We had the pleasure of speaking with Britton Jimenez, SVP of Sales and Marketing at Codexis, about the continued momentum in oligonucleotide therapeutics. As the modality matures and clinical pipelines expand, manufacturing efficiency and scalability are becoming critical considerations, and Britton shares his perspective on how the field is evolving and what it will take to support the next wave of oligo programs.

To start, can you tell us a little bit about your background.

I joined Codexis in July 2024 and assumed responsibility for all commercial activities across the business, which includes RNAi manufacturing and small molecule pharma biocatalysis. I was previously with Catalent Pharma Solutions, where I served as Vice President, Global Partners, overseeing all key strategic relationships. Before Catalent, I was with Mayne Pharma, where I managed commercial activities and drove the growth of their CDMO business, Metrics Contract Services.

Codexis has been thinking about the oligo space for quite some time. Can you provide a bit of an overview of how the company narrowed in on oligos and the field at present?

Codexis’s entry into oligonucleotide manufacturing is a natural evolution of its 24+ years of leadership in enzyme engineering. The company’s deep expertise in developing high-performance biocatalysts for small molecule API manufacturing laid the foundation for its transition into RNAi therapeutics. Recognizing the growing demand for RNA-based medicines and the limitations of traditional solid-phase oligonucleotide synthesis (SPOS), Codexis identified enzymatic RNAi synthesis as a strategic opportunity to apply its core strengths in enzyme design, process development and scalability. The result is the ECO Synthesis® Manufacturing Platform, a proprietary enzymatic solution designed to meet the needs of modern RNAi manufacturing: scalable, high-quality and sustainable methods for large indications.

While cell and gene therapies have seen ups and downs, oligo-based therapeutics seem to be growing considerably. Why do you think that is? What is the value of this modality? Can you put the demand in perspective?

Oligo-based therapeutics, particularly siRNA and antisense oligonucleotides (ASOs), offer a unique combination of precision, modularity and versatility. Unlike cell and gene therapies, which often face delivery and regulatory complexities, oligos can be designed to target specific genes with high fidelity and are increasingly being applied to large patient populations. The RNAi therapeutics market is projected to reach $18 billion by 2030, driven by chronic diseases such as cardiovascular conditions, cancer, and diabetes. These indications require manufacturing at multi-metric-ton scales, underscoring the need for efficient, scalable production methods to meet clinical and commercial demand.

Do you think present synthesis methods, and specifically, chemical synthesis, can produce drug product at those scales? What are some of the limitations of solid-phase synthesis?

Solid-phase oligonucleotide synthesis (SPOS) is reliable for short, simple sequences but faces significant hurdles as constructs grow longer and more complex. Key limitations include low yields with increasing sequence length, limited scalability (often peaking at 5–10 kg per run), high infrastructure and solvent requirements, and sustainability concerns due to chemical waste. These constraints become especially problematic when manufacturing duplexed or chemically modified RNAi constructs at commercial scale. SPOS also requires significant facility investment, such as building large tank farms, to produce these materials, whereas alternative manufacturing methods can be done with existing equipment and require a small footprint.  

Are these challenges not surmountable? Why are enzymes the right answer for synthesis?

Codexis sees enzymatic synthesis as a transformative solution to the bottlenecks of SPOS. Enzymes offer a fundamentally different approach, operating under mild, water-based conditions, eliminating harsh reagents and reducing the number of synthetic steps. This not only simplifies process design but also improves yield, quality and sustainability. Codexis’s ECO Synthesis platform is designed to perform under process-relevant conditions, enabling scalable production of complex RNAi therapeutics.

Can you tell us a bit more about Codexis’s ECO Synthesis?

ECO Synthesis brings together a suite of enzymatic tools and processes designed to manufacture RNAi modalities more efficiently. The platform improves scalability, purity and yield sustainably while offering flexibility in how molecules are built. It encompasses both sequential enzymatic synthesis, in which polymerases build RNA strands nucleotide-by-nucleotide, and ligation-based assembly workflows. In ligation, short RNA fragments (made enzymatically, chemically or through a combination of both) are joined using engineered enzymes called ligases. Codexis supplies optimized dsRNA ligases specifically developed to enable high-efficiency assembly of duplexed RNAi constructs under manufacturing-relevant conditions. 

Is an efficient enzyme the key limiter to enabling enzymatic-based synthesis? What was the breakthrough?

Yes, enzyme efficiency, especially under process-relevant conditions, is critical. Codexis’ breakthrough came through its ability to engineer ligases and polymerases that maintain activity at high substrate concentrations, tolerate modified bases, and operate under scalable water-based conditions. Additionally, enzymes enable exquisite stereocontrol; thus, unlike SPOS, ECO Synthesis can be used to make stereo-defined RNAi assets that may be advantageous for efficacy, potency, and biological stability.

And what does this enable in terms of sequence length, complexity or modifications? Are there sequence chemistries that enzymatic methods struggle with today?

Codexis’s ECO Synthesis platform supports both short and long RNAi constructs, including duplexed and chemically modified sequences. The platform incorporates multiple approaches, including fully enzymatic sequential synthesis, ligation-based assembly and hybrid chemoenzymatic methods, allowing teams flexibility and efficiently address a range of modalities with high purity and yield. While enzymatic technologies are advancing rapidly, certain highly complex modifications or ultra-long sequences may still benefit from hybrid strategies or additional enzyme optimization, areas where Codexis continues to invest.

This sounds like a relatively different process, with different facility requirements. What would it take for a manufacturer to stand up an enzymatic process at scale?

Enzymatic synthesis is designed to be modular and compatible with existing infrastructure. Codexis’s ECO Synthesis uses water-based solvents and fewer steps, reducing the need for specialized equipment, large solvent-handling systems, and harsh chemicals. The platform has a small manufacturing footprint and can be implemented using standard bioprocessing equipment, enabling CDMOs to integrate enzymatic workflows into their operations with minimal disruption. This supports larger batch sizes (>25-50 kg) and fewer runs, both of which are critical for meeting commercial demand. In addition, because the process is water-based and less infrastructure-intensive, capital outlay is significantly lower, allowing CDMOs to build new capabilities cost-effectively while advancing sustainability objectives.

Is anyone running a commercial-scale process? What do you think it will take for groups to adopt this technology?

While full commercial-scale enzymatic RNA manufacturing is still emerging, Codexis is actively scaling its ECO Synthesis platform and conducting proof-of-concept projects with multiple partners. In 2025, our ligase was used to generate a 3 kg siRNA clinical batch at a leading CDMO. Adoption will depend on demonstrated performance, regulatory alignment, and the ability to meet GMP standards. Codexis recently committed to building a GMP facility, the ECO GMP Manufacturing Center, near our headquarters in Hayward, California, which should come online in late 2027.

What will be the capacity of that facility? What sort of scale manufacturing will it be able to produce and how will its cost per batch compare to traditional solid phase synthesis?

The ECO GMP Manufacturing Center is a 34,000‑square‑foot facility located near Codexis’ headquarters in Hayward, California. This multi‑purpose facility expands Codexis’ internal capabilities to include GMP manufacturing of siRNA and other oligonucleotides using the ECO Synthesis platform. The ECO GMP Manufacturing Center will support kilo scale and beyond for GLP, Phase I and Phase II clinical supply needs.  Together with the ECO Innovation Lab and Codexis’ global CDMO network, this GMP center enhances our ability to support a wide range of customer programs across development stages—from GLP toxicology studies to large‑scale GMP RNA manufacturing and locations.

The ECO Synthesis platform delivers value across the entire RNA manufacturing lifecycle, integrating scalability, exceptional purity and quality, and sustainability into a single enzymatic platform. While traditional approaches face rising complexity and resource demands as scale increases, ECO Synthesis enables efficient scale‑up with consistent RNA quality—without adding process burden or long‑term manufacturing risk.

How does Codexis view its role in the manufacturing process and getting this technology out to the market? Will this facility form the backbone of CDMO services?

Codexis is focused on enabling manufacturing through innovative enzymatic technology, process development and collaborative partnerships. Codexis focuses on transforming therapeutic manufacturing working closely with CDMOs and drug developers to integrate ECO Synthesis into their workflows. The company also offers diversified manufacturing options through the ECO Innovation Lab, our global network of CDMO partners or our ECO GMP Manufacturing Center.  Our goal is to get this technology out into the industry so that everyone has access.  We believe the value of ECO Synthesis extends not only to CDMOs and drug innovators but also to patients waiting for innovative treatments.

We’ve seen recent new and ongoing investments in manufacturing capacity from the likes of Alnylam investing in a hybrid approach, Agilent continuing their capacity investments, and then several additional groups focused on enzymatic, with the likes of Hongene, EnPlusOne, and others. How do you view this landscape? Is there a place for all manufacturing methods?

Codexis welcomes continued innovation across the pharmaceutical manufacturing landscape, particularly in enzymatic synthesis. Specifically, the Alnylam investment further supports exactly what we believe, which is enzymatic manufacturing is the future of the industry.  The current manufacturing landscape cannot meet the needs and demand of the market and we believe the ECO Synthesis platform can an excellent adjunct. Each therapeutic asset has unique characteristics and requirements; successful development depends on fit‑for‑purpose manufacturing strategies and the right partners. As therapeutics continue to evolve, operational and manufacturing approaches must advance in parallel. Building on decades of enzyme engineering leadership, Codexis applies its expertise and proven platform to RNA therapeutics, delivering scalable, differentiated performance at industrial scale while advancing sustainability.

Hongene recently announced manufacturing support for a Chinese drug asset that leveraged a chemoenzymatic ligation process. Do you see this as a pitstop on the road to full enzymatic-based synthesis?

Yes, chemoenzymatic approaches are a valuable transitional strategy. Codexis supports hybrid workflows that combine SPOS and enzymatic ligation, enabling partners to adopt enzyme-enabled manufacturing without overhauling their entire process. These hybrid models serve as a bridge to fully enzymatic synthesis, which Codexis is actively developing and scaling.

Where else might this technology be applied, for example, diagnostics or synthetic biology? Certainly, there’s strong interest in the production of ultra-long, complex sequences for a variety of applications.

Absolutely. Codexis’s enzyme technologies extend beyond therapeutics. The ECO Synthesis platform and CodeEvolver® Technology Platform can be applied to diagnostics, synthetic biology and bioconjugates: any area requiring high-fidelity, scalable nucleic acid synthesis. As the demand for ultra-long and complex sequences grows, Codexis is well-equipped to support innovation across multiple modalities.

Finally, what are you most looking forward to in 2026?

Looking ahead to 2026, we’re encouraged by the continued expansion of siRNA medicines in development and the growing need for scalable, high-fidelity manufacturing. We’re advancing the ECO Synthesis platform with stereoisomer control—a new capability designed to enable higher potency and purity—with supporting data to be presented at TIDES US.  In parallel, we are continuing to build out the ECO GMP Manufacturing Center, strengthening our ability to support customers as programs progress toward the clinic. Operationally, we plan to scale from 100 grams today to 0.5 kilograms by yearend 2026, supported by ISO 9001 certification and successful quality inspections by a large pharmaceutical customer. 2026 is off to a strong start with a recent contract to produce 50 grams of siRNA, providing additional line of sight to an ECO Synthesis enabled program advancing into human studies.