THE INTEGRATION IMPERATIVE: ADVANCING TIDES MANUFACTURING THROUGH BIOCATALYSIS AND FLOW TECHNOLOGIES

For the past decade, biocatalysis and continuous flow have redefined small-molecule manufacturing, offering enhanced safety, efficiency, and sustainability. Yet, accessing these technologies often forces drug innovators into a fragmented model—stitching enzyme discovery from one vendor, flow reactors from another, and process development from a third.

At Asymchem, we view this fragmentation as a strategic weakness. True manufacturing innovation requires an integrated platform built from the ground up. This philosophy of manufacturing-led innovation guides our approach, industrializing biocatalysis and continuous flow not as isolated services, but as core, interconnected capabilities within a single, end-to-end operational framework.

Integration alone, however, is not enough—at Asymchem, we are built on deep investments in enabling technologies, including proprietary enzyme carriers, a high-throughput screening platform, a self-developed resin database, and custom-engineered flow reactors designed and fabricated in-house. That is why, as the TIDES revolution accelerates, this infrastructure uniquely positions us to help partners navigate the transition from lab-scale complexity to commercial-scale reality.

The Integration Imperative: Beyond Point Solutions

The industry’s fragmented approach creates a hidden tax on innovation. Asymchem’s model serves as the antidote, offering a fully integrated biocatalysis value chain that leverages AI-guided enzyme evolution, automated high-throughput screening, and dedicated GMP manufacturing—all within a single ecosystem. This ensures enzymes are designed from day one for real-world manufacturing constraints.

Crucially, we couple this technical depth with flexible IP strategies, allowing partners to license proprietary enzymes, buy them out, or co-develop new IP.

Our continuous flow platform follows the same principle of deep integration, where chemists, chemical engineers, and equipment designers collaborate from the earliest stages. By designing and fabricating our own reactor systems—from dynamic tubular reactors for hazardous chemistries to custom skids for solid handling—we seamlessly scale processes from grams in the lab to hundreds of kilograms per hour.

From Small Molecules to TIDES: Transferring the Continuous Mindset

When the industry confronted the scalability limits of TIDES manufacturing, the solutions that transformed small-molecule manufacturing proved equally applicable: biocatalysis for exquisitely selective bond formation, continuous flow for overcoming diffusion-limited bottlenecks, and the combination of the two to achieve productivity neither could deliver alone.

These technologies deliver the greatest impact where the need is most acute: large-volume, cost-sensitive manufacturing. So even as Asymchem advanced its TIDES platform, we took a deliberate strategic step: deploying continuous immobilized enzyme reactors in upstream amino acid production.

The results were transformative: achieving >98% conversion with an immobilized enzyme under flow mode, while extending enzyme lifetime from hours to weeks, reducing enzyme consumption by over 70%, and cutting COGS by double-digit percentages. More importantly, the operational data and engineering confidence gained now flow directly into Asymchem’s peptide and oligonucleotide programs.

Breaking the TIDES Bottlenecks: Extending Flow Thinking Downstream

In peptide manufacturing, the true constraints on throughput and cost lie in cleavage, deprotection, and downstream processing. Asymchem’s integrated continuous cleavage platforms apply flow principles to resin cleavage, with proven results across multiple commercial programs:

• Manufacturing cycles shortened by 3 days per batch
• Productivity improved 2-fold versus batch cleavage
• Solvent consumption significantly reduced while maintaining purity and yield

The same thinking now extends to continuous precipitation and continuous deprotection, creating an increasingly integrated workflow from crude intermediate to purified API.

In downstream purification, multi-column countercurrent solvent gradient purification (MCSGP) has emerged as a powerful tool for continuous chromatography. When paired with continuous upstream operations, the approach delivers yield improvements of 10–15% while reducing solvent consumption by half and cutting purification and IPC cycles by 80%.

Enabling Efficient Oligonucleotide Assembly: Chemoenzymatic Synthesis

Nowhere is the power of integration more evident than in Asymchem’s chemoenzymatic oligonucleotide platform. By combining AI-driven design with continuous-enabled process architecture, we are redefining what is possible in siRNA manufacturing.

At the core of the platform is AI-driven ligation-site prediction, with in silico tools identifying optimal fragment boundaries at >95% success rate—transforming trial and error into a deterministic workflow.

In a recent siRNA program, enzymatic ligation achieved >99% conversion within hours, yielding 90.4% crude purity without chromatography, and 97.7% final purity after a single chromatographic step. The overall process reduced PMI by more than 70% compared to a solid-phase-only approach.

The platform has been validated under GMP at hundred-gram scale and successfully applied to divalent siRNA, sgRNA, and multiple commercial programs. It is not a future aspiration—it is a manufacturing reality at Asymchem, today.

A Unified Platform for an Integrated Future

The biocatalysis and continuous flow chemistry are pillars of a unified TIDES manufacturing ecosystem at Asymchem, underpinned by infrastructure designed for scale.

Asymchem’s facilities house 60 solid-phase synthesizers and 14 commercial manufacturing trains for oligonucleotides, with capacity exceeding 180 mol/year. For peptides, total SPPS reactor volume now exceeds 45,000 L, corresponding to more than 22.5 metric tons of annual production capacity—and with new facilities underway, we are on track to reach approximately 69,000 L by the end of 2026.

As modalities grow more complex—divalent siRNA, peptide conjugates, novel oligonucleotide architectures—the ability to combine biocatalysis, continuous flow, and advanced downstream processing becomes not just an advantage, but a necessity.

For our partners, this means faster timelines, lower costs, reduced risk, and a clear path from early-stage development to commercial-scale production. More importantly, it means working with a partner who thinks not in terms of individual reactions, but in terms of integrated manufacturing systems—as what the future of TIDES therapeutics demands.

Contact
inquiry@asymchem.com
www.asymchem.com