QEDDI has capabilities to prosecute the key phases in a drug discovery program.
Identification of hit compounds for a specific target by various methods including high-throughput screening, focused library screening, in silico screening (ligand- or target-based structural modelling), fragment screening. Prioritisation of hits following triage around early Structure-Activity Relationships (SAR), path to novel chemical matter, synthetic tractability, absence of toxicophores or frequent-hitter flags.
Development of SAR using ligand-based and/or structure-based drug design to support the hit-to-lead phase. Optimisation of activity in primary and secondary assays. Early profiling of the ADME-T properties of the lead series. Proof of concept for in vivo efficacy in a disease-relevant model.
Iterative optimisation with the lead series to capture the desired in vivo efficacy, safety and DMPK profiles in a pre-clinical development candidate. Demonstration of efficacy in a range of model systems that are relevant to human disease. Development of biomarkers that aim to increase the probability of success in the clinic.
Each project within QEDDI will have a defined target product profile (TPP) to describe the key attributes of a differentiated therapeutic. QEDDI has the capability to perform iterative cycles of medicinal chemistry and pharmacology to identify and optimise promising compound lead series against the TPP criteria to select a preclinical candidate. Attributes for a preclinical candidate include:
- Evidence of defined mechanism-of-action in potent and selective compounds;
- Defined, optimised physicochemical, ADME-T and pharmaceutical properties;
- Proof of concept in vivo efficacy at suitable doses in a translatable model;
- Appropriate safety pharmacology and toxicological profiles;
- Suitable DMPK for intended delivery route;
- Intellectual property.
- Hit identification by various modalities
- Rational drug design and synthesis of analogues
- SAR development
- Hit-to-Lead and Lead Optimisation
- Focused, chemoinformatics guided library synthesis
- Optimisation of compound potency and selectivity in biochemical and cell-based assays
- Evidence for efficacy in disease-relevant models
- Development of PK/PD relationships to support translation to humans
- Development of biomarkers for evidence of target engagement in the clinic
Preclinical Candidate Selection
- Safety pharmacology
- Pharmacokinetic and metabolite profiling
- Early toxicity studies
- Early pharmaceutical development and CMC assessment
- Human dose prediction
- IP management
- Business development