- Detailed results to be presented at AACR 2021 Annual Congress
- Intravenous administration could allow oncolytic viruses from
Transgene’s Invir.IO™ platform to be used to treat a broad range of
solid tumors
Regulatory News:
Transgene (Paris:TNG) (Euronext Paris: TNG), a biotech
company that designs and develops virus-based immunotherapeutics
against cancer, today announces initial promising results from a
Phase I study combining intravenous (IV) oncolytic virus TG6002 and
oral 5-FC in patients with advanced gastrointestinal carcinomas.
These data provide a clinical proof of concept for Transgene’s
double deleted VVcopTK-RR- patented virus backbone: after IV
administration, TG6002 reached the tumor, multiplied within tumor
cells, and induced the local expression of its payload (the FCU1
gene).
These results will be presented at the American Association
for Cancer Research (AACR) virtual meeting taking place from April
10-15, 2021.
DATA CONFIRM THAT THE CHEMOTHERAPY AGENT 5-FU IS PRODUCED IN
PATIENTS’ TUMORS AFTER INTRAVENOUS ADMINISTRATION
TG6002 is a novel oncolytic virus that has been engineered to
combine multiple mechanisms of action. It has been designed
to:
- selectively replicate within cancer cells. This is due to the
deletion of the viral genes encoding TK and RR, which reduces the
virus’s ability to grow in normal cells. This selective viral
replication leads to the breakdown of the infected tumor cells in a
process called oncolysis,
- prime an immune response against the primary tumor and
metastases,
- and to induce the local expression of a biologically active
enzyme able to convert 5-FC into its active cytotoxic metabolite
5-FU, directly in the tumor.
The data demonstrate that high concentration and continuous
production of 5-FU chemotherapy can be obtained within the tumors
through the local conversion of the pro-drug 5-FC (administered
orally). This mechanism of action is based on the in-tumor
expression of the proprietary FCU1 gene that has been integrated
within the genome of TG6002.
In this study, extensive analyses are being performed
including metastasis biopsy with synchronous blood sampling,
assessment of virus presence, quantification of 5-FC and 5-FU and
assessment of neutralizing antibody titers.
These analyses have allowed Transgene to document TG6002’s
pharmacokinetics (PK) and biodistribution, and the functioning of
the FCU1 gene when given by IV administration.
Detailed results:
✔ TG6002 infects tumors after intravenous administration,
remains active and effectively express FCU1 gene selectively in
tumor tissue; ✔ Absence of widespread virus distribution in the
body and association of FCU1 activity with high virus concentration
in tumor tissue suggest that the replication of TG6002 is
concentrated in tumor cells; ✔ None of the patients presented
clinical signs of extra-tumoral dissemination of the virus
suggesting a high tumor specificity of the viral replication; ✔ The
study is continuing with escalating dosing of TG6002.
CLINICAL PROOF OF CONCEPT OF THE FEASIBILITY OF THE IV
ADMINISTRATION OF TRANSGENE’S PROPRIETARY ONCOLYTIC VIRUS
To-date, the only oncolytic virus that has received
regulatory approval is only approved for intra-tumoral
administration, restricting its use to superficial lesions.
Transgene aims to enlarge the number of solid tumors, such as
gastro-intestinal tumors, that could be addressed by an oncolytic
virus, by developing oncolytics that can be administered
intravenously.
The findings that will be presented at AACR demonstrate the
relevance of intravenous administration of Transgene’s next
generation oncolytic viruses including TG6002.
These data also suggest that candidates derived from
Transgene’s unique Invir.IO™ platform could also be given
intravenously, extending the use of these therapies to a broad
range of solid tumors.
- Title of the poster: “Oncolytic virus TG6002 locates to
tumors after intravenous infusion and induces tumor-specific
expression of a functional pro-drug activating enzyme in patients
with advanced gastrointestinal carcinomas”
- Authors: Kaidre Bendjama, Philippe Cassier, Victor
Moreno, Bernard Doger, Emiliano Calvo, Maria De Miguel, Christiane
Jungels, Philippe Erbs, Damien Carpentier, Alain Sadoun.
- Abstract/Poster Number: LB179
- Session: PO.IM02.11 - Vaccines
The e-poster presentation will be available on the AACR website
beginning at 8:30 am US EDT on Saturday, April 10, until Monday,
June 21. The text of this abstract will be posted at 12:01 am US
EDT on Friday, April 9 on the AACR website.
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 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., PhD, 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.
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version on businesswire.com: https://www.businesswire.com/news/home/20210408005698/en/
Transgene: Lucie Larguier Director Corporate
Communications & IR +33 (0)3 88 27 91 04
investorrelations@transgene.fr
Media: Citigate Dewe Rogerson David Dible/Sylvie
Berrebi + 44 (0)20 7638 9571
transgene@citigatedewerogerson.com
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