company intends to vigorously defend against these complaints and pursue its counterclaims, with the amount or range of possible loss currently **not estimable**[118](index=118&type=chunk) [NOTE 10. INCOME TAXES](index=32&type=section&id=NOTE%2010.%20INCOME%20TAXES) - The company did not record income tax expense for the three months ended March 31, 2022, and 2021, due to expected **taxable losses**[120](index=120&type=chunk) - Net deferred tax assets are fully offset by a valuation allowance, as it is **not more likely than not** that the benefit will be realized[120](index=120&type=chunk) [Item 2. Management's Discussion and Analysis of Financial Condition and Results of Operations](index=33&type=section&id=Item%202.%20Management%27s%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, detailing its clinical-stage biopharmaceutical focus, product pipeline, intellectual property, the impact of COVID-19, and a breakdown of operating expenses, liquidity, and capital resources [Overview](index=33&type=section&id=Overview) - Iovance Biotherapeutics is a **clinical-stage biopharmaceutical company** focused on pioneering Tumor Infiltrating Lymphocyte (TIL) therapy to cure cancer[123](index=123&type=chunk) - The company has developed a new, shorter proprietary TIL manufacturing process known as **Generation 2 (Gen 2)**, which yields a cryopreserved TIL product[123](index=123&type=chunk) - Lead product candidates include **lifileucel** for metastatic melanoma and metastatic cervical cancer, and **LN-145** for metastatic non-small cell lung cancer (NSCLC)[123](index=123&type=chunk) - The company is also investigating combinations of TIL therapy with immune checkpoint inhibitors (ICIs), peripheral blood lymphocyte (PBL) therapy, genetically edited TIL products (**IOV-4001**), and an alternative interleukin-2 (IL-2) co-therapy (**IOV-3001**)[123](index=123&type=chunk) [Product Candidate Pipeline and Clinical Development](index=34&type=section&id=Product%20Candidate%20Pipeline%20and%20Clinical%20Development) - **Lifileucel** for metastatic melanoma (C-144-01 trial, Cohort 4) completed patient dosing in **January 2020**, with a Biologics License Application (BLA) submission expected by **August 2022**[127](index=127&type=chunk)[128](index=128&type=chunk) - **Lifileucel** for metastatic cervical cancer (C-145-04 trial, Cohort 2) received **Breakthrough Therapy Designation (BTD)** and completed enrollment in **January 2021**[129](index=129&type=chunk) - The **IOV-LUN-202 clinical trial** is enrolling patients with metastatic NSCLC, with Cohort 3 exploring TIL manufacturing from core biopsies using the **third-generation (Gen 3) process**[130](index=130&type=chunk) - The Iovance Cell Therapy Center (iCTC) successfully manufactured and delivered its first clinical batch of **LN-145** for the IOV-COM-202 trial in **September 2021**[136](index=136&type=chunk) - The FDA allowed an Investigational New Drug (IND) to proceed for the first genetically modified TIL therapy, **IOV-4001**, in **March 2022**, with the first clinical trial expected to initiate in **2022**[140](index=140&type=chunk) [Intellectual Property](index=38&type=section&id=Intellectual%20Property) - The company owns over **40 U.S. patents** related to TIL therapy, including compositions and methods of treatment in a broad range of cancers[144](index=144&type=chunk) - More than **30 of these patents** are related to the Gen 2 TIL manufacturing processes and are anticipated to extend to **January 2038**[144](index=144&type=chunk) - The intellectual property portfolio also includes patent applications for frozen tumor-based TIL technologies, remnant TIL and digest TIL compositions, costimulatory molecules, genetically-modified TIL therapies, and ICI combination methods[144](index=144&type=chunk) [Impact of COVID-19 on our Business Operations and Liquidity](index=38&type=section&id=Impact%20of%20COVID-19%20on%20our%20Business%20Operations%20and%20Liquidity) - The COVID-19 pandemic has **not had a material impact** on the company's liquidity or results of operations for the three months ended March 31, 2022[145](index=145&type=chunk) - Clinical trial enrollment has **not been significantly affected** by the pandemic to date[145](index=145&type=chunk) - The company believes its current cash reserves are **well-positioned** to manage its business through the ongoing crisis[146](index=146&type=chunk) - The dynamic nature of the COVID-19 pandemic makes it **difficult to forecast future effects** on financial condition, results of operations, or cash flows[147](index=147&type=chunk)[149](index=149&type=chunk) [Components of Results of Operations](index=40&type=section&id=Components%20of%20Results%20of%20Operations) - The company has **not generated any revenues** since its formation and does not anticipate significant revenues from product sales or licensing in the next **12 months**[150](index=150&type=chunk) - Research and development expenses are expected to **increase** due to preparations for commercial manufacturing and ongoing clinical trials[153](index=153&type=chunk) - General and administrative expenses are anticipated to **increase** as the company prepares for commercialization and expands its internal team and corporate infrastructure[155](index=155&type=chunk) [Results of Operations for the Three Months Ended March 31, 2022 and 2021](index=42&type=section&id=Results%20of%20Operations%20for%20the%20Three%20Months%20Ended%20March%2031%2C%202022%20and%202021) Operating Results Comparison (in thousands) | Metric | Three Months Ended March 31, 2022 (in thousands) | Three Months Ended March 31, 2021 (in thousands) | Change (in thousands) | Change (%) | | :-------------------------- | :--------------------------------------- | :--------------------------------------- | :-------------------- | :--------- | | Research and development expense | $68,300 | $55,949 | $12,351 | 22 | | General and administrative expense | $23,413 | $19,621 | $3,792 | 19 | | Interest income, net | $106 | $121 | $(15) | (12) | | Net loss | $(91,607) | $(75,449) | $(16,158) | 21 | - The increase in research and development expense was primarily due to a **$6.5 million increase** in payroll and related expenses and a **$4.4 million increase** in stock-based compensation, driven by increased hiring and facility costs, partially offset by a **$5.8 million decrease** in clinical trial costs[158](index=158&type=chunk) - The increase in general and administrative expenses was mainly due to a **$1.4 million increase** in payroll and related expenses, a **$0.9 million increase** in stock-based compensation, and a **$1.5 million increase** in other costs to support business growth and pre-commercialization activities[159](index=159&type=chunk) [Liquidity and Capital Resources](index=43&type=section&id=Liquidity%20and%20Capital%20Resources) - The company has incurred losses and generated negative cash flows from operations since inception, with an accumulated deficit of **$1.3 billion** as of March 31, 2022[162](index=162&type=chunk) - As of March 31, 2022, the company had **$516.0 million** in cash, cash equivalents, and investments, which is believed to be sufficient to fund operations for at least the **next twelve months**[162](index=162&type=chunk) - Future funding requirements are expected to **increase** due to expanded research and development, pre-commercial activities, and completion of the iCTC facility[162](index=162&type=chunk) Cash Flow Activities (in thousands) | Cash Flow Activity | Three Months Ended March 31, 2022 (in thousands) | Three Months Ended March 31, 2021 (in thousands) | | :--------------------------------------- | :--------------------------------------- | :--------------------------------------- | | Net cash used in operating activities | $(73,802) | $(62,391) | | Net cash provided by investing activities | $86,516 | $77,211 | | Net cash provided by financing activities | $1,417 | $50,364 | - The increase in cash used in operating activities was due to **increased net loss** and higher non-cash charges, partially offset by changes in operating assets and liabilities[170](index=170&type=chunk) - The decrease in net cash provided by financing activities was primarily due to **lower proceeds from common stock sales** through the 'at the market' offering program in Q1 2022 compared to Q1 2021[172](index=172&type=chunk) [Off-Balance Sheet Arrangements](index=45&type=section&id=Off-Balance%20Sheet%20Arrangements) - As of March 31, 2022, the company had **no obligations** that would require disclosure as off-balance sheet arrangements[173](index=173&type=chunk) [Significant Accounting Policies and Recent Accounting Standards](index=46&type=section&id=Significant%20Accounting%20Policies%20and%20Recent%20Accounting%20Standards) - There were **no recently issued accounting standards** applicable to the company, and no accounting standards were adopted during the three months ended March 31, 2022[174](index=174&type=chunk) [Inflation](index=46&type=section&id=Inflation) - Inflation has **not had a material effect** on the company's business, financial condition, or results of operations over the two most recent fiscal years[175](index=175&type=chunk) [Item 3. Quantitative and Qualitative Disclosures About Market Risk](index=46&type=section&id=Item%203.%20Quantitative%20and%20Qualitative%20Disclosures%20About%20Market%20Risk) The company's market risk is primarily limited to interest income sensitivity from its investment portfolio, which consists mainly of short-term U.S. government debt securities - The company's exposure to market risk is primarily limited to **interest income sensitivity**, affected by changes in U.S. interest rates[176](index=176&type=chunk) - The investment policy limits amounts invested in securities by credit rating, maturity, industry group, investment type, and issuer, except for U.S. government securities[176](index=176&type=chunk) - As of March 31, 2022, **$489.2 million** was invested in marketable securities with maturity dates of **less than two years**[176](index=176&type=chunk) - A **1% change in interest rates** as of March 31, 2022, would result in an approximate **$2.0 million increase or decrease** in the fair value of the investment portfolio[176](index=176&type=chunk) [Item 4. Controls and Procedures](index=46&type=section&id=Item%204.%20Controls%20and%20Procedures) Management concluded that the company's disclosure controls and procedures were effective as of the end of the period covered by this report, and there were no material changes in internal control over financial reporting during the quarter ended March 31, 2022 - The company's principal executive officer and principal financial officer concluded that disclosure controls and procedures were **effective** as of March 31, 2022[177](index=177&type=chunk) - There have been **no material changes** in internal control over financial reporting during the quarter ended March 31, 2022[178](index=178&type=chunk) [PART II OTHER INFORMATION](index=47&type=section&id=PART%20II%20OTHER%20INFORMATION) Presents additional information including legal proceedings, risk factors, sales of securities, and exhibits [Item 1. Legal Proceedings](index=47&type=section&id=Item%201.%20Legal%20Proceedings) This section incorporates by reference the legal proceedings detailed in Note 9 to the Condensed Consolidated Financial Statements, confirming no other material pending legal matters - Information on legal proceedings is incorporated by reference from **Note 9** to the Condensed Consolidated Financial Statements[180](index=180&type=chunk) - There are **no other matters** that constitute material pending legal proceedings[180](index=180&type=chunk) [Item 1A. Risk Factors](index=47&type=section&id=Item%201A.%20Risk%20Factors) This section outlines the significant risks and uncertainties facing the company, including those related to its business operations, government regulation, intellectual property, and securities - The company is **substantially dependent** on the success of its product candidates, which may not complete development, receive regulatory approval, or be commercialized[183](index=183&type=chunk) - **Significant risks** include substantial delays in clinical trials, difficulties in manufacturing and scaling capabilities, and the need for additional financing[183](index=183&type=chunk) - The company is subject to **extensive and costly regulation**, faces **significant competition**, and its business could be **adversely affected** by health epidemics like COVID-19[186](index=186&type=chunk) [Risks Related to Our Business](index=50&type=section&id=Risks%20Related%20to%20Our%20Business) - The company has a history of operating losses, with an accumulated deficit of **$1.3 billion** as of March 31, 2022, and expects to continue incurring losses[187](index=187&type=chunk) - Success is entirely dependent on the development and commercialization of product candidates (**lifileucel, LN-145, IOV-2001, IOV-3001**), which may never occur[191](index=191&type=chunk) - Reliance on third parties (CROs, CMOs, clinical trial sites) for clinical trials and manufacturing exposes the company to risks of **delays, failures, and lack of control**[197](index=197&type=chunk)[199](index=199&type=chunk)[200](index=200&type=chunk) - Clinical trials are **expensive, time-consuming, and uncertain**, with risks of undesirable side effects, failure to demonstrate safety and efficacy, and difficulties in patient enrollment[222](index=222&type=chunk)[223](index=223&type=chunk)[231](index=231&type=chunk) - Manufacturing of product candidates is complex, highly regulated, and susceptible to **product loss, contamination, and scaling difficulties**, potentially delaying supply or increasing costs[234](index=234&type=chunk)[236](index=236&type=chunk) - The company needs **additional financing** to fund future operations, with risks of dilution to stockholders, increased debt, or relinquishing rights to technologies[254](index=254&type=chunk)[256](index=256&type=chunk) - The ongoing military conflict between Russia and Ukraine and resulting geopolitical instability could **materially adversely affect** the global economy, capital markets, and the company's business[323](index=323&type=chunk)[325](index=325&type=chunk) [Risks Related to Government Regulation](index=98&type=section&id=Risks%20Related%20to%20Government%20Regulation) - The FDA regulatory approval process is **lengthy, time-consuming, and uncertain**, especially for novel cell therapies, with no prior BLA submission experience[329](index=329&type=chunk)[330](index=330&type=chunk) - Obtaining regulatory approval in one jurisdiction does **not guarantee approval in others**, and foreign regulatory requirements can vary significantly[333](index=333&type=chunk) - Ongoing regulatory obligations post-approval, such as REMS and Phase 4 studies, will result in **significant additional expense** and potential penalties for non-compliance[335](index=335&type=chunk)[336](index=336&type=chunk)[339](index=339&type=chunk) - Failure to comply with federal and state healthcare and promotional laws (e.g., fraud and abuse, off-label promotion) could lead to **substantial penalties** and adverse business impact[341](index=341&type=chunk)[344](index=344&type=chunk)[347](index=347&type=chunk) - Coverage and reimbursement for product candidates may be **limited or unavailable**, impacting profitability, particularly for novel therapies in inpatient settings[349](index=349&type=chunk)[351](index=351&type=chunk)[357](index=357&type=chunk) - New legislation, regulatory proposals, and healthcare payor initiatives (e.g., ACA, drug pricing controls) may **increase compliance costs** and adversely affect marketability and profitability[358](index=358&type=chunk)[362](index=362&type=chunk) [Risks Related to Our Intellectual Property](index=111&type=section&id=Risks%20Related%20to%20Our%20Intellectual%20Property) - The company may be involved in lawsuits to protect or enforce its patents or those of its licensors, or lawsuits accusing its products of patent infringement, which could be **expensive, time-consuming, and unsuccessful**[368](index=368&type=chunk) - Issued patents covering product candidates could be found **invalid or unenforceable** if challenged in court or the USPTO, leading to a loss of patent protection[372](index=372&type=chunk) - The patent law relating to biotechnology is still evolving, leading to **uncertainty in patent positions** and potential for competitors to license similar intellectual properties or duplicate the business model[374](index=374&type=chunk)[377](index=377&type=chunk)[378](index=378&type=chunk) - The use of the company's technologies could potentially **conflict with the rights of others**, requiring alterations, licensing fees, or cessation of activities[379](index=379&type=chunk) - Changes in U.S. patent law could **diminish the value of patents**, and limited foreign intellectual property rights may hinder global protection efforts[381](index=381&type=chunk)[382](index=382&type=chunk) [Risks Related to Our Securities](index=117&type=section&id=Risks%20Related%20to%20Our%20Securities) - Officers, directors, and principal stockholders own a **substantial percentage** of the company's stock, enabling them to exert significant control over matters subject to stockholder approval[385](index=385&type=chunk) - The market price of the common stock is likely to be **volatile** and could fluctuate widely due to clinical trial results, regulatory developments, competition, and general market conditions[386](index=386&type=chunk) - Future sales of common stock in the public market, including from equity offerings or the exercise of common stock equivalents, could cause the stock price to **fall** and result in **substantial dilution** to existing stockholders[387](index=387&type=chunk)[388](index=388&type=chunk)[389](index=389&type=chunk) - The company does **not anticipate paying cash dividends** for the foreseeable future, so investors should not expect cash dividends[396](index=396&type=chunk) - Provisions in corporate charter documents and Delaware law may **prevent or frustrate attempts** by stockholders to change management or acquire a controlling interest in the company[397](index=397&type=chunk)[398](index=398&type=chunk) [Item 2. Unregistered Sales of Securities and Use of Proceeds](index=122&type=section&id=Item%202.%20Unregistered%20Sales%20of%20Securities%20and%20Use%20of%20Proceeds) This section states that there is nothing to report regarding unregistered sales of securities and use of proceeds for the period - **Nothing to report**[405](index=405&type=chunk) [Item 3. Defaults Upon Senior Securities](index=122&type=section&id=Item%203.%20Defaults%20Upon%20Senior%20Securities) This section indicates that there are no defaults upon senior securities to report for the period - **Nothing to report**[406](index=406&type=chunk) [Item 4. Mine Safety Disclosure](index=122&type=section&id=Item%204.%20Mine%20Safety%20Disclosure) This section states that there is no information to disclose regarding mine safety for the period - **Nothing to report**[407](index=407&type=chunk) [Item 5. Other Information](index=122&type=section&id=Item%205.%20Other%20Information) This section indicates that there is no other information to report for the period - **Nothing to report**[408](index=408&type=chunk) [Item 6. Exhibits](index=123&type=section&id=Item%206.%20Exhibits) This section lists the exhibits filed as part of the Form 10-Q, including certifications from the Chief Executive Officer and Chief Financial Officer, as well as various Inline XBRL documents - Includes Rule 13a-14(a)/15d-14(a) Certifications of Chief Executive Officer and Chief Financial Officer (**Exhibits 31.1 and 31.2**)[410](index=410&type=chunk) - Includes Section 1350 Certifications of Chief Executive Officer and Chief Financial Officer (**Exhibits 32.1 and 32.2**)[410](index=410&type=chunk) - Includes Inline XBRL Instance Document and various Inline XBRL Taxonomy Linkbase Documents[410](index=410&type=chunk) [SIGNATURES](index=124&type=section&id=SIGNATURES) Confirms the due authorization and signing of the Quarterly Report on Form 10-Q by the company's executive officers [SIGNATURES](index=124&type=section&id=SIGNATURES) This section confirms the due authorization and signing of the Quarterly Report on Form 10-Q on May 5, 2022, by the company's Interim Chief Executive Officer and President, and General Counsel, and its Chief Financial Officer and Treasurer - The report was signed on **May 5, 2022**[413](index=413&type=chunk) - Signed by **Frederick G. Vogt, Ph.D., J.D.**, Interim Chief Executive Officer and President, and General Counsel (Principal Executive Officer)[413](index=413&type=chunk) - Signed by **Jean-Marc Bellemin**, Chief Financial Officer and Treasurer (Principal Financial and Accounting Officer)[413](index=413&type=chunk)

1 I OVANCE 1 Corporate Overview March 2022 © 2022, Iovance Biotherapeutics, Inc. Forward-Looking Statements Certain matters discussed in this presentation are "forward-looking statements" of Iovance Biotherapeutics, Inc. (hereinafter referred to as the "Company," "we," "us," or "our") within the meaning of the Private Securities Litigation Reform Act of 1995 (the "PSLRA"). All such written or oral statements made in this presentation, other than statements of historical fact, are forward-looking statements ...

Financial Data and Key Metrics Changes - As of December 31, 2021, Iovance held $602.1 million in cash, cash equivalents, investments, and restricted cash, a decrease from $635 million on December 31, 2020, indicating a strong cash position expected to last into 2024 [37] - The net loss for Q4 2021 was $99.3 million or $0.63 per share, compared to a net loss of $68.4 million or $0.47 per share in Q4 2020 [38] - For the full year 2021, the net loss was $342.3 million or $2.23 per share, compared to a net loss of $259.6 million or $1.88 per share in 2020 [39] Business Line Data and Key Metrics Changes - Research and development expenses for Q4 2021 were $75.6 million, an increase of $23.1 million from $52.5 million in Q4 2020, primarily due to growth in the internal R&D team and increasing clinical trial costs [40] - General and administrative expenses for Q4 2021 were $23.8 million, up from $16.1 million in Q4 2020, attributed to growth in the internal team and increased intellectual property filing costs [43] Market Data and Key Metrics Changes - The company is focused on onboarding at least 40 authorized treatment centers (ATCs) for the commercialization of lifileucel, informed by CAR-T market data indicating that top centers account for a significant portion of treated patients [22] Company Strategy and Development Direction - The company aims to submit its Biologics License Application (BLA) for lifileucel in metastatic melanoma in the first half of 2022 and expand TIL therapy into non-small cell lung cancer and cervical cancer [13][14] - Iovance is preparing for commercial manufacturing and launch, with a focus on owning its manufacturing capabilities to ensure success [14] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the strength of Iovance's position to lead in developing TIL therapies for cancer, emphasizing the importance of their manufacturing capabilities [14] - The company is actively engaged in discussions with the FDA regarding regulatory plans and is preparing for potential BLA submission [9][10] Other Important Information - The Iovance Cell Therapy Center (ICTC) has completed commissioning activities and initiated TIL clinical supply, with the first patient receiving TIL manufactured at ICTC in September 2021 [16][17] - The company has a robust intellectual property portfolio with over 35 granted or allowed patents, providing exclusivity into 2038 [18][19] Q&A Session Summary Question: Resolution on potency assay for BLA submission - Management confirmed the need for resolution on the potency assay to proceed with BLA submission and indicated ongoing discussions with the FDA [51][52] Question: Filing and validation process - Management clarified that the BLA submission process involves ongoing interactions with the FDA, and they aim to address any concerns raised during the review period [60][62] Question: Cervical cancer filing timelines - Management acknowledged changes in the treatment landscape for cervical cancer and is planning a registrational strategy based on FDA feedback [70] Question: Cohort 4 data status - Management stated that Cohort 4 data is still being worked on and will be included in the BLA submission [58][59] Question: European filing strategy - Management indicated that the European strategy hinges on the outcome of the FDA submission, with plans to move quickly if the FDA approval is granted [124][125]

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, 2021 ☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the transaction period from __________ to __________ Commission file number: 001-36860 IOVANCE BIOTHERAPEUTICS, INC. (Exact Name of Registrant as Specified in Its Charter) Del ...

| --- | --- | --- | --- | --- | |-------|-------|-------|-------|-------| | | | | | | | | | | | | | | | | | | | | | | | | 1 Certain matters discussed in this presentation are "forward-looking statements" of Iovance Biotherapeutics, Inc, Inc. (hereinafter referred to as the "Company," "we," "us," or "our") within the meaning of the Private Securities Litigation Reform Act of 1995 (the "PSLRA"). All such written or oral statements made in this presentation, other than statements of historical fact, are forwar ...

| --- | --- | --- | --- | --- | |-------------------------------------------|-------------------------------------------------------------------------|-------------------|-------|-------| | | | | | | | | | | | | | | | | | | | | | | | | | Conference Call & Webcast: Annual Meeting | Clinical Data Highlights at Society for Immunotherapy of Cancer (SITC) | | | | | | | November 13, 2021 | | | | | © 2021, Iovance Biotherapeutics, Inc | | | | 1 Certain matters discussed in this presentation are "forward-looking st ...

Financial Data and Key Metrics Changes - As of September 30, 2021, Iovance held $660.8 million in cash, cash equivalents, investments, and restricted cash, compared to $635 million on December 31, 2020, indicating a strong cash position sufficient to support operations into 2023 [40] - The net loss for Q3 2021 was $86.1 million or $0.55 per share, compared to a net loss of $58.6 million or $0.40 per share for Q3 2020 [41] - Research and development expenses increased to $65.4 million for Q3 2021, up from $43.1 million in Q3 2020, primarily due to growth in the internal R&D team and clinical trial costs [42][43] - General and administrative expenses rose to $20.9 million for Q3 2021, compared to $15.9 million in Q3 2020, attributed to team growth and higher stock-based compensation [45] Business Line Data and Key Metrics Changes - The company continues to advance its tumor-infiltrating lymphocyte (TIL) platform into new indications and earlier treatment settings, with a focus on lifileucel for metastatic melanoma [9][10] - Clinical data shows promise for TIL therapy across four solid tumor types, with ongoing studies demonstrating increasing long-term durability following treatment [11][12] Market Data and Key Metrics Changes - The FDA granted Fast Track designation for lifileucel in combination with pembrolizumab for metastatic melanoma, allowing for potential accelerated approval and priority review [13] - Initial clinical data in metastatic non-small cell lung cancer showed a 21.4% overall response rate in heavily pretreated patients, highlighting a significant unmet need [14] Company Strategy and Development Direction - Iovance aims to be a global leader in TIL cell therapy, focusing on enhancing partnerships with leading U.S. cancer centers and ensuring timely access to lifileucel upon approval [26][27] - The company is advancing a next-generation TIL product, IOV-4001, and a novel IL-2 analog, IOV-3001, through IND-enabling studies [15] Management's Comments on Operating Environment and Future Outlook - Management remains confident in the anticipated BLA submission for lifileucel in the first half of 2022, despite ongoing discussions with the FDA regarding potency assays [10][51] - The company is focused on maintaining operational excellence and ensuring timely access to lifileucel for patients [29] Other Important Information - The Iovance Cell Therapy Center (iCTC) in Philadelphia has initiated manufacturing of investigational TIL therapies, with a manufacturing success rate above 90% [19] - The company has over 30 granted and allowed patents in the U.S. and internationally, with a robust IP portfolio supporting its TIL therapies [23][24] Q&A Session Summary Question: Update on FDA discussions regarding potency assays - Management confirmed ongoing engagement with the FDA and reiterated the plan to submit the BLA in the first half of 2022 [50][51] Question: Clarification on filing guidance and what is being awaited - Management indicated that they are not waiting on any specific item and are continuing to prepare for the BLA submission while engaging with the FDA [58][59] Question: Concerns about potential FDA requests for randomized trials - Management stated that the FDA is not currently asking for randomized trials and they plan to use existing pivotal study data for the submission [64] Question: Guidance on potency assays and patent protection - Management discussed the complexity of potency assays and indicated that they have multiple assays under consideration, some of which have associated IP [97][99] Question: Timing for data collection related to clinical trials - Management explained that patient assessments are ongoing and data collection will proceed according to predefined schedules without additional patient calls [91][92]

Table of Contents U. S. SECURITIES AND EXCHANGE COMMISSION WASHINGTON, DC 20549 FORM 10-Q ☑ QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the quarterly period ended September 30, 2021 ☐ 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 001-36860 IOVANCE BIOTHERAPEUTICS, INC. (Exact name of issuer as specified in its charter) (State or other jurisdiction of (I.R.S. e ...

Start Time: 16:30 January 1, 0000 5:12 PM ET Iovance Biotherapeutics, Inc. (NASDAQ:IOVA) Q2 2021 Earnings Conference Call August 05, 2021, 16:30 PM ET Company Participants Frederick Vogt - Interim President and CEO Igor Bilinsky - COO Jim Zigler - SVP, Commercial Friedrich Finckenstein - CMO Jean-Marc Bellemin - CFO Madan Jagasia - SVP of Medical Affairs Sara Pellegrino - VP, Investor and Public Relations Conference Call Participants Michael Yee - Jefferies Mark Breidenbach - Oppenheimer Benjamin Burnett - ...