Our Technology

  • Background to the Drug Conjugate Field

    Drug Conjugates are primarily deployed to deliver a targeted therapy to cancer cells. Conceptually, this is achieved through the selective release of a therapeutic payload within a tumor.

    ADCs, SMDCs and our TDCs all use three basic components. A ligand designed to recognize the cell surface protein (which is often a receptor for a naturally occurring ligand) that is being targeted. A drug conjugation chemistry component (or linker) that is designed to be cleavable (usually within the target cell), thereby releasing the third component, the payload. The payload is a therapeutic moiety (typically a cytotoxic agent) that is designed to kill the targeted cancer cell. ADCs are the leading class of drug conjugate therapeutics and they use antibodies directed against the target cell surface protein (usually a receptor) as the ligand. After receptor binding, the ADC is internalized into the cancer cell (by a process call “endocytosis”) and processed through a specific compartment of the cell interior called an endosome to typically end up being cleaved in another compartment of the cell called the lysosome. The goal is that the linker will be cleaved inside the cell and the payload released to kill the cancer cell. Both the number of receptors on the cancer cell surface and payload molecules connected to the ligand impact the potential levels of toxin that can be delivered to the cancer cell.

    There are multiple elements that make up an optimal drug conjugate including the targeting moiety and the linker chemistry, both of which are crucial elements in achieving a favorable Therapeutic Index (a measure of the balance of anticancer activity and the toxic side-effects suffered by the patient). If the linker is too stable under conditions inside the cell, not enough payload will be released quickly enough (and some can actually be “recycled” to the cell surface). Conversely, if the linker is not stable enough under the physiological conditions outside the cancer cell, it will cleave and release the toxic payload causing harmful toxicity to normal cells. This is also influenced by the time it takes to clear the drug conjugate from the systemic circulation. As such, the longer the drug conjugate is in the circulation the more important linker stability is in order to minimize cleavage and release of payload systemically.

    Another challenge is the uniformity of the expression of the targeted receptor or other cell surface protein in the various tumor lesions present in advanced metastatic cancer. It is now well understood that as a patient’s advanced cancer progresses the expression of targeted receptors both within a single lesion and between lesions can vary (a phenomenon termed “heterogeneity”). The development of the optimal drug conjugate demands the effective balancing of all these elements: an ideal ligand that binds receptors or cell surface proteins that are abundantly present on cancer cells but much less so on normal tissues; multiple payload molecules to enhance the overall toxicity to the cancer cell and a linker that – when matched to the rate of clearance of the drug conjugate – is sufficiently stable in the patient’s body. The additional ability to release payload selectively within the tumor itself – while still outside the cancer cell – could be an additional advantage in dealing with the heterogeneity of target protein expression.

    Tunable Drug Conjugates for the treatment of cancer and other diseases

    BlinkBio’s Tunable Drug Conjugates (TDCs) use a rapid payload release/rapid systemic clearance approach. Our SiLinker and payload cassette technology allows early payload release in the endosome in order to drive high payload concentrations within tumor cells. The intention is to overwhelm cellular resistance mechanisms and induce rapid killing of the cancer cells. Our TDCs are designed to be cleared from the body quickly which should further improve the Therapeutic Index (TI).

  • TDC Platform Illustration_769p

  • BlinkBio’s Tunable Drug Conjugates technology platform is comprised of three unique components designed to provide superior properties in order to achieve potent tumor cell killing while minimizing side effects:

    A DVD-Fab ligand moiety equips our conjugates with a high affinity receptor targeting function
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    A SiLinker™ conjoining the DVD-Fab with the Payload Cassette to stably carry them to tumors where they can be rapidly and completely released
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    A Payload Cassette which can deliver both multiple and mixed payloads
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  • We believe that our technology has the following unique overall characteristics that differentiate it from other drug conjugate technologies.

  • TDC Characteristics_769