Transgene Presented Additional Phase I Data with TG4050 (myvac® platform) at ASCO 2022

Strasbourg, France, June 6, 2022, 8:00 am CEST - Transgene (Euronext Paris: TNG), a biotech company that designs and develops virus-based immunotherapies for the treatment of cancer, today announced that it presented updated preliminary Phase I data on TG4050, its individualized neoantigen cancer vaccine, in a poster session at the American Society of Clinical Oncology (ASCO) annual meeting. TG4050 is based on Transgene’s myvac® platform and powered by NEC’s cutting-edge AI capabilities.

These additional positive initial data, including molecular (ctDNA) response, have been generated from the first patients with ovarian cancer and HPV-negative head and neck cancer enrolled in the two ongoing Phase I trials assessing TG4050. They were presented in-person in Chicago, IL, June 5, 2022.

“These new results, though early, are very encouraging” said Dr. Maud Brandely, MD, PhD, Chief Medical Officer of Transgene. “So far we accumulated promising preliminary data with TG4050: good tolerability, consistent immunogenicity and encouraging molecular response. We are particularly impressed by the effective priming of the immune system and the early signs of clinical activity. These results suggest that our individualized vaccine, TG4050, has the potential to extend the remission period, thus providing a new hope for cancer patients. In addition, the information we gather from the two ongoing Phase I studies will be pivotal in designing the Phase II trial of TG4050 which could start as early as 2023.”

Prof. Jean-Pierre Delord, MD, PhD, General Manager of IUCT Oncopole of Toulouse and first author of the poster, added: “Neoantigen vaccination such as TG4050 is a relevant strategy for the treatment of patients with high risk of cancer relapse for whom the medical need is particularly high. In this setting, the vaccine is expected to deliver clinical benefit by controlling the residual disease. To date, this non-invasive treatment is well tolerated by the patients and although preliminary, the data presented at ASCO clearly suggest that TG4050 could become a new treatment option for cancer patients. I am looking forward to seeing this potential game-changing therapy moving forward.”

For the first time, ctDNA data were generated following treatment with TG4050

Liquid biopsies were performed to measure the circulating tumor DNA (ctDNA) levels. ctDNA is an emerging modality that is used to detect subclinical disease or asymptomatic relapse in an increasing number of indications. Use of such highly sensitive and specific marker seeks to identify patients whose disease is very likely to relapse in the near future, before their disease becomes detectable with current standard methods such as imaging. Moreover, it allows a non-invasive monitoring of treatment effectiveness. For instance, in at least one ovarian cancer patient in the study, a decline in ctDNA was concomitant with CA-125 normalization and disease control. Analyses are ongoing in more recently included patients.

Clinical follow-up data continue to demonstrate the potential of TG4050 in ovarian and head and neck cancer patients

In the head and neck cancer trial, patients were randomized to immediately receive vaccination with TG4050 (early treatment arm, arm A) or at relapse (delayed vaccination arm, arm B). All evaluable patients randomized to arm A (n=8) are still in complete response as of mid-May 2022. In arm B (n=8), two patients have experienced relapse.

In the ovarian cancer trial (n=5), a fifth patient initiated her treatment with TG4050 recently. One patient treated after an elevation of CA-125 experienced a normalization of CA-125 without clinical progression for 9 months until death from an unrelated chronic illness. Another patient was treated upon onset of radiological evidence of relapse and remained stable for 11.4 months.

To date, the vaccine has been well tolerated and no related Serious Adverse Events have been reported across the two studies.

In both clinical studies, enrollment and patient dosing are progressing in line with our expectations. Overall, Transgene plans to treat 13 patients in the ovarian cancer trial and 30 patients in the head and neck cancer trial.

Immune cell response data demonstrated an effective priming of the immune system which is associated with disease regression

Transgene presented a comprehensive set of immunological data at ASCO. Circulating immune cells quantification (in particular monocytes, DC, NK cells, subcells of CD8, CD4, Treg) and expression of immune checkpoints (ICOS and PD1) suggest that the vaccine is able to effectively induce innate and adaptive immune responses in patients.

In an ovarian cancer patient, clinical resolution and biological responses (CA-125 and ctDNA responses) were concomitant to an immune response against multiple epitopes and to the onset of markers of an effective immune response (switch in circulating CD4 and CD8 cells toward an effector phenotype, increase in CD16neg NK cells; peak in circulating cytokines).

All evaluable patients developed a robust T-cell response against multiple targeted neoantigens (median of 10 positive responses per patient). T-cell responses were observed for class I and class II epitopes, they consisted of de novo responses and amplifications of preexisting responses.

The poster can be downloaded from the ASCO and Transgene websites.

Poster title: Phase 1 studies of personalized neoantigen vaccine TG4050 in ovarian carcinoma (OC) and head and neck carcinoma (HNSCC)

• Abstract number: 2637
• Session title: Developmental Therapeutics—Immunotherapy
• Authors: J.P. Delord, M. Block, C. Ottensmeier, G. Colon-Otero, C. Le Tourneau, A. Lalanne, O. Lantz, KL. Knutson, G. Lacoste, A. Tavernaro, M. Brandely, N. Silvestre, B. Grellier, Y. Yamashita, O. Kousuke, N. Yamagata, Y. Tanaka, B. Malone, E. Quemeneur, K. Bendjama