IOVANCE BIOTHERAPEUTICS INC

Previous wording

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. 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 the first and the only one-time, individualized T cell therapy to receive U.S. Food and Drug Administration, or the FDA, approval for a solid tumor cancer. 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 was approved in February 2024 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™ and Proleukin® are part of a treatment regimen that also includes lymphodepletion.

Current wording

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. 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 and in other applications. Amtagvi® is the first and the only one-time, individualized T cell therapy to receive U.S. Food and Drug Administration, or the FDA, approval for a solid tumor cancer. 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 was approved in February 2024 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® and Proleukin® are part of a treatment regimen that also includes lymphodepletion.

Previous wording

In addition to the U.S., we plan to launch Amtagvi TM into additional markets with a high prevalence of advanced melanoma, including the European Union, or EU, United Kingdom, Canada, Switzerland, and Australia. In June 2024, we submitted a centralized marketing authorization application, or MAA, to the European Medicines Agency, or the EMA, for lifileucel. In August 2024, the MAA was validated and accepted for review by the EMA. In October 2024, an MAA was submitted to the Medicines and Healthcare products Regulatory Agency in the United Kingdom, and a new drug submission, or NDS, was deemed eligible for Notice of Compliance with Conditions or NOC/c by Health Canada. The NOC/c policy includes a prioritized 200-day review process for potential NDS approval in mid-2025. If approved, lifileucel is expected to be the first and only approved therapy in this treatment setting in these markets. Across the U.S. and other targeted global markets, Amtagvi TM has the potential to address more than 20,000 previously treated advanced melanoma patients annually.

Current wording

Beyond the U.S., we plan to launch Amtagvi® into additional markets with a high prevalence of advanced melanoma, including the European Union, or EU, United Kingdom, or UK, Canada, Switzerland, and Australia. In June 2024, we submitted a centralized marketing authorization application, or MAA, to the European Medicines Agency, or the EMA, for lifileucel. In August 2024, the MAA was validated and accepted for review by the EMA. In October 2024, an MAA was submitted to the Medicines and Healthcare products Regulatory Agency in the UK. A new drug submission, or NDS, was deemed eligible for Notice of Compliance with Conditions or NOC/c by Health Canada and submitted in December 2024 and then accepted in January 2025. The NOC/c policy includes a prioritized 200-day review process for potential NDS approval in mid-2025. If approved, lifileucel is expected to be the first and only approved therapy in this treatment setting in these markets. Across the U.S. and other targeted global markets, Amtagvi® has the potential to address more than 20,000 previously treated advanced melanoma patients annually.

Previous wording

Iovance was founded to build upon the promise of TIL cell therapy that was previously demonstrated in single-center clinical trials at academic research 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 thousands of patients with cancer can access.

Current wording

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

Previous wording

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. We are conducting 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, or NSCLC, following standard of care chemo-immunotherapy. We are also developing next generation therapies, such as genetically modified and gene edited TIL cell therapy and next generation cytokines.

Current wording

Our development pipeline includes multicenter trials of TIL cell therapies in additional treatment settings and indications for solid tumor cancers. To potentially improve outcomes for patients, we are investigating TIL monotherapies for patients previously treated with standard of care therapies and TIL cell therapy in combination with standard of care therapies for patients in earlier treatment settings. We are conducting two ongoing registrational trials to support a supplementary BLA, or sBLA, of lifileucel in frontline advanced melanoma and in advanced non-small cell lung cancer, or NSCLC, following standard of care chemo-immunotherapy. We are also developing next generation therapies, such as genetically modified TIL cell therapy and next generation cytokines.

Previous wording

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

Current wording

A global leader in innovating, developing, and delivering TIL cell therapy

Previous wording

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.

Current wording

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. As we continue to execute the U.S. launch of Amtagvi® and advance our pipeline, we are committed to continuous innovation to develop TIL cell therapies and optimize TIL treatment regimens that may extend and improve life for patients with cancer.

Previous wording

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

Current wording

Successfully commercialize our lead product Amtagvi® for the treatment of post-anti-PD-1 advanced melanomain the U.S.

Previous wording

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.

Current wording

Following U.S. FDA approval of Amtagvi® for the treatment of patients with post-anti-PD-1 advanced melanoma on February 16, 2024, our top priority is continuing to leverage our experienced marketing, payer access, and distribution teams, as well as a sales force with extensive experience in oncology and cell therapy for our commercialization efforts. Our medical affairs team is also educating key opinion leaders, or KOLs, about Amtagvi® and TIL cell therapy, as well as presenting and publishing our clinical results.

Previous wording

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.

Current wording

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 a 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.

Previous wording

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 administer Amtagvi™ to patients as part of a treatment regimen that includes lymphodepletion and a short course of high-dose Proleukin® (aldesleukin).

Current wording

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. Amtagvi® is administered to patients as part of a treatment regimen that includes lymphodepletion and a short course of high-dose Proleukin® (aldesleukin).

Previous wording

●**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 FDA-approved, centralized manufacturing facility.

Current wording

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

Previous wording

●**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. The cells are then 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.

Current wording

•Step 2: Manufacturing. Upon arrival at the manufacturing 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. 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.

Previous wording

●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.

Current wording

•Step 3: Treatment Regimen. The Amtagvi® treatment regimen begins with non-myeloablative lymphodepletion, or NMA-LD, to suppress the immunosuppressive tumor microenvironment, which we believe enhances the efficacy of TIL cell therapy. After NMA-LD, Amtagvi® is infused and followed by a short course of up to six doses of Proleukin® to promote T cell activity.

Previous wording

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

Current wording

Prior to the FDA approval of Amtagvi®, there were no FDA approved therapies for patients with advanced melanoma following anti-PD-1 therapy.

Previous wording

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.

Current wording

Proleukin® (aldesleukin) is an IL-2 product used in the Amtagvi® treatment regimen and manufacturing process, as well as other commercial, clinical, manufacturing, and research settings, which provides additional revenue. In May 2023, we acquired the worldwide rights to Proleukin® 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, secures our Proleukin® supply chain, lowers cost of goods, and reduces clinical trial expenses for Proleukin® used with our TIL cell therapies.

Previous wording

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.

Current wording

Proleukin® has received regulatory approvals for treatment of adults with metastatic melanoma and metastatic renal cell carcinoma in the U.S. Proleukin® is also licensed in multiple countries around the world for treatment of patients with metastatic renal cell carcinoma and/or metastatic melanoma. We also sell aldesleukin for clinical trial use and for use in the manufacturing of various cell and gene therapies to numerous third-party clients.

Previous wording

Establish manufacturing capacity to meet forecasted commercial and clinical demand

Current wording

Manufacturing capacity for forecasted commercial and clinical demand

Previous wording

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. In clinical trials prior to FDA approval, more than 700 patients were 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, theiCTC, and by a CMO.iCTC is FDA-approved for commercial manufacturing of Amtagvi™. In addition, our CMO is FDA-approved for additional capacity to supplement our internal manufacturing. The two facilities together have capacity as built to treat several thousands of cancer patients annually.

Current wording

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. In clinical trials, 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, theiCTC, and by a CMO. The FDA authorizediCTC for commercial manufacturing of Amtagvi® as well as our CMO for additional capacity to supplement our internal manufacturing. As built, the two facilities together have capacity to treat several thousands of cancer patients annually with commercial product and clinical supply.

Previous wording

TheiCTC is the first centralized and scalable current Good Manufacturing Practice, or cGMP, manufacturing facility dedicated to producing TIL, as well as the first FDA-approved facility for commercial TIL cell therapy. Located in Philadelphia, Pennsylvania, the 136,000 square footiCTC is also among the largest cell therapy manufacturing facilities. Expansion at theiCTC is underway, which is expected to increase capacity to supply over five thousand patients annually, with a long-term goal of establishing a manufacturing network to supply TIL therapy to over ten thousand patients per year. The proximity of theiCTC to multiple airports facilitates delivery of TIL cell therapies to treatment centers, with theiCTC 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. TheiCTC has a flexible design that allows expansion within existing shell space and an option to build on an adjacent lot to support future growth and capacity needs.

Current wording

TheiCTC is the first centralized and scalable current Good Manufacturing Practice, or cGMP, manufacturing facility dedicated to producing TIL cell therapies, as well as the first FDA-approved facility for commercial TIL cell therapy. Located in Philadelphia, Pennsylvania, the 136,000 square footiCTC is among the largest cell therapy manufacturing facilities globally.iCTC expansion is underway which is expected to increase capacity to supply over five thousand patients annually. Our long-term goal is to establish a manufacturing network that can supply TIL cell therapies to over ten thousand patients per year. The proximity of theiCTC to multiple airports facilitates delivery of TIL cell therapies to treatment centers. TheiCTC is expected to cover logistics and delivery of TIL cell therapies in North America, Europe, and Australia. Ownership of our manufacturing facility allows us to control internal manufacturing capacity and product quality, manage supply and delivery logistics, implement process improvement and realize potential cost efficiencies for TIL cell therapies that we may develop and commercialize. We are also exploring next generation TIL cell therapy manufacturing processes, treatments and technologies that may further streamline development timelines and costs. TheiCTC has a flexible design that facilitates our expansion within the existing shell space and an option to build on an adjacent lot to support future growth and capacity needs.

Previous wording

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 Note 11. Licenses and Agreements of the notes to the condensed consolidated financial statements included in Part I. Financial Information of this Quarterly Report on Form 10-Q.

Current wording

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 Note 12. Licenses and Agreements section of this Quarterly Report on Form 10-Q.

Previous wording

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 and tumor. We believe this polyclonal cell therapy is potentially applicable to many solid

Current wording

Our TIL cell therapy platform and manufacturing process have been initially validated through the FDA approval of Amtagvi®. 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 may be applicable to many solid tumor cancers, where the majority of immune targets are patient-specific.

Previous wording

We have investigated TIL cell therapy in global, multicenter clinical trials in advanced melanoma, gynecological cancers, 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.

Current wording

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.

Previous wording

We have established a leading intellectual property portfolio developed internally and licensed from third parties. We currently own more than 230 granted or allowed U.S. and international patents and patent applications pertaining to Amtagvi™ and other TIL-related technologies that are expected to provide Amtagvi™ with exclusivity into 2042. More than 70 U.S. patents are 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; 11,857,573; 11,865,140; 11,866,688; 11,939,596; 11,969,444; 11,975,028; 12,024,718; and 12,031,157. More than 40 of these patents are related to our Gen 2 TIL manufacturing processes and have terms that we anticipate will extend to October 2037 or 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.

Current wording

We have established a leading intellectual property portfolio developed internally and licensed from third parties. We currently own more than 75 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; 11,857,573; 11,865,140; 11,866,688; 11,939,596; 11,969,444; 11,975,028; 11,981,921; 12,023,355; 12,024,718; 12,031,157; 12,104,172; 12,121,541; 12,159,700; 12,170,134; 12,188,048; 12,194,061; and 12,226,434. More than 40 of these patents are related to our Gen 2 TIL manufacturing processes and have terms that we anticipate will extend to October 2037 or 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 immune checkpoint inhibitor, or ICIs, in combination with TIL cell therapies; TIL selection technologies; and methods of treating patient subpopulations.

Previous wording

Revenues for the three and nine months ended September 30, 2024 represent product sales of Amtagvi™, as well as Proleukin®, primarily driven from sales in the United States to support the ongoing commercial launch of Amtagvi™, which received FDA approval in February 2024. Proleukin®, which we acquired the worldwide rights to in May 2023, is also sold in markets outside the United States, primarily in the EU and United Kingdom. Prior to May 2023, we had not recognized any revenue.

Current wording

Revenues for the three months ended March 31, 2025 represent product sales of Amtagvi®, as well as Proleukin®, primarily driven from sales in the U.S. to support the ongoing commercial launch of Amtagvi®, which received FDA approval in February 2024. Proleukin®, which we acquired the worldwide rights to in May 2023, is also sold in markets outside the U.S., primarily in the EU and UK. Prior to May 2023, we had not recognized any revenue.

Previous wording

Amtagvi™ revenue is recognized upon patient infusion, while Proleukin® revenue is recognized upon delivery to specialty distributors, clinical manufacturers, and ATCs. Revenue is reduced at the time of recognition for expected chargebacks, discounts, rebates, and sales allowances, collectively referred to as gross to net adjustments, or GTN adjustments. In the U.S., these GTN adjustments are attributable to various commercial arrangements and government programs. In addition, non-U.S. government programs include different pricing schemes such as cost caps and volume discounts.

Current wording

Amtagvi® revenue is recognized upon patient infusion, while Proleukin® revenue is recognized upon shipment or delivery to customers, which include specialty distributors, clinical manufacturers, research organizations, and ATCs. Revenue is reduced at the time of recognition for expected chargebacks, discounts, rebates, and sales allowances, collectively referred to as gross to net adjustments, or GTN adjustments. In the U.S., these GTN adjustments are attributable to various commercial arrangements and government programs. In addition, non-U.S. government programs include different pricing schemes such as cost caps and volume discounts.

Previous wording

Cost of sales includes inventory and period costs, as well as non-cash expenses, related to overhead and manufacturing costs of Amtagvi™ during the period from approval through September 30, 2024, as well as the cost of inventories and other costs, and non-cash expenses that are directly associated with the purchase and sales of Proleukin®. In addition, cost of sales includes royalties payable on sales of our products, as well as non-cash expenses including amortization of the fair value step-up of acquired Proleukin® inventory which is recognized as the acquired inventory units are sold, amortization expense for the developed technology intangible asset and the milestone payment recorded as part of the Acquisition, and the intellectual property license intangible assets.

Current wording

Cost of sales includes inventory and period costs, as well as non-cash expenses, related to overhead and manufacturing costs of Amtagvi®, as well as the cost of inventories and other costs, and non-cash expenses that are directly associated with the purchase and sales of Proleukin®. In addition, cost of sales includes royalties payable on sales of our products, as well as non-cash expenses including amortization of the fair value step-up of acquired Proleukin® inventory which is recognized as the acquired inventory units are sold, amortization expense for the developed technology intangible asset and the milestone payment recorded as part of the Acquisition, and the intellectual property license intangible assets.

Previous wording

Research and development expenses include personnel and facility-related expenses, outside contracted services including clinical trial costs, including Amtagvi™ infusions under expanded access programs or single-patient INDs, 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.

Current wording

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.

Previous wording

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

Current wording

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 an 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

Previous wording

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. Selling, 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.

Current wording

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 capitalized in inventory or 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. Selling, 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.

Previous wording

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 in the U.S. market and outside of the U.S. of the internal selling, general and administrative team to support the overall growth in our business.

Current wording

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 in the U.S. market and outside of the U.S. of the internal general and administrative team to support the overall growth in our business.

Previous wording

Interest income, net is derived from our interest-bearing cash, cash equivalents and investment balances.

Current wording

Interest and other income, net is derived from our interest-bearing cash, cash equivalents and investment balances as well as other income associated with non-recurring activities such as lease terminations.

Previous wording

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

Current wording

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

Previous wording

Results of Operations for the Three and Nine Months Ended September 30, 2024 and 2023

Current wording

Results of Operations for the Three Months Ended March 31, 2025 and 2024

Previous wording

Revenue for the three and nine months ended September 30, 2024 increased by $58.1 million, or 12,385%, and $89.7 million, or 12,683%, compared to the same periods in 2023, respectively. The increase was driven by the completion of the acquisition of worldwide rights to Proleukin® in May 2023, or the Acquisition, as well as the commercial launch of Amtagvi™ in February 2024. Through the first quarter of 2024, product revenue was comprised entirely of product sales of Proleukin® in markets outside of the U.S. With the BLA approval of Amtagvi™ in February 2024, we began generating revenue for Amtagvi™ in the second quarter of 2024 as infusions occurred at our ATCs. Furthermore, in the second quarter of 2024, we began selling Proleukin® in the U.S. market. The Proleukin® inventory that was previously with distributors at the time of the acquisition to support the U.S. market has been substantially sold, and as a result we experienced significant re-stocking demand from specialty distributors in both the second and third quarter of 2024 to support ongoing and anticipated infusions related to the strong commercial launch of Amtagvi™. GTN adjustments did not materially affect net product revenue in the three and nine months ended September 30, 2024 and 2023.

Current wording

Revenue for the three months ended March 31, 2025 increased by $48.6 million, or 6,798%, compared to the same period in 2024. The increase was driven by the completion of the acquisition of worldwide rights to Proleukin® in May 2023, or the Acquisition, as well as the commercial launch of Amtagvi® in February 2024. Through the first quarter of 2024, product revenue was comprised entirely of product sales of Proleukin® in markets outside of the U.S. With the BLA approval of Amtagvi® in February 2024, we began generating revenue for Amtagvi® in the second quarter of 2024 as infusions occurred at our ATCs. Furthermore, in the second quarter of 2024, we began selling Proleukin® in the U.S. market. The Proleukin® inventory that was previously with distributors at the time of the Acquisition to support the U.S. market has been substantially sold, and as a result we experienced significant re-stocking demand from specialty distributors in the second half of 2024 to support ongoing and anticipated infusions related to the strong commercial launch of Amtagvi®. GTN adjustments did not materially affect net product revenue in the three months ended March 31, 2025 and 2024.

Previous wording

Cost of sales for the three and nine months ended September 30, 2024 increased by $35.5 million, or 818%, and $72.1 million, or 1,128%, respectively, driven by the increase in sales of Amtagvi™ and Proleukin®, as well as costs related to the manufacturing of Amtagvi™. Cost of sales included $5.5 million and $15.5 million for the three and nine months ended September 30, 2024, respectively, compared to $4.0 million and $5.9 million for the three and nine months ended September 30, 2023, of non-cash amortization expense for the developed technology intangible asset and the milestone payment recorded as part of the Acquisition as well as intellectual property license intangible assets. In addition, cost of sales included non-cash expense for the amortization of the fair value step-up of acquired Proleukin® inventory sold of $1.4 million and $4.8 million for the three and nine months ended September 30, 2024, respectively, compared to $0.1 million for each of the three and nine months ended September 30, 2023. This expense is recorded as the units acquired in the Acquisition are sold, and we expect this amount to decrease over the next six to twelve months as this inventory is sold. In addition to the non-cash amortization expense, cost of sales included $3.9 million and $8.2 million, respectively, of royalties payable related to sales of our products in the three and nine months ended September 30, 2024. There were no royalties payable in the three and nine months ended September 30, 2023.

Current wording

Cost of sales for the three months ended March 31, 2025 increased by $42.5 million, or 585%, compared to the same period in 2024. The increase was driven by the increase in sales of Amtagvi® and Proleukin®, as well as costs related to the manufacturing of Amtagvi®. Cost of sales included $5.4 million for the three months ended March 31, 2025, compared to $4.6 million for the three months ended March 31, 2024, of non-cash amortization expense for the developed technology intangible asset and the milestone payment recorded as part of the Acquisition as well as intellectual property license intangible assets. In addition, cost of sales included non-cash expense for the amortization of the fair value step-up of acquired Proleukin® inventory sold of $0.1 million for the three months ended March 31, 2025, compared to $0.4 million for the three months ended March 31, 2024. This expense is recorded as the units acquired in the Acquisition are sold, and we expect this amount to decrease over the next six to twelve months as this inventory is sold. In addition to the non-cash amortization expense, cost of sales included $1.3 million of royalties payable related to sales of our products in the three months ended March 31, 2025. There were no royalties payable in the three months ended March 31, 2024.

Previous wording

Cost of sales for the three and nine months ended September 30, 2024 also included $8.3 million and $17.2 million, respectively, of period costs primarily related to patient drop-off driven by patient health and ability to receive the Amtagvi™ treatment, as well as manufacturing results that did not meet required specifications, and were not otherwise utilized under an expanded access program or single-patient IND to generate clinical data, resulting in manufacturing costs in the period for which we were not able to recognize revenue. In addition, to a lesser extent such costs included period costs related to overhead and manufacturing costs at theiCTC during the period from approval resulting from under absorption of overhead costs during the period, which was driven by our decision to launch with capacity sufficient to address anticipated commercial demand in 2024 and beyond. We continue to focus on manufacturing execution as the launch of Amtagvi™ continues but expect to incur such period costs through the upcoming fiscal quarters while we continue to implement initiatives associated with manufacturing quality and until such time that we can fully utilize our manufacturing capacity.

Current wording

Cost of sales for the three months ended March 31, 2025 also included $15.0 million, of period costs primarily related to patient drop-off driven by patient health and ability to receive the Amtagvi® treatment, as well as manufacturing results that did not meet required specifications, and were not otherwise utilized under an expanded access program or single-patient IND to generate clinical data, resulting in manufacturing costs in the period for which we were not able to recognize revenue. In addition, to a lesser extent such costs included period costs related to overhead and manufacturing costs at theiCTC during the period from approval resulting from under absorption of overhead costs during the period, which was driven by our decision to launch with capacity sufficient to address anticipated commercial demand in 2024 and beyond. We continue to focus on manufacturing execution as the launch of Amtagvi® continues but expect to incur such period costs through the upcoming fiscal quarters while we continue to implement initiatives associated with manufacturing quality and until such time that we can fully utilize our manufacturing capacity.

Previous wording

Research and development expense for the three months ended September 30, 2024 decreased by $19.3 million, or 22%, compared to the same period in 2023. The decrease was primarily attributable to (i) a $28.7 million decrease in clinical manufacturing costs, driven by capitalization of qualified costs for Amtagvi™ manufacturing resulting from our BLA approval and the transition to commercial manufacturing to support the commercial launch of Amtagvi™, (ii) a $1.5 million decrease in clinical and other costs, driven primarily by lower patient enrollment across certain studies, and (iii) a $1.4 million decrease in costs associated with qualifyingiCTC suites for commercial manufacturing readiness, driven by the completion of such activities in prior periods. These decreases were partially offset by (i) a $10.9 million increase in payroll and related costs, including stock-based compensation, primarily driven by an increase in the number of employees and the number of stock awards granted at a higher average stock price, and a (ii) $1.4 million increase in lab and consumable costs to develop next generation candidates.

Current wording

Research and development expense for the three months ended March 31, 2025 decreased by $2.9 million, or 4%, compared to the same period in 2024. The decrease was primarily attributable to a $30.5 million decrease in manufacturing costs, driven by capitalization of qualified costs for Amtagvi® manufacturing resulting from our BLA approval and the transition to commercial manufacturing to support the commercial launch of Amtagvi®. This decrease was partially offset by (i) a $16.3 million increase in payroll and related costs, including stock-based compensation, primarily driven by an increase in the number of employees (ii) a $7.5 million increase in clinical costs, driven primarily by continued enrollment in TILVANCE-301 and the resumption the LUN-202 study, and (iii) a $3.8 million increase in lab and consumable costs to develop next generation candidates.

Previous wording

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.” Lifileucel monotherapy includes our TIL monotherapy clinical trials, including clinical trials previously reported as LN-145. 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.

Current wording

categories: “TIL, including combination therapy,” “Next Generation,” and “Other clinical, preclinical and research programs under development.” Lifileucel monotherapy includes our TIL monotherapy clinical trials, including clinical trials previously reported as LN-145. 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.

Previous wording

Selling, general and administrative expenses for the three months ended September 30, 2024 increased by $12.6 million, or 47%, compared to the same period in 2023. The increase was primarily attributable to (i) a $8.8 million increase in payroll and related expense, including stock-based compensation, driven by an increase in headcount to support the growth in the overall business as well as to support the commercialization of Amtagvi™, and an increased number of stock awards granted at a higher average stock price, (ii) a $1.3 million increase in costs incurred in support of the distribution and commercialization of Amtagvi™ and Proleukin®, (iii) a $0.8 million increase in legal costs driven by a reduction in legal costs in 2023 resulting from the capitalization of previously expensed costs directly associated with the Acquisition, and (iv) a $1.7 million increase in other costs, including costs associated with software license costs related to the expansion of our information technology infrastructure and professional fees.

Current wording

Selling, general and administrative expenses for the three months ended March 31, 2025 increased by $12.5 million, or 40%, compared to the same period in 2024. The increase was primarily attributable to (i) a $7.8 million increase in payroll and related expense, including stock-based compensation, driven by an increase in headcount to support the growth in the overall business including the commercialization of Amtagvi® (ii) a $1.7 million increase in costs incurred in support of the distribution and commercialization of Amtagvi® and Proleukin®, and (iii) a $3.0 million increase in other costs, including costs associated with increased travel, software license costs related to the expansion of our information technology infrastructure and legal and professional fees.

Previous wording

Interest income, net for the three and nine months ended September 30, 2024 increased by $0.6 million, or 19%, and $0.8 million, or 8%, compared to the same periods in 2023, respectively. The increase was primarily driven by an increase in average investment balances, resulting from net proceeds from recent public and at-the-market financings as well as a higher rate of return on our investments.

Current wording

Interest income, net for the three months ended March 31, 2025 decreased by $0.1 million, or 4%, compared to the same period in 2024. The decrease was primarily driven by a slightly lower rate of return on our investments, partially offset by an increase in average investment balances, resulting from net proceeds from recent public and at-the-market financings.