Summary
Assessment of the anti-inflammatory efficacy of new drugs in humans during early drug development is challenging. In general, the therapeutic efficacy of such drug can only be estimated in phase 2. However, assessment of potential therapeutic efficacy in earlier stages greatly stimulates and facilitates a more rational development of anti-inflammatory compounds. CHDR bridges this gap by offering in vitro and ex vivo inflammatory challenges: reliable and accurate methodology to induce inflammatory responses in whole blood or isolated immune cells, allowing evaluation of the immune-modulating effects of new drugs in the earliest phase.
We provide a GCP and GCLP compliant environment that combines all the necessary components for successful drug development. We offer state-of-the-art assays carried out by fixed partner labs, ensuring the highest content (academic) quality combined with the mandatory process quality. Importantly, our well-established partnerships with leading Dutch academic medical centres and teaching hospitals facilitate access to key opinion leaders in various specialisations in internal medicine, as well as relevant patient populations. Our extensive collaborations with experts in the field of PK/PD modelling, systems biology, and systems pharmacology enable us to provide the most efficient and advanced data analysis. This integrated service promotes swift timelines and seamless cooperation for our sponsors.
Developing powerful and innovative new treatments
Advances in both basic and clinical immunology during the past few decades are now rapidly being translated into effective new treatments for a wide range of conditions. Because the immune system is highly complex, all new immune-based treatments must be evaluated thoroughly. Moreover, early clinical development of new immunologically active drugs requires both scientific and clinical expertise in order to ensure the subjects’ safety and to maximise the resulting clinical and economic benefits. CHDR is committed to overcoming the scientific and practical challenges associated with the early clinical development of these new treatments. Specifically, several new methods for evaluating immunologically active compounds have been developed and validated at CHDR. With access to in vivo, in vitro, and ex vivo systems, we can systematically evaluate the efficacy and safety of new test compounds in the earliest stages of development.
Bridging preclinical and clinical drug development
One of our key areas of interest is the transition from preclinical research to clinical drug development. We carefully select, validate, and apply a wide range of biomarkers, challenge models, and clinical strategies to find answers to our sponsors’ questions. A well-informed translational strategy also increases the safety of our subjects and the safety of participants in future clinical trials. Given the complexity of the immune response, our knowledge-intensive approach is particularly important in the field of immunology.
CHDR has its roots in academia, and our staff are closely involved in research. In addition, we have an extensive network of research groups and clinicians who share their expertise with us when needed. We also have direct access to several highly specialised laboratories, in addition to our own research facilities. This unique combination of resources and expertise allows us to offer each sponsor a tailor-made approach to translational drug development.
Cutting-edge immunological biomarkers to measure drug effects
We use in vitro, ex vivo, and in vivo approaches to study the effects of new test compounds. One powerful approach involves the use of biomarkers.
Our general approach involves building upon the groundwork laid by the preclinical scientists who originally developed the compound or treatment. Wherever possible, we attempt to include the tests and/or procedures that were used in preclinical testing. The primary goal in early clinical drug development is to demonstrate a pharmacological effect, ideally using highly sensitive biomarkers. However, because the setting in these early studies often differs somewhat from clinical practice, these biomarkers may not necessarily be the same biomarkers that are commonly used in a clinical setting. In this context, the primary goal when selecting a biomarker is to demonstrate that the drug reaches its intended target. Of course, if desired we can also include clinically relevant biomarkers.
We have an extensive library of biomarkers, which we are continuously
expanding – we are always keen to discuss any questions or special
requests that you may have, so do not hesitate to get in touch.
In vitro measurements using human cells
Thanks to CHDR's close ties with the Leiden University Medical Center and other hospitals, it is relatively easy to obtain fresh human samples from specific patient populations and healthy volunteers. These biological materials can then be used in an in vitro setting to measure the pharmacological activity of a test compound. In some cases, the immunological effects of a compound on whole blood samples, isolated peripheral blood cells, or skin samples can be determined by measuring changes in the cells’ physiology. Sometimes, however, this will not be sufficient to demonstrate that the compound has the intended effect. For example, a compound that was designed to modify the inflammatory response by acting on a specific pathway may not have any measurable effect on non-activated blood cells. In this case, we first need to activate the inflammatory response using the relevant pathway using a challenge model. Using this technique, we are able to measure the compound’s effects on these activated cells.
