Codexis (CDXS) investor relations material

Industry trends and siRNA landscape

• siRNA therapies are expanding from rare to large indications, with over 400–600 assets in development and more than 100 in FDA clinical trials.

• siRNA is considered a powerful modality due to its safety, efficacy, and broad transcriptome targeting.

• Production technologies for advanced medicines have lagged behind scientific advances, limiting commercial and patient impact.

• There is growing interest in siRNA for cardiovascular, obesity, and CNS indications.

Manufacturing challenges and ECO Synthesis advantages

• Traditional solid-phase synthesis faces scale limitations (max 7–10 kg per batch) and high solvent use, especially acetonitrile, raising environmental and supply concerns.

• Scaling to commercial levels requires significant capital investment, with $1 billion in stainless steel needed for a 1-ton annual output.

• ECO Synthesis is estimated to be 70% more capital efficient and uses an aqueous process, reducing environmental impact and solvent needs.

• The platform enables scalable, reproducible, and high-quality siRNA production, with routine 100 g batches and plans to reach kilo scale by 2027.

Technical innovations and customer needs

• ECO Synthesis allows for precise stereochemical control of phosphorothioate linkages, potentially improving potency and stability.

• The platform can initiate enzymatic polymerization from a single nucleotide, eliminating the need for a chemical starter oligo.

• Customers seek solutions for scale, product quality, and stereocontrol, with ECO Synthesis addressing these needs.

• The process mass intensity of ECO Synthesis is much lower than traditional methods, with over 90% less solvent use.