Phase I Clinical Trial Completes Using Cell Line Expertise At Cobra Biologics

Cobra’s maxXpress platform used to enable rapid and high-yielding expression of protein ADC-1013 for Alligator Bioscience Immuno-Oncology study in advanced solid tumours

Cobra Biologics (Cobra), an international CDMO of biologics and pharmaceuticals, recently announced that the immuno-oncology antibody ADC-1013 manufactured as part of the company’s cell line development programme for Alligator Bioscience AB (Alligator), a Swedish biotechnology company, has completed its first Phase 1 clinical trial.

As an essential step in the antibody production process, Cobra’s experienced and expert team developed the cell line expressing ADC-1013 for CD40 agonistic immuno-oncology using Cobra’s maxXpress service. The maxXpress platform harnesses the power of Ubiquitous Chromatin Opening Element (UCOE) technology and enables rapid and high-yielding production of correctly folded and glycosylated antibodies, complimented 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 allowing rapid selection of the most suitable construct.

Having produced the cell line for ADC-1013, Cobra also analysed the Drug Substance (DS) and Drug Product (DP) for this particular trial, also performing DS and DP stability studies.

Peter Coleman, CEO Cobra Biologics, commented: “Congratulations to Alligator for their successful completion of their Phase I clinical trial with ADC-1013. For our cell line development team such announcements are extremely rewarding seeing their hard work contributing to the success of Alligator’s clinical trial.”

Dr Per Norlén, CEO, Alligator Bioscience, commented: “We are very happy to have completed the first clinical Phase I trial with ADC-1013. Alligator has a long-standing and successful collaboration with Cobra and has seen very good results using their maxXpress system for both ADC-1013 and other cell lines. ”

The Phase I trial was a dose-escalation study involving intratumoral and intravenous administration of ADC-1013 at five clinical sites in Sweden, Denmark and the UK (ClinicalTrials.gov: NCT02379741) including 24 patients and ten different tumour types. Results are expected Q4 2017 and will focus on safety and tolerability, pharmacokinetics, immunogenicity, biomarker response and clinical response evaluation.

In May 2015 Cobra released details of its involvement in manufacturing immuno-oncology antibody ADC-1013, as part of Alligator’s Phase I trial in advanced solid tumours. Following on from this success, in January 2016 Cobra was also contracted to develop a second cell line ATOR-1015 for Alligator.

About Cobra Biologics
Cobra Biologics is a leading international contract development and manufacturing organisation (CDMO) providing biologics and pharmaceuticals for pre-clinical, clinical and commercial supply.

Cobra has three GMP approved facilities in Sweden and the UK, each with expertise tailored to serving our customers around the world. We offer a broad range of integrated and stand-alone contract development and manufacturing services for clinical trials and the commercial market.

As a trusted provider and a key partner in the drug development and commercialisation process, we take pride in our manufacturing excellence and comprehensive range of services to the pharmaceutical and biotech industries. For more information, visit www.cobrabio.com

About maxXpress Ubiquitous Chromatin Opening Elements (UCOEs)
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’ de-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, SP2/0 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, visi: www.cobrabio.com

About Alligator Bioscience
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.

In the discovery of novel antibody based drugs, Alligator uses its proprietary technology platforms ALLIGATOR-GOLD and FIND®: ALLIGATOR-GOLD is a synthetic svFv library containing several billion distinct fully human antibodies. FIND® (Fragment Induced Diversity) is an antibody optimization technology based on single-stranded DNA.

Alligator has a strong pipeline of innovative antibody-based compounds within immune oncology of cancer; ADC-1013 is an immune activating antibody developed for metastasized cancer. It entered clinical trials in cancer patients early 2015. ADC-1015 is a bispecific immune activating antibody. It is developed to induce superior immune activation and is currently is pre-clinical phase. ADC-1016 is a systemic localizing immunotherapy, a bispecific immune activator that is administered systemically while the effects are restricted to the tumour area. For more information, visit www.alligatorbioscience.se.