Linkers as conductors of the ADC orchestra.

Getting all the parts of an ADC working in synergy could be seen as analogous to an orchestra – lots of different parts all contributing to the production of a complimentary output. In the case of the orchestra, this is a generating a wonderful aural creation. And in the case of an ADC, it is generating successful candidates that have a suitable safety profile that offer therapeutic benefits.

Just as the conductor unifies the orchestra, sets the tempo and delivers the sound of the ensemble, so an ADC linker unifies the bioconjugate, sets the stability profile and delivers the appropriate payload concentration; in effect acting as the conductor.

It reminded me of the comedic sketch when a piano-playing Eric Morecambe turns to the famous conductor Andre Previn after being told he is playing all the wrong notes: “I’m playing all the right notes—but not necessarily in the right order.”

Getting the parts of an ADC in the wrong order, or in the wrong combination, can have devastating effects on whole clinical programs resulting in failures, company closures and a hugely negative impact on patients’ lives. But get their pieces in the right order and conduct them in the right way can have life-changing and transformative effects for patients.

So what is the right order? One thing the ADC linker can offer is it’s optimisability. Whether this is linker architectural design through incorporation of a suitable polymer component, inclusion of the appropriate payload (or other termed cargo being delivered) release mechanism, or being able to tune the conjugation functionality and therefore site of attachment, this optimisability is key to why the ADC linker is so critical to successful development of ADC.

One real driver of this being able to tune the amount of payload being delivered, and by being able to increase the drug-antibody ratio (DAR) through high DAR linker technologies. And why accessing lower potent payloads through linker design can be the difference between a successful ADC program or not. ADC linkers will continue to conduct the ADC orchestral field for a while to come, with the richness of sounds being generated only continuing to rise in volume.