Corcept Therapeutics (CORT) Q4 2021 Earnings Call Transcript

Corcept Therapeutics (CORT -2.83%)
Q4 2021 Earnings Call
Feb 15, 2022, 5:00 p.m. ET

Contents:

• Prepared Remarks
• Questions and Answers
• Call Participants

Prepared Remarks:

Operator

Thank you for standing by, and welcome to the Corcept Therapeutics conference call. At this time all participants are in a listen-only mode. After the speaker presentation, there will be a question-and-answer session. [Operator instructions] Please be advised that today's conference may be recorded.

[Operator instructions] I would now like to hand the conference over to your speaker today, Atabak Mokari. Please go ahead. 

Atabak Mokari

Good afternoon. And thank you for joining us. I'm Atabak Mokari, Corcept's chief financial officer. Today, we issued a press release announcing our financial results for the fourth quarter and providing a corporate update.

The copy is available at corcept.com. Our complete financial results will be available when we file our Form 10-K with the SEC. Today's call is being recorded. A replay will be available at the investors' past events tab of our website.

Statements during this call, other than statements of historical fact, are forward-looking statements based on our plans and expectations that are subject to risks and uncertainties, which might cause actual results to differ materially from those such results -- from those statements expressed or implied. These forward-looking statements are described in today's press release and the risks and uncertainties that may affect them are described in our annual report on Form 10-K and our quarterly reports on Form 10-Q. Please refer to those documents for additional information regarding these forward-looking statements and the factors that may affect them. We disclaim any intention or duty to update forward-looking statements.

Our revenue in the fourth quarter of 2021 was $98.8 million, an increase of 15% compared to the prior-year period. We expect our growth to continue and have provided 2022 revenue guidance of $400 million to $430 million, compared to 2021 revenue of $366 million. GAAP net income was $32.1 million in the fourth quarter and $112.5 million for the full year 2021. Non-GAAP net income, which excludes noncash expenses related to stock-based compensation, the utilization of deferred tax assets, together with related income tax effects, was $42.6 million in the fourth quarter and $149.5 million for the full year.

Our cash and investments of $335.8 million at December 31 reflects the purchase of 10 million Corcept shares, or about 9% of our shares outstanding, for $207.5 million in the fourth quarter. And now, Charlie Robb, our chief business officer, will provide a legal update. Charlie?

Charles Robb -- Chief Business Officer

Thank you, Atabak. I'll begin by reminding everyone that in December of last year, there was an important positive development in our dispute with Teva Pharmaceuticals. As many of you know, in March 2018, we sued Teva in federal district court to prevent it from marketing a generic version of Korlym in violation of our patents. Two years ago, in the midst of our federal court litigation, Teva challenged one of our patents, the '214 patent, before the Patent Trial and Appeals Board in a procedure known as post-grant review, or PGR.

In November of 2020, PTAB rejected Teva's arguments, upholding the '214 patent in its entirety. Teva appealed its loss to the Federal Circuit Court of Appeals, where in December -- this past December, it lost again. The deadline for Teva to file further appeals or seek reconsideration of its claims have passed. This matter is closed.

This now final determination by the PTAB means that Teva is barred from challenging the '214 patent's validity in District Court and so is reduced to arguing that its proposed product would not infringe, position we believe has no legal or factual support. So where do things stand? Last April, the District Court granted us permission to file for summary judgment based on Teva's infringement of the '214 patent. Teva responded by filing its own summary judgment motion. Summary judgment, as a reminder, is a procedure whereby courts can decide a case without holding a trial.

We believe the court has all it needs to decide the case in our favor. If it grants our motion, we will have won. Teva will be barred from marketing generic Korlym into the '214 patent expires in 2037. If the court rules in Teva's favor, we will proceed the trial, perhaps sometime this year.

There is at present no timetable for the court summary judgment ruling, no trial date, and no schedule for any trial-related activities. In March 2021, we sued another ANDA filer, Hikma Pharmaceuticals, in the same federal district court that is hearing our case against Teva. In this matter, the court has set a fact discovery deadline of July 1. Nothing is scheduled after that.

With respect to both Teva and Hikma, we are confident in the strength of our legal position. I will now turn the call over to Dr. Joseph Belanoff, our chief executive officer. Joe?

Joseph Belanoff -- Chief Executive Officer, President, and Director

Thank you, Charlie. The past two years have shown how sensitive the growth of our commercial business is to pandemic conditions. Public health restrictions and precautions taken by patients and physicians make it more difficult for physicians to identify, diagnose and optimally treat all of their patients and especially those with the complex disorders, such as Cushing's syndrome. Having acknowledged the challenges posed by the pandemic, I want to stress how optimistic we are about the present and the future of our Cushing's syndrome business.

Our Cushing's syndrome business is built on a strong foundation, an effective lifesaving medication promoted by a dedicated commercial team that puts the interests of patients first. Leading endocrinologists increasingly believe that there are substantially more patients with Cushing's syndrome than was once assumed. For many of these patients, Korlym is an excellent treatment. As pandemic conditions and fears recede, as they already have in certain locations, we expect our growth to continue.

And we are providing 2022 revenue guidance of $400 million to $430 million. We are also extremely optimistic about our clinical development programs. We have said for years that cortisol modulation has the potential to help treat many serious diseases. In 2021, the data generated by our ovarian cancer and NASH programs provide an evidence of cortisol modulation's broad application.

In 2022, we will see important results for many of our ongoing clinical programs. These programs are examining lead candidates from our portfolio of more than 1,000 proprietary cortisol modulators, many of which are attractive candidates for development. Like Korlym, these compounds bind strongly to the glucocorticoid receptor or GR. Unlike Korlym, they have no affinity for the progesterone receptor and so don't cause some of Korlym's most serious off-target effects.

Beyond sharing the qualities of strong cortisol modulation and not determining the progesterone receptor, preclinical and clinical testing have shown that our molecules behave differently from one another in important ways. Some cross the blood-brain barrier. Others do not. Some perform best in models of solid tumors.

Others are more potent in models of metabolic disease. Some appear to be tissue-specific. Others have more global effects. These diverse qualities have allowed us to initiate clinical trials in a wide variety of disorders, including ovarian, adrenal, and prostate cancer, antipsychotic-induced weight gain, NASH, and of course, Cushing's syndrome.

We plan to start a phase 2 trial in patients with ALS in the second quarter and have additional compounds in phase 1 and preclinical development. Korlym's commercial success has provided the funds to advance all of these programs. Our oncology program is testing three anti-cancer mechanisms, first postulated by investigators at the University of Chicago and confirmed by other prominent researchers. One mechanism is increasing apoptosis, the programmed cell death that chemotherapy is meant to induce in solid tumors.

Cortisol suppresses apoptosis, meaning cortisol works against the beneficial effects of chemotherapy. In our successful trial in women with advanced ovarian cancer, the addition of our selective cortisol modulator, relacorilant, enhanced the effect of chemotherapy likely by blunting cortisol's anti-apoptotic effect. While these patients' disease had progressed on two or more previous lines of treatment, relacorilant appeared to resensitize some of these patients to the beneficial effects of chemotherapy. As a reminder, our phase 2 trial is a controlled multicenter study of 178 women with platinum-resistant ovarian cancer who were randomized to one of three treatment arms.

Sixty women received a higher dose of relacorilant on the day before, the day of, and the day after they received nab-paclitaxel. We call this the intermittent arm. Fifty-eight women received a lower daily dose in combination with nab-paclitaxel. We call this the continuous arm.

And 60 women received nab-paclitaxel alone, called the comparator arm. The trial's primary endpoint was progression-free survival or PFS. The women who participated in our study were very ill and included those with platinum-refractory disease. All had experienced disease progression despite prior lines of therapy.

Their median number of prior treatments was three. As a result, we presented at the European Society for Medical Oncology, ESMO, Congress, clearly showed relacorilant provided benefits to many of these women. Those who received relacorilant intermittently exhibited a statistically significant improvement in PFS compared to the group that received nab-paclitaxel monotherapy. Their hazard ratio was 0.66 with a p-value of 0.038.

Their median PFS was 5.6 months, 1.8 months longer than the nab-paclitaxel monotherapy group, which is 3.8 months. The women in the intermittent arm also experienced a statistically significant improvement in their duration of response relative to those in the comparator arm, 5.6 months versus 3.7 months, with a hazard ratio of 0.36 and a p-value of 0.006. While the overall survival or OS data collection had accumulated only 63% of the target 120 events at the time of the database cutoff for the progression-free survival results, at that time, the women in the intermittent arm exhibited a median OS of 12.9 months compared to 10.4 months in the comparator arm. Safety and tolerability data for the two groups were comparable.

We expect that we would be able to present final overall survival results from this study last quarter. We currently expect that the primary analysis of the overall survival data will be available later this quarter. We are quite heartened that women in our study are living longer than we and our investigators anticipated. We received very positive feedback from leading gynecological oncologists regarding the promise of relacorilant as a potential treatment for women with this dire disease.

In their view, relacorilant's potential benefit delays disease progression without increased side effect burden would constitute an important medical advance. We plan to meet with the FDA in the coming months to discuss the optimal path forward. A second mechanism by which cortisol modulation may prove useful is by blocking an important tumor growth pathway. Cortisol stimulation is a major reason why patients with metastatic prostate cancer treated with widely prescribed androgen receptor antagonist, enzalutamide, eventually experience resurgent disease.

Deprived of androgen stimulation, their tumor switched to cortisol activity to stimulate growth. Our hypothesis is that adding a cortisol modulator to androgen deprivation therapy will close this tumor escape route. We recently completed enrollment in our dose-finding study of our selective cortisol modulator, exicorilant, combined with enzalutamide in men with castration-resistant prostate cancer. Investigators at the University of Chicago are conducting a similar study of relacorilant, combined with enzalutamide in the same patient population.

We expect to select an optimum dose of either relacorilant or exicorilant to take forward in the second quarter of this year. A third therapeutic mechanism seeks to reduce cortisol suppression of the immune system, a quality of cortisol that likely blunts the effectiveness of immunotherapy. We are conducting an open-label phase 1b trial of relacorilant, plus the PD-1 checkpoint inhibitor, pembrolizumab, Merck's drug, KEYTRUDA, in patients with advanced adrenal cancer whose tumors produce excess cortisol. These patients suffer the effects of adrenal cancer and Cushing's syndrome, a usually quickly lethal combination.

Pembrolizumab is rarely effective as monotherapy in these patients. We believe that these patients' cortisol excess may be counteracting the intended effects of pembrolizumab, which is to stimulate the immune system. Our trial is evaluating with relacorilant can treat these patients' Cushing's syndrome by reducing cortisol activity and by reversing cortisol-induced immune suppression, allowing pembrolizumab to achieve its full cancer-killing effect. We plan to enroll 20 patients at five sites in the United States.

The primary endpoint of this study is objective response rate, with secondary endpoints, including progression-free survival, duration of response, and overall survival. I'll now turn to our programs in metabolic disease and the recent findings of our selective cortisol modulator, miricorilant, in patients with NASH, a serious liver disorder. Patients who receive miricorilant in our phase 2 trial, exhibited large rapid reductions in liver fat, but also substantial transient elevations of liver enzymes, ALT, and AST. The improvement in liver fat in these patients was greater and occurred much more rapidly than we had expected and are rarely seen over any period of treatment.

As a reminder, the trial's primary endpoint was a 30% reduction in liver fat after 12-weeks of treatment. In fact, patients exhibited reductions ranging from 38.5% to 73.8% after receiving miricorilant for just a month. It may be that the rapidity of miricorilant's fat-reducing effect caused the patient's ALT and AST to rise. One way the liver sheds fat is by metabolizing it into fatty acids, which, in excessive amounts, irritate liver.

Interestingly, lipids in the blood of these patients did not increase, providing support for the idea that miricorilant caused the excess fact to be metabolized within the liver. The goal of our phase 1b dosing -- dose-binding trial for patients with presumed NASH is to identify a dosing regimen that significantly reduces fat without causing excessive liver irritation. We are also evaluating miricorilant as a potential treatment for patients with another serious and widespread disorder, antipsychotic-induced weight gain. In the United States, 6 million people take antipsychotic medications such as olanzapine and risperidone to treat illnesses, including schizophrenia, bipolar disorder, and depression.

While these drugs are very effective, they exact a steep price in the form of rapid and sustained weight gain, which leads to cardiovascular and metabolic disease. The average life expectancy of patients in the United States who chronically take antipsychotic medication has decreased by 20 years, frequently due to increased cardiovascular events such as heart attacks and strokes. We are conducting two double-blind placebo-controlled phase 2 trials of miricorilant in patients with this disorder, GRATITUDE and GRATITUDE 2. I'm pleased to say that enrollment in GRATITUDE 2 is complete, and we expect GRATITUDE to be fully enrolled by mid-year.

These trials seek to build on the positive data from our study of miricorilant in healthy subjects. In 2020, we completed a trial in which 96 healthy subjects received olanzapine and either 600 milligrams of miricorilant, 900 milligrams of miricorilant or placebo for 14 days. Subjects who received miricorilant gained significantly less weight than those who received placebo. They also exhibited a smaller increase in triglycerides and in ALT and AST, which typically exhibit sharp transient increases at the start of olanzapine therapy.

A paper describing these results was published in the Journal of Clinical Psychopharmacology. The GRATITUDE trial has a planned enrollment of 100 patients and is evaluating with miricorilant in reverse recent antipsychotic-induced weight gain. Patients with schizophrenia or bipolar disorder will receive, in addition to their established dose of antipsychotic medication, either 600 milligrams of miricorilant or placebo for 12 weeks. GRATITUDE is being conducted at 30 centers in the United States.

Our GRATITUDE 2 study enrolled 150 patients and is testing miricorilant as a treatment for long-standing antipsychotic-induced weight gain. Patients with schizophrenia have received, in addition to their established dose of antipsychotic medication, either 600 milligrams or 900 milligrams of miricorilant or placebo for 26 weeks. GRATITUDE 2 is being conducted at 35 centers in the United States. The primary endpoint in both studies is reduction in body weight.

Other important measures of metabolic activity will also be examined. We look forward to the data readouts from both trials, which we expect in the fourth quarter. As most of you know, relacorilant is our planned successor to Korlym for the treatment of hypercortisolism. We are evaluating it in two phase 3 trials, GRACE and GRADIENT.

Like all of our proprietary molecules, relacorilant is a selective cortisol modulator. Like Korlym, it achieves its effect by competing with cortisol at the glucocorticoid receptor. Unlike Korlym, it does not bind to the progesterone receptor, PR for short. It is not the abortion pill, and it does not cause other PR-related side effects, including endometrial thickening and vaginal bleeding.

By a different mechanism, relacorilant also does not appear to cause hypokalemia, low potassium, a serious side effect experienced by 44% of patients in Korlym's pivotal trial. Korlym-induced hypokalemia is a leading cause of Korlym discontinuation. Relacorilant's phase 2 efficacy and safety data were strong. Patients experienced meaningful improvements in hypertension and glucose control, as well as in a variety of other signs and symptoms of Cushing's syndrome.

There were no relacorilant-induced instances of endometrial thickening or vaginal bleeding and no drug-induced hypokalemia. The trial results were published in Frontiers in Endocrinology. Our GRACE trial has a planned enrollment of 130 patients with any etiology of Cushing's syndrome. As a reminder, GRACE has a randomized withdrawal trial design.

All patients receive relacorilant for 22 weeks in an open-label phase. Those who meet response criteria for improvement in glucose control, hypertension or both are randomized to continue treatment with relacorilant or placebo for 12 weeks. While the pandemic has and continues to impact the execution of this trial, we and our investigators are eager to take GRACE to the finish line. We expect GRACE to serve as the basis for our NDA submission in Cushing's syndrome, which we plan to submit in the second quarter of 2023.

Our second phase 3 trial, GRADIENT, is studying relacorilant's effects in patients whose Cushing's syndrome is caused by an adrenal adenoma or adrenal hyperplasia. Patients with this etiology of Cushing's syndrome often experience a less rapid decline, but ultimately, their health outcomes are poor. GRADIENT has a planned enrollment of 130 patients and is being conducted at many of the sites participating in GRACE. GRADIENT is the first controlled study dedicated solely to patients with this type of Cushing's syndrome.

While we do not expect our NDA in Cushing's syndrome to depend on data from GRADIENT, we do expect that its findings will help improve the care of these increasingly recognized patients. Finally, a brief word about dazucorilant, previously known as CORT 113176, which has shown promise in animal models of ALS. We have been refining our development plans with leading clinicians and regulators in the United States and Europe and plan to initiate a phase 2 trial in the second quarter. We expect our commercial growth to continue as pandemic conditions improve.

Remember, even in the most challenging periods of the pandemic, our commercial business generated more than enough cash to fund our advancing development activities. We believe cortisol modulation can treat many serious disorders, a belief for which our development programs have provided a growing body of evidence. Korlym for patients with Cushing's syndrome is one example of cortisol modulation's benefit. In 2021, the data generated by our ovarian cancer and NASH programs provided evidence of cortisol modulation's broad application.

In 2022, we expect to see very important clinical results. Our oncology program is evaluating two of our proprietary cortisol modulators in three tumor types; ovarian, prostate and adrenal. Our metabolic program is following up encouraging clinical data in NASH and antipsychotic-induced weight gain. We continue to enroll patients in our phase 3 trials of relacorilant in Cushing's syndrome.

Next quarter, we will start a phase 2 trial using another of our proprietary compound, dazucorilant, to treat patients with ALS. Additional proprietary compounds are advancing toward the clinic. This is an exciting time at Corcept. I'd like to thank our employees for their tremendous effort and dedication.

We are expanding our team to support what we believe is a substantial commercial opportunity and an incredibly broad and strong pipeline. I'll stop here for questions.

Questions & Answers:

Operator

Thank you. [Operator instructions] Our first question comes from Matt Kaplan with Ladenburg Thalmann. You may proceed with your question.

Matt Kaplan -- Ladenburg Thalmann -- Analyst

Hi, good afternoon, and congrats on the progress. Just wanted to, I guess, one for Charlie, just to follow up on the legal update. What's your sense in terms of the potential timing for the summary judgment motion decision?

Charles Robb -- Chief Business Officer

Well --hi, Matt, the answer to that is as simple as it is unsatisfying. I have no idea. The case was assigned to a new judge some time ago, and that's always -- new judges take a while to get their feet under them. They have a backlog of cases already.

Criminal cases take priority or civil cases. And so, really, things have been extremely quiet, and we just can't say. I just cannot tell you. 

Matt Kaplan -- Ladenburg Thalmann -- Analyst

OK. OK. Fair enough. Good.

And then in terms of your clinical development programs, what's your current thinking or current plan for the pivotal study in ovarian cancer? And what will your proposal look like to FDA when you meet with them?

Joseph Belanoff -- Chief Executive Officer, President, and Director

Thanks, Matt. And good to hear from you. I'm going to turn you over to Bill Guyer, who is our Chief Development Officer, to address that question. 

Bill Guyer -- Chief Development Officer

Great. Thanks very much. First and foremost, I got to reiterate what Joe had stated, and I'm really excited about 2022 because I've even told my team that this is going to be an epic year for not only development but for Corcept because there are a lot of ongoing trials, where we will see results throughout this year that may move this company forward, one of those being in ovarian cancer. So, our planned next study in ovarian cancer is going to be with the intermittent dose of relacorilant plus nab-paclitaxel in a controlled study versus investigator choice of treatment.

While the study will be larger than our phase 2 trial, we plan to have approximately 360 patients, but we basically just want to replicate the great results we saw in phase 2, where we saw statistically significant improvements in PFS and duration of response. We've actively worked with two leading organizations, one being the GOG, which is the Gynecological Oncology Group here in the US and another being ENGOT, which is the European Network of Gynecological Oncological Trial groups in Europe. Collectively, they are both very excited to partner with us in starting this trial, and we plan to start this trial in the second quarter.

Matt Kaplan -- Ladenburg Thalmann -- Analyst

Great. OK. Thanks for taking the question.

Joseph Belanoff -- Chief Executive Officer, President, and Director

Thanks, Matt.

Operator

Thank you. Our next question comes from Chris Howerton with Jefferies. You may proceed with your question.

Chris Howerton -- Jefferies -- Analyst

Great. Thanks so much and congratulations on all the progress. For me, I think maybe just two. Just maybe two quick questions for me.

One is on the phase 3 GRACE trial. I know you just kind of went through the high-level design, but is there -- maybe you could help us understand what the timelines are leading up to your expected 2Q '23 NDA submission? Just -- what kind of gives you the confidence in those timelines at this point? The second question I have would be around the commercial business and the guidance that you're expecting. Just -- to what degree do you expect kind of dose titration and in-person visits to be a continued headwind? And how has that kind of played into your thinking in terms of those top-line numbers for next year? Thank you.

Joseph Belanoff -- Chief Executive Officer, President, and Director

Thanks, Chris. I think we caught both of your questions. But if you need clarification, let us know. For the first question, let me turn you back to Bill to talk about the GRACE trial.

Bill Guyer -- Chief Development Officer

So for the GRACE trial, we're driving toward our timeline of submitting an NDA in the second quarter of 2022. And here at Corcept, we're taking an all hands-on deck approach with the Corcept team internally, as well as with our partnership with investigators to drive toward those timelines. Just recently, we've completed two investigator meetings, one in the US and one in Europe. Both meetings were very successful because we personally saw the engagement of each investigator and their excitement for the trial.

But I think most importantly, their commitment to increasing recruitment for this trial to help us drive toward those timelines. 

Joseph Belanoff -- Chief Executive Officer, President, and Director

Hey, Chris, and just one small thing. I think Bill said 2022 for the NDA? 

Chris Howerton -- Jefferies -- Analyst

I was going to say the same thing. 

Joseph Belanoff -- Chief Executive Officer, President, and Director

All right. Let me next turn this over to Sean Maduck, who runs all of our hypercortisolism business commercially, and I think has the answer to your question. 

Sean Maduck -- Chief Commercial Officer -- Analyst

Thanks, Joe. And thanks, Chris, for the question. As you all know, forecasting revenue during the pandemic has been and continues to be challenging, but we're confident that the forecasting range that we have put forth accounts for both sort of internal and external drivers that we believe have the potential to impact our Korlym business. Something I said in the past, in-person visits matter.

It's really a key driver for our business, both for patients and for clinical specialists. And as restrictions continue to ease, we're going to be able to engage more frequently with physicians and more patients are going to be screened, which ultimately we believe will lead to more Korlym prescriptions. But we are seeing an improvement in access after the omicron surge back at the end of last year and through the first part of this year. The only other thing I'll touch on quickly is dose, as you brought that up.

And I want to remind everybody, just on previous calls, we've talked a little bit about how we have seen a modest decrease in our average dose over the course of the pandemic, and we were concerned that patients were not being optimally treated. We've actually seen that dose decline stabilized. And in fact, we've seen a modest reversal of that trend. So positive on both fronts. 

Chris Howerton -- Jefferies -- Analyst

Excellent. No, that's fantastic. I really appreciate it. I don't know if you will let me, but I do have another quick question, if you wouldn't mind. 

Joseph Belanoff -- Chief Executive Officer, President, and Director

Yeah. Go ahead, Chris. 

Chris Howerton -- Jefferies -- Analyst

Great. Yes. So, I was actually -- I was thinking about a couple of years ago, when I initiated coverage on the company, there was a discussion around urinary biomarker of activity of Korlym and glucocorticoid receptor blockade. And as we're kind of getting closer to the GRACE finish line, I guess, I was just curious if there is any updates or progress on that scientific front in terms of how you could evaluate glucocorticoid receptor blockade clinically? 

Joseph Belanoff -- Chief Executive Officer, President, and Director

Yeah. Chris, at the risk of taking people off a little bit into the scientific, I'm really pleased to, A, you remember that; and B, you gave me a chance to really talk about just a little bit. So what Chris is really referring to is that all of the measures we have now at cortisol are all cortisol level, the amount of cortisol in the urine or their blood or their saliva, but they don't really represent in a one-for-one way. What's really important, which is the amount of cortisol activity.

This really stems from the fact that patients who have modestly elevated cortisol levels can actually have very bad symptoms of Cushing's syndrome. And people with pretty high cortisol levels can have only moderate symptoms of Cushing's syndrome. So clearly, what matters is, in fact, the activity really at the gene level. And so we began work on a specific gene, which is measuring the activity of a specific gene, which is activated by cortisol, and it's called FKBP5.

That's just the name of the gene. And although we haven't talked about it in a while, our research to it has continued. In fact, there's a very interesting publication from late last year. We were able to demonstrate in study of surgically treated patients with Cushing's disease that FKBP5 levels are, in fact, quite high for successful surgery and then decline to normal levels with surgery.

And if the surgery is unsuccessful, they don't decline. So, that measure is actually being captured, Chris, in all of our studies. We think it's really potentially a very important advance for -- actually maybe both diagnosing and treating patients with Cushing's syndrome. I don't have sort of anything further to tell you, except that the research continues.

And since I know you're an avid reader of the scientific literature, if you ping us, I'll be sure to send you a copy of the published paper.

Chris Howerton -- Jefferies -- Analyst

 OK. Well, that's fantastic. I really appreciate it, Joe. Thanks so much.

Joseph Belanoff -- Chief Executive Officer, President, and Director

Sure.

Operator

Thank you. Our next question comes from Greg Fraser with Truist Securities. You may proceed with your question.

Greg Fraser -- Truist Securities -- Analyst

Thanks. Afternoon, folks. I was wondering if you could comment perhaps high level on Korlym demand trends year to date and whether you've seen any breaks from the typical trends that you see early in the year that might be SEISMIC-related. 

Joseph Belanoff -- Chief Executive Officer, President, and Director

Yeah. I'm going to just turn you back to Sean just so everyone knows who's speaking. 

Sean Maduck -- Chief Commercial Officer -- Analyst

Hi, Greg, thanks for the question. I'll just speak a little bit on sort of omicron, the impact it did have on our business. It definitely affected the end of 2021 and the early part of this year, I would say similar to other times during the pandemic. Over the last two years, restrictions increased, and it became much more difficult for us to meet with physicians and physicians to meet with patients.

And I just mentioned in the last question that obviously, that's a key to our business. The other interesting thing about this wave is with omicron and its broad rapid spread, we actually had some of our own field employees to track the virus. And although everybody vaccinated and is fine, it did require quarantine, which affected time in the field and affected some normal promotional activity. I would say, though, that the positive -- if there is a positive in any of this with omicron is that the surge was rapid.

And unlike what we saw with the prolonged impact of Delta, things seem to be improving very quickly. So restrictions are easing throughout the country, and our sales personnel are healthy and back out there. And things are slowly returning to normal, and we're optimistic that we'll continue on that path.

Greg Fraser -- Truist Securities -- Analyst

Got it. That's helpful. I know it's early days for Recorlev. But I'm curious if any feedback has come through your sales team on how docs are viewing that drug and whether there's been any counter detailing to Korlym that you heard about?

Joseph Belanoff -- Chief Executive Officer, President, and Director

It's very early with Recorlev. We have not heard that feedback, but I'll say both with Recorlev and history to this date, we have not seen any impact on our business. And truthfully, I mean, we're happy that other companies are out there educating physicians on the illness, on hypercortisolism, and on proper screening because this improves patient care overall. So it's a good thing. 

Greg Fraser -- Truist Securities -- Analyst

Got it. OK. And then for prostate cancer, once you select the optimal dose of either exicorilant or relacorilant in the second quarter, will you then move immediately into a phase 2 study this year? 

Bill Guyer -- Chief Development Officer

So thank you for that question. We're going to take a look at both of the study data in the second quarter of this year and make that decision. It depends upon which drug we choose. Both drugs we are excited about, exicorilant and relacorilant.

But we'll evaluate the safety data. We'll evaluate what efficacy data we get from that trial. And then we will determine internally what the best path forward is for us to take either one of those drugs into a phase 2 trial. But the plan would be, yes, we would go to a next trial with one of the drugs and pick the optimal dose.

Greg Fraser -- Truist Securities -- Analyst

Great. Thank you.

Operator

Thank you. Our next question comes from Tazeen Ahmad with Bank of America. You may proceed with your question.

Tazeen Ahmad -- Bank of America Merrill Lynch -- Analyst

Hi, good afternoon and thank you for taking my questions. Can I ask two? The first would be on the GRATITUDE studies. So can you just remind us, Joe, about what is the average amount of weight gain a patient endures during treatment with antipsychotics? And is there a minimum amount of weight loss that you think would be needed to be clinically meaningful just based on your conversations with physicians? And then a second question is on ovarian cancer. So, you did give some guidance on what you think trial design will be for the pivotal study.

But is there anything that you would want to wait to see from your upcoming update of the phase 2 data, which is due later this quarter, where I think you're going to have an update of overall survival data that you would need to potentially tweak that trial design for the pivotal? Thank you.

Joseph Belanoff -- Chief Executive Officer, President, and Director

I think -- Tazeen, thank you. And I think I do understand both of your questions. And I know, Tazeen, just because she knows the company for a very long time. But I'm a psychiatrist by training.

And so the weight gain and metabolic issues are very close to me because these are my patients and they need to take antipsychotic medications, which are often very effective for the psychosis, but really have a tremendous metabolic Achilles' heel. It is rare for patients to not gain weight. And sometimes the weight gain they gain is, I think, you would be very surprised. I mean, I personally have patients who have gained between 50 pounds to 100 pounds on these medications.

Weight gain tends to be rapid, which is why there's actually really an issue about treating healthy people in phase 1 studies for very long. The average amount of weight gain that we saw in two weeks in patients in our healthy studies is about 10 pounds, which really is, obviously, would be problematic for all of us. So it's a very potent effect and one that is a great concern to all treating psychiatrists. So, you asked me a question which is a little harder to answer, which is how much of a weight loss would actually be beneficial to patients.

I don't really know exactly what the answer to that is. I will tell you this that weight gain is -- weight loss would be looked at in the context of what are the other metabolic perturbations together. It's not just the amount of weight. It's all the other things that happens when people gain weight.

It's really very meaningful. And I think as treating psychiatrists, she would want to look at that entire picture. So for instance, a drug which caused less weight gain or created small amount of weight loss without affecting any of the other variables isn't as valuable as a drug, which creates the exact same amount of weight loss or prevents the same amount of weight gain and does some of those other things. So, it's really going to be a picture of, in total, for what's going on.

This is the first study. In fact, both -- these are the first studies, I should say, that we've actually ever done in patients. And I think we're going to learn a tremendous amount as to how the drug works, how the patients respond to it in both tolerability and in efficacy way. And we'll go from there.

But I really wanted to highlight this because this is the first time we treated patients and have been very pleased by what we've seen in healthy people. We'll see how much of that translates to what really is a terrible problem in patients who must take these medications. So that's the answer to that question. I think the second question related to the ovarian cancer's program.

And I think I'd like to turn that over to Bill. And, Bill, if there's anything that I need to?

Bill Guyer -- Chief Development Officer

Great. Thank you for that question. So regarding the OS data, to me, we have a solid regulatory path forward with or without the OS data with what we have today. Because I have to remind you, we saw great results from the phase 2 study showing that the intermittent arm of relacorilant plus nab-paclitaxel showed statistically significant improvements in PFS.

That was the primary endpoint of that study. That will be the primary endpoint of our next study as well. So, that's the key piece there. But then also back to OS, this study, the phase 2 study was not powered to see a difference in OS.

And to be honest, there's no study or no drug that has shown a statistical significance and improvement in overall survival in these types of patients, the recurrent platinum-resistant ovarian cancer patients. And so if we were to see a significant difference in OS that would be unprecedented and very positive. We will see when we reach that total, when we get the total events, the 120 events, which we hope to see later this quarter. 

Tazeen Ahmad -- Bank of America Merrill Lynch -- Analyst

OK. And would that be in a press release that you would reveal the some updated data?

Bill Guyer -- Chief Development Officer

Once we get the data, we will make it available, sooner we have the data.

Tazeen Ahmad -- Bank of America Merrill Lynch -- Analyst

OK. Excellent. Thanks for taking my questions.

Joseph Belanoff -- Chief Executive Officer, President, and Director

Thanks, Tazeen.

Operator

Thank you. Our next question comes from Michelle Gilson with Canaccord Genuity. You may proceed with your question.

Michelle Gilson -- Canaccord Genuity -- Analyst

Hi, thank you for taking my question. I was hoping that you guys could give us a better sense of what's in the guidance and what might get you to the high end of that guidance and some of the factors that you considered in there. And then you spoke already about the in-person interactions and the dose starting to normalize or trends toward the dose starting to normalize from what you've seen previously prior to COVID. But I was wondering if you are also seeing any upticks in terms of the diagnostic, I guess, the diagnosis of patients with Cushing's syndrome and maybe some of those COVID delays in diagnosis starting to subside? 

Joseph Belanoff -- Chief Executive Officer, President, and Director

Yeah. Thank you, Michelle. And I'm going to again just so people recognize the person, turn you over to Sean again. 

Sean Maduck -- Chief Commercial Officer -- Analyst

Yes. Perfect. Thank you for the question. Michelle.

In terms of the first question of sort of the range, again, interactions are really an important part of this. So, that's been built in, assuming that we're going to see an easing of some of the restrictions that have existed for quite a window of time here where practices have been closed to the clinical specialists and in some cases, some of their patients. The other piece that I haven't touched on yet today is field expansion that we actually undertook prior to actually COVID occurring. We scaled up our sales force.

They were new to the field and immediately, they were basically at home and not able to go into the field. And so with the opening up of the country, we're going to have a more clinical specialist actively calling on physicians than we've ever had. And I believe that will also add to the value and the ability to educate more physicians and through that seeing more patients being screened. So to your second part of your question around diagnosis.

Patients are -- when they are able to see their doctors and the physician has been educated on this, they are actively being screened. During COVID, that was not occurring because it takes many visits to take a patient from sort of first concern and first test through the multitude of tests and following the guidelines. And as again, restrictions have eased, patients are seeing their physicians more frequently through that are able to get sort of the multiple tests that they may need to be diagnosed. And through that, we've seen an increase in the diagnosis. 

Michelle Gilson -- Canaccord Genuity -- Analyst

And if I can also ask a question on relacorilant. Previously, you've said that the market for relacorilant, you would expect to be substantially larger than the market for Korlym. And I was wondering if you could just expand on that a bit more and sort of the biggest drivers that you would expect for relacorilant to be able to grow the market if it's your persistence or patients dropping off, coming back on, or patients that never have considered Korlym that maybe would consider relacorilant? If you could expand a little bit on what you would expect from the Cushing's syndrome market for relacorilant versus Korlym? 

Joseph Belanoff -- Chief Executive Officer, President, and Director

Yeah, Michelle. Glad you asked. And it's an important question. So first, again -- and I know we have listeners who work through various degrees of their understanding, Korlym is an excellent medication.

For people who have hypercortisolism, it really turns that thermostat down in a way, which makes for much more of a normal situation. And just remind people, it's now almost a decade ago when we did our clinical study, which got the drug approved. Eighty-seven percent of the patients saw a substantial clinical improvement as adjudicated by outsiders. So it really works in that regard.

And so we love Korlym. But unfortunately, Korlym or its active ingredient, mifepristone, is not a specific drug for cortisol. It does a couple of things, which actually are problematic. One, and it was known as this before was ever used for Cushing's syndrome is a potent progesterone receptor antagonist.

And as we've said, it's the active ingredient that's frequently called the abortion pill. It's nothing to do with cortisol, but is affected entirely by progesterone receptor antagonism. And so our full discovery program was really to see if we can find a mechanism which could takeaway that problem. And in fact, our wonderful head of medicinal chemistry at that time, now our chief scientific officer, Hazel Hunt, was actually able to create three different series of compounds in which relacorilant comes from [Inaudible] series to do exactly that, potent cortisol modulation no effect on progesterone.

And so that was really sort of the first and obvious benefit to takeaway that particular medical problem and frankly political problem. But the second one as it turned out was really something that we discovered as we were developing it which is that -- is that relacorilant unlike Korlym doesn't seem to cause what's called hypokalemia or low potassium. We understand the mechanism why that occurs with Korlym. It's a manageable problem.

We really have to pay attention to it with Korlym. Relacorilant, it does not seems that's really an issue at all. And it just creates for ease of use. So, I think those medical things are really important reasons why relacorilant is not just another purple pill.

It really is a significantly better medication. And I just -- I have to say in the United States, the idea of being related to termination of pregnancy or abortion creates political toxicity that I think will also be -- it's meaningful that, that will really be not an issue with relacorilant. 

Michelle Gilson -- Canaccord Genuity -- Analyst

Great. Thank you. And maybe if I can just ask one more. The phase 1b that you're running in NASH, the dose exploration study, are you starting to see anything in that study so far that's validating your hypothesis that the LFT signals were may be related to the magnitude or the rapidity that you saw in the phase 2 around the liver fat reductions? 

Joseph Belanoff -- Chief Executive Officer, President, and Director

Michelle, I'm going to have to keep you on the edge of your seat. We do -- actually, I'm not -- we have information. It's an open label study, but we will release all that information when we have it accumulated. 

Michelle Gilson -- Canaccord Genuity -- Analyst

All right. Thanks for taking my questions.

Joseph Belanoff -- Chief Executive Officer, President, and Director

Sure.

Operator

Thank you. Our next question comes from Arthur He with H.C. Wainwright. You may proceed with your question.

Arthur He -- H.C. Wainwright and Company -- Analyst

Hey, good afternoon, Joseph. So I -- just follow up on the NASH study. Could you guys give us more color on the enrollment status for the dosing escalation part? 

Joseph Belanoff -- Chief Executive Officer, President, and Director

Yeah. Bill, would you like to answer that question? 

Bill Guyer -- Chief Development Officer

Sure. So for the enrollment status, I mean, our phase 1b study started with multiple cohorts looking at lower doses of miricorilant. Each cohort was gated by devaluation safety and efficacy every six weeks, and we saw great enrollment at the end of the year and even at the beginning of this year. We see great excitement by the investigators and for patients into this trial.

So, we're seeing good steady enrollment for this trial. 

Joseph Belanoff -- Chief Executive Officer, President, and Director

And I'll just add to that, Arthur, an important thing. We really think we have hooked a big one here. We really do think that this medication is very potent. All the investigators we've worked with have really described it as perhaps not just a potent medication, but the most potent medication that they've ever seen for liver.

And so we really do think it's worth doing the work to get it as precise dose as is possible to actually provide the maximum benefit and with the greatest ease of use. And so I'll just reiterate Bill's point. We've had no trouble attracting people to be in this study. I think it offers them even in this space, real benefit.

And we're going to work hard to get to the fastest dose as quickly as we can, but we can't tell you exactly when that is because the protocols are in the process of running. 

Arthur He -- H.C. Wainwright and Company -- Analyst

Thank you. And regarding the GRATITUDE study, could you remind like besides the weight loss data, is there any biomarker data we can get from the data update later this year? 

Joseph Belanoff -- Chief Executive Officer, President, and Director

Yes. The answer is all of the standard metabolic deal like triglycerides and lipids and so forth. All of those things are being measured in the study. And again, as a practitioner, I can tell you all of them are meaningful. 

Arthur He -- H.C. Wainwright and Company -- Analyst

That's great. Thanks for that. The last one I would want to pick up your brain for -- considering the current macro environment, what's your appetite for the BD idea? 

Joseph Belanoff -- Chief Executive Officer, President, and Director

All right. Well, I was wondering when someone would ask us that question. The answer is that we have good business. We produce enough money to run our development programs, as you know.

And so we -- I'd just sort of get you to the bottom line. I'm pitched ideas on a very regular basis. But let me really give you the most important understanding. We really like what we're doing.

We think our development program is terrific and it's going to provide benefit to many different types of patients. It is by far our highest priority to make sure that those programs run to their finish line, get us the best results we can, and that we are not distracted from doing that in the optimal way. So, yeah, we take a look at a lot of things that come in the door. Some are easy to dismiss.

Some require more thought and then, obviously, some -- it's potentially I suppose something could be so attractive that we really have to give it serious thought. But keep in mind that's not our priority. Our priority is really to optimize cortisol modulation and all the diseases that we feel can be effective and treated.

Arthur He -- H.C. Wainwright and Company -- Analyst

Sounds great. Thank you. Thank you for answering my questions.

Operator

Thank you. Our next question comes from Greg Fraser with Truist Securities. You may proceed with your question.

Greg Fraser -- Truist Securities -- Analyst

Thanks for taking the follow-up. I just wanted to check to see if there's been any progress or if there is anything new to report on the New Jersey USAO investigation. Thanks. 

Joseph Belanoff -- Chief Executive Officer, President, and Director

Yeah. Happy to answer that. So, there's been no developments to report. But I think there are a couple of things that folks should keep in mind as they think about that.

And before I sort of talk about that, let me just back up and give just a little bit of background for those who aren't familiar with what you're talking about. Back in December of last year, we disclosed that we've received a document subpoena from the Department of Justice, actually, the New Jersey US Attorney's Office, seeking documents related to sort of broadly speaking for our commercial business, our relationships with healthcare providers, our promotional practices, the Korlym prior authorization information, things of that nature. And I think the first thing to keep in mind is that the subject matter covered by those documents is the same as the sort of swirl that's been picked up around us for years, starting with the short seller report that was published back in January 2019, which read sort of as night follows day to the securities class action suit that we are grinding through right now. And now we have this Department of Justice entry.

That's the first thing that you keep in mind. It's sort of an entire ecosystem. The second thing is that it's very common to say as is true with us that we are cooperating fully with the government's investigation because we most certainly are. Because, first and foremost, that's the right thing to do.

But what is not as commonly seen or is almost never seen is that many companies, not all, but many companies while they cooperate, simultaneously hope that things will move as slowly as possible. That is not the case with us. As I should have mentioned with respect to the Teva lawsuit and it's certainly true here, we want things to go as quickly as possible. We are producing documents and information to the Department of Justice as fast as we can, and our goal is to always be ahead of the curve.

Because we believe that the best path forward, the best outcome for Corcept and our shareholders is to get the -- all of the facts before the government as quickly as we can. And that's what we're going to do. So nothing to announce at the moment, but I think it's important for folks to keep those couple of things in mind. 

Greg Fraser -- Truist Securities -- Analyst

Great. Thanks for the color.

Joseph Belanoff -- Chief Executive Officer, President, and Director

Thanks. Sure. For all those who've tuned in, thank you very much. We'll talk to you in another quarter.

This is really a very exciting year for Corcept. I really -- if you're just being introduced to the company, this is a good time to take a serious look. We'll talk to you in another quarter. Thank you very much.

And have a good rest of the day. 

Operator

[Operator signoff]

Duration: 63 minutes

Call participants:

Atabak Mokari

Charles Robb -- Chief Business Officer

Joseph Belanoff -- Chief Executive Officer, President, and Director

Matt Kaplan -- Ladenburg Thalmann -- Analyst

Bill Guyer -- Chief Development Officer

Chris Howerton -- Jefferies -- Analyst

Sean Maduck -- Chief Commercial Officer -- Analyst

Greg Fraser -- Truist Securities -- Analyst

Tazeen Ahmad -- Bank of America Merrill Lynch -- Analyst

Michelle Gilson -- Canaccord Genuity -- Analyst

Arthur He -- H.C. Wainwright and Company -- Analyst

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