Question-and-Answer Session
Operator
(Operator Instructions) Your first question is from Amy Wang with MDB Capital.
Amy Wang - MDB Capital
How do you see PL-3994 fitting into the [inaudible] market? Do you think that will be taken along with beta blockers and other drugs that are currently available.
Trevor Hallam, Ph.D.
Absolutely. We will develop that. It could be used as mono-therapy but I think in this chronic treatment paradigm which really does have very poor prognosis at the moment, there is plenty of room for an adjunct therapy on top of those other medications. So I think that’s how this will be actually used in anchoring that patient population.
Amy Wang - MDB Capital
And secondly, what aspect of PL-3994 do you think differentiates itself from NATRECOR and in particular can you address if it has perhaps a better safety profile and can you touch a little bit on hypotension or the risk of hypotension?
Trevor Hallam, Ph.D.
Yes, of course. Firstly, in any chronic treatments of any chronic disease you need the ability to get coverage 24 hours a day so that you can have the maximum possible benefits. And the Fusion 2 studies with nesiritide were really trying to get to a more chronic cover in those patients visiting outpatient clinics, but they only amounted to a couple of infusions per week.
Remember, nesiritide and NATRECOR has a 22 minute half-life and there are two very active mechanisms for getting rid of it when dosed. One is an anti-peptidace in the plasma which degrades it and the other is because the compound nesiritide binds to the NPRC receptor and gets rapidly cleared.
So it’s very difficult to actually adjust dose because as soon as you infuse it’s getting churned out by two mechanisms. So getting it accurately dosed is tough.
Trying to infuse something 24 hours a day, 7 days a week is not feasible, of course, for chronic treatment. So the reason why we have developed PL-3994 is to really go for the same receptor, which is so fundamentally linked to the heart remodeling and the survival outcomes, and that’s the genetic evidence I covered, but also supported by clinical precedence of the other agonist, ANP, which is commercialized in Japan, and they have the continuous infusions to greater than 3 days and can show a signal that you’re improving heart remodeling measured 3-4 weeks later.
So I think the clinical precedence efforts to coming back to PL-3994, PL-3994 has got a 3 hour half-life, certainly twice a day will cover the 24 hour exposure you need on a chronic basis.
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