Byondis Debuts Dual Antibody-Drug Conjugates to Fight Cancer Treatment Resistance

NIJMEGEN, The Netherlands – April 17, 2026 – In a significant move to address two of modern oncology’s most stubborn challenges, Dutch biopharmaceutical firm Byondis B.V. is unveiling data on a pair of innovative antibody-drug conjugate (ADC) technology platforms at the American Society for Cancer Research (AACR) Annual Meeting in San Diego this week. The presentations detail a two-pronged strategy aimed at outmaneuvering cancer's defenses: one platform designed to overcome acquired drug resistance and another engineered to help patients who do not respond to current immunotherapies.

The research highlights the potential of what the company calls its first-in-class antifolate and phosphonate ADC platforms. These technologies represent the next evolution in ADCs—highly targeted therapies often described as “biological missiles” that deliver potent cancer-killing agents directly to tumor cells while minimizing damage to healthy tissue. Byondis's new approaches could usher in a new generation of treatments for patients with limited options.

A Strategy to Overcome Cancer's Defenses

The ADC market is one of the hottest areas in oncology, projected to grow into a more than $50 billion industry by 2035. However, the effectiveness of current ADCs can be limited. Many rely on similar types of toxic payloads, such as topoisomerase-I and tubulin inhibitors. As cancers are exposed to these agents, they can evolve and develop resistance, rendering the treatments ineffective. Similarly, while immune therapies have revolutionized cancer care, a large percentage of patients do not respond, often because their tumors have found ways to become invisible to the immune system.

Byondis aims to tackle these issues head-on with its new platforms. “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,” said Wim Dokter, PhD, Chief Scientific Officer at Byondis. “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... 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.”

Reviving a Classic to Break Through Resistance

The first platform is a novel antifolate linker-drug designed to combat acquired resistance. Antifolates are a well-established class of cancer drugs, but older versions were often limited by systemic toxicity. Byondis has revisited this clinically validated approach, using modern ADC technology to create a highly targeted and potent payload.

The key is its orthogonal mechanism of action. This means it kills cancer cells in a way that is fundamentally different from the most common ADC payloads. For patients whose cancer has become resistant to a standard ADC, a treatment with Byondis's antifolate ADC could provide a powerful new option, enabling sequential therapy where it was not previously possible.

Data presented at AACR shows the proprietary payload is highly potent, demonstrating strong inhibition of its target, dihydrofolate reductase (DHFR). Critically, it shows no interaction with key cellular pumps (BCRP, PGP) that cancers often use to expel drugs and develop resistance. In preclinical patient-derived xenograft models of non-small cell lung cancer (NSCLC) and head and neck squamous cell carcinoma (HNSCC), the lead antifolate ADC produced robust tumor regressions with no significant toxicity at active doses. With GMP-scale manufacturing of the linker-drug already underway, the platform is advancing through IND-enabling studies, moving it one step closer to human clinical trials.

Activating the Immune System from the Inside-Out

Byondis's second platform, ByonBoost™, addresses a completely different but equally critical challenge: the significant number of patients who do not benefit from immune checkpoint inhibitors. One primary reason for this is that tumors can hide from the immune system by downregulating or losing MHC molecules, the surface proteins that T-cells typically use to identify threats.

The ByonBoost™ platform circumvents this problem by activating a unique type of immune cell: Vγ9Vδ2 (gamma delta) T cells. These potent killers do not rely on MHC presentation to recognize and eliminate tumor cells. Previous attempts to harness these cells were hampered by a lack of tumor specificity and short half-life. Byondis's phosphonate ADCs solve this by using an antibody to deliver a phosphonate payload directly to the tumor. Once inside the cancer cell, the payload triggers an “inside-out” activation of nearby gamma delta T cells, directing their potent killing activity specifically to the tumor microenvironment.

Preclinical studies have shown this modular platform works across multiple cancer targets, including CD123, CD20, TROP2, and HER2, demonstrating its broad applicability. The ADCs drive robust immune activation and tumor cell killing in lab studies, even when using primary patient material. Importantly, in non-human primate models—a crucial safety test before human trials—the lead candidate was well-tolerated with no clinical signs of cytokine release syndrome (CRS), a dangerous potential side effect of some immunotherapies.

Navigating a Competitive and Evolving Market

Byondis is advancing these technologies in a fiercely competitive landscape dominated by giants like Pfizer, AstraZeneca, and Roche. However, the company's focus on novel payloads and mechanisms provides a clear strategic differentiator. While many competitors focus on optimizing existing payload classes, Byondis is creating entirely new tools to add to the oncology arsenal.

This innovation is built on the foundation of a fully integrated, independent company. With over 200 employees and in-house capabilities spanning from early-stage R&D to GMP manufacturing in its Nijmegen facilities, Byondis controls the entire development process. This model allows for agility and deep integration of expertise, which is evident in its broader pipeline. The company is already in later-stage clinical trials with other ADCs, such as [vic-]trastuzumab duocarmazine for HER2-positive breast cancer, and is advancing other novel agents into the clinic.

The data presented at AACR 2026 marks a pivotal moment for the company, showcasing two distinct platforms that are not merely incremental improvements but potential game-changers. By developing solutions for both drug resistance and immunotherapy failure, Byondis is positioning itself to make a significant impact on the future of targeted cancer treatment. As these platforms progress toward the clinic, they offer new hope for patients facing the most challenging and difficult-to-treat cancers.