We support every stage of compound progression, from target identification/toxicological risk assessment, through lead-generation/optimisation, to life-cycle maintenance. Our extensive experience will help you design, run and interpret the studies necessary for your IND/IMPD submission and we will guide you through the associated FDA/EMA/PMDA interactive process.
From an initial analysis of the clinical plan, our experts will assist you in the compilation of a full and comprehensive safety-profiling schedule.
We will assess the known expression of your target, in both normal and diseased tissue, and highlight potential functional effects and clinical consequences of test-article binding.
A comprehensive gene-based analysis of systemic target expression and sequence homology, combined with a literature-based assessment of knockout data and target organ distribution, will help you to formulate your preclinical strategy.
Having defined your early-stage theoretical risks, we can then work with you to select specific endpoints that can be incorporated into your preliminary in vivo toxicity screens. By utilizing appropriate soluble and solid-tissue biomarkers, we will maximize the value of your early safety package, avoiding the need for costly additional bioassays.
For example, the analysis of vascular knockdown within systemic organ beds, in the development of novel anti-cancer agents, may predict the likelihood of clinical hypertension, assisting the planning of therapeutic indices.
Safety Liability/Toxicological Risk Assessment:
The analysis of pancreatic islet vascularity, via CD31 immunohistochemistry, demonstrates a treatment-related vascular regression (rarefaction), not visible via conventional staining. This may correlate with alterations in circulatory and functional biomarkers such as insulin.