ADCs are not one-size-fits-all. Dolasynthen is a platform that generates site-specific, homogeneous ADCs utilizing Mersana’s clinically validated DolaLock microtubule inhibitor payload with controlled bystander effect at a drug-to-antibody ratio (between 2-24) matched to the target to maximize the therapeutic index. The Dolasynthen scaffold has been precisely balanced to provide optimal water solubility, charge balance, linker stability and DAR. Dolasynthen retains the favorable properties of Dolaflexin, including our proprietary DolaLock technology for a controlled bystander effect, with even better physicochemical and pharmacokinetic properties.
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 Mersana’s clinically validated DolaLock microtubule inhibitor 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 consistent with the features of our unique DolaLock payload. 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.