NEW YORK (GenomeWeb) – AB Sciex this week announced a collaboration with Dalton Pharma Services through which the mass spec vendor plans to develop methods for analysis of antibody-drug conjugates.
The company plans to build assays on its TripleTOF 5600+ and TripleTOF 6600 instruments for portions of the ADC development workflow including characterization of the conjugates' structures and analysis of their behavior and breakdown in vivo.
Consisting of a drug linked to an antibody, ADCs are considered promising due to their use of antibodies to target therapeutic agents directly to diseased cells, potentially allowing for more efficient drug delivery and a reduction in side effects.
While only three ADCs have been approved for patient use to date, the space is a busy one with more than 30 different ADCs currently in clinical trials, Suma Ramagirl, global technical marketing manager, pharma/CRO Business at AB Sciex, told ProteoMonitor.
As such, ADCs are a potential growth area for mass spec-based biopharma analysis, an area in which AB Sciex has been active.
In 2012, for instance, the company launched its BiologicsFocus Initiative aimed at developing tools for biologics analysis. At this year's American Society for Mass Spectrometry annual meeting, it released its BioPharma View software, which allows researchers to analyze batches of therapeutics and monitor various quality attributes.
The Dalton collaboration will help AB Sciex move into ADC work by providing the company with a variety of conjugates with which it can develop mass spec-based analysis methods.
"Dalton brings their chemistry knowledge and are providing us with different types of [ADCs] with different [drug] payloads and different linker chemistries that help us develop assays," said Ramagirl.
For Dalton, the payoff includes potentially new ADC analysis methods that it can offer its customers down the line, Kevin McCarthy, the company's associate director, sales and marketing, told ProteoMonitor.
"It puts us in a good place as a contractor," he said. "We have access to this really leading edge analytical tool that will enable us to do this job better and faster than we could previously."
Traditionally, ADC analysis requires a variety of different methods, including capillary electrophoresis, chromatography, and ligand-binding assays, to collect information on different aspects of the molecules – for instance, where the drug binds the antibody, how much drug is delivered by the antibody, and how the drug is metabolized by a subject.
Additionally, noted Harpreet Kaur, chemistry team leader at Dalton, different approaches work best on different ADCs and determining which methods will be best for a particular conjugate can require considerable amounts of time and material.
This latter concern – material – is key given the complexity and high expense of many ADCs, McCarthy said.
"These ADCs [use] complex proteins and tend to be very expensive," he said. "So having an analytical technique that can get at loading, site specification, and those kind of details very quickly using a small amount of material is a big advance. It gets rid of having to do specific tests based on what type of molecule it is and doing a lot more manual analysis."
Kaur said that Dalton has used MALDI-TOF-based mass spec analysis for ADC work in the past, but this approach lacked accuracy, particularly when it came to quantifying the amount of drug molecules attached to an antibody, she told ProteoMonitor.
McCarthy noted that to date Dalton has not done any of the mass spec work in its collaboration with AB Sciex but, rather, has focused on providing different types of ADCs to the vendor.
"The initial exercise was for us to manufacture and then they ran the [analysis] and shared that with us," he said. "So we haven't run the instruments ourselves but we have looked at the data from it and have been impressed by the results."
Eventually, he said, provided the mass spec methods developed ultimately prove useful, Dalton plans to offer them to its pharma customers – either in-house or through outsourcing.
ADC analysis consists of two primary areas, said Ramagirl, a product development stage focused on determining the structure of the molecules including where the antibody and drug are linked and how much drug is carried by the antibody, and a second stage that focuses on the behavior and metabolism of the ADC in vivo.
She said that the company's BioPharma View software would be particularly applicable to the initial product development stage, allowing researchers to address and identify impurities in conjugates as well as more easily generate structural data.
For the second stage, she cited the company's MetabolitePilot software as a key tool for allowing researchers to better monitor the in vivo metabolism of ADCs, improving safety and efficacy testing.
Generally speaking, Ramagirl said, ADC research could benefit from the heightened specificity, sensitivity, and speed offered by mass spec.
"Given regulatory concerns around safety and efficacy and the complex nature of the molecules, the demand from regulators and researchers is for more specific data and more accurate results," she said. "So that drives you towards mass spec techniques, which provide accuracy, the ability to go faster, and an additional dimension in terms of selectivity."
AB Sciex is not alone in bringing mass spec technology to such analyses, Ramagirl said, citing Thermo Fisher Scientific and Waters as vendors that have likewise shown an interest in the ADC space.
Last year at the Human Proteome Organization's annual meeting, Thermo Fisher launched its Exactive Plus EMR instrument, which offers an extended mass range of up to 20,000 m/z and is aimed at the biopharma market, including ADCs, Andreas Huhmer, proteomics marketing director at Thermo Fisher, told ProteoMonitor at the time.
Waters has also put together a series of systems and software for ADC analysis, including its Acquity UPLC and Xevo G2-XS QTOF mass spec and its MassLynx Software with BiopharmaLynx.
Agilent, Bruker, and Shimadzu have products aimed at this market, as well.