Alligator Bioscience AB Phase I Trial Benefits From Cobra Biologics' maxXpress Platform

Cobra Biologics, an international CDMO of biologics and pharmaceuticals, has developed a cell line for Alligator Bioscience, a Swedish biotechnology company, expressing monoclonal antibodies for a Phase I clinical trial which commenced in April 2015.

Development of the cell line expressing the antibodies for CD40 Agonistic Immuno-Oncology ADC-1013 was performed by Cobra using the maxXpress platform, which harnesses the power of Ubiquitous Chromatin Opening Element (UCOE) technology. Combined with Cobra’s experienced and expert cell line development team, and the added benefit of the Ambr robotic system, the platform enables rapid and high-yielding production of correctly folded and glycosylated recombinant proteins, complemented by Cobra’s in-house cell-based potency assays and high-resolution mass spectrometry analytical capability. The maxXpress service can assess up to nine constructs at a time and can generate purified mixed clonal pool material in just 10 weeks.

The study, led by Alligator Bioscience, will determine the safety, pharmacokinetics, and pharmacodynamics of intratumorally administered ADC-1013, enrolling up to 40 patients during the dose escalation and expansion phases at five centers in the United Kingdom, Denmark, and Sweden.

“I am delighted that we have had the opportunity to work with Alligator on this promising clinical program and would like to congratulate the team on their success to date,” said Peter Coleman, CEO Cobra Biologics. “Cobra has been manufacturing protein therapeutics since 1995, and our maximum protein expression platform, maxXpress, has proven to be very popular to customers looking for both speed and quality.”

“ADC-1013 has been found to have good developability properties; manufacturing resulted in a very pure and stable Drug Product that has now been successfully administered to patients,” added Dr. Per Norlén, CMO & VP Development, Alligator Bioscience.

Cobra Biologics is a leading international contract development and manufacturing organisation (CDMO) providing biologics and pharmaceuticals for preclinical, clinical, and commercial supply. Eukaryotic genes are organised into chromatin domains, which exist in either a ‘closed’ state in which the genes are tightly condensed with proteins and are transcriptionally silent, or in an ‘open’ do-condensed state: a prerequisite for efficient gene expression.

When transfected genes integrate into mammalian chromosomes the structure of the chromatin at the site of integration has a profound effect on expression of the transgene. Consequently, only relatively rare transfected clones in which the expression vector has integrated into open chromatin show efficient expression of the transgene.

maxXpress Ubiquitous Chromatin Opening Elements (UCOEs) have been isolated which ensure efficient expression in a wide range of cell types including CHO-K1, CHO-S, HeLa, and NSO cells. UCOE containing vectors have been shown to markedly enhance the expression of a wide variety of intracellular, secreted and membrane-bound proteins. Inclusion of a UCOE (4-8 kb in size) in a eukaryotic expression vector permits efficient expression in the vast majority of stable clones, whereas with conventional vectors only a minor proportion of transfectants demonstrate high-level expression.

There is therefore no need for amplification and expression has been demonstrated to be stable over 130 generations. The combination of UCOE and CHO-S allows the generation of high yields of recombinant proteins. For more information, visit www.cobrabio.com

Alligator Bioscience discovers and develops innovative antibody-based immunotherapies for the treatment of cancer. Alligator Drug Discovery and Development span early research phases with lead identification up to proof of concept phase I/II clinical studies in cancer patients. For more information, visit www.alligatorbioscience.se.