Christian Schwarz, Chief Executive Officer at Numaferm, introduced pepteins: pepteins lie in between peptides and proteins regarding their amino acid length. Furthermore, pepteins have unique functionalities and are difficult to produce because neither chemical synthesis nor recombinant proteins can be easily adjusted for short proteins. Schwarz categorised nanobodies, antibody fragments, and disulfide-rich proteins as pepteins.
Numatech is a platform that allows members of the biopharma community to produce peptides independently of sequence, length, or functionality. The platform relies on two central technologies: Numasec and Numaswitch.
Numasec genetically fuses a target to a Sectag protein and co-expresses a transport complex in the cell wall of Gram-negative bacteria like E. coli. However, this technology relies on a recombinant approach which is slow in comparison to chemical synthesis because the recombinant process requires adjusting the process and conditions to the target. As a result, the technology is no longer used at Numaferm despite its effectiveness.
Despite the initial disappointment, Schwarz learned from this technology and developed Numaswitch, which secretes Sectag proteins are highly soluble and contain calcium-binding domains and binding events convert the entire protein into a stable soluble form. The platform also aimed to produce inclusion bodies which are usually considered as waste, but inclusion bodies carry major advantages such as their high expression and purity and their ability to refold proteins in the presence of calcium ions. Schwarz explained: “We developed a technology to prevent intermolecular interactions during the refolding step. So we wanted to come up with a platform that grants access to the advantages of inclusion bodies while enabling the efficient, biochemical refolding of unfolded into functional proteins.” So this technology allows for the production of functional proteins up to 600 amino acids.
Although this marks good progress, Numaferm’s clientele desire a platform that can cleave off the switchtag protein which lead to the development of the Numacut TEV protease platform. The Numacut TEV protease can cleave off the switch tag protein from the target independently of the N-terminus, making the production process more efficient.
The combination of the Numacut and Numaswitch technology allows for the production of targets independent of sequence. The technology is also adaptable to peptides up to 600 amino acids in length, meaning it is scalable and can cater to a wide range of customer needs. Furthermore, production timelines are very short: milligram sampling is offered within a month, and gramme scale samples within two months. Overall, Numaferm’s approach bridges the gap between chemical synthesis and recombinant technologies, offering speed, purity, and scalability. The Numacut TEV protease is now commercially available on the market.
