The Situation
A California-based biotechnology startup was preparing to advance its therapeutic program from discovery into pre-clinical development. The program depended on a reliable, high-volume supply of Alpha-2-Macroglobulin (A2M)—a large, complex native plasma protein that is notoriously difficult to purify at scale while maintaining biological activity.
The company had initially sourced 30 mg of A2M for early-stage research. As their program advanced, pre-clinical studies required 20 grams—more than 600 times the original volume and 100 times Athens' existing production capacity at the time. They also needed the protein delivered to customized QC specifications—including defined purity thresholds, tailored aliquoting, and validated lot-to-lot consistency—to ensure reliable performance across sensitive animal models. Any delay in supply would push their entire development timeline backward.
Why This Was Hard
Scaling native protein production is not simply a matter of running a larger batch. A2M is a 720 kDa tetrameric glycoprotein—one of the largest proteins in human plasma. Maintaining its native conformation, protease-trapping activity, and endotoxin levels during scale-up demands precise control at every stage of isolation and purification. Most suppliers either cannot manufacture this protein at the required volume or would need to outsource portions of the process, introducing delays, quality variability, and loss of traceability.
For this startup, the challenge was threefold: the volume required was 100 times Athens' existing production capacity, the QC requirements were more stringent than standard catalog specifications, and the timeline was compressed to align with their pre-clinical milestones. To meet the customer's needs, Athens would need to expand internal capacity from 200 mg/year to 50 grams/year—a 250-fold increase—in under four months.
The Athens Approach
Athens began with a technical kick-off to align on the client's exact specifications—purity requirements, activity thresholds, aliquot volumes, and delivery milestones. This upfront alignment is a hallmark of how Athens works with development-stage customers: defining the target before committing to a production strategy.
From there, Athens' R&D and production teams designed a focused scale-up plan, drawing on the company's proprietary library of purification protocols developed over four decades of native protein chemistry. Because Athens manufactures entirely in-house at its USA-based facility, the team was able to iterate quickly—adjusting process parameters in real time without the delays inherent in outsourced or multi-site production.
Continuous project management kept the client informed at every stage, from raw material sourcing through final QC release. This transparency reduced the uncertainty that early-stage companies often face when working with contract suppliers on high-stakes deliverables.
The Result
Athens successfully expanded production capacity from 200 mg/year to 50 grams/year within four months. The client received 20 grams of validated A2M that met all customized QC specifications—enabling them to enter their next development phase on schedule and without interruption.
By scaling production through its own facility, Athens also provided meaningful cost efficiencies compared to what the client had been paying at research-scale volumes. Equally important, the validated QC protocols Athens established for this program created a repeatable framework—giving the client confidence in consistent supply as their program progresses toward later-stage studies.
What This Means for You
Whether you are a startup navigating the transition from discovery to pre-clinical development, or an established manufacturer scaling a validated process, Athens provides the technical depth and manufacturing flexibility to support your growth. Our scientists partner with you to solve problems, not just fill orders.
