Topos Bio Secures $10.5M to Tackle ‘Undruggable’ Proteins Driving Alzheimer’s and Cancer

Topos Bio, a biotechnology company pioneering AI-driven drug discovery for intrinsically disordered proteins (IDPs), today emerged from stealth with $10.5M in seed funding from Boldstart, Threshold, and Neo, with participation from notable angel investors including Dara Khosrowshahi (CEO of Uber) and Naveen Rao (CEO of Unconventional AI). The company is also releasing a technology report demonstrating state-of-the-art performance of its AI model on this challenging protein class.

The Problem: Drugging the Undruggable

Traditional drug discovery relies on the “lock-and-key” model: proteins fold into stable 3D structures, and drugs are designed to fit precisely into their binding pockets. Intrinsically disordered proteins (IDPs) break this paradigm entirely. Rather than adopting a single fixed shape, IDPs rapidly fluctuate through many different conformations. Without stable binding pockets, traditional drugs have nowhere to anchor. Current computational tools fail here because they predict static structures, not dynamic ensembles of constantly shifting shapes. This leaves roughly one-third of the human proteome – including the primary drivers of Alzheimer’s, Parkinson’s, and many aggressive cancers – effectively undruggable by conventional methods.

“Disordered proteins represent one of the last major frontiers in drug discovery – they’re central to devastating diseases but nearly impossible to target with existing methods,” said Ryan Zarcone, co-founder and CEO of Topos Bio. “Our platform tackles this by modeling protein dynamics as ensembles rather than static structures. This approach enables rational drug design and opens up an entirely new category of previously undruggable biology.”

Topos Bio’s Solution: Frontier AI for disordered proteins

Topos Bio has developed an AI-native integrated discovery platform specifically designed for intrinsically disordered proteins. The company’s AI models generate ensembles that capture how these proteins fluctuate through millions of conformations, then identify binding opportunities within these dynamic structures. Using generative chemistry, the platform designs small molecules optimized to modulate these disordered regions. An integrated wet lab validates and refines these predictions, generating experimental data that continuously improves model accuracy and expands the platform’s capabilities. The company’s initial programs focus on neurodegenerative disorders, followed by oncology and metabolic diseases.

Alongside the announcement, Topos Bio released its first technical report detailing the development and validation behind Topos-1, its foundation model for intrinsically disordered proteins. Across a broad benchmarking suite, Topos-1 outperformed every leading protein foundation model, including AlphaFold, Chai, and Boltz.

“We invested in Topos at inception because Amir and Ryan can solve a fundamental computational problem that’s blocking progress on many of medicine’s most important targets,” said Ellen Chisa, Partner at Boldstart. “No one else has the AI and wet lab infrastructure to model disordered proteins, and a reliable model unlocks therapeutic opportunities that no one else can access.”

Strategic Collaboration with Gladstone Institutes

To validate its platform in established disease models, Topos Bio is partnering with Gladstone Institutes. The collaboration will focus on discovering novel modulators for alpha-synuclein, a disordered protein central to Parkinson’s disease pathology.

Steven Finkbeiner, MD, PhD, Director of Gladstone’s Center for Systems and Therapeutics said: “This partnership embodies the spirit of translational collaboration. By combining advanced imaging and disease modeling from our lab with Topos Bio’s novel computational methods, we’re taking a powerful step toward tackling intrinsically disordered proteins, one of the greatest frontiers in neurodegenerative disease biology.”

World-class Research Team

The company is led by a team with deep roots in physics, AI, and neuroscience. Co-founder and CEO Ryan Zarcone previously led AI at Fountain Therapeutics and trained as a biophysicist at UC Berkeley’s Redwood Center for Theoretical Neuroscience. He co-founded Topos with his former labmate 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 top academic and industry labs.

Interested partners and potential employees can learn more at https://toposbio.ai.

About Topos Bio

Topos Bio is an AI-powered biotechnology company developing therapies for intrinsically disordered proteins (IDPs). Headquartered in San Francisco, the company’s platform integrates physics with generative AI to target proteins involved in neurodegeneration, oncology, and metabolic diseases. Topos Bio is backed by Boldstart, Threshold, Neo, and notable angel investors. Interested partners and potential employees can learn more at https://toposbio.ai.

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