Antibody-drug conjugates, or ADCs
Some think that they will never attain the paradigm shifting, multi-blockbuster status of the Checkpoint inhibitors, but you know, they continue to make significant therapeutic impact in high unmet need patient segments.
Overall, since 1990, 10 ADCs have been approved in the US, and notably, 3 of these in the last 6 months alone. Today, more than 85 of these ADCs are in clinical or preclinical development spanning more than 40 different molecular targets.
So what are these rationally designed constructs? Well, in short, a cytotoxic payload, or toxophore, linked to a carrier monoclonal antibody.
Slide 2 – Toxophores
The toxophores, or the cytotoxic agents to date have been primarily drawn from maytansine and aurastain classes, but next generation ADCs are now exploring known potent agents that in the past were found to be too toxic to be delivered by a conventional IV route of administration. This targeted delivery of these new agents to malignant tissue could now let them realize their fullest therapeutic potential
Slide 3 – Linkers
Second, conjugation chemistry can now deliver linkers that are very stable in peripheral circulation so as to decrease off-target AEs, but with very efficient intracellular degradation kinetics to release the payload and effect a potent cytotoxic insult to the tumor.
Slide 4 – Antibody
And finally, targeting is only limited by the ability to direct an mAb against an external receptor that internalizes it upon binding. And the challenge of low exreprssion of mAb targets on tumour cells may be in part mitigated by increasing the drug-to-antibody ratio, by conjugating multiple, or multiply different cytotoxic molecules to a single carrier mAb.
Slide 5 – Antibody Drug Conjugates
With this targeting potential, and with trials in tumors spanning hematologic, gynecologic, GI, GU, pulmonary and other organ system malignancies, it might be a tactical oversight to dismiss how ADCs might impact your target patients segments.
Slide 6 – Antibody Drug Conjugates
Key questions that must be addressed include:
- How will ongoing ADC pipeline development impact my target patient segments?
- Are emerging ADCs competitors or combination partners?
- What must I do to deliver sustainable differentiation for my asset?
Slide 7 – We are SmartAnalyst
We are SmartAnalyst. Ask us. It is our business to know. We have delivered more than 700 projects in oncology in the past 5 years, and we will deliver you the Intelligent insights and the Smart Results that you need.