Antibody-Drug Conjugates: Overcoming the Next Wave of Challenges in 2025–2026

Antibody-drug conjugates (ADCs) have moved from niche innovation to a rapidly expanding class of targeted cancer therapies. With more than a dozen approvals and hundreds of candidates in development, ADCs are reshaping the oncology landscape. Yet alongside their success, the industry faces new scientific, clinical, and supply chain hurdles that must be addressed to fully realize their promise.

In a recent interview, Brian Fiske, co-founder of Mythic Therapeutics, discussed how their proprietary FateControl™ technology is designed to enhance ADC uptake and overcome delivery barriers, with early success seen in their cMET-targeting candidate, MYTX-011. His insights highlight the type of breakthroughs required to tackle today’s challenges in ADC design and clinical development.

At Antibody Engineering & Therapeutics 2025, our dedicated track on Antibody-Drug Conjugates – Novel Payloads and Engineering will bring together global experts to address exactly these issues — from dual-payload design to novel non-cytotoxic payloads. Here’s a look at the key challenges facing ADCs in 2025 and 2026, and how our sessions will provide cutting-edge solutions.

Dual Payloads: Tackling Efficacy and Resistance

The challenge: Single-payload ADCs can face tumor resistance, limited efficacy, or narrow therapeutic windows. As tumors adapt, many single-mechanism ADCs lose their effectiveness.

Sessions addressing this:

• Development of Site-Specific, High-DAR Dual-Payload ADCs will showcase how precisely controlled conjugation strategies enable the delivery of two different payloads simultaneously — enhancing efficacy and combating resistance.
• Dual Payload ADCs will further explore how this approach can improve clinical outcomes.

Expanding Beyond Antibodies: Multispecific & Peptide Conjugates

The challenge: Tumor heterogeneity means that single-antigen targeting often fails, particularly in solid tumors. Expanding targeting strategies is essential.

Sessions addressing this:

• Expanding the Reach of Targeted Cancer Therapy Using Multispecific Peptide-Drug Conjugates will highlight how PIP technology enables multi-target binding to overcome resistance and broaden ADC utility across solid tumors.

Combining Modalities: ADCs and Radiotherapy

The challenge: Radiotherapy remains a backbone of treatment, but its effectiveness is limited by normal tissue toxicity and tumor resistance. Combining ADCs with radiotherapy offers a precision-based path forward.

Sessions addressing this:

• Precision Meets Power: Antibody-Drug Conjugates to Potentiate Radiotherapy in Solid Tumors will demonstrate how ADCs directed at radiation-inducible tumor antigens can enhance responses while reducing systemic toxicity.

Rethinking Payload Design for Better Therapeutic Index

The challenge: Traditional cytotoxic payloads, while potent, often drive safety concerns that limit dosing. There is a need for more selective, non-pan-cytotoxic payloads to improve the therapeutic index (TI).

Sessions addressing this:

• Exploring Targeted, Non-pan-cytotoxic ADC Payloads Across Different Targets for Efficacy and Enhanced TI will present early data on novel payloads designed to exploit cancer cell vulnerabilities while minimizing off-target effects.

Lessons from the Clinic: Two Decades of Vedotin ADCs

The challenge: With decades of clinical experience behind certain ADC platforms, the field has rich data to guide smarter target selection and trial strategies — but applying these lessons to new tumor types is complex.

Sessions addressing this:

• Insights from a Decade of Clinical Experience with Vedotin ADCs will share how 50+ targets and extensive trial data are shaping next-generation approaches, including successes in challenging tumor types such as NSCLC.

Conclusion: The Future of ADC Innovation

The next wave of ADC development will be defined by dual-payload designs, multispecific targeting, smarter conjugation chemistries, and payload diversification — all while addressing manufacturing, safety, and clinical trial complexity.

Join us this December in San Diego at Antibody Engineering & Therapeutics 2025, where leaders from industry and academia will present the latest strategies to overcome these hurdles in our Antibody-Drug Conjugates – Novel Payloads and Engineering track.

👉 Watch the full interview with Brian Fiske here
👉 Explore the full ADC track agenda here
👉 Register today to secure your place at AET 2025