Non-nucleoside reverse transcriptase inhibitors (NNRTIs) represent a cornerstone of antiretroviral therapy for the treatment of HIV infected patients. Current market leading NNRTIs are dosed once-daily (QD) as a component of combination therapy. Lifelong adherence to HIV therapy remains a challenge for many patients. Extended duration dosing with forgiving agents is a potential means to address this issue. Towards this goal, we targeted the development of a once-weekly (QW) oral NNRTI. Central to the success of this approach is the ability to produce an orally bioavailable NNRTI with a long plasma half-life sufficient to enable QW dosing with forgiveness. Our strategy to deliver on this relatively unprecedented objective, along with key elements of the design and optimization effort leading to a clinical candidate, will be presented. The initial clinical data, which support the potential for QW dosing for HIV treatment, will also be discussed. It is envisioned this compound will be a component of a future QW regimen that has the potential to improve adherence and clinical outcome as a new paradigm for the treatment of HIV infection.

Discovery of a once-weekly NNRTI clinical candidate: A new paradigm for treating HIV-1 infection

256th National Meeting (2018)

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