Pyronaridine as an oral Treatment for Ebola

We have identified the small molecule pyronaridine as a potent EBOV inhibitor in vitro with excellent ADME properties, resulting in 100% survival at 21 days against Ebola infected mice after a single 75 mg/kg i.p. dose (t1/2 146hr). A window study in these infected mice suggested we could dose 2h or 24h post exposureto result in good efficacy in mouse against EBOV. A recent Guinea Pig EBOV study also demonstrated 40% survival after a single 300mg/kg oral dose of pyronaridine (t1/2 90hr). Likely the first small molecule antiviral to show any efficacy in this animal model. Our proposed studies will now expand on these data by generating maximum tolerated dose and pharmacokinetics data in non-human primates before we progressto oral delivery in this species to determine the optimal oral dosing regimen. Once we have performed these in vivo studies we will prepare a preIND application for pyronaridine. This will then enable us to obtain direction for any further toxicology studies and animal rule studies. Our goal would be to deliver pyronaridineas a single dose treatment for Ebola infection in humans. As a result, we would be able to obtain a neglectedtropical disease voucher from the FDA which could be monetized to reinvest in developing additional treatments for rare and neglected diseases.