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    Phoebe Tan • Jefferies Financial Group Inc.

    Phoebe Tan's questions to Zymeworks Inc (ZYME) leadership

    Phoebe Tan's questions to Zymeworks Inc (ZYME) leadership • Q1 2025

    Question

    Phoebe Tan from Jefferies asked about Zymeworks' TOPO ADCs, questioning if the higher maximum tolerated doses seen preclinically compared to Enhertu could imply lower potency. She also requested information on the planned go-forward doses for ZW191 and ZW251.

    Answer

    Chief Scientific Officer Dr. Paul Moore addressed the potency question by stating that direct preclinical benchmarking shows their payload has a very comparable efficacy profile to deruxtecan (Enhertu's payload). While he could not specify go-forward clinical doses, he confirmed that the high preclinical tolerability allows for higher starting doses in patients, consistent with standard ADC development practices.

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    Phoebe Tan's questions to Cytokinetics Inc (CYTK) leadership

    Phoebe Tan's questions to Cytokinetics Inc (CYTK) leadership • Q3 2024

    Question

    Phoebe Tan of Jefferies asked about the clinical utility of a cardiac myosin inhibitor that provides gradient relief without affecting LVEF, particularly in hypercontractile HCM patients.

    Answer

    Fady Malik, EVP of R&D, explained that hypercontractility (e.g., 80% LVEF) is abnormal and a key therapeutic target. He argued that reducing contractility to normal levels is crucial for favorable cardiac remodeling and that simply treating the obstruction without addressing hypercontractility is likely insufficient for long-term patient outcomes.

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