E. coli is a well-established host that has been commonly used for large-scale production of recombinant proteins, including the production of synthetic insulins. But according to BioPlan Associates’ 14th Annual Report and Survey of Biopharmaceutical Manufacturing Capacity and Production, mammalian cell culture – specifically Chinese hamster ovary (CHO) – is by far the dominant platform in the industry. Mammalian cell culture operations have grown over the past decade, while microbial - including E. coli - have declined, according to the survey respondents.
But Vancouver, Washington-based AbSci is hoping to bring biomanufacturing back to its E. coli roots through its SoluPro expression platform. The technology is based on semi-oxidizing cytoplasm, engineered from the E. coli genome, which the firm says is ideal for protein production, even at commercial scale, and can drastically reduce the need for CHO and other mammalian expression platforms.
We spoke with AbSci’s founder and CEO Sean McClain to find out whether SoluPro is, as the company suggests, a potential CHO stopper:
Biopharma-Reporter (BPR): What is your SoluPro platform?
Sean McClain (SM): Through a proprietary genetic engineering, we’ve produced a biomanufacturing platform that enables ultra-high efficiency manufacturing, specifically conferring significant COGS reduction, capacity gains, and enabling the producing difficult-to-express proteins.
BPR: What types of therapeutic proteins can it make?
SM: It is able to produce the full spectrum of therapeutic proteins, including full-length antibodies, Fabs, antibody scaffolds, enzymes, and hormones.
BPR: And what sort of yields are you able to achieve?
SM: SoluPro achieves unprecedented yields of high-quality product, in some cases exceeding 20 g/L for difficult to express products such as insulin.
BPR: But at the end of the day it is still an E. coli based systems, right? How does it compare with traditional systems?
SM: Traditionally, protein expression in E. coli is achieved either through cytoplasmic production as inclusion bodies (misfolded agglomerated protein that must be solubilized and refolded) or through secretion into the periplasmic space. Cytoplasmic production, is desirable because it has significantly higher capacity than the periplasm, places no restrictions on protein size, and achieves dramatically shorter production cycles (1-2 days) compared to secretion-based expression systems.
Through careful engineering of the E. coli genome, AbSci has developed a unique cytoplasmic environment: the semi-oxidized cytoplasm. A semi-oxidizing cytoplasm is ideal for protein production because it is capable of producing complex, disulfide bonded proteins, yet maintains a healthy, viable cell population that grows to high-cell densities, even at commercial scale.
BPR: And how does it compare with CHO cell expression systems?
SM: The ability to produce complex, disulfide bonded proteins makes SoluPro a threat to CHO mammalian systems due to dramatically shorter production cycles, 1-2 days compared to 20-24 days, while achieving even higher titers. The platform is capable of producing any protein currently produced in a mammalian system that does not require glycosylation, including IgG4.
BPR: Industry seems pretty stuck in its ways with CHO expression systems dominating monoclonal antibody production. Can SoluPro challenge this?
SM: The industry has been looking for other ways to rapidly and less expensively produce biologics for years. Our partners have already communicated their interest to us in using SoluPro to produce a variety of Fc-fusions, Fabs, and full-length monoclonal antibodies (primarily IgG4s).
In addition to dramatic plant productivity increases, SoluPro offers advantages throughout the entire drug development pipeline. During research and development, SoluPro can produce gram quantities of material for preliminary screenings in a matter of days instead of weeks. Promising molecules can then be seamlessly scaled to high-cell density fermentations, starting with clinical lots and ultimately used for commercial production. Because it is E. coli, SoluPro also eliminates the costly and time-consuming cell-line development process (6-12 months), which can significantly delay entry of products into the market.
BPR: What are your plans for SoluPro?
SM: Our vision is for SoluPro to be used as a true platform for biopharmaceutical companies. If you use it during drug discovery and it offers continued and dramatic savings during commercial manufacturing, why would you switch? The platform can scale directly to meet clinical and market demand.
BPR: How do you plan to bring this expression platform through to commercialization, and in what sort of timescale?
We’re currently working with multiple partners on a few of our lead programs. We can’t disclose specifics, but the technology is fully scalable and we’re excited about the progress we’ve made with our partners in commercializing the technology.
BPR: There is interest among biomanufacturers for ‘next-generation’ expression systems. Biogen, for example, has been pretty vocal about this. Have you has any direct interest from Big Biopharma?
SM: Yes, we have received considerable interest from some of the world’s largest pharmaceutical companies along with smaller companies interested in applying the technology to molecules in their clinical and pre-clinical pipelines.
We are also engaged in discussions with large pharmaceutical companies for implementing SoluPro for the production of marketed biopharmaceuticals. We are rapidly scaling our laboratory footprint and scientific staff to keep up with this interest.
BPR: Let’s talk about the appointment of Coherus’ Alan Herman (AbSci has just appointed Coherus Biosciences’ chief scientific officer, Alan Herman, to its Scientific Advisory Board). What will he bring to AbSci?
SM: Dr. Herman paved the way for biologic characterization at the US FDA. Having that experience and perspective informing our scientific development is critical to AbSci as we commercialize our technology. We strive to have the best biomanufacturing technology on the market, and that means that we must have the best downstream analytics to support our work. Dr. Herman brings considerable expertise in this regard. We produce revolutionary titers, but don’t compromise when it comes to product quality. Quality is just as important as quantity.
BPR: Coherus is a biosimilar producer. Could your tech platforms offer a competitive advantage to Herman’s firm or any other firm looking to compete in biosimilars?
Absolutely. One of our primary missions as a company is to drive down drug costs and make them more attainable to everyone that needs access. Biosimilars offer a lot of potential in that regard and we’re excited about their entry into the market.
Our technologies bring dramatic cost savings to biomanufacturers. We can do so in partnership with innovators or work with biosimilar manufacturers to make their products even more competitive. In particular, the non-antibody biologics that are coming off patents, such as insulin, are an ideal fit for our technology.