VRTX
#Yes, (inaudible), this is <UNK> <UNK>.
I'll start with the first one, <UNK> can take the second, and <UNK> will take the third.
With respect to Galapagos, just as <UNK> emphasized, <UNK> said, we really don't comment on any of the competitor compounds or programs.
I would just reiterate what <UNK> said about our program, which is we like our position really for three reasons.
Number one, we have two drugs in the combination 661 in KALYDECO that are either approved or very well characterized, so when you put a three-drug combination together, we feel that's a nice position to be in.
Number two, we've spent a lot of time optimizing the pharmaceutic properties of both next-gen correctors.
That's important as you put a three-drug combination together.
And number three, we showed you the chloride data from the HBE cells with that three drug combination, which are getting us levels which are at or north of what KALYDECO does in G551d.
And so far, those assays have predicted quite well what we see in the clinic.
We're excited to see the first Phase 2 results.
We'll start those studies next year.
I would say just to round out your questions, I'll just state again, we're committed to driving this business forward and having high operating margins.
We get to that position by revenue growth and controlling our operating expenses.
We have a business and we're in an area where we can do that.
And so for us it's execution on the launch, both in the US and then in Europe, continue to reinvest for growth of the future, yet still having significant operating margins.
I'll take the second one, which is about the additional correctors.
Maybe I'll broaden it out just a little bit, if you don't mind.
Our goal is to create the best portfolio of medicines for each one of these patient populations.
So certainly a big part of that is going to be next-gen correctors, and as I've said several times before, we have multiple ---+ we have discovered multiple next-gen correctors.
These are the first two, but there are others behind them.
And assuming they pan out as they go through lead off and [tox], yes, our intent would be to put additional correctors in, particularly if they have different and interesting properties so that we can study them.
Beyond that, I'd also remind you of things like the ENaC inhibitors, like gene editing, we're really looking at a variety of modalities, and so over the next few years, you can expect to see us bring multiple compounds, and frankly, multiple modalities into the clinic to try to create the best combinations.
Operator, it's now ---+
Operator, it's now 6:00.
We will take two more questions.
Thank you for the question, and you're absolutely right, it will obviously in the end be driven by the data, which is why we're going to explore these in Phase 2.
If you think about it at a high level, from a high level strategic standpoint, second-generation correctors in a triple combination would be expected to address anybody who has a single or a double delta 508 allele, so that's about 80% to 90% of all patients.
ENaC inhibitors, again, theoretically and we're going to have to demonstrate this in the clinic, should be us useful for anybody with any mutation.
In fact, as you know, Parion is running an initial Phase 2 trial with an all comer trial.
We're going to run a Phase 2 trial with ENaC plus ORKAMBI.
Based on the data there, we'll be able to determine you how to craft these regimens for each patient subset.
That would be the theoretical expectations based on what we've seen in HBE cell.
Does that make sense.
Sure.
We appreciate everyone joining us on the call tonight.
The Investor Relations team will be in the office if you have additional questions.
Thank you and have a good evening.
