Chargement Évènements

« Tous les Évènements

  • Cet évènement est passé

Dr. Pierre FONS & Dr. Michaël ESQUERRE, EVOTEC / « Les vendredis de l’Oncopole »: introducing Evotec immuno-oncology/clinical translation expertise through EVT801: a selective VEGFR3 inhibitor proposed as single therapy and for combination with immune-checkpoint therapies (ICT)

janvier 25 @ 13:00 - 14:00

Dr. Pierre FONS & Dr. Michaël ESQUERRE, EVOTEC / « Les vendredis de l’Oncopole »: introducing Evotec immuno-oncology/clinical translation expertise through EVT801: a selective VEGFR3 inhibitor proposed as single therapy and for combination with immune-checkpoint therapies (ICT)

Evotec is a drug discovery alliance company with mainly a European footprint. Evotec has its own R&D portfolio of projects (EVT Innovate). We are also supporting R&D efforts of other pharma or biotech companies (EVT Execute) and creating bridge initiative with academic labs. Toulouse site, with today 440 employees, is dedicated to R&D in Oncology. One group of scientists is fully dedicated to Immuno-Oncology with a particular interest into the clinical translation for biomarkers identification or validation trying to fill the gaps for drug discovery between in vitro and in vivo animal models.

We have identified EVT801 as a highly selective VEGFR3 inhibitor drug candidate, which strongly inhibits angiogenesis without inducing hypoxia, reputed as one of the main causes of cancer-associated immunosuppression. Combination of EVT801 and Immune Checkpoint Therapy (ICT) could be thus synergistic as hypoxia-induced-immunosuppression should be avoided.

We have demonstrated that EVT801 displays a higher selectivity for the inhibition of the VEGFR3 tyrosine kinase in cells, with residual activity against VEGFR2, in contrast to other VEGFR inhibitors such as Fruquitinib and Lenvatinib.

For proof-of-concept as single agent, we transfected the mouse BNL hepatoma cell line with VEGFR3. EVT801 displayed a strong therapeutic activity by acting on both VEGFR3+ tumor cells and on the Tumor Microenvironment (TME). In addition to its immunomodulatory properties, EVT801 decreased angiogenesis without increasing hypoxia.

For proof-of-concept for combination with ICT, we have used different syngeneic tumor mouse models. We selected the 4T1 orthotopic mammary carcinoma mouse model as it is known to be less sensitive to anti-PD-1 antibody therapy. We demonstrated that EVT801 in combination with aPD-1 mAb was significantly superior to each single agent treatments; besides, a decrease of lung metastasis spreading was observed. We observed that decrease of MDSCs in blood in response to EVT801 was correlated with the decrease of tumor weight. By IHC analysis, we showed that treatment with EVT801 increases CD8+ T-cells infiltration inside the tumor. Taken together, these results indicate that EVT801 represents an innovative anti-angiogenic drug for cancer immunotherapy, which may improve the frequency of response to ICT.

In collaboration with the IUCT/Oncopole, we have selected cancer indications for single agent therapy when tumor cells express VEGFR3 and for combination with ICT when VEGFR3 is highly expressed in the tumor microenvironment. Moreover, with the Clinical Trial Phase I department of the Oncopole, we have designed the clinical trial for EVT801 in order to perform the first administration of EVT801 to patients in 2019.

Détails

Date :
janvier 25
Heure :
13:00 - 14:00
Catégorie d’Évènement:

Organisateur

Mary Poupot
Téléphone :
+33(0) 5 83 74 16 62
E-mail :
mary.poupot@inserm.fr

Lieu

Auditorium Claudius Regaud
Institut Universitaire du cancer de Toulouse-Oncopole, 1 avenue Irène Joliot-Curie
Toulouse, 31100 France
+ Google Map
Téléphone :
+33(0) 5 31 15 50 50
Site Web :
https://www.iuct-oncopole.fr/iuct-oncopole