DMPK Insights #1: Candidate Survival – 3 Pillars to 5Rs and Beyond

In this podcast, Dr. Paul Morgan, Head of DMPK at Grünenthal Group, discusses the development of the publication that introduced the “5R framework” and improved the likelihood of AstraZeneca candidate survival from candidate drug nomination to Phase III. We will then discuss how the area has developed since then and where the field may go in the future.

The episode addresses the following questions:

• What was the situation like that led to the development of the 5Rs?
• How was the analysis conducted?
• How was this analysis accepted both within the organization and externally?
• What changes occurred as a result of this?
• As we sit here today has this work led to the improvements suggested?
• What do you see as the future? Have we done enough? What else is needed?

Speaker:
Paul Morgan, Ph.D. - Head of DMPK at Grünenthal Group

Dr Paul Morgan has worked in Pharma R&D for 30 years across multiple therapeutic areas taking projects from early discovery through all stages of drug development and registration.  With specialism in Drug Metabolism and Pharmacokinetics (DMPK), he has led R&D departments in Pfizer, AstraZeneca, Sosei Heptares and now Grunenthal working across the interface between DMPK and Med Chem, Pharmacology, Safety, Clinical and CMC.  He has a keen interest in R&D productivity enhancement and has contributed to major initiatives at both Pfizer and AstraZeneca to introduce frameworks for the improvement of drug survival.   Paul is an honorary senior lecturer in Department of Pharmacology at University of Liverpool where he did his PhD.   

Paul is originally from Belfast, Northern Ireland and is currently based in North-West England just outside Manchester.  He is married with two grown-up children and a lively dog!

References:

1. Morgan, P., et al, 2018. Impact of a five-dimensional framework on R&D productivity at AstraZeneca. Nature reviews Drug discovery 17.3: 167-181.
2. Summerfield, S.G., Yates, J.W. and Fairman, D.A., 2022. Free Drug Theory–No Longer Just a Hypothesis?. Pharmaceutical Research, 39(2): 213-222. 
3. Smith, D.A., and Rowland, M., 2019. Intracellular and intraorgan concentrations of small molecule drugs: theory, uncertainties in infectious diseases and oncology, and promise. Drug Metabolism and Disposition 47.6: 665-672.
4. Smith, D.A., Di, L. and Kerns, E.H., 2010. "The effect of plasma protein binding on in vivo efficacy: misconceptions in drug discovery." Nature reviews Drug discovery, 9.12: 929-939.

Stay tuned for more podcasts in our Pharmaron DMPK Insights Series!