Corcept Therapeutics - Earnings Call - Q2 2020

Transcript

Speaker 0

Good day. Hello, everyone.

Speaker 1

And welcome to the Corcept Therapeutics conference call. Today's conference is being recorded. If you would like to ask a question, please signal by pressing star one Call. At this time, I would like to turn the conference over Charlie Robe. Please go ahead, sir.

Speaker 2

Thank you. Good afternoon, everyone. Today, we issued a press release announcing our financial results for the second quarter and providing a corporate update. A copy is available at corecept.com. Complete results will be available when we file our Form 10 Q with the SEC.

Today's call is being recorded. A replay will be available through August 18 at (888) 203-1112 in The United States and (719) 457-0820 internationally. The passcode will be six eight zero zero seven zero six. 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 nineteen 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 risks related to the development of our product candidates, including their clinical attributes, regulatory approvals, mandates, oversight, and other requirements, and the impact of the COVID nineteen pandemic on our employees, consultants, and and vendors as well as on physicians, patients, insurers, regulators, and the practice of medicine generally.

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 our 2020 revenue guidance, cash flow and expected growth, impact of the COVID-nineteen pandemic on our commercial operations, financial performance, clinical development programs, physicians, payers and patients, physician awareness of hypercortisolism and the selection of Korlym as the optimum medical treatment, the timing, cost, and outcome of litigation, including our lawsuits against Teva Pharmaceuticals and Sun Pharmaceuticals, and Teva's challenge to our intellectual property before the patent trial and appeals board, the scope and protective power of our intellectual property, the benefits of orphan drug designation, the progress enrollment timing, design and results of our clinical trials, and the clinical and commercial attributes of relacorilant, exicorilant, miricorilant and our other selective cortisol modulators. We disclaim any intention or duty to update forward looking statements. Our revenue for the second quarter was $88,600,000 a 23% increase from the 2019. It was $4,700,000 lower than in the first quarter of this year, primarily because in March, some patients refilled their prescriptions a few days earlier than usual so as to have a small amount of extra medicine on hand to safeguard against pandemic related delivery delays.

These early refills increased our first quarter tablet shipments and revenue. When patients consumed their small safety stocks in the second quarter, they postponed refilling the prescriptions by a few days, which decreased our second quarter tablet shipments and revenue by a similar amount. Let me illustrate with a hypothetical example. A patient who filled her Korlym prescription on March 2 and who would normally have refilled on April 2 instead refills on March 29. That is to say in the first quarter rather than the second quarter.

In April, when it becomes clear that no deliveries are being delayed, she consumes those few extra tablets and rather than refilling her prescription on April 29, waits until May 2, skipping April. She then returns to her normal monthly refill cadence, receiving another shipment on June 2. This patient received six six shipments in the 2020, an average of one per month as one would expect. But four of those shipments were in the first quarter and only two were in the second. Variations in refill timing such as I just described caused our shipments of Korlym tablets and our revenue to increase in March then decrease in the second quarter by a comparable amount then resume their normal cadence.

In effect, about $4,000,000 of revenue we would have recognized in the second quarter got shifted to March. We did not see this sort of early refill behavior in the second quarter. Our second quarter GAAP net income was $28,300,000 compared to $20,200,000 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 second quarter was $39,700,000 compared to $31,000,000 in the 2019.

Our cash and investments increased $60,600,000 in the second quarter to a balance of $409,600,000 at June 30. Now a brief legal update. In March 2018, we sued Teva Pharmaceuticals in federal district court to stop it from marketing a generic version of Korlym in violation of our patents. Our lawsuit stayed final FDA approval of Teva's proposed product for thirty months, a period which ended at midnight on August 1. Discovery is underway.

Trial is set to begin 02/02/2021. In addition, Teva has challenged the validity of one of our patents, the two one four patent, in a proceeding known as a post grant review or PGR before the US Patent Office's Patent Trial and Appeals Board or PTAB. Briefing in the PGR is complete. Oral argument is set for September 2. We expect the PTAB's decision on November 19.

The losing party may appeal to the Federal Circuit Court of Appeals, during which time those portions of the PTAB decision that are under appeal will have no effect. Federal Circuit appeals usually take about one year to resolve. The soonest we expect definitive resolution of the PGR is the 2021. 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 12/08/2021, that is next year, and a decision by the district court that the patents we have asserted against Sun are invalid, unenforceable, or not infringed.

Despite o overlaps and subject matter and legal issues, our dispute with Sun is separate from our litigation against Teva, and it's following its own timeline. A Markman hearing in the Sun case is set for November. No trial date has been set. The impact of the COVID nineteen pandemic on the timing of these disputes is impossible to know with certainty. We do not expect delays in the PGR because the patent office conducts much of its work, including PTAB hearings remotely as a matter of course.

Predicting the ultimate timing of our district court litigation is more difficult. The judge hearing our Teva and Sun lawsuits has not delayed our February trial date with Teva or our November Markman hearing in the Sun case. That being said, I would not be surprised if our district court timelines are extended. Of course, we will be ready whether there are delays or not. We're confident in our intellectual property and look forward to putting our case before the judge.

I will now turn the call over to doctor Joseph Belanoff, our chief executive officer.

Speaker 0

Joe? Thank you, Charlie. I wanna start by commending our clinical specialists, patient advocates, and medical science liaisons who have worked hard and successfully to assure patients continued access to Korlym during the COVID nineteen pandemic. Over the past quarter, we have seen physicians adapt their practices so they can safely care for their patients. Managing the complex multi step process of diagnosing and treating patients with Cushing's syndrome is hard even under normal conditions.

Adding the stress and uncertainty of Zoom office visits, patients who are reluctant to leave the safety of their homes, and limited access to laboratory and scanning centers increases the challenge. In person meetings of our clinical specialists and medical science liaisons with physicians and their staff are quite limited at this point. Our commercial team has done an excellent job devising ways to support physicians by video and teleconference, but these methods are just developing. We are focused intently on helping physicians provide optimal care because COVID nineteen is especially dangerous for patients with Cushing's syndrome. The coronavirus enters cells by binding to the ACE two receptor.

Cortisol causes the ACE two receptor to proliferate, putting patients with Cushing's syndrome at heightened risk. In addition, excess cortisol activity suppresses the immune system. As a result, patients with Cushing's syndrome are four to five times more likely to suffer from severe infections of any type. Hypercortisolism also increases the risk of blood clots and thromboembolism, a leading cause of death in patients with COVID-nineteen. I want to underscore our full confidence in the commercial potential of Korlym and its planned successor relacorilant.

There remain many patients who could benefit from treatment with a cortisol modulator who have not yet received it. The challenges temporarily posed by the pandemic are likely to vary in their impact and are subject to rapid change. We believe any further changes will be manageable and have reaffirmed our standing revenue guidance of $355,000,000 to $375,000,000 We are now testing our proprietary selective modulator, relacorilant, our planned successor Korlym for patients with Cushing's syndrome in two phase three trials. Like Korlym, relacorilant achieves its effect against Cushing's syndrome by competing with cortisol to bind to the glucocorticoid receptor, GR for short. Unlike Korlym, relacorilant does not bind to the progesterone receptor, PR for short, which means it does not cause the off target effects, including termination of pregnancy, endometrial thickening, and vaginal bleeding caused by Korlym's affinity for PR.

By a different mechanism, relacorilant also does not appear to cause hypokalemia, low potassium, a serious side effect experienced by forty four percent of patients in Korlym's pivotal trial that is a leading cause of Korlym discontinuation today. Relacorilant's clinical data have been positive. Patients in its phase two trial experienced meaningful improvements in hypertension and glucose control as well as in a variety of secondary endpoints. There were no relacorilant induced instances of endometrial thickening, vaginal bleeding, or hypokalemia. A poster presentation of relacorilant's phase two results can be found at the Investors Post Events tab of our website.

Relacorilant's Phase three GRACE trial, t r m c e trial, which we believe will serve as the basis for our NDA submission, continues enroll continues to enroll patients and open additional clinical trial sites. Recruitment is now underway at 60 sites in The United States, Canada, Europe, and Israel. Planned enrollment is 130 patients. We expect to submit our NDA in the 2022. We dosed the first patient in relacorilant's other phase three trial as a treatment for patients with Cushing's syndrome, GRADIENT, last week.

GRADIENT will study relacorilant's effects in patients whose Cushing's syndrome is caused by an adrenal adenoma or adrenal hyperplasia. Although patients with this etiology of Cushing's syndrome usually have a less rapid decline in their condition, they ultimately have poor health outcomes. BRADEN is the first controlled study in patients with this etiology of Cushing's syndrome. Study participants will receive either relacorilant or placebo for twenty two weeks. The trial's primary endpoints will be statistically significant improvements in either hypertension or glucose metabolism.

Planned enrollment is 130 patients at sites in The United States and Europe. Many of the investigators who are participating in GRACE will also participate in GRADIENT. You can find the poster presentation of GRADIENT's design at the research and pipeline publications tab of our website. I will now turn to our oncology program, which has its origin and theories postulated by our academic collaborators at the University of Chicago more than twelve years ago. Our program now consists of multiple clinical trials, one of which our controlled phase two trial in patients with recurrent platinum resistant ovarian cancer, just completed enrollment.

We are investigating three mechanisms by which cortisol modulation may be helpful in the treatment of cancer. Cortisol activity blunts the effects of chemotherapy by suppressing the genes that trigger apoptosis, the programmed cell death chemotherapy is meant to cause. By reversing cortisol's anti apoptotic effect, cortisol modulation may also allow chemotherapy to achieve its full cancer killing potential. We have tested this hypothesis in an open label Phase onetwo trial in which patients with advanced solid tumors received relacorilant combined with nab paclitaxel, that Celgene's drug Abraxane. Our results were striking.

Tumors in seven of twenty five patients with metastatic pancreatic cancer and in five of eleven patients with platinum resistant ovarian cancer either shrank or ceased growing for sixteen weeks or longer. Two patients with metastatic pancreatic cancer exhibited tumor shrinkage for more than fifty weeks. One patient's ovarian tumor exhibited shrinkage for sixty five weeks. The tumors in all of these patients had progressed despite multiple lines of prior therapy, including therapy with taxanes. You can find our poster presentation of these results at the investorpast events tab of our website.

We're excited to report that in July, we closed enrollment in our one hundred and seventy eight patient controlled phase two study of relacorilant plus nab paclitaxel in patients with recurrent platinum resistant ovarian cancer, a disease with a very poor prognosis. All of the patients in the trial received nab paclitaxel. One third of them also received relacorilant every day. Another third of them received relacorilant the day before, the day of, and the day after each infusion with NAP paclitaxel. The trial's primary endpoint is progression free survival, with secondary endpoints including objective response rate, duration of benefit, and overall survival.

We expect results in the first half of next year. We're equally excited to report that in June, we began dosing patients in a phase three trial of relacorilant plus nab paclitaxel in patients with metastatic pancreatic cancer, a disease for which there are no good treatment options. The trial is called RELiNT. RELiNT is an open label trial in which eighty patients will receive relacorilant plus nab paclitaxel with the primary endpoint being objective response rate assessed by resist criteria, with secondary endpoints including progression free survival and overall survival. RELIGNET will be conducted at 30 sites in The United States.

We will perform an interim analysis of data from the first 40 patients and expect to have results of that analysis in the first half of next year. It is important to note that the expected response rate of patients with such advanced disease to nab paclitaxel monotherapy is zero. For this reason, we believe sufficiently positive results in RELiant would support accelerated approval. Cortisol activity suppresses system, an effect that is often beneficial, as it controls the inflammatory response and helps protect against autoimmune diseases. Unfortunately, cortisol induced immune suppression limits the body's ability to kill tumor cells and blunts the efficacy of medications such as checkpoint inhibitors, which enlist the immune system to fight cancer.

Modulating cortisol activity bolsters the immune system and may help checkpoint inhibitors and other immunotherapies achieve their full potential. This quarter, we are starting an open label phase one b trial of relacorilant plus the PD one checkpoint inhibitor pembrolizumab, Merck's drug Keytruda, in twenty patients with advanced adrenocortical cancer. Because adrenocortical tumors produce cortisol, these patients also suffer from Cushing's syndrome. Our trial will examine whether relacorilant can, by reducing the effects of excess cortisol activity, treat these patients' Cushing's syndrome, and by reversing cortisol induced immune suppression, help pembrolizumab achieve its maximum effect. We presented posters at this year's virtual ASCO and AACR with preclinical and clinical biomarker data supporting this hypothesis.

They are available at the research and pipeline publications tab of our website. I will conclude with an update on our program in metabolic diseases. As many of you know, we are developing a proprietary cortisol modulator, miricorilant, as a treatment for antipsychotic induced weight gain and nonalcoholic steatohepatitis, or NASH. Like relacorilant and exicorilant, miricorilant is a selective cortisol modulator, binding potently to GR but not PR. Miricorilant was safe and well tolerated in its phase one trial.

Millions of patients rely on antipsychotic medications to treat schizophrenia, bipolar disorder, major depression, and other serious illnesses. Unfortunately, patients often pay a terrible price in the form of extreme weight gain, impaired glucose and lipid metabolism, and other manifestations of metabolic syndrome. These adverse effects reduce patient adherence and pose major health risks of their own. For example, death by heart attack or stroke is common in patients taking antipsychotic medication. Cardiovascular disease is the leading cause of death in patients with schizophrenia.

Cortisol modulators are potent animal models of antipsychotic induced weight gain. More importantly, we have conducted three double blind, placebo controlled clinical trials in which a cortisol modulator meaningfully reduced weight gain and other metabolic adverse events caused by antipsychotic medications. In two of these trials, healthy subjects received daily doses of either olanzapine or risperidone, along with either mifepristone, the active ingredient in Korlym, or placebo. Subjects who received Korlym experienced significantly less weight gain and other metabolic adverse events than those who received placebo. These results were published in the journals Advances in Therapy and Obesity in 02/2010.

Unfortunately, we could not advance mifepristone because its qualities as an abortive fashion disqualify it as a treatment for common disorders. Miracorilant can be advanced, however, because it is a selective cortisol modulator with no affinity for the PR. It is not the abortion pill, and if approved, could be widely distributed. Last quarter, we completed a double blind, placebo controlled Phase 1b trial in which healthy subjects receive olanzapine and either six hundred milligrams of miricorilant, nine hundred milligrams of miricorilant, or placebo for 14. Study participants who received miricorilant gained significantly less weight than those who received placebo.

In addition, they exhibited a significantly smaller increase in triglycerides and in the liver enzymes AST and ALT, markers of liver damage that rise at the onset of olanzapine therapy. The full results of this study will be published later this year. Our double blind placebo controlled Phase II trial of miricorilant to reverse recent antipsychotic induced weight gain, known as GRATITUDE, is in progress. One hundred patients with schizophrenia will receive, in addition to their established dose of antipsychotic medication, either six hundred milligrams of miricorilant or placebo for twelve weeks. GRATITUDE will be conducted at approximately 20 centers across The United States.

I'm pleased to announce that we have completed, one quarter ahead of schedule, development of a miricorilant formulation available for use in Phase III trials and beyond. As a result, we have moved up the start of two additional miricorilant trials. This quarter we plan to start a placebo controlled, double blind, Phase II trial in patients with longstanding antipsychotic induced weight gain called GRATITUDE II. By year end, we also plan to start a double blind, placebo controlled phase two trial of miricorilant in patients with NASH, a serious liver disease that affects millions of patients. In animal models, miricorilant prevents and reverses both fatty liver and liver fibrosis, two precursors of NASH.

Corcept had a strong second quarter. We reaffirmed our revenue guidance. Our cash and investments grew by $60,000,000 $410,000,000. Our strong financial position allows us to advance our growing portfolio of drug candidates even in times

Speaker 3

of

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great uncertainty. Recently, our development programs achieved significant milestones. More are on the horizon. Although the COVID nineteen pandemic continues to slow enrollment and make site activation more difficult, recruitment continues at 60 sites in relacorilant's pivotal GRACE trial with an expected NDA submission in the 2022. In addition, enrollment is now underway in gradient, a double blind phase three trial of relacorilant in patients with Cushing's syndrome from an adrenal origin, an understudied etiology of the disease.

Our clinical trials in oncology have been less affected by the pandemic, most likely because our study participants are so gravely ill. They must seek treatment no matter the conditions. We have completed enrollment in our controlled Phase II trial of relacorilant plus nab paclitaxel in patients with recurrent platinum resistant ovarian cancer. We will have results in the first half of next year. Our Phase III RELiANT trial of relacorilant plus nab paclitaxel in patients with metastatic pancreatic cancer is underway.

We expect to perform an interim analysis of data from Reliant's first 40 patients in the first half of next year. We believe sufficiently positive results from Reliant will qualify relacorilant for accelerated approval in this indication. This quarter, we plan to start an open label Phase 1b trial of relacorilant combined with a PD-one checkpoint inhibitor pembrolizumab to treat patients with advanced adrenal cancer. Finally,

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by the

Speaker 0

end of this year, we expect to select a dose for advancement in a controlled Phase II trial of exicorilant in combination with enzalutamide to treat patients with castration resistant prostate cancer. Our program in metabolic diseases has also made significant gains. Enrollment and site activation of resumed INCLIRLENT two, our double blind placebo controlled phase two trial of miricorilant to reduce recent antipsychotic induced weight gain, although the COVID nineteen pandemic continues to slow the pace of both activities. Completion of formulation work in miricorilant has allowed us to advance the start dates of our other planned trials. GRATITUDE II, a double blind, placebo controlled Phase II trial of miricorilant in patients with longstanding antipsychotic induced weight gain, is planned to start in the third quarter.

We plan to start a double blind, placebo controlled phase two trial of miricorilant in patients with NASH I'll by year stop here for questions.

Speaker 1

Thank you. If you would like to ask a question, please signal by pressing star one on your telephone keypad. If you are using a speakerphone, please make sure that your view function is turned off to allow your signal to reach our equipment. Again, please press star one to ask a question. We will pause momentarily to allow everyone an opportunity to signal for questions.

And we will take our first question. This will come from Chris Howerton with Jefferies.

Speaker 3

Great. Good afternoon, and thanks for taking the questions. So I guess maybe the the first question might be on the quarterly numbers. So I think maybe, Charlie, just to confirm, you know, I think that you were saying that most of the discrepancy was respect to the refill rate. Can you just confirm to us that you're seeing the same patient numbers there between the first and second quarter or some way for us to calibrate that in another way?

Speaker 2

Yes. We're sure. Yes. We are. It was a phenomenon that occurred in the first quarter.

We didn't see it in the second quarter, or, in July, although our analysis of July isn't complete yet. And so it doesn't it didn't reflect a a drop off of patients or anything else. It is really patients worried about, you know, FedEx delays, taking their refills a couple of days early so they have a little bit of extra medicine on hand. And, you know, by shifting things up a few days, what that ended up doing was shifting some stuff into q one and then other stuff, you know, that that would have been in q two, and that's all that was going on. So so, you know, just giving our sort of average dose and and, you know, price per tablet and so forth.

You can think of it as about about 80 to a 100 patients, something like that. Okay. And those patients remain on medicine. There's nothing no interruption in their care at all.

Speaker 3

Excellent. Okay. And then, with respect to the the pancreatic cancer trial, just curious if, duration response would be part of the analysis. And if so, you know, what what in your view, Joe or or Andreas, would you see as clinically meaningful in this patient population?

Speaker 0

Yeah, Chris. And thanks for the question. Good to talk to you. Yes. Certainly, duration of response is important.

I mean, we're looking at all of those variables. Now the second question you asked is a harder one because in in some sense, you know, these are about the sickest patients you you get in oncology. I think as I've said before, sadly, we had patients who passed away in the earlier study between the time they consented in their first dose. So how long their responses last is difficult to assess. The expectations for longevity are quite low.

And I think actually one of the things that was impressive in the study that has already been completed is that there were several patients whose duration of response and disease control went out far longer than wasn't expected. You know, a couple of them went out the duration of a year. So I don't have a firm number for you, but that is a variable that is consequential, and I'm certain in the same way we will look at it, the FDA will look at it as well.

Speaker 3

Got it. Okay. And then, you know, perhaps, this is a naive question, and I apologize. But just curious how we should think about the the safety databases for relacorilant, you know, utilization within an oncology setting relative to Cushing's syndrome and and how that may or may not impact, any kind of view from a regulatory perspective?

Speaker 0

Well, you know you know, know I know that you, know this, Chris, but all of the data for relacorilant becomes part of the safety package for everything that you do. And and and and so, you know, it it gets counted together in that way. I think the difference, you know, with some diseases is that you had two diseases where, for instance, the risk profile of the disease was very different, you can understand that there would be certain, you probably would need a smaller safety database, and you probably, would be able to tolerate a worse adverse event profile if the disease was more severe. Now, really from our perspective, Cushing's syndrome and the oncology diseases that we're talking about are really all severe diseases. And we actually think that the safety profile would be looked at roughly in the same way.

Speaker 3

Okay. Okay. Very good. And, you know, maybe one more question if I may. Just curious what, what has been your experience with respect to, medication compliance in the antipsychotic induced weight gain and kind of how you view that in terms of, you know, combination strategies with multiple oral oral therapies for for patients that that might be taking psychotics antipsychotics.

Speaker 0

Excuse me. No. That that that's actually a a prescient question because, you know, as a psychiatrist myself, I can tell you that, patients' adherence to regimens is not, a 100%. And so I can't give you actually any data. That study that we're actually running is still in progress right now.

But we'll, I think, have a better sense of that as we go along because we look at PK measures, we know where people stand and so forth. Gives me an opportunity, I wanna just be a little bit tangential just so people understand it. I know you do because you're you're much more steeped in the story. But what we've been able to show so far is that first Korlym, but now especially miricorilant, is clearly active in an antipsychotic induced weight gain model.

We've given healthy people antipsychotic medication in really pretty potent ways in a short period of time. We can see that we've reduced the effects, adverse metabolic effects, of antipsychotic medication. The studies that we're now conducting are really our first studies in patients. And so you've asked one of the questions, which is important, but there are other questions that relate to the efficacy of the medication that we'll get our first pieces of information on next year. Obviously, we're excited and optimistic about it, but I just want to draw a difference between what we've seen so far, which is good medicine activity in animals and healthy people, and how excited we are to actually see what happens in patients.

And to return to your question, ability to adhere the regimen, is also a meaningful thing that we will we will observe.

Speaker 3

Sure. Okay. Well well, thank you so much, and I'll hop back in the queue in the in the case that, maybe follow-up questions are available. Thanks again for taking

Speaker 0

the question. Nice to talk to you, Chris. Thank you.

Speaker 3

Okay. Thanks, Kencho. And

Speaker 1

we will take our next question. This will come from Matt Kaplan with Ladenburg Thalmann.

Speaker 4

Hi, guys. Thanks for taking my questions. And just wanted to follow-up on on Chris' question with respect to the RELIGENCE study. With on the internal analysis of of 40 patients, what are you what are you looking to see there, and what would what would kinda represent a a go, no go, decision on that interim of about half the patients you plan?

Speaker 0

Yeah. We we don't have a firm no go go level there. You know, again, as I started out by saying, the response rate was really presumed to be zero or very close to it for patients with pancreatic cancer. You know, I could tell you, you know, stream numbers, obviously. If almost all of the people had a tumor shrinkage, that would be a fantastic result.

And if none of them do, well, that gives us something as well. I think that this is one disease where even a modest response rate, I think, would be viewed positively by practitioners. But beyond that, you know, I I don't really have any more information than that for you.

Speaker 4

Okay. Okay. Very good. And then similar in terms of the phase two study where in in platinum resistant ovarian cancer

Speaker 0

Yes.

Speaker 4

And you complete enrollment data coming in in the first half as well. What what what some of the benchmarks there that that that we should be looking for?

Speaker 0

Yes. You know, again, this this is a dire illness, not probably to the degree that pancreatic cancer is. But I'll give you sort of rough numbers for sort of how the study is powered. We expect that there's about, for NAPPAClipaxil alone, about a three and a half month average period for progression free survival. And we're our study to add about another three months to that.

Speaker 4

Okay. Great. That's very helpful. Great. Thank you.

Then, just shifting to to to the GRACE study. What what's really now the the rate limiting step for filing the NDA, in the 2022? Is it the completion of the GRACE study? Are there is there another moving part there that you need to Nope.

Speaker 0

That yeah. That that's it, Matt. That everything else should be ready to go before then.

Speaker 4

Okay. Fair enough. And then last question, I guess, maybe more for Charlie on the litigation. Just to be clear in terms of the the next kind of announcements we're expecting on on the Teva lawsuit will be a decision in November from from the oral arguments on on the PTAV. Is that correct?

Speaker 2

As far as the litigation's concerned, yeah. I mean, there's it's the November November 19 is the scheduled date, and I would expect it to be, you know, plus or minus a day or two from there. Trials in February. And, you know, the one other date that's significant has already passed, which just, you know, to remind folks, you know, when we sued Teva back in March 2018, our lawsuit, instituted a thirty month stay of FDA approval of Teva's product for final approval. And that stay expired midnight August 1 this weekend.

So as far as the FDA is concerned, you know, Teva is free to launch its product at risk. I have no evidence they've done so. I've not seen it. And I, you know, from a business perspective, I think it makes it doesn't make sense for Teva to do that. They'd be at risk of trouble damages, and they meant they were go on go on to lose their case with us.

So it's not, an eventuality I expect. Although, of course, I'm not the Teva manager, and I don't get to decide. So and and we are ready to, we are ready to respond to them no matter what they do. But in terms of getting a full calendar in front of people, there's a date in the past that they should also just be aware of.

Speaker 4

Fair enough. And then similarly with the with the Sun, litigation, you mentioned the December, 2021. And then, I guess, early before that this year, the Markman hearing as as as as times that that that we should expect. And then in in in in terms of other things that we should hear out of some litigation, are those the two kind of dates that we we should expect?

Speaker 0

Yes.

Speaker 4

Very good. Well, thanks for taking my questions, guys.

Speaker 0

Yeah, Matt. Good to good to hear. And if I if I could just add

Speaker 2

it revise and extend my, response to Chris briefly about the the revenue blip. Because I know it's a it's a little bit of an abstract concept. And I, you know, I really was at pains to make sure people could follow what happened. Just wanted another way to look at it and want everyone to understand. We are right.

You know, with with six months of the year down halfway through, we are right where we expected to be, which is why we could reiterate our guidance. So, you know, as explained kind of the movement of a refill from one quarter to the other by a few days and the impact of that, Understand that at the halfway mark of the year, the net result of us all is that we are where we expected to be. Just wanna make that clear with folks.

Speaker 1

And we can take our next question. This will come from Swayampakula Ramakanth with H. C. Wainwright.

Speaker 5

Thank you. Let's start with the colon for one one one question, and then I have a couple of pipeline ones. On the colon itself, regarding the uptake, thanks, Charlie, for explaining what has been going on during the second quarter. But my question is on the third quarter. How how do you see things moving along in this current quarter, in the q three, for the for the last month or so?

Speaker 2

Well so, you know, just as background for folks, know, we're we provide annual revenue guidance, you know, not quarterly revenue guidance. And at the the start of the year, we you know, our guidance range was 355,000,000 to $375,000,000, and that's and that's still the case. And so I can't really give you any particulars beyond saying that, you know, we're still comfortably within that that case in that range, and that's that's what we're seeing seeing now.

Speaker 5

Okay. Thank you. And then on on the on the pipeline, so for gradient, which is for which is for adrenal hyperplasia, is there any expectation of an interim analysis? Yeah. And, also, you know, could you give us a little bit of a little bit of an idea of data expectations from the study?

Speaker 0

Yes. I can I I think I can answer your questions, RK? The answer is no. We're not expecting to do an interim analysis. But just for the whole group, let me explain a little bit more about the study.

I think as probably, at this point, anyone who's followed the company knows, Cushing's syndrome is a very severe illness, and it's difficult to do the standard double blind placebo controlled study, because placebo is really not perceived, and I would certainly share this point of view, to really work at all. Very difficult for investigators to accept a study like that. It's difficult for their IRBs to accept a study like that. And so that's background. Now it's been increasingly discovered in the last ten years that what were once thought to be perhaps derisively called incidentalomas, or officially adrenal adenomas, really are a serious medical problem over time.

But many of these patients at this point are treated for their symptoms, they're treated for their blood glucose abnormalities, for their hypertension, for infections that they get, but they're not necessarily treated for hypercortisolism. But as the field has really gotten more and more evidence that these patients are really patients who are deserving of hypercortisolism treatment, we really came up with the idea, since none had ever been done, that it was possible to do the first and I think really definitive study on treating patients for hypercortisolism with a cortisol modulating agent, in this case with relacorilant. And that investigators, since they weren't already treating these patients in many cases for hypercortisolism, but were just treating symptoms around this, would accept the idea that we could do a double blind study. And that's exactly what we're doing. We're doing sort of the gold standard double blind, placebo controlled study for twenty two weeks.

At that point, we'll break the blind, and we'll see how, how we get in this disorder. We think that, obviously, that we have a lot of confidence that it's that that that that it will work well. And we the main reason really we embarked on this is because so many people in the field said, now that we know this is a problem, really see if you can create a study that will give us confidence to treat it. And the second question, plea please repeat, RK. I I think I lost it there.

Speaker 5

I was just wondering if there is any interim analysis or any

Speaker 0

No interim analysis.

Speaker 5

Perfect. Yeah. Yeah. Okay. So K.

My next question is on what's the patient population for metastatic unresectable adrenal cancer that is caused due to excess cortisol production?

Speaker 0

What is the population? So these are patient patients with adrenal cancer. And and a adrenal cancer is itself a rare disease, but a fair percentage of the people with adrenal cancer also have Cushing's syndrome because their tumors produce cortisol. And again, this is for those of us who have followed us for a very long time. In the study that we used to get Korlym approved, we called the SEISMIC study, we had patients with, amongst other etiologies of Cushing's syndrome, patients with adrenal cancer.

And Korlym was equally effective in reducing the symptoms of Cushing's syndrome in those patients, which was very meaningful to them, although it did not treat their cancer. And one of the things which happened after that study was the advent of immunotherapy. But unfortunately, immunotherapy has had very poor responses in adrenal cancer where cortisol production is part of the picture. And so again, because we have quite a few academic connections with people who treat adrenal cancer, the idea came, could you improve the response to immunotherapy and treat these people's Cushing syndrome, the effects of hypercortisolism, by adding cortisol modulating agent like relacorilant to a drug like Keytruda. And that's the study that we're doing.

So we're very excited to give that a try. But if I was to order it, what I would say, and I think what really made it past our bar, is we have a great deal of confidence that we will treat these patients Cushing's syndrome, and that has great benefit to them. We also now hope and are certainly are testing to see if we can actually improve their cancer by improving the efficacy of the, at this point, not very well working immunotherapy.

Speaker 5

Okay. Thank you. Thank you both for taking my questions.

Speaker 0

Yeah. Good to talk to Arnabay.

Speaker 1

And we will take our final question in queue. This will come from Alan Leong with BioWatch News.

Speaker 6

Hey, Joe. This is Charlie. Hello. Good to hear the progress on all fronts. You know, the first question, can you can you provide some color on the competitive profile for adrenal adenoma?

And what I want I can't imagine it's the same as traditional Cushing. Some of those common competitors sort of aren't even in the ballpark for treating adrenal based disease. I I may be wrong on that, but if you could provide some color.

Speaker 0

Yeah. I think that that's very important, and you're you're making an important distinction. I think that, you know, sometimes it's overlooked. So just to back up a little bit, Cushing's syndrome comes from the activity of cortisol. So higher cortisol activity causes hypercortisolism.

And Cushing's syndrome really comes from two different sources. One, adrenal tumors that produce cortisol. Or two, ACTH tumors, which stimulate the body to produce excess cortisol. ACTH tumors, which are found in the pituitary gland, are called Cushing's disease. And that is a subset of patients with Cushing's syndrome.

Now the interesting thing, as I said before about Cushing's syndrome caused by adrenal tumors is that although it was always recognized a part of Cushing's syndrome, the amount of people with Cushing's syndrome caused by adrenal tumors and the pathology and morbidity of adrenal tumors has really only recently come forward in the last decade. Prior to that, these were tumors that were sometimes picked up on scans for other things, and doctors didn't know what to do with them, and so forth. The interesting thing about that is that while measures like urinary free cortisol can pick up cases of very severe Cushing's syndrome from ectopic ACTH producing tumors or Cushing's disease, they often do not pick up Cushing's syndrome that are caused by adrenal adenomas. Adrenal adenomas are more commonly picked up, it's recommended by European American guidelines, to use a different test, dexamethasone suppression test, to begin your analysis of whether somebody has Cushing's syndrome caused by adrenal adenoma. And of course you have to image an adrenal adenoma.

But the bottom line is that Korlym, for instance, is approved for the treatment of all etiologies of Cushing's syndrome. Other drugs, for instance, a drug I know you're familiar with Signifor, is approved only for Cushing's disease, the subset of patients that have pituitary tumors that produce ACTH that in the end cause Cushing's syndrome. So adrenal adenomas really are sort of the newest frontier. Not that they're a new disease, but I think that their morbidity and the seriousness of the morbidity is really a last decade event. And as a consequence, as really the leaders in cortisol treating diseases, we've had a lot of interest in this.

And this was really the first opportunity to again combine kind of the gold standard study design with a disease that really is badly in need of further study.

Speaker 6

I wanna switch gears and get into the pancreatic RELIGENT trial, and congratulations with launching that.

Speaker 2

Yeah.

Speaker 6

There's lots of clinical trials out there for pancreatic cancer. Are you getting any feel about the reception for the RELiant trial, the clinical sites? And and are many of the Reliant sites, were they also used for the ovarian, cancer trial?

Speaker 0

You know, the let let's again, let me just ask that question more broadly. You know, in this, pandemic, clinical trial enrollment has really been roiled, you know, not just for Corcept, but for every company that does clinical trials. It was really very interesting to see how it divided up because at this time our portfolio really covers many different diseases. And the interesting thing was most severe diseases, like as an example, metastatic platinum resistant ovarian cancer, continue to enroll briskly right through all of this. These patients really need care.

Their life expectancy is short. They're coming to the hospital anyway. They're getting enrolled in clinical trials. You know, at the other end of the spectrum, something like antipsychotic induced weight gain, which is often a chronic illness, doesn't kill people tomorrow, less priority was put on enrolling in that sort of study. And, of course, all the companies you follow, you can figure out those things as you go through them.

Pancreatic cancer, I think everyone's estimation, is really in the severe end of the spectrum. And we think that these patients will enter clinical trials. There's, at the stage of disease we're talking about, there aren't a whole lot of other proven drugs with efficacy. And we think that that study will enroll at, relative to others, quite a brisk pace. And we are confident that we will enroll the first half of the trial in a quick enough period of time to be able to give out results in the first half of next year.

Speaker 6

No. That's great. Thank you.

Speaker 0

Alright. Well, thank you very much. Thanks for everybody, and, hoping that, by the time we see you again in November, things will be a little bit more open. We'll be a little bit more back to normal. But in the meantime, really, everybody stay healthy, and, and we'll we'll report progress as we make it.

Thank you very much.

Speaker 1

This concludes today's call. Thank you for your participation. You may now disconnect.