GLP-1 Peptide Therapeutics
Constructive.bio produces GLP-1 receptor agonists through fermentation-based manufacturing, incorporating up to 3 different non-canonical amino acids per molecule with multiple instances of each. This replaces conventional solid-phase peptide synthesis (SPPS) — eliminating the 30+ step chemical processes, reducing cost of goods by an estimated 50–70%, and enabling production at scales that SPPS cannot achieve for blockbuster demand.
The Problem
GLP-1 therapeutics face a manufacturing bottleneck. Semaglutide requires ~30 synthetic steps via SPPS, with yields that drop at each coupling. Global demand for GLP-1 agonists is projected to exceed 2 billion doses annually by 2030, but SPPS manufacturing capacity cannot scale to meet this. Raw material costs for Fmoc-protected amino acids compound the problem, making current production both slow and expensive.
Fatty acid acylation — adds molecular bulk
Backbone ncAA incorporation — intrinsic stability
Our Approach
Constructive.bio’s BioForge platform produces GLP-1 analogues through engineered E. coli fermentation using expanded genetic code technology. Our organisms incorporate ncAAs — including Aib (α-aminoisobutyric acid) for protease resistance, lipidated lysine derivatives for albumin binding and extended half-life, and D-amino acid substitutions at specific positions — directly during ribosomal translation. A single fermentation run replaces the entire SPPS workflow: no protecting groups, no coupling reagents, no iterative purification. The platform achieves production levels compatible with commercial-scale manufacturing in standard bioreactor infrastructure.
Key Capabilities
Up to 3 different ncAAs per GLP-1 molecule, with multiple instances of each
Estimated 50–70% reduction in cost of goods vs SPPS
Scalable from lab bench to 10,000L+ fermentation using standard infrastructure
Single fermentation step replaces 30+ synthetic coupling steps