Byondis to Present Data from its Novel ADC Technology Platforms at the American Society for Cancer Research Meeting 2026
Byondis B.V., an independent biotechnology company focused on developing next-generation targeted therapies for cancer, is showcasing its latest scientific advances at the AACR Annual Meeting 2026, taking place in San Diego through April 22. The company’s presentations highlight two of its proprietary antibody-drug conjugate (ADC) technology platforms—antifolate-based and phosphonate-based systems—both designed to address critical limitations in current oncology treatment approaches.
These platforms represent a strategic effort by Byondis to push beyond the boundaries of existing ADC therapies, which have shown promise but continue to face challenges such as drug resistance, limited durability of response, and toxicity concerns. By leveraging novel mechanisms of action and innovative linker-drug designs, the company aims to expand the therapeutic potential of ADCs and improve outcomes for patients across a broad spectrum of cancers.
A New Generation of Antifolate-Based ADCs
One of the central highlights of Byondis’ AACR presentations is its first-in-class antifolate linker-drug platform, which is being featured in the Experimental and Molecular Therapeutics track. This platform is designed to overcome one of the most pressing challenges in oncology: resistance to commonly used ADC payloads, particularly those based on topoisomerase-I inhibitors and tubulin-targeting agents.
Traditional ADC payloads often lose effectiveness over time as cancer cells develop mechanisms to evade their cytotoxic effects. In response, Byondis has revisited the antifolate class of compounds—an established category in cancer therapy—and re-engineered it into a modern ADC-compatible format. Antifolates work by inhibiting enzymes involved in folate metabolism, which is essential for DNA synthesis and cell proliferation. By integrating this mechanism into an ADC framework, the company aims to deliver targeted cytotoxicity while minimizing systemic exposure.
The proprietary antifolate payload developed by Byondis demonstrates impressive potency, with activity in the low- to sub-nanomolar range. It strongly inhibits dihydrofolate reductase (DHFR), a key enzyme in folate metabolism, and exhibits broad cytotoxic activity across multiple cancer cell lines in vitro. Importantly, the payload does not interact with major drug resistance transporters such as BCRP and PGP, which are often implicated in reduced drug efficacy. This characteristic suggests a lower likelihood of cross-resistance with existing therapies.
From a development and manufacturing standpoint, the antifolate payload also offers favorable physicochemical properties, supporting scalability and compatibility with Good Manufacturing Practice (GMP) standards. The inclusion of a glucuronide-based linker further enhances the therapeutic index by improving stability and enabling controlled release of the active drug within tumor cells. This design also opens the possibility of dual-payload ADC strategies, where two complementary mechanisms of action can be delivered simultaneously.
Byondis’ lead antifolate ADC candidate, which targets an undisclosed tumor-associated antigen, has demonstrated strong preclinical performance. In vitro studies show potent anti-tumor activity, while in vivo experiments using patient-derived xenograft models have revealed robust tumor regression in cancers such as non-small cell lung cancer (NSCLC) and head and neck squamous cell carcinoma (HNSCC). Notably, these effects were achieved without significant toxicity at therapeutically active doses, highlighting the platform’s potential for a favorable safety profile.
The versatility of this antifolate ADC approach positions it for use across multiple lines of therapy, from first-line treatment to later-stage or combination regimens. Its differentiated mechanism of action may also make it particularly valuable in patients who have developed resistance to other ADCs.
Phosphonate ADCs and Immune Activation
Complementing the antifolate platform is Byondis’ phosphonate-based ADC technology, branded as ByonBoost™, which is being presented in the Immunology track at AACR. This platform represents a novel class of immunostimulatory ADCs designed to engage the immune system directly within the tumor microenvironment.
A key focus of this approach is the activation of Vγ9Vδ2 (gamma delta) T cells, a subset of immune cells known for their potent cytotoxic activity against tumor cells. Unlike conventional T cells, gamma delta T cells can recognize and eliminate cancer cells independently of major histocompatibility complex (MHC) presentation, making them an attractive target for immunotherapy. Their activity has been associated with improved clinical outcomes in various cancers.
However, previous attempts to harness gamma delta T cells have faced significant limitations, including lack of tumor specificity and short-lived activation. Byondis’ phosphonate ADCs are designed to overcome these challenges by combining targeted delivery with localized immune activation.
The platform uses antibodies directed against tumor-associated antigens (TAAs) to deliver a cleavable phosphonate payload directly to cancer cells. Once inside the tumor microenvironment, the payload triggers “inside-out” activation of Vγ9Vδ2 T cells, leading to a cascade of immune responses. These include cytokine release, immune cell degranulation, and targeted tumor cell killing.
Preclinical studies have demonstrated that these phosphonate ADCs can induce robust immune activation and anti-tumor effects in vitro, including experiments using primary patient-derived samples. The platform has been successfully applied to multiple targets, including CD123, CD20, TROP2, and HER2, underscoring its broad applicability across different tumor types.
Importantly, safety data from non-human primate studies indicate that the lead phosphonate ADC candidate is well tolerated, even at high doses. No clinical signs of cytokine release syndrome (CRS)—a common concern with immunotherapies—were observed, suggesting a potentially favorable safety profile.
A Dual-Mechanism Strategy for Oncology
One of the most compelling aspects of Byondis’ phosphonate ADC platform is its ability to combine two distinct mechanisms of action: direct tumor targeting and immune activation. This dual approach allows the therapy to attack cancer cells both directly and indirectly, potentially enhancing efficacy and reducing the likelihood of resistance.
At the same time, the platform preserves the natural effector functions of the antibody component, maintaining its ability to engage the immune system through established pathways such as antibody-dependent cellular cytotoxicity (ADCC). This multi-layered mode of action represents a sophisticated and potentially transformative approach to cancer therapy.
The modular design of the platform also enables flexibility in development, allowing researchers to pair different antibodies with the phosphonate payload to target a wide range of cancers. This scalability is particularly important in the rapidly evolving field of precision oncology, where treatments are increasingly tailored to specific tumor characteristics.
Strategic Vision and Future Outlook
Byondis’ presentations at AACR 2026 highlight the company’s commitment to innovation in the ADC space. By focusing on novel payloads and mechanisms of action, the company is addressing key gaps in current treatment paradigms, including resistance to existing therapies and limited response to immunotherapy in certain patient populations.
The antifolate and phosphonate platforms together form a complementary strategy: one focused on overcoming resistance through targeted cytotoxicity, and the other on enhancing immune engagement within the tumor microenvironment. This dual approach reflects a broader trend in oncology toward combination and multi-mechanism therapies that can deliver more durable and effective responses.
As these platforms continue to advance through preclinical and clinical development, they have the potential to redefine the role of ADCs in cancer treatment. By integrating cutting-edge science with practical considerations such as manufacturability and safety, Byondis is positioning itself at the forefront of next-generation oncology therapeutics.
In summary, the company’s research presented at the AACR Annual Meeting 2026 underscores the promise of innovative ADC technologies to address unmet needs in cancer care. With strong preclinical data, differentiated mechanisms of action, and broad applicability, Byondis’ platforms represent an important step forward in the quest to develop more effective and personalized treatments for patients with cancer.
About Byondis
Driven to improve patients’ lives, Byondis is an independent, fully integrated biopharmaceutical research and development company creating innovative targeted medicines for cancer. The company is developing new biological entities (NBEs) with a focus on antibody-drug conjugates.
Byondis’ development portfolio leverages expertise in linker-drug (LD) technology, antibody-drug conjugation and disease biology. Byondis’ fully integrated drug development capabilities cover all stages from pre-clinical and clinical R&D, production of clinical batches of the selected product candidates and regulatory filings, which are all done in-house.
The company has a dedicated team of more than 200 staff working in its state-of-the-art R&D and GMP manufacturing facilities in Nijmegen, the Netherlands.
Source Link:https://www.businesswire.com/
