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.
The Evotec approach
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.
Selected collaborations
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.
Efficacy models in IBD
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.