Presented by Stewart McNaull (senior vice president of business development, KBI Biopharma) 11:40 am–12:00 pm

Founded in 2004, KBI Biopharma operates a core facility in Durham, NC. In 2013, the company needed more space and set up laboratories in Research Triangle Park, NC. Using mammalian cell lines, it has developed both monoclonal antibody (MAb) and non-MAb platforms. It acquired a former Merck site in Boulder, CO, in 2014 and retained staff experts in fermentation expression, refolding, and mass spectrometry. With manufacturing of clinical and commercial products in 1,500-L stainless steel bioreactors, the site is building a 300-L single-use fermentation suite that will be ready this autumn. Its world-class particle characterization group and modeling–simulation group also works with the University of Boulder. In February 2017, KBI acquired Opexa Therapeutics in Woodlands, TX, where staff perform phase 1 and 2 manufacturing of cell therapy products (including cell-based assays).

Analytical, Formulation, and Stability (AFS): Analytically, KBI has covered more than 220 molecules (antibodies and other complex proteins). In formulation development, KBI has worked with more than 110 distinct molecules (60 antibody products) in late-stage and commercial projects.

Process and Analytical Development: In mammalian cell culture, KBI has worked on more than 80 molecules (both first-in-human, early-phase rapid development and high-throughput, late-phase development). The company has performed cell-line development for more than 30 molecules, either using client host systems or its own system (KBI has partnered with Selexis and uses Selexis cell lines). Program types include cell-line development through GMP manufacturing, technology transfer, and modifying processes for facility fit. On the microbial side, the company has clinically developed more than 50 recombinant proteins (10 through manufacturing, with many client and regulatory audits). It has been involved with five late-stage experiments through process validation, three programs through process performance qualification (PPQ) batches, and one commercial product pending approval.

Emerging Therapies: KBI optimizes MAb platforms for early development and late phases. But for bispecific antibodies, Fc-fusion proteins, and other complex molecules, a simple platform won’t work. The company’s scientists determine what parameters need to be studied to develop a good process for each product.

McNaull described several case studies: a MAb product for which KBI optimized production and robustness to prepare it for commercial manufacturing; a bispecific that the staff migrated to a platform for production; and an HIV vaccine (with sponsorship by the Gates Foundation). For the latter, vaccine scientists considered a number of HIV envelope proteins in a strategy to elicit an immune response. At least five molecules have gone through development and manufacture, and KBI scientists now are developing a platform that is working so far for these complex molecules (which also require advanced analytics).

McNaull is excited about his company’s work in cell therapy and productivity of difficult-to-express proteins. Five clinical trials in Texas have included processing of >1,500 patient samples for 30 clinics with no errors. Products made in Texas include CAR-T, CAR- and K-antigen–specific T cells, and others. KBI can also make regenerative medicine products. It has developed cell lines for multiple molecules and is reporting good titers. The real benefits of Selexis lines is their speed and reliability, McNaull said: “Early clones are representative of your final clones.” The company’s future plans are to leverage analytical tools and focus on the goal moving from DNA to drug substance in nine months (gene to GMP manufacturing).

Questions and Answers
What about transient expression? KBI can perform transient protein expression and has done so at its Durham site. “But we believe that if you can get a Chinese hamster ovary (CHO) clonal pool within three weeks, why would you go transient? Because it might be less expensive, we would have a discussion with our client about the best way to proceed.”

Watch these full presentations online at www.bioprocessintl.com/BIO2017.