What You Should Know
– Topos Bio has emerged from stealth with $10.5M in seed funding to solve one of the most persistent challenges in medicine: targeting intrinsically disordered proteins (IDPs). The seed funding was led by Boldstart, Threshold, and Neo, with participation from notable angel investors including Dara Khosrowshahi (CEO of Uber) and Naveen Rao (CEO of Unconventional AI).
– While traditional models like AlphaFold focus on static structures, Topos Bio’s foundation model, Topos-1, captures millions of dynamic fluctuations, outperforming every leading protein model in benchmarking tests and opening a new therapeutic category for Alzheimer’s, Parkinson’s, and aggressive cancers.
The Problem: Why One-Third of the Proteome is ‘Undruggable’
Traditional drug discovery is built on the “lock-and-key” model, which requires stable, 3D binding pockets. However, IDPs—which drive some of the world’s most devastating diseases—rapidly fluctuate through millions of shapes, leaving traditional drugs with nowhere to anchor.
Topos-1 represents a paradigm shift by modeling protein dynamics as ensembles rather than static snapshots. This allows the platform to identify “binding opportunities” within dynamic structures that were previously invisible to computational tools.
The Benchmarking Breakthrough: Topos-1 vs. The Giants
In a technology report released alongside the funding, Topos Bio demonstrated that its Topos-1 foundation model outperformed the industry’s heaviest hitters:
- AlphaFold (Google DeepMind): Surpassed in handling the dynamic complexity of disordered regions.
- Chai & Boltz: Outperformed across a broad benchmarking suite focused on IDP-specific challenges.
Many “AI-only” biotech firms fail because their predictions don’t survive a wet lab. Topos Bio differentiates itself through an integrated wet lab that continuously refines model accuracy with real-world experimental data. Led by Amir Khosrowshahi (former CTO of Intel AI) and Ryan Zarcone, the team has the technical pedigree—at the intersection of physics and AI—to handle the high-stakes complexity of protein ensembles.
“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.”
Strategic Collaboration: The Gladstone Partnership
The partnership with Gladstone Institutes (led by Dr. Steven Finkbeiner) is a massive validation signal combining Gladstone’s advanced imaging and disease modeling with Topos-1’s computational insights. The team is taking a step toward discovering modulators that can actually cross the translational gap from lab to clinic.
