Byondis Unveils Novel ADC Platforms to Combat Cancer Drug Resistance at AACR 2026
Key Insights
Byondis (search) presented two first-in-class ADC technology platforms at AACR 2026, targeting limitations in current cancer treatments through differentiated mechanisms of action.
The company's antifolate linker-drug platform demonstrated robust tumor regressions in NSCLC and HNSCC models while addressing acquired resistance to existing ADC payloads.
Byondis (search)' phosphonate platform ByonBoost™ activates gamma delta T cells for immunostimulatory effects, showing excellent tolerability without cytokine release syndrome in primate studies.
Byondis (search) B.V., a Netherlands-based biopharmaceutical company, showcased breakthrough antibody-drug conjugate (ADC) technology platforms at the American Society for Cancer Research (AACR) Annual Meeting 2026 in San Diego, addressing critical limitations in current cancer therapeutics through two distinct mechanisms of action.
Antifolate Platform Targets ADC Resistance
The company's first-in-class antifolate linker-drug platform represents a strategic response to increasing resistance against widely used ADC payloads, including topoisomerase-I and tubulin inhibitors. Wim Dokter, PhD, Chief Scientific Officer at Byondis (search), emphasized that "our first-in-class antifolate linker-drug platform features an orthogonal mechanism of action based on clinically validated biology."
The optimized antifolate payload demonstrates low- to sub-nanomolar potency with strong inhibition of dihydrofolate reductase (DHFR) and broad in vitro cytotoxicity across cell lines. Critically, the payload shows no interaction with key resistance-associated transporters BCRP and PGP, while maintaining favorable physicochemical properties that support GMP-scale manufacturing and ADC compatibility.
Byondis (search)' lead antifolate ADC, targeting an undisclosed tumor antigen, achieved robust tumor regressions in non-small cell lung cancer (NSCLC) and head and neck squamous cell carcinoma (HNSCC) patient-derived xenograft models, with no significant toxicity observed at active doses. The glucuronide-based linker enhances the therapeutic index while preserving ADC stability and enabling potential dual-payload strategies.
ByonBoost™ Platform Activates Immune Response
Addressing the critical need for patients who do not respond to immune therapy, Byondis (search) developed the ByonBoost™ phosphonate linker-drug platform, engineered to activate Vγ9Vδ2 (search) gamma delta T cells within the tumor microenvironment. These cytotoxic effectors eliminate tumor cells independently of MHC presentation and are associated with improved clinical outcomes.
The tumor-targeting phosphonate ADCs combine tumor-associated antigen (TAA)-targeting antibodies with cleavable phosphonate payloads, successfully applied across multiple targets including CD123 (search), CD20 (search), TROP2 (search), and HER2 (search). In vitro studies demonstrated robust and targeted immune activation, inducing cytokine release, degranulation, and tumor cell killing, including in studies using primary patient material.
Notably, in non-human primate models, the lead candidate displayed excellent tolerability with no clinical signs of cytokine release syndrome (CRS), even at high doses. This safety profile addresses a significant concern with immunostimulatory approaches.
Broad Clinical Applications
Both platforms demonstrate broad applicability across tumor types and compatibility with multiple antibodies. The antifolate platform is positioned for use from first-line therapy through combination approaches, while the phosphonate platform offers a differentiated and scalable approach to targeted immunotherapy.
Dokter noted that the phosphonate platform "offers a complementary mechanism that can provide new treatment options for patients, including those who may not respond to immune therapy." The modular design enables dual mechanisms of action through direct tumor targeting and immune activation while preserving antibody effector function.
Company Profile
Byondis (search) operates as an independent, fully integrated biopharmaceutical company with more than 200 staff working in state-of-the-art R&D and GMP manufacturing facilities in Nijmegen, the Netherlands. The company's development portfolio leverages expertise in linker-drug technology, antibody-drug conjugation, and disease biology, covering all stages from pre-clinical research through regulatory filings in-house.