Codexis (CDXS) Status Update summary

Major technical achievements

• Achieved the first-ever continuous end-to-end enzymatic synthesis of a full siRNA molecule, including enzymatic incorporation of a tissue-targeting moiety, under milder, aqueous conditions that reduce chemical waste and improve product quality.

• Successfully synthesized a complete siRNA drug, Inclisiran, using the ecosynthesis platform via four different methods, demonstrating flexibility and reliability.

• Demonstrated the ability to mix enzymatic and chemical synthesis routes without compromising quality or yield, with >98% coupling/incorporation efficiency and high-quality, full-length oligonucleotides.

• Engineered ligases tailored to specific molecules, resulting in improved performance, higher volumetric productivity, and substrate versatility, validated in collaboration with Bachem.

• Ligases enabled higher conversion rates of oligonucleotide fragments into siRNA at increased raw material concentrations, with robust performance in customer case studies, including faster reaction times and improved conversion at elevated temperatures.

Commercial and customer engagement updates

• Completed a proof-of-concept collaboration with a major siRNA innovator, leading to a revenue-generating development contract.

• High customer interest and engagement at the Tides Europe meeting, with multiple discussions for process development and multi-asset collaborations.

• ECO Innovation Lab on track to launch by end of 2024, expected to be at capacity due to strong customer demand.

• Customers are interested in both ligation and sequential synthesis services for process development and scale-up.

• Manufacturing ramp-up for preclinical testing is expected after the ECO Synthesis Innovation Lab buildout.

Competitive positioning and industry trends

• Enzymatic synthesis, once seen as futuristic, is now recognized as a near-term reality, with Codexis perceived as a leader.

• Ligation is now widely discussed in the industry, but Codexis differentiates itself by evolving and optimizing enzymes for specific ligation steps.

• Codexis' ligases have consistently outperformed competitors in productivity and versatility, sometimes by up to tenfold.

• Traditional chemical synthesis of RNAi therapeutics faces challenges in quality, quantity, and economics, with demand projected to outpace current production capabilities by decade's end.

• The ECO Synthesis platform is designed to address scalability and cost limitations, enabling commercial-scale manufacture of RNAi therapeutics with high coupling efficiency, reduced impurities, and improved sustainability.