Experts from biotech company ADC Biotechnology, have issued a warning that poor aggregation will cause problems in the antibody-drug conjugate (ADC) pipeline, with millions being wasted in development costs.
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“There is a major challenge in the ADC pipeline that conventional manufacturers have not addressed and which pharma companies are obliged to work around,” commented Charlie Johnson, chief executive officer at ADC Bio. “The ultimate problem is that you have a candidate that may look promising but in practice it can’t be commercialised — unless aggregation control systems are put in place.”
This warning comes as more full service contract development and manufacturing organisations (CDMOs) are investing in conjugation and ADC facilities. According to ADC Bio experts these CDMOs are not necessarily equipped to develop products capable of working successfully in clinical testing or that are economically viable.
“We are seeing a great deal of excitement from pharma companies seeking to invest in ADC therapeutics. But applying conventional manufacturing techniques will see the drugs fail or endure very long periods in development,” Johnson added. “From the vendor side, there is considerable investment across the industry in facilities — but that alone will not give you the capabilities to commercialise optimal ADC therapeutics and that is ultimately a failure to patients desperately in need of new life-saving therapies.”
These issues, raised by ADC Bio’s experts, are particularly true for best in class ADCs — those that predominantly incorporate PBD or duocamycin payloads. Problems develop with these ADCs as the payloads of very hydrophobic and even though they only comprise 2% of the overall ADC they gave a dramatic effect on the propensity to aggregate. Therefore, effective aggregation control solutions are now critical.
“Effective aggregation control technologies are now essential and can be the difference between whether an ADC makes it to the market as a commercially viable product or fails. Indeed, much of our future customer base will come in as the industry realises that not all CDMOs are equal and you require not just facilities, but also highly specialist technologies when it comes to aggregation control,” continued Johnson. “We’re coming to the ADC market from a completely different direction — we are not an all purpose CDMO. We realised that there was a problem and consequently developed a proprietary technology. As a result, we are expanding our facilities to meet ADC production demand.”
ADC Bio’s proprietary ‘Lock-Release’ technology platform has been developed over the past six years and works by immobilising the antibodies onto a solid-phase support — segregating them and preventing aggregation during the conjugation steps.