It's no problem. Yeah, great points!
I have not done the research necessary, and so I don't claim to be an authority on this. I guess value is something that BP will have to work out. Something that stood out for me was that preclinical models support 4-HPR in multiple different virus types, which is a great selling point. The 'Asian' Zika virus strain (PF13-251013-18) used in the preclinical work is structurally very similar to the American strain - 4-HPR showed better potency towards this strain than the African. This was some years ago and things may have changed since then, but I imagine a treatment for something afflicting Americans would be more interesting for BP.
Good work,
@Spuderman. One thing I am curious about is the treatment regimen. I'll need to do some more reading on this, but they are dosing 4-HPR (ISLA-101 -> 4-HPR sounds better)
before they infect participants with the dengue virus. I'm assuming that this is done to showcase the best results as they are loading the body with drug before infection. From a real world perspective, you would get infected first, have symptoms, and then take the drug, so this doesn't make sense to me from a functional stand point. Unless this is how these first trials are run.
Here is some evidence supporting the use of 4-HPR 12-hours
after infection in an in vitro model. The authors suggested that this indicated 4-HPR could be efficacious against established infections, although it would need to be confirmed. They used a mice model with dosing starting at the time of infection, but it is not what I'm looking for.
And so, I think something to consider for clinical risk here is if the drug can inhibit a matured dengue virus after infection, when a patient would be experiencing symptoms. So far, there is evidence to suggest that is the case.
