Going “Cell Free” Can Put a Rush on COVID-19 Antibody Therapies

A biopharma company anxious to bring a COVID-19 therapeutic to market might feel calmer if it learned about SwiftScale Biologics, a company that has developed a novel cell-free protein manufacturing technology. According to SwiftScale, the technology not only fills a longstanding gap in cell-free technology, it also promises to speed antibody production as much as 10-fold.

Although SwiftScale’s technology has applications beyond COVID-19 therapeutics, the company is emphasizing how it can help others respond to the current pandemic. SwiftScale is positioning itself as a “COVID-19 Treatment Accelerator,” and companies such as Centrivax and Bioinformatics Solutions have taken notice. (Both companies recently entered partnerships with SwiftScale.)

“Now, more than ever, the speed of getting treatments to patients is key,” declares David Mace, SwiftScale’s CEO and co-founder. “Our goal from the start has been to bring new drugs to trials faster. Initially, we focused on oncology, autoimmune diseases, and rare disease drugs.” Now the company and its partners are tightly focused on COVID-19.

SwiftScale Biologics’ cell-free method of manufacturing proteins eliminates the need for CHO-based manufacturing. “The CHO-cell method takes about 18 months to go from a DNA sequence to clinical doses for patients,” Mace points out. “That has been a big limiting factor to bringing drugs to the clinic.” In contrast, SwiftScale’s method goes from DNA sequence to individual patient doses in just a few months. “That speed,” Mace emphasizes, “allows a lot more flexibility in developmental and manufacturing timelines.”

Because the manufacturing system is agnostic to the drug, the specific drug qualities are determined entirely by the developer rather than any cellular manufacturing limitations.

“With a cell-free method, you lyse the cell. You have no cell walls. There is no enclosure around the protein expression components—which remain functional. You can control the conditions in a finely tuned manner,” he explains. “Then, you put in the DNA and energy components. The ribosomes are in solution, and they can generate protein within hours. It’s a complex, finely tuned process.”

More specifically, the cell-free system is based on extracts from an optimized strain of Escherichia coli that are enriched with certain components that set up a simple reaction, a reaction that produces a specific protein when the DNA instructions to produce that protein are added.

That’s the technology developed by SwiftScale co-founders Matt DeLisa, PhD, an engineering professor at Cornell University, and Michael Jewett, PhD, a chemical and biological engineering professor at Northwestern University. Since its formation, the company has moved this technology to handle large-scale production.

Fulfilling unmet needs

The company evolved from an unmet need. “When I was a potential customer,” Mace recalls, “I wanted a way to produce protein quickly. I wanted 100 different variants in a day. And I wanted the ability to go through a few cycles quickly to get drugs to patients as quickly as possible.”

As an entrepreneur in residence at 8VC, a venture capital firm, he was in position to comb through scores of technologies still in academia to improve drug development by speeding discovery, target identification, manufacturing, and other elements. “I was really excited by the advances in synthetic biology,” he says.

Ultimately, it was the passion and expertise of DeLisa and Jewett that convinced him that theirs was the project to advance. “They had a desire to bring drugs to patients quicker,” Mace affirms, “and they had a practical sense of what it would take to translate their work from academia to practical reality.” SwiftScale Biologics was founded in 2018 as a Cornell and Northwestern University spinout.

The challenge, until recently, has been to optimize the platform to make clinical- and commercial-scale quantities of proteins. “Initially,” Mace notes, “it was a theoretical pursuit.”

To develop the platform, SwiftScale had to clear a series of hurdles. “We had the leaders in synthetic biology as the co-founders. They optimized a lot of the processes in their labs, but there are many different levels of optimization,” Mace acknowledges. Optimization tasks that Mace cites include finding the right chemicals and proteins for the cell-free culture broth, selecting the right fermenters and other process equipment, and determining the best ways to configure the equipment. Although the platform incorporates standard bioprocessing equipment, there are, Mace notes, “a lot of nuances” to how the equipment is used.

Now, two years in, SwiftScale has achieved what may be its most important milestone: producing clinical-scale microbial batches and establishing commercial-scale capacity. “It’s not a turning point,” he says, “but it does change the conversation.”

From candidate selection to clinical quantities

SwiftScale prefers to work early on with partners. Typically, SwiftScale and a development partner come together when the partner has between 1 and 100 variants in consideration. To narrow the candidates, SwiftScale produces hundreds of proteins in small, parallel reactions for characterization.

Once clinical candidates are selected, production can be scaled up to quantities for small-scale animal studies; to larger quantities for human trials; and then, ultimately, to 5000-L GMP batches. “We’re quite differentiated in our ability to provide a protein at various scales,” Mace asserts, “and we can provide a protein under GMP conditions very quickly.”

“Most of our platform is for antibody drugs, but we also have worked on other classes of biologics,” Mace continues. The company can produce microbial-based batches as well as cell-free-based batches. It offers purification expertise, and it can tap into a network of consultants to bring regulatory expertise to its partners, to help them ensure that the necessary parameters are met and that the necessary studies are performed for specific drug classes. “It’s simple until it isn’t,” he quips.

If speed is the company’s strength, small size is its weakness. “We’ve been intensely focused on our COVID-19 programs this spring and are dedicated to providing better service than a group would get with a larger company,” Mace says. Even though the company is adding staff, it still lacks the bandwidth to work with multiple partners simultaneously. If you’re already a SwiftScale partners, though, you benefit from the company’s almost undivided attention. “We pride ourselves on being ‘high touch,’ efficient, and quick,” Mace insists.

Companies interested in working with SwiftScale should, ideally, contact it early in the development process. That’s when the company can provide the most value. “There are always a lot of nuances for each drug,” Mace observes. “Let us optimize the drug and ensure it’s compatible with our cell-free manufacturing system.”

SwiftScale partner Centivax plans to launch clinical trials this summer, as early as late July. If the trials succeed, SwiftScale can expect to produce 100,000 doses per month.

Once the initial COVID-19 therapeutics are completed, SwiftScale plans to expand its work to non-COVID-19 programs with its partners. Oncology and autoimmune diseases continue to be of interest. Mace adds, “We’d like to apply this technology to as many different drugs as we can.” Seeing this cell-free technology cited in many scientific journals is another goal.

At present, however, Mace is focused on COVID-19. “COVID needs therapeutics fast,” Mace stresses, “and we’re excited to be a part of that.”