Novel Payloads and Multispecific Antibodies Fuel ADC Innovation

BioPharm International spoke with Sabeen Mekan, MD, Vice President of Clinical Development at Zymeworks and BIO 2026 panelist for The Next Generation of ADCs: Building Kinder, Gentler Cancer Therapeutics. The discussion explored how advances in safety, patient selection, and biomarker strategies are helping define the next generation of targeted cancer therapies.

How are novel payloads reshaping ADC development?

In the third part of a three-part interview, Sabeen Mekan, MD, of Zymeworks Inc, about the technologies she believes will shape the future of antibody-drug conjugate (ADC) development. While advances in linker chemistry and conjugation methods continue, Mekan pointed to innovations in payload design and antibody engineering as the areas likely to have the greatest impact on the next generation of targeted cancer therapies.

According to Mekan, topoisomerase inhibitor-based ADCs have delivered significant clinical success across multiple tumor types and targets. However, as more companies develop therapies using similar payload classes, the field is beginning to explore new approaches that may offer additional opportunities for differentiation and improved outcomes.

"I think the biggest innovation moving forward is on the payload side," Mekan said.

Among the approaches generating interest are novel payloads that target pathways beyond traditional cytotoxic mechanisms. Mekan highlighted growing efforts to develop ADCs that interfere with cancer-driving pathways, including RAS signaling, as well as payloads designed to function as degraders or target other molecular pathways such as EGFR.

At the same time, innovation is occurring on the antibody side of ADC design. While early ADCs largely relied on conventional monoclonal antibodies, developers are increasingly exploring bispecific, trispecific, and multispecific formats. These more complex antibody structures are designed to improve targeting precision and enhance therapeutic activity by engaging multiple epitopes or biological mechanisms simultaneously.

Mekan noted that these advances could help create ADCs that are more selective and effective than earlier generations of the technology.

Although linker technologies and conjugation methods remain important areas of development, she believes the industry's primary focus has shifted toward improving payload design and antibody engineering. Efforts to refine conjugation strategies continue as developers seek greater consistency and control over ADC construction.

These advances reflect the rapid pace of innovation across the ADC field as companies work to develop more targeted therapies with the potential to improve outcomes for patients with cancer.

Watch part one of this interview here. Watch part two of this interview here. Click here for more conference coverage.

About the speaker

Sabeen Mekan, MD, senior VP and chief medical officer, Zymeworks, Inc.

Dr. Priyanka Mekan is senior vice president and chief medical officer at Zymeworks, a position she has held since April 2025. She brings extensive experience in oncology drug development, having previously held leadership roles at Gilead Sciences, Daiichi Sankyo, and Bristol Myers Squibb. Prior to joining industry, she served as an assistant professor and practicing hematologist/oncologist in New York. Board certified in internal medicine, oncology, and hematology, Dr. Mekan has led the development of multiple cancer therapies and authored numerous scientific publications.