NIJMEGEN, THE NETHERLANDS -- Byondis B.V., an independent biopharmaceutical company creating innovative targeted medicines for patients with cancer, will profile the Company’s first-in-class antifolate and phosphonate antibody-drug conjugate (ADC) technology platforms in poster sessions at the American Society for Cancer Research (AACR) Annual Meeting 2026 in San Diego, CA, until 22 April.

Wim Dokter, PhD, Chief Scientific Officer at Byondis, said: “The research we are presenting at AACR highlights the potential of two of our state-of-the-art ADC technology platforms to address significant limitations with current therapeutic approaches in cancer treatment. Our first-in-class antifolate linker-drug platform features an orthogonal mechanism of action based on clinically validated biology. This approach is engineered to address acquired resistance that can develop with current ADC treatments, positioning it for use across treatment lines. Our phosphonate linker-drug platform offers a complementary mechanism that can provide new treatment options for patients, including those who may not respond to immune therapy. Both platforms underscore our mission to deliver breakthrough solutions and enable a new generation of cancer therapeutics for patients.”

Antifolate ADCs, a novel linker-drug platform for targeted therapy with a clearly differentiated mechanism of action (abstract #: 3178/13)
Session Category: Experimental and Molecular Therapeutics
Session Title: Targeting Cell Surface Vulnerabilities to Overcome Therapeutic Resistance
Time: 20 April, 2:00 PM - 5:00 PM

Resistance to widely used ADC payloads, such as topoisomerase-I and tubulin inhibitors, is increasing, underscoring the need for differentiated approaches. Byondis has revisited the clinically validated antifolates class and developed a proprietary antifolate linker-drug platform that provides a differentiated and validated mechanism of action with a payload designed to overcome systemic side effects.

The optimized payload demonstrates low- to sub-nanomolar potency, strong inhibition of dihydrofolate reductase (DHFR), and broad in vitro cytotoxicity cell lines. It also shows no interaction with key resistance-associated transporters (BCRP, PGP) and favorable physicochemical properties, supporting GMP-scale manufacturing and ADC compatibility. A glucuronide-based linker enhances therapeutic index while maintaining favorable physicochemical properties, preserving ADC stability and enabling potential dual-payload strategies.

Byondis’ lead antifolate ADC, targeting an undisclosed tumor antigen, has shown strong in vitro activity and 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 at active doses. This differentiated profile supports broad tumor applicability, positioning it for use from first-line therapy through to combination approaches.

Phosphonate antibody-drug conjugates, an innovative, immunostimulatory class of ADCs that drive inside-out activation of Vγ9Vδ2 T cells, enabling selective tumor cell killing (abstract #: 6921/2)
Session Category: Immunology
Session Title: Antibody-Drug Conjugates 2
Time: 22 April, 9:00 AM - 12:00 PM

Addressing a critical need for patients who do not respond to immune therapy, Byondis’ linker-drug platform, ByonBoost™, is engineered to activate Vγ9Vδ2 (γδ) T cells in the tumor microenvironment, enabling targeted delivery with an immunologic antitumor effect and compatibility with single and dual-payload concepts.

Gamma delta (γδ) T cells are potent cytotoxic effectors that eliminate tumor cells independently of MHC presentation and are associated with improved clinical outcomes. However, prior approaches to activate Vγ9Vδ2 T cells have been limited by lack of tumor specificity and short half-life.

To address these limitations, Byondis has developed tumor-targeting phosphonate ADCs that selectively deliver payloads to tumor cells, enabling inside-out activation of Vγ9Vδ2 T cells. These ADCs combine a tumor-associated antigen (TAA)-targeting antibody with a cleavable phosphonate payload and have been successfully applied across multiple targets, including CD123, CD20, TROP2, and HER2. They drive robust and targeted immune activation, inducing cytokine release, degranulation and tumor cell killing in vitro, including in studies where primary patient material was used. 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 modular platform enables the dual mechanisms of action of direct tumor targeting and immune activation while preserving antibody effector function. With broad applicability across tumor types and compatibility with multiple antibodies, it represents a differentiated and scalable approach to targeted immunotherapy.