Replies to post #2264 on Enanta Pharmaceuticals Inc (ENTA)

[vinmantoo]

ENTA’s PR on EDP-235 phase-1/1b data:

Thanks Dew. It looks good to me.

EDP-235 exposure increased approximately proportionally with increasing single and multiple doses, with a consistent half-life ranging from 13 to 22 hours, resulting in a PK profile suitable for once-daily dosing. Exposure was enhanced with food administration of a standard meal. EDP-235 once-daily taken with food, resulted in mean trough plasma levels at steady state that were higher than the plasma protein adjusted EC90 of EDP-235 in Vero cells as follows:

200mg: 3-fold for Alpha and 6-fold for Delta variant
400mg: 6-fold for Alpha and 12-fold for Delta variant
Considering a preclinical lung to plasma ratio of 4:1, lung levels are predicted to be as follows:

200mg: 12-fold for Alpha and 24-fold for Delta variant
400mg: 24-fold for Alpha and 48-fold for Delta variant

So if we take the mid-zone for half-life of 18 hours, let's look at 200mg and 400mg doses on delta in the lung.

Estimated Lung levels, fold higher than EC50 after last dose:
200mg: 6 fold at 18hrs, 3 fold high a 36hr and 1.5 times higher at 54 hrs.

400mg: 24 fold at 18hr, 12 fold at 36hr, 6 fold at 54hr, 3 fold at
72hr and 1.5 fold after 90hrs.

That means people might be less likely to suffer from rebound like sometimes seen with Paxlovid. I wouldn't be surprised if the 200mg dose is used and perhaps for 7 days rather than 5 days.