Reactive amanitin for bioconjugation to antibodies**

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This proposal addresses unmet needs in targeted therapy for cancer in collaboration with Iprogen, Inc. a biopharmaceutical company dedicated to the production of antibody-drug conjugates (ADCs). Iprogen is strategically positioned to create new targeted therapies from novel warheads. My lab is poised to provide Iprogen with new warheads based on amanitin. Targeted therapies for cancer represent a rapidly expanding class of anticancer agents that use a cancer-specific targeting agent (e.g. an antibody) to deliver a potent, but usually non-specific, cytotoxic agent to cancer cells. Antibodies or peptides alone are often ineffective but become effective against cancer when conjugated to a suitable toxin that otherwise would be too toxic. ADCs now offer definitive hope to cancer patients. Yet in terms of industrial translation, there is a significant unmet need for new toxic payloads that that can be targeted to cancer as well as a means of producing new ADCs for testing and clinical translation. ****My lab, which specializes in bioconjugation and natural product synthesis, has recently accomplished the first total synthesis of amanitin, a potent and validated payload toxin for ADC development. Iprogen, Inc. is an established biotechnology company in Richmond, B.C., with an interest in generating new antibody-drug conjugates for preclinical and clinical applications. This Engage Grant will forge a unique research synergy between my lab's research interest where we will develop new amanitin-based toxic payloads and Iprogen's commercial interests in applying these toxins to various therapeutic antibodies to create new IP based on their conjugation to diseased-mitigating antibodies. My lab will provide scientists at Iprogen with the needed payload toxins and novel linker-arm technologies. In turn, staff scientists at Iprogen will generate new ADCs and will test them in suitable toxicity assays**