The Time Point Changes Everything - Kevin Pfleger

An endpoint assay gives you a number. It does not tell you whether you measured at the right time. In bias pharmacology - and in receptor signaling more broadly - the time point you choose determines what you find. Miss the kinetic peak and you miss the biology entirely. Pfleger has been making this case for two decades, and building the live-cell BRET and NanoBRET platforms that remove the guesswork about when to look. This conversation covers how those tools were built, how they reached patients through a phase 2 clinical trial in kidney disease, and why most of the field is still screening GPCRs as if they exist in isolation. About Kevin Pfleger Pfleger is Professor, Director of Biomedical Innovation, and Head of Molecular Endocrinology and Pharmacology at the University of Western Australia and the Harry Perkins Institute of Medical Research. His research spans arrestin biology, GPCR functional interactions, and the angiotensin and chemokine receptor systems. He developed BRET and NanoBRET-based live-cell platforms now standard across the GPCR field, and co-founded a publicly listed biotech that recently completed phase 2 clinical trials in focal segmental glomerulosclerosis and diabetic kidney disease. What You'll Learn Why the time point you choose in a bias assay is not a technical detail - it is a pharmacological decision that changes the result How BRET went from a tool used by a handful of labs to the go-to platform for GPCR molecular pharmacology - and what drove that adoption How a lab discovering arrestin interactions in HEK cells built a compound that reduced urinary protein levels in patients with kidney disease Why the angiotensin receptor system became unexpectedly relevant to COVID-19 - and what Pfleger's team is investigating with DMX200 in the REMAP-CAP trial What happens to your funding strategy when you stop treating grants and industry partnerships as separate worlds Why the scientist who says "I have no idea what comes next" might be better positioned than the one who has mapped out every step Episode Timeline 00:00 Introduction 01:36 Pfleger's philosophy: science as a team sport 03:54 Cambridge, Edinburgh, and a PhD that redirected a career 06:10 Working on biosignaling before the term was coined 09:12 From GnRH receptors to arrestins - the postdoc pivot 12:47 From lab discovery to phase 2 clinical trials - how a spin-out was built 16:56 Why grant-only funding is becoming unsustainable - and what to do instead 22:21 What a PhD is actually training you for 25:42 NanoBRET and the evolution of live-cell GPCR assay design 27:54 Why endpoint assays miss the peak - the case for real-time kinetics 29:44 Bias signaling has a kinetic problem 32:26 Receptors in complexes vs. receptors in isolation 40:03 When cell data became a patient outcome Every tool, every assay, every signaling platform starts with someone asking whether the current approach is actually capturing what matters. GPCR University is built the same way - for scientists who want to go deeper: https://www.ecosystem.drgpcr.com/gpcr... Get to know our Partners: Eurofins DiscoverX - https://www.ecosystem.drgpcr.com/euro... GeneTex - https://www.ecosystem.drgpcr.com/genetex #DrGPCR #GPCR #LiveCellAssays #BiasedAgonism #GPCRPharmacology #DrugDiscovery #NanoBRET TAGS gpcr pharmacology, nanobret assay, bret technology, live cell assay, arrestin signaling, receptor complexes, biased agonism, angiotensin receptor, gpcr drug discovery, molecular pharmacology, receptor kinetics, gpcr signaling, kidney disease clinical trial, gpcr research, drug discovery tools