BIOTECHNOLOGY 101
Accelerating ADC development
Sharon Goodkowsky presents a case study on how a biotech firm fast-forwarded work on its antibody drug conjugates (ADCs).
I
genica Biotherapeutics, a US biotechnology company with a promising anti- cancer antibody in a Phase 1 clinical trial, has innovative technology platforms to discover and develop antibody drug conjugates (ADCs) for cancer treatment. To fulfil the company’s goal of quickly moving ADC-based therapeutics out of preclinical development and into the clinic, Igenica wanted new, dedicated instrumentation to fully analyse the complexity and variation within an ADC’s three parts: the antibody; the toxic drug; and the linker that binds them together.
As a result, Igenica deployed the Waters Biopharmaceutical Platform Solution with Unifi, which includes the Acquity UPLC H-Class system, Xevo G2-S QTof mass spectrometer, and Unifi scientific information system.
“Te platform has provided a superior window of insight into the molecules we are making,” said Mark R. Flory, Ph.D., a principal scientist at Igenica. “It will help in our efforts to accelerate clinical trials with ADCs.”
Fig. 1. (Above) The Waters Biopharmaceutical Platform Solution with Unifi.
Before ADCs Igenica had existing capillary HPLC/MS technology in place to drive its targeted discovery efforts. Te company had anticipated using the same for ADC analysis, but wanted to improve proteomics workflows for ADC characterisation. It sought an instrument to handle different chemistries for conjugations and linkers, and to improve its characterisation of the population of antibody conjugates once the toxic payload
was added by its proprietary SNAP chemistries. Its existing ion trap and orbitrap LC/ MS systems worked for small molecule and peptide qualitative analyses, but the company wanted to increase the range for analysis of intact monoclonal antibody (mAb) conjugates, and increase the capability to readily determine drug loading on ADCs.
Ingenica wanted a quadrupole time-of-flight (QTof) MS dedicated to complex, large- molecule mixtures, including ADCs. It also wanted the ability to look at intact mass profiles of ADC species in both native and denaturing electrospray ionisation modes. Tis became the driving force to find a new instrument that would expand
its tools for analysis and expand current and future capabilities of the organisation.
Te company initially evaluated single-vendor solutions from three companies and quickly narrowed down the evaluation to only Waters and one other vendor. To make a data-driven decision, Ingneica’s chemists ran a well-characterised ADC mixture through both companies’ LC/MS systems and compared analytical results, looking at drug-to-antibody ratio (DAR) results from hydrophobic interaction chromatography (HIC) LC-UV data. Te team then considered other variables, including informatics quality, speed of installation and service, and ultimately selected the Waters platform.
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