Iovance Biotherapeutics, Inc. (NASDAQ:IOVA) is a commercial-stage biotechnology 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. The company recently achieved a significant milestone with the U.S. Food and Drug Administration (FDA) approval of its lead product, Amtagvi™ (lifileucel), 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.
Amtagvi™ is the first and only one-time, individualized T cell therapy to receive FDA approval for a solid tumor cancer. The company is now executing a successful U.S. commercial launch of Amtagvi™ while also marketing Proleukin® (aldesleukin), an interleukin-2 (IL-2) product used in the Amtagvi™ treatment regimen. In addition to its commercial activities, Iovance continues to advance a robust pipeline of tumor infiltrating lymphocyte (TIL) cell therapy candidates across multiple solid tumor indications.
Financial Overview
For the full year 2023, Iovance reported annual revenue of $1,189,000, which was primarily derived from the sales of Proleukin® in licensed markets outside of the U.S. following the company's acquisition of the worldwide rights to the product in May 2023. The company's annual net loss for 2023 was $444,037,000, and its annual operating cash flow and free cash flow were -$361,820,000 and -$384,110,000, respectively.In the first quarter of 2024, Iovance reported revenue of $715,000, which was also from Proleukin® sales. The company's net loss for the quarter was $112,976,000. Research and development expenses were $79,783,000, a decrease of $2,951,000 compared to the first quarter of 2023, primarily due to the transition to commercial manufacturing of Amtagvi™. Selling, general, and administrative expenses were $31,393,000, an increase of $3,271,000 compared to the same period in 2023, driven by increased headcount and related costs to support the growth of the business and commercialization activities.
As of March 31, 2024, Iovance had cash, cash equivalents, investments, and restricted cash of approximately $362.6 million, which the company believes will be sufficient to fund its anticipated operating expenses and capital expenditures well into the second half of 2025.
Successful U.S. Commercial Launch of Amtagvi™
Iovance's top priority is the successful commercialization of Amtagvi™ in the U.S. for the treatment of patients with post-anti-PD-1 advanced melanoma. The company has experienced marketing, payer access, and distribution teams, as well as a sales force with extensive experience in oncology and cell therapy, to support the launch.Since the FDA approval of Amtagvi™ in February 2024, the company has made significant progress in the U.S. launch. As of the first quarter of 2024, more than 100 patients have been enrolled for Amtagvi™ therapy, and the company expects most of these patients to be ready for infusion across the second and early third quarters of 2024. Additionally, more than 60 additional patients have been identified at authorized treatment centers (ATCs) and are expected to enroll soon.
Iovance is on track to have 50 total ATCs by the end of May 2024 and has set a new goal of at least 70 ATCs by the end of the year, representing the largest ever number of ATCs for a cell therapy launch. The company is also seeing positive reimbursement trends, with more than 75% of enrolled patients being commercially insured and 13 payers responsible for approximately 90 million covered lives having already published medical coverage policies consistent with Amtagvi™'s label and clinical trials.
Robust Manufacturing Capabilities and Capacity Expansion
Manufacturing is a core competency for Iovance, and the company has built its own manufacturing facility, the Iovance Cell Therapy Center (i CTC), in Philadelphia, which is one of the largest cell therapy manufacturing facilities in the world and the only one specifically designed for TIL manufacturing. The i CTC is now FDA-approved for the commercial manufacturing of Amtagvi™ for the U.S. market and continues to serve patients in the company's clinical trials.In addition to the i CTC, Iovance has a second FDA-approved contract manufacturer site for the commercial manufacturing of Amtagvi™, providing the company with additional flexibility and capacity for both commercial and clinical patients. The company's manufacturing capabilities and capacity are setting a new bar for cell therapy launches, with a turnaround time of approximately 34 days from receipt of tumor tissue to return shipment of Amtagvi™ to the ATC.
To fulfill the anticipated demand for Amtagvi™ in the U.S. and support the company's advancing clinical pipeline, Iovance is already underway with further capacity expansion at the i CTC. This expansion is expected to enable the facility to supply TIL therapies for more than 5,000 patients annually, with a longer-term vision to supply sales for over 10,000 patients annually from the i CTC campus.
Advancing a Robust Pipeline of TIL Cell Therapies
In addition to the successful commercialization of Amtagvi™, Iovance continues to advance a robust pipeline of TIL cell therapy candidates across multiple solid tumor indications.One of the company's key priorities is expanding the label for Amtagvi™ to address the need of patients with advanced melanoma in the frontline treatment setting. Iovance's registrational Phase III trial, TILVANCE-301, is well underway and on track to support accelerated and full approval of Amtagvi™ in combination with pembrolizumab in frontline advanced melanoma, as well as regular approval of Amtagvi™ in post anti-PD-1 melanoma.
In non-small cell lung cancer (NSCLC), Iovance reported positive updates for its single-arm registrational Phase II trial, IOV-LUN-202, in post anti-PD-1 NSCLC. Enrollment has restarted with high demand, which is driven by encouraging data and further augmented by excitement from the approval of Amtagvi™. The company expects the registrational cohorts to be fully enrolled in 2025.
Iovance is also starting a Phase II trial of lifileucel in post anti-PD-1 endometrial cancer, a significant opportunity for TIL cell therapy. Given the unmet medical need and enthusiasm from gynecological oncologists, the company expects to enroll the trial quickly and looks forward to seeing first data soon.
Beyond its current pipeline, Iovance is at the forefront of next-generation approaches that have the potential to address unmet needs for patients and solidify the company's long-term leadership in the TIL cell therapy space. This includes the company's genetically modified TIL cell therapy, IOV-4001, which utilizes TALEN technology licensed from Cellectis to inactivate PD-1 during the TIL manufacturing process. Iovance also plans to submit an investigational new drug (IND) application for a Phase I/II trial of IOV-3001, a modified interleukin-2 (IL-2) fusion protein, in the third quarter of 2024, and is introducing a new next-generation program, IOV-5001, a genetically engineered TIL cell therapy with inducible and tethered IL-12, which is currently in IND-enabling studies.