On January 23, 2023 Iovance Biotherapeutics, Inc. (NASDAQ: IOVA), a late-stage biotechnology company developing novel T cell-based cancer immunotherapies (tumor infiltrating lymphocyte, TIL, and peripheral-blood lymphocyte, PBL), reported corporate, clinical, and regulatory updates (Press release, Iovance Biotherapeutics, JAN 23, 2023, View Source [SID1234626450]).

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CORPORATE UPDATE

Acquisition of Proleukin

Under a definitive agreement between Iovance and Clinigen Limited, Iovance will acquire worldwide rights to Proleukin (aldesleukin), an interleukin-2 (IL-2) product used to promote T-cell activity following TIL infusion. Iovance expects the benefits of this transaction to include immediate and future revenue, securing the IL-2 supply chain and logistics surrounding TIL therapy administration, and lower cost of goods and clinical trial expenses for Proleukin used with TIL therapies.

Terms of the agreement include an upfront payment of £166.7 million, a £41.7 million milestone payment upon first approval of lifileucel in advanced melanoma, and double-digit Proleukin global sales royalties from Iovance to Clinigen. The transaction is expected to close in the first quarter of 2023, subject to required regulatory approvals and clearances and other customary closing conditions.

Iovance is financing the acquisition with existing cash. As of January 20, 2023, Iovance’s unaudited cash position is approximately $477.0 million, which includes net proceeds from an at-the market (ATM) equity financing facility of approximately $227.1 million raised during the fourth quarter of 2022 and early 2023. In addition, Iovance has agreed to terms for a secured line of credit of up to $100 million from Quogue Capital. These proceeds are expected to fund the acquisition of Proleukin and Iovance’s operating plan well into 2024.

CLINICAL AND REGULATORY UPDATES

Lifileucel in Advanced Melanoma

TILVANCE-301 Phase 3 Confirmatory Trial: During the fourth quarter of 2022, Iovance reached agreement with the U.S. Food and Drug Administration (FDA) regarding the Phase 3 TILVANCE-301 trial of lifileucel in combination with pembrolizumab in frontline advanced melanoma. The TILVANCE-301 trial will randomize 670 patients and will investigate lifileucel in combination with pembrolizumab (experimental arm) compared with pembrolizumab monotherapy (control arm).

The FDA agreed to dual primary endpoints of objective response rate (ORR) to support accelerated approval and progression free survival (PFS) to support full approval of lifileucel in frontline advanced melanoma. The TILVANCE-301 confirmatory trial will also support full approval of lifileucel in post-anti-PD-1 advanced melanoma and is expected to be well underway at the time of potential BLA approval for lifileucel. Further details will be shared later in 2023.

Updated results from nearly 20 patients treated in Cohort 1A of the IOV-COM-202 trial of lifileucel in combination with pembrolizumab in frontline advanced melanoma remain consistent with previously reported data1 demonstrating robust ORR by RECIST 1.1 and durability of response. Additional data will be shared later in 2023 and continue to support the opportunity for lifileucel in frontline advanced melanoma.

Lifileucel in Anti-PD-1 Naïve Metastatic Non-Small Cell Lung Cancer (NSCLC)

IOV-COM-202 Cohort 3A: Confirmed ORR by RECIST 1.1 of 47% (n=8/17) was observed in patients treated with a combination of TIL therapy (LN-145) and pembrolizumab in Cohort 3A of the IOV-COM-202 trial. Responses were observed regardless of PD-L1 status. Safety was consistent with other studies of Iovance TIL therapies in combination with pembrolizumab. Study enrollment remains ongoing.

ORR by Clinical Subset: Cohort 3A comprises three distinct clinical subsets of anti-PD-1 naïve metastatic NSCLC: 1) treatment-naïve, 2) post-chemotherapy, and 3) EGFR-mutant after prior treatment with tyrosine kinase inhibitors (TKI). Response rates were highest in patients who were treatment-naïve (80% ORR; n=4/5) and post-chemotherapy anti-PD-1 naïve (43% ORR, n=3/7) compared with EGFR-mutant after prior treatment with TKI (20% ORR, n=1/5). Two patients achieved complete responses and remain on study (post-chemotherapy anti-PD-1 naive, n=1 and EGFR-mutant after prior treatment with TKI, n=1). The observed differences in ORR between the patient subsets are informing the design of a subsequent potential registration study. Detailed clinical results will be shared at a future medical meeting.

Regulatory Strategy: Iovance plans to meet with FDA in 2023 to discuss Cohort 3A results and a potential registration trial of lifileucel in frontline advanced NSCLC patients who are EGFR wild-type. The proposed design will be a frontline maintenance study of standard-of-care pembrolizumab and limited duration chemotherapy followed by treatment consisting of TIL therapy in combination with pembrolizumab compared with pembrolizumab monotherapy in responding patients. This design takes advantage of the findings of Cohort 3A and has the potential to offer frontline advanced NSCLC patients improved responses and PFS compared with single agent maintenance pembrolizumab.

BLA Submission

The rolling BLA submission for lifileucel in post-anti-PD-1 advanced melanoma commenced in August 2022 and is on track to complete during the first quarter of 2023.

Investor Webcast

Iovance will host a webcast on Monday, January 23, 2023, at 8:30 a.m. ET to discuss these corporate, clinical and regulatory updates. To participate in the webcast, please register at https://register.vevent.com/register/BIb01d5a16742c4d99b3dfe1b02bad8147. The live webcast and replay can be accessed in the Investors section of the company’s website at ir.iovance.com.