Novel Payloads

Resistance to existing payloads limits how long ADCs can work for patients. Byondis is pioneering new payload approaches to expand treatment options: a first-in-class antifolate payload built to overcome resistance, a first-in-class immunostimulatory phosphonate payload that drives tumor-selective activation of γδ T cells, and other undisclosed novel payloads. Each can be used on its own or combined with our other platforms to address multiple hallmarks of cancer.

First-in-Class Antifolate Linker-Drug Platform

As ADCs move into earlier treatment lines and combination therapies, resistance to existing payloads is driving the need for novel payload classes. Byondis’s first-in-class antifolate payload platform addresses this challenge, leveraging a clinically validated mechanism of action not previously used in targeted therapy to overcome resistance to existing ADCs and offer new treatment options for non-responders.

Treatment resistance to TOPO1i and TUBi payload ADCs is an apparent problem for cancer patients

Unlike the TOPO1i and TUBi payloads that comprise approximately 85% of ADCs entering the clinic, our antifolate platform provides a differentiated approach designed to expand treatment options for patients facing difficult-to-treat cancers. Preclinical results demonstrate both in vitro and in vivo efficacy across solid tumor indications, with optimal ADC properties that overcome resistance to TOPO1 and tubulin payloads. The platform is advancing to the clinic and available for partnering, offering a novel solution to an emerging challenge in oncology.

ByonBoosT™: First-in-Class Phosphonate Linker-Drug Platform

Checkpoint inhibitors (CPIs) provide durable responses and are a key treatment for many types of cancer. However, 60-80% of patients do not respond to immunotherapy, resulting in a need for well-tolerated treatments that complement currently approved CPIs and overcome resistance and toxicity.  One of the main resistance mechanisms is MHC downregulation, which occurs in 40-90% of tumors and limits recognition by classical αβ T cells, the primary target of current immunotherapies.

Need for well-tolerated immunotherapy that complements currently approved checkpoint inhibitor therapies

Byondis’s first-in-class ByonBoosT™ phosphonate platform addresses this critical unmet need through a fundamentally different approach: powering tumor-selective activation of γδ T cells, which provide MHC-independent recognition of cancer cells. Unlike conventional immunotherapies that depend on MHC expression, our immunostimulatory phosphonate payload indirectly activates γδ T cells to selectively eliminate cancer cells, overcoming checkpoint inhibitor resistance and toxicity. Our ByonBoost ADCs have shown a clean profile in initial NHP safety and PK/PD studies.

ByonBoosT™: A First-in-Class Phosphonate ADC Platform for Targeted Delivery of Phosphonates to Tumor Cell

ByonBoost™ can be targeted to heme and solid TAAs, delivering a phosphonate payload that activates BTN2/3 receptors and triggers cytotoxic γδ T cell–mediated tumor killing

Masking Technology

Many tumor-associated antigens (TAAs) targeted by antibody therapies are also present in health tissue, causing on-target off-tumor toxicity, affecting treatment safety and limiting combination options. This fundamental challenge forces clinicians and patients to choose between efficacy and safety.

Platforms

Our modular ADC platforms are generating potential first and best in class assets, including novel proprietary payloads, advanced masking technologies, and linker and drug conjugation strategies.