For decades, the pharmaceutical industry has operated on a singular, rigid principle: the “lock-and-key” model. If a protein is the lock driving a disease like For decades, the pharmaceutical industry has operated on a singular, rigid principle: the “lock-and-key” model. If a protein is the lock driving a disease like

Ex-Intel AI CTO Launches Topos Bio with $10.5M to Tackle ‘Undruggable’ Proteins Driving Alzheimer’s and Cancer

For decades, the pharmaceutical industry has operated on a singular, rigid principle: the “lock-and-key” model. If a protein is the lock driving a disease like Alzheimer’s or cancer, scientists must find a chemical “key” that fits perfectly into its static, three-dimensional structure to turn it off.

The problem? Nearly one-third of the human proteome doesn’t have a fixed shape at all.

These are Intrinsically Disordered Proteins (IDPs), biological shape-shifters that flicker through millions of different conformations every second. Because they lack a stable “lock,” they have earned a frustrating reputation in biotech circles as being “undruggable.” They are the dark matter of biology: essential to life, central to our most devastating diseases, and historically invisible to our best drug-discovery tools.

Today, Topos Bio is emerging from stealth to change that. With $10.5 million in seed funding and a pedigree that bridges the gap between Silicon Valley’s elite AI circles and elite academic biophysics, Topos is betting that the solution to the “undruggable” problem isn’t better keys, but a better map of the chaos.

The company was founded by a world class technical team with deep experience in physics, AI, and neuroscience. Co-founder and CEO Ryan Zarcone led AI at Fountain Therapeutics and trained as a biophysicist at UC Berkeley’s Redwood Center for Theoretical Neuroscience. He is joined by Amir Khosrowshahi, former CTO of Intel AI and co-founder of Nervana (acquired by Intel for $400M). Together, they have built a team of leading AI and biology researchers from UC Berkeley, Stanford, Harvard, Caltech, UCSF, Verge Genomics, Genentech, Fountain Therapeutics, and Verily Life Sciences.

The Architecture of Chaos

“Traditional drug discovery is like trying to take a photograph of a person running a marathon and assuming they stay in that exact pose forever,” says Zarcone, co-founder and CEO of Topos Bio. “If you design a shoe based on that one frozen frame, it’s not going to work when they take the next step. Disordered proteins are in constant motion. To drug them, you have to model the entire race, not just the snapshot.”

The company’s breakthrough lies in Topos-1, a foundation model designed specifically for these high-velocity proteins. While Google DeepMind’s AlphaFold revolutionized biology by predicting how proteins fold into stable shapes, it, and its successors like Chai and Boltz, struggle with IDPs precisely because these proteins refuse to stay folded. The company also published a technology report today on their research breakthroughs. 

Topos Bio’s platform treats protein dynamics as ensembles rather than static structures. By modeling the “statistical cloud” of shapes a protein might take, Topos can identify fleeting “binding pockets”, windows of opportunity that appear for only a fraction of a second but are stable enough for a small molecule to grab onto.

Top tier backers

The investment community is taking notice. The $10.5 million round was led by Boldstart, Threshold, and Neo, with heavy-hitters like Uber CEO Dara Khosrowshahi and Unconventional AI CEO Naveen Rao joining as angels.

This fusion of “hard” AI expertise and deep biological physics is what Topos believes gives them an edge. “We invested in Topos at inception because they are solving a fundamental computational bottleneck,” says Ellen Chisa, Partner at Boldstart. “A reliable model for disordered proteins unlocks therapeutic opportunities that literally no one else can access.”

From Code to Clinic: The Gladstone Partnership

Topos isn’t content staying in the realm of digital simulations. The company has already established an integrated “wet lab” to validate its AI’s predictions in real-time, creating a feedback loop where experimental data continuously sharpens the model’s accuracy.

The first major test of this platform is a strategic collaboration with the Gladstone Institutes. The focus? Alpha-synuclein, the notorious disordered protein that clumps together in the brains of patients with Parkinson’s disease.

“This partnership embodies the spirit of translational collaboration,” says Dr. Steven Finkbeiner, Director of Gladstone’s Center for Systems and Therapeutics. “By combining our disease modeling with Topos Bio’s computational methods, we’re taking a powerful step toward tackling one of the greatest frontiers in neurodegenerative biology.”

The Multi-Trillion Dollar Frontier

The implications of “cracking” IDPs extend far beyond Parkinson’s. These proteins are the primary drivers of:

  • Neurodegeneration: Including Alzheimer’s and ALS.
  • Oncology: Many “master regulator” proteins in aggressive cancers are disordered.
  • Metabolic Diseases: Identifying new pathways for insulin regulation and obesity.

By moving the industry from “serendipitous discovery” to “rational design” for disordered proteins, Topos Bio is positioning itself at the center of what could be the next great wave of biotechnology. If they succeed, the term “undruggable” may soon become a relic of the past.

“Disordered proteins represent one of the last major frontiers,” Zarcone concludes. “We finally have the computational tools to match the complexity of the biology.”

Companies and employees can learn more at https://www.toposbio.ai/.

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