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PF-1 proposes active-site geometries around the target transition state, then builds a backbone that holds them. Roughly 105 candidate sequences per campaign, none of them derived from a natural homologue.
Most industrial reactions have no natural enzyme to borrow. We generate catalysts for them from scratch — so steps that need palladium, chlorinated solvents and cryogenic reactors can run in water, at room temperature.
PF-1 · designed backbone
78 residues · 3 helices · 2 strands
A modern small-molecule drug takes eight to twelve synthetic steps. Most of them still run on chemistry inherited from petroleum processing: precious-metal catalysts, halogenated solvents, sub-zero reactors, and a waste stream twenty to a hundred times the mass of the product.
Enzymes do the same transformations at ambient temperature, in water, with the stereochemistry right the first time — when one happens to exist. For most reactions a process chemist actually needs, none does. The industry's answer has been to screen natural diversity for a distant relative and then evolve it: eighteen to thirty months of mutagenesis to reach a catalyst that survives a manufacturing plant, and no guarantee of a starting point at all.
We think that is a design problem wearing a search problem's clothes. Given the transition state you want stabilised, the active site that stabilises it can be generated — and the protein that holds it in place can be generated around it.
PF-1 is a sequence–structure diffusion model conditioned on reaction geometry rather than on a homologous protein family. It is trained on public structural data and on our own paired library of variants and measured kinetics — the part that cannot be downloaded. Every campaign runs the same four stages, and every campaign ends by feeding the model.
PF-1 proposes active-site geometries around the target transition state, then builds a backbone that holds them. Roughly 105 candidate sequences per campaign, none of them derived from a natural homologue.
Folding, docking and stability models score every candidate for expressibility, melting temperature and predicted transition-state binding. Around a thousand survive to the bench — the step that makes the wet lab affordable.
Genes are synthesised and expressed in E. coli, arrayed in 384-well plates. Cell-free expression runs alongside it for the designs we want an answer on this week rather than next month.
Kinetics by LC–MS on every variant, on the real substrate, under conditions a plant would use. Failures are measured with the same care as hits, because they carry as much signal.
↺ Every measurement returns to training. Each campaign shortens the next.
Reaction classes chosen for how often they appear in routes that process chemists would rather not run.
| Program | Reaction class | Sponsor | Stage |
|---|---|---|---|
| PF-201 | Stereoselective C–N coupling | Undisclosed pharma partner | Scale-up · 100 L |
| PF-118 | Ketone → chiral amine (transaminase) | Internal | Lead optimisation |
| PF-095 | Late-stage C–H hydroxylation | Internal | Lead optimisation |
| PF-233 | Nitrile hydrolysis, non-natural substrate | Internal | Discovery |
| PF-260 | Macrocyclisation | Internal | Discovery |
A campaign is worth running only if the design and ranking stages finish faster than the plates come back. That makes infrastructure a scientific constraint, not an IT one.
We take on a small number of partnered programs a year, alongside our internal pipeline. We are also hiring scientists and engineers who want to work where the model meets the plate.