Transgene — Preclinical Proof-of-Concept Data of Oncolytic Virus TG6050 Published in JITC

These data, published in The Journal for ImmunoTherapy of Cancer (JITC), demonstrate that TG6050 induces tumor regression and profound remodeling of the tumor microenvironment

TG6050 has also shown to avoid toxicity associated with systemic administration of IL-12 and anti-CTLA-4

TG6050 is currently being evaluated in a Phase I clinical trial (Delivir) for non-small cell lung cancer

Strasbourg (France), August 27, 2024, 7:30 am CET – Transgene (Euronext Paris: TNG), a biotech company that designs and develops virus-based immunotherapies for the treatment of cancer, announces the publication in the Journal for ImmunoTherapy of Cancer (JITC) of a peer-reviewed article which illustrates that TG6050 induces profound immune remodeling of the tumor microenvironment in animal models. The paper highlights TG6050’s potential to induce sustained intratumoral expression of interleukin-12 (IL-12) and anti-cytotoxic T-lymphocyte associated antigen-4 (CTLA-4) antibody at active concentrations without the toxicity observed with systemic administration.

TG6050 is an oncolytic virus derived from Transgene’s invir.IO® platform encoding interleukin-12 (IL-12) and an anti-CTLA4 antibody, with the potential to trigger a powerful localized antitumor immune response.

The JITC paper reports that in addition to consistent multiplication and propagation of TG6050 in tumor cells, functional transgenes are expressed in the tumor with a sustained intratumoral accumulation of IL-12 and anti-CTLA-4 antibody. The three components of TG6050 (oncolytic viral backbone, IL-12 and anti-CTLA-4 antibody transgenes) act together to induce tumor regression in numerous “hot” and “cold” murine tumor models investigated in these studies. This antitumoral activity was further amplified when TG6050 was combined with an anti-PD1.

Moreover, these studies show that TG6050 triggers a strong adaptive antitumoral immune response, accompanied by a profound modification of the tumor microenvironment based on infiltration of both innate and adaptive immune cells, altering it to a more inflamed state (from “cold” to “hot”).

TG6050 was also shown to be safe. Upon intravenous administration in non-human primates for toxicology evaluation, it did not induce any of the IL-12 related adverse effects that are associated with systemic administration. TG6050 has now progressed into Phase 1 clinical development (the Delivir trial) in metastatic non-small cell lung cancer (NCT05788926).

“These strong preclinical data demonstrate the ability of our invir.IO® oncolytic virus platform to generate promising candidates for further development and support our decision to advance TG6050 into the clinic in metastatic non-small cell lung cancer. We have thoroughly explored the mechanism of action of TG6050, with local delivery of functional IL-12 and anti-CTLA-4 resulting in strong antitumor activity. Moreover, in toxicology studies after repeated intravenous administrations in non-human primates, TG6050 did not display any observable adverse effects,” commented Dr. Maud Brandely, MD, PhD, Chief Medical Officer of Transgene.

The JITC paper is titled “TG6050, an oncolytic vaccinia virus encoding interleukin-12 and
anti-CTLA-4 antibody, favors tumor regression via profound immune remodeling of the tumor microenvironment” and can be accessed here.