Corcept Therapeutics Inc (CORT) 2021 Q1 法說會逐字稿

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

At this time, I'd like to turn the conference over to Atabak Mokari. Please go ahead.

Good afternoon. I'm Atabak Mokari, Corcept's Chief Financial Officer. Today, we issued 3 press releases: one, announcing the positive outcome of our 178-patient Phase II trial of relacorilant in combination with nab-paclitaxel to treat patients with platinum-resistant ovarian cancer.

Second, announcing markedly decreased liver fat in patients in our Phase II trial of miricorilant as a potential treatment for nonalcoholic steatohepatitis of NASH; and the third, providing a clinical update and announcing our financial results for the first quarter. Copies of all of these are available at corcept.com. Our complete financial results will be available when we file our Form 10-Q with the SEC.

Today's call is being recorded. A replay will be available on 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 statements expressed or implant.

These risks and uncertainties include, but are not limited to, our ability to operate our business and achieve our goals during the COVID-19 pandemic and thereafter, including our ability to generate revenue and cash reserves sufficient to fund our commercial operations and development programs; the availability of competing treatments, including generic versions of Korlym; the initiation or outcome of litigation; our ability to obtain acceptable prices or adequate insurance coverage and reimbursement for Korlym, and the risks related to the development of our product candidates, including their clinical attributes, regulatory approvals, mandates, oversights and other requirements and the impact of the COVID-19 pandemic on our employees, consultants and vendors as well as on physicians, patients, insurers, regulators and the practice to medicine general. These and other risks are set forth in our SEC filings, which are available at our website and the SEC.

On this call, forward-looking statements include those concerning the safety, efficacy and other clinical and commercial attributes of relacorilant, exicorilant, miricorilant, CORT 113176, and our other selective cortisol modulators for the treatment of patients with solid tumors, liver disease, hypercortisolism, antipsychotic-induced weight gain, amyotrophic lateral sclerosis or ALS and other disorders.

The progress, enrollment, timing, design and results of our clinical trials, our revenue guidance, cash flow and expected growth, our stock repurchase program and its intended funding sources, the impact of the COVID-19 pandemic on our commercial operations, financial performance, clinical development programs, physicians, payers and patients and expectations regarding our financial performance in the clinical development program after the COVID-19 dynamic is controlled.

The timing, cost and outcome of litigation, including our lawsuits against Teva, Sun and Hikma Pharmaceuticals, have us appeal its defeat in the post-grant review and brought before the Patent Trial and Appeals Board known as PTAB. As well as the scope and protective power of our intellectual property and the benefits of orphan drug designation. We disclaim any intention or duty to update forward-looking statements.

I will now provide a financial update. Our revenue in the first quarter of 2021 was $79.4 million compared to $93.2 million in the first quarter of 2020. First quarter GAAP net income was $23.5 million compared to $30.1 million in the same period last year. Excluding noncash expenses related to stock-based compensation and the utilization of deferred tax assets, together with related income tax effects, non-GAAP net income in the first quarter was $25.8 million compared to $41.2 million in the first quarter of 2020.

COVID-19 pandemic depressed our first quarter financial results. Many physicians have not been able to see patients frequently enough to diagnose and treat a complex disorder such as Cushing's syndrome. Pandemic-related public health restrictions and other protective measures have made it hard for physicians to guide patients receiving Korlym to an optimal dose, an exercise, which requires multiple in-person visits and careful monitoring.

We are confident our business will grow as the pandemic is brought under control. There remain many patients who might benefit from Korlym and many physicians who have yet to prescribe it. Our modified revenue guidance of $355 million to $385 million assumes that pandemic-related restrictions will ease substantially by the third quarter of this year.

Our cash and investments totaled $454.8 million at March 31, 2021. In the first quarter of this year, we repurchased 2.1 million shares of our common stock, 1.3 million shares pursuant to our stock repurchase program and 800,000 shares in connection with the net exercise of employee stock options. The total cost of these repurchases was $50 million. Under the current terms of our stock repurchase program, $156.8 million remains available for the repurchase of shares. We will determine the timing and size of future repurchases, if any, based on market conditions, our stock price and other factors.

And now Charlie Robb, our Chief Business Officer, will provide the legal update. Charlie?

Thanks, Atabak. In March 2018, we sued Teva Pharmaceuticals in Federal District Court to prevent it from marketing a generic version of Korlym in violation of our patents. Originally, trial was set to start February 2, 2021. Last quarter, the court vacated that date and ordered the parties to be ready for trial by March 17. The court then vacated that date as well. We expect the complete discovery by the end of this month. No trial date or trial-ready date has been set. Last month, we asked the court to issue an order, known as summary judgment, deciding the case in our favor. Summary judgment is a procedure whereby judges can side a case without holding a trial. In the court where we have sued Teva, a party needs the court's approval even to request summary judgment. We received that approval in March. We filed our motion on April 8, basing it on only one of our patents, the 214 patent. Having agreed to hear our summary judgment motion, the court will consider the brief submitted by us and Teva, briefing will be complete in June 9, and we'll then review the material facts of our dispute.

The court concludes the material facts are not in dispute, it can decide the case without holding a trial. We believe the court has all it needs to decide in our favor. Having lost the PGR, Teva cannot now challenge the 214 patent's validity in District Court. Teva only argue that its product would not infringe position, we believe, has no legal or factual support. If the court disagrees and denies our motion, we will proceed to trial sometime later this year or perhaps next.

If the court grants our motion, we will have won the case. Teva will be barred from marketing generic Korlym until the 214 patent expires in 2037. Teva can appeal its loss, of course, although the court's bar would remain in place until the appeal is resolved, process, which typically takes 12 to 18 months.

In parallel with our summary judgment motion, Teva has, as expected, appealed as PTAB loss to the Federal Circuit Court of Appeals. Briefing in this matter will be complete June 11 with the Federal Circuit decision most likely coming about 12 to 16 months after that.

Sun Pharmaceuticals is also seeking the market generic Korlym. A lawsuit against Sun has stayed final FDA approval of Sun's proposed product until the earlier of December 8 of this year and the decision by the District Court that our patents are invalid, unenforceable or not infringed. Our dispute with Sun is separate from our litigation against Teva and is following its own more indolent time line. There is no trial date or discovery deadlines in this action.

Finally, on February 1 of this year, we received notice of another ANDA filer, Hikma Pharmaceuticals. On March 12, we sued Hikma in the same Federal District Court that is adjudicating our cases against Teva and Sun. Hikma's answer is due May 17. With respect to all of these disputes, we are confident in the strength and validity of our intellectual property, which we will continue to assert vigorously.

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

Thank you, Charlie. Before I turn to our recent clinical developments, I want to underscore a point Atabak made about our financial results. Pandemic-related public health measures and the steps both physicians and patients have taken to reduce their risk of infection, have made it very hard for our business to grow. Diagnosing and treating patients with the complex disease, such as Cushing's Syndrome, requires frequent close in-person contact. Since March of last year, this level of contact was impossible.

Only now and not everywhere and not fully, our contact's starting to move towards their pre-pandemic state. We are confident conditions will continue to improve. Our revised revenue guidance of $355 million to $385 million assumes that by the third quarter of this year, the pandemic will be brought under control, public health restrictions will ease and our growth will resume.

Leading physicians increasingly believe that the number of patients with hypercortisolism substantially greater than once thought. Korlym is an excellent treatment for hypercortisolism. Relacorilant, if approved, will be even better. The foundation of our business, an effective life-saving medication promoted by a dedicated commercial team that puts the interest of patients first, remains rock solid.

With confidence in our commercial business as my backdrop, I will say this. The positive findings we released today in oncology and liver disease are the most consequential for Corcept since we announced the results for Korlym's most pivotal trial. We've taken a big step toward achieving our long-held goal of becoming a company that harnesses cortisol modulation to provide treatments for patients with a wide range of serious disorders.

From the beginning, Corcept's research and development efforts have built on the hypothesis that cortisol activity plays an important role in many diseases and the cortisol modulation can be a powerful therapeutic mechanism. We have proven this hypothesis with respect to one medication and one disorder, Korlym for the treatment of patients with Cushing's Syndrome. Forum's commercial success has provided and will continue to provide the funds needed to continue adding to our large portfolio of proprietary selective cortisol modulators and to develop the most promising of these molecules. Many of these molecules are attractive candidates for development. Like Korlym, they bind strongly to the glucocorticoid receptor or GR. Unlike Korlym, they have no affinity for the progesterone receptor and so don't cause on a Korlym's most serious off-target effects.

Beyond sharing the qualities of strong cortisol modulation and not perturbing 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, while others have more systemic effects. These diverse qualities have allowed us to initiate clinical trials in a wide variety of disorders, including ovarian, pancreatic, adrenal and prostate cancer, antipsychotic-induced weight gain and NASH and, of course, Cushing syndrome.

We are now planning a Phase II trial in patients with ALS, and we have additional compounds in Phase I or latter stages of preclinical development. Cortisol modulations broad clinical promise has given us many opportunities to help patients, which brings me to our announcements today.

I'll begin by discussing our positive results in ovarian cancer. Our oncology program is testing 3 mechanisms, first postulated by investigators at the University of Chicago. Our successful trial in women with advanced ovarian cancer concerns apoptosis, the program cell death chemotherapy is meant to induce. Cortisol suppresses apoptosis.

In our trial, addition of the selective cortisol modulator relacorilant, enhance the effect of chemotherapy in some women by blunting this anti-apoptotic effect. Our study is a controlled multicenter Phase II trial. 178 women with platinum-resistant ovarian cancer were randomized in 1 of 3 treatment arms. 60 women received 150 milligrams of relacorilant intermittently, the day before, the day of and the day after their weekly nab-paclitaxel infusion.

58 women received in addition to nab-paclitaxel a lower daily relacorilant dose of 100 milligrams per day with titration of 150 milligrams per day permitted at the investigator's discretion. 60 women received nab-paclitaxel alone. The trial's primary endpoint was progression-free survival or PFS. The women who participated in our study were very ill. All had experienced disease progression despite prior lines of therapy, the median number of prior treatments was 3. I'm delighted to say that relacorilant benefited many of these women. Those who received relacorilant intermittently, exhibited a statistically significant decline in their rate of disease progression when compared to the group that received nab-paclitaxel monotherapy. Their hazard ratio was 0.66, with a p-value of 0.038. The median PFS was 5.6 months, 1.8 months longer than the control groups, which is 3.8 months.

Safety data and tolerability data for the 2 groups were comparable. The women who received relacorilant every day also saw their disease progress more slowly. Their median PFS was 1.5 months longer than the controls groups. Their hazard ratio was 0.83, although this result was not statistically significant. We believe, and more importantly, our investigators believe that these results, a 1.8 month increase in PFS without an increase in side effects, are clinically meaningful.

The trial also tracked important secondary endpoints, including duration of response and overall survival. Overall survival understandably has not yet reached its final values. In the next few months, we will also receive data quantifying the degree to which each women's tumors express glucocorticoid receptors. If the degree of the tumor's GR positivity correlates to response, we may be able to enrich the population of patients we study next.

We will monitor our developing data closely as we plan our Phase III pivotal trial. Meanwhile, our Phase III RELIANT trial in patients with metastatic pancreatic cancer is on track to provide interim data by the end of this quarter. Advanced pancreatic cancer is a truly dire disease with no good treatment options. The expected response rate of nab-paclitaxel monotherapy is 0.

RELIANT has a planned enrollment of 80 patients with a planned interim analysis of data from the first 40 patients to enroll. RELIANT's primary endpoint is objective response rate with secondary endpoints, including progression-free survival, duration of response and overall survival.

Another mechanism we are studying concerns cortisol's ability to stimulate tumor growth in men with castration-resistant prostate cancer. Cortisol stimulation is a major reason patients treated with the widely prescribed androgen receptor antagonist enzalutamide, eventually experience resurgent disease. Deprived of androgen stimulation, their tumor switched to cortisol activity as a growth pathway. Our hypothesis is that adding a cortisol modulator to androgen deprivation therapy will close this tumor escape route.

We are conducting a dose-finding study of our selective cortisol modulator, exicorilant, combined with enzalutamide in men with castration-resistant prostate cancer and remain on track to conclude it next quarter.

Our third mechanism concerns cortisol's ability to reduce inflammation and suppress the immune system, effects that are often beneficial in healthy people. Unfortunately, in patients with solid tumors, cortisol suppression of the immune system diminishes the effectiveness of immunotherapy. We are conducting an open-label Phase Ib 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. We believe these patients' cortisol excess may be counteracting the intended effects of pembrolizumab, which is rarely effective as monotherapy in this group of patients.

Our trial is evaluating with a relacorilant can treat these patients' Cushing's Syndrome by reducing the effects of excess cortisol activity and by reversing cortisol-induced immune suppression also allow pembrolizumab to achieve its full cancer-killing effect. We plan to enroll 20 patients in 5 sites in the United States. The primary endpoint is objective response rate of secondary endpoints, including progression-free survival, duration of response and overall survival.

I will now turn to our program in metabolic diseases and the recent findings with our proprietary selective cortisol modulator, miricorilant, in patients with presumed NASH, serious liver disorder. Last December, following positive results in animal models where miricorilant prevented and reversed fatty liver disease and liver fibrosis. We initiated a double-blind placebo-controlled Phase IIa trial with a planned enrollment of 120 patients with presumed NASH. A safe presumed NASH because as is typical at this stage, we relied on noninvasive liver scans to qualify study participants.

To our surprise, 4 of the first 5 patients who received miricorilant for 4 weeks exhibited sharp increases in the liver enzymes, AST and ALT. We immediately suspended dosing and enrollment to investigate. We learned 2 things: first, after discontinuation of miricorilant, the increased liver enzymes resolved without further incidents; second, all of the patients who experienced elevated AST and ALT also experienced large and rapid reductions in liver fat. We have powered the trial to detect a 30% reduction after 12 weeks. These patients exhibited reductions ranging from 38.5% to 73.8% after receiving miricorilant for just 4 to 6 weeks. Further, the MRIs that measured these data were performed 19 to 64 days after cessation of dosing, which suggests either that the reductions have been greater when dosing actually stopped when the miricorilant's effect is durable or some combination of the 2.

The purpose of a Phase IIa trial is to confirm that a drug is active and to determine appropriate dose range for further study. By that measure, this trial was a great success. Reductions in liver fat of this magnitude are rarely seen over any period of treatment. It may be that the rapidity of miricorilant's fat-reducing effect actually caused AST and ALT to rise. The liver may shed that by breaking it down into fatty acid, which in excessive amounts, irritate the liver. We'll now perform study to determine miricorilant's optimum dose and dosing regimen.

We are excited to advance miricorilant as a treatment for patients with NASH. As many of you know, we are also evaluating miricorilant as a potential treatment for patients with another serious (inaudible) disorder, antipsychotic-induced weight gain. In the United States, 6 million people take antipsychotic medications such as olanzapine and risperidone to treat illnesses such as schizophrenia, bipolar disorder and major depression. While these drugs are very effective, they exact a steep price in the form of rapid and sustained weight gain, cardiovascular disease and other metabolic disturbances. Patients can gain more than 50 pounds while taking these medications and their life expectancy has decreased on average by 20 years due in part 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. These trials seek to build on the positive data from our study of miricorilant in healthy subjects. Last year, we completed a Phase Ib 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 an AST and ALT. We plan to publish a paper describing these results later this year.

The GRATITUDE trial is evaluating whether miricorilant can reverse recent antipsychotic-induced weight gain. 100 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 II study is testing miricorilant as a treatment for long-standing antipsychotic-induced weight gain. 150 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 will be 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 expect to complete enrollment in GRATITUDE II by the end of this year and a GRATITUDE in mid-2022.

My discussion of our development program in Cushing's Syndrome, which continues to progress, can be briefed. As many of you know, we are evaluating relacorilant, our planned successor to Korlym for the treatment of hypercortisolism in 2 Phase III trials: GRACE and GRADIENT.

To repeat what I said earlier, relacorilant is a selective cortisol modulator. Like Korlym, it achieves its effects 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. Our GRACE trial has a planned enrollment of 130 patients with any etiology of Cushing's Syndrome at sites in the United States, Canada, Europe and Israel. We are excited for it to complete. 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 of Cushing's Syndrome. There were no relacorilant-induced instances of endometrial thickening or vaginal bleeding, and also no drug-induced hypokalemia.

We and our investigators are eager to take race to the finish line. We expect GRACE to serve as the basis for our NDA submission in Cushing's Syndrome, which we remain on track to submit in the second quarter of 2023.

Our second Phase III trial, GRADIENT is studying relacorilant's effects in patients whose Cushing's Syndrome is caused by an adrenal adenoma or adrenal hyperplasia. Patients with the 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 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 CORT 113176, which has shown promise in animal models of ALS. We are discussing our proposed development plan with leading clinicians in the FDA and plan to initiate a Phase II trial by the end of this year.

In conclusion, our belief has always been that cortisol modulation can help treat many serious disorders. Korlym for patients with Cushing's Syndrome is one such treatment. The clinical findings we announced today, positive results in women with platinum-resistant ovarian cancer when relacorilant is combined with nab-paclitaxel and large and rapid reductions in liver fat in patients with presumed NASH who received miricorilant, take us a big step towards proving cortisol modulations broad worth.

While the pandemic depressed our first quarter financial results, we are confident growth will resume as conditions improve later this year. Even in a difficult quarter, our commercial business generated more than enough cash to fund our advancing development activities. At present, our oncology program is evaluating 2 of our proprietary cortisol modulators in combination with 3 different anticancer agents in 4 tumor types. Meanwhile, our metabolic program is conducting important trial in NASH and antipsychotic-induced weight gain.

We continue to enroll patients in our flagship Phase III trials of relacorilant in Cushing's syndrome and further studies are planned in other indications. We will advance CORT 113176 to treat patients with ALS later this year, new early-stage compounds continue to advance towards the clinic.

The breadth of our program reflects the power of our fundamental scientific hypothesis. Cortisol modulation is a powerful therapeutic modality. We have proven that in patients with Cushing's Syndrome. Today, we added to the body of evidence that proves its worth for patients with other serious disorders. I'll stop here to answer questions.

(Operator Instructions) And we'll go first to Chris Howerton of Jefferies.

Congratulations on, certainly, the ovarian cancer data, great result there. So maybe just a couple of questions from me. First on that program itself. With the -- maybe if you could give us just some of your initial thoughts in terms of what the Phase III trial might look like there? And I guess, is there any opportunity whatsoever to have a discussion with the agency to say, look, these are clinically meaningful data, is there any opportunity for accelerated approvals? So I guess that's one general question, or I suppose, 2 there.

A quick one for Charlie on the legal update. Just wanted to clarify with respect to the PGR that Teva can no longer challenge the validity. Is it all arguments of validity or just those that were used during the PGR proceeding?

And then the final question just relates to the commercial business. Obviously, I think the discussion around dose titration and getting the right new patients to the right dose certainly makes a lot of sense. And I just wanted to check in on some of the status of existing patients if there's any kind of changes with respect to discontinuation rates.

Chris, thank you very much for all of those questions. And I'll take a breath just for a second, and I'll assign these questions to various members of my executive team who are here, and then I'll come back at the end. So first, let's take your patent question to Charlie.

Yes. Chris, so Teva is barred from using in District Court any arguments it raised or could have raised before the patent office. And that's actually quite a high standard. It can't just be well, we didn't argue this because we didn't think of it at the time, but now we've thought of it, so we'd like to throw it out there. They have to have essentially a very good reason. And the classic example would be the -- they learned something from discovery in the litigation that they did not know at the time of PGR. But in our case, discovery was over before the PGR was over. So nothing. So I think that they've got this very limited path, and they will not be able to challenge to validity in District Court.

All right. A question you asked, Chris. I'll let Andreas Grauer, our Chief Medical Officer, answer that. He'll be able to answer it, which is potential design for the Phase III study.

Yes. Thank you for the question. And obviously, that is what we are working on very hard right now. We will compare the combination of relacorilant and -- of relacorilant, nab-paclitaxel. And I think we will look at the intermittent dose that, based on the data that we have, seems to be the more effective use of relacorilant in this particular tumor type. And we'll have to figure out what the best comparator to that is. Most likely, I think we will pick paclitaxel. That makes a lot of sense as a comparator in a large freight trial.

Alternative considerations are, we might look into a dealer's choice comparator where we would give investigators the opportunity between a number of established standard and approved treatments for this condition.

Size will have to be figured out dependent on the expected overall survival benefit that we'll be looking for. And that is obviously also a key factor from the ongoing trial that we're still waiting for. It's not gating planning, but it will gate the launch of a Phase III trial to see the overall survival data from this study.

And Chris, let me handle your other question, which, of course, is a really intriguing one. So as Andreas just said, we're already really at the heart of the serious stage of planning for a Phase III study. And your question was is it possible that the data would be sufficient actually at the end of this study, the result's all in to take that to the FDA to submit an FDA -- submit an NDA?

And I'll give you the top line answer to that question is it's a slim possibility. Or really, our expectation is that we will have to do a Phase III study. But let me give you a little bit more color on that. It's highly likely that the primary endpoint for a Phase III study, and in fact, for approval is overall survival. And we're very pleased, obviously, with the statistically significant improvement in progression-free survival. Overall survival is still being determined at this point. But -- and I'll leave it at this because obviously, that data will come out towards the end of the year, and we want to release other data as we have it.

We like what we're seeing. We promised nothing at this point. But I can imagine an unusual circumstance where that data on overall survival was so strong that it could lead to a discussion with the FDA at that point. I don't want anybody to count on that. I think it's not the likely direction. But yes, we're thinking about that in the same way that you are. The last questions you asked were commercial questions, Chris. And I'm going to push us over to Sean Maduck, who is our Chief Commercial Officer.

Chris, thanks for the questions. Your question was a 2-part one. One was around for discontinuation of the existing patient base. Is there -- have we seen a change there? And the answer to that is no.

And your next question was around titration. So I thought I'd spend a minute talking about from what success looks like and what we need for sort of Korlym growth. There's really 3 key factors that were affected by the pandemic. One is, of course, it's the ability to educate doctors on hypercortisolism and Korlym.

Two would be doctor's ability to actually see their patients multiple times for extensive workup prior to a diagnosis. And then the last one being once a patient actually starts Korlym, the frequent follow-up that's required with their physician to monitor progress and to guide appropriate titration.

And with new patients that have come on during the pandemic, that's something that's really been a challenge. New patients have either not titrated or titrating at a much more slow rate to get to their optimal dose. And again, directly related to their ability to see their position with the appropriate frequency or even their access to labs or their willingness to go and get labs that they may need to do so. So in time, as things open back up, we believe that, that titration will catch up. But for the time being in aggregate, this has decreased our average overall dose.

We'll go next to the Arthur He of H.C. Wainwright.

Congratulations on the ovarian data. And I just want to -- so at which venue could we expect the overall survival data for the informative study?

I'm Sorry, I didn't hear the question.

What we're going to release...

Which venue -- yes. At this point in time, the answer is, first, overall survival is likely to take some amount of months from here. We will get other data before we actually get the final overall survival date. And all I can tell you is that we will present this to conferences as quickly as we can, just depending on conference deadline. So we're really examining that as we go forward here. But whatever we receive in any kind of bolus of things, we will send out to a conference and we will present it there. I can't say with certainty which ones yet.

Okay. That's great. And my second question is regarding to the NASH study. So I'm just wondering, beside the trends in ALT and AST elevation, is there any other safety signal observed in these 4 patients?

I'm going to give you, again, back to Andreas Grauer.

Yes. No, that was the safety signal that we did observe and which obviously, that was what we had seen first, right? That's why we stopped dosing and halted the trial, the benefit that we observed that came after because we did a thorough investigation of all aspects of what happened to these patients. And quite frankly, we were surprised to see such an improvement in liver fat so quickly, and we shared that with some of our advisers, and they were surprised. They had never seen something like quite like that before, which, again, encouraged us to say what we really want to try to figure out how we can find a sweet spot and find a dose or schedule of giving this drug in a way that is both effective and safe.

But Arthur, the short answer to your question is we did not see anything besides elevated liver function tests at the time that we halted dosing.

That's great. And just a follow-up on the efficacy signal wise. The fat reduction is really impressive. Just curious, have you guys measured or take a look at the fibrosis for these patients?

Yes. So first of all, this was noninvasive, right? So this was not a biopsy trial, so we didn't look at fibrosis in this particular trial. We also did not repeat like, for example, a FibroScan measurement, the MRI data is really the only thing that we have. Seeing a change in fibrosis within 4 weeks, which was the treatment duration, most of these patients would be absolutely unexpected. But we wouldn't know. We didn't know.

But just, Arthur, for comparison, in almost all the studies, the issue -- the threshold number is 30% in terms of fat reduction is presumed to -- and actually, there are studies which show really correlates with reduction in NASH in fibrosis and NASH. And that's how we have set our 30% target, and that's how I think others do the same thing.

So I'm just going to reiterate what Andreas said. It was really extraordinary to see after such a short period of time for these patients to have much greater in some cases, reduction in fat than 30%. And so it's really a potent medication and now we really have to figure out how to harness it.

And so we'll move to our next question from Tazeen Ahmad of Bank of America.

Congrats as well for me on the ovarian data To go back to Korlym for one second. You talked in depth about all of the ways in which COVID has impacted sales, and that is consistent with what we are hearing from other companies across multiple indications. I am curious to know if you're getting any feedback from your sales force on if they're seeing any kind of competitive risk from the Recordati drug that recently launched, and if it's just feedback from a nonquantitative aspect? Would be curious to hear your thoughts on that. And then I have a couple of follow-ups.

Sure, Tazeen. I'm going to pass you back to Sean, who really runs all of the Korlym business.

Yes. Thanks, Tazeen, for the question. The short answer is no, we're not seeing an impact on our business from ISTURISA specifically, which you're referencing. Not seeing virtually any impact on our existing base, and we continue to add patients at Korlym at our expected rate.

I just want to remind everybody on the call that ISTURISA is actually approved for Cushing's disease, which is a subset of Cushing's Syndrome, and Korlym, of course, is approved for the broader syndrome, which encompasses all etiologies of the disease.

Okay. And then while we're on the topic, you had mentioned some factors to highlight, including getting doctors educated about Korlym. Now for a drug that's been on the market, it's a relatively mature drug. What percent of the doctor population -- targeted doctor population do you think is still yet to be fully educated on the benefits of the drug?

Yes. So I mean we have -- we reach out to as best we can sort of all endocrinologists within the country. I mean ultimately, we believe that every one of them could potentially have a patient with Cushing's Syndrome. We target a list of 1,500 to 2,000 with greater frequency. But there are many that have yet to prescribe. So there's real opportunity within the existing endocrinology base to write their first prescription of Korlym.

Yes. And what I'd add to that, Tazeen, is that as Sean said, we focus on about 1,500 to 2,000 of about 7,000 or 8,000, But as I know, I know you know this that most endocrinologists these days are diabetologists. They're not really looking at other things like Cushing's Syndrome. But we now actually think that, in fact, as a result of peer-reviewed publications and more looking to this, is that some of those diabetologists who have not previously taken Cushing's Syndrome is something that they really want to take a look at are starting to do that. And that's what makes us hopeful that we can reach all of the patients who have pitching syndrome as opposed to the fraction we've reached a far.

Okay. Cool. And then maybe one question on the RELIANT study. If I could, you are going to have this interim rate of 40 patients. What is the bar of efficacy that we should be looking for? And could you potentially file after that interim read?

I'm going to pass you to Andreas in a second, but I guess, could is a pretty broad term. It is definitely not our expectation that, that would be possible to file after just those 40 patients. And the bar, I think, as we've mentioned in previous calls, when you compare to a 0% response rate and something like above 20% is something that everyone would say, "Well, that must be your medicine." If it's 10% to 20%, you have to think about there's something going on. And if it's below 10%, it's hard to know whether that's different than what you would ordinarily expect.

And we're very interested in seeing. Now if we sort of pick the great white whale of cancers, I mean pancreatic cancer is terrible and metastatic pancreatic cancer is really terrible. So we'll just have to wait and see where that is.

Yes. I ask that only because of the undermet need.

Yes. No, no, right. And that, of course, is the other side of it is that the bar is lower, of course, because of that.

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

My congrats for the ovarian cancer top line results here. I just wanted to dig in a little bit to the differences that you're seeing in the dosing regimen and what to make of those? I guess maybe how many patients in the 100-milligram daily dose were up titrated to 150 milligrams in the study?

Matt, I'm going to give you -- the questions over to Andreas.

Yes. So overall, 30% of the patients in the 100 milligram dose were up titrated. Not all of them to 150, about 2/3 of the one that were up titrated were up titrated to 150. So that -- those are the exact data.

Yes. The other thing, and Matt, maybe this is a longer answer, so taking offline. There really is a theory as to why intermittent dosing actually might be effective in terms of the glucocorticoid receptor genes that are sort of needed at that zone. And of course, treatment is always a combination of efficacy and potential for adverse events.

And so there's a real theory behind intermittent dosing. It wasn't just a random event. And it was interesting to see that, in fact, it was both superior at this point to everyday therapy at a lower dose and then it was superior to the background therapy with (inaudible).

Okay. And then in the study, what's your sense in terms of the overall response rate that you're seeing? And was there a differentiated overall response rate in the 2 dosing arms?

All right. So I don't want to give too much information because from one of our early questions, we don't want to spoil our chance to present this at important conferences. And so really want to limit as to what we would materially have to talk about. But I can give you a general answer to that question, which is that the overall response rate, and I say this without specific numbers, was relatively the same among the groups. But what was really different was the duration of response to those who responded, and that's why (inaudible).

Okay. And just shifting gears to the GRACE study for Cushing's Syndrome. What's your sense in terms of enrollment there? Is it starting to accelerate now as we turning the corner in the pandemic here, hopefully, at least in some parts of the world. Are you seeing an acceleration in enrollment?

Yes. I think we're -- enrollment starts to pick up again. And the winter was pretty disappointing for us. But now in the spring, we're seeing signs of progress, both in the U.S. and in Europe. In Europe, obviously, somewhat slower than in the U.S. So we're positive and hopeful that we can deliver what we told you we are planning to deliver.

Yes. And just to underscore that, just again, I know you know this Matt because you follow the story for a long time, but those you don't. This is, to some degree, a euro-centric study. We expect in the end, our overall enrollment to probably be, I don't know, 70% European, that's what it was in the Phase II study. So it's a bit more of a wildcard. But the general answer, as you know, is things are getting better, and we're, at this point, completely hopeful that we will keep our current time line.

Okay. Great. And then last question in terms of relacorilant. The increase in liver enzymes, liver function test that you're seeing in the NASH study. Can you talk about what you're seeing kind of across the board in general with relacorilant in other indications, other patient populations? Are you seeing any indications of liver enzyme increases.

Matt, I just want to clarify one thing. The drug in the NASH study and for instance antipsychotic-induced weight gain study is a mere correlate. relacorilant doesn't -- has never produced any of that particular issue. But I'll leave you to Andreas here to answer the question related to miricorilant.

Yes. So for miricorilant, again, we've seen this elevation of liver enzymes in the NASH study. And interestingly, we've seen it in the patients that have shown the massive reduction in liver fat. So our best assumption at the moment is that those 2 events are related. And maybe we're simply resolving the liver fat too much too quickly, and we'll have to slow down the effect in order to make this palatable for the liver as a long-term benefit.

In our antipsychotic-induced weight gain studies where we are using the same doses that we have initially used in NASH. We are not seeing these changes. And therefore, there seems to be a true influence of the underlying disease on the side effect profile that we're observing.

And we'll hear next form Alan Leong of BioWatch News.

Congratulations. Going to the NASH trial. When you had this amount of fat reduction, did you see it global in the body? I know it was only 1 month, but are you seeing overall rate reductions? And were you able to even do any influences on fat reductions in the other organs?

So Alan, is this a personal question?

Yes.

In a month, Andreas can tell you if he would look at that, but we were not expecting general weight loss. Do you have an answer to that?

Especially in 4 patients, right? We wouldn't have any...

Yes. But it's an interesting question, and we will look at that out.

Yes. I'm trying to go on the side door on antipsychotic weight gain. Well, let's take the antipsychotic weight gain and any -- you've assured us that any of them, the red signals were slight. Is the current thinking of the consumption of antipsychotics puts a break on how much fatty acid gets released?

Yes, that's -- I hope everyone heard that because it's sort of an intriguing idea. So I'm just going to say it out loud, and then I'll give you my opinion that somehow antipsychotic medications are protective against this. Probably not. That's probably not the case. I think it's just coincidental.

But I want to underscore what Andreas said. Even a bit more than I might have thought, I've learned about this that NASH is really a different disease in the sense that the agent NASH hepatitis is its own real problem. You already have people who have inflammation. And so perhaps that's what makes the diseases really different.

And we're still studying about that because Andreas has really given you kind of a more global response to it. As I said, I don't think it's the antipsychotic medication. I think it's just the underlying group of patients that are not as identical as one might have thought.

That's helpful. Last question on ovarian cancer. Anything stick out for the responders? For example, was the number of prior treatments show any separation of the curves or whether they had been on Avastin before or not?

As you always do, you've push me to the end of the map. To be released, okay?

This is a wonderful time. Looking forward to what's happening in the next -- over the next several months.

Thank you, Alan. And so with that, we have used an hour of your time. Thank you. I'm very excited about what we've seen today. As I mentioned before, I really do think this is the most important result we've had since the pivotal trial of Korlym. That was 8 years ago. So this is a big day for us, and we're very glad to answer any more questions offline. I'm very glad to update you as the year goes along. Thank you.

And so ladies and gentlemen, that does conclude this call. We would like to thank you for your participation. You may now disconnect.