Target-specific reagents and immunoassay formats smoothen validation and transfer between CMC, preclinical, and clinical applications, and also to a CRO
Robust, accurate, precise, and time effective ligand binding assay platforms are crucial for the development of advanced bioassays for analyzing therapeutic antibody mixtures due to the inherent complexity of these drugs. This is why Symphogen A/S, Denmark chose Gyrolab system to develop assays to support chemistry, manufacturing, and controls (CMC) release and stability programs, and pharmacokinetics preclinical and clinical studies on Sym015, a novel anti-cancer biotherapeutic comprising two humanized monoclonal antibodies (mAbs).
Symphogen has developed a B-cell based platform for cloning from different species and their high throughput platform is used to identify functionalities, including synergistic effects to develop antibodies with unique properties in the field of oncology and immuno-oncology. The company has several products in clinical development, including Sym015, which is in Phase 2a.
Sym015 is an antibody drug product comprising a mixture of two mAbs that each bind specifically to non-overlapping epitopes of the MET receptor. This receptor is involved in the regulation of multiple cellular processes that stimulate cell proliferation, invasion, and angiogenesis, and Sym015 has entered a phase 2a trial in patients with MET-amplified and METexon14-deleted non-small cell lung cancer.
2-plex immunoassays for PK and target binding studies
The Bioassay team at Symphogen needed to develop and qualify assays to characterize the individual mAbs in the Sym015 mixture to assess critical quality attributes (CQA) such as target binding. These target-binding assays could be used for in-house GSP stability programs, and to support process development and CMC, and validated at the CRO for batch release and ICH stability programs. They also needed assays for preclinical and clinical pharmacokinetic studies of the individual mAbs following dosing with Sym015. These assays would then be transferred to a CRO for GLP toxicology studies and clinical studies. The most promising approach was to develop 2-plex immunoassays.
Exploiting the advantages of Gyrolab system
With challenging timelines of approximately 18 months required to develop an IND from a lead, Symphogen had already appreciated many of the properties of the Gyrolab system in running CMC, studying target binding, and for pharmacokinetics (PK) studies. These include the ability to run multiple assays without cross talk, high sensitivity, high throughput, and the low consumption of reagents and samples. The Bioassay team therefore saw the potential of Gyrolab system in running 2-plex assays for the two mAbs in Sym015, and the Gyrolab methods they developed are now being used for manufacturing control and for bioanalysis during clinical studies.
At the latest Gyrolab User Meeting, held in Milan in June, 2019, Rikke Hald, Senior Scientist, presented the experiences of the Bioassay team at Symphogen. You can find out more by viewing her webinar, ‘Biopharmaceutical drug development: from CMC to clinical PK’