Dolaflexin - Mersana Therapeutics

The Dolaflexin platform was designed to increase the efficacy, safety, and tolerability of ADCs. We believe this platform overcomes the limitations of traditional ADCs in which drugs are directly conjugated to antibodies. Dolaflexin utilizes our proprietary Fleximer polymer, a biodegradable, highly biocompatible, water-soluble polymer able to carry multiple drug molecules. Instead of direct conjugation to an antibody, drug molecules are attached through an optimized, cleavable linker to the Fleximer scaffold, which is then conjugated to the antibody through a non-cleavable linker. Fleximer dramatically improves drug solubility, pharmacokinetics, and immunogenicity, and significantly increases the number of drug molecules carried by each ADC.

Our lead asset, upifitamab rilsodotin (UpRi), is a first-in-class Dolaflexin ADC targeting NaPi2b that is being studied in UPLIFT, a single-arm registrational trial in patients with platinum-resistant ovarian cancer; UPGRADE-A, a Phase 1 trial evaluating UpRi in combination with carboplatin; and UP-NEXT, a Phase 3 clinical trial of UpRi as monotherapy maintenance following treatment with platinum doublets in recurrent platinum-sensitive ovarian cancer.

Dolaflexin Advantages:

Proprietary DolaLock Payload: Dolaflexin 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.

Higher Drug-to-Antibody Ratio (DAR): Historically, ADCs have been limited to a DAR of 3-4. The Dolaflexin platform can deliver ADCs with DAR of about 10 allowing for greater efficacy while also maintaining pharmacokinetics and drug-like properties.

Expanded Range of Addressable Tumor Targets: The higher DAR enabled by Dolaflexin results in more chemotherapeutic drug released into the tumor cell for every ADC internalized. As a result, Dolaflexin ADCs have efficacy against tumor targets with lower levels of antigen expression where traditional ADCs have not been effective.