Transgenic — Preclinical Proof-of-Concept Data of Oncolytic Virus TG6050 published in JITC | 27.08.24

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

Research has shown that TG6050 also avoids the 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, 07:30 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 illustrating that TG6050 induces profound immune remodeling of the tumor microenvironment in animal models. The article highlights the potential of TG6050 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 induce a potent local anti-tumor immune response.

The JITC paper reports that in addition to consistent replication and propagation of TG6050 in tumor cells, functional transgenes are expressed in the tumor with 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) cooperate to induce tumor regression in numerous “hot” and “cold” mouse tumor models examined in these studies. This antitumor activity was further enhanced when TG6050 was combined with an anti-PD1.

Furthermore, these studies demonstrate that TG6050 induces a strong adaptive antitumor immune response, accompanied by a profound alteration of the tumor microenvironment based on infiltration of both innate and adaptive immune cells, transforming it into a more inflamed state (from “cold” to “warm”).

TG6050 was also shown to be safe. When administered intravenously to non-human primates for toxicological evaluation, it did not cause any of the IL-12-related adverse effects associated with systemic administration. TG6050 is now in Phase 1 clinical development (the Deliver 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 to the clinic in metastatic non-small cell lung cancer. We have thoroughly investigated the mechanism of action of TG6050, with local delivery of functional IL-12 and anti-CTLA-4 resulting in strong antitumor activity. Furthermore, in toxicology studies, TG6050 showed no observable adverse effects after repeated intravenous administrations in non-human primates,” responded Dr. Maud Brandely, MD, PhD, Chief Medical Officer of Transgene.

The JITC the article is titled “TG6050, an oncolytic vaccinia virus encoding interleukin-12 and
anti-CTLA-4 antibody promotes tumor regression via profound immune remodeling of the tumor microenvironment“and is accessible here.

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About TG6050

TG6050 is an oncolytic virus developed using Transgene’s invir.IO® platform for intravenous administration. Invir.IO® viruses are based on the patented high-capacity Vaccinia virus Copenhagen strain genetically modified with the double deletion TK-RR- (VV_COPTK^–RR^–). TG6050 is designed to encode human IL-12, a cytokine that triggers a potent anti-tumor immune response, and a full-length anti-CTLA4 antibody. It is also optimized with the deletion of the gene encoding the viral M2L protein that targets CD80 and CD86, two ligands of CD28 (source: Kleinpeter et al., J. Virol. June 1, 2019; 93(11): e00207-19). The use of an oncolytic virus to deliver these immunotherapies locally and selectively to the tumor microenvironment allows for high intratumoral concentrations of both therapeutic proteins, eliciting a stronger and more effective antitumor response. Furthermore, by reducing systemic exposure to very low levels, this local therapeutic activity allows for an increase in the safety and tolerability profile of IL-12 and the anti-CTLA4 antibody.
TG6050 is being evaluated in the Deliver study, a Phase I study being conducted in patients with advanced non-small cell lung cancer (NSCLC).

A short video explaining the mechanism of action of TG6050 can be found here.

About the Delivir Study (NCT: 05788926)

The Delivir trial is a multicenter, open-label, dose-escalation Phase I trial evaluating TG6050 as a single agent. The trial will enroll up to 36 patients with metastatic/advanced NSCLC who have failed standard therapeutic options, including immunotherapies such as immune checkpoint inhibitors. Patients will receive single and repeated ascending doses of TG6050 intravenously to determine the recommended dose and best administration schedule for subsequent clinical development.

About Transgen
Transgene (Euronext: TNG) is a biotechnology company focused on the design and development of targeted immunotherapies for the treatment of cancer. Transgene’s programs use viral vector technology to kill cancer cells indirectly or directly.
The Company’s clinical programs consist of a portfolio of therapeutic vaccines and oncolytic viruses: TG4050, the first individualized therapeutic vaccine based on the myvac® platform, TG4001 for the treatment of HPV-positive cancers, as well as BT-001 and TG6050, two oncolytic viruses based on the invir.IO® viral backbone. With Transgene’s myvac® platform, therapeutic vaccination enters the field of precision medicine with a new immunotherapy that is fully tailored to each individual. The myvac® approach enables the development of a virus-based immunotherapy that encodes patient-specific mutations identified and selected by partner NEC’s artificial intelligence capabilities.
With the patented invir.IO® platform, Transgene is building on its expertise in viral vector engineering to design a new generation of multifunctional oncolytic viruses.
Additional information about Transgene is available at: www.transgene.nl
Follow us on social media: @TransgeneSA – LinkedIn:@Transgene

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Disclaimer
This press release contains forward-looking statements that are subject to numerous risks and uncertainties that could cause actual results to differ materially from anticipated results. The occurrence of any of these risks could have a material adverse effect on the Company’s business, prospects, financial condition, results of operations, regulatory approvals for development phases and development. The Company’s ability to commercialize its products is dependent on, but is not limited to, the following factors: positive preclinical data may not be predictive of clinical outcomes in humans, the success of clinical trials, the ability to obtain funding and/or partnerships for product manufacturing, development and commercialization, and marketing approval by government regulatory authorities. For a discussion of risks and uncertainties that could cause the Company’s actual results, financial condition, performance or achievements to differ from those in the forward-looking statements, please see the Risk Factors (“Facteurs de Risque”) section of the Universal Registration Document, available on the AMF website (http://www.amf-france.org) or on the Transgene website (www.transgene.fr). Forward-looking statements speak only as of the date on which they are made and Transgene assumes no obligation to update these forward-looking statements, even if new information becomes available in the future.

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