ADC crash course: The five question crib sheet on MedImmune’s next-generation Antibody-Drug Conjugate platform

Ahead of this month’s World ADC Congress in Berlin, BioLogical sat down with Steve Coats, Vice President, R&D and External Science Strategy at MedImmune. In five questions, Steve explains why this next generation cancer therapy has the potential to change the industry and patient health, and why MedImmune is a leader in the pursuit.

Q: First – let’s level set. Can you describe an ‘Antibody-Drug Conjugate’?
A: An antibody drug conjugate – or ADC – combines a targeted monoclonal antibody (mAb) with a potent cytotoxic agent or, ‘warhead’ that selectively targets cancer cells. “Targeted chemotherapy,” is a commonly used analogy to describe the class of cancer therapeutics.

Q: Are ADCs a new cancer therapy?
A: Antibody drug conjugates (ADCs) have been around for a while, but historically, the class has faced challenges related to stability and toxicity.  However, more recently, emerging science and the development of newer technologies have primed the growth of next-generation of ADCs that enable scientists to address previous concerns and have confidence in their potential.

Q: What are the top three things that set apart MedImmune’s next-generation ADC platform?
A: First, we believe our ‘warheads’ are among the most potent in the industry. Bolstered by our Spirogen acquisition, our ADC portfolio carries the very potent proprietary pyrrolobenzodiazepine (PBD) technology to attack cancer cells upon activation.

Second, our expertise in antibody development and protein engineering (ADPE) allows us to create the most sophisticated monoclonal antibody acting as an extremely sophisticated navigation system, enabling us to deliver the warhead directly to a specific tumor ‘address.’

Third, we are leveraging our ADPE expertise to develop novel therapeutics that have the potential to provide benefit to patients who currently don’t have any options. For example, we have a novel HER2 bispecific mAb ADC in Phase I clinical testing. In short, the bispecific mAb allows us to target cells with both high and lower levels of HER2 expression. There is a high unmet medical need for patients whose tumors express very low levels of HER2 or whose tumors are HER2 positive but the patients have failed prior therapies. The preclinical data for MEDI4276 demonstrates very potent activity in tumor models that represent these distinct patient populations.

Q: What excites you the most about the potential of ADCs?
A: Combinations, which are the cornerstone of our oncology strategy. In preclinical studies, we’ve seen strong scientific rationale for combining ADCs with immuno-oncology (IO) and DNA damage response (DDR) agents. Our investigational IO and DDR portfolios are robust, and pursuing these combinations may further enhance benefits to patients. The ability to potentially combine our ADC therapies with either IO or DDR therapies may provide clinical benefit to a broader population of patients. Translational and biomarkers studies are currently underway to identify which patient populations may benefit the most from these combination approaches.

Q: Can MedImmune do it alone?
A: Absolutely not. And it’s one of my favorite parts about developing our next-generation ADCs. Keeping with our values – we follow the science, which has led us to some exciting industry partnerships to collectively drive this science forward. Our work with both Regeneron and Tanabe Research are exciting pursuits we’ve undertaken to work with other experts in the field.

Steve Coats is speaking at the 7th Annual World ADC Berlin summit on “Antibody Drug Conjugates: Development of a HER2 bispecific antibody-drug conjugate in breast and gastric cancers,” on Feb 22.