ADCs are not one-size-fits-all. Dolasynthen is a platform that generates site-specific, homogeneous ADCs, utilizes a proprietary payload and has the ability to match the drug-to-antibody ratio (between 2-18+) to specific targets, providing the potential to maximize the therapeutic index. The Dolasynthen scaffold has been precisely balanced to provide optimal water solubility, charge balance, linker stability and DAR.
Precise Control over DAR: Because ADCs are not one-size-fits-all, the optimal DAR will vary among different targets and antigens. Dolasynthen allows for precise DARs between 2-18+, enabling optimization of the DAR for specific antigens and antibodies.
Illustrated by our preclinical data, optimized Dolasynthen ADCs exhibit a broad therapeutic index as a cancer therapy. These data demonstrate the potential for the Dolasynthen platform to generate the optimal ADC for a given target and antibody.
XMT-1660 is a B7-H4-directed Dolasynthen antibody drug conjugate with a precise, target-optimized drug-to-antibody ratio (DAR 6) and a proprietary cytotoxic payload with controlled bystander effect. B7-H4 is expressed in high unmet need tumors, including breast, endometrial and ovarian. Expression occurs both on both tumor cells and immunosuppressive tumor-associated macrophages (TAMs). Targeting B7-H4 provides the potential both for a direct, cytotoxic antitumor effect and for additional payload delivery to the tumor microenvironment that can further contribute to immunogenic cell death, dendritic cell activation, and stimulation of an immune response. In preclinical studies, XMT-1660 demonstrated robust in vivo activity against multiple breast cancer models and against an ER+/HER2- breast cancer model, all of which express B7-H4.