Dolasynthen

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.

Dolasynthen Advantages

  • 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 2-24, enabling optimization of the DAR for specific antigens and antibodies.
  • Site-Specific Bioconjugation: The site of scaffold bioconjugation to an antibody impacts the overall properties of that ADC. Dolasynthen enables site-specific bioconjugation allowing further ADC optimization.
  • Homogeneous ADC Development: The DAR and antibody bioconjugation is consistent throughout ADCs developed with the Dolasynthen platform allowing for consistent and precise drug delivery to targeted cancer cells, every time.
  • Increased Hydrophilicity: The precise optimization of the hydrophilic moiety on Dolasynthen ADCs allows for increased aqueous solubility and enhanced PK properties.
  • Proprietary DolaLock Payload: Dolasynthen is loaded with our proprietary auristatin chemotherapeutic drug, which is a highly potent anti-tubulin agent selectively toxic to rapidly dividing cells, with the advantages of the DolaLock controlled bystander effect.