CORT
#No, the answer to your first question is, yes, the time is now come and gone.
And I think the most important thing to understand is that this is a regular phenomenon for us.
And so in sort of thinking about the year before the year had begun, this is really part of our thinking as well.
So ---+ because it's something that we face basically in all the years that we've launched in other particularly Orphan Drugs phase as well.
So yes, we don't provide quarter-by-quarter guidance.
But yes, what we expected to see was not so different than what we actually saw.
I'm going to give you a very brief statement, and then I want to introduce you to the fourth person who is in our room, is <UNK> <UNK>, who runs all of our commercial franchise.
The answer is it comes from both places, both existing physicians, who are prescribing to more patients, as they've seen the medicine work.
And it also be ---+ comes from new doctors prescribing to patients, who were not previously prescribed.
And it's actually a little bit more of the latter than it is the former, but I'll keep ---+ I'll introduce you to <UNK>, and he can provide a little more color.
Yes.
Thanks for the question.
I think that was most of the answer, I think.
The only other piece to add to that is that for the last couple of quarters, we really, on an increasing basis added more new prescribers, and as Joe stated as, doctors ---+ the hardest thing for us as a company commercially is to get physicians to write their first prescription, and when they do and they see the benefit of Korlym, they look for more patients.
So from a dispersion standpoint from the business, we have many unique prescribers, new prescribers that come into the business, we have many multi-prescribers and we're seeing prescriptions from all over the country.
Well, I think, that in terms of efficacy, it would be surprising to get something which was better because Korlym works on pretty much everybody, and that's terrific.
But it really does have this Achilles' heel, that's very, very consequential of the progesterone receptor side effects.
In addition to the medical side effects causing endometrial hypertrophy and irregular vaginal bleeding, it has both political and actual logistical problem that this is the same ingredient which is in the abortion pill and has to have very restricted distribution as a consequence.
I can tell you this, and it's always sort of hard to prove it a negative, although I've really had some anecdotal evidence and this is the case.
There are places in the country where Korlym is not prescribed, and I can tell you with certainty that there are doctors who prescribe to men who like the medicine very much but don't prescribe to women.
So this is not a small thing.
And taking away the progesterone receptor side effect is a major clinical advance for people who want to use this medication.
And again, I'll just repeat, it's in 2 different ways: One, it's a serious medical advance; and two, it allows potentially for far less restricted distribution than is currently necessary.
Well, I think the way to think about this is just as our clinical programs advance, our clinical spending advances with them.
And so they're going to become ---+ yes, they ---+ as they advance across year, there will be more patients taking medicine, more sites opened, more product being purchased.
And I think you just need to figure that into your forecast.
As for the sort of the administration portion of our spending, I think that we really are and it has been true for quite some time, that we generate marginal revenue with very little additional administrative expense.
And that's going to continue to be true.
Well, the Phase III study for ---+ we have no Phase III studies for relacorilant so far.
But is the question, how do we expect to enroll.
How do we expect to deal with the enrollment as we get to Phase III.
Bob.
Yes.
As I said, we really have the opportunity, and that's the great thing about a Phase II study is to really try to test all the dose that we could.
And as I said earlier, the lack of toxicity we saw at lower doses really enabled us to add a higher dose than we had even anticipated at the beginning of the study.
And that's the reason it's there.
And our first and most important thing with the Phase II study is really to learn as much as we could and that's what we're doing.
And it's our expectation that dosed appropriately, which means for each individual patient, the relacorilant will be just as potent as Korlym is, but without the important detriment of progesterone activity.
Yes.
Without really sort of pinning it down to very specific numbers as you know we don't give on a call.
We feel like our penetration is still a fraction of what it might be.
And we feel like the ---+ and I think ---+ I'll elaborate in 2 ways: One, I think that even with Korlym, there are many doctors who we think have patients who would benefit from the medication, who have not yet tried it.
And I just want to echo something that <UNK> said.
Sort of the proof of that to us is the growth in new prescribers every quarter.
And we think of that as really something that we have not seen the end of.
So that's the first part.
Second thing is, I think, the overall market size is probably grown, not that the patients weren't there, but they weren't being screened for previously.
So many times in the past because it was really what was in the literature, we said, we thought there was about 10,000 patients with Cushing's syndrome.
And clearly, there are millions of patients with Cushing's syndrome, but could there be somewhat more than 10,000.
I think the answer to that is yes, because I think there are patients who are now being screened for hypercortisolism, who are just kind of suffering along with all the various symptoms, not in medicines that weren't getting at the core of it.
So I think that in some sense the penetration rate is not what it would be even with a static number, but it's actually lower than you might think it is, because I think there are patients who will be added to the potential patients to be treated.
No.
Our anticipation will be that it will be a 6-month study, same as the SEISMIC study for Korlym.
And I think that's actually another thing just to think about.
I don't want to put too much emphasis, I want to just make sure that people understand the difference.
The results we're seeing with the relacorilant are in essentially what you've seen so far, 3-month study.
And there are certainly good effects with Korlym in 3 months, but the effects continue not just over months 4, 5 and 6, but even beyond that when we saw them in the ---+ in their extension study.
All right.
Look, sorry <UNK>.
Okay, sorry, <UNK>, didn't mean to interrupt you.
No, what I'm saying is that it's ---+ this is a very important biological characteristic of cortisol, which is that it is not released in a static way.
It's highest when we wake up in the morning, and then it's drop through the day, and then it rises through the night, and it's got this very nice sine curve and that's very, very important.
I think for most of people who know me know I'm a psychiatrist by training, and I can tell you that the nadir in ---+ that you need with cortisol is very important for psychiatric effects.
Not the least of which is sleep.
In order to get a good night of sleep, your cortisol access has to really turn off.
On the other hand, you have to really be ready to kind of greet the day with a higher cortisol level.
So that's a very, very ---+ it has evolved over a long-period time, a very, very important biological characteristic of cortisol.
So a medicine that simply gave you an average in the appropriate range, but obliterated the diurnal rhythm of cortisol, would leave you in a condition where you're not feeling well.
That would not be a good thing to do.
And that's in fact something that Korlym does not do.
Korlym, if anything, exacerbates the diurnal rhythm, and it actually makes sure that you have a high peak and a nadir.
And I think that one of the interesting things clinically is that people will notice with Korlym that even in the first week they start to sleep better.
And that's actually very important characteristic of this type of medication.
A good corticoid receptor competitive antagonist that Korlym is, and that we're developing.
What I\
