CODEXIS, INC.

Codexis, Inc. is a leading provider of technology solutions to improve therapeutics manufacturing, operating within the pharmaceutical and life science tools markets. The company focuses on impacting the manufacturing process by using its proprietary CodeEvolver directed evolution technology platform to discover, develop, enhance, and commercialize novel, high-performance enzymes and other classes of proteins. As of December 31, 2025, there were eight approved siRNA therapeutics on the market in the United States, primarily targeting rare disease indications, but hundreds of RNAi therapeutic assets are in development, including 41 assets in Phase 2 and Phase 3 clinical trials. The RNAi pipeline is pivoting from rare conditions to high-prevalence diseases like Alzheimer's, hyperlipidemia and hypertension, and the company expects worldwide demand for RNAi therapeutics to grow significantly.

In the ECO Synthesis manufacturing platform market for RNAi therapeutics, primary competitors include CDMOs such as Agilent Technologies, which have made significant capital investment to expand their RNA manufacturing capabilities using phosphoramidite chemistry. There are also multiple early-stage competitors pursuing fully enzymatic approaches, including EnPlusOne Biosciences and a UK-based consortium led by CPI. In pharma biocatalysis, primary competitors include companies marketing conventional catalysts such as Solvias AG, BASF, Johnson-Matthey and Takasago International Corporation, as well as large industrial enzyme companies and subsidiaries of larger contract research organizations like DSM Firmenich, Cambrex Corporation, Lonza, WuXi STA and Almac Group Ltd. The company's competitive advantages stem from its proprietary CodeEvolver technology platform, which has the power to transform the performance of an enzyme, tailoring it for a specific application and/or process using powerful machine learning tools and sophisticated workflows.

The company generates revenue through two primary streams: product revenue and research and development revenue. Product revenue consists of sales of biocatalysts used in the manufacture of small molecule active pharmaceutical intermediates, enzymes such as dsRNA ligase used in the manufacture of siRNA molecules, enzymes for the molecular biology and diagnostic markets, and Codex biocatalyst panels and kits. Research and development revenue includes license, technology access and exclusivity fees, research services fees, milestone payments, royalties, optimization and screening fees. The business model for the ECO Synthesis manufacturing platform involves several points of interaction with customers, including contract development and manufacturing services at smaller scale non-GMP conditions in the ECO Synthesis Innovation Lab, providing purified enzymes from its non-GMP manufacturing facility, and future services from a planned GMP manufacturing facility.

The company's ECO Synthesis manufacturing platform is comprised of enzymatic tools and processes designed to enable large-scale manufacture of RNAi therapeutics. In November 2024, the company presented data demonstrating the successful end-to-end enzymatic synthesis of an entire commercially approved siRNA therapeutic asset with the ECO Synthesis manufacturing platform. At the end of 2024, the company completed the build out of its ECO Synthesis Innovation Lab, a facility where the platform is deployed to synthesize gram-scale quantities of a customer's desired siRNA construct suitable for pre-clinical testing. In 2025, the company successfully manufactured non-GMP-grade siRNA drug substance for customers in its Innovation Lab under development services contracts. The company also entered into partnerships with three large-scale CDMOs to evaluate its ECO platform to ultimately synthesize GMP-grade siRNA drug substance for its customers.

In the small molecule pharma biocatalysis business, the company utilizes its CodeEvolver technology platform to develop optimized enzymes used by some of the world's largest pharmaceutical companies. As of December 31, 2025, the company sold enzymes as biocatalysts to pharmaceutical manufacturers for 18 therapeutic drugs that are currently approved for commercial sales. As of December 31, 2025, Codexis is selling enzymes to pharmaceutical manufacturers for 15 drug candidates currently in Phase 2 and Phase 3 clinical trials, or to customers working to convert to an enzymatic manufacturing process for drugs that have been commercially approved. The company also has licensed its CodeEvolver technology platform to pharmaceutical companies, having entered into platform technology licensing agreements with each of GlaxoSmithKline, Merck & Co., Inc. and Novartis Pharma AG.

In November 2025, the company signed a lease for a GMP manufacturing facility in Hayward, California, and is currently working on designs to retrofit this facility to manufacture RNAi therapeutics for customers in quantities sufficient for Phase 1 and potentially Phase 2 clinical trials. The company anticipates beginning construction in the fall of 2026, with the facility in full production capability by the end of 2027. In November 2025, the company announced it was reducing its emphasis on seeking new projects in its small-molecule biocatalysis business, primarily due to reduced pricing opportunity of the broader enzyme market. During the year ended December 31, 2025, 7,244,966 shares of common stock were issued and sold pursuant to the Cantor Sales Agreement, all during the second quarter of 2025, and the company received net proceeds of $16.4 million after Cantor's commissions and direct offering expenses. On June 27, 2025, the second tranche of $10.0 million under the Innovatus Loan was funded upon achievement of certain financial milestones.

Total revenues for the year ended December 31, 2025 were $70.387 million, compared to $59.345 million in 2024 and $70.143 million in 2023. Net loss for 2025 was $43.974 million, or a net loss per basic and diluted share of $0.50, compared to a net loss of $65.276 million, or $0.89 per basic and diluted share, for 2024. The decrease in net loss was primarily related to higher revenues and lower costs and operating expenses in 2025. As of December 31, 2025, the company had an accumulated deficit of $606.8 million.

A key growth vector is the advancement and commercialization of the ECO Synthesis manufacturing platform, designed to enable the commercial scale manufacture of RNAi therapeutics. The company expects worldwide demand for RNAi therapeutics to grow significantly as RNAi therapeutic assets progress through clinical development and are commercially approved. The company believes the ECO Synthesis manufacturing platform presents several advantages to potentially address the limitations of SPOS and phosphoramidite chemistry, including the potential to manufacture tens to a hundred kilograms of high-purity RNA per run. The company expects to expand its enzymatic tools and process offerings as it further enhances the ECO Synthesis platform to address the overall market needs for scalable and sustainable RNAi manufacturing. The company expects to advance at least one of its CDMO partnerships, including initiating a technology transfer to that organization, in 2026.

Another growth vector involves the company's planned GMP manufacturing facility in Hayward, California, which the company believes to be of high strategic importance to its ECO Synthesis business, capturing more of the economics of the drug supply chain. The company anticipates beginning construction in the fall of 2026, with the facility in full production capability by the end of 2027. The company is exploring expanding its services to include GMP manufacturing, which would enable it to provide clinical grade material to clients for at least Phase 1 clinical studies. The company also continues to provide services to existing and prospective customers in its small-molecule biocatalysis business who have challenging products that require unique solutions, where it can engineer more value-added and differentiated enzymes.

Product gross margins increased to 64% in 2025 as compared to 56% in 2024. The changes in cost of product revenue and product gross margin are primarily due to shift in sales toward more profitable products, and declines in less profitable legacy products. The company's ability to control and improve product gross margins is a factor that may contribute to fluctuations in operating results.

In November 2025, the company signed a lease for a GMP manufacturing facility in Hayward, California, and is currently working on designs to retrofit this facility to manufacture RNAi therapeutics. The company expects to partner with one or more CDMOs for bulk GMP-grade siRNA production to supply customers' clinical trials and beyond in the near term. The company's research and development operations include efforts directed towards engineering biocatalysts, bioprocess development, cellular engineering, biocatalyst screening, metabolites, strain improvement, fermentation development and process engineering. As of December 31, 2025, the company had 146 full-time employees and part-time employees worldwide.

Research and development expenses were $52.307 million in 2025 compared to $46.263 million in 2024. Selling, general and administrative expenses were $47.074 million in 2025 compared to $55.148 million in 2024. The company's primary uses of capital for the foreseeable future, including the next 12 months, are for compensation and related expenses, research and development expenses including manufacturing costs, laboratory and related supplies, legal and other regulatory expenses, and general overhead costs. As of December 31, 2025, $26.4 million remained available for sale under the Cantor Sales Agreement.

The company faces headwinds including that the enzymatic route for nucleic acid synthesis is novel and has not yet been commercialized, and the company may be faced with unforeseen results, delays and setbacks. The company also faces risks related to its dependence on a limited number of customers, as for the year ended December 31, 2025, one customer accounted for approximately 51% of total revenues. Additionally, the company faces risks from international trade policies, including tariffs, sanctions and trade barriers, which may adversely affect its business, as the U.S. government has recently announced substantial new tariffs affecting a wide range of products and jurisdictions.

The company faces constraints including that some of its product supply agreements with customers have finite duration, may not be extended or renewed and generally do not require the customer to purchase any particular quantity or quantities of products. The company also faces risks related to its dependence on a limited number of third-party contract manufacturers for large scale production of substantially all of its enzymes, as it manufactures enzymes primarily at its in-house facility and at three third-party CMOs: Lactosan in Kapfenberg, Austria, ACS Dobfar S.p.A. in Anagni, Italy, and Sekisui Diagnostics in Maidstone, United Kingdom.

The company has a history of net losses, with losses of $44.0 million ¹, $65.3 million ², and $76.2 million ³ for the years ended December 31, 2025, 2024, and 2023, respectively, and an accumulated deficit of $606.8 million ⁴ as of December 31, 2025. The company is dependent on a limited number of customers, as for the year ended December 31, 2025, one customer accounted for approximately 51% ⁵ of total revenues. The company has invested significant resources to enable enzymatic nucleic acid synthesis, which is based on novel ideas and technologies that are largely unproven, and failure to validate performance at scale could impede customer adoption. The company is dependent on a limited number of third-party contract manufacturers for large scale production of substantially all of its enzymes, manufacturing primarily at three CMOs: Lactosan in Kapfenberg, Austria, ACS Dobfar S.p.A. in Anagni, Italy, and Sekisui Diagnostics in Maidstone, United Kingdom. The company's ability to use its net operating loss carryforwards to offset future taxable income may be subject to limitations under Section 382 of the Internal Revenue Code, and as of December 31, 2025, the company had federal NOL carryforwards of $182.918 million ⁶ expiring between 2026 and 2037 and $237.257 million ⁷ that do not expire.

Management's message emphasizes the company's focus on impacting therapeutics manufacturing through its proprietary CodeEvolver directed evolution technology platform across two key areas: the ECO Synthesis manufacturing platform and the small molecule pharma biocatalysis business. Management highlights the successful end-to-end enzymatic synthesis of an entire commercially approved siRNA therapeutic asset and the completion of the ECO Synthesis Innovation Lab build-out at the end of 2024. Management notes that in 2025, the company successfully manufactured non-GMP-grade siRNA drug substance for customers in its Innovation Lab under development services contracts and entered into partnerships with three large-scale CDMOs. Management states that the company expects to advance at least one of these partnerships, including initiating a technology transfer to that organization, in 2026. Management also highlights the signing of a lease for a GMP manufacturing facility in Hayward, California in November 2025, and the anticipation of beginning construction in the fall of 2026, with the facility in full production capability by the end of 2027. Management emphasizes the strategic priorities of advancing and commercializing the ECO Synthesis manufacturing platform and continuing to provide services in the small-molecule biocatalysis business for challenging products requiring unique solutions.