First Patient Treated in a Phase 1b/2 Trial of TG4001 in Combination with Avelumab in HPV-Positive Cancers

Transgene a biotech company that designs and develops viral-based immunotherapies, today announces that the first patient has been treated at the Curie Institute, Paris, France, in a Phase 1b/2 clinical trial evaluating the combination of TG4001 with avelumab* as a treatment for human papillomavirus type 16 positive (HPV-16+) recurrent or metastatic cancers, such as oropharyngeal squamous cell carcinoma of the head and neck (SCCHN).

This subtype of cancer represents more than 80% of oropharynx cancers.

This multi-center, open-label trial will assess the safety and tolerability, as well as the anti-tumor activity and efficacy of this immunotherapy combination regimen in up to 50 patients (NCT03260023).

Prof. Christophe Le Tourneau, M.D., Head of the Early Phase Program at the Curie Institute, and a world expert in head and neck cancers, is the Principal Investigator of the study.

More information on the trial is available on clinicaltrials.gov

TG4001: an investigational viral-based therapeutic vaccine that has shown efficacy

TG4001 is an active immunotherapeutic designed by Transgene to express the coding sequences of the E6 & E7 tumor-associated antigens of HPV-16 and the cytokine, IL-2. This therapeutic vaccine, which is based on a non-propagative, attenuated vaccinia vector (MVA), has already been administered to more than 300 subjectsin previous clinical trials. TG4001 has demonstrated promising activity in terms of HPV viral clearance and was well tolerated.

TG4001 + avelumab: a promising immunotherapy regimen

Avelumab is a human anti-PD-L1 IgG1 monoclonal antibody. Avelumab is designed to potentially engage both the adaptive and innate immune systems. By binding to PD-L1, avelumab is thought to prevent tumor cells from using PD-L1 for protection against white blood cells, such as T-cells, thereby exposing them to the anti-tumor responses.

Immunotherapeutic agents, and in particular the therapeutic vaccine TG4001 together with the PD-L1 blocker avelumab, by targeting two distinct steps in the immune response, are hoping to improve efficacy for patients who have not responded to or have progressed after first line treatment.

Commenting on the potential of this immunotherapy combination regimen, Maud Brandely, Chief Medical Officer of Transgene, added: “The preclinical and clinical data obtained with TG4001 clearly indicate that this therapeutic vaccine can induce HPV clearance in patients with HPV-16 associated diseases. Avelumab has also demonstrated a promising pre-clinical and clinical efficacy in multiple tumor types, pointing to potential synergies with TG4001. We believe an immunotherapy combination regimen,such as the combination of TG4001 and avelumab shows significant promise for patients with recurring or resistant advanced HPV-16+ oropharyngeal cancers. We are very pleased to start this Page 2 / 3 Phase 1b/2 trial with Merck KGaA, Darmstadt, Germany, and Pfizer as partners to assess the potential of this novel immunotherapy regimen in an effort to improve the outcomes of these patients.”

Commenting on this novel immunotherapy regimen, Prof. Christophe Le Tourneau, MD, Head of the Early Phase Program at the Curie Institute, and Principal Investigator of the trial, added: “HPV-positive cancer patients suffer from the lack of a specific treatment regimen that addresses the underlying etiology of their disease. I am confident that immunotherapy combination regimens, based around TG4001, could deliver better outcomes for patients who have not responded to or have progressed after a first line of treatment.”

*Avelumab is under clinical investigation for treatment of HPV-16+ recurrent or metastatic cancers, such as oropharyngeal SCCHN in combination with TG4001 and has not been demonstrated to be safe and effective for these indications. There is no guarantee that avelumab will be approved for HPV-16+ recurrent or metastatic cancers, such as oropharyngeal SCCHN by any health authority worldwide.