Mersana Therapeutics products

UpRi, a first-in-class ADC targeting the sodium-dependent phosphate transport protein NaPi2b, utilizes the Dolaflexin platform to deliver about 10 DolaLock payload molecules per antibody. The NaPi2b antigen is broadly expressed in ovarian cancer and non-small cell lung cancer (NSCLC) adenocarcinoma. UpRi is being studied in UPLIFT, a single-arm registration strategy, in patients with platinum-resistant ovarian cancer as well as the expansion portion of a Phase 1 proof-of-concept clinical study in patients with NSCLC adenocarcinoma.

Immunosynthen is our novel immunostimulatory ADC platform designed to take ADCs beyond traditional cytotoxic drugs to targeted stimulation of the innate immune system. Through the safe and efficient delivery of a novel immunomodulatory STING agonist, ADCs created with our Immunosynthen platform have the potential to address the challenges of efficacy, delivery and tolerability. Stimulator of Interferon Genes (STING) is a well-studied innate immune pathway capable of inducing anti-tumor immune activity. Our preclinical data show that the anti-tumor activity of Immunosynthen STING-agonist ADCs involves the targeted activation of the STING pathway in both tumor-resident immune cells and in tumor cells, in an antigen binding-dependent manner. This one-two punch provides the potential for enhanced anti-tumor activity with a STING-agonist ADC when compared to other innate immune approaches that activate only the immune cells. 

ADCs are not one-size-fits-all. The Dolasynthen platform enables an iterative approach to develop the right ADC for a given indication through customization and optimization. Dolasynthen utilizes a synthetic scaffold for precise control of DAR (from 2-24) and site-specific antibody bioconjugation. The platform is also able to homogeneously generate ADCs with precisely defined DARs for consistent drug delivery to cancer cells. 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

The Dolaflexin platform was designed to increase the efficacy, safety, and tolerability of ADCs. 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.

Once ADCs release their cytotoxic payload into targeted cells, the drug is often able to cross cell membranes, entering and potentially killing neighboring cells whether those cells are cancerous or not. This effect is called bystander-killing, which is advantageous when bystander cells are cancerous but toxic if the cytotoxic drug is able to enter adjacent healthy cells. The DolaLock payload controls the bystander effect by locking the cytotoxic drug inside cells after allowing a short period of diffusion throughout the tumor. As the drug diffuses through neighboring tissue, the DolaLock payload is metabolized to a form that is still highly potent but no longer able to cross the cell membrane. DolaLock effectively locks the drug inside cells, controlling the bystander effect for a safer and more effective cancer therapy.