- Initial Phase I data will be presented at ESMO Congress 2021
(poster presentation) starting today
- Clinical Proof of Concept for the feasibility of the
intravenous administration of Transgene’s patented oncolytic virus
backbone behind the Invir.IO™ platform
Regulatory News:
Transgene (Paris:TNG) (Euronext Paris: TNG), a
biotech company that designs and develops virus-based
immunotherapeutics against cancer, today announces the presentation
of data from a Phase I study combining intravenous (IV) oncolytic
virus TG6002 and oral 5-FC in patients with advanced
gastrointestinal carcinomas at the European Society for Medical
Oncology (ESMO) virtual meeting taking place from September 16-21,
2021.
These important data further confirm that Transgene’s double
deleted VVcopTK-RR- patented virus backbone, which forms the basis
of the company’s Invir.IO™ platform, has the potential to be given
intravenously. After IV administration, TG6002 is able to
selectively replicate and persist in tumor cells leading to the
local expression of its functional payload (the FCU1 gene).
INTRAVENOUS ADMINISTRATION COULD ALLOW ONCOLYTIC VIRUSES FROM
TRANSGENE’S INVIR.IO™ PLATFORM TO BE USED TO TREAT A
BROAD RANGE OF SOLID TUMORS
To date, the only oncolytic virus to have received regulatory
approval has to be given via intra-tumoral administration,
restricting its use to superficial lesions. Transgene’s
ambition is to significantly enlarge the number of solid tumors,
such as gastro-intestinal tumors, that could be addressed by an
oncolytic virus, by developing oncolytics administered
intravenously.
TG6002 has been designed to combine multiple mechanisms of
action: the lysis of tumor cells, the production of a chemotherapy
agent 5-FU directly in the tumor and the induction of an immune
response against cancer cells. This concept is presented in a short
video available by clicking here.
The Phase I data that will be presented at the ESMO congress
further demonstrate that TG6002 persists selectively in cancer
cells while expressing its transgene of interest. This finding
supports the potential of IV administration of Invir.IO™-based
oncolytic virus, extending the use of these therapies to a broad
range of solid tumors.
DATA CONFIRM THE PERSISTENCE OF THE CHEMOTHERAPY AGENT 5-FU
IN PATIENTS’ TUMORS AFTER INTRAVENOUS ADMINISTRATION
The data also demonstrate that the chemotherapy agent 5-FU is
produced in the tumor across the three dose-level cohorts
(3x108 pfu, 1x109 pfu and 3x109 pfu). 5-FU results from the local
conversion of the pro-drug 5-FC (administered orally) allowed by
the in-tumor expression of the proprietary FCU1 gene that has been
integrated within the genome of TG6002.
5-FU and its final metabolite F-BAL were detected in tumor
tissue and in peripheral blood at days 5, 7 and 14 in most of the
evaluable patients across the three dose-level cohorts.
Interestingly, patients with the highest levels of 5-FU in blood
and tumor were patients for which there was direct evidence of
TG6002 in the tumor.
As of today, dose escalation has been completed. The trial is
currently enrolling patients in additional cohorts assessing
several administration schedules.
- Title of the poster: “Bioavailability and activity of
oncolytic virus TG6002 after intravenous administration in patients
with advanced gastrointestinal carcinomas”
- Authors: Philippe Cassier, Victor Moreno, Bernard Doger,
Emiliano Calvo, Maria De Miguel, Christiane Jungels, Kaïdre
Bendjama, Philippe Erbs, Damien Carpentier, and Alain Sadoun
Detailed results:
- Direct evidence of TG6002 in the tumor, after intravenous
administration, which remains active and effectively express FCU1
gene selectively in tumor tissue;
- Detection of 5-FU and its final metabolite F-BAL in tumor
tissue and in peripheral blood in most of the evaluable patients
across the three dose-level cohorts;
- Replication of TG6002 is concentrated in tumor cells as
suggested by the absence of widespread virus distribution in the
body and the clear association of FCU1 activity with high virus
concentration in tumor tissue;
- TG6002 is well tolerated and no major toxicities limiting the
dose escalation process were observed.
The abstract and the e-poster are available on the ESMO congress
website here and the e-poster can be downloaded on the Transgene
website here as well.
About the trial (NCT03724071)
This trial is a single-arm open-label Phase I/II trial
evaluating the safety and tolerability of multiple ascending doses
of TG6002 administered intravenously in combination with oral 5-FC,
a non-cytotoxic pro-drug that can be converted in 5-FU, its active
metabolite. Based on the safety profile of TG6002, several dose
levels and administration schedules have been added to the initial
Phase I clinical protocol. At the end of this Phase I part, Phase
II patients will receive the recommended dose of TG6002. The trial
has safety as primary endpoint for the Phase I part and efficacy
for the Phase II part. The trial also evaluates pharmacokinetic
properties and biodistribution of TG6002, along with immune
modulation of the tumor micro-environment. This European study will
enroll up to 40 patients suffering from advanced gastrointestinal
carcinomas who have failed and/or are intolerant to standard
therapeutic options in the Phase I part. Patients with colon cancer
and liver metastases will be enrolled in the Phase II part.
Dr. Philippe Cassier, M.D., Ph.D., head of the early-phase
trials unit at Centre Léon Bérard (Lyon, France), is the principal
investigator of the trial.
About TG6002
TG6002 has been engineered to directly kill cancer cells
(oncolysis), to enable the production of a chemotherapy agent
(5-FU) within the tumor, and to elicit an immune response by the
body against the tumor cells. In preclinical experiments, TG6002
has been shown to induce the shrinkage of the primary tumor as well
as the regression of distant metastases (Foloppe, et al., Molecular
Therapy Oncolytics,
https://doi.org/10.1016/j.omto.2019.03.005).
The production of 5-FU directly in the tumor aims to achieve a
better anti-tumoral effect with limited chemotherapy-induced side
effects.
TG6002 induces the production of 5-FU in the cancer cells it has
infected, by enabling the local conversion of the pro-drug 5-FC
(administered orally) into 5-FU. 5-FU is a common chemotherapy
agent for patients with gastro-intestinal cancers. This mechanism
of action is based on the in-tumor expression of the proprietary
FCU1 gene that has been encoded in the genome of TG6002, taking
advantage of the virus selective replication in the tumor
cells.
When administered systemically, 5-FU is associated with side
effects that can lead to treatment discontinuation. With TG6002,
5-FU is produced within the tumor where it is expected to be
present at a high concentration level in contrast to the very low
levels anticipated in the rest of the patient’s body.
About Transgene
Transgene (Euronext: TNG) is a biotechnology company focused on
designing and developing targeted immunotherapies for the treatment
of cancer. Transgene’s programs utilize viral vector technology
with the goal of indirectly or directly killing cancer cells.
The Company’s clinical-stage programs consist of two therapeutic
vaccines (TG4001 for the treatment of HPV-positive cancers, and
TG4050, the first individualized therapeutic vaccine based on the
myvac® platform) as well as two oncolytic viruses (TG6002 for the
treatment of solid tumors, and BT-001, the first oncolytic virus
based on the Invir.IO™ platform).
With Transgene’s myvac® platform, therapeutic vaccination enters
the field of precision medicine with a novel immunotherapy that is
fully tailored to each individual. The myvac® approach allows the
generation of a virus-based immunotherapy that encodes
patient-specific mutations identified and selected by Artificial
Intelligence capabilities provided by its partner NEC.
With its proprietary platform Invir.IO™, Transgene is building
on its viral vector engineering expertise to design a new
generation of multifunctional oncolytic viruses. Transgene has an
ongoing Invir.IO™ collaboration with AstraZeneca.
Additional information about Transgene is available at:
www.transgene.fr
Follow us on Twitter: @TransgeneSA
Disclaimer
This press release contains forward-looking statements, which
are subject to numerous risks and uncertainties, which could cause
actual results to differ materially from those anticipated. The
occurrence of any of these risks could have a significant negative
outcome for the Company’s activities, perspectives, financial
situation, results, regulatory authorities’ agreement with
development phases, and development. The Company’s ability to
commercialize its products depends on but is not limited to the
following factors: positive pre-clinical data may not be predictive
of human clinical results, the success of clinical studies, the
ability to obtain financing and/or partnerships for product
manufacturing, development and commercialization, and marketing
approval by government regulatory authorities. For a discussion of
risks and uncertainties which could cause the Company’s actual
results, financial condition, performance or achievements to differ
from those contained in the forward-looking statements, please
refer to the Risk Factors (“Facteurs de Risque”) section of the
Universal Registration Document, available on the AMF website
(http://www.amf-france.org) or on Transgene’s website
(www.transgene.fr). Forward-looking statements speak only as of the
date on which they are made, and Transgene undertakes no obligation
to update these forward-looking statements, even if new information
becomes available in the future.
View source
version on businesswire.com: https://www.businesswire.com/news/home/20210915005941/en/
Transgene: Lucie Larguier Director Corporate
Communications & IR +33 (0)3 88 27 91 04
investorrelations@transgene.fr
Transgene media: MEDiSTRAVA Consulting David
Dible/Sylvie Berrebi +44 (0)7714 306525
transgene@medistrava.com
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