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Evotec

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Discover Evotec’s Best in Class In Vivo Human Antibody Discovery Platform

Posted by Evotec on Jan 5, 2022 11:21:51 AM

Evotec strives to provide partners and customers with less expensive, faster, and more flexible approaches for discovering, developing and manufacturing biotherapeutics.

With the acquisition of Just Biotherapeutics in 2019, Evotec made a major push into biologics, and has successfully built a fully-integrated platform to drive monoclonal antibody (“mAb”) programmes from concept through to commercialisation. The company generates antibody lead candidates by providing access to in vivo and in vitro sources of antibodies, combined with state-of-the-art technologies to ensure success for a broad range of targets and disease states. In addition, if needed, selected lead candidates can be further optimised using powerful computational platforms such as Evotec’s proprietary Abacus™ in silico tool suite to enhance the productivity, but also ease of manufacturing and formulation stability.

For in vivo immunisation, Evotec is offering the ATX-GxTM mouse platform developed by its collaboration partner Alloy Therapeutics. This platform is a suite of immunocompetent transgenic mice for best-in-class in vivo discovery of fully human monoclonal antibodies. These mice are engineered to drive the greatest potential diversity and broadest epitopic coverage of unique human antibodies binding to a specific target of interest.

ATX-GxTM mice provide:

  • a fully human heavy chain repertoire,
  • human kappa and human lambda chain repertoire,
  • haplotype diversity, and
  • limited immunodominance.

Taken together, these immunocompetent transgenic mice represent the complete functional human antibody repertoire, and their fully functional, robust immune response is equivalent to the response of wild type mice. They are also available on multiple genetic backgrounds such as BALB/c or BL/6.

ATX-GxTM has been extensively validated and continuously expanded for more than 12 years and is currently used by over 75 antibody discovery groups in large biopharma and small-to-midsize biotech companies as well as academic research labs.

DDup#11_PPT-Grafiken_211102_Fig3

Following immunisation, Evotec is combining traditional hybridoma technology with automated devices for high throughput clone selection, screening, recombinant expression and purification to shorten and simplify the process of hybridoma establishment. Screening is performed with high-throughput technologies, such as the iQue® Advanced Flow Cytometry Platform. Next-generation sequencing is used to obtain VH/VL information, followed by an in silico analysis using Just – Evotec Biologics Abacus® software tool. Once VH/VL information is available, several hundred mAbs can be produced in parallel in small scale. This high quality material can then be used for further downstream characterisation, such as functional activities that allow the selection of potential lead candidates.

This streamlined workflow to generate high-quality antibody panels for functional assessment adds to Evotec’s comprehensive suite of large molecule discovery tools, disease biology, state-of-the-art cell line development, machine learning design tools, manufacturing, preclinical IND-enabling studies, as well as FIH clinical support, and commercialisation.

Evotec’s AI-driven antibody discovery can be accessed as stand-alone services or through Evotec’s seamlessly integrated antibody drug discovery platform

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Tags: Blog, Biologics, In vivo Pharmacology

AI-Driven Antibody Discovery DDup #11

Posted by Evotec on Jan 4, 2022 3:42:49 PM

The 11th edition of our Drug Discovery Update (DDup) is dedicated to biotherapeutics discovery and development with a focus on artificial intelligence and machine learning and its opportunity in transforming antibody discovery.

In this edition, it covers:

  • an introduction to antibodies including:
    • an overview of monoclonal antibodies as therapeutic agents
    • a history of antibody drug discovery platforms
  • how Just - Evotec Biologics are exploiting artificial intelligence and machine learning to generate a novel humanoid antibody library biased towards highly desirable features
  • a description of the process from idea to IND and beyond for antibody discovery and development
  • facts and figures on the market for therapeutic antibodies
  • an overview of function-focused antibody (FFmab) screening
  • an interviews with the experts

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Tags: Articles & Whitepapers, Biologics

BTS Annual Congress 2022

Posted by Evotec on Jan 4, 2022 3:14:14 PM

Date: 4-6 April 2022

Location: Hilton Gateshead, Newcastle UK

Attendee: Oksana Nikolayenko & Tim Potter

Learn more about BTS Annual Congress 2022

Tags: Events, Cyprotex

Discovery of Pyrazolo[1,5-a]pyrazin-4-ones as Potent and Brain Penetrant GluN2A-Selective Positive Allosteric Modulators Reducing AMPA Receptor Binding Activity

Posted by Evotec on Dec 22, 2021 9:22:41 AM

N-Methyl-D-aspartate receptors (NMDARs) are members of the ionotropic glutamate receptor family and play a crucial role in learning and memory by regulating synaptic plasticity. Activation of NMDARs containing GluN2A, one of the NMDAR subunits, has been recently identified as a promising therapeutic approach for neuropsychiatric diseases such as schizophrenia, depression, and epilepsy.

Identification of a new hit for GluN2A PAMs is however difficult due to the similarity of PAM binding sites between GluN2A and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPARs), another member of the ionotropic glutamate receptor family.

In this collaborative publication with Takeda, we focus on:

  • Identification of an hit compound with moderate AMPAR-binding activity, though a Ca2+ influx-based high throughput screening campaign with a compound set including an internal AMPAR-focused compound library
  • The strategy using a structure-based drug design (SBDD) approach to minimize the AMPAR-binding activity while improving GluN2A activity
  • The use of the potent and brain-penetrable GluN2A-selective positive allosteric modulators GluN2A PAM discovered as in vivo tool exhibiting significant neuroplastic enhancement in the rat hippocampus 24h after oral administration, having potential application for cognitive enhancement in neuropsychiatric diseases

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Tags: Neuroscience, Medicinal Chemistry, Articles & Whitepapers, In vitro Biology, Age-Related Diseases

Mouse Pneumonia Model by Acinetobacter baumannii Multidrug Resistant Strains

Posted by Evotec on Dec 21, 2021 2:49:52 PM

Pneumonia induced by multidrug resistant (MDR) Acinetobacter baumannii strains is among the most common and deadly forms of healthcare acquired infections. Animal models play a critical role during the preclinical assessment of novel therapeutic approaches, however, only a self-limiting pneumonia with no or limited local bacterial replication is frequently obtained when MDR A. baumannii is the pathogen.

To strengthen and characterise a sustained lung infection model, in this publication, we focus on:

  • the ability of intranasal inoculation, intratracheal instillation and oropharyngeal aspiration methods of administration of the bacterial challenge to induce a robust pneumonia in mice
  • the characterisation of the infection model obtained after intratracheal instillation and oropharyngeal aspiration in terms of histopathological examination of pulmonary lesions, biomarkers of inflammation and leukocytes cells infiltration after treatment with either vehicle or with the antibiotic tigecycline efficacious into reducing lung bacterial load.

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Tags: Respiratory, Articles & Whitepapers, In vivo Pharmacology

Regulated LC/MS Bioanalysis Fact Sheet

Posted by Evotec on Dec 21, 2021 1:56:16 PM

Learn more about Evotec's regulated LC/MS bioanalysis capabilities and expertise including:

  • High quality service across all phases of pre-clinical and clinical drug development in compliance with GLP and GCP regulations
  • More than 25 years of experience to perform LC/MS activities in a regulated environment
  • Extensive bioanalytical method development expertise to meet the most demanding and challenging client needs
  • Multidisciplinary collaboration enabling integrated solutions to accelerate the drug development process

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Tags: Fact Sheets, Proteomics, Metabolomics & Biomarkers, IND Enabling Studies/Preclinical Development, Sample Management

Small-Molecule Inhibition of METTL3 as a Strategy Against Myeloid Leukaemia

Posted by Evotec on Dec 21, 2021 1:49:54 PM

This article published in Nature describes a first-in-class METTL3 inhibitor for the treatment of acute Myeloid Leukaemia.

The publication covers:

  • Development of STM2457 following high-throughput screen
  • Selectivity screening across the panel of 45 human methyltransferases
  • Crystal structure of METTL3-14 complex with STM2457, part of structure-based drug design strategy for this target
  • Compound validation in cellular assays and in vivo efficacy

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Tags: Medicinal Chemistry, Oncology, Articles & Whitepapers, SBDD, crystallography, epigenetics

Polymerase Chain Reaction Services Fact Sheet

Posted by Evotec on Dec 16, 2021 6:24:35 PM

Learn more about Evotec’s polymerase chain reaction (PCR) services including:

  • Therapeutic modalities
  • Sample management capabilities
  • PCR applications 
  • Quantitative real time PCR (qPCR) and reverse transcription qPCR (RT-qPCR) applications, including copy number estimation assays, gene expression profiling and genotyping assaysRegulated PCR services

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Tags: Fact Sheets, Proteomics, Metabolomics & Biomarkers, IND Enabling Studies/Preclinical Development, Sample Management

Ligand Binding Assays Fact Sheet

Posted by Evotec on Dec 16, 2021 12:36:06 PM

Learn more about our ligand binding assays and how they can support biological drug testing in a regulated environment, including:

  • Regulated bioanalysis
  • Immunogenicity
  • Immunotoxicity
  • Biomarkers (safety and efficacy)
  • Clinical Pathology
  • Sample Management
  • Additional activities

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Tags: Fact Sheets, Proteomics, Metabolomics & Biomarkers, IND Enabling Studies/Preclinical Development, Toxicology & Safety, Sample Management

Recombinase-based Targeted Integration Systems for Exogenous Protein Production

Posted by Evotec on Dec 14, 2021 6:37:44 PM

Stable expression of recombinant protein therapeutics in CHO cells often relies on random or semi-random genomic integration events which results in a widely heterogenous cell population. This leads to significant effort in clone screening during cell line development in order to identify clones with high expression, growth and product quality. 

In this publication, we focus on:

  • the development of two targeted integration systems that express high levels of recombinant protein in CHO cells by: 
    • the installation of rationally designed piggyBac-based chromosomal landing pads
    • the use of site specific recombinases including PhiC31 and CRE 
  • demonstration of the functional integration of several donor vectors encoding various therapeutic proteins including two monoclonal antibodies and one Fc-fusion molecule

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Tags: Articles & Whitepapers, Biologics, In vitro Biology