“The more you engineer a protein, the less natural it becomes,” says Pfenex executive Patrick Lucy. The firm is using its clinically validated microbial expression platform to overcome these challenges for both its own product pipeline and its partners.
In May, Pfenex announced positive Phase III data showing its lead candidate PF708 is comparable with Eli Lilly’s osteoporosis drug Forteo (teriparatide).
The candidate – classed as a biosimilar in Europe but being filed in the US as a therapeutic equivalent via the 505(b)(2) pathway – is produced using the Pfenex Expression Technology platform based on the bacterium Pseudomonas fluorescens.
Pfenex’s chief business officer Patrick Lucy told BioProcess Insider at BIO earlier this month that the data helped to validate the platform, and signaled its potential to drive Pfenex forward both in its internal pipeline and its programs with biopharma partners.
“The Phase III data was ideal,” he said, speaking as part of the BPI Theater. “We’ve demonstrated that our product is very similar to the Forteo product that’s made in E. coli.”
If successful, the product will be commercialized by Alvogen in the US.
From Industrial Enzymes to Biotherapeutics
Dow Chemical Company developed the technology to make large-scale industrial enzymes with high titers, something Lucy said he recognized could be replicated for therapeutic proteins and vaccines.
“When I first saw this technology in 2001, Dow Chemical was producing 25 grams per liter at a 125,000 L scale, so this is a powerhouse platform in terms of protein expression,” he told us.
Pfenex span out from Dow in 2009, and while clearly expression rates are not all in double-digit grams per liter for its therapeutic products, the system has many other benefits, Lucy said, including the ability to make soluble proteins.
“One of the biggest challenges with some systems is the need to refold protein that not only costs you your product but it creates waste streams as well as capital infrastructure for large volume refold tanks. So being able to avoid that and manufacture a much smaller footprint is really a long-term advantage for any product made in the system.”
‘More You Engineer a Protein, the Less Natural it Becomes’
As well as developing a pipeline of its own products, Pfenex is looking to forge co-development partnerships for difficult to produce proteins, with its expression platform used as the enabling technology.
“What we saw over the past 15 years using this technology is not only its ability to express protein robustly but when partners are doing a lot of genetic modifications to either instill a half-life extension technology or look for mutant variants.”
He cited Pfenex’s PF745, a recombinant crisantaspase with half-life extension technology being developed in partnership with Jazz Pharmaceuticals as an example.
“What you see is the more you engineer a protein, the less natural it becomes and the harder it is to produce, and we’ve been able to overcome those challenges in heterologous protein expression platform given the fact we have a thousand shots on net to figure out which strain plasmid combination can deliver the product of interest, and that’s where the power of the platform comes in.”