Building Flagship Pioneering With Noubar Afeyan: Paranoid Optimism, “What If?” Questions, and Defying Convention

What if you could build breakthrough companies systematically?

In this episode of Building One, Tomer Cohen sits down with Noubar Afeyan, founder and CEO of Flagship Pioneering, the company-building platform behind more than 100 companies, including Moderna.

Noubar has spent nearly four decades building at the edge of science. His approach starts with a deceptively simple question: “What if?”

At Flagship, teams explore roughly 100 of these questions each year. The most promising become proto-companies, which are then actively stress-tested — and sometimes killed — before becoming full-fledged companies.

It’s a radically different approach to innovation: don’t start with what already exists and incrementally improve it. Move beyond the boundaries of what we know and work backwards from what might be possible.

Tomer and Noubar discuss:

• How Flagship developed a repeatable system for creating companies from scratch• Why the most interesting opportunities can exist beyond the edge of expertise• Noubar’s philosophy of “paranoid optimism” and “urgency-oriented patience”• Why Flagship prototypes companies, not just products• How a “what if” question eventually led to Moderna• Why platforms can become product-generation engines• How little we still understand about the human body — and why drug development remains so difficult• Why Noubar believes AI could fundamentally transform the process of scientific discovery• His idea of “polyintelligence” — bringing together human, machine, and nature’s intelligence• Why breakthrough innovation is about “taking the fiction out of science fiction”

It’s a conversation about science, company building, AI, and what it takes to pursue ideas that initially sound unreasonable.

Listen to the full episode of Building One with Noubar Afeyan.