Why choosing the right assay could make or break your first-in-man trial.
In GLP toxicology studies, it’s an obvious choice to select a physiologically relevant animal model but when completing the safety assessment with in-vitro assays, researchers tend to get puzzled, often thinking that no results means “go”.
The toxicity of monoclonal antibodies (mAbs) can often be predicted based on the understanding of the intended function of the drug and the results of appropriate preclinical studies. However, the well-published adverse events observed in the first-in-man trial with the anti-CD28 superagonist mAb, known as TGN-1412,1 highlighted the potential toxicity of therapeutic antibodies and the complexity in interpreting and translating preclinical findings to the clinical setting. The profound toxic effects in this trial shed light on the urgent need to select the right animal model as well as the need to develop physiologically relevant human-based tests to accurately predict risks and aid the selection of a safe starting dose. To minimize risk in first-in-man trials, researchers should expect the unexpected and when there is theoretical risk, the investigators should plan for its potential occurrence.
In recent years, significant progress has been achieved in the development of new human-based in-vitro assays which better can predict serious pharmacological risks that cannot be discovered in animal models. EMA has issued guidelines on strategies to identify and mitigate risks for early clinical trials and one of the key elements include preclinical safety evaluation of biotechnology-derived pharmaceuticals. You can access the guidelines here.
Maximize the outcome of first-in-human trials
Potent biological molecules, especially those with a novel mechanism of action, can benefit from in-vitro testing on human material prior to the clinical trial. Insights from such testing is invaluable for risk mitigation and management of symptoms in the clinic. Human-based assays can aid the screening process, determine the first dose in humans and in many ways contribute to the overall success of early clinical trials.
Let us discuss your challenges
Whether you are looking to better understand the functional aspects of a molecule, evaluate safety, immune related reactions or biodistribution – we’re your trusted partner all the way, from tailored study design to IND-filing.
Immuneed’s platform enables multiple read-outs from a single sample and provides a unique opportunity to study blood-drug interactions in real time. Circulating, fresh human blood with all components present (all cells, active complement and cascade systems) recreates human-like conditions and is the only system of its kind that is commercially available. Interested in the science behind our platform? Click here for further reading.
Are you ready to take the leap into truly meaningful preclinical testing? You can reach us here
1. Brennan FR, et al. Safety and immunotoxicity assessment of immunomodulatory monoclonal antibodies. MAbs 2010; 2(3):233–255.