Note: This article was developed for Bio Europe Supplement, EBR Autumn Edition 2024, Samedan Ltd
Discover how an optimized hit identification strategy, integrating advanced tools – including AI and machine learning – can provide the best possible chemical starting points. Explore how Evotec’s collaborative approach is key to identifying high-quality hits at lightning speed, saving on costs and time, while reducing the risk of attrition.
Tags: Articles & Whitepapers, Hit & Target ID/Validation, In vitro Biology
At Evotec, our expert immunologists drive your immuno-oncology projects from target identification to clinical trials. We offer comprehensive support for integrated projects and specialized expertise at critical stages. Our services include bespoke in vitro immunological assays, genetic engineering of primary immune cells, and advanced preclinical models. By integrating cutting-edge technologies and leveraging our extensive clinician network, we ensure the successful translation of innovative cancer immunotherapies from the lab to the clinic. Partner with Evotec to advance your cancer immunotherapy research and achieve breakthrough results.
Tags: Oncology, immuno-oncology, Fact Sheets, In vitro Biology, Proteomics, Metabolomics & Biomarkers, Cell Therapy
Quality Hits At Lightning Speed - Accelerated Hit Finding Through Innovative Screening Approaches.
Read our fact sheet to learn about Evotec’s capabilities, infrastructure and expertise for hit identification and HTS projects.
Tags: Fact Sheets, Hit & Target ID/Validation, In vitro Biology
In the evolving landscape of cancer treatment, Immuno-Oncology (IO) has been at the forefront for the past 15 years, revolutionizing our approach to battling this formidable disease. Immunotherapy, which harnesses the body's immune system to fight cancer, offers hope where traditional therapies have often fallen short. For instance, in advanced stage IV melanoma, the median survival has improved from 6 months to 6 years over the past decade thanks to immunotherapy.
However, the journey from discovery to clinical application is fraught with challenges. Why do some patients respond to immunotherapy while others do not? What opportunities exist for developing the right combination therapies? How can we better select the right cancer indications for a particular IO target? How can we ensure the success of these treatments across diverse patient populations?
At Evotec, our immunologists are equipped with the expertise and experience to support your IO projects from target identification through to clinical trials. Whether you require a comprehensive and strategic partnership or targeted support at critical stages, our capabilities can synergize with your efforts to make a tangible difference.
Our team’s knowledge spans from innate to adaptive immunity, providing a robust foundation for developing cutting-edge cancer immunotherapies. We offer:
● Genetic Engineering of Primary Immune Cells: Optimizing target validation for effective therapy development.
● Bespoke In Vitro Immunological Assays: Custom-designed assays to evaluate immune responses and the potency of immunotherapeutic candidates.
● Single-Cell Level Immunotherapy Assessment: Utilizing Immunological Synapse technology for precise drug discovery.
Moving forward with candidates within the drug discovery journey requires robust and tailored in vivo models for IO:
● Syngeneic Mouse Models: Developed with various tumor-immune phenotypes and responsiveness to checkpoint inhibitors; these models help in assessing therapeutic efficacy, modulation of the immune response (tumor microenvironment and periphery), as well as pharmacodynamics features (PK/PD).
● Humanized Mouse Models: Presenting a functional human immune system with the possibility of xenografting a human tumor. These models are pivotal for particular therapeutic modalities such as biologic therapeutics (e.g., immune cell engagers) or cell therapies; they could also be interesting for early toxicology studies looking at immune-related adverse events.
To bridge the gap between in vitro models done with primary human immune cells isolated from healthy donors and in vivo models in the drug discovery process:
● Broad Clinical Network: Collaborations with hospitals and clinicians to select the relevant samples for the project.
● Translational Validation of Therapies: Access to cancer patient samples ensures that therapies are effective in a patient context.
● Enhanced Target Validation: Possibility to develop on-target biomarker assays or validate target expression in a particular indication.
Our approach integrates cutting-edge technologies to de-risk your drug development strategy:
● High-Throughput Imaging and Analysis: Tools like the ImageStream X and Operetta provide high-speed, high-resolution insights into immune cell interactions.
● Complex Flow-Cytometry and Functional Assays: These analyses on fresh human tumor samples facilitate target engagement validation and biomarker identification.
● Omics Technologies: Including scRNAseq, TCR sequencing, and proteomics, to uncover novel biomarkers and therapeutic targets.
By incorporating biomarker strategies early in the discovery process, we enhance the understanding of disease mechanisms and improve patient stratification for clinical trials. Our efforts in precision medicine are aimed at identifying the right therapeutic interventions for the right patients, thereby increasing the likelihood of clinical success.
Evotec’s experienced IO team supports your projects from the lab bench to the patient bedside. Our comprehensive services include:
● Functional In Vitro Immunological Assays: Supporting programs for small molecules, biologics, and cell therapies.
● In Vivo Rodent Models: Essential for preclinical testing of therapeutic efficacy and safety.
● Translational Research and Patient Sample Access: Enhancing the relevance and translatability of preclinical findings.
Our integrated approach, combining deep immunological expertise with advanced technologies and translational capabilities, ensures that we address the complex challenges of IO drug discovery. By partnering with Evotec, you gain access to a wealth of knowledge and resources designed to propel your project forward, from the initial stages of discovery to the clinical validation of novel therapies.
For more information on how Evotec can support your Immuno-Oncology projects, visit our website or contact us at info@evotec.com.
The revolution in cancer immunotherapy is just beginning, and the journey to effective treatments requires collaboration, innovation, and expertise. At Evotec, we are committed to advancing the field of Immuno-Oncology, providing the tools and support necessary to transform groundbreaking discoveries into life-saving therapies. Join us in this mission and let’s make a difference in the fight against cancer.
Contact us today to speak with one of our immunologists and explore how we can progress your IO projects together.
Tags: Oncology, Blog, Biologics, In vitro Biology, Immunology & Inflammation, Rare Diseases, in vivo
Targeting RNA represents a paradigm shift for drug discovery. The ability to seek out and destroy, or modify, a faulty RNA template, before the toxic protein has even been made, has only recently begun to be harnessed for the benefit of patients.
At the time of writing, 21 Oligonucleotide drugs have been approved for human use, with an exponential increase in clinical trials and development projects involving this new modality.
There exist several different mechanisms of action for Oligonucleotide drugs, all of which are transient and reversible and do not lead to alteration of patient DNA, unlike Gene therapy.
Antisense Oligonucleotides harness endogenous systems already existing within a cell to achieve their purpose, with the only limitation being accessibility of the target tissue.
Once bound with great specificity to its RNA target, a short synthetic Oligonucleotide can trigger degradation, upregulation of the translated protein, or alteration of a splicing event leading to a correctly folded protein. Longer Oligonucleotides can fold into 3 dimensional shapes called Aptamers with similar target affinities and applications as antibodies, and shorter Oligonucleotides can act as MicroRNA mimetics or antagonists to alter multiple targets or pathways concurrently with subtle but broader effect.
The precision of an Oligonucleotide and its ability to correct a faulty RNA produced by an error in the genetic code, lends itself to applications in the fields of rare disease therapeutics and toxic gain of function mutations. The field of Oligonucleotide therapeutics is developing to address this as a whole and to pioneer a new preclinical and regulatory path that could be adapted for these unique disease biologies to make this type of therapeutic innovation more accessible.
Evotec is a leader in integrated end-to-end Research and Development and has built substantial drug discovery expertise and technical capabilities that can drive new innovative and diverse modalities into the clinic. In addition, Evotec has developed a deep internal knowledge base in key therapeutic areas including neuroscience, pain, immunology, respiratory, women’s health, aging, fibrosis, inflammation, oncology, metabolic and infectious diseases. Leveraging these skills and expertise, Evotec successfully delivers on superior science-driven discovery and development alliances with pharmaceutical and biotechnology companies.
The global interest in this new modality area has led to high demand in Oligonucleotide synthesis and related chemistry applications, from modified Oligonucleotides to conjugates and complex formulations.
Evotec offers Oligonucleotide research and development capabilities as well as ligand and linker chemistry expertise to support projects from discovery through to development.
This fully integrated suite of capabilities allows for the synthesis, purification, isolation, and quality control of complex modified Oligonucleotides (ASOs, siRNAs, etc) on a scale from milligrams up to 25 g (up to 12 millimoles). The objective is to support Oligonucleotide drug discovery and development projects from the earliest phases of discovery, such as the generation of screening libraries, up to the selection of a preclinical development candidate followed by manufacture and release of material to support initial preclinical development studies.
All these activities are supported by an experienced Oligonucleotide chemistry team operating across two sites and at different scales, to ensure flexible support for projects with highly efficient information and process transfer.
Evotec capabilities also include expert analysts for Analytical Development and QC, capable of developing and validating the analytical procedures needed for a full characterization and routine testing of Oligonucleotide drug substances up to and including IND enabling studies. In addition, Evotec’s support can encompass the release of preclinical batches according to regulatory requirements, including stability and formulation studies.
The journey to commercialization can be challenging. Scaling up production while maintaining process consistency, product quality, and regulatory compliance, requires expert process development capabilities, and the adoption of innovative science and risk management methodologies. A common pitfall for the Sponsor of an innovative therapy is to under-estimate the complexity and intricacy of this enterprise, which involves the coordinated optimization of strategies for process control, risk management, data management, and supply chain management.
With ever-evolving regulatory requirements and the increasing urge to shorten drug development timelines, getting your drug to market can seem like a daunting undertaking. That’s why taking some of the pressure off your organization by outsourcing your drug development and manufacturing activities to an expert partner can be the smartest decision. This will ensure your drug is commercialized in the fastest and most cost-efficient way possible, utilizing expertise, facilities, equipment, and processes to anticipate and overcome any challenges thrown at your program with ease.
Evotec offers an integrated end-to-end solution for innovative drug R&D, with the capabilities to support all phases of your drug development program. Your projects are in safe hands with our team of expert scientists who are pioneers in QbD, process design, scale-up, and validation, operating to full cGMP within FDA, MHRA, AIFA and BfArM approved facilities.
Our experts are just a click away!
Don’t miss our educational webinar series on “Oligonucleotides Therapeutics: Discovery to Development”
Tags: Drug Discovery, Medicinal Chemistry, Blog, Formulation & CMC, Hit & Target ID/Validation, In vitro Biology, IND Enabling Studies/Preclinical Development, oligonucleotides
Autoimmune diseases (ADs) represent a significant challenge in healthcare, affecting millions worldwide. These conditions arise when the body's immune system mistakenly attacks healthy tissues, leading to chronic inflammation and tissue damage. While current treatments for ADs focus on immunosuppression, they often come with significant side effects and provide only symptomatic relief. In recent years, there has been growing interest in cell-based therapies, particularly CAR (chimeric antigen receptor) cell therapy, as a potential solution to address the underlying causes of ADs.
Autoimmune diseases encompass a wide range of conditions, including rheumatoid arthritis, lupus, multiple sclerosis and inflammatory bowel disease, among others. Despite their diverse manifestations, these diseases share a common underlying pathology of immune dysregulation. In healthy individuals, the immune system is finely tuned to distinguish between self and non-self antigens, but in autoimmune disorders, this distinction becomes blurred, leading to an attack on the body's own tissues.
CAR cell therapy offers a promising approach to treating ADs by depleting disease-driving immune cells and rebalancing immune homeostasis. CAR T cells, which are engineered to express synthetic receptors targeting antigens expressed on the surface of pathogenic cells, have shown remarkable success in treating certain cancers. Now, researchers are exploring the potential of CAR T cells and their counterparts, CAR iNK (natural killer) cells, in targeting the aberrant autoreactive cells implicated in autoimmune diseases to reset the immune sytsem1. We believe that cell therapy approaches could provide long-lasting drug-free remission and potentially a curative treatment for AD patients.
CAR T cell therapy first emerged as a groundbreaking treatment modality for hematological malignancies, such as leukemia and lymphoma. Building on this clinical success, researchers have recently turned their attention to applying CAR cell therapy to treat autoimmune diseases.
In the context of ADs, CAR T cells have been investigated for their ability to target autoreactive T cells or B cells. B cells, in particular, play a central role in many autoimmune disorders by producing autoantibodies and driving inflammation. One promising target for CAR cell therapy in ADs is the cell surface protein CD19. High-level expression of CD19 is maintained throughout the majority of B-cell differentiation stages. By targeting CD19-positive B cells, CAR T cells or CAR NK cells can selectively eliminate the autoreactive B cell populations responsible for driving autoimmune responses2.
A recent early clinical study showed promising results for using CD19 CAR T cell therapy to treat ADs. Patients with systemic sclerosis, severe Systemic Lupus Erythematosus (SLE), and idiopathic inflammatory myositis showed remission following therapy3. However, CAR NK cell therapy may be beneficial over CAR T cell therapy, particularly in ADs that have dysfunctional T cells. CAR T cell therapy may also result in side-effects such as GvHD (Graft-versus-host disease, worsening the AD symptoms), neurotoxicity, and cytokine release syndrome; CAR NK cell therapy may offer a safer alternative4.
Despite the potential of CAR cell therapy in ADs, several challenges remain, including scalability, persistence, and off-target effects. Evotec's innovative approach to addressing these challenges involves the use of induced pluripotent stem cells (iPSCs) to generate allogeneic off-the-shelf CAR iNK cells with enhanced scalability and precision. iPSCs, reprogrammed from adult somatic cells, offer a potentially inexhaustible source of immune cells that can be genetically engineered and differentiated into various cell types to tackle a range of diseases.
A study by researchers at Evotec investigated the performance of iPSC-derived CD19 CAR iNK cells as a novel therapeutic approach for ADs. Using Evotec’s validated GMP iPSC line, researchers produced genetically modified cells with a knock-in of CD19-CAR. The modified cells successfully differentiated into CD19 CAR iNK cells using a feeder-free 3D differentiation process, which could be confirmed by flow cytometry. The established protocol can ensure high purity and functionality of the resulting cells. Results showed that iNKs generated from the GMP iPSC line were homogenous and phenotypically comparable to blood-derived (BD) NK cells form healthy donors.
Figure 1: Cytotoxicity against SLE patient B cells. NK killing assays of effector cells - iNK without CAR (WT), CD19 CAR iNK or healthy donor BD NK cells (BD-NK) co-cultured 1:1 (E:T) with SLE patient B cells, + 10μg/ml anti-CD20 antibody (Obinutuzumab (Obi)) or isotype control (Iso) (n=2).
In vitro experiments demonstrated the cytotoxic effector function of CD19 CAR iNK cells in selectively targeting and eliminating CD19-positive B cells. Co-culture assays using patient-derived primary B cells from patients with SLE autoimmune disease, showed robust cytotoxicity of CD19 CAR iNK cells. The CD19 CAR iNK cells were more efficient than iNK cells without a CAR or BD NK cells in depleting the patient-derived primary B cells. These findings highlight the therapeutic potential of CD19 CAR iNK cells in treating ADs, offering a targeted and scalable alternative to conventional immunosuppressive therapies.
Evotec's commitment to allogeneic cell therapy innovation is exemplified by its scalable therapeutics approach, which leverages cutting-edge technologies and infrastructure to develop next-generation therapies for ADs. Central to this approach is the use of iPSCs as a platform for generating CAR iNK cells with enhanced scalability and precision. By introducing CARs targeting CD19 into iPSCs and differentiating them into iNK cells, Evotec aims to create scalable and precise off-the-shelf therapies for ADs.
Figure 2: Evotec’s pipeline to co-create iPSC-based cell therapeutics with partners in Inflammation & Immunology.
Evotec's end-to-end process for iPSC-based therapeutics encompasses differentiation, gene editing, preclinical and clinical development, ensuring the efficient generation and characterization of CAR iPSC-derived cells. By utilizing validated GMP iPSC lines and GMP-compatible differentiation protocols, Evotec ensures the safety and quality of its allogeneic cell therapy products, paving the way for clinical translation.
Figure 3: Evotec’s end-to-end process for iPSC-based therapeutics.
The scalability of Evotec's approach enables the production of large quantities of CAR iNK cells, making them suitable for widespread use in treating ADs. Additionally, the precision of iPSC-derived CAR iNK cells allows for targeted and personalized therapies tailored to individual patients' needs, reducing the risk of off-target effects and enhancing treatment efficacy.
Evotec's iPSC-derived CD19 CAR iNK cells represent a promising new approach to treating autoimmune diseases. By harnessing the power of iPSC and CAR technology, allogeneic cell therapy can help revolutionize the treatment landscape for ADs, offering patients a targeted, scalable and potentially curative alternative to conventional therapies.
As research in this field continues to advance, Evotec remains at the forefront of allogeneic cell therapy innovation, driving the development of next-generation treatments for ADs (Figure 2). Evotec’s GMP-compliant production pipelines provides an efficient, reproducible, and scalable way to produce CAR iNK cells derived from iPSC for clinical development. With its commitment to precision medicine and scalable therapeutics, Evotec is well-positioned to meet the growing demand for effective and accessible off-the-shelf therapies for autoimmune diseases.
See more iPSC-based Cell Therapies for I&I Diseases
To discover more about this research, download our scientific poster
(1) Blache, U.; Tretbar, S.; Koehl, U.; Mougiakakos, D.; Fricke, S. CAR T Cells for Treating Autoimmune Diseases. RMD Open 2023, 9 (4), e002907. https://doi.org/10.1136/rmdopen-2022-002907.
(2) Jin, X.; Xu, Q.; Pu, C.; Zhu, K.; Lu, C.; Jiang, Y.; Xiao, L.; Han, Y.; Lu, L. Therapeutic Efficacy of Anti-CD19 CAR-T Cells in a Mouse Model of Systemic Lupus Erythematosus. Cell. Mol. Immunol. 2021, 18 (8), 1896–1903. https://doi.org/10.1038/s41423-020-0472-1.
(3) Müller Fabian; Taubmann Jule; Bucci Laura; Wilhelm Artur; Bergmann Christina; Völkl Simon; Aigner Michael; Rothe Tobias; Minopoulou Ioanna; Tur Carlo; Knitza Johannes; Kharboutli Soraya; Kretschmann Sascha; Vasova Ingrid; Spoerl Silvia; Reimann Hannah; Munoz Luis; Gerlach Roman G.; Schäfer Simon; Grieshaber-Bouyer Ricardo; Korganow Anne-Sophie; Farge-Bancel Dominique; Mougiakakos Dimitrios; Bozec Aline; Winkler Thomas; Krönke Gerhard; Mackensen Andreas; Schett Georg. CD19 CAR T-Cell Therapy in Autoimmune Disease — A Case Series with Follow-Up. N. Engl. J. Med. 2024, 390 (8), 687–700. https://doi.org/10.1056/NEJMoa2308917.
(4) Műzes, G.; Sipos, F. CAR-Based Therapy for Autoimmune Diseases: A Novel Powerful Option. Cells 2023, 12 (11), 1534. https://doi.org/10.3390/cells12111534.
Tags: Induced pluripotent stem cells, Blog, Biologics, In vitro Biology, In vivo Pharmacology, Immunology & Inflammation
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
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
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
Biomarkers are very useful tools for drug developers as well as for clinicians. In drug research and development, they add value as they improve the success rate of clinical trials. In the clinic, they validate the eligibility of patients as well as the efficacy of an approved treatment. In the recent Evotec webinar on aging, Elizabeth van der Kam, SVP, Translational Biomarkers and Human Sample Management, gave an overview on biomarkers in general and the role of biomarkers in aging.
In fact, the success rate of clinical studies can by doubled by introducing biomarkers early on, that can predict efficacy and potential safety issues. Biomarkers also may be important to reduce costs by running smarter trails in smaller groups of patients and if translated to companion diagnostics, biomarkers enhance the readiness of payers to reimburse a novel drug, but they also enable higher profits as the drug can be sold together with a diagnostic test. Therefore, Evotec´s strategy is to develop a biomarker as early as possible during the R&D process.
Types of biomarkers
There are several types of biomarkers. Useful for early studies are biomarkers that demonstrate target engagement, meaning they show that a drug candidate hits the target in the relevant organ and triggers a response. However, target engagement not necessarily means that this is relevant for the disease.
Another classification consists of surrogate biomarkers, which exhibit correlations with the disease or its progression and could hold relevance in the context of the disease More useful are efficacy markers which are not just correlated but causative for the disease. Another important class of biomarkers are safety biomarkers which, as an example, alert a clinical trial leader or a physician that the drug also hits another target and could potentially cause an issue. Then there are stratification markers indicating the likelihood of a patient to respond to treatment. This is important as non-responders should not be included in trials or prescribed an ineffective treatment. Last but not least, there are diagnostic and prognostic biomarkers that help to better understand the disease and its progression, to establish the right dosage, assess efficacy and predict disease progression and monitor the patients.
In any case, a biomarker needs to be translatable and relevant, and its measurement should be feasible, robust, reliable, and durable.
Biomarkers in aging
The situation is complex in aging. Chronological age is not the best inclusion criterium for clinical trials of medicines trying to improve the health span of elderly patients as chronological age can be very different from biological age.
But how to define biological age? What markers are out there? Of course, there are a lot of markers of biological age, e.g., body composition, body fat, physical appearance and function, muscle mass, grip strength, walking speed, balance, wrinkles, grey hair, but also blood-based changes in terms of hormone and vitamin levels and progressing diseases such as poor eyesight, osteoporosis, declining kidney function, and many more.
However, none of these markers is sufficient as a stand-alone data point. Some of the changes observed in elderly people can also be found in younger people or in patients with non-age-related diseases. The best biomarkers are the ones that can be established without subjective assessments.
The situation is further complicated by the fact that aging is not a disease, and that any intervention should be made early before the onset of typical signs of aging. Ideally, one would have biomarkers that can tell which category of older people will develop certain diseases. At present however, there are biomarkers indicating changes in many pathways and targets, but these often only indicate a certain chance of getting a disease.
The challenge
At present, biomedicine does not have access to markers that can predict certain biological deteriorations, let alone predict potential success of a treatment. And how to define a subpopulation and forecast treatment success without waiting for years to see an effect?
Currently one of the best overall indicators of biological aging is inflammaging. It demonstrates changes in the immune system, inflammation, and an imbalance in the innate or the adaptive immune system, thereby predicting a high risk of unhealthy aging. However, inflammaging can also be caused by lifestyle and gender, so it is not an ideal biomarker. Recently, under review of the U.S. National Institute for Aging, the TAME BIO (Targeted Ageing with MEtformin) project tried to establish a basis for future biomarker discovery and validation and accelerate the pace of ageing-research.
The project started out with more than 200 potential biomarker candidates that were screened for feasibility, dependency on gender, and environmental factors, etc., bringing down the list of candidates to less than 90. Then they were assessed for disease-relation, robustness, their association to multi-morbidity and the usefulness to clinical trials, leaving a final set of eight candidates. This was, however, a purely theoretical exercise and whether these candidates are useful in real life needs to be proven. At present, the jury is still out on useful biomarkers for trials and therapies to prolong health span and quality and duration of life.
Learn more in the webinar "A Spotlight on Ageing" by Elizabeth van der Kam, SVP, Translational Biomarkers and Human Sample Management at Evotec
Tags: Articles & Whitepapers, Blog, In vitro Biology, Proteomics, Metabolomics & Biomarkers, Age-Related Diseases, Clinical Development
