GENEVA—Selexis SA, a life-sciences company specializing in mammalian (suspension-adapted CHO-K1) cell line generation, has struck yet another commercial cell license agreement, this time with Boston-based Pieris Pharmaceuticals. Pieris will use Selexis’ cell line development technology to advance development of its lead immuno-oncology candidate, PRS-343, which is designed to promote CD-137 clustering.
PRS-343 is a bivalent, bispecific fusion protein. The candidate is set to enter the clinic in the first half of 2017.
The licensing agreement provides Pieris Pharmaceuticals with access to the Selexis SUREtechnology Platform and SURE CHO-M Cell Line to advance the development of PRS-343, Pieris’ lead bispecific immuno-oncology drug candidate. PRS-343 is a CD137/HER2 bispecific that is designed to promote CD137 clustering by bridging CD137-positive T cells with HER2-positive tumor cells, thereby providing a potent costimulatory signal to tumor antigen-specific T cells.
“Prior to signing the licensing agreement, Pieris worked with Selexis to determine that the cell lines generated with the SUREtechnology Platform could effectively and robustly express PRS-343,” according to Igor Fisch, CEO of Selexis. “From these initial cell lines, a manufacturing cell line expressing PRS-343 will be generated and the PRS-343 product will support pre-IND enabling studies and clinical testing.”
This is the fourth announced licensing agreement for Selexis in as many months. Fisch believes that it shows the continued interest in (and need for) cell line development technology that enables mammalian cells to express complex and difficult-to-express proteins, such as bispecific fusion proteins.
The growth and production properties of the Selexis SURE CHO-M Cell Line are well defined, and have provided many pharmaceutical companies cost-effective solutions for development of innovative biological drug candidates, according to Fisch. Selexis is a pioneer in the sequencing and annotation of the genome and transcriptome of its proprietary CHO-K1 cell line. By combining whole genome sequencing with bioinformatics. some pharmaceutical companies have been able to speed up or salvage drug development programs.
“Through the innovation behind Selexis’ technology, our dedicated researchers are driven to provide companies such as Pieris with high-performance, cost-effective solutions for development of innovative biological drug candidates,” said Dr. Marco Bocci, Selexis’ vice president of licensing and business development. “Earlier this year, Pieris announced encouraging in-vivo proof-of-concept data for PRS-343, a bispecific protein produced with the Selexis SUREtechnology Platform and cell line that is expected to enter the clinic in the first half of 2017. We look forward to the continued progression of this important and unique drug candidate.”
The Selexis SURE CHO-M Cell Line, a proprietary high-performance mammalian cell line that is derived from CHO-K1 cells, is used for the production of therapeutic recombinant proteins and monoclonal antibodies (mAbs). The growth and production properties of the Selexis SURE CHO-M Cell Line are well defined, and the feed strategy has been optimized, allowing for faster and more efficient scale-up to bioreactors. Therapeutics that are generated using Selexis SURE CHO-M cells are in both clinical trials and marketed products.
Leveraging next-generation sequencing, Selexis has sequenced the genome and transcriptome of its proprietary CHO-K1 cell line, the Selexis SURE CHO-M Cell Line, according to Fisch. With this data, Selexis has been able to genetically manipulate the CHO-M Cell Line to support “even greater expression of a whole range of proteins, including difficult-to-express proteins.” In combination with the SUREtechnology Platform, Selexis can generate manufacturing cell lines in as little 14 weeks, “resulting in the fastest timelines for cell line development and highest levels of protein production in the industry.” This supports fast development timelines and allows for use of smaller bioreactors, saving on manufacturing costs.
“Selexis will work with the Pieris team to select the best manufacturing cell line based on a number of criteria, including PRS-343 activity (which will be assessed by Pieris),” Fisch said. “Once a final manufacturing cell line is chosen, Selexis will generate a research cell bank along with the appropriate regulatory package. The research cell bank will be transferred to the contract manufacturing organization of Pieris’ choice with SOPs for the Selexis SUREfeed strategy to facilitate manufacturing scale-up.”
Parameters for maximal secretion can vary significantly between proteins. Transcriptional, metabolic, folding, post-translational modifications and transport requirements can be quite different, even among mAbs, according to Fisch. By having sequenced the whole genome and transcriptome and having developed propriety bioinformatics tools to analyze that data, Selexis can determine and address potential secretion issues of “particularly challenging proteins.” This, in turn, allows Selexis to modify the CHO-M cell line to overcome those issues on a case-by-case basis. Using this approach, Selexis has been able to express proteins at clinically viable levels that other platforms could not, salvaging development programs that were otherwise slated for termination.
“With more than 95 partners worldwide, nearly 80 drug candidates in clinical manufacturing and two commercial products, the Selexis SUREtechnology platform continues to have strong commercial value in areas such as oncology, inflammation, blood disorders, asthma, allergies, respiratory and dermatology,” Fisch concluded.