Corcept Therapeutics Inc (CORT) 2018 Q2 法說會逐字稿

Good day, and welcome to the Corcept Therapeutics Conference Call. Today's conference is being recorded. (Operator Instructions)

At this time, I would like to turn the conference over to Charlie Robb. Please go ahead, sir.

Good afternoon. I'm Charlie Robb, Corcept's Chief Financial Officer. Thank you all for joining us.

Earlier today, we issued a press release giving our second quarter financial results, announcing a stock repurchase program and providing a clinical update. A copy is available at corcept.com. Complete financial results are available in our Form 10-Q.

Today's call is being recorded. A replay will be available through August 23, 2018, at (888) 203-1112 from the United States, and (719) 457-0820 internationally. The passcode will be 6703650.

Statements during this call other than statements of historical fact are forward-looking statements based on our plans and expectations and are subject to risks and uncertainties that might cause actual results to differ materially from those such statements expressed or implied.

These risks and uncertainties include but are not limited to our ability to generate sufficient revenue to fund our commercial operations and development programs, the protections afforded by Korlym's orphan drug designation and our intellectual property, the availability of competing treatments, including generic versions of Korlym, our ability to obtain acceptable prices or adequate insurance coverage and reimbursement for Korlym, and the scientific regulatory management and financial risks related to the development of our product candidates. These and other risks are set forth in our SEC filings, which are available at our website and the SEC's website.

On this call, forward-looking statements will include those concerning our 2018 revenue guidance and expected growth in 2019 and beyond; our stock repurchase program and its intended funding sources, physician awareness of hypercortisolism and selection of Korlym as the best medical treatment for many patients and continued shifts in medical practice.

The clinical attributes of relacorilant, data from the dose finding portion of our Phase I/II study of relacorilant plus Abraxane as justification for expanding our oncology program and the progress and results of our development programs, including our current and planned clinical trials of relacorilant, CORT125281 and CORT118335.

We disclaim any intention or duty to update forward-looking statements made in this press release or on this call.

Now, I will review our financial results. Corcept's revenue in the second quarter was $62.3 million, a 75% increase from the second quarter of 2017. This increase was primarily due to broad-based organic growth, more physicians prescribing Korlym to more patients. There was no price increase in the quarter.

We have reduced our 2018 revenue guidance from a range of $275 million to $300 million to a range of $250 million to $270 million, which constitutes growth of between 57% and 70% compared to our revenue last year.

We expect significant growth in 2019 and beyond. Our fully diluted net income in the second quarter was $0.14 per share compared to $0.10 per share in the second quarter of 2017. Excluding noncash expenses related to the stock compensation and use of our deferred tax assets, second quarter non-GAAP net income was $25.4 million compared to $16 million in the second quarter of 2017. Cash and investments at June 30 were $159.9 million, up from $140.4 million at March 31.

We announced today that our Board of Directors, upon consideration of our strong financial position and prospects, has approved a program running through June 30, 2019, to repurchase up to $100 million of our common stock. We will determine timing and size of any repurchases based on market conditions, our stock price and other factors.

We believe revenue from our Cushing’s syndrome franchise, together with our cash on hand, will be sufficient to fully fund our commercial business, conduct Phase II and Phase III trials of relacorilant in both Cushing’s syndrome and solid tumors, conduct Phase I, II and III trials of CORT125281 for castration-resistant prostate cancer and CORT118335 for antipsychotic-induced weight gain and NASH, advancing the clinical additional proprietary selective cortisol modulators and fund our plan to repurchase up to $100 million of our common stock.

I will now turn the call over to Dr. Joseph Belanoff, our Chief Executive Officer. Joe?

Thank you, Charlie. Thank you everyone for joining us today.

Corcept had another strong quarter. Revenue grew to $62.3 million, 75% more than our revenue in the second quarter last year. Excluding significant noncash items, our non-GAAP net income was $25.4 million, a 59% increase over the second quarter last year. Our cash and investments grew by $19.6 million to $159.9 million.

The second quarter growth in our Cushing’s syndrome franchise was driven by the factors I've described on previous calls. Korlym, our first-generation cortisol modulator, works very well in practically all patients with hypercortisolism.

At the same time, physicians are increasingly aware that every instance of hypercortisolism is serious and merits treatment. As they screen more thoroughly for the disorder, physicians are identifying more patients and, in many cases, choosing cortisol modulation with Korlym as the best medical treatment.

This shift in medical practice is not slowing down. We are reducing our revenue guidance for the year because we do not think we will see revenue growth accelerate past the 60% to 65% growth rate we are currently seeing.

An important reason for confidence in the future of our hypercortisolism franchise is our proprietary selective cortisol modulator, relacorilant. Today, we released positive interim data from relacorilant's Phase II trial.

To understand the promise relacorilant holds for our business, I need to explain how relacorilant's clinical data suggests it would benefit patients. As many of you know, Korlym competes with cortisol at the glucocorticoid receptor, GR for short, the receptor which is activated when cortisol levels are high. Patients with hypercortisolism have too much cortisol activity at GR, which is what causes their symptoms.

By reducing excess cortisol activity, Korlym makes patients better. Unfortunately, Korlym also binds to the progesterone receptor or PR. Korlym's affinity for PR makes it an abortifacient and causes in many women endometrial thickening and vaginal bleeding. A cortisol modulator that does not cause these adverse events would constitute a major clinical and commercial advance.

This is why our objective when we set out to design relacorilant years ago was simple, create Korlym without PR affinity. We succeeded.

Preclinical and clinical studies demonstrate that relacorilant does not bind to PR and so it does not cause Korlym's progesterone related off-target effects. But relacorilant's clinical data demonstrates another important benefit, one we did not fully anticipate.

By reducing cortisol's negative feedback at the hypothalamus and pituitary gland, Korlym usually causes a patient's cortisol levels to rise even as their hypercortisolism symptoms abate.

Unfortunately, through the activation of an off-target receptor, elevated cortisol often causes a patient's potassium levels to drop, a potentially life-threatening condition known as hypokalemia. Physicians prescribing Korlym must monitor patients closely for hypokalemia for as long as their patients take Korlym, since this condition can develop at any time. The Korlym label has a section expressly directed to this risk.

Despite their physicians' diligence, hypokalemia remains common in patients taking Korlym. 44% of the subjects in Korlym's pivotal trial developed hypokalemia. It's one of the most frequently reported adverse events and causes a discontinuation in patients taking Korlym today.

Our clinical data shows that relacorilant does not cause this off-target effect. It modulates cortisol activity at GR, which is why patients in its Phase II trial experience clinical benefit. But unlike Korlym, relacorilant does not cause cortisol levels to rise very much. As a result, it did not cause hypokalemia. This is very good news for patients and for Corcept.

Now I will briefly describe the results we released today. Relacorilant's Phase II trial is a 35-patient open-label study conducted at sites in the United States and Europe. Its purpose is to evaluate the efficacy and safety of relacorilant over a range of potential doses so that the optimum range can be advanced to Phase III.

The trial consists of 2 cohorts. An initial low-dose cohort received a daily dose of 100 milligrams of relacorilant for 4 weeks, then 4 weeks of 150 milligrams and finally 4 weeks of 200 milligrams. This group has completed the study.

The trial's second high-dose cohort followed the same 4-week titration protocol, but with doses of 250 milligrams per day, followed by 300, then 350 and finally 400 milligrams per day.

We have data from this group through 8 weeks of treatment, which includes completion of the 250 and 300 milligram dose levels.

Based on feedback from the FDA, we have applied to this Phase II data the response criteria we plan to use in relacorilant's Phase III trial. These endpoints mark clinically meaningful improvements in glucose control and hypertension, 2 of hypercortisolism's most prominent and pernicious symptoms.

As measured against these endpoints, the response of patients in the high-dose cohort after 8 weeks was impressive. 58% of patients with hyperglycemia achieved improved glucose control as shown by either a 0.5% or greater reduction in hemoglobin A1c, where a 50-milligram per deciliter or greater reduction or normalization in 2-hour glucose is measured in the oral glucose tolerance test or a meaningful decrease in antidiabetic medications.

By comparison, 48% had met this endpoint after 10 weeks of treatment in Korlym's pivotal trial. And 23% had done so at the conclusion of 12 weeks of treatment in the relacorilant low-dose cohort.

In addition, 55% of patients in the relacorilant high-dose cohort with uncontrolled hypertension achieved a 5-millimeter or greater drop in either systolic or diastolic blood pressure as measured by 24-hour ambulatory monitoring.

The comparable figure for Korlym's pivotal trial was 44%. For the relacorilant low-dose cohort, it was 45%. These positive interim data frame well our clinical and commercial expectations for relacorilant. It has the potential to provide clinically meaningful benefits to patients with hypercortisolism without the 2 off-target effects that cause Korlym's most frequent and potentially serious adverse events. We look forward to confirming these findings in a Phase III trial, which we plan to start this year.

I'll turn now to our oncology program, which is about to expand significantly. As some of you know, cortisol modulators may help treat solid tumors through several mechanisms. In cancers where the tumors express GR, such as ovarian, pancreatic and triple-negative breast cancer, cortisol stimulates genes that prevent apoptosis, a programmed cell death chemotherapies are meant to provoke.

Preventing the stimulation of apoptosis suppressing genes by adding a cortisol modulator to a chemotherapy regiment should allow that regimen to achieve its optimal effect.

Cortisol modulators may also help the body's immune system fight cancer. A healthy body produces cancer cells all the time, but the immune system identifies and destroys them. Cortisol suppresses the immune system. The stress of cancer and its treatment increase cortisol activity, creating even greater immunosuppression. Cortisol modulators administered either as monotherapy or in combination with immunotherapy medications may counter this effect, allowing the immune system to act more potently.

At the ASCO meeting this May, we reported positive data from our Phase I/II study of relacorilant plus Abraxane to treat patients with solid tumors.

At the minimum therapeutic dose, 4 of 7 patients with metastatic ovarian cancer and 4 of 9 patients with metastatic pancreatic cancer demonstrated durable disease control. These patients all had aggressive metastatic disease and had progressed on one or more prior taxane-based treatments, and yet they benefited when a cortisol modulator was added to their taxane treatment.

Based on these findings and compelling preclinical data, we plan to initiate a placebo-controlled Phase II trial of relacorilant plus Abraxane in metastatic ovarian cancer by year-end. By year-end, we also expect to have collected sufficient data from patients with metastatic pancreatic cancer to determine if we can proceed to a pivotal study for that indication.

As we advance relacorilant to Phase II, our collaborators at the University of Chicago were conducting their own clinical trials using Korlym to treat solid tumors. With financial support from Celgene, they continue to enroll patients in their 64-patient double-blind placebo-controlled multicenter Phase II trial of Korlym plus Abraxane to treat patients with triple-negative breast cancer. They are also enrolling patients in a 74-patient open label Phase II trial of Korlym in conjunction with Merck's immunotherapy agent, KEYTRUDA, to treat patients with triple-negative breast and HER2-negative breast cancer. Merck is providing financial support for that trial.

We are providing Korlym to both trials and possess the intellectual property covering the use of these combinations of medications for these indications.

As some of you know, our oncology program is pursuing an additional lethal disease, castration-resistant prostate cancer. Androgens stimulate growth in tumors in the prostate, which is why androgen deprivation known as chemical castration is a common treatment. Unfortunately, patients treated with an androgen receptor blocker, such as Pfizer's drug, XTANDI, often quickly develop tumors where cortisol is the primary growth factor. Combining a cortisol modulator with an androgen modulator, such as XTANDI, from the outset of treatment may block this cancer escape route.

We are currently in the dose ranging portion of our clinical program, testing our proprietary selective cortisol modulator, CORT125281, plus XTANDI to treat patients with metastatic castration-resistant prostate cancer.

At the same time, University of Chicago investigators continue to advance their 84-patient controlled multicenter Phase II trial of Korlym plus XTANDI. The Department of Defense and the Prostate Cancer Foundation are funding this trial. Pfizer is providing XTANDI, we are providing Korlym and possess the intellectual property for use of this combination of medications.

I will close with a brief discussion of one of our most promising selective cortisol modulators, CORT118335, which is currently undergoing Phase I testing. CORT118335 has particularly potent effects in the liver, which makes it a promising candidate to treat 2 serious disorders, the weight gain and other metabolic ill effects experienced by patients taking antipsychotic medications and nonalcoholic steatohepatitis currently referred to as NASH.

Millions of people rely on antipsychotic medications, such as ZYPREXA and Risperdal, to treat psychosis. These drugs work well but cause serious metabolic side effects including weight gain, hyperglycemia and hyperlipidemia. There are no good treatment options for the millions of patients suffering these ill effects.

We have demonstrated in placebo-controlled clinical trials that, in healthy human subjects, Korlym significantly mitigates the metabolic side effects caused by ZYPREXA and Risperdal. The study results were published in the Journal's Advances in Therapy in October 2009 and in Obesity in December 2010.

Unfortunately, Korlym's PR affinity, to be blunt, its status as the abortion pill, prevented us from developing it for this important use.

In animal models, CORT118335 prevents and reverses antipsychotic-induced weight gain more potently than Korlym does. And because it is a selective cortisol modulator with no affinity for PR, CORT118335 can be developed and potentially distributed to the millions of patients with this disorder.

Many of you are already familiar with NASH, a form of liver inflammation that is often a precursor to cirrhosis. NASH afflicts millions of people in the United States, and there are no good treatment options.

We know that cortisol modulation may offer a treatment for NASH because we have observed Korlym reversing fatty liver disease in patients with Cushing’s syndrome.

In animal models, CORT118335 is more potent than Korlym in preventing and reversing fatty liver disease. These great clinical results are compelling. They are made even more compelling by our positive clinical findings with Korlym.

If CORT118335's Phase I trial is successful, we plan to advance it to Phase II for both antipsychotic-induced weight gain and NASH by year end.

To recap, Corcept had another strong commercial quarter. Revenue increased by 75% over the same period last year. We expect 2018 revenue of between $250 million and $270 million with significant growth in 2019 and beyond. Excluding significant noncash items, our non-GAAP net income increased by 59% over the second quarter last year.

Our cash and investments grew by $19.5 million in the first quarter to $159.9 million. We have no debt. Our Phase II trial of relacorilant is fully enrolled and continues to generate positive data, including the surprising and very important finding that relacorilant does not cause hypokalemia, one of Korlym's most common adverse events. We are on track to begin relacorilant's Phase III trial this year.

Our oncology program has taken significant steps forward. By year-end, we plan to file the positive data we released in May, with a placebo-controlled Phase II trial of relacorilant plus Abraxane in patients with metastatic ovarian cancer. We also expect to collect by year-end sufficient data to decide whether a registrational study of relacorilant plus Abraxane is warranted in patients with metastatic pancreatic cancer.

Our Phase I trial of CORT118335 is nearing completion, and we plan to advance the compound to Phase II for both antipsychotic-induced weight gain and NASH by year-end, serious disorders suffered by millions of people for which there are no good treatment options.

I'll stop now to answer questions.

(Operator Instructions) We'll go first to Adam Walsh with Stifel.

This is Neil Carnahan, on for Adam. Would you guys mind providing some detail on the number of patients that ended up making it to the 350 and 400-milligram cohorts? And then, just any more detail you could provide around the discontinuation? What dose that occurred at?

I'm not sure I exactly follow your question. I apologize, Neil, please again.

Like what percentage of patients made it to -- and the dose escalation, made it up to the 350, 400-milligram dose? And then, on the SAE, do you have any detail around what dose that occurred at?

Yes, okay. I think I can get to that. We have data now through 300 milligrams. That's what we presented to date and we'll present the rest of the data as we actually have it in completion. And I want to just turn over for a second to Bob Fishman, who I think can answer the question about the adverse events.

Yes.

By the way, for those of you who don't know, who haven't been on oncology before, Bob is our Chief Medical Officer.

Right, the -- well, to clarify, the one serious adverse event was a pilonidal abscess. And this is a complication of a congenital defect. It starts out as a pilonidal cyst, and it simply became infected. So I don't recall the exact dose at which it occurred but it was clearly, by the investigator judgments, [NRS-unrelated].

And the second question was about the person who discontinued, at which dose was that?

It was on a -- go ahead, sorry.

Yes, I believe it was at the 300-milligram dose.

At the 300-milligram dose, Adam (sic) [Neil].

We'll go next to Tazeen Ahmad with Bank of America.

Would you mind just giving us an update on I guess where the Teva situation is with the patents litigation, in terms of when we should expect the next update either from you or from Teva or just from the court in general?

Yes, very glad to do so. I'm just turning the call back over to Charlie Robb, our Chief Financial Officer.

Hi, Tazeen. Yes, sure. I'm happy to answer it. Let me just stop by giving just a -- I got to give a little bit of background for others on the call who might not be as up to speed on it as you are. So understand, I can't -- for others, I really can't comment on the substance of our legal positions or Teva's legal positions or our strategy and so forth. All that we have referred to are sort of publicly available documents and those to date are just very, very few. But with that understood for everyone, Tazeen, I can answer your question. In broad terms, what we're seeing now is what we believe you should get used to seeing for quite some time, sort of complex legal process and argument and paperwork exchanges between us and Teva, that we think is going to go on for -- in one form or another, for quite a while. Quite a while. Now with that sort of bit of context, I can answer your question directly. As most of you know, in February, we received noticed that Teva had filed an abbreviated new drug application, or an ANDA, with the FDA seeking approval to sell a generic version of Korlym. Under the statute that governs these things, the Hatch-Waxman Act, we then had 45 days to sue Teva for infringement of what are called Orange Book patents. These are the patents that the owner of a branded product, such as Korlym, believes a generic would infringe. So on March 15, we sued Teva for infringement of what at the time were our 2 Orange Book patents. Under Hatch-Waxman, our lawsuit automatically stayed or, in nonlegal terms, prevented the FDA's approval of Teva's proposed generic product for 30 months or the resolution of our lawsuit with respect to those patents, whichever comes first. So in June, Teva moved to dismiss our complaint. In July, we amended our complaint. And among other things, our new complaint added allegations of infringement of a third newly issued Orange Book patent. So now we're serving 3 patents against Teva. As we expected, later in July, Teva moved to dismiss our new complaint. And that's where we are right now. Now our response to Teva's new motion is due later this month, I think August 21 or thereabouts. Teva then will have a chance to reply to that response. And some time in the fall, we expect to be arguing the issue in front of the judge. So that's where we are with the back and forth. And I think yes it cannot be more descriptive than that.

We'll go next to Corey Davis with Seaport.

Sorry, jumped on the call late, [I don't know] if you answered this. But in general, how enthusiastic would you say you are in the relacorilant data in terms of these lower doses continuing to show a higher response in the last 2 doses that you have yet to report on?

Well, I'm going to again turn this over to Bob (inaudible) general answer to your question is very enthusiastic. I mean these are significant clinical effects in the absence of, as expected, progesterone receptor antagonism. But again, we commented on it when we presented on the low dose group in a minor way because we weren't sure whether that would continue as we increase the dose. But the striking lack of hypokalemia is a very, very meaningful advance and one that we think makes the medication, in some respects, much easier to use for many practitioners than Korlym. But I'll turn it over to Bob if you have any additional comments.

I would just add that the investigators' impression of the benefit that they're seeing in their individual patients was reflected in the acceleration of the patient enrollment this year. So that was a strong indicator that the investigators were seeing the benefit that adds up to the data displays that we showed you.

And then, again, I apologize if I you answered this already. But how quickly can you start enrollment of the Phase III? And do you need to wrap certain things up before you can finalize the protocol, get the sights on board et cetera, et cetera?

Bob?

Yes, thanks for your question. Just to provide some context, we had the very unusual and enormously helpful position of being able to ask FDA for guidance while Phase II was ongoing because we have an open-label trial. And so we submitted interim data and a proposal for our Phase III plan to FDA and they took our request seriously and gave meaningful guidance. So that we're confident we settled on endpoints that are going to meet their expectations. And so we have the design we've shown you in our press release, our plan response criteria by which we will measure clinical benefit in these patients.

And what it all really funnels down to, I think to answer your question, Corey, is we are fully expecting to be able to start the study this year.

So is there anything left to do that is contingent upon completion of the ongoing study?

Again, we are in active planning for the Phase III study and expect to begin it in -- some time in the near future. I don't really have any more detail for you than that in some sense. You've seen all the important data that we've seen.

All right, and then lastly just is it safe to assume then that the -- in its guidance to you, that the FDA agrees that the endpoints as presented in this press release are going to be sufficient for endpoints in your Phase III program?

Bob?

Well, first just to clarify, we don't have a special protocol assessment so they haven't officially approved them. But the guidance, as I mentioned, was very meaningful. So yes, we have a high confidence that these endpoints will meet FDA's expectations, and we're confident that we're collecting the data necessary to show the clinical improvement in the patients with Cushing’s syndrome.

We'll go next to Matt Kaplan with Ladenburg Thalmann.

Just wanted to focus a little bit more on the Phase III plan for relacorilant. Can you give us a little bit more detail in terms of what the Phase III would look like, the time line? And I guess, will you have to go head-to-head versus Korlym in the study?

Bob?

Yes, happy to do so. So we've planned a Phase III, that will be about 120 patients. It will be an international study. And it will be a placebo-controlled randomized withdrawal study. And I'll loop back to that in just a moment. We will enroll patients who have endogenous Cushing’s syndrome who, as you heard, also have hyperglycemia and/or uncontrolled hypertension. And the patients will enter a 6-month open label phase that starts with dose escalation, and this will remind many on the call of the structure of the SEISMIC trial. And then patients who meet the response criteria, which you've seen laid out and are the basis for our data displays in the press release, those patients who meet response criteria will then enter a randomized withdrawal phase. And in the randomized withdrawal phase, patients either stay on medicine or they switch to placebo and that's done in a blinded fashion. And once they randomize, we expect patients on medicine to maintain their response and the patients on placebo to start to lose some of the benefit that they had gained previously. And then we compare the differences in glucose control and in blood pressure between the medicine group and the placebo group. One of the benefits of this is that it helps minimize the amount of time that these very sick patients spend on placebo. And in all of these trials as well as in ours, there will be a rule that anyone with a significant relapse of their disease can go right back on drug.

Great. And the potential time line for a study like that?

Well, as Joe mentioned, planning to start this year, assume 2 years end-to-end, which brings us to mid-2020.

So just want to repeat that, that's 2 years, first patient in to last patient out. Because I think there was a little confusion in the past call about -- just because I think it was misstated, 2 years in enrollment. That's not what we mean. 2-years from first patient in to last patient out.

Got it. And then just going back to the interim Phase II results that you reported. Initially, you showed a dose response in terms of glucose control at the lower dose. Are you continuing to see that at the higher dose cohort?

We're certainly seeing it, and the best display of that is the, I'll point you in particular to the graph on the number of responders for improvements in glucose control, which was 3 in the low-dose group and 7 in the high-dose group. So yes, we're seeing continued benefit in terms of that increased number of responders.

Great. And I guess this is -- the study you're just going to need a single study for the approval, potentially?

Bob?

Yes, that's our expectation. We have no indication of anything otherwise.

And how many patients do you need to get into the withdrawal phase, randomized withdrawal phase?

Into the what?

How many patients need to make it through the dose escalation 6-month open label dose escalation to get to...

Rough number is out of the 120 open-label phase, we'll need about 60 completer responders, meaning people who both complete and are responders, and therefore both qualify and are available to enter the randomized withdrawal phase.

And we'll take a follow-up from Adam Walsh with Stifel.

Can you just walk us through the rationale behind -- you guys obviously had kind of a track record of beat and raise. Can you just talk to us about what's changed since you originally issued guidance back in February and then just the rationale behind the buyback program?

Yes, very good. So 2 questions in there, and I'm going to sort them in a different way. First, again, I want to reintroduce you to Sean Maduck. He's our Senior Commercial Officer, who runs the Cushing’s syndrome franchise for the commercial question. And then I think Charlie will answer the second question.

Hi, Neil, thanks for the question. Our business is rapidly growing. And in the Orphan Drug space, I think, as many people know, the law of small numbers exists, which can make it very difficult to predict future revenues. I definitely don't say this as an excuse as we -- as our organization are always trying to be as accurate as we possibly can. But that being said, predicting whether we're going to grow at 60% or 80% is not a perfect science. As a reminder to everybody on the call, we raised our guidance multiple times last year because we underestimated the accelerated uptake that occurred, and we were lowering our projections. If you look back historically, our revenues have grown by approximately 60% to 90% annually over the last 3 years. And we have definitely seen fluctuations in our growth over that window of time. For this year, remainder of this year, further acceleration off of our current 60% to 68% growth rate doesn't seem likely as Joe has previously mentioned, which is why we adjusted our revenue range down. Again, as an organization, we strive to be as accurate as possible on our estimates. And this guidance shift does not change our belief in the longer-term size and value of this market. In terms of our actual business this year, we continue to experience revenue growth from both new and existing prescribers, and we expect that to continue through this year and into next and beyond. Our prescriber base is growing. And in the first 6 months of 2018, we actually added more new prescribers and saw more active prescribers which is any physician has written one or more prescription than in any equivalent window of time since launch. In fact, over half of our prescriptions this year in 2018 have come from physicians that prescribed Korlym for the first time over the last 12 months, and we believe this bodes very well for the future. And we've said this many times before, but there are many naive -- Korlym-naive physicians who have yet to write their first prescription. And we believe there are many more hypercortisolism patients who could benefit from a GR receptor antagonist.

And then just on the buyback?

Yes, this is Charlie. The reason -- the rationale for the buyback is really -- is very straightforward as I sort of said in my introductory remarks. Looking at our cash reserves, our prospects and our planned development activities, we felt that we would be able to do all of those things and return money in the sort of tax efficient way to shareholders. And we've got that sort of at our company, that's our obligation to do that. So that's why we've announced the program.

We'll go next to Alan Leong with BioWatch News.

First set of questions, really goes back to the recent results, but really I want to take a different tack on it. I want to talk -- see if I get a discussion on the impact on labeling because Korlym didn't earn a blood pressure label. What can you say now about the FDA's approach for earning such a label within Cushing's? And then as you -- and then the follow-up on that is as you sit back and look at your results, what were major lessons learned or carryovers into your general metabolic program?

Okay, let me see if I can really sort those questions out. I mean I think really the first thing to begin with, Alan, is that a GR modulator like relacorilant, since that's the one you asked about, what's really a point of approval is for the treatment of Cushing’s syndrome. We have highlighted 2 symptoms, glycemic control and hypertension, as kind of lead symptoms for Cushing’s syndrome but there are many others. I believe that we actually test for 24. Because cortisol goes everywhere in the body. When you have aberrant cortisol activity, you have many other things which are wrong as well. People get -- and I think you know this, but they gain weight. They gain weight particularly around their middle. They have cognitive issues. They have thin skin, they are immunosuppressed, so they get infections. So there are many, many things that we measure. But ultimately, what we want is the broadest label and most appropriate label, which is for the treatment of Cushing’s syndrome. And there isn't at this point in time just in the field a validated index for the treatment of Cushing’s syndrome. So in some sense you're obligated to prove improvements sort of a symptom at a time. And obviously, hyperglycemia and hypertension are 2 particularly pernicious systems so that they're easy to measure, to see when improvement occurs. And certainly, people are 100% in agreement that if you improved those, you've improved something significantly. So I think that's really -- I hope that's addressed your question. I think that's really how we're looking at it. And the second question I think was you're asking about how this reads over to metabolic diseases. At the core of it, Cushing’s syndrome is a metabolic disease. Many of the systems you see are metabolic aberrations not all of the symptoms, obviously, as I just talked about, but many in fact actually are. And so, we feel like that relacorilant, because of the way it penetrates all the organs of the body, and so forth, is a very good medicine as it's already proving for the treatment of Cushing’s syndrome because it is -- it can affect both the metabolic symptoms and other symptoms that are involved with Cushing’s syndrome. Now we centered in on CORT118335 because it is a particularly potent drug in the liver. And it isn't particularly active throughout all of the organs of the body. And this is one of those things I think I've mentioned many times during calls, but it's very clear to us that although all of our cortisol modulators do just that, modulate cortisol, and none of them touch progesterone, they are not identical. And we really started to see that in preclinical testing, and now we're beginning to see that in clinical testing as well. So we think that CORT118335, where we'd aimed it, is particularly useful because we think that an antipsychotic-induced weight gain, as an example, it has particularly potent effects on a milligram per kilogram basis. As we said, the direct comparison has been through Korlym which was clearly effective in the preclinical models. 118335 is even more effective. But the important extra fact is that Korlym was very effective in the clinical models we could test. But just because of its abortifacient qualities, could not go any further in development.

What can you tell us about the Phase I results with 118335? And of special interest is really the prednisone challenge. What can you say at this point about the anti-inflammatory versus metabolic outcomes?

Well, we'll give you all the results when they are filled. That study is still in progress, Alan, and I don't want to really get ahead of ourselves. But I can -- I guess the one thing I will comment to you because I've already made that comment is in terms of tolerability, which is really is what Phase I is about, so far so good.

At this time, I would like to hand the call back over to Charlie Robb for any additional or closing remarks.

That's all. Thank you very much everyone for joining us. And we'll be speaking to you again next quarter. Thanks.

That does conclude today's conference. We thank you for your participation.