[Webinar] NEW INTERACTIVE PANEL WEBINAR] DRIVE™: Brothers in Arms to support small molecule drug discovery from Hit to IND

[Webinar] [NEW INTERACTIVE PANEL WEBINAR] DRIVE™ : Brothers in Arms to support small molecule drug discovery from Hit to IND[Webinar] [NEW INTERACTIVE PANEL WEBINAR] DRIVE™ : Brothers in Arms to support small molecule drug discovery from Hit to IND

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7 July 2020
5 pm CEST


Outsourcing drug discovery has become an overwhelmingly accepted approaches across the pharmaceutical industry from virtual biotech to large pharmaceutical companies as part of the globalization process. It does represent a cost-effective opportunity to access specialized technologies and expert scientist resources having a broad knowledge of pharmaceutical drug discovery development. Oncodesign’s objective with DRIVE™ offer is to provide its customers with the best possible options and state-of-the-art technologies to progress their drug discovery in the shortest possible time with the highest quality.

Oncodesign is doing so by setting up under a single leadership, privileged partnering with selected and trusted companies sharing the same values of innovation and quality as its own. 
Hits finding and validation are important phases in early drug discovery. With Program, Oncodesign is providing DNA encoded libraries, fragments screening along with Hit validation using NanoDSF, MST, SPR, ITC and Structural Biology (Cryo-EM and X-Ray crystallography) supported by artificial intelligence. 

Key learning objectives

  • Introduction to a solution provider from hits finding to IND filing
  • Advantages of drug discovery integrated provider vs silos approach
  • Special focus on Hit identification and validation across DNA encoded libraries, Artificial Intelligence, Biophsysics and Biostructures  

Discover our speakers

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L’évaluation de l’immunothérapie du cancer nécessite l’utilisation de modèles animaux précliniques appropriés reflétant suffisamment la situation physiologique chez l’homme.

[Congress] AACR Virtual Meeting II – 22 -24 June 2020

AACR Virtual Meeting II – 22 -24 June

The AACR Annual Meeting program covers the latest discoveries across the spectrum of cancer research—from population science and prevention; to cancer biology, translational, and clinical studies; to survivorship and advocacy—and highlights the work of the best minds in research and medicine from institutions all over the world.

Modelling the liver diseases from chronic inflammation injury to hepatocellular carcinoma for development of new liver treatments | Abstract #5638

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Introduction: Anemia is a condition characterized by low Hemoglobin levels. Anemia is observed during tumor development through the release of inflammatory cytokines, which will affect iron availability, a key component of red blood cells. In recent years, consequences of anemia of cancer on patients is getting growing recognition from a quality of life perspective, as well as its impact on the treatment scheme and hospitalization duration. Cancer-induced anemia has been identified in 30% of treatment-naive cancers (ECAS study, 2011 – WHO methodology). The proportion of anaemic patients reaches 70% following treatments, such as chemotherapies. Current approaches consider erythropoietin derivatives, formulated iron or transfusions, which does not address underlying chronic inflammation. Moreover, their use is limited as a consequence of toxicities (EPO, formulated iron) or availability (transfusion).
Increased expression of Hepcidin, a peptidic hormone regulating the storage of bioavailable iron, has been demonstrated as downstream effector of key inflammatory cytokines activation of ALK2/Smad axis. ALK2 (Activin-like receptor kinase 2) plays a critical role in the Smad signaling pathway and the production haemoglobin, through the regulation Hepcidin production in the liver. As a consequence, the selective inhibition of ALK2 as emerged as a valuable target for the treatment of Hepcidin-driven anemia of cancer to provide an alternative to current treatments.
Results: OD52, a potent and selective macrocyclic ALK2 inhibitor identified from Nanocyclix® technology platform, was used as in vitro pharmacological tool to investigate the impact of ALK2 inhibition on Hepcidin expression level in HepG2 cells, as well as in mice hepatocytes. BMP6-induced expression of Hepcidin mRNA was completely inhibited by LDN-193189 to low detectable levels, whereas OD52 normalized its expression. Further validation was performed in mice hepatocytes, where OD52 decreased Hepcidin expression to a lower extend as compared with LDN-193189. These experiments confirmed the importance of selectivity within BMP-kinase receptor family, where ALK3 component represents an undesired off-target.
In vivo evaluation of the compound in the acute model of turpentine-induced anemia demonstrated a normalization of haemoglobin level. In contrast, LDN-193189 increased haemoglobin above vehicle group to a level mimicking hemochromatosis, likely due to its ALK3 component.
Through further medicinal chemistry optimization, OD66 was identified as suitable in vivo pharmacological tool and was evaluated in a cancer-induced anemia mouse model. The compound demonstrated a normalization of haemoglobin levels to comparable levels with the tumor-free group without displaying toxicity.
Conclusion:  The identification of potent and selective Nanocyclix® ALK2 inhibitors and their evaluation in relevant in vitro and in vivo models demonstrated a normalization of haemoglobin levels through the modulation of Hepcidin expression. This collaborative work warrants further optimization towards the identification of a preclinical candidate.

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Macrocyclic ALK2 inhibitors as potential anemia of cancer treatment | Abstract #4028

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Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related death and accounts for >80% of primary liver cancer worldwide. Early stage HCC can be treated by local ablation, surgical resection or liver transplantation. Systemic pharmacological options are limited and only a few available (kinase and immune-checkpoint inhibitors). Most cases of liver cancer occur in the setting of chronic liver diseases. Risk factors include chronic Hepatitis B and C, alcohol addiction and metabolic diseases. HCC is a multistep process comprising chronic liver injury, inflammation, fibrosis/cirrhosis and cancer formation. Therefore, providing palliative and curative options remains a high medical need.
In order to better evaluate new preventive and curative treatments of liver cancers we developed complementary and integrated strategies to mimic the liver cancer initiation and progression steps in mouse models. These models involve chemotoxic agents, diet-induced disorders and implantation strategies.
We first established an orthotopic syngeneic model using Hepa1.6 mouse liver hepatoma cells. Hepa1.6-derived tumor growth was characterized through liver index, alpha-fetoprotein measurement in serum and liver, and MRI. The response to chemotherapy (Sorafenib) and immunotherapy (anti PD-1) was also assessed. Moreover, a panel of Patient-Derived Xenograft models (PDXs) are available to assess new treatment options in human HCC with regards of the genetic mutations and the variety of etiologies seen in human.
During the course of HCC formation, the liver undergoes cycles of inflammation, necrosis with regeneration, fibrosis, cell dysplasia and ultimately HCC. Thus, we developed two models of non- alcoholic steato-hepatitis (NASH); The first model involves chronic administration of hepatotoxic CCL4 associated with a high-fat and high-fructose diet. Mice develop steatohepatitis and fibrosis within 4 to 8 weeks as assessed with biochemistry parameters (AST, ALT…), gene expression levels of inflammatory and fibrotic genes as well as histological scores and MRI. The effect of obeticholic acid was successfully evaluated in this model. The second model is the STAM model induced by a low dose of Streptozotocin and high fat diet regimen. In this model, mice develop metabolic syndrome (increased body weight gain, hyperglycemia and hyperlipidemia), NASH (steatosis, inflammation, fibrosis) within 12 weeks and HCC within 16 weeks. The responses to standard of care and to immunotherapy together with the characterization of the immune cell populations are currently under investigation.
Altogether, these results demonstrate the usefulness of this liver diseases development program to discover and identify new treatments that could circumvent the progression of liver cancer.

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[Webinar] How to assess the interplay between tumor, microbiota and therapies? A comprehensive platform to investigate bacteria as immuno-modulating vectors or agents.

[Webinar] How to assess the interplay between tumor, microbiota and therapies?

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Sylvie Maubant, PhD, Study Director
25 June 2020
5 pm CEST


A comprehensive platform to investigate bacteria as immuno-modulating vectors or agents.
Preclinical and clinical studies have shed light on the beneficial role of bacteria for cancer therapy. Indeed, these works have demonstrated that these microorganisms have properties that allow them to selectively colonize tumor tissue and that they could also be considered as predictive drug efficacy biomarkers. Based on these results, bacteria are now used 1) for delivering therapeutic proteins into tumor cells or antigens into body, 2) for shaping gut microbiota.
Ultimately these approaches lead to the activation of an immune response against the tumor. Owing to our scientific and technological expertise at manipulating microbes, Oncodesign proposes tailor-made strategies to clients for investigating the efficacy of their bacteria-based treatments and/or the effect of their therapies on microbiota in vitro and in vivo.

Key learning objectives

  • Introduction to bacteria-mediated cancer therapy.
  • How can Oncodesign support your evaluation of bacterial therapies and/or the impact of your treatments on microbiota?
  • Case study examples

Discover our speaker Sylvie Maubant

Sylvie Maubant has more than 15 years of experience in preclinical research in oncology field.
She obtained a Ph.D in Biology, Medicine and Health from the University of Caen in France then she continued her career as a postdoctoral researcher at several institutes to work on projects related to the identification of new therapeutic targets, drug development and/or validation of therapeutic tools in collaboration with industry. In 2014, Sylvie joined Oncodesign in vivo department as a study director.
Since 2018, she has been mainly involved in bacteria-oriented programs for clients

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L’évaluation de l’immunothérapie du cancer nécessite l’utilisation de modèles animaux précliniques appropriés reflétant suffisamment la situation physiologique chez l’homme.

[Webinar] How to recruit immune cells against tumor? Bispecific compounds are the key for new oncology therapeutic strategy

[Webinar] How to recruit immune cells against tumor? Bispecific compounds are the key for new oncology therapeutic strategy

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18 June 2020
5pm CEST


Bispecific compounds are now considered as a new therapeutic strategy in oncology.
A number of bispecific compounds are under development at various clinical stages and two have already been approved. Given that these compounds are antibody-like and species-specific, new tools are subsequently needed to characterize them on a preclinical level.
From in vitro models up to in vivo humanized mouse models, including imaging as an option to track immune cells, all of these strategies will be exemplified in the context of compounds that recruit immune cells against tumors.

Key learning objectives

  • In vitro characterization
  • In vitro pharmacology
  • In vivo pharmacology (incl. Imaging) 

Discover our speaker Jean-François Mirjolet

Jean-François has been working for Oncodesign for 17 years. Jean-François obtained his Ph.D. from the University of Nancy, France, in cellular pharmacology of anticancer drugs, followed by post-doctoral position at the IRIBHM, Brussels, Belgium, in chemokines and chemokine receptors implication in cancer cell migration. At Oncodesign, Jean-François started as a study director and then the position of Technology Director, directly supporting our Business Development activity and working closely with our clients to select the most appropriate study designs for the evaluation of their therapies through preclinical studies. Jean-François has been the Head of the In Vitro Sciences Department since 2018. In this capacity, he manages both services and R&D related in vitro activities.

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L’évaluation de l’immunothérapie du cancer nécessite l’utilisation de modèles animaux précliniques appropriés reflétant suffisamment la situation physiologique chez l’homme.