IOVANCE BIOTHERAPEUTICS, INC. (IOVA) FY 2023 MD&A

Item 7.          Management’s Discussion and Analysis of Financial Condition and Results of Operations

The following discussion and analysis of our results of operations and financial condition should be read in conjunction with our financial statements and the notes to those financial statements that are included elsewhere in this report. Our discussion includes forward-looking statements based upon current expectations that involve risks and uncertainties, such as our plans, objectives, expectations and intentions. Actual results and the timing of events could differ materially from those anticipated in these forward-looking statements as a result of a number of factors, including those set forth under the “Business” section and elsewhere in this report. We use words such as “may,” “will,” “might,” “could,” “would,” “should,” “expect,” “intend,” “plan,” “anticipate,” “believe,” “estimate,” “predict,” “project,” “aim,” “potential,” “continue,” “ongoing,” “goal,” “forecast,” “guidance,” “outlook,” or the negative of these terms or other similar expressions to identify forward-looking statements, although not all forward-looking statements contain these words. All forward-looking statements included in this report are based on information available to us on the date hereof and, except as required by law, we assume no obligation to update any such forward-looking statements.

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Overview

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We are a commercial-stage biopharmaceutical company pioneering a transformational approach to treating cancer by harnessing the human immune system’s ability to recognize and destroy diverse cancer cells using therapies personalized for each patient. Our mission is to be the global leader in innovating, developing and delivering tumor infiltrating lymphocyte, or TIL, cell therapies for patients with solid tumor cancers. With the recent approval of our biologics license application, or BLA, we are executing the U.S. launch of Amtagvi™ (lifileucel), the first product within our autologous TIL cell therapy platform, while also marketing Proleukin® (aldesleukin), an interleukin-2, or IL-2, product used in the Amtagvi™ treatment regimen. Amtagvi™ is a tumor-derived autologous T cell immunotherapy indicated for the treatment of adult patients with unresectable or metastatic melanoma previously treated with a PD-1 blocking antibody, and if BRAF V600 mutation positive, a BRAF inhibitor with or without a MEK inhibitor. This indication is approved under accelerated approval based on an endpoint of overall response rate, or ORR. Continued approval for this indication may be contingent upon verification and description of clinical benefit in future confirmatory trials. Amtagvi™ is the first and the only one-time, individualized T cell therapy to receive U.S. Food and Drug Administration, or FDA, approval for a solid tumor cancer. Amtagvi™ and Proleukin® are part of a treatment regimen that also includes lymphodepletion.

Iovance was founded to build upon the promise of TIL cell therapy that was previously demonstrated in single-center clinical trials at academic centers, including the National Cancer Institute, or the NCI. Our multi-center trials, novel TIL products, manufacturing processes, facilities, and bioanalytical platforms have transformed TIL cell therapy into a commercially viable treatment which many more patients with cancer can access.

We manufacture Amtagvi™ and our investigational TIL cell therapies using a centralized, scalable and proprietary 22-day manufacturing process which rejuvenates and multiplies polyclonal T cells unique to each patient into the billions and yields a cryopreserved, individualized therapy.

Our development pipeline includes multicenter trials of TIL cell therapies in additional treatment settings for solid tumor cancers. We are investigating TIL monotherapies for patients with later stage disease who were previously treated with standard of care therapies and TIL combinations with standard of care therapies to potentially improve outcomes in patients who are earlier in their disease. These trials include two ongoing registrational trials to support a supplementary BLA, or sBLA, of our TIL cell therapies in frontline advanced melanoma and in advanced non-small cell lung cancer following standard of care chemo-immunotherapy. We are also developing next generation therapies using TIL, such as genetically modified TIL cell therapy.

Corporate Strategy

Be the global leader in innovating, developing and delivering TIL cell therapy

Our mission is to be the global leader in innovating, developing and delivering TIL cell therapy for patients with solid tumor cancers. We are pioneering this transformational approach to cure cancer by harnessing the human immune system’s ability to recognize and destroy diverse cancer cells in each patient. Through the U.S. launch of Amtagvi™ and the advancement of our pipeline, we are committed to continuous innovation in developing TIL cell therapy and optimizing TIL treatment regimens that may extend and improve life for patients with cancer.

Successfully commercialize our lead product Amtagvi™ for the treatment of post-anti-PD-1 advanced melanoma

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Our top priority is commercialization of Amtagvi™ in the U.S. for the treatment of patients with post-anti-PD-1 advanced melanoma, for which we received FDA approval on February 16, 2024. We have experienced marketing, payer access and distribution teams as well as a sales force with extensive experience in oncology and cell therapy. Our medical affairs team is also in the field educating key opinion leaders, or KOLs, about Amtagvi™ and TIL cell therapy, as well as presenting and publishing our clinical results. More than half of the members of our field teams have prior cell therapy experience.

The four primary areas of our Amtagvi™ launch efforts include:

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Prepare for commercial manufacturing to meet forecasted demand

We are the first company to obtain FDA approval for a TIL cell therapy product. We believe that we are the only company in the U.S. to have a centralized, scalable, and commercially viable TIL manufacturing process. To date, more than 700 patients have been treated with Iovance TIL cell therapy products manufactured using our proprietary processes across multiple indications. Iovance TIL cell therapies are manufactured for commercial use and clinical trials at our manufacturing facility, the Iovance Cell Therapy Center, or the iCTC, and by a contract manufacturing organization, or CMO.

We are building capacity to treat several thousands of cancer patients annually at the iCTC, which is the first centralized and scalable current Good Manufacturing Practice, or cGMP, manufacturing facility dedicated to producing TIL. Located in Philadelphia, Pennsylvania, the 136,000 square feet iCTC is also among the largest cell therapy manufacturing facilities in existence. Additional expansion at the iCTC is under way which will significantly increase this capacity. The proximity of the iCTC to multiple airports facilitates delivery of TIL cell therapies to treatment centers, with the iCTC expected to cover logistics and delivery of TIL cell therapies in both North America and Europe. Owning our own facility allows us to control manufacturing capacity and product quality, manage logistics around supply and delivery, implement process improvement and realize potential cost efficiencies for TIL cell therapies that we may develop and commercialize. We are also exploring future TIL manufacturing processes, as well as next-generation treatments and technologies, which may further streamline development timelines and costs. The iCTC has a flexible design that allows future expansion within existing shell space and an option to build on an adjacent lot to support future growth and capacity needs.

In 2018, we began using our Gen 2 TIL manufacturing process, which reduced TIL manufacturing time to 22 days while producing a cryopreserved TIL product. The Gen 2 process was used to manufacture Amtagvi™ for the clinical trial that supported FDA approval, and most of our ongoing clinical trials use the Gen 2 process.

Amtagvi™ is approved for commercial manufacturing at the iCTC. In addition, our CMO is approved for additional capacity to supplement our internal manufacturing. We plan to carefully manage our cost structure and reduce the long-term cost of manufacturing our products. Details of related agreements are provided in the Research, Development, Manufacturing and License Agreements for TIL Cell Therapy section of this Annual Report on Form 10-K.

U.S. Commercial Launch of the First TIL Cell Therapy in Advanced Melanoma

Amtagvi™

Amtagvi™ (lifileucel) was approved by the FDA on February 16, 2024, for the treatment of adult patients with unresectable or metastatic melanoma previously treated with a PD-1 blocking antibody, and if BRAF V600 mutation positive, a BRAF inhibitor with or without MEK inhibitor. The approval is based on safety and efficacy results from the C-144-01 clinical trial, a global, multicenter trial investigating Amtagvi™ in patients with advanced melanoma previously treated with anti-PD-1 therapy and targeted therapy, where applicable. We completed the BLA submission in March 2023, which the FDA accepted in May 2023 for Priority Review. Based on the unmet need in post-anti-PD-1 advanced melanoma, as well as initial clinical data, lifileucel previously received a Regenerative Medicine Advanced Therapy, or RMAT, designation from the FDA in 2018.

Amtagvi™ is manufactured using a proprietary process to collect and multiply a patient’s unique T cells from a portion of their tumor. Amtagvi™ returns billions of the patient’s T cells back to the body to fight cancer. ATCs will administer Amtagvi™ to patients as part of a treatment regimen that includes lymphodepletion and a short course of high-dose Proleukin®  (aldesleukin).

There are three key steps in the Amtagvi™ treatment process.

●Step 1: Sample Collection. At an ATC, a tumor tissue sample of at least 1.5 cm in diameter is removed and collected during a surgical resection and shipped to an approved, centralized manufacturing facility.

●Step 2: Manufacturing. Patient-specific TIL are manufactured using our commercial Gen 2 manufacturing process. Upon arrival at the facility, TIL are separated from other cells within the patient’s tumor tissue sample. Over the next 22 days, the cells are multiplied into the billions, so they can be returned to the patient to fight cancer cells. Upon completion of manufacturing, Amtagvi™ is quality tested to meet specific product release criteria. The final product is cryopreserved and sent back to the ATC for administration to the patient. Additional details on the Gen 2 manufacturing process are provided in the Manufacturing Process section of our Annual Report on Form 10-K.

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●Step 3: Treatment Regimen. The patient’s cell therapy treatment begins with a preparative regimen of non-myeloablative lymphodepletion, or NMA-LD, to suppress the immunosuppressive tumor microenvironment, which we believe will enhance the efficacy of TIL cell therapy. After NMA-LD, the patient is treated at the ATC with Amtagvi™, followed by a short course of up to six doses of Proleukin® to promote T cell activity in the body after TIL infusion.

Until now, there were no FDA approved therapies in this treatment setting for advanced melanoma after anti-PD-1 therapy.

Proleukin®

In May 2023, we acquired the worldwide rights to Proleukin® (aldesleukin) as well as the manufacturing, supply, and commercialization income generated from such rights and associated operations from Clinigen Holdings Limited, Clinigen Healthcare Limited, and Clinigen, Inc, which we refer to collectively as Clinigen. Ownership of Proleukin® provides an additional revenue source, allows Iovance to secure its supply chain and logistics surrounding TIL cell therapy administration and lowers cost of goods and clinical trial expenses for Proleukin® used with TIL cell therapies.

Proleukin® is an IL-2 product used in the Amtagvi™ treatment regimen. Proleukin® has also received regulatory approvals for treatment of adults with metastatic melanoma and metastatic renal cell carcinoma in the United States. Proleukin® is also licensed in multiple countries around the world for treatment of patients with metastatic renal cell carcinoma and/or metastatic melanoma.

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TIL Cell Therapy Clinical Development in Advanced, Metastatic or Unresectable Solid Tumor Cancers

TIL cell therapy is a T cell-based immunotherapy technology platform that leverages patient-specific cells to recognize and attack diverse cancer cells that are unique to each patient. Unlike other cell therapies that act on a single or small number of shared antigen targets common to certain tumors, our individualized T cell therapies are polyclonal or designed to target a variety of neoantigens that are unique to the patient or tumor. We believe this polyclonal cell therapy is potentially applicable to many solid tumor cancers, where the majority of immune targets are patient-specific. Our TIL cell therapy platform and manufacturing process have been initially validated through the FDA approval of Amtagvi™.

We have investigated TIL cell therapy in global, multicenter clinical trials in advanced melanoma, cervical cancer, non-small cell lung cancer, or NSCLC, and head and neck squamous cell carcinoma, or HNSCC. Through ongoing academic collaborations, as well as government and other partners, we are investigating the next frontier for TIL cell therapy in other tumor types and treatment settings.

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Next-Generation TIL Therapy Product Candidates

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Our next-generation technology platforms are designed to optimize outcomes with TIL cell therapy across three key initiatives: genetic modifications, potency, and new treatment regimens.

Intellectual Property

We have established a leading intellectual property portfolio developed internally and licensed from third parties. We currently own more than 60 U.S. patents related to TIL cell therapy, including patents directed to compositions and methods of treatment in a broad range of cancers, such as U.S. Patent Nos. 10,130,659; 10,166,257; 10,272,113; 10,363,273; 10,398,734; 10,420,799; 10,463,697; 10,517,894; 10,537,595; 10,639,330; 10,646,517; 10,653,723; 10,695,372; 10,894,063; 10,905,718; 10,918,666; 10,925,900; 10,933,094; 10,946,044; 10,946,045; 10,953,046; 10,953,047; 11,007,225; 11,007,226; 11,013,770; 11,026,974; 11,040,070; 11,052,115; 11,052,116; 11,058,728; 11,083,752; 11,123,371; 11,141,438; 11,168,303; 11,168,304; 11,179,419; 11,202,803; 11,202,804; 11,220,670; 11,241,456; 11,254,913; 11,266,694; 11,273,180; 11,273,181; 11,291,687; 11,304,979; 11,304,980; 11,311,578; 11,337,998; 11,344,579; 11,344,580; 11,344,581; 11,351,197; 11,351,198; 11,351,199; 11,364,266; 11,369,637; 11,384,337; 11,433,097; 11,517,592; 11,529,372 ; 11,541,077; 11,713,446; 11,819,517; and 11,866,688. More than 40 of these patents are related to our Gen 2 TIL manufacturing processes and have terms that we anticipate will extend to January 2038, not including any patent term extensions or adjustments that may be available. Our owned and licensed intellectual property portfolio also includes patents and patent applications relating to TIL, marrow-infiltrating lymphocytes, or MIL, and peripheral blood lymphocyte, or PBL, therapies; frozen tumor-based TIL technologies; remnant TIL and digest TIL compositions, methods and processes; methods of manufacturing TIL, MIL, and PBL therapies; the use of costimulatory and T cell modulating molecules in TIL cell therapy and manufacturing; stable and transient genetically-modified TIL cell therapies, including genetic knockouts of immune checkpoints; cytokine-tethered TIL cell therapies; methods of using ICIs in combination with TIL cell therapies; TIL selection technologies; and methods of treating patient subpopulations.

Components of Operating Results

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Revenues

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Subsequent to the acquisition of Proleukin® in May 2023, or the Acquisition, we began to sell Proleukin®. Proleukin® is currently being used in multiple active studies across multiple therapeutic areas and indications and investigated alongside TIL cell therapies within a number of oncology indications. Proleukin® is also part of our regimens of TIL cell therapy, including Amtagvi™ (lifileucel), and is used in our multiple clinical trials. Revenues for the year ended December 31, 2023 represents product sales of Proleukin® primarily in licensed markets outside of the U.S. To date, there have been no product sales of Proleukin® in the U.S. market.

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With the recent BLA approval, we expect to generate revenues from the sale of our product Amtagvi™. However, such revenues for Amtagvi™ and Proleukin® may not be material during the 12 months from the date the consolidated financial statements are issued and this Annual Report on Form 10-K is filed. Our ability to generate revenues in the future will depend on our ability to successfully execute the launch of Amtagvi™, integrate the Proleukin® business and market Proleukin®, and complete the development of our product candidates and obtain regulatory approval for them.

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Costs and Expenses

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Cost of sales

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Cost of sales includes the cost of Proleukin® inventories and other costs that are directly associated with the purchase and sales of Proleukin®. In addition, amortization expense for the fair value step-up of acquired Proleukin® inventory and the acquired intangible asset related to the developed technology are included in cost of sales.

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Research and development

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Research and development expenses include personnel and facility-related expenses, outside contracted services including clinical trial costs, manufacturing and process development costs, research costs and other consulting services. Research and development costs are expensed as incurred. Nonrefundable advance payments for goods or services that will be used or rendered for future research and development activities are deferred and amortized over the period that the goods are delivered, or the related services are performed, subject to an assessment of recoverability.

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Clinical development costs are a significant component of research and development expenses. We have a history of contracting with third parties that perform various clinical trial activities on our behalf in connection with the ongoing development of our product candidates. The financial terms of these contracts are subject to negotiations and may vary from contract to contract and may result in uneven payment flow. We accrue and expense costs for clinical trial activities performed by third parties based upon estimates of work completed to date of the individual trial in accordance with agreements established with contract research organizations and clinical trial sites. The duration, costs and timing of our clinical trials and development of our product candidates will depend on a number of factors that include, but are not limited to, the number of patients that enroll in the trial, per patient trial costs, number of sites included in the trial, discontinuation rates of patients, duration of patient follow-up, efficacy and safety profile of the product candidate, and the length of time required to enroll eligible patients.

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We expect to continue to incur research and development expenses for the foreseeable future as we continue to conduct our clinical trials for our various product candidates. We expect our research and development expenses to decrease in conjunction with an expected increase in commercial activities and selling, general and administrative expense due to the approval of AmtagviTM (lifileucel). However, it is difficult to determine with certainty the duration and completion costs of our current or future preclinical programs and clinical trials of our product candidates.

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Selling, general and administrative

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Selling, general and administrative expenses consist primarily of salaries and other related costs, including stock-based compensation, for personnel in executive, finance, procurement, legal, investor relations, facilities, business development, marketing, commercial, information technology and human resources functions. Other significant costs include facility costs not otherwise included in research and development expenses, legal fees relating to corporate matters and intellectual property, insurance, public company expenses relating to maintaining compliance with Nasdaq listing rules and SEC requirements, investor relations costs, and fees for accounting and consulting services. General and administrative costs are expensed as incurred, and we accrue for services provided by third parties related to the above expenses by monitoring the status of services provided and receiving estimates from its service providers and adjusting its accruals as actual costs become known.

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We anticipate selling, general and administrative expenses will increase as we execute the launch of Amtagvi™ and market Proleukin®, as well as execute an expected expansion of the internal general and administrative team to support the overall growth in our business.

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Interest income, net

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Interest income, net results from our interest-bearing cash and investment balances.

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Income tax benefit

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Income tax benefit pertains to the operations in the United Kingdom and realization of related deferred taxes.

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Results of Operations for the Years Ended December 31, 2023 and 2022

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Revenue

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Revenue for the year ended December 31, 2023 was $1.2 million and related entirely to product sales of Proleukin® in licensed markets outside of the U.S following the completion of the acquisition of worldwide rights to Proleukin® in May 2023. To date, there have been no product sales of Proleukin® in the U.S. market, which at the time of the Acquisition had sufficient Proleukin® inventory in existing distributors to support U.S. market demand. There was no revenue for the year ended December 31, 2022.

Costs and expenses

The following table summarizes the period-over-period changes in our costs and expenses:

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Cost of sales

Cost of sales for the year ended December 30, 2023 was $10.7 million, which consists of $1.0 million cost of inventory and related inventoriable costs associated with sales of Proleukin® and $9.7 million of amortization expense for the developed technology intangible asset recorded as part of the Acquisition. No cost of sales was incurred for the year ended December 31, 2022.

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Research and development expense

Research and development expense for the year ended December 31, 2023 increased by $49.3 million, or 17%, compared to the year ended December 31, 2022. The increase was primarily attributable to (i) a $40.0 million increase in payroll and related expenses, driven by increased hiring of research and development employees to support our manufacturing at iCTC and clinical development activities, (ii) a $10.3 million increase in manufacturing costs to support the increased production and qualifying iCTC suites for commercial manufacturing readiness, (iii) a $7.0 million increase in clinical trial costs driven primarily by the initiation of our Phase 3 TILVANCE-301 clinical trial, (iv) a $5.9 million increase in facility and related costs, including depreciation, maintenance, environmental monitoring and other costs primarily related to the iCTC build-out intended to expand manufacturing capacity, and (v) a $2.4 million increase in other costs, including license costs related to the expansion of our information technology infrastructure to support our clinical activities and research alliance costs. These expenses were partially offset by (i) a $15.3 million decrease in stock-based compensation expenses, primarily driven by a lower average stock price, and (ii) a $1.0 million decrease in costs associated with travel and medical affairs activities such as publications and medical conferences.

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Research and development activities are central to our business model. Product candidates in later stage of clinical development generally have higher development costs than those in earlier stages of clinical development, primarily due to the increased size and duration of later-stage clinical trials. We separate our research and development expenses into two broad categories: direct and indirect. Additionally, with respect to direct research and development expenses, we further divide expenses into the following sub-categories: “TIL, including combination therapy,” “Next Generation,” and “Other clinical, preclinical and research programs under development.” For direct research and development expenses, we track specific project research and development expenses that are directly attributable to our preclinical and clinical development candidates that have been selected for further development. Such direct research and development expenses include third-party contract costs relating to the manufacturing of TILs as well as preclinical and clinical trial activities.

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All remaining research and development expenses are categorized as indirect research and development expenses. Such indirect

research and development expenses include employee salaries and benefits, stock-based compensation, consulting and contracted services to supplement our in-house activities, and costs associated with our facilities. These expenses are not directly tied to any individual project and are generally deployed across multiple projects. As such, we do not maintain information regarding those costs incurred on a project specific basis.

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The table below summarizes our research and development expenses by therapeutic area (in thousands):

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Selling, general and administrative expense

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Selling, general and administrative expense for the year ended December 31, 2023, increased by $2.8 million, or 3%, compared to the year ended December 31, 2022. The increase was primarily attributable to (i) a $12.6 million increase in payroll and related expenses, resulting from increases in headcount to support the growth in the overall business and related corporate infrastructure, and  (ii) a $5.0 million increase in professional fees and travel costs, including costs associated with Proleukin® integration. These increases were partially offset by (i) a $6.1 million decrease in stock-based compensation expenses, primarily driven by a lower average stock price, (ii) a $4.3 million decrease in legal costs related to intellectual property related matters, and (iii) a $4.4 million decrease in other costs, including marketing, advertising and software license costs.

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Interest income, net

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Interest income results from our interest-bearing cash and investment balances. Net interest income increased by $10.1 million, or 337%, primarily due to increases in interest rates as well as a shift in our portfolio to interest bearing investments such as U.S. treasury securities and money market funds.

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Income tax benefit

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Income tax benefit for the year ended December 31, 2023 was $3.5 million as a result of the tax benefit from the realization of the related deferred taxes for operations in the United Kingdom. No benefit or expense was recorded for the year ended December 31, 2022.

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Net loss

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Net loss for the year ended December 31, 2023, increased by $48.1 million or 12.0%, compared to the year ended December 31, 2022. The increase in our net loss was due to the continued expansion of our research and development activities, ongoing and newly initiated clinical trials, and the overall growth in our workforce and corporate infrastructure as well as our pre-commercialization activities for lifileucel. We anticipate that we will continue to incur net losses in the future as we further invest in our clinical and internal research and development programs as well as the execution of the launch of Amtagvi™, the Proleukin® business integration, and both clinical and internal development programs.

Results of Operations for the Years Ended December 31, 2022 and 2021

Revenue

No revenue was recorded for the years ended December 31, 2022 and 2021.

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Costs and expenses

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The following table summarizes the period-over-period changes in our costs and expenses:

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Research and development expense

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Research and development expense for the year ended December 31, 2022 increased by $35.7 million, or 14%, compared to the year ended December 31, 2021. The increase was primarily attributable to (i) a $23.9 million increase in payroll and related expenses and a $9.4 million increase in stock-based compensation expenses, both driven by increased hiring of research and development employees to support our on-going and planned clinical development activities, (ii) a $16.2 million increase in facility related expenses, including depreciation expenses associated with the iCTC and the build-out of our new corporate headquarters office, (iii) a $3.5 million increase in research and research alliance activities due to increased spend in lab supplies and consumables to support preclinical activities, (iv) a $2.7 million increase in patient advocacy and physician outreach and travel to support our planned commercial launch, and (v) a $2.4 million increase in license costs associated with the expansion of our information technology infrastructure to support our clinical and manufacturing activities at the iCTC. These increases were partially offset by a $17.4 million decrease in clinical trial costs, including clinical trial drug costs, and a $5.0 million decrease in manufacturing costs driven by completion of enrollment in pivotal cohorts of our clinical trials.

We separate our research and development expenses into two broad categories: direct and indirect. Additionally, with respect to

direct research and development expenses, we further divide expenses into the following sub-categories: “TIL, including combination

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therapy,” “Next Generation,” and “Other clinical, preclinical and research programs under development.” For direct research and development expenses, we track specific project research and development expenses that are directly attributable to our preclinical and clinical development candidates that have been selected for further development. Such direct research and development expenses include third-party contract costs relating to the manufacturing of TILs as well as preclinical and clinical trial activities.

All remaining research and development expenses are categorized as indirect research and development expenses. Such indirect research and development expenses include employee salaries and benefits, stock-based compensation, consulting and contracted services to supplement our in-house activities, and costs associated with our facilities. These expenses are not directly tied to any individual project and are generally deployed across multiple projects. As such, we do not maintain information regarding those costs incurred on a project specific basis.

The table below summarizes our research and development expenses by therapeutic area (in thousands):

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Selling, general and administrative expense

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Selling, general and administrative expense for the year ended December 31, 2022, increased by $20.4 million, or 24%, compared to the year ended December 31, 2021. The increase was primarily attributable to (i) a $10.0 million increase in payroll and related expenses and a $4.8 million increase in stock-based compensation expenses, both resulting from increases in headcount to support the growth in the overall business and related corporate infrastructure, (ii) a $3.4 million increase in marketing, advertising and travel related costs related to branding awareness to support our planned commercial launch, (iii) a $1.7 million increase in other costs, including professional fees and costs associated with the build-out of our new headquarter office and our information technology infrastructure to support the continued growth in the overall company, and (iv) a $0.5 million increase in depreciation expenses and facility related costs associated with the build-out of our new corporate headquarters.

Interest income, net

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Interest income results from our interest-bearing cash and investment balances. Net interest income increased by $2.5 million, or 562%, primarily due to an increase in interest rates as well as a shift in our portfolio to interest bearing investments such as U.S. treasury securities and money market funds.

Net loss

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Net loss for the year ended December 31, 2022, increased by $53.6 million or 16%, compared to the year ended December 31, 2021. The increase in our net loss was due to the continued expansion of our research and development activities, and the overall growth of our corporate infrastructure.

Liquidity and Capital Resources

We have incurred losses and generated negative cash flows from operations since inception. Historically, we have funded our operations from various public and private offerings of our equity securities, both common stock and preferred stock, from option and warrant exercises, and from interest income. Since 2017, our primary source of funds has been from the public sale of our common stock. With the recent approval of our BLA, we expect to generate revenue from the sale of our product, Amtagvi™ (lifileucel). Furthermore, upon the completion of the closing of the acquisition of the worldwide rights to Proleukin® in the second quarter of 2023, we began to generate revenue from the sales of Proleukin®. However, such revenues for Amtagvi™ and Proleukin® may not be material during the 12 months from the date the consolidated financial statements are issued and this Annual Report on Form 10-K is filed. As of December 31, 2023, we had $346.3 million in cash, cash equivalents, investments, and restricted cash ($114.9 million of cash and cash equivalents, $165.0 million in short-term investments, and $66.4 million in restricted cash).

We expect to continue to incur significant expenses to support our execution of the commercial launch of Amtagvi™, fund ongoing clinical programs, including our NSCLC registration study, IOV-LUN-202, and our frontline advanced melanoma Phase 3 confirmatory trial, TILVANCE-301, continue the development of our pipeline candidates, and for other general corporate purposes. Based on the funds we have available as of the date our consolidated financial statements for the year ended December 31, 2023 are issued, which include estimated net proceeds (after deducting underwriting and other offering expenses) of approximately $197.1 million from the public offering of our common stock completed on February 22, 2024, we believe that we have sufficient capital to fund our anticipated operating expenses and capital expenditures as planned for at least the next twelve months following the issuance of our consolidated financial statements included in this Annual Report on Form 10-K.

Corporate Capitalization

As of December 31, 2023, we had outstanding 256,135,715 shares of our $0.000041666 par value common stock, 194 shares of our $0.001 par value Series A Convertible Preferred Stock, and 2,842,158 shares of our $0.001 par value Series B Convertible Preferred Stock. The outstanding shares of Series A Convertible Preferred Stock are currently convertible into 97,000 shares of our common stock, and the outstanding shares of Series B Convertible Preferred Stock are currently convertible into 2,842,158 shares of our common stock. The shares of Series A Convertible Preferred Stock and Series B Convertible Preferred Stock do not have voting rights or accrue dividends.

On February 8, 2021, we entered into an Open Market Sale Agreement, or the 2021 Sale Agreement, with Jefferies LLC, or Jefferies, with respect to an “at the market” offering program, under which we were able to, from time to time, in our sole discretion, issue and sell through Jefferies, acting as sales agent, up to $350.0 million of shares of our common stock.

On November 18, 2022, we entered into a new Open Market Sale Agreement, or the 2022 Sale Agreement, with Jefferies with respect to an “at the market” offering program. Under the terms of the 2022 Sale Agreement, we were able to, from time to time, in our sole discretion, issue and sell up to $500.0 million of shares of our common stock pursuant to the “at the market” offering program. The 2022 Sale Agreement superseded and replaced in its entirety the 2021 Sale Agreement, which was terminated by the Company.

On June 16, 2023, we entered into a new Open Market Sale Agreement, or the 2023 Sale Agreement, with Jefferies with respect to an “at the market” offering program. Under the terms of the 2023 Sale Agreement, we may, from time to time, in our sole discretion, issue and sell up to $450.0 million of shares of our common stock pursuant to the “at the market” offering program. The 2023 Sale Agreement superseded and replaced in its entirety the 2022 Sale Agreement, which was terminated by the Company. The issuance and sale, if any, of shares of our common stock under the 2023 Sale Agreement was or will be made pursuant to a prospectus supplement dated June 16, 2023 to our Registration Statement on Form S-3ASR, which became effective immediately upon filing with the U.S. Securities and Exchange Commission on June 16, 2023. We received $301.7 million in proceeds, net of offering costs, through the sale of 44,080,226 shares of our common stock during 2023.

On July 13, 2023, we closed an underwritten public offering of 23,000,000 shares of our common stock, which included 3,000,000 shares issued pursuant to the exercise of the option granted to the underwriters, at a public offering price of $7.50 per share, before underwriting discounts and commissions. The total estimated net proceeds to us from the offering, including the exercise of the option

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by the underwriters, were $161.5 million after deducting underwriting discounts and commissions and estimated offering expenses payable by us.

On February 22, 2024, we closed an underwritten public offering of 23,014,000 shares of our common stock at a public offering price of $9.15 per share, before underwriting discounts and commissions. The total estimated net proceeds to us from the offering are expected to be approximately $197.1 million after deducting underwriting discounts and commissions and estimated offering expenses payable by us.

In the future, we may periodically offer one or more of these securities in amounts, prices and terms to be announced when and if the securities are offered. If any of the securities covered by the 2020 Shelf Registration Statement are offered for sale, a prospectus supplement will be prepared and filed with the SEC containing specific information about the terms of such offering at that time.

Cash Flows

Cash flows from operating, investing and financing activities (in thousands):

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Operating Activities

Net cash used in operating activities represents cash disbursements related to all of our activities other than investing and financing activities. Operating cash flow is derived by adjusting our net loss for non-cash items and changes in operating assets and liabilities. Net cash used in operating activities for the year ended December 31, 2023 was $361.8 million compared to $292.8 million for the same period in 2022. The increase of $69.1 million in cash used in operating activities was primarily due to a $48.1 million increase in net loss related to increased costs in research and development, including the overall expansion of our clinical trials for new TIL cell therapies as well as our pre-commercialization activities for lifileucel, and the overall growth in our workforce and corporate infrastructure. In addition, it reflects a decrease in non-cash charges of $17.3 million primarily driven by lower stock-based compensation expenses and accretion of discount on investments, partially offset by increases in amortization of intangible assets driven primarily by the amortization associated with the developed technology intangible asset acquired as part of the Acquisition and in depreciation expense resulting primarily from additional fixed assets put in service at the iCTC. Further, net cash used by changes in operating assets and liabilities increased by $27.1 million, driven primarily by cash used for the purchase of Proleukin® inventory as part of the Acquisition and an increase in lease payments for our lease arrangements, resulting primarily from the full utilization of tenant improvement allowances offered under our lease agreements during 2022. These increases in the use of cash were partially offset by a net $23.4 million decrease in cash used, driven by an increase in accounts payable and accrued expenses, which primarily resulted from the timing of vendor invoicing and related payments.

Net cash used in operating activities for the year ended December 31, 2022, was $292.8 million compared to $227.9 million for the same period in 2021. The increase of $64.8 million in cash used in operating activities was primarily due to an increase in net loss driven by increased costs in research and development and pre-commercial activities, which was partially offset by an increase in non-cash charges of $16.3 million primarily driven by higher stock-based compensation expenses, operating right-of-use assets associated with our office and manufacturing facility as well as embedded leases, and depreciation expenses, partially offset by accretion of discount on investments. In addition, it reflects a $31.4 million increase in cash used by assets and liabilities driven primarily by changes in accruals and accounts payable as well as prepaid assets, resulting from the increased workforce, overall growth in the business and operations, and the timing of vendor invoicing and related payments. These increases were offset by a net increase in our operating lease liabilities primarily driven by receipts of tenant improvement allowances for our new corporate headquarters office.

Net cash used in operating activities for the year ended December 31, 2021 was $227.9 million compared to $205.1 million for the same period in 2020. The increase of $22.8 million in cash used in operating activities was primarily due to an increase in net loss

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driven by increased costs in research and development and pre-commercial activities, which was partially offset by an increase in non-cash charges of $38.3 million primarily driven by higher stock-based compensation expenses, amortization of premiums on investments and operating right-of-use assets associated with our office and manufacturing facility as well as embedded leases, and depreciation expenses. In addition, it reflects a $5.6 million reduction in our operating lease liabilities associated with payments on lease arrangements, offset by a $16.0 million increase in accruals and accounts payable primarily related to our increased workforce, overall growth in the business and operations, and the timing of vendor invoicing and related payments.

Investing Activities

Net cash (used in)/provided by investing activities primarily relates to the cash utilized to fund the Acquisition and the purchases and maturities of our investments and capital expenditures. Net cash used in investing activities for the year ended December 31, 2023 was $155.2 million compared to net cash provided by investing activities of $256.5 million for the same period in 2022. The increase in cash used of $411.7 million was driven by the $212.6 million payment for the acquisition of the Proleukin® business, excluding the payment of acquired inventories, which is presented in operating activities, and a $1.9 million increase in capital expenditures, offset by a $197.2 million net increase in the timing of maturities and purchases of investments.

Net cash (used in) / provided by investing activities primarily consists of purchases, maturities of our investments and capital expenditures. Net cash provided by investing activities for the year ended December 31, 2022 was $256.5 million compared to net cash provided by investing activities of $0.1 million for the same period in 2021. The increase in cash provided by investing activities of $256.4 million was primarily due to the timing of maturities and purchases of investments and lower capital expenditures in 2022.

Net cash provided by investing activities for the year ended December 31, 2021 was $0.1 million compared to net cash used in investing activities of $317.9 million for the same period in 2020. The increase in cash provided by investing activities of $318.0 million was primarily due to the timing of maturities and purchases of investments and lower capital expenditures in 2021.

Financing Activities

Net cash provided by financing activities for the year ended December 31, 2023 was $463.0 million compared to net cash provided of $190.2 million for the same period in 2022. The increase in net cash provided by financing activities of $272.8 million was driven by a $273.8 million increase in net proceeds received from sales of common stock pursuant to the June 2023 underwritten public offering and our “at the market” offering program as well as $0.8 million received from the issuance of common stock under the 2020 Employee Stock Purchase Plan, or the 2020 ESPP. These increases were partially offset by a $1.6 million decrease in proceeds from the issuance of common stock upon the exercise of stock options.

Net cash provided by financing activities for the year ended December 31, 2022 was $190.2 million compared to net cash provided of $239.3 million for the same period in 2021. The net cash provided by financing activities during the year ended December 30, 2022, related to $189.5 million net cash proceeds from our “at the market” offering, $1.7 million of cash receipts from the issuance of common stock under the 2020 ESPP, and $1.6 million of cash receipts from the issuance of common stock upon the exercise of stock options. This was offset by cash used of $2.6 million for tax payments related to vested RSUs.

Net cash provided by financing activities for the year ended December 31, 2021 was $239.3 million compared to net cash provided of $576.4 million for the same period in 2020. The net cash provided by financing activities during the year ended December 30, 2021, related to $203.2 million net cash proceeds from our “at the market” offering and $33.5 million of cash receipts from the issuance of common stock upon the exercise of stock options. The net cash provided by financing activities during the year ended December 31, 2020, primarily related to $567.0 million net cash proceeds received in the June 2020 public offering and $9.7 million cash proceeds from issuance of common stock upon exercise of stock options in 2021.

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Contractual Obligations

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The following table summarizes our non-cancellable contractual obligations as of December 31, 2023, and the effects that such obligations are expected to have on our liquidity and cash flows in future periods (in thousands):

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Off-Balance Sheet Arrangements

As of December 31, 2023 we did not have, and currently do not have, any off-balance sheet arrangements.

Critical Accounting Policies and Significant Judgements and Estimates

Our accounting policies are more fully described in Note 2 of the consolidated financial statements included in this Annual Report on Form 10-K. As described in Note 2, the preparation of our consolidated financial statements requires us to make estimates and judgments that affect the reported amounts of assets and liabilities and the disclosure of contingent assets and liabilities at the date of our financial statements as well as the reported revenues and expenses during the reported periods. We base our estimates on historical experience and on various market-specific and other relevant assumptions that we believe to be reasonable under the circumstances, the results of which form the basis for making judgments about the carrying value of assets and liabilities that are not readily apparent from other sources. Estimates are assessed each period and updated to reflect current information. Actual results may differ from these estimates under different assumptions or conditions.

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We believe the following critical accounting policies reflect the more significant judgments and estimates used in the preparation of our consolidated financial statements:

Asset Acquisitions

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We make certain judgments to determine whether transactions should be accounted for acquisitions of assets or business combinations using the guidance in Accounting Standard Codification, or ASC, Topic 805, Business Combinations by first applying a screen test to assess if substantially all of the fair value of the gross assets acquired is concentrated in a single identifiable asset or group of assets. If the screen test is met, the transaction is accounted for as an asset acquisition. If the screen test is not met, further assessment is required to determine whether we have acquired inputs and processes that have the ability to create outputs, which would meet the requirements of a business.

If the assets acquired do not constitute a business, we account for asset acquisitions using the cost accumulation and allocation method. Under this method, the cost of the acquisition, including direct acquisition-related costs, is allocated to the assets acquired on a relative fair value basis. Goodwill is not recognized in an asset acquisition and any difference between consideration transferred and the fair value of the net assets acquired is allocated to the identifiable assets acquired based on their relative fair values.

Deferred tax liabilities arising from basis differences in assets acquired are calculated using the simultaneous equations method under ASC 740, Income Taxes and based on the effective tax rate. The resulting deferred tax liability is recorded against the carrying amount of the acquired intangible assets on a relative fair value basis.

Contingent consideration in the scope of ASC Topic 815, Derivatives and Hedging, is included in the cost of the asset acquisition at its acquisition date fair value. Contingent consideration in the scope of ASC Topic 450, Contingencies, is recognized when it is both probable and reasonably estimable.

Intangible Assets

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Our intangible assets are initially measured based on an allocation of the cost of the acquisition to the assets acquired on a relative fair value basis and are recorded net of accumulated amortization. We amortize the intangible assets on a straight-line basis over their estimated useful lives.

When contingent consideration is a component of the cost of an asset acquisition, we capitalize the amount of incremental cost from the contingent consideration related to the intangible asset acquired in the period the underlying contingency is resolved. When this occurs, we will recognize a cumulative catch-up to reflect amortization on the intangible assets that would have been recognized had the incremental cost from the contingent consideration been recorded as of the acquisition date.

We review intangible assets for impairment at least annually and whenever events or changes in circumstances have occurred which could indicate that the carrying value of the assets are not recoverable. If such indicators are present, we assess the recoverability of affected assets by determining if the carrying value of the assets is less than the sum of the undiscounted future cash flows of the assets. If the assets are found to not be recoverable, we measure the amount of impairment by comparing the carrying value of the assets to their fair values. We determined that no indicators of impairment existed as of December 31, 2023. No intangible assets existed as of December 31, 2022.

Revenue Recognition

We recognize revenue from product sales in accordance with ASC 606, Revenue from Contracts with Customers. Under ASC 606, revenue is recognized when a customer obtains control of promised goods or services in an amount that reflects the consideration which the entity expects to receive in exchange for those goods or services. To the extent the transaction price includes variable consideration, we estimate the amount of variable consideration that should be included in the transaction price using the most likely method based on historical experience as well as applicable information currently available.

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Accrued Research and Development Costs

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Research and development costs are expensed as incurred. Clinical development costs compose a significant component of research and development costs. We have a history of contracting with third parties, including CROs, independent clinical investigators, and CMOs, that perform various clinical trial activities on our behalf in connection with the ongoing development of our product candidates. The financial terms of these contracts are subject to negotiations and may vary from contract to contract and may result in

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uneven payment flow. We accrue and expense costs for clinical trial activities performed by third parties based upon the work completed to date for each clinical trial in accordance with agreements established with CROs, hospitals, and clinical investigators. Accruals for CROs and CMOs are recorded based on services received and efforts expended pursuant to agreements established with CROs, CMOs, and other outside service providers. We determine our costs through discussions with internal clinical stakeholders and outside service providers as to the progress or stage of completion of clinical trials or services and the contracted fee to be paid for such services.

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Included in our clinical development costs are investigator costs, which are costs associated with treatments administered at clinical sites as required under each clinical trial protocol. Our estimates for clinical investigator costs and timing of expense recognition will depend on a number of factors that include, but are not limited to, (i) the overall number of patients that enroll in the trial at each individual site, (ii) the length of clinical trial enrollment period, (iii) discontinuation and completion rates of patients, (iv) duration of patient safety follow-ups, (v) the number of sites included in the clinical trial, and (vi) the contracted fee of each participating site for patient treatment while on clinical trial, which can vary greatly for several reasons including, but not limited to, geographic region, medical center or physician costs, and overhead costs. In addition, our estimates for per patient trial costs will vary based on a number of factors that include, but are not limited to, the extent of additional treatments that may be administered by investigators as a result of patient health status, recoverability of patient costs through insurance carriers of patients, and unanticipated cost of injuries incurred as a result of the clinical trial treatment. We accrue estimated expenses resulting from obligations under investigator site agreements as the timing of payments does not always timely align with the periods over which the treatments are administered by the clinical investigators. These estimates are typically based on contracted amounts, patient visit data, discussions with internal clinical stakeholders and outside service providers, and historical look-back analysis of actual payments made to date.

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We make judgements and estimates in determining the accrual balance in each reporting period. In the event advance payments are made to a CRO, CMO, or other outside service provider, the payments are recorded within prepaid expenses and other current assets and subsequently recognized as research and development expense when the associated services have been performed. As actual costs become known, we adjust our estimates, liabilities and assets. Inputs used in our determination of estimates discussed above may vary from actual, which will result in adjustments to research and development expense in future periods.

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Recent Accounting Standards

In December 2023, the FASB issued ASU 2023-09, Income Taxes (Topic 740): Improvements to Income Tax Disclosures, which enhances the disclosures of income taxes. ASU 2023-09 is effective for us in our annual reporting for fiscal year 2025 on a prospective basis. Early adoption and retrospective reporting are permitted. We are currently evaluating the impact of ASU 2023-09 on our consolidated financial statements.

In November 2023, the FASB issued ASU 2023-07, Segment Reporting (Topic 280): Improvements to Reportable Segment Disclosures, which enhances the disclosures required for operating segments in annual and interim consolidated financial statements. ASC 2023-07 is effective for us in our annual reporting for fiscal year 2024 and for interim period reporting beginning in fiscal year 2025 on a retrospective basis. Early adoption is permitted. We are currently evaluating the impact of ASC 2023-07 on our consolidated financial statements