BUILDING THE BACKBONE

Mersana’s approach to building novel drug conjugates starts with our Fleximer polymer, which can dramatically improve drug solubility and pharmacokinetics, reduce immunogenicity and optimize drug load. Our Fleximer polymer is uniquely biodegradable, well tolerated with a favorable safety profile and has been clinically validated. The Fleximer polymer serves as the backbone for our drug conjugates. We customize the size of the backbone based on the type and quantity of therapeutic payloads, as well as the nature of the targeting protein being attached.

CUSTOM-DESIGNED LINKERS

We determine which and how many linkers to use to attach the payload to the backbone. Mersana’s diverse array of linker chemistries allows us to arm our drug conjugates with significantly higher loads of anti-cancer agents than conventional ADC technologies, as well as to potentially arm a single immunoconjugate with a combination of payloads. The custom-designed linkers allow us to control the rate, mechanism and localization of drug release, potentially increasing efficacy and minimizing off-target side effects.

Using a chemically distinct linker from those used to attach the therapeutic payload, we then attach an antibody, or alternative targeting moiety such as an antibody fragment, to the backbone. The ability to attach a variety of targeting agents to the Fleximer backbone allows us to choose the one that will most effectively reach, bind to and penetrate the tumor cell, while sparing healthy cells. By using separate linker chemistries to attach the targeting agent and drug payload, we can choose the best linkers for each task.

MAXIMIZING THERAPEUTIC BENEFIT

While in the bloodstream, our Fleximer polymer protects the drug payload, ensuring stability. Through optimized design and careful control of numerous parameters, our immunoconjugates are preferentially taken up by cancer cells, accumulating and persisting in the tumors to deliver a prolonged therapeutic effect. Once the drug payload has been released, the Fleximer polymer and linkers biodegrade into safe byproducts, further supporting the potential safety benefits of this novel approach.

Mersana’s Fleximer platform represents an evolutionary leap in immunoconjugate technology, allowing us to overcome many of the limitations of current ADC technologies. Using our proprietary Fleximer polymer and linker chemistries, we can custom design a drug conjugate with a unique combination of properties aimed specifically at attacking a particular type of cancer. By engineering a drug conjugate with industry-leading payloads of anti-cancer agents and precisely controlling when, where and how those agents are released, Mersana’s ADC therapies have the potential to more effectively treat broader populations of cancer patients while minimizing undesired side effects.

Significantly higher Drug-to-Antibody ratio (DAR) (20+ versus 3-4 with traditional technologies) resulting in higher efficacy in head to head studies

Strong efficacy in low expressing tumors for a variety of targets not amenable to traditional ADCs

Robust data supporting a variety of payload classes and mechanisms-of-action allowing a more appropriate match of drug to tumor type

Can be deployed with a variety of  targeting moieties beyond antibodies for improved tumor penetration of solid tumors and thereby enhanced efficacy

Dolaflexin is currently Mersana’s most advanced Fleximer antibody drug conjugation platform. It pairs our Fleximer polymer backbone with our custom linker chemistries to create ADC therapies armed with high doses of a proprietary derivative of the dolastatin family of cytotoxic agents. Preclinical data on the Dolaflexin platform supports that it could generate a portfolio of highly potent and well-tolerated therapies against multiple cancers and significantly broaden the patient populations that could benefit from ADCs.

Using this platform, we can engineer ADCs with drug-to-antibody ratios in the range of 15-20, much higher than those from conventional approaches, while ensuring stability in the circulation and maintaining essential drug-like properties. This dramatically increased payload capacity allows for more efficient delivery and greater efficacy in a variety of tumors, particularly those that don’t express sufficient levels of the target receptor protein to benefit from current antibody therapies or other ADC approaches with lower drug loads. Our Dolaflexin immunoconjugates have been shown to be well tolerated and highly active in a variety of models in multiple cancer indications.

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