Our fifth webinar in the MDC Connects Series 2021 | A Guide to Complex Medicines. This slide deck takes a closer look at how you can determine efficacy in vivo. Jenny Worthington (Axis Bio)

1. Complex Medicines: Understanding safety and
efficacy
Determining efficacy in vivo
15th June 2021
Jenny Worthington

2. Jenny Worthington – Founder and Director of Science at Axis Bioservices
• Brief background to Axis Bio
• Steps involved in preclinical analysis of Complex Medicines
• How analysis of Complex Medicines differs from other medicines
• Round-up
• Questions

3. Axis Bioservices – Who are we?

4. Preclinical in vivo testing
PK Biodistribution Efficacy Toxicity
Essentially there is no difference between the process for Complex
Medicines BUT…..

5. PK Questions/Considerations
1. Circulation
2. Stability
3. Clearance
1. Bioanalysis method
2. Collection of samples

6. Biodistribution
Administration route
Extravasation
Targeting
Physical Barriers (tight junctions)
Vasculature
Interstitial fluid
ECM concentration
Mucus
Cellular uptake
Cell heterogeneity
General
Within target organ
Within cell
Given the target and proposed mechanism of action the
biodistribution issues/opportunities will be project specific

7. Biodistribution
Administration route
Extravasation
Targeting
Physical Barriers (tight junctions)
Vasculature
Interstitial fluid
ECM concentration
Mucus
Cellular uptake
Cell heterogeneity
General
Within target organ
Within cell
Given the target and proposed mechanism of action the
biodistribution issues/opportunities will be project specific

8. Biodistribution

9. Efficacy: DO NOT expect that your first efficacy study will be the definitive one!
Significant
control of
tumour
growth
Best model
system
Adverse effects
Dosing
occasions
Tissue collection
Important consideration: generating sufficient material
for the in vivo studies – significant £££ implications

10. Toxicology: Complex medicines = complex toxicology?
• Collect bloods from in vivo studies – initial tox issues
• Biodistribution/adverse effects give some clues
Bottom line: Get toxicology expertise on-board as part of your project team as
early as possible

11. Summary/Recommendations
• Ultimately an efficacy study is an efficacy study there is no practical difference
between complex medicines and others BUT…..
• PK – need to know this – there may be special conditions needed for
sample collection/bioanalysis
• Biodistribution – essential – gives really important information for the
whole project (targeting, efficacy, toxicology)
• Efficacy – be prepared for more than one study – make sure that you can
generate enough to carry out all possible studies.
• Toxicology – get expert advice as soon as possible to ensure correct
samples are taken