Enhancing therapeutic efficacy and overcoming resistance with a novel dual-payload antibody-drug conjugate technology

Presented at AACR Annual Meeting 2026

Antoine Attinger¹, Léo Marx², Diana Bianca Rocha Gomes¹, Vincent Gerusz², Min Ma¹, Viktoriia Postupalenko², Alain Monjardet¹, Nicolas Quesnot¹, Christophe Chardonnens², René Wuttke¹, Noémie Luong¹

¹ Debiopharm International SA, Switzerland
² Debiopharm Research & Manufacturing SA, Switzerland

Summary

Antibody-Drug Conjugates (ADCs) are promising oncology therapeutics that deliver cytotoxic payloads selectively to tumors. However, their efficacy is often limited by tumor heterogeneity, acquired resistance to single-agent payloads and off-target toxicity caused by premature linker cleavage. There is a critical need for next-generation ADCs to address these issues and broaden the therapeutic use of such modality and to exploit potential payload synergies. To address these challenges, we developed MLINK Duo, a dual-payload ADC technology combining plasma stability and controlled tumor-specific dual payload release. This technology enables the conjugation of a diverse range of dual payloads to antibodies, including combinations of well-established cytotoxic agents such as MMAE and Exatecan, as well as innovative new payload combinations. Here we show an in vitro and in vivo proof of concept using a MLINK Duo ADC simultaneously delivering MMAE and Exatecan (MLINK Duo MMAE/Exatecan) conjugated either to Trastuzumab (TmAb-MLINK Duo MMAE/Exatecan) or to our internal monospecific and bispecific ADC programs (mAb-MLINK Duo MMAE/Exatecan and BsAb-MLINK Duo MMAE/Exatecan,respectively)