Synthesizable by Design: Rethinking AI's Role in Small Molecule Drug Discovery

In this episode of Data in Biotech, host Ross Katz sits down with Paul Finn, Chief Scientific Officer at Oxford Drug Design, for a conversation on what it actually takes to find a drug molecule that works not just on paper but also in the lab, in the cell, and, ultimately, in the clinic. Paul brings four decades of experience across what became GSK, Pfizer, and a series of Oxford-area spinouts and has shepherded a compound all the way to a marketed drug. That perspective gives him a particular kind of skepticism toward AI results that look too good to be true because he's done the work of checking whether they are. The conversation moves through synthesizability as a first-class constraint, why chemistry has proven so much harder for AI than biology, how 3D molecular representation gets closer to the physics that actually matters, and what rigorous multi-parameter optimization looks like when you're trying to kill cancer cells and drug-resistant bacteria at the same time. What you'll learn in this episode: >> Why synthesizability is chronically underestimated and why changing a single atom in a structure can take a molecule from trivially easy to make to practically impossible >> How Oxford Drug Design constrains the generative search to reaction schemes and purchasable building blocks, and why that chemical space is still so vast that novelty is not meaningfully sacrificed >> Why most generative AI models learn from a 2D string representation of a molecule; two steps removed from the 3D physics that govern how a drug actually binds to its target >> How Bayesian optimization over reagent space, rather than molecular space, allows an active learning loop to focus on the structural patterns associated with activity >> Why benchmarking complex models against simple ones is the discipline that exposes false correlations and why Paul and his co-authors were able to recover the Halicin result using methods decades older than deep learning >> What a pharma company should actually ask an AI drug discovery vendor before buying what they're selling Meet our guest: Paul Finn is Chief Scientific Officer at Oxford Drug Design, a computational drug discovery company with roots in Oxford's chemistry department. His career spans over 40 years of computational drug discovery, from early structure-activity modeling in the 1980s through to modern generative AI methods, with deep experience at what became GSK and Pfizer before moving into the Oxford spinout ecosystem. At Oxford Drug Design, Paul leads internal programs in oncology and antibacterial resistance, combining novel computational methods with a rigorous, synthesizability-first approach to multi-parameter optimization. Connect with Paul Finn on LinkedIn: https://uk.linkedin.com/in/paul-finn-2250616 About the host: Ross Katz is Principal and Data Science Lead at CorrDyn. Ross specializes in building intelligent data systems that empower biotech and healthcare organizations to extract insights and drive innovation. Connect with Ross Katz on LinkedIn: https://www.linkedin.com/in/b-ross-katz/ Connect with us: Follow the podcast for more insightful discussions on the latest in biotech and data science.Subscribe and leave a review if you enjoyed this episode! Sponsored by… This episode is brought to you by CorrDyn, the leader in data-driven solutions for biotech and healthcare. Discover how CorrDyn is helping organizations turn data into breakthroughs at CorrDyn. https://www.linkedin.com/company/corrdyn/