Corcept Therapeutics Inc

NASDAQ:CORT

Earnings Call Transcript 2021-Q1

[Operator]

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.

[Atabak Mokari, Chief Financial Officer]

Good afternoon. I'm Atabak Mokari, Corcept's Chief Financial Officer. Today, we issued three press releases, one announcing the positive outcome of our 178 patients Phase 2 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 2 trial of miricorilant as a potential treatment for nonalcoholic steatohepatitis or 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 express or imply. 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 of medicine general. These and other risks are set forth in our SEC filings which are available at our website and the SEC's website.

On this call forward-looking statements include those concerning the safety, efficacy and other clinical and commercial attributes of relacorilant, exicorilant, miricorilant, CORT113176, and our other selective cortisol modulators for the treatment of patients with solid tumors, liver disease, hypercortisolism, anti-psychotic-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 clinical development program after the COVID-19 pandemic is controlled; the timing, costs, and outcome of litigation, including our lawsuits against Teva, Sun, and Hikma Pharmaceuticals have us appeal of its defeat in the post-grant review brought before the Patent Trial and Appeals Board known as PATB, 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 non-cash 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 the complex disorders 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, and 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 are yet to prescribe it. Our modified revenue guidance of $355 million to $385 million since the pandemic-related restrictions were eased 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 remain 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?

[Charlie Robb, Chief Business Officer]

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 17th. The court then vacated that date well. We expect to 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 decide the 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 receive that approval in March. We filed our motion on April 8th basing it on only one of our patents, the 214 patent. Having agreed to hear our summary judgment motions, the court will consider the brief submitted by us and Teva briefing will be complete in June 9th and will 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 can only argue that its product were not infringed, position we believe has no legal or factual support. If the court disagrees and denies our motion, we will proceed the 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 could appeal its loss, of course. So the court's borrow 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 its PTAB loss to the Federal Circuit Court of Appeals. Briefing in this matter will be completed in June 11 with the Federal Circuit decision most likely coming about 12 to 16 months after that.

Sun Pharmaceuticals is also seeking to market generic Korlym. Our lawsuit against Sun has stayed final FDA approval of Sun's proposed product until the earlier of December 8th 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 timeline. There is no trial date or discovery deadlines in this action.

Finally, on February 1st of this year, we received notice of another ANDA filer, Hikma Pharmaceuticals. On March 12th, we sued Hikma in the same Federal District Court that is adjudicating our cases against Teva and Sun. Hikma's answer is due May 17th. 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 will now turn the call over to Dr. Joseph Belanoff, our Chief Executive Officer. Joe?

[Joseph Belanoff, Chief Executive Officer]

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 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 starting to move toward 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 is 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 a liver disease are the most consequential for Corcept since we announced the results of Korlym's 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 powerful therapeutic mechanism.

We have proven this hypothesis with respect to one medication and one disorder, Korlym for the treatment of patients with Cushing syndrome. Korlym's commercial success has provided and will continued 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 some of Korlym's serious off target effects. Beyond sharing the qualities, 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 two birth 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's syndrome. We are now planning a Phase 2 trial in patients with ALS and we have additional compounds in Phase 1 with latter stages to preclinical development. Cortisol modulation's 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 three 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 of this anti-apoptotic effect. Our study is a controlled multicellular Phase 2 trial. 178 women with platinum-resistant ovarian cancer were randomized to one of three 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 receive in addition to nab-paclitaxel a lower daily relacorilant of 100 milligrams per day with titration of 150 milligrams per day permitted at the investigators 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 three. I'm delighted to say that relacorilant benefited many of these women. Those who received relacorilant intermittently exhibited a statistically significant decline in the 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 of just 3.8 months. Safety data and tolerability data for the two groups were comparable. Women who received relacorilant every day also saw their disease progressed 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 tumors is TR positivity correlates to response, we maybe be able to enrich the population of patients we study next. We will monitor our developing data closely as we plan our Phase 3 pivotal trial.

Meanwhile, our Phase 3 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 zero. 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, 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 tumors 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. We are conducting a dose-finding study of our selective cortisol modulator exicorilant combined with enzalutamide in men with castration-resistant prostate cancer. We remain on track to conclude it next quarter.

Our third mechanism concerns cortisol's ability to reduce inflammation and suppress the immune system that's 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 1b trial of relacorilant plus the PD-1 checkpoint inhibitor pembrolizumab makes 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 ex -- 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 the 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 at five sites in the United States. The primary endpoint is objective response rate, 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, a 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 2a trial with the planned enrollment of 120 patients with presumed NASH. I say presumed NASH because as is typical at this stage we relied on non-invasive liver scans to qualify study participants.

To our surprise, four of the first five patients who received miricorilant for four weeks exhibited sharp increases in the liver enzymes AST and ALT. We immediately suspended dosing and enrollment to investigate. We learned two things. First, after discontinuation of miricorilant, the increased liver enzymes resolved without further incident. Second, all of the patients who experienced elevated AST and ALT also experienced large and rapid reductions in liver fat. We had powered the trial to detect 30% reduction after 12 weeks. These patients exhibited reductions ranging from 38.5% to 73.8% after receiving miricorilant for just four to six 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 two.

The purpose of a Phase 2a trial is to confirm that the 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 fat by breaking it down into fatty acids, which in excess of amounts irritate the liver. We'll now perform studies to determine miricorilant's optimum dose and dosing regimen. We're excited to advance miricorilant as a treatment for patients with NASH. As many of you know, we were also evaluating miricorilant as a potential treatment for patients with another serious anti-psychotic-induced weight gain.

In the United States, 6 million people take anti-psychotic 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 is decreased on average by 20 years due in part to increased cardiovascular events such as heart attacks and strokes.

We are conducting two double-blind placebo-controlled Phase 2 trials of miricorilant in patients with this disorder, GRATITUDE and GRATITUDE II. These trials seek to build on the positive data from our study of miricorilant in healthy subjects. Last year we completed Phase 1b trial in which 96 healthy subjects received olanzapine and either 600 milligrams of miricorilant, 900 milligrams of miricorilant or placebo for 14 days. Subjects who received miricorilant gained significantly less weight than those who received placebo. They also exhibited a smaller increase in triglycerides and in 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 anti-psychotic-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 anti-psychotic-induced weight gain. 150 patients with schizophrenia will receive in addition to their established dose of anti-psychotic 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 in GRATITUDE in mid-2022.

My discussion of our development program in Cushing's syndrome, which continues to progress, can be brief. As many of you know, we are evaluating relacorilant our planned successor to Korlym for the treatment of hypercortisolism in two Phase 3 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 2 efficacy and safety data was 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 GRACE 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 3 trial GRADIENT, studying relacorilant's effects in patients whose Cushing's syndrome is caused by an adrenal adenomas or adrenal hyperplasia. Patients with this etiology of Cushing's syndrome often experience a less rapid decline, but ultimately their health outcomes are poor. GRADIENT, has a planned enrollment of 130 patients and is being conducted at many of the sites participating in GRACE. GRADIENT has a 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 recognize patients.

Finally, a brief word about CORT113176 which has shown promising animal models of ALS. We're discussing our proposed development plan with leading clinicians in the FDA and plan to initiate a Phase 2 trial by the end of this year. In conclusion, our belief has always been 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 toward proving cortisol modulation's broad work.

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 two of our proprietary cortisol modulators in combination with three different anti-cancer agents in four tumor types. Meanwhile, our metabolic program is conducting important trials in NASH and antipsychotic induced weight gain.

We continued to enroll patients in our flagship Phase 3 trials of relacorilant in Cushing's syndrome and further studies are planned in other indications. We will advance CORT113176 to treat patients with ALS later this year. New early stage compounds, continue to advance toward the flag. 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 work for patients with other serious disorders.

I'll stop here to answer your questions.

[Operator]

Thank you. [Operator Instructions] And we'll go first to Chris Howerton of Jefferies.

[Chris Howerton, Jefferies]

Great, wonderful. Thanks so much for taking the questions and congratulations on certainly the ovarian cancer data, great results there. So maybe just a -- yes, of course. 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 3 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 an accelerated approval? So I guess that's one general question or I suppose two is 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 is any kind of changes with respect to discontinuation rates. Thanks.

[Joseph Belanoff, Chief Executive Officer]

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

[Charlie Robb, Chief Business Officer]

Yes. Hi, Chris. 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 they just, 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 chance the validity in District Court.

[Joseph Belanoff, Chief Executive Officer]

The question you asked, Chris, I'll let Andreas Grauer, our Chief Medical Officer answer that. Andreas will be able to answer it, which is potential design for the Phase 3 study.

[Andreas Grauer, Chief Medical Officer]

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 seen, it seems to be the more effective use of relacorilant in this particular tumor type. And we'll have to figure out what the best competitor to that is. Most likely I think we will pick paclitaxel. That makes a lot of sense as a competitor in a large Phase 3 trial. Alternative considerations are we might look into a dealer's choice competitor 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 for the ongoing trial that we're still waiting for. It's not getting planning, but it will get the launch of our Phase 3 trial to see the overall survival data from this study.

[Joseph Belanoff, Chief Executive Officer]

And Chris, let me handle your other question, which of course is obviously intriguing one. So, as Andreas just said, we're already in really the hot up -- the serious stage of planning for a Phase 3 study and your question was, is it possible that the data would be sufficient to actually at the end of this study, the results I'll have to take that to the FDA to submit an FDA, that's just submit an NDA. And I'll give you the top line answer to that question is, it's a slim possibility. Our really our expectation is that we will have to do a Phase 3 study.

But let me give you a little bit more color on that, it's highly likely that the primary endpoint for Phase 3 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 toward the end of the year and we want to release other data as we have it. We like what we're seeing. I -- we promise 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 are thinking about that in the same way that you.

The last question you asked were commercial questions, Chris. And I'm going to push this over to Sean Maduck, who is our Chief Commercial Officer.

[Sean Maduck, Chief Commercial Officer]

Hi, Chris, and thanks for the questions. Your question was a two-part one. One was around for discontinuation of existing patient base, is there -- have we seen a change there, and the answer to that is no. And your next question was around titrations, so I thought I'd spend a minute talking about to what success looks like and what we need for us to call it growth. There's really three key factors that were affected by the pandemic. One is this core sensibility to educate doctors on hypercortisolism and Korlym. Two would be a doctor's ability to actually see their patients multiple times for an extensive work-up 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. News patients have either not titrated or titrating at a much more slow rate to get to the optimal dose and again directly related to durability to see their position with the appropriate frequency or even their access to labs or the willingness to go and get labs that they may need to do so. So in time as things open back up, we believe that titration will catch up, but for the time being, in aggregate, this has decreased our average overall dose.

[Chris Howerton, Jefferies]

Okay, OK. Well that -- first of all, thanks for shimmering me on my questions and I'll hop back in the queue. Thanks again.

[Joseph Belanoff, Chief Executive Officer]

Thank you, Chris.

[Operator]

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

[Joseph Belanoff, Chief Executive Officer]

Hello, Arthur.

[Arthur He, H.C. Wainwright]

Hey, good afternoon, gentlemen. 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?

[Joseph Belanoff, Chief Executive Officer]

I'm sorry, I didn't quite hear the question, which submitted.

[Arthur He, H.C. Wainwright]

Where we are going to...

[Joseph Belanoff, Chief Executive Officer]

Which venue we will -- 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 data. And all I can tell you is that we will present this to conferences as quickly as we can just depending on conference deadlines. 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 present it there. I can't say with certainty which ones yet.

[Arthur He, H.C. Wainwright]

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

[Joseph Belanoff, Chief Executive Officer]

I'm going to give you get back to Andreas Grauer.

[Andreas Grauer, Chief Medical Officer]

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 advisors 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 the dose or schedule of giving this drug in a way that is both effective and safe.

[Joseph Belanoff, Chief Executive Officer]

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

[Arthur He, H.C. Wainwright]

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

[Andreas Grauer, Chief Medical Officer]

Yes, no. So they -- first of all, this was a non-invasive. So this was a -- was not a biopsy trial. So we didn't look at fibrosis in this particular trial. We also did not repeat, like for example of a fibroscan measurement. The MRI data is really the only thing that we have. Seeing a change in fibrosis within four weeks, which was the treatment duration for most of these patients would be absolutely unexpected but we wouldn't know, we didn't know.

[Joseph Belanoff, Chief Executive Officer]

But just, Arthur, for comparison, in almost all of the studies, the issue, this threshold number is 30% in terms of fat reduction is presumed to -- and actually there's studies which show really correlates with reduction in NASH, in fibrosis and NASH. And that's how we incent our 30% target and that's how like others did 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 that these patients to have much greater in some cases reduction back then 30% and so it's really a potent medication. Now we really have to figure out how to harness it.

[Arthur He, H.C. Wainwright]

Okay, that's great. Thank you very much for taking my question.

[Operator]

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

[Tazeen Ahmad, Bank of America]

Hi, good afternoon, guys. Thanks for taking my question and congrats as well from me on the ovarian data. To go back to...

[Joseph Belanoff, Chief Executive Officer]

Thank you, Tazeen.

[Tazeen Ahmad, Bank of America]

If you go back to Korlym for one second, you've 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 kinds of competitive risk from the retro drug that recently launched and is just feedback from a non-quantitative aspect we will be curious to hear your thoughts on that. And then I have a couple of follow-ups.

[Joseph Belanoff, Chief Executive Officer]

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

[Sean Maduck, Chief Commercial Officer]

Yes, thanks, Tazeen, for the question. Short answer is no, we're not seeing an impact on our business from Isturisa of specifically what you're referencing, not seeing virtually any impact on our existing base and we continue to add patients to our 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 broader symptom, which encompasses all etiology businesses.

[Tazeen Ahmad, Bank of America]

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 has 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?

[Sean Maduck, Chief Commercial Officer]

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 syndrome. We target list of 1,500 to 2,000 with greater frequency, but there are many that have yet to prescribe. So there is real opportunity within the existing endoncronology base to write their first prescription approval.

[Joseph Belanoff, Chief Executive Officer]

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

[Tazeen Ahmad, Bank of America]

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

[Joseph Belanoff, Chief Executive Officer]

I am 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 these 40 patients. And the bar, I think as we've mentioned in previous calls, what you compare it to is 0% response rate and something like above 20% it's something that everyone would say, well, that must be your medicine. If it's 10% to 20%, you have to think about there is something going on. And if it's below 10%, it's hard to know whether that's different than what you had ordinarily expect. And we're very interested in seeing now -- if we were sort of pick the Great White Well of cancers, I mean pancreatic cancer is terrible and metastatic cancer pancreatic cancer is really terrible. So we'll just have to wait and see where that is.

[Alan Leong, BioWatch News]

Yes, I asked that already because of the undermet need. Okay, thank you.

[Atabak Mokari, Chief Financial Officer]

No, no. Right. And then of course is the other side of is the bar is lower, of course, because of that.

[Operator]

Will go next to Matt Kaplan of Ladenburg Thalmann.

[Matthew Kaplan, Ladenburg Thalmann]

Hi, good afternoon. Thanks for taking the questions. And yes, and my congrats to 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 hundred milligram daily dose were up titrated 150 milligrams in the study?

[Atabak Mokari, Chief Financial Officer]

Matt, I'm giving your question over to Andreas.

[Andreas Grauer, Chief Medical Officer]

Yes. So overall 30% of the patients in the hundred milligram dose for up titrated, not all of them to 150, about two-thirds of the one that were up titrated, were up titrated to 150. So that, those are the exact data.

[Atabak Mokari, Chief Financial Officer]

Yes. The other thing and Matt, maybe if this is a longer answer sort of take it offline. There is a theory as to why intermittent dosing actually might be effective in terms of the glucocorticoid receptor genes that that are sort of needed at that zone and of course treatment is always the combination of efficacy and potential for adverse events. And so there is 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 every day therapy at a lower dose and then it was superior to the background therapy with statistics.

[Matthew Kaplan, Ladenburg Thalmann]

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

[Atabak Mokari, Chief Financial Officer]

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 a limit as to what we 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 crews, but what was really different was the duration of response to those who responded and that's where the separates.

[Matthew Kaplan, Ladenburg Thalmann]

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

[Andreas Grauer, Chief Medical Officer]

I think we -- 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 and 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.

[Atabak Mokari, Chief Financial Officer]

Yes. And just to underscore that just again, I know, this Matt coz' you follow us through 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 enrollments should probably be -- I don't know 70% European that's what it was in this Phase 2 study. So to 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 timeline.

[Matthew Kaplan, Ladenburg Thalmann]

Okay, great. And then last question, in terms of relacorilant, the increase in liver enzymes, liver function tests 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 and other indication other patient populations? Are you seeing any indications of liver enzyme increases?

[Atabak Mokari, Chief Financial Officer]

Hey, Matt I just want To clarify one thing, the drug in the NASH study

[Matthew Kaplan, Ladenburg Thalmann]

Oh, that's miricorilant, yes.

[Atabak Mokari, Chief Financial Officer]

Miricorilant, relacorilant doesn't -- has never produced any of these that type particular issue. But I'll leave you to Andreas here to answer the question related to miricorilant.

[Andreas Grauer, Chief Medical Officer]

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 two 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.

[Atabak Mokari, Chief Financial Officer]

Thanks, Matt.

[Matthew Kaplan, Ladenburg Thalmann]

Thanks, thanks.

[Operator]

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

[Alan Leong, BioWatch News]

Hi, there. Congratulations.

[Joseph Belanoff, Chief Executive Officer]

Thank you, Alan.

[Alan Leong, BioWatch News]

Going to the NASH trial, when you had this amount of fat reduction. Did you see a global in the body? I know it was only one month but are you seeing overall weight reductions? And if you were able to even give any inferences on fat reductions and the other organs?

[Joseph Belanoff, Chief Executive Officer]

So Alan is this a personal question? Yes. Yes, in a month. Andres can tell you if he even looked at that though, but we were not expecting general weight loss. Do you have an answer to that?

[Andreas Grauer, Chief Medical Officer]

Well especially in our inflow for patients right, where we wouldn't have any

[Atabak Mokari, Chief Financial Officer]

But it's an interesting question. And we will look at that out.

[Alan Leong, BioWatch News]

Yes, I'm trying to go on the side door antipsychotic weight gain. Let's take antipsychotic weight gain and any you can service any of them that signals were slight, is the current thinking of that the consumption of antipsychotic puts a break on how much fatty acid gets your waist?

[Joseph Belanoff, Chief Executive Officer]

Yes -- I hope everyone heard that because it sort of an intriguing idea. So I'm just going to settle out. And then I'll give you my opinion that somehow antipsychotic medications are protective against this, probably not as probably not the case. I think it is coincidental, but I want to underscore what Andreas said even a bit more than I might have thought, I have learned about this that NASH is really a different disease, in the sense that the patients with 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 is really giving you kind of more global response to it. As I said, I don't think it's the anti-psychotic medication. I think it's just the underlying group of patients are not as identical as one might have thought.

[Alan Leong, BioWatch News]

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?

[Atabak Mokari, Chief Financial Officer]

As you always do you push me to the end of the map to be released. Okay.

[Alan Leong, BioWatch News]

I understand. This is a wonderful time. Thanks for having me ask the questions. Looking forward to what's happening in the next, over the next several months. Thank you.

[Atabak Mokari, Chief Financial Officer]

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

[Operator]

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