Topos Bio Raises $10.5M Seed to Target ‘Undruggable’ Proteins in Alzheimer’s and Cancer

Topos Bio has emerged from stealth with $10.5 million in seed financing to advance a new approach to drug discovery focused on intrinsically disordered proteins, a class of biological targets long considered inaccessible to conventional therapeutics. The funding round was led by Boldstart, Threshold, and Neo, with participation from angel investors including Dara Khosrowshahi and Naveen Rao.

Intrinsically disordered proteins differ fundamentally from the structured proteins that underpin most modern drug discovery. Rather than adopting a stable three-dimensional form, these proteins exist as dynamic ensembles that rapidly shift across many conformations. This behavior undermines traditional structure-based drug design, which assumes fixed binding pockets. As a result, roughly one-third of the human proteome, including proteins implicated in Alzheimer’s disease, Parkinson’s disease, and multiple aggressive cancers, has remained largely beyond reach.

“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 has developed an AI-native discovery platform designed specifically for this challenge. Its models generate large-scale ensembles that capture protein dynamics, identify transient binding opportunities within these fluctuating structures, and apply generative chemistry to design small molecules tailored to modulate disordered regions. The platform is integrated with an in-house wet lab, enabling experimental validation and continuous feedback to improve model performance. Initial discovery programs are focused on neurodegenerative diseases, with planned expansion into oncology and metabolic disorders.

Alongside the financing, the company released a technical report describing Topos-1, its foundation model for intrinsically disordered proteins. In internal benchmarking, the model demonstrated improved performance compared with existing protein models, including AlphaFold, Chai, and Boltz.

Strategic validation will be supported through a collaboration with Gladstone Institutes, centered on alpha-synuclein, a disordered protein closely associated with Parkinson’s disease. “This partnership embodies the spirit of translational collaboration,” said Steven Finkbeiner, MD, PhD, Director of Gladstone’s Center for Systems and Therapeutics. “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.”

Topos Bio was founded by researchers from UC Berkeley and Stanford and is led by a team with backgrounds spanning physics, artificial intelligence, and neuroscience, positioning the company at the intersection of computational modeling and experimental biology.

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