Pythia Labs, a biotechnology company building frontier AI models for therapeutic discovery, today announced its launch alongside a preprint in bioRxiv introducing Pythia-1, the all-atom generative model at the core of its antibody design platform.
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Pythia’s AI technology platform can design antibodies against traditionally challenging targets such as multi-pass membrane proteins.
Pythia’s technology is built to create antibodies against targets that have challenged conventional discovery, including multi-pass membrane proteins such as G protein-coupled receptors (GPCRs). Generating antibodies that activate these receptors has been a longstanding goal in antibody discovery. Pythia-1 reasons jointly over amino acid sequence, three-dimensional atomic structure and explicit design specifications. The platform provides control over where an antibody binds, the conformational state of the target it recognizes, and key antibody attributes. This allows functional objectives and development requirements to shape designs from the outset.
Pythia’s proof-of-concept study, published this week in bioRxiv, evaluated full-length human IgGs designed from scratch across 22 therapeutic targets. Following a single computational design round, experimental screening of around 48 candidates per target identified antibodies with single-digit nanomolar affinities for soluble proteins and single-digit nanomolar cell-binding EC50 values for GPCRs. Cell-based functional assays demonstrated both GPCR agonism and antagonism, including single-digit nanomolar inhibitory potency against multiple GPCRs. Characterized antibodies also exhibited biophysical properties that compared favorably with clinical-stage therapeutic antibodies.
The study and its compelling results were made public this week in a bioRxiv preprint entitled “Design of Full-Length Agonist and Antagonist Antibodies for Hard Targets”. Pythia is also sharing complete sequences of all lead antibodies presented in the study at pythialabs.com, to support independent validation and further research.
By extending antibody discovery into areas of biology that conventional methods have struggled to access, Pythia’s technology creates new opportunities to develop transformative medicines previously beyond reach.
About Pythia Labs
Pythia Labs builds frontier AI models for therapeutic discovery. The company is beginning with next-generation antibodies for hard-to-drug targets. Its scientists and engineers combine expertise in generative modeling, computational biology and drug discovery to open new possibilities for creating better medicines.
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