The optimistic case for protein foundation model companies

Summary

Note: apologies for the double-send if you got two of these, I messed something up in the settings!Introduction The optimistic argumentsMultiproperty optimizationThe value of infinite explorationOpen-source models will not be as common anymore if datasets grow more complexPharma prioritizes convenience more than you think Let’s be honest with each other: the funding for protein foundation model startups got a little crazy for a moment. EvolutionaryScale got $142M in mid-2024, Latent Labs got $50M in early-2025, Chai Discovery got $70M in mid-2025. And, of course, the giant two: Isomorphic Labs with $600M in funding in early 2025, and Xaira Therapeutics with an insane $1B in funding in mid-2024. Things have calmed down since then, so I think it’s a good moment to look back at this with some fresh eyes and ask: was any of this a good idea? It’s become quite common to tell one another that no, obviously not, these were a series of escalating, FOMO-y investments that had basically zero basis in objective reality. I empathize with this viewpoint. Protein models are increasingly recognized as commoditized things, where the open-source stuff is actually quite good, and, even at the private level, there didn’t seem to be a strong differentiation between one group’s pretrained weights and another’s. If you really squinted, maybe, just maybe, the open-source Boltz-1 was slightly worse than Alphafold3 by a few percentage points in a few domains, but how much does that matter? Surely it’s all within a standard deviation of one another? How could this justify the immense investments needed to train these models? But this view has also become so universally held that, honestly, it’s getting a little boring. Increasingly, I have grown more and more curious about what actually was the opinion of people who invested into these things. People knock on VC’s a lot, but I have a pretty high opinion of nearly every biotech VC I’ve met, and it’s difficult for me to imagine that it was all...