Transgene shares fall after Phase II cancer trial misses key goal

Transgene’s stock has seen a significant drop following the unsuccessful Phase II trial of its therapeutic vaccine candidate, TG4001 (tipapkinogene sovacivec). The trial, which aimed to improve progression-free survival (PFS) in solid tumors, did not meet its primary endpoint. This led to an 18.8% decrease in Transgene’s share price, dropping from €1.17 at the close of 11 October to a low of €0.95 on the morning of 14 October, eventually stabilizing at around €1 per share.

The trial, identified as NCT03260023, sought to evaluate the efficacy of TG4001 in combination with Merck KGaA’s Bavencio (avelumab), a PD-L1 checkpoint inhibitor. The study involved 150 patients with recurrent or metastatic HPV16-positive cervical and anogenital cancers. These patients were either treatment-naïve or had undergone one prior systemic chemotherapy but had not received earlier immunotherapy. Unfortunately, the addition of TG4001 did not result in statistically significant improvements in PFS across the entire study population.

Despite the overall results, Transgene remains hopeful. A subgroup analysis of patients with cervical cancer, who made up about 54% of the trial participants, indicated a possible trend towards improved PFS. The French biotech firm plans to conduct further analysis, including evaluating data based on PD-L1 status, before making decisions on the subsequent steps for TG4001’s development. PD-L1 status indicates the level of expression of the PD-L1 protein on tumor cells, which can affect the efficacy of Bavencio in treating cancer.

TG4001 is a viral-based vaccine designed to trigger an immune response against cells expressing HPV16 E6 and E7 antigens. Its effectiveness is enhanced by the inclusion of human IL-2, which bolsters the immune reaction. Despite the setback, Transgene’s CEO Alessandro Riva expressed cautious optimism: “Failure to meet the primary objective in our Phase II study with TG4001 is disappointing. Nevertheless, we are encouraged by the positive efficacy trend in favor of the combination regimen in cervical cancer patients.”

Transgene continues to focus on its leading candidate, TG4050, an individualized cancer vaccine currently in a Phase I/II trial (NCT04183166) for head and neck cancer patients. TG4050 is developed using Transgene’s myvac platform, which creates personalized treatments based on patient-specific mutations known as neoantigens. These treatments are intended to induce a T cell response targeting tumor cells. The company plans to present 24-month data on Phase I patients in November at the Society for Immunotherapy of Cancer (SITC) conference.

According to a report by GlobalData, cancer vaccines represent a significant trend in immuno-oncology development. While TG4050 is a personalized vaccine, TG4001 is an off-the-shelf standardized treatment. Feedback from a 2023 GlobalData survey indicates that personalized mRNA vaccines are considered the most promising type of cancer vaccine by more than half of the high-prescribing key opinion leaders.

In addition to TG4001 and TG4050, Transgene is also working on an oncolytic virus therapy, BT-001, developed in collaboration with BioInvent International. This therapy is being tested in a Phase I/IIa clinical trial (NCT04725331) both as a monotherapy and in combination with MSD’s PD-1 checkpoint inhibitor Keytruda (pembrolizumab).

Transgene’s journey with oncolytic virus therapies has faced significant challenges. In May 2023, AstraZeneca ended its four-year partnership with Transgene. This collaboration, initiated in 2019 with an upfront payment of $10 million to Transgene for developing oncolytic virus candidates, encountered difficulties early on. One of Transgene’s candidates, Pexa-Vec, failed a Phase III trial (NCT02562755) just months after the deal was signed, marking a notable setback in their efforts.