Corcept Therapeutics Inc (CORT) 2018 Q3 法說會逐字稿

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

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

Thank you. Good afternoon, everyone. I am Corcept's Chief Financial Officer, and thank you all for joining us. Earlier today, we issued a press release announcing our third quarter financial results and reviewing our clinical progress. Copy is available at corcept.com. Complete financial results will be available when we file our Form 10-Q with the SEC.

Today's call is being recorded. A replay will be available through November 15 at (888) 203-1112 from United States and (719) 457-0820 internationally. Passcode will be 7489528.

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 express or imply. 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 for 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, physician awareness of hypercortisolism and selection of Korlym as the best medical treatment for many patients; the timing, cost and outcome of our lawsuit against Teva Pharmaceuticals USA; the clinical attributes of relacorilant; data from the dose-finding portion of our Phase I/II study of relacorilant plus Abraxane; and the progress and results of our discovery and 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 on this call.

Now I'll review our financial results. Corcept's revenue in the third quarter was $64.4 million, a 51% increase from the third quarter of 2017. The increase was due to broad-based organic growth, more physicians in every part of the country prescribing Korlym to more patients. We've not raised prices since the net 4% increase at the beginning of the year. We reaffirm our 2018 revenue guidance of between $250 million and $270 million.

Our fully diluted GAAP net income in the third quarter was $0.14 per share compared to $0.11 per share in the third quarter of 2017. Excluding noncash expenses related to stock-based compensation, use of deferred tax assets, interest on our retired royalty financing obligation and related income tax effects, fully diluted non-GAAP net income in the third quarter was $27.9 million compared to $17.4 million in the third quarter of 2017. A reconciliation of GAAP to non-GAAP net income is contained in our press release.

Cash and investments were $196.7 million at September 30 compared to $159.9 million at the end of the second quarter. We repurchased 674,000 shares of our common stock in the third quarter at a total cost of $8.9 million. Under the currently authorized terms of our stock repurchase program, $91.1 million remains available to acquire shares. The timing and size of any future repurchases will be based on market conditions, our stock price and other factors.

I want to take a moment to emphasize an important legal development. As many of you know, Teva Pharmaceuticals is seeking approval to market a generic version of Korlym. We have sued Teva for alleged patent infringement. Teva moved to dismiss our complaint. Last week, 7 months after we first filed the suit, the judge denied Teva's motion. The judge's ruling means that the Hatch-Waxman Act's automatic stay of FDA approval remains in place and our lawsuit can proceed. We expect and are prepared for a lengthy litigation.

In closing, we believe our revenue 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 Cushing's Syndrome and both pancreatic and ovarian cancer; conduct Phase I, Phase II and Phase III trials of core 125281 for castration-resistant prostate cancer and CORT118335 for antipsychotic-induced weight gain and NASH; advance to the clinic 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. Last quarter, Corcept made important progress. Our revenue increased, as more physicians prescribed Korlym for the first time and experienced prescribers with second and third prescriptions. We expect growth to continue, because there are so many patients we've yet to reach.

As a reminder, at least 20,000 people in the United States have been diagnosed with Cushing's Syndrome. 3,000 new cases Cushing's Syndrome are diagnosed each year. Half of these cases are cured by surgery, but that leaves at least 10,000 patients in need of medical therapy. Some of these patients have been treated with Korlym, but there are many more that can benefit from it. Our success with Korlym allows us to fully fund development of proprietary selective cortisol modulators as treatments for a broad range of serious endocrine, oncologic and metabolic disorders. At this moment especially, no one should lose sight of the breadth of our development program and the steady progress of our drug candidates.

To help investors and patients follow Corcept's rapid evolution, we have completely overhauled our website, corcept.com, to make it a better resource for anyone interested in cortisol modulation and our development programs. These programs are the future of Corcept, and the future is rapidly approaching.

Relacorilant, our planned successor to Korlym in Cushing's Syndrome, has begun its Phase III trial. Before describing the trial, let me explain why relacorilant is such a promising compound. Like Korlym, we expect relacorilant to be an effective treatment for patients with Cushing's Syndrome, because the 2 drugs operate by the same well-understood mechanism, modulating or turning down the excess cortisol activity that causes patients harm. Cortisol modulation is very effective. In Korlym's Phase III trial, 87% of patients experienced significant clinical benefit. Similarly, relacorilant's clinical data shows clear indications of efficacy. Earlier this year, we released analyses applying the primary endpoints we're using in relacorilant's Phase III trial to data from its Phase II trial. Patients taking relacorilant exhibited clinically meaningful improvement in hyperglycemia and hypertension at a rates comparable to those seen at the same point in Korlym's pivotal trial.

We expect relacorilant to offer many patients important safety benefits. As many of you know, Korlym's affinity for the progesterone receptor, PR for short, gives rise to significant off-target effects. The most notorious of these, of course, is that the active ingredient in Korlym is used to terminate early pregnancy. PR affinity also causes many women who take Korlym, regardless of their age, to experience endometrial thickening and vaginal bleeding, adverse events they and their physicians would strongly prefer to avoid. Korlym has another off-target effect that is less politically sensitive, but quite important, hypokalemia, which means low potassium. In many patients, Korlym causes cortisol levels to rise, sometimes sharply. This has not diminished Korlym's efficacy, but it activates the minimum glucocorticoid receptor, causing the body to lose potassium. Korlym patients require careful monitoring for hypokalemia, which is relatively common among them. 44% of patients in Korlym's pivotal trial experience hypokalemia, and it remains one of the most frequently reported adverse events and causes of discontinuation in patients taking the drug today. Low potassium can cause muscle weakness and arrhythmias and can be quite dangerous if not managed properly.

Because relacorilant has no affinity for PR, as expected, it did not cause endometrial thickening or vaginal bleeding in its Phase I and Phase II trials. And because it does not increase cortisol levels to the extent Korlym does, relacorilant also did not cause hypokalemia. We're excited to start relacorilant's Phase III trial, which we expect will confirm these benefits. We plan to enroll 130 patients with Cushing's Syndrome at sites in the United States, Canada and Europe.

The trial has a 2-phase design. In the initial open-label portion, all patients will receive relacorilant for 22 weeks with dose starting at 100 milligrams per day, then increasing at 100-milligram increments, as clinically indicated, to a maximum of 400 milligrams per day. After 22 weeks, patients who exhibit prespecified improvements in glucose tolerance or hypertension will enter a double-blind, placebo-controlled, randomized withdrawal phase lasting 12 weeks. Half of the patients entering this phase will continue to receive relacorilant. The rest will be switched to placebo. The rate and degree of relapse in patients receiving placebo will be measured against the rate and degree of relapse in those continuing medicine.

I will now turn to our oncology program, which is examining several approaches to cortisol modulation therapy. As some of you know, in cancers with tumors express GR, glucocorticoid receptor, such as ovarian, pancreatic and triple-negative breast cancer, cortisol stimulates genes that prevent apoptosis, a cell that chemotherapies are meant to provoke. Having a cortisol modulator should allow chemotherapy to achieve its optimal effect. We have been testing this mechanism in a Phase I/II trial of relacorilant combined with taxane nab-paclitaxel, which is Celgene's drug Abraxane, in patients with solid tumors. The data hsd been very encouraging. At the ASCO conference earlier this year, we reported that 4 of 9 patients with metastatic pancreatic cancer had exhibited durable disease control, meaning that tumors are either remaining stable or shrunk for at least 3 months. These are outstanding results in patients with aggressive metastatic disease, all of whom have progressed on one or more prior taxane-based treatments. We expect by year-end to have sufficient data to decide whether the appropriate next step is pursuing a pivotal trial.

The FDA's recent designation of relacorilant as an orphan drug for pancreatic cancer is helpful. The tax and fee savings are significant, and the 7 years' marketing exclusivity will supplement our composition of matter and method-of-use patents, which expire in 2033 and 2037, respectively. You may remember that we also reported at ASCO that of 7 patients with metastatic ovarian cancer treated with Abraxane and relacorilant, 4 exhibited durable disease control, including one patient with a complete response. All of these patients had previously failed taxane therapy. We plan to open a controlled, multicenter Phase II trial of relacorilant plus Abraxane in patients with metastatic ovarian cancer by year-end.

As we advance relacorilant as a treatment for patients with solid tumors, investigators at the University of Chicago are leading a 64-patient, double-blind placebo-controlled multicenter Phase II trial of Korlym plus Abraxane in patients with triple-negative breast cancer. Celgene is providing financial support for this trial. We are providing Korlym.

Turning to a second potential therapeutic mechanism, University of Chicago investigators are studying whether cortisol modulators can treat cancer by stimulating the immune system. A healthy body regularly produces cancer cells, 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. The University of Chicago researchers are leading a 74-patient, open-label, Phase II trial of Korlym in combination with pembrolizumab, a HER2-negative breast and triple-negative breast cancer. Merck is providing financial support for the trial. We're providing Korlym.

Finally, we are exploring the use of cortisol modulators to treat castration-resistant prostate cancer. Androgens stimulate growth in tumors of the prostate, which is why androgen deprivation and androgen synthesis inhibitors are common treatments. Unfortunately, patients treated with an androgen receptor block such as enzalutamide, Pfizer's drug XTANDI, eventually develop tumors where cortisol is the primary growth factor. This shift in gene expression allows the disease to progress. Combining a cortisol modulator with an androgen modulator such as XTANDI from the outset of treatment may block this escape route. We're continuing to dose patients in our Phase I/II trial of our proprietary selective cortisol modulator CORT125281 in combination with XTANDI to treat patients with metastatic castration-resistant prostate cancer. We expect to have enough data next year to determine whether a controlled Phase II trial is warranted.

As we work to advance CORT125281, University of Chicago investigators continue to enroll patients in their 84-patient, controlled, multicenter Phase II trial of Korlym plus XTANDI. Department of Defense and the Prostate Cancer Foundation are funding this trial. Pfizer is providing XTANDI, and we are providing Korlym. In all of the University of Chicago trials I have described, we possess the intellectual property covering the use of cortisol modulators plus anticancer agents in these indications.

I will end my remarks by noting that one of our most promising compounds, CORT118335 was safe and well-tolerated in its Phase I trial. We are now optimizing its formulation for a more advanced clinical development and plan to start placebo-controlled Phase II trials in antipsychotic-induced weight gain and nonalcoholic steatohepatitis commonly referred to as NASH, early next year. It is hard to overstate the potential benefit of these programs. Millions of people rely on antipsychotic medications such as Zyprexa and Risperdal to treat psychosis. Although these drugs work well, their metabolic side effects, including weight gain, hyperglycemia and hyperlipidemia are so severe as to substantially shorten the lives of many patients. We have demonstrated in placebo-controlled clinical trials in healthy human subjects that cortisol modulation with Korlym significantly mitigates the metabolic side effects caused by Zyprexa and Risperdal. The results were published in the journals Advances in Therapy in October 2009 and in obesity in December 2010. Unfortunately, we could not develop Korlym further for this use, because its status as the abortion pill made broad distribution for common disorder impossible.

CORT118335 is more potent in Krohn in preventing and reversing antipsychotic-induced weight gain in animal models of the disease. Because CORT118335 is a selective cortisol modulator with no affinity for PR, bluntly put, because it is not the abortion pill, it can be developed, and if approved, distributed to the millions of patients who could benefit.

Our other plan Phase II trial will study CORT118335 as a treatment for NASH, a form of liver inflammation that is often a precursor to cirrhosis. We know cortisol modulation, they offer treatment for NASH, because we have observed Korlym reversing fatty liver disease in patients with Cushing's Syndrome. CORT118335 is more potent than Korlym in animal models with fatty liver and fibrosis, results that are made even more compelling by positive clinical findings with Korlym.

I think when you look back at this moment as one where the bright future of Corcept came fully into view. Korlym is a potent effective medication. It has helped many patients with Cushing's Syndrome, and it has made Corcept a rare, self-funding biotech company. Korlym has allowed us to establish and continue to broaden the platform of cortisol modulation across a variety of disease states. We expect its revenues to grow substantially in the coming years. Nonetheless, for all of Korlym's terrific qualities, it remains the abortion pill. Our selective cortisol modulators, relacorilant, CORT125281, CORT118335 and other molecules that are progressing towards the clinic, are the future and the future is rapidly approaching. Relacorilant's Phase III trial in patients with Cushing's Syndrome has just opened. By year-end, we'll have collected sufficient clinical data from our ongoing Phase I/II trial of relacorilant plus Abraxane to decide whether we think a pivotal trial is warranted in patients with metastatic pancreatic cancer. We also plan to open a controlled Phase II trial of relacorilant plus Abraxane in patients with metastatic ovarian cancer by year-end.

As we've reported, the FDA recently designated relacorilant an orphan drug medication for both Cushing's Syndrome and pancreatic cancer. Our dose-binding trial of CORT125281 combined with XTANDI continues to dose patients. If these results are positive, we plan to start a controlled Phase II trial in the indication next year.

Finally, our lead drug candidate for metabolic disorders, CORT118335 was well tolerated in its Phase I trial. We are currently optimizing its formulation and plan to start placebo-controlled, multicenter Phase II trials in patients with antipsychotic-induced weight gain and nonalcoholic steatohepatitis, NASH, early next year. I'll stop now to answer questions.

(Operator Instructions) We have a question from Matt Kaplan.

Thanks for all the added detail on the programs beyond what Korlym is doing in the marketplace. Just wanted to focus first on Korlym just for a minute. Can you give us a little bit more color in terms of where you are with Teva and the litigation there? You mentioned a recent refusal of a judge to dismiss the case. But what does that mean, and what are the next steps here?

Yes. I'm very glad to pass that over to Charlie to answer the question.

Hey, Matt, this is Charlie Robb. So just -- let me just give a very brief background for those who aren't completely up on the story. So I think everybody does know that Teva is seeking approval to market a generic version of Korlym following expiration of Korlym's orphan drug protection next -- in February of next year. We received notice of that back in February of this year. And as part of the requirements of the Hatch-Waxman Act, Teva certified as part of that notice that their generic product would not infringe the 2 patents we had listed at that point in the FDA's Orange Book. Now in March, we sued Teva alleging that they would indeed infringe those 2 patents. And what has been going on for the past 7 months is Teva's attempts to have our complaint dismissed. So on October 23, just last week, the judge ruled against Teva. So what does that mean? Well, most immediately, it has -- Teva is now in a position to actually having to respond to our lawsuit, I imagine, to deny our allegations and so forth. And the back-and-forth that's involved with that will occupy one or 2 months up towards the end of this year. It's just going to be spent with Teva answering our complaint and us responding to that. The other immediate implication of this is under the terms of the Hatch-Waxman statute, our lawsuit in March triggered a 30-month automatic stay of FDA approval of Teva's generic product, beginning in February of 2018, there's a 30-month stay, pending our litigation. And so our victory against Teva and its motion to dismiss means that 30-month stay remains in effect and our lawsuit will proceed. So for the next month or 2, Teva will answer our complaint finally. And at that point, the parties will go to court and establish a schedule for the upcoming litigation discovery timelines and things of that nature. And so while I don't have a crystal ball about exactly what the timing of all this will be, I mean, these lawsuits take a very long time, and we are prepared for and anticipating really lengthy litigation. So that's what's sort of on the immediate horizon. I think the other development to note is actually something that happened several months ago, which is in the midst of the back-and-forth with Teva about their motion to dismiss, we obtained an additional Orange Book patent, a third patent, which we added to our claims against Teva. So we started with 2 patents, and right now, we have 3 patents in the lawsuit. And if we are issued additional applicable patents, and we work diligently every day to expand our intellectual property portfolio, if that work results in additional applicable patents, we will assert those also sort of at the appropriate time and place. So my anticipation is lengthy litigation and for able to obtain additional patents that litigation will also become more complex and wide ranging.

Okay. That's very helpful. And just shifting gears now to relacorilant. Joe, thank you for the detail on the Phase III study design. Can you help us understand in terms of the initial 22-week period? How many -- what percentage of those patients do you expect to have sufficient meaningful benefit improvements to make it to the 12-week withdrawal phase?

Thanks, Matt. I think we understand the question. I'd just like you to reintroduce you to Bob Fishman, who is our Chief Medical Officer, and I think he's really the best able to tease in -- in that study every single day to answer that question. Go ahead, Bob.

It's Bob here. The best indicator of that would be the preliminary results that we showed last time. And you'll recall that across improvements in glucose control and improvements in hypertension using our Phase III response criteria, it was about half or a bit more of the patients who showed meaningful clinical benefit. And that's essentially the assumption that we're making in our Phase II about our ability to accrue enough responders to move on to the randomized withdrawal phase.

And also with that -- I'm sorry, I cut you off.

Go ahead, Matt, please.

And then with the withdrawal phase, how durable do you expect the relacorilant effect to be after it's withdrawn and patients are switched to placebo?

It will depend on the indications. We have to keep in mind that one of the benefits of the drug that we expect is that patients' Cushing's Syndrome will improve in general. We are hopeful that they will lose weight. And so there will be, if successful, improvement across many elements. And the specific timeline may be different, but from our past experience with Korlym, what we're confident about is that within these 3 months -- that the 3-month window of the randomized withdrawal phase should be more than sufficient to observe if true a separation of the patients who stay on drug versus those who switch over to placebo.

Now let me give you a little context for that. It's now a long time ago, but in the pivotal study for Korlym, the FDA required at that point everyone to come up medicine at the end of the 6-month study. And in it, if they chose, to 6 weeks later, enter into a extension study. And what we found in that study was that we're relatively rapidly, in fact, there were some patients who after 2 weeks -- we knew this, because we got complaints from their physicians that taking them off the medicine was unethical and they needed to restart it right away, symptoms reemerged. So our experience with Korlym was the symptoms reemerged quickly, certainly within that 6-week period that I discussed that was true with Korlym, and that really informs the timing of what we're doing with relacorilant.

Our next question comes from Adam Walsh.

I have just a few here. First of all on the relacorilant trial, you have previously talked about it taking maybe 2 years. But I am looking at clinicaltrials.gov and its says estimated primary completion date of January 2020 and then a study completion date of January 2021. Can you just true up the 2-year guidance with what I'm seeing here and what the differences would be?

That sounds like about 2 years. No -- I mean, it's a little over 2 years.

No, I totally get that. But the prime -- estimated primary completion date is January 2020. I assume that you had some input into the primary completion date. What is the difference between those 2? In other words, the 2 years, it sounds like is 2020, but the 2021 date, I'm just -- I am sorry, 2 years is 2021. But the 2020 date, I'm just trying to true that up with the 2 years of guidance. Would that 2020 data point be meaningful, the primary completion? I didn't mean to pull up clinicaltrials.gov and stump you guys, but I'm just curious, the 2-year guidance should come sooner. The data could -- my question is could the data....

I understand the input of your question. No, the answer is it's a 2-year study, soup to nuts, and January 2021 is about correct.

Okay. Perfect. And then, obviously, an exciting development program with 335 in the antipsychotic-induced weight gain and the NASH. And you talked about planning to start the study in the first quarter of 2019. When could we see initial data flow from that project?

I suspect that's going to come in parts, and we'll really roll out exactly when those studies are going forward. I don't think you should really expect anything before the really -- the very end of next year. And those studies are basically -- and we haven't actually spoken to exactly the design of those studies, but they're going to -- it's going to be roughly a year, maybe a little less with the quickest one before they produce any results.

Okay, that's helpful. And then, Joe, you mentioned that you're optimizing formulation for 335? What does that mean? And how does -- how should we think about that?

I think one of the really critical things for us, 118335 is a very interesting molecule versus very big disorders. And we really thought this was the moment in time -- we had a decent formulation, but we really thought that this is a molecule that has legs and rather than have that being issued later in the development program, we wanted to pause for a little bit to see if we could really optimize it at this point in time and expect to. And we're, as I said, planning to begin the study, the Phase II studies early next year.

Okay. That's perfect. And then finally, just I get this question from investors sometime. I mean, you did Korlym guidance last quarter. How confident are you in your ability to kind of predict forward-looking Korlym sales? And that's it.

Thanks very much, Adam. I'd like to -- just because it's -- we really -- all of our team is very important. This might be a good place in the call to reintroduce you to Sean Maduck who runs all of our Cushing's Syndrome franchise and Korlym and beyond. And he's really responsible for all of our commercial activities. So Adam, if you just allow me to bring Sean on to the call, he'll give you that information and maybe some others that you'd find useful.

Adam, thanks for the question on forecasting of sort of future revenues. Before I answer that, I thought I'd take a minute to just give a high-level overview to everybody on the call of our commercial business. In doing so, there's really 3 key points I want everybody to focus on. Number one, Korlym is being prescribed by physicians throughout the country for all etiologies of Cushing's Syndrome, both in academic centers and then in the community. Number two, we continue to add new prescribers every quarter, and both our prescriber base and our patient base are growing. And the third important point is that we continue to experience very favorable insurance reimbursement. So now diving into each of these specifically. In terms of our prescribing, as everybody may remember, we discussed this on previous calls, we have 6 sales regions that are comprised of 40 clinical specialists that are evenly distributed across the country in those regions. Since our Korlym launch in 2012, we've actually had over 1,200 healthcare providers write one or more prescriptions for Korlym. And over that time, no region has accounted for more than approximately 20% of our unique prescriber base. Our enrollment activity has experienced a very similar distribution to that, with no single region accounting for, again, more than approximately 20% of patient enrollments. And in fact, there have been patient enrollments for Korlym in all but 2 states in the country. So to sum it up -- and we have a very healthy business and our patient population is very dispersed. We believe that hypercortisolism, patients who can benefit from treatment exist in every single endocrinology practice. So moving on to our growing prescriber and patient base, again, as I stated on previous calls, this is a highly scientific cell. I mean, we educate physicians on a spectrum of disease and the appropriate screening tools that are available to them. Many more sick patients are being diagnosed today because of our educational efforts and our commitment to patient identification. It takes many contacts, sometimes 5 to 7 or more with each naive -- Korlym-naive physician to start the process of screening patients, of confirming a diagnosis and then choosing an appropriate treatment path moving forward. Screening for these patients is absolutely a new paradigm for many endocrinologists and mindsets are being changed one physician at a time. Many patients who are diagnosed with the disease are followed without treatment and disease progression is monitored. For others, they are diagnosed for the very first time and then may go to the first-line treatment, which is directly the surgery. And for others, the physician, the diagnosis of them determines whether medical therapy is the best treatment path for them and all available medical therapies become an option including Korlym. So physician-by-physician, we continue to add new prescribers and patients every single quarter. The last thing I'm going to talk about at a high level before I get into the question is around managed care and insurance reimbursement. So 99% of our Korlym patients are on label -- prescription, sorry, are on-label and we continue to see favorable insurance reimbursement. So far in 2018, over 90% of patients prescribed Korlym have required a prior authorization. And these prior authorizations have very rigorous approval criteria that is very closely aligned with Korlym's label, and this is consistent with what we are seeing this year and what we've seen in previous years. Now to obtain PA approval, prescribing physician has to provide supporting lab evidence of both confirmed hyperglycemia and hypercortisolism and evidence of a failed surgery or lack of candidacy for surgery. So overall, from NASH care standpoint, we have an overall prior authorization approval greater than 90%. And the last thing I'd add on that is as we stated in the past, every patient who was prescribed Korlym who has Cushing's Syndrome, will get the drug regardless of their insurance situation. So they will get free drug if they're unable to get approved. So summarize the 3 points quickly again. Korlym continues to be prescribed throughout the country for all etiologies and in all settings. We continue to add new prescribers every quarter, and we expect that to continue as we grow. And we continue to realize favorable reimbursement environment. So in terms of our ability to predict the future, I think we're still in a world, as I described on the last call, of small numbers. I mean, we're in our seventh year post-launch, and we've grown our business year-over-year and we continue that growth to continue. We stated on the call, we expect that growth will continue to fund our pipeline. Again, scientific cell -- the challenges we have today, again, are the challenges that we've had since launch. It's a new challenge to convert physicians who have legacy mindsets and it takes time to shift them. And we've been successful in doing that up to this point, and we expect that to continue in the future. So in short, I mean, we expect steady growth to continue, because we know we haven't come close to saturating the potential prescriber of patient population.

Our next question comes from David Buck.

Just a couple of questions. First, maybe Joe or maybe Sean, can you talk a little bit about what the trend has been in terms of dose for patients, any changes there throughout the year? And has there been any kind of mix shift that's lead to some of the fluctuation in revenues in the last couple of quarters? And separately for Charlie, can you just talk about when you see potentially the additional patents in the Orange Book, but that will lead to some additional and there are currently 4 patents in the FDA Orange Book, when you see the remaining patents after the litigation. And then just for Joe, can you talk a little bit more about how you expect to get a sense of differentiation of relacorilant as you move into Phase III from Korlym itself? You mentioned hyperkalemia. You mentioned obviously not having the PR receptor. But anything else you'd like to see elucidate in Phase III?

Well, let me just sort of sort out those questions. The first question is dose changing. The answer is no, not really. I mean we think modestly over time, it will go up a little bit just as the market -- as the patient base matures only in the sense that the average dose is always affected by how many new patients are coming on. And at some point in time, patients on medicine will greatly outnumber those who are coming on -- at the beginning of each month. But the simple answer to your question is no. Dose is not really changing in any serious way, maybe a few milligrams up or down, usually up. But that's not really a factor. Now the second clinical question, yes, you've really picked out the important things. I mean, relacorilant is a selective cortisol modulator. Unlike Korlym, it does not touch the progesterone receptor. That's a huge deal not just medically, but politically and in terms of distribution and so forth. So that's a very big thing. Now that was, of course, completely anticipated. I mean, we could tell preclinically that this molecule and our other selected modulators don't touch the progesterone receptor. And of course, it turned out to be -- that was no surprise that, that turned out to be true in, of course, our Phase I and phase II studies. The interesting thing is that we had noticed it early on and we actually have made just a little bit of a comment in Phase I. But it's clear to us now that relacorilant does not block the feedback mechanism of the HPA axis to the degree that Korlym does. The cortisol doesn't rise as much. And cortisol rise, which you can deal with in terms of the glucocorticoid receptor, essentially for some patients, floods the mineralocorticoid receptor and causes hyperkalemia. Today, we haven't seen anything in terms of hyperkalemia that's associated with the medicine. That's a very -- again, not a sexy, taking away the abortion pill status, but medically, a very important thing because that's a side effect that really has to be managed and is quite common. It is manageable, but for many physicians new to the drug, they really aren't as quite attentive to it. Their patients may fall off the medicine. So that's actually -- if it pans out, a very large differentiating factor in addition to the lack of progesterone antagonism. And I'll leave out the last question, the pack of question to Charlie.

Well, I can give you one bit of information, which is we've had -- and this is public information. We've had a patent allowed for the differential diagnosis and treatment with mifepristone of patients with atopic Cushing's Syndrome, which is a fair size piece of the business. So those -- claims have been allowed. The patent will issue as soon as the administrative -- we'll finish turning it to patent office, and that will be added to the Orange Book. With respect to our other applications, both of those have been published and are publicly known and those that have not been, I really can't say anything. As they're allowed, we'll let folks know about them. And we will add them to the lawsuit as we think best, and I really can't comment beyond that.

The only thing I wanted to add to that, David, is just -- and you can probably -- you understand. But just for the general audience as a whole, the way it works is there are patents, which you can now see, because they are published. There are also patents that you cannot even see their application, because they are yet to be published. And I can tell you that those are certainly in that category. I mean, this is an area that we obviously have really studied for a long period of time. We think we've made important discoveries. And so in some sense, there is a conveyor belt of intellectual property that's operating right now. And just to reiterate what Charlie said, you will see it as they come along.

And just, I guess, to wrap that part up, the time line and the complexity of litigation, I think, is probably -- there'll be something we'll see.

Yes. And I think I sometimes joke a little bit about it. I mean, the one thing I've learned, this is my n of one dealing with this kind of litigation is that it is expensive and protracted. And fortunately, we have the money to pay for it. Okay. Next question?

Our next question comes from Alan Leong.

Congratulations on the clinical progress and my greetings to the team. I also follow the public listing for the Cushing's pivotal trial and the target goal set for 100 milligrams. And what if you can just put a little more color around that? I mean, I expect you saw nothing concerning at the higher doses. But were there any signals towards incremental efficacy or perhaps greater proportion of patients covered? I expect some patients, there must be an amazing amount of excess cortisol. So feel free to provide some color on it.

This is Bob Fishman. Thanks so much for your question. Yes, a few comments. First of all, and we'll -- just to set it up, we look forward to presenting at the next endocrine session. But just a general theme, we were pleased to see that in our higher dose group, there was evidence of greater response we showed that to you last time, that's continued to be true. And among all of the patients, of course, we followed them individually very carefully and there were the outcomes included clear instances in which patients who escalated to the higher dose, there was evidence of additional benefit. So when you combine the evidence of response combined with the tolerability, we're really pleased with the definition of the workable dose range that came out of Phase II.

Bob, if I may ask a little bit maybe related to it. On the ongoing testing with the new assay test, is that relating well to disease activity? Is it coming out as you expected so far?

Referring to the FKBP5?

Oh, yes.

Oh, yes, on FKBP5, just -- yes, on FKBP5, just to -- as a reminder to everyone, a marker of the signaling through is part of the glucocorticoid receptor and there's to be a good index of its activity and the signaling going through. And we're -- we have validated assay and are collecting in all of our studies. The short answer is we're continuing to collect those data to make -- to learn as much as we can about it. We're collecting the assay, in fact, in all of the studies. And it will be an exploratory endpoint and data is still accumulating. And I think we'll have an update at the timing of the results of the study overall.

But to remind you, Alan, at the Endocrine Society meeting, we released the first data in patients, which I think was really very consequential and very interesting, which is that we had a study of patients who were first tested presurgically for Cushing's disease. And what we found first, and again, always nice to find out what you're hoping to, the patients with Cushing's syndrome indeed had very elevated levels of FKBP5 activity. And then when they have successful surgery, it normalized. And that's public information that's out. So that was actually really the first information we had in patients, not just it helped the surgeons giving prednisone, what we thought would happen would actually happen, and that really spurred us to make sure and now to segue with what Bob was saying that we are now testing that finding in every study we're doing, including the oncology studies and metabolic studies in addition to the Cushing's Syndrome. So we're really developing a real body of information, because I think that from a scientific point of view, that is an important that we're working on in the entire company. Because I think I've it turns out to be correct, it's going to change the entire way that the disease is assayed.

Let me ask one more quick question. Of course, investigators have a full suite of early trials using 2 different drugs to treat prostate cancer, the lab and preclinical data saw some good stuff with CORT285181. You now have a new trial with relacorilant. Is that covering the basis? Or is the solid tumors trials continuing to give a green light? I guess, if you can provide some color on the motivation for putting a full suite of trials on to the prostate cancer?

Well, I have a simple answer, and then I'll give you a more complicated answer. The simple answer is there's a tremendous amount of interest in testing each of these compounds, because preclinically, they all look very good and in modest ways. But I think the more interesting answer -- and I think maybe all things work in oncology, the one where the scientific story is best understood is castration-resistant prostate cancer. It's very clear that we have, in the world, very nice medications to modulate androgen activity like enzalutamide. But unfortunately, where enzalutamide is given, within hours of it being given, they begin to develop colonies of cells for which androgen is no longer a growth factor, cortisol is the growth factor. And there was a very good New England Journal editorial on this and so forth. So I think that there really is a lot of interest in this mechanism. And unfortunately, we were able to fund the study with Korlym as being funded by Michael Milken Foundation and the Department of Defense. We, of course, are doing our own study with CORT125281, and the relacorilant study in castration-resistant prostate cancer also was recently grant funded. So I think there's a lot of interest in the mechanism and that's how it came to be. Obviously, as we get data, we'll probably -- now we're working on it. But at this point, we really give lots of information in an important field.

Thank you all of you out there for being so patient.

We look forward to talking to you next quarter, and hope you have a good evening. Thank you.

Thank you, ladies and gentlemen. This concludes today's teleconference. You may now disconnect.