Corcept Therapeutics Inc

NASDAQ:CORT

Earnings Call Transcript 2021-Q4

[Operator]

00:04 Hello. 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 question-and-answer session. [Operator Instructions] Please be advised that today's conference maybe recorded. [Operator Instructions]. 00:26 I would now like to hand the conference over to your speaker today, Atabak Mokari. Please go ahead.

[Atabak Mokari, Chief Financial Officer]

00:34 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 on the Investors Past Events tab of our website. 01:00 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 -- those statements express or imply. 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. 01:40 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. 02:00 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 non-cash 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. 02:26 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. 02:39 And now, Charlie Robb, our Chief Business Officer will provide a legal update. Charlie?

[Charlie Robb, Chief Business Officer]

02:44 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-grand review, or PGR. 03:18 In November of 2020 the 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. 03:43 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? 04:01 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 this case in our favor. If it grants our motion, we will have won. 04:25 Teva will be barred from marketing generic Korlym until 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. 04:48 In March 2021, we sued another ANDA filer at 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. 05:09 I will now turn the call over to Dr. Joseph Belanoff, our Chief Executive Officer. Joe?

[Joseph Belanoff, Chief Executive Officer]

05:15 Thank you, Charlie. The past 2 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, diagnosing and optimally treat all of their patients. And especially those with the complex disorders, such as Cushing syndrome. Having acknowledge the challenges posed by the pandemic, I want to stress how optimistic we are about the present and the future of our Cushing syndrome business. 5:48 Our Cushing's syndrome business is built on a strong foundation and effective lifesaving medication promoted by a dedicated commercial team that puts the interests of patients first. Leading endocrinologist increasingly believe that there are substantially more patients with Cushing syndrome and was once assumed. For many of these patients Korlym is an excellent treatment. 06:09 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 the 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 broad application. In 2022, we will see important results for many of our ongoing clinical programs. 06:49 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 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 with solid tumors, others are more potent in models of metabolic disease. Some appear to be tissue specific, others have more global effects. 07:39 That these diverse qualities have allowed us to initiate clinical trials in a wide variety of disorders, including ovarian, adrenal and prostate cancer, anti-psychotic-induced weight gain, NASH and, of course, Cushing syndrome. We plan to start a Phase II trial in patients with ALS in the second quarter and have additional compounds in Phase I and preclinical development. Korlym's commercial success has provided the funds to advance all of these programs. 08:08 Our oncology program is testing 3 anti-cancer mechanisms, first postulated by investigators at the University of Chicago and confirmed by other prominent researchers. One mechanism is increasing apoptosis that program cell death when 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 enhance the effect of chemotherapy likely by blunting cortisol anti-apoptotic effect. 08:53 While these patients disease had progressed on 2 or more previous lines of treatment, relacorilant appears to re-sensitize some of these patients to the beneficial effects of chemotherapy. As a reminder, our Phase II trial is a controlled multicenter study of 178 women with platinum-resistant ovarian cancer who were randomized to one of three treatment arms. 60 women received a higher dose of relacorilant on the day before, the day of and the day after they receive nab paclitaxel, we call this the intermittent arm. 58 women received a lower daily dose in combination with nab paclitaxel, we this the continuous arm. And 60 women received nab paclitaxel alone. We call this the comparator arm. 09:39 The trial's primary endpoint was progression-free survival or PFS. The women who participated in our study were very ill and including those with platinum-refractory disease, all had experienced disease progression, despite prior lines of therapy. Their median number of prior treatments was 3. As the results we presented at the European Society for Medical Oncology, ESMO, congress clearly showed relacorilant providing 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 groups, which is 3.8 months. 10:36 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 cut off 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. 11:18 Safety and tolerability data for the 2 groups were comparable. We had expected that we would be able to present final overall survival results from this study the 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 have been longer than we and our investigators anticipate. We received very positive feedback from leading gynecological oncologist regarding the promise of relacorilant as a potential treatment [indiscernible] disease. In their view, relacorilant's potential benefit delays the 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. 12:11 Our second mechanism by which cortisol modulation improved useful is by blocking an important tumor growth pathway. Cortisol stimulation is a major reason why my patients with metastatic prostate cancer treated with widely prescribed androgen receptor antagonist, enzalutamide, eventually experienced resurgent disease. Deprived of androgen stimulation their tumors 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. 13:24 Our third therapeutic mechanism that seeks to reduce cortisol suppression of the immune system. Quality of cortisol that likely blunts the effectiveness of immunotherapy. We are conducting an open label Phase Ib trial of relacorilant plus the PD1 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 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. 14:16 Our trial is evaluating with the relacorilant can treat these patients Cushing 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 5 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. 14:49 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 received miricorilant in our Phase II 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. 15:25 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 fat reducing effect caused the patients ALT and AST to rise. One way the liver shifts fat is by metabolizing it into fatty acid, which in excessive amounts irritates the liver. Interestingly lipids in the blood of these patients did not increase, providing support to the idea that miricorilant cause the excess fat to be metabolized within the liver. 16:08 The goal of our Phase Ib dosing -- dose finding trial in 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, anti-psychotic-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. 16:42 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 medications decreased by 20 years. Frequently due to increased cardiovascular events, such as heart attacks and strokes. We are conducting 2 double blind placebo-controlled Phase II trials of miricorilant in patients with this disorder, GRATITUDE and GRATITUDE II. 17:16 I'm pleased to say that enrollment in GRATITUDE II 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 than in ALT and AST, which typically exhibit sharp transient increases in the start of olanzapine therapy. 18:00 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 whether miricorilant can 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. 18:31 Our GRATITUDE II study enrolled 150 patients and is testing miricorilant as a treatment for long standing antipsychotic induced weight gain. Patients with schizophrenia will receive in addition to their established dose of antipsychotic medication either 600 milligrams or 900 milligrams of miricorilant or placebo for 26 weeks. GRATITUDE II 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. 19:12 As most of you know relacorilant is our planned successor to Korlym for the treatment of hypercortisolism. We are evaluating it in 2 Phase III trials, GRACE and GRADIENT. Like all of our proprietary molecules relacorilant is a selective cortisol modulator. Like Korlym it achieves its efficacy -- 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 intravitreal thickening and vaginal bleeding. By a different mechanism relacorilant also does not appear to cause hyperkalemia, low potassium, a serious side effect experienced by 44% of patients in Korlym's pivotal trial. 20:04 Korlym induced hyperkalemia is a leading cause of Korlym discontinuation. Relacorilant's Phase II 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 Cushing syndrome. There were no relacorilant induced instances of endometrial thickening or vaginal bleeding and no drug-induced hyperkalemia. The trial results were published in Frontiers in endocrinology. 20:36 Our GRACE trial has a planned enrollment of 130 patients with any etiology of Cushing syndrome. As a reminder GRACE has a randomized withdrawal trial design, all patients received relacorilant for 22 weeks in an open label phase. Those who need response criteria for improvement in glucose control, hypertension or both are randomized to continue treatment with relacorilant or placebo for 12 weeks. 21:03 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 syndrome, which we plan to submit in the second quarter of 2023. Our second Phase III trial GRADIENT is studying relacorilant impacts in patients whose Cushing's syndrome is caused by an adrenal adenomas or adrenal hyperplasia. Patients with this etiology of Cushing syndrome often experience a less rapid decline, but ultimately their health outcomes are poor. 21:40 GRADIENT has a planned enrollment of 130 patients and is being conducted at many of the sites participating in GRACE. GRADIENT is a first-controlled study dedicated solely to patients with this type of Cushing's syndrome. While we do not expect our NDA in Cushing syndrome to depend on data from GRADIENT, we do expect that is finding will help improve the care of these increasingly recognize patients. 22:06 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 [indiscernible] in the United States and Europe and plan to initiate a Phase II trial in the second quarter. 22:28 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 quarter to hold cortisol modulation can treat many serious disorders. I believe, for which our development programs have provided a growing body of evidence. Korlym for patients with Cushing syndrome is one example of cortisol modulations benefit. 23:00 In 2021 the data generated by our ovarian cancer and NASH programs provided evidence cortisol modulation broad application. In 2022, we expect to see very important clinical results. Our oncology program is evaluating 2 of our proprietary cortisol modulators and 3 tumor types ovarian, prostate and adrenal. 23:25 Our metabolic program is following up encouraging clinical data in NASH and antipsychotic induced weight gain. We continue to enroll patients in our Phase III trials of relacorilant in Cushing syndrome. Next quarter we will start a Phase II trial using another of our proprietary compounds dazucorilant to treat patients with ALS. Additional proprietary compounds are advancing towards the clinic. 23:50 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.

[Operator]

24:10 Thank you. [Operator Instructions] Our first question comes from Matt Kaplan with Ladenburg Thalmann. You may proceed with your question.

[Matt Kaplan, Ladenburg Thalmann]

24:24 Hi, good afternoon, and congrats on the progress. I just wanted to -- I guess, one for Charlie, just a follow-up on the legal update. What's your sense in terms of the potential timing for the summary judgment motion decision?

[Charlie Robb, Chief Business Officer]

24:46 Well -- Hi, Matt. The answer to that is simple as it is unsatisfying. I have no idea [indiscernible]new judge some time ago and that's always -- new judges take a while to get their feet under them, they have the backlog in place already, criminal cases take priority over civil cases. And so, really things have been extremely quiet and we just can't say, just cannot tell you.

[Matt Kaplan, Ladenburg Thalmann]

25:18 Okay, fair enough. 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 I guess, what were your proposal look like to FDA when you meet with them?

[Joseph Belanoff, Chief Executive Officer]

25:39 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]

25:48 Great. Thanks very much. First and foremost, I going to reiterate what Joe had stated. 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 of Corcept, because there are a lot of ongoing trials and we will see results throughout this year and that would may move this company forward. 26:07 One of those being in ovarian cancer. So our plan 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 II trial, we plan to have approximately 360 patients, but we basically just want to replicate the great results we saw in Phase II where we saw statistically significant improvements in PFS and duration of response. 26:36 We actively work with 2 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 Oncologist Trial Group 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]

26:59 Great. Okay. Thanks for taking the question.

[Joseph Belanoff, Chief Executive Officer]

27:04 Thanks, Matt.

[Operator]

27:06 Thank you. Our next question comes from Chris Howerton with Jefferies. You may proceed with your question.

[Chris Howerton, Jefferies]

27:13 Great. Thanks so much and congratulations on all the progress. For me, I think, maybe just two -- Yeah. Hey, thanks, Joe. Just maybe two quick questions from me. One is on the Phase III 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? 27:46 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 in 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]

28:11 Thanks, Chris. I think we got both of your questions, but if need clarification let us know. The first question, let me turn you back to Bill to talk about the GRACE trial.

[Bill Guyer, Chief Development Officer]

28:20 So for the GRACE trial we're driving towards our timeline of submitting an NDA in the second quarter of 2022 and here at Corcept we're taking all hands on deck approach with the Corcept team internally as well as with our partnership with investigators to drive towards those timelines. Just recently, we've completed 2 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 towards those timelines.

[Joseph Belanoff, Chief Executive Officer]

28:55 Hey, Chris. Just one small thing, I think Bill said 2022 for the NDA [Multiple Speakers] Let me next turn this over to Sean Maduck who runs all of our hypercortisolism business commercially. And I think has got the answer to your question.

[Sean Maduck, Chief Commercial Officer]

29:16 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 put forth accounts for both sort of internal and external drivers that we believe have the potential to impact our whole business. It's something I've said in the past, in-person visits matter. It's really a key driver for our business, both for patients and for 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 follow on discussions. 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. 30:07 The only other thing I'll touch on briefly 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 had seen a modest decrease in our average dose. I mean, 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]

30:34 Excellent. That's fantastic. I really appreciate it. And I don't know if you let me, but I do have another quick question if you wouldn't mind.

[Joseph Belanoff, Chief Executive Officer]

30:42 Yeah. Go ahead, Chris.

[Chris Howerton, Jefferies]

30:44 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 update or progress on that scientific front in terms of how you could evaluate glucocorticoid receptor blockade clinically?

[Joseph Belanoff, Chief Executive Officer]

31:16 Yeah. Chris, At the risk of taking people off a little bit into the scientific [indiscernible] I'm really pleased that A, you remember that, and B, to give me a chance really talk about just a little bit. So what Chris is really referring to is that, all of the measures we have now in cortisol are all cortisol level, the amount of cortisol in the urine or the blood or the saliva. But they don't really represent [indiscernible] one way. What's really important, which is the amount of cortisol activity. And it's really stems from the fact that patients who have modestly elevated cortisol levels can actually have very bad symptoms of Cushing syndrome and people with pretty high cortisol levels can have only moderate symptoms of Cushing syndrome. So clearly what matters is in fact the activity really at the gene level, and so we began to work on a specific gene, which is measuring that can't be specific which is activated by cortisol, and it's called FKBP5, that's just the name of the gene. 32:15 And although we haven't talked about it in a while, research has continue that there is a very interesting publication from late last year where we really able to demonstrate a study up surgically treated patients with Cushing's disease that FKBP5 levels are in fact quite for successful surgery and then decline to normal levels with surgery and if the surgery is unsuccessful, they don't decline. So that measures actually being captured, Chris, in all of our studies, we think it's really a potentially very important advance of actually maybe both diagnosing and treating patients with Cushing 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 paying us, I'll be sure to send you a copy of the published paper.

[Chris Howerton, Jefferies]

33:07 Okay. Well, that's fantastic. I really appreciate it, Joe. Thanks so much.

[Joseph Belanoff, Chief Executive Officer]

33:12 Sure.

[Operator]

33:15 Thank you. Our next question comes from Greg Fraser with Truist Securities. You may proceed with your question.

[Greg Fraser, Truist Securities]

33:22 Thank. Good afternoon folks. I was wondering if you could comment perhaps higher 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 pandemic related?

[Joseph Belanoff, Chief Executive Officer]

33:37 Yeah. I'm going to just turn it back to Sean just so everyone knows who speak.

[Sean Maduck, Chief Commercial Officer]

33:40 Hi, Greg. Thanks for the question. I'll just speak a little bit on sort of Omicron and the impact it did have on our business. It definitely effected the end of 2021 and the early part of this year. I would say similar to other times during the pandemic, over the last 2 years, restrictions increase and it became much more difficult for us to meet with physicians and physicians to meet with patients. And I just mentioned on the last question that obviously that's a key to our business. 34:03 And the other interesting thing about this wave is with Omicron and it's broad and rapid spread, we actually had some of our own field employees attract the virus. And although everybody is vaccinated and is fine, they require quarantine which affected time in the field and affected some normal promotional activity. I would say though that the positive -- 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]

34:48 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 has been a counter-detailing the Korlym that you've heard about?

[Joseph Belanoff, Chief Executive Officer]

35:01 It's very early with Recorlev and we have not heard that feedback, but I'll say, both with Recorlev history to this date we have not seen any impact on our business. And interestingly, I mean we're happy that other companies are out there educating physicians on the illness, on hypercortisolism and on proper screening, because this improve patient care overall. So to get back.

[Greg Fraser, Truist Securities]

35:25 Got it, okay. 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 II study this year?

[Joseph Belanoff, Chief Executive Officer]

35:38 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're excited about, exicorilant end relacorilant, but we will evaluate the safety data, we will evaluate what efficacy data we get from that trial and then we will determine internally with the best path forward is for us to take either one of those drugs into a Phase II trial. 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]

36:13 Great. Thank you.

[Operator]

36:19 Thank you. Our next question comes from Tazeen Ahmad with Bank of America. You may proceed with your question.

[Tazeen Ahmad, Bank of America]

36:25 Hi, good afternoon and thank you for taking my questions. Could 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 endorse 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? 36:56 And then the second question is on ovarian cancer. So you did give some guidance on what you think the 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 II data, which is due later this quarter? Or I think you're going to have updated overall survival data that you would need to potentially tweak that trial design for the pivotal? Thank you.

[Joseph Belanoff, Chief Executive Officer]

37:24 I think I -- Tazeen, thank you. And I think I do understand both your questions. And I know Tazeen [indiscernible] 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 anti-psychotic medications, which are often very effective for the psychosis, but really have tremendous metabolic achilles heel. It is rare for patients to not gain weight and sometimes the weight gain they gain is, I think, you'd very surprised. I mean, I personally have had patients who between 50 to 100 pounds on these medications. Weight gain tends to be rapid which is why there is actually really an issue about treating healthy people in Phase I studies for very long. 38:17 The average amount of weight gain that we saw in 2 weeks in patients in our healthy studies, it's about 10 pounds, which really is obviously would be problematic for all of us. So it's a very potent effect and when that -- of 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 -- we 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 it's treating psychiatrists should want to look at that entire picture. 39:13 So for instance a drug which cause less weight gain or create a 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, what's going on. This is the first studies -- these are the first study, 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 efficacy way and we'll go from there. 39:54 But I really wanted to highlight this, because this is the first time we treated patients and I'm 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 that question. 40:12 I think the second question is related to the ovarian cancers program. And I think I'd like to turn that over to Bill and I'll fill in if there's anything that I need to.

[Bill Guyer, Chief Development Officer]

40:20 Great. Thank you for that question. So in 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 will remind you, we saw great results from the Phase II 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 II study was not powered to see a difference in OS. And to be honest, there is no study or no drug that has shown a statistic significance and improvement in overall survival in these types of patients with 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. But we will see when we reach that total, when we get the total events of 120 events, which we hope to see later this quarter.

[Tazeen Ahmad, Bank of America]

41:21 Okay. And would that be in a press release that you would reveal some updated data.

[Bill Guyer, Chief Development Officer]

41:26 Once we get the data, we will make it available, as soon we get the data.

[Tazeen Ahmad, Bank of America]

41:31 Okay. Excellent. Thanks for taking my questions.

[Joseph Belanoff, Chief Executive Officer]

41:34 Thanks Tazeen.

[Operator]

41:37 Thank you. Our next question comes from Michelle Gilson with Canaccord Genuity. You may proceed with your question.

[Michelle Gilson, Canaccord Genuity]

41:44 Hi, thank you for taking my question. So 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 towards 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 syndrome. And maybe some of those COVID delays in diagnosis starting to subside?

[Joseph Belanoff, Chief Executive Officer]

42:33 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]

42:40 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 it. So that's been built in, assuming that we're going to see easing of some of the restrictions that have existed for quite a window of time here, where practices have been close to becoming specialists and in some cases some of their patients. The other piece that I haven't touched on yet today is our 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 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. 43:37 So to your second part of your question around diagnosis. Patients are -- when they are able to see their doctors and their 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 half through, the multitude of tests and following the guidelines. And as again restrictions have eased, these patients are seeing their physicians more frequently through that are able to get sort of the multiple tests that they need to be diagnosed and through that we've seen an increase in the diagnosis.

[Michelle Gilson, Canaccord Genuity]

44:15 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 in sort of the biggest drivers that you would expect for relacorilant to be able to grow the market if it's 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 syndrome market for relacorilant versus Korlym.

[Joseph Belanoff, Chief Executive Officer]

45:00 Yes, yes. Michelle glad you ask. And it's an important question. So first, again and I know we have listeners have various degrees of their understanding, Korlym is an excellent medication, people have hypercortisolism. It really turns that down in a way which makes for a much more of a normal situation. And I'd just remind people, it's now, I missed a decade ago. But when we did our clinical study, which got the drug approved 87% of the patients got substantial clinical improvement as adjudicated by outsiders. So it really works in that regard. And so, we love Korlym. Unfortunately Korlym were active ingredient. It is not a specific drug for cortisol, it does a couple of things, which actually are problematic. 45:54 One and it was known as this before it was ever used for Cushing syndrome is a potent progesterone receptor antagonist. And as you know, as we've said, it's the active ingredient what's frequently call the abortion pill. So nothing to do with cortisol it's affected entirely by progesterone receptor antagonism and so our full discovery program was really to see if we can find a mechanism which could take away that problem. And in fact our wonderful Head of Medicinal Chemistry at that time is our Chief Scientific Officer, Hazel Hunt was actually able to create 3 different series of compounds of which relacorilant comes from [indiscernible] series and do exactly that. 46:33 Potent cortisol modulation, no effective progesterone. And so that was really sort of first and obvious benefit to take away that particular medical problem and frankly political problem. But the second one is, it turned out to really something that we discovered. As we were developing it which is that, is the relacorilant unlike Korlym doesn't seem to cause what's called hyperkalemia 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. 47:11 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]

47:44 Great. Thank you. And maybe if I can just ask one more. The Phase Ib 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 of the LFT signals were may be related to the magnitude or the rapidity of that you saw in the Phase II around the liver fat reductions.

[Joseph Belanoff, Chief Executive Officer]

48:13 Michelle, I'm going to have to keep you on the edge of your seat. We do actually -- I'm not -- tonight we have information, it's an open label study, but we will resell all that information only after accumulated.

[Michelle Gilson, Canaccord Genuity]

48:26 All right, thanks for taking my questions.

[Joseph Belanoff, Chief Executive Officer]

48:29 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]

48:40 Hey, good afternoon, Joseph. And thank you for taking my question. So I just follow up on the NASH study. Could you give us more color on the enrollment status for the dosing escalation part?

[Joseph Belanoff, Chief Executive Officer]

48:56 Yes. Bill would you like to answer that question.

[Bill Guyer, Chief Development Officer]

48:59 Sure. So for the enrollment status. I mean our Phase Ib study is started with multiple cohorts looking at lower doses of miricorilant. Each cohort was gated by valuation safety and efficacy every 6 weeks, and we saw great enrollment in the end of the year and even at the beginning of this year. We see great excited by the investigators and for patients into this trial. So we're seeing good steady enrollment for this trial.

[Joseph Belanoff, Chief Executive Officer]

49:25 And I'll just add to that, Arthur [indiscernible] important thing, we really think we have hoped a big one here. We really do think that this medication is very potent, all the investigators we work with have really describe it as perhaps not just a potent medication, but the most potent medication that we have ever seen for a [indiscernible] from the 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 some fastest dose as quick as we can, we can't tell you exactly when that is, because the protocols are in the process of running.

[Arthur He, H.C. Wainwright]

50:19 Thank you for that additional color. And regarding the GRATITUDE study, beside the -- could you remind like, besides the way lot data, is there any biomarker data we can get from the data update later this year?

[Joseph Belanoff, Chief Executive Officer]

50:40 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]

50:54 That's great, thanks for that. The last one I would want to pick up your brand for -- considered the current macro environment what's your appetite for the BD idea?

[Joseph Belanoff, Chief Executive Officer]

51:11 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 just sort of get you to the bottom line, un pitched ideas on a very regular basis. But let me really say 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 this program is going to their finish line, get us the best results we can and then we are not distracted from doing that in the optimal way. 51:59 So yes, we take a look at a lot of things that have come in the door, some are easy to dismiss, some require more thought and then obviously some -- it's potentially [indiscernible] something could be so attractive that we really have to give a serious thought. But keep in mind, that's not our priority, our priority is really to optimize cortisol modulation and all of the diseases that we feel can be effective in treat.

[Arthur He, H.C. Wainwright]

52:25 Sounds great. Thank you. Thank you for answering my questions.

[Operator]

52:30 Thank you. Our next question comes from Greg Fraser with Truist Securities. You may proceed with your question.

[Greg Fraser, Truist Securities]

52:38 Thanks for taking the follow-up. I just want to see if there's been any progress or if there is anything new to report on than New Jersey, USA investigation? Thanks.

[Joseph Belanoff, Chief Executive Officer]

52:49 Yeah. I'm happy to happy to answer that. So there has been no developments put forth. But I think there are a couple of things that folks should keep in mind as they think about that. And some -- and before I sort of talked about that. Let me just back up and give just a little bit of background for those who aren't familiar with what we were talking about. Back in December of last year we disclosed that we 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 commercial business, our relationships with health care providers, our promotional practices to Korlym prior authorization information, things of that nature. 53:36 And I think the first thing to keep in mind is that, a subject matter covered by those documents is the same as the sort of swirled which has been kicked up around us for years, starting with the short seller report that was published back in January in 2019 which led sort of as night follows day, it's a mysterious class action suit that we are grinding through right now. And now we have this Department of Justice. And the first thing that's to keep in mind. It's sort of an entire ecosystem. 54:12 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. First and foremost, that's the right thing to do. But what is not as commonly seen where it is don't never stated is that many companies, not all, but many companies while the cooperate simultaneously hope that things will move it slowly. 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 that. Because we believe that the best half forward, the best outcome for course of and our shareholders is to get all the facts before the government as quickly as we can and that's what we are going to do. So nothing to announce in the moment, but I think it's important for folks to keep those couple of things in mind.

[Greg Fraser, Truist Securities]

55:19 Great, thanks for the movements.

[Joseph Belanoff, Chief Executive Officer]

Thanks for all those who 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]

55:47 Thank you. This concludes today's conference call. Thank you for participating. You may now disconnect.