Download the highlights from our DCAT presentation to learn how continuous biomanufacturing reduces the environmental impact of antibody production.
The continuous manufacturing of therapeutic antibodies in agile facilities with a small cleanroom footprint allows:
Just-Evotec Biologic's unique continuous biomanufacturing platform for antibody therapeutics and innovative J.POD facility design are reducing manufacturing costs and increasing the sustainability of bioproduction.
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Tags: Presentations, Formulation & CMC, Biologics
4’-Phosphopantetheinyl transferase (PptT) is a crucial enzyme for the survival and virulence of Mycobacterium tuberculosis (Mtb), making it an attractive target for tuberculosis treatment. In recent research, our collaborators at University of North Carolina (UNC ); Weill Cornell Medical College, Texas Agricultural and Mechanical University (TAMU) explored ways to replace the amidinourea moiety in the previously known PptT inhibitor AU 8918. These findings hold promise for developing new drugs to combat mycobacterial infections.
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Evotec and Sanofi scientists, together with TBAlliance and Tuberculosis Drug Accelerator (TBDA) partners, have been involved in the discovery of sequanamycins, a class of compounds that combat drug-resistant tuberculosis. The original compound , the SEQ-503 was a macrolide from the Sanofi Natural Product patrimony, discovered in 1962 in Vitry-sur Seine and named after sequana, the seine goddess in the Gallo-Roman religion. Optimization of SEQ-503 has given rise to SEQ9 with a remarkable efficacy against Mycobacterium tuberculosis (Mtb).
Key findings:
Promising prospects for TB clinical candidates!
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We are honoured to be part of the TBDA consortium and would like to congratulate our colleagues on the release of their new publication
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Inflammatory Bowel Disease (IBD) is the umbrella term for a group of diseases characterized by chronic, idiopathic and remitting inflammation of the gastrointestinal tract. Common symptoms include diarrhea, abdominal pain, and fatigue. However, extraintestinal manifestations such as inflammatory arthralgias/arthritides, primary sclerosing cholangitis (PSC), ocular or cutaneous involvement are often present and add to the complexity of the clinical picture.
The two most common forms of IBD are Crohn's disease and ulcerative colitis. Crohn's disease can cause inflammation anywhere in the gastrointestinal tract from the mouth to the anus, while ulcerative colitis is usually confined to the colon, where it can cause inflammation and ulceration. In about one in ten people, the two diseases cannot be clearly distinguished, and the condition is called indeterminate colitis. With approximately 6-8 million IBD patients worldwide (2 million in Europe and 1.5 million in North America), there is a huge unmet medical need.
IBD is an immune-mediated disease, but the exact causes are unknown. Crohn's disease, for example, involves a complex interplay of genetic predisposition, immune dysregulation, environmental influences, and microbial factors.
This complexity poses many challenges for drug development, as exemplified by the recent failure of a drug approved for ulcerative colitis that failed in late-stage clinical trials for Crohn's disease. The important lesson here is the need for proper patient stratification.
With its multimodal approach and patient stratification tools, Evotec is well positioned to develop innovative medicines. The Company is focused on development of IBD medicines through in-house research and through collaborations. Evotec’s strategy is modality agnostic, utilizing Evotec’s entire scope of technology platforms - from small molecules to biologics as well as iPSC-based cell therapies.
Drug discovery at Evotec always starts with patient data. Evotec's drug discovery efforts are based on its proprietary panOmics approach and a proprietary portfolio of molecular patient databases (E.MPD). panOmics combines both data generation and analysis platforms to industrialize OMICs data generation and AI/ML-based omics data analysis. Based on proprietary molecular patient data, panOmics fundamentally improves the understanding of disease processes, in vitro and in vivo disease modeling, identification of novel high value targets, biomarker discovery and patient selection.
Another integral aspect of drug development at Evotec is precision medicine. For this approach, Evotec has developed a comprehensive patient stratification toolbox via its panOmics-driven diagnostic approach – EVOgnostic.
Therefore, IBD patients are an integral part of a pilot study in which Evotec is performing plasma and metabolomic analyses on samples from autoimmune disease patients to combine these clinical data with experimental data and data science approaches to identify potentially novel biomarker signatures.
Evotec aims to develop medicines that allow an early intervention and or, ideally, a cure for patients suffering from IBD. Evotec is engaged in several drug discovery programs tackling various aspects of IBD such as restoration of epithelial barrier function, modulation of inflammation, or resolution of intestinal fibrosis. Depending on the different aspects of the disease. Evotec’s experts are engaged in the IBD community and you can see our recent poster summarizing our IBD activities here.
Evotec also is constantly seeking to enhance its capabilities through strategic investments and collaborations. For example, in 2022 it invested in IMIDomics Inc., a company focused on immune-mediated inflammatory diseases (IMIDs). IBD constitutes a large part of IMIDs. The aim is to jointly develop and use IMIDomics' Precision Discovery™ Engine. This technology enables a deep understanding of how inflammatory diseases work in patients. It applies a combination of clinical and computational expertise to clinical data and biological samples from more than 17,000 patients in a biobank, generating proprietary biomolecular signatures.
With the Crohn's & Colitis Foundation, Evotec is advancing drug discovery for two novel IBD drug targets originating from academic research. The targets address fibrosis, the excessive accumulation of scar tissue in the intestinal wall, and the restoration of intestinal barrier function in IBD to reduce the increased intestinal permeability and chronic intestinal inflammation often seen in IBD patients.
Another challenge in IBD is the lack of adequate animal models. While more than two dozen mouse and rat models of colitis have been developed and implemented, the multifactorial etiology and highly heterogeneous manifestations of the disease have prevented the development of a model that fully represents the pathophysiology of human IBD and related complications. Each mouse model has its strengths in elucidating the pathogenesis of colonic inflammation, fibrosis, or CAC, but each has a self-limiting nature and shows marked variability in drug development. While these IBD models cannot fully recapitulate the disease features commonly seen in humans (genetic and environmental influences, gut microbiota interactions, etc.), they have led to the identification of three key elements for disease etiology: T lymphocytes (T cells) mediate chronic intestinal inflammation; intestinal inflammation is initiated and maintained by certain commensal intestinal bacteria; the onset and severity of the disease is largely dependent on the genetic background.
Therefore, Evotec has carefully selected several preclinical models that recapitulate key aspects of IBD: inflammation, leukocyte trafficking, breakdown of epithelial barrier integrity, T cell-mediated injury. These models are routinely used and complemented by the current gold standard: the T cell transfer model of chronic colitis. This mouse model best reflects the clinical pathology observed in IBD and dissects the initiation, induction, and regulation of T cell-mediated immunopathology.
In summary, Evotec is advancing breakthrough solutions for IBD using the most advanced technologies and platforms available. The Company's primary focus is on precision medicine and leading-edge approaches with the goal of providing tailored, effective, and minimally invasive treatments by taking into account the unique characteristics of each patient.
Tags: Induced pluripotent stem cells, Blog, In vitro Biology, In vivo Pharmacology, Immunology & Inflammation
Our recent publication, "Crystal structure of human peptidylarginine deiminase type VI (PAD6) provides insights into its inactivity", written in collaboration with our partners the Bill & Melinda Gates Foundation, has been accepted and released by the IUCr Journal. You can freely access it below.
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Tags: Articles & Whitepapers
IBD is a collective term for a range of clinical phenotypes caused by chronic, idiopathic and remitting inflammation of gastrointestinal tract. Crohn’s disease and ulcerative colitis are the two most common forms. Despite many advancements in the treatment of IBD, there remains a high unmet medical need to provide patients with an early intervention of highly effective therapy, preferably with curative potential.
Evotec is currently engaged in several drug discovery programs tackling various aspects of the disease such as restoration of epithelial barrier function, modulation of inflammation and intestinal fibrosis.
Given the heterogeneity of the disease, we actively invest into efforts leading to increased disease understanding and stratification of patients based on the disease endotypes.
Tags: Induced pluripotent stem cells, In vitro Biology, In vivo Pharmacology, Immunology & Inflammation
Biopharma and biosimilar companies are increasingly considering final production costs during early-stage process development rather than blindly racing to the clinic with an inferior process that must undergo redesign during subsequent clinical stages. Furthermore, the most advanced companies have a laser-like focus on product quality and consider this early on in development. This ensures that they progress the best product candidate into the clinic and avoid costly failures.
Just-Evotec Biologics is helping partners with antibody product candidates achieve the highest product quality with Cost of Goods Manufactured (COGM) below $50/g by combining our new J.CHO™ High Expression System (J.CHO™) with our unique continuous manufacturing platform. This extraordinary productivity represents a 75% reduction in industry standard COGM and is driven by the exceptionally high titers exceeding 4g/L/day in perfusion achieved utilizing J.CHO™. This performance is equivalent to a titer of approximately 30 g/L in fed-batch mode.
The J.CHO™ High Expression System comprises:
Just-Evotec Biologics developed product sales royalty-free cell lines to work perfectly with our upstream perfusion platform process and to scale seamlessly from 3L to 500L or 1000L bioreactors for clinical or commercial production.
Figure 1: Comparison of antibody yields in a 20-day continuous perfusion culture using an industrystandard CHO (Chinese Hamster Ovary) cell line
Seamlessly Integrating Product and Cell Line Development
Just-Evotec Biologics can leverage its unique J.MD™ Molecule Design suite of services to create multiple variants of an antibody candidate with improved developability characteristics. Our innovative high-throughput cell line development workflows allow us to produce up to 96 stable transfectant pools of variants and screen for productivity and product quality in parallel. Expression in stable pools produces more representative material for testing than from transients and by combining candidate development with cell line development we can save partners up to two months from your timelines. Most importantly, we identify antibody candidate variants with excellent manufacturability properties that have been shown to increase expression titer by 3-fold compared to parental sequences. We are delivering elevated levels of productivity for monospecific, bispecific- and multi-specific antibodies, Fc-fusion proteins, and single-chain Fv-antibody fusion proteins.
Perfusion Delivers Superior Product Quality
Just - Evotec Biologics has demonstrated that our perfusion platform delivers superior antibody product quality compared to fed-batch systems. Perfusion cultures give healthier cells with more complete glycosylation patterns while shorter product residence times in the bioreactor result in lower levels of oxidation and deamidation. We modulate media and bioreactor conditions to meet our partners’ product quality requirements.
Our J.CHO™ High Expression System provides partners with opportunities to refine the product quality attributes of their candidate. Partners may choose to do this for a variety of reasons, for example, we collaborate with companies developing biosimilar products that must match the product quality profile of innovator molecules and innovator companies developing novel biologics with unique features. Our additional capabilities within the J.CHO™ High Expression System service offering includes:
Our cell line development process can take as little as 14-weeks and uses the latest high-throughput cell culture methods and analytics to maximize efficiency.
Figure 2: Typical cell line development program at Just-Evotec Biologics to select clones with optimum performance in continuous perfusion culture; DWP = deep-well plates, tfxn = transfection
Highest Titers and Best Product Quality
In conclusion, in an increasingly mature and competitive market, biopharma companies are finding ways to differentiate themselves based on product quality attributes and on cost. Just-Evotec Biologics is supporting partners with its new J.CHO™ High Expression System that integrates with its continuous manufacturing platform for antibodies and delivers the highest titers in the industry and the product quality our partners demand.
Evotec specializes in antifungal drug discovery with a focus on WHO and CDC priority human pathogens such as Aspergillus fumigatus, Candida spp, and Cryptococcus neoformans. Their track record in late-stage drug discovery is proven, aided by a range of established in vivo models of fungal infection that facilitate seamless progression from in vitro to in vivo studies.
Their expertise encompasses various areas, including in vitro compound characterization, invasive and localized in vivo fungal infection models, PK/PD mathematical modeling, and custom assay development tailored to individual project needs. They conduct comprehensive antifungal susceptibility testing to industry standards and offer specialized modalities such as combination testing to determine synergy or antagonism.
Tags: Antibiotic Resistance, infectious diseases, Fact Sheets, In vitro Biology, Anti-Infectives