Reprogramming ADC Resistance Through Mechanistically Matched Payload Combinations

• Analyze ADC resistance mechanisms in topoisomerase and tubulin payloads, including drug efflux pumps and tumor bypass pathways, and distinguish where evidence remains strong versus where it is still incomplete
• Explore approaches to overcoming resistance through rational payload selection, including combining topoisomerase inhibitors with PARP or ATR inhibitors and using translation inhibition strategies to prevent efflux pump expression and resensitize tumors
• Define key requirements for effective dual payload ADC design, including matched payload potency, coordinated intracellular release timing, and engineering strategies that ensure both payloads reach and act in tumor cells simultaneously

Speakers:

Tara Arvedson

Chief Scientific Officer

Hexagon Bio