The a16z Show

Box co-founder and CEO Aaron Levie joins MTS hosts Theo Jaffee and Sofia Puccini to make the case for open-weight AI, unpack the economics of open versus closed models, and explain why he believes more openness could strengthen rather than undermine the U.S. AI ecosystem. Aaron argues that open models create more use cases, push closed labs to innovate faster, and don't fundamentally change where the economics of AI ultimately accrue. They debate model distillation, America's competition with China, why restricting access may simply accelerate competing AI ecosystems, and whether U.S. labs should begin releasing open-weight versions of previous-generation models. They also get into what the latest frontier models mean for knowledge work, how AI has changed software engineering at Box, and why Aaron believes companies cutting engineers may simply not be ambitious enough. Finally, they discuss why enterprises are unlikely to bet on a single model and why the layer that routes between models, data, and workflows could become increasingly valuable.

World Labs co-founders Fei-Fei Li, Justin Johnson, and Ben Mildenhall join a16z General Partner Martin Casado to discuss Atlas, their latest world model, and what it reveals about the pursuit of spatial intelligence. At the center of Atlas is what the team calls “new view prediction”: given images or views of a scene, the model predicts what that environment should look like from a different position in space and time. This brings generation and 3D reconstruction into the same model, and raises a broader question about whether predicting views could become a useful primitive for understanding the physical world. They discuss the technical bets behind the model, what it can and can’t yet capture, and the importance of dynamics, editability, and simulation as world models develop. The conversation also explores applications in creative work, architecture, and robotics, where Fei-Fei argues that one of today’s biggest constraints is access to real-world training data.

Erik Torenberg is joined by a16z General Partner Alex Rampell and Affirm Co-Founder and CEO Max Levchin for a conversation on 25 years of fintech, from the early days of digital payments to the origins of Affirm and the next generation of agentic commerce. Max and Alex revisit what surprised them most about how payments evolved, why the card interface has been so difficult to displace, and why even the smallest corners of payments can become enormous markets. They also trace the early idea maze behind Affirm, from "pay with your identity" and the pajama problem to the realization that installment financing could dramatically increase merchant conversion. The conversation also gets into real versus "fake" 0% financing, what people misunderstand about Affirm today, why negative customer acquisition cost can be such a powerful business model advantage, and why Max is more bullish on agentic payments than on agents choosing what people buy.

a16z General Partner Jorge Conde sits down with Moderna CEO Stéphane Bancel to discuss a major milestone for mRNA technology: positive Phase 3 results from Moderna and Merck’s individualized treatment for melanoma, after more than a decade of work on personalized cancer vaccines. Stéphane explains how the treatment works by sequencing an individual patient’s tumor and healthy cells, identifying the mutations most relevant to their cancer, and encoding up to 34 of them into an mRNA designed specifically for that patient. Rather than simply unleashing the immune system, the goal is to teach it exactly what to recognize and attack. They also unpack the engineering challenge of manufacturing a different medicine for every patient, how Moderna has brought the process down to roughly 42 days from biopsy to treatment, and what it would take to manufacture personalized medicines at scale. Finally, Stéphane looks beyond melanoma to lung, kidney, bladder, pancreatic, and gastric cancers, as well as Moderna’s longer-term work applying mRNA to rare genetic and autoimmune diseases.

a16z’s Lisha Li sits down with Daniel Litt, Assistant Professor of Mathematics at the University of Toronto, to unpack AI's rapid progress in mathematics, what today's frontier models can actually do, and what they're still missing about the way mathematicians think. Daniel explains why some recent AI-generated results are genuinely impressive, including an autonomous solution to the Erdős unit distance problem, but argues that solving problems is only one part of mathematics. Today's models can grind through calculations, combine known techniques, and search enormous spaces, but still struggle with intuition, theory building, identifying the right questions, and developing the kind of big-picture understanding that drives much of mathematical progress. Lisha and Daniel also explore how AI is already changing mathematical research, why an explosion of AI-generated papers could distort academic incentives, and what happens if researchers outsource the work of thinking rather than use AI to deepen it. Ultimately, they ask a question that extends far beyond mathematics: as AI gets better at intellectual work, how do we make sure humans keep getting better at thinking too?