Bill Taylor, Director, Business Development & Commercial Operations at San Diego-based Pfenex, explains what his company’s bacterial strain engineering technology is capable of, and why the new partnership with SAFC is great business for both companies – and their customers.
Can you tell us a little about Pfenex’s history?
Pfenex is a venture backed privately held biotechnology company based in San Diego, California. After developing the Pfēnex Expression Technology™ platform within The Dow Chemical Company, Dow made the strategic decision to establish Pfenex Inc as an independent entity. Pf enex is currently backed by a single venture capital firm, Signet Healthcare Partners and Dow is a minority shareholder. Following the separation from Dow, Pfenex has grown the business significantly by building on the strain engineering business, establishing Reagent Proteins.com, developing Biosimilar products and developing vaccine products via multiple United States government contracts. Currently, Pfenex supports drug developers through the expression and provision of reagent proteins, discovery proteins and lead proteins. This partnership with SAFC will help to facilitate the ability to meet our partners’ needs from discovery through to cGMP manufacturing.
What’s different about your technology?
The Pfēnex Expression Technology™ platform is a very powerful protein expression technology, based on a novel host, Pseudomonas fluorescens. Legacy recombinant protein expression hosts such as E. Coli and yeast tend to have high failure rates with regard to expression of soluble active protein. In addition, the time required to identify the optimal expression strain in these systems is protracted, resulting in significant opportunity cost for the drug developer. The Pfēnex Expression Technology™ platform offers a robust solution to the real and opportunity costs incurred through the maintenance of several recombinant expression platforms. For a multitude of reasons, including cost of goods, quality and speed, non-glycosylated proteins are best produced by a prokaryotic host. This ensures the protein of interest can be produced while avoiding unnecessary and often heterogeneous post-translational modifications.
After screening in excess of eighty proteins that failed to express successfully in E. coli, and in most cases both E.coli and yeast, the Pfēnex Expression Technology™ platform has maintained a success rate approaching 90%. Recent strategic deals between Pfenex Inc and large biopharmaceutical companies, including Boehringer Ingelheim, MedImmune, and Merck & Co. Inc. confirm this trend. Biopharmaceutical developers are leveraging the Pfēnex Expression Technology™ platform earlier in discovery to avoid the opportunity costs that arise from the challenges caused by legacy expression hosts.
Tell us more about how the protein expression platform.
The Pfēnex Expression Technology™ platform expresses proteins at high titers, and high quality; a production strain capable of producing soluble, active protein can be identified within five weeks. The platform combines a powerful Pseudomonas fluorescens production organism, a vast array of expression components and unique engineered host strains, with an advanced, unique, robotic strain screening platform to achieve an unprecedented success rate approaching 90% with proteins that failed to express in other hosts. This robotically-enabled combinatorial approach allows Pfenex scientists to screen thousands of unique expression strains in parallel within five weeks while generating titer, functionality and quality data for the expressed protein. The platform also enables the expression of a single or several genes of interest in parallel thus supporting and integrating the entire product development value chain, including discovery, development and manufacturing.
What would you highlight as the main advantages of your technology over others?
1) Opportunity Cost Avoidance – This is the greatest value driver derived from the Pfēnex Expression Technology™ platform. The opportunity cost involved in having to evaluate several expression hosts each time a candidate comes through the pipeline is extraordinary. The typical routine is to try E.coli, then yeast and then mammalian; this is extremely costly in hard cash as well as time. All of this work takes a lot of time involving not only molecular biology resources but also analytical, fermentation etc. Our success rate in terms of successful expression (high titer of soluble active protein) in the first screen approaches 90% thus avoiding repeat work and unnecessary delays.
2) Quality – The second greatest value driver. If a protein does not require glycosylation then the host used to produce that protein should not be capable of glycosylation. In this scenario the glycosylation simply becomes a contaminant leading to heterogeneity and hence low quality. Another quality attribute of Pfēnex Expression Technology™ is our library of protease knockout strains. This aspect of the toolbox is routinely leveraged in our screens to resolve proteolytic degradation issues. Having a system that can produce high quality protein at the small scale research stage which can be easily scaled for clinical and commercial quantities significantly reduces your long term quality risk with any product.
3) Cost of Goods – The third greatest value driver. Given the rapid 36 hour fermentation cycle time combined with the extremely low cost media and high cell densities Pfēnex Expression Technology™ offers the best cost of goods profile of any expression technology in the market today. In fact a recent study that was performed by Biopharm Services (UK) confirms this.
So why are you going into partnership with SAFC?
We realized that while we are an industry leader in strain engineering, provision of reagent and discovery proteins, large-scale process development and optimization, we do not have cGMP manufacturing capabilities. While chatting with SAFC’s Dave Backer at a conference it became evident that there was a great deal of synergy between the capabilities of SAFC and Pfenex. This partnership combines Pfenex’s world class protein expression platform and process development scientists with SAFC’s scientific team and their state of the art cGMP manufacturing facility. Pfenex delivers production strains that are capable of producing soluble, active protein in high titers thus driving efficient utilization of SAFC’s cGMP manufacturing assets ultimately resulting in a win, win, win situation for our partners, Pfenex and SAFC. In addition, SAFC’s bioconjugation development and manufacturing facility enables a partner who is developing a conjugate vaccine to work with Pfenex to source the carrier protein, and the SAFC team can leverage their expertise in developing an optimal conjugation unit operation. The partnership consists of complementary capabilities – we work together to provide our partners with a seamless offering from discovery through to cGMP production.
How do you see your relationship with SAFC evolving and expanding?
The relationship will begin through providing our technology and services to our partners throughout the industry. Our strict focus will be to progress our partners’ innovative products at a success rate and pace unparalleled in the industry. SAFC’s commitment to financially support a portion of the upfront costs of strain engineering on behalf of the partner in return for a cGMP manufacturing commitment will enable a broad range of biopharmaceutical developers to access the Pfēnex Expression Technology™. As we build a reputation for delivering on our commitments, on budget and on time, we are confident that the pipeline of opportunities will significantly expand. Any aglycosylated protein, regardless of complexity or application, is a perfect candidate for this partnership.