On May 9, 2024 Iovance Biotherapeutics, Inc. (NASDAQ: IOVA), a commercial biotechnology company focused on innovating, developing, and delivering novel polyclonal tumor infiltrating lymphocyte (TIL) therapies for patients with cancer, reported first quarter 2024 financial results and corporate updates (Press release, Iovance Biotherapeutics, MAY 9, 2024, View Source [SID1234642996]).

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Frederick Vogt, Ph.D., J.D., Interim President and Chief Executive Officer of Iovance, stated, "The first quarter of 2024 was transformative for Iovance following our first FDA approval and our strong start for the U.S. commercial launch of Amtagvi for patients with advanced melanoma. Immediate demand for Amtagvi is very high and continues to significantly increase across initial ATCs. As of today, more than 100 patients have already enrolled for Amtagvi therapy. We have successfully manufactured and delivered Amtagvi to many ATCs where commercial patients are being treated. We expect our launch momentum to remain strong and continue to build as we ramp up the U.S. launch throughout 2024 with the authorization of additional ATCs. We also continue to execute across our broad clinical pipeline. As a fully integrated company, Iovance is well positioned to remain the global leader in innovating, developing, and delivering TIL cell therapy for patients with cancer."

Recent and First Quarter 2024 Highlights and Corporate Updates

Amtagvi (Lifileucel) U.S. Approval and Launch Highlights in Advanced Melanoma

The U.S. FDA approved Amtagvi (lifileucel) on February 16, 2024, as the first treatment option for advanced melanoma after anti-PD-1 and targeted therapy. Amtagvi is also the first and only FDA-approved T cell therapy for a solid tumor indication.
Since approval, more than 100 patients have enrolled for Amtagvi therapy. The first patients have been successfully treated and the balance are moving through the stages of the journey, which includes surgery for cell collection, manufacturing, and the Amtagvi treatment regimen.
Onboarding is complete at more than 40 U.S. ATCs, up from 30 initial ATCs at approval. Iovance remains on track to onboard approximately 50 ATCs by the end of May 2024 and expects to have more than 70 ATCs onboarded by the end of 2024.
Manufacturing turnaround time has been on-target with initial launch expectations of approximately 34 days from inbound to return shipment to ATCs. The commercial manufacturing experience to date is consistent with prior clinical experience.
The U.S. launch of Amtagvi, and additional sales of Proleukin used with the treatment regimen, are expected to drive significant revenue for Iovance in 2024.
Amtagvi was added as a preferred second-line or subsequent therapy in the National Comprehensive Cancer Network guidelines for treatment of cutaneous melanoma.
Reimbursement remains strong and on track at the ATCs with progress toward coverage policies successful in many cases. As anticipated, more than 75% of enrolled Amtagvi patients are covered by private payers. To date, payers covering more than 200 million lives have already authorized Amtagvi treatment for their patients, setting a strong precedent for reimbursement success.
Lifileucel Launch Expansion into New Markets and Indications

Geographic expansion can more than double the total addressable patient population for Amtagvi in advanced melanoma. Regulatory dossiers remain on track for submission in the following markets with significant populations of advanced melanoma patients:
EU in the second quarter of 2024
UK and Canada in the second half of 2024
Australia and additional countries in 2025
Iovance TIL Cell Therapy Pipeline Highlights

Lifileucel in Frontline Advanced Melanoma
The registrational Phase 3 TILVANCE-301 trial is well underway to support accelerated and full U.S. approvals of Amtagvi in combination with pembrolizumab in frontline advanced melanoma as well as regular approval of Amtagvi in post-anti-PD-1 melanoma.
Global site activation and patient enrollment continue with strong momentum in the U.S., Europe, Australia, Canada, and additional countries.
An oral presentation of updated clinical data from Cohort 1A of the IOV-COM-202 trial, which strongly supports the rationale for TILVANCE-301 and the frontline melanoma opportunity, will be presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting on May 31, 2024.
Lifileucel in Non-Small Cell Lung Cancer (NSCLC)
Enrollment resumed for new patients in the IOV-LUN-202 registrational Phase 2 trial in post-anti-PD-1 NSCLC soon after the U.S. FDA lifted a partial clinical hold in the first quarter. The IOV-LUN-202 trial includes clinical sites in the U.S., Canada, and Europe, with plans to include additional regions with strong track records for enrollment in lung cancer studies over the next few months. Enrollment has restarted with high demand and the registrational cohorts are expected to be fully enrolled in 2025.
At a recent Type D meeting, the FDA provided positive regulatory feedback on the proposed potency matrix for lifileucel in NSCLC. The FDA previously provided positive regulatory feedback that the design of the single-arm IOV-LUN-202 trial may be acceptable for approval of lifileucel in post-anti-PD-1 NSCLC.
Lifileucel in Endometrial Cancer
A Phase 2 trial of lifileucel in advanced endometrial cancer patients is on track to initiate in the second quarter of 2024. The trial will enroll patients with advanced endometrial cancer who progressed after platinum-based chemotherapy and anti-PD-(L)1 therapy regardless of mismatch repair (MMR) status. This clinical program and trial design are supported by preclinical and manufacturing success data to be presented at a conference in 2024 and has received positive feedback from gynecological oncology experts.
In 2024, an estimated 67,880 new cases of uterine cancer (>90% of which are endometrial cancer) are expected to be diagnosed, with 13,250 deaths expected in the US.1 There are no currently approved therapies in the emerging second-line setting after frontline post-anti-PD1 therapy and chemotherapy. Endometrial cancer represents a significant opportunity for TIL cell therapy to address an additional unmet medical need in the post-anti-PD-1 treatment setting and may address both MMR deficient and proficient patients.
Next Generation TIL Pipeline
IOV-4001 (PD-1 Inactivated TIL Cell Therapy): The Phase 1 safety portion concluded in the first in human IOV-GM1-201 trial to investigate PD-1 inactivated TIL cell therapy (IOV-4001) in previously treated advanced melanoma and NSCLC, and the trial is progressing successfully into the multi-center Phase 2 efficacy stage. Iovance continues to utilize the TALEN technology licensed from Cellectis to develop other investigational gene-edited TIL cell therapies with multiple knockout targets to potentially improve efficacy.
Next Generation IL-2 for TIL Treatment Regimen: Iovance plans to submit an Investigational New Drug application (IND) for a Phase 1/2 clinical trial of IOV-3001, a modified interleukin-2 (IL-2) fusion protein, for use in the TIL therapy treatment regimen in the third quarter of 2024. Results from non-human primate and IND-enabling studies of IOV-3001 will be presented in a poster at ASCO (Free ASCO Whitepaper) 2024 and demonstrate the potential for improved safety with strong effector T cell expansion.
Next Generation, Cytokine-Tethered TIL Therapy: A genetically engineered, inducible, and tethered IL-12 TIL cell therapy, designated IOV-5001, is in IND-enabling studies. In preclinical studies, IOV-5001 augmented anti-tumor activity in vitro, and a clinical trial of a prior generation IL-12 TIL therapy at the National Cancer Institute showed improved efficacy. An INTERACT meeting is planned with the FDA to discuss IOV-5001 in the third quarter of 2024, followed by an IND submission in early 2025.
Manufacturing Capacity Expansion

The Iovance Cell Therapy Center (iCTC), and a nearby FDA-approved contract manufacturer, are built today for capacity for several thousands of patients annually. Capacity expansion is currently underway at iCTC to supply TIL cell therapies for more than 5,000 patients annually in the next few years.
Upcoming ASCO (Free ASCO Whitepaper) 2024 Highlights for Iovance

Oral Presentation: Efficacy and safety of lifileucel, an autologous tumor-infiltrating lymphocyte cell therapy, and pembrolizumab in patients with immune checkpoint inhibitor-naive unresectable or metastatic melanoma: updated results from IOV-COM-202 Cohort 1A
Session: Melanoma/Skin Cancers, Friday, May 31, 2024, 2:45 – 5:45 p.m. CDT
Poster: IOV-3001, a modified interleukin-2 fusion protein, for potential use in tumor-infiltrating lymphocyte cell therapy regimens
Session: Developmental Therapeutics – Immunotherapy – Saturday, June 1, 2024; 9:00 a.m. – 12:00 p.m. CDT
Poster: Dynamics of circulating cytokines and chemokines during and after tumor-infiltrating lymphocyte cell therapy with lifileucel in advanced melanoma patients
Session: Melanoma/Skin Cancers: Saturday, June 1, 2024, 1:30-4:30 p.m. CDT
Corporate Updates

As of March 31, 2024, Iovance had cash, cash equivalents, investments, and restricted cash of approximately $362.6 million, compared to $346.3 million at December 31, 2023. The current cash position and anticipated revenue from Amtagvi and Proleukin are expected to be sufficient to fund current and planned operations well into the second half of 2025.
Iovance is now recognizing all Proleukin revenues for commercial and clinical use and has recently commenced significant sales to distributors. In the first quarter of 2024, Iovance completed the transfer of marketing authorizations and began distribution of Proleukin. Beginning in the second quarter of 2024, Iovance expects to recognize significant incremental revenues for Proleukin as part of the Amtagvi treatment regimen.
Iovance currently owns more than 120 granted or allowed U.S. and international patents for TIL-related technologies, including TIL compositions and methods of treatment and manufacturing in a broad range of cancers, with Gen 2 patent rights expected to provide exclusivity into 2038 and additional patent rights, including patents related to potency assays expected to provide exclusivity into 2042. More information on Iovance’s patent portfolio is available on the Intellectual Property page on www.iovance.com.
First quarter 2024 Financial Results

Net loss for the first quarter ended March 31, 2024, was $113.0 million, or $0.42 per share, compared to a net loss of $107.4 million, or $0.50 per share, for the first quarter ended March 31, 2023. The net loss for the first quarter 2024 includes amortization of intangible assets acquired as part of the Proleukin transaction.

Revenue for the first quarter ended March 31, 2024, was $0.7 million from sales of Proleukin in licensed markets outside of the U.S. Cost of sales was $7.3 million, primarily related to inventoriable costs associated with sales of Proleukin and non-cash amortization expense for the acquired intangible asset for developed technology during the first quarter of 2024. No revenue or cost of sales were incurred for the first quarter ended March 31, 2023.

Research and development expenses were $79.8 million for the first quarter ended March 31, 2024, a decrease of $2.9 million compared to $82.7 million for the first quarter of 2023. The decrease was primarily attributable to the transition to commercial Amtagvi manufacturing in the most recent quarter, partially offset by increased costs associated with the purchases of raw materials, clinical trials driven primarily by the Phase 3 TILVANCE-301 clinical trial, and the planned EU regulatory submissions for lifileucel.

Selling, general and administrative expenses were $31.4 million for the first quarter ended March 31, 2024, an increase of $3.3 million compared to $28.1 million for the first quarter of 2023. The increase was primarily attributable to increases in headcount and related costs, including stock-based compensation, to support the growth in the overall business and related corporate infrastructure, as well as costs incurred to support the commercialization of Amtagvi and Proleukin, partially offset by a decrease in legal costs.

For additional information, please see the Company’s Selected Condensed Consolidated Balance Sheet and Statement of Operations below.

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1. National Cancer Institute Surveillance, Epidemiology and End Results (SEER) Program. 2024 Estimates. View Source