Q2 2022 Corcept Therapeutics Inc Earnings Call

Okay.

Good day and thank you for standing by welcome to the course, that's Therapeutics conference call. At this time all participants are in a listen only mode. After the speaker presentation, there will be a Q&A session.

Good day, and thank you for standing by.

Operator: Welcome to the Corcept Therapeutics conference call.

At this time, all participants are in a listen-only mode. After the speaker presentation, there will be a Q&A session. To ask a question during the session, you will need to press star 11 on your telephone. You will then hear an automated message advising your hand is raised.

Please be advised that today's conference is being recorded.

Ask a question during the session you will need to press star one one on your telephone you will then hear an automated message advising your hand is Reyes. Please be advised that today's conference is being recorded.

Operator: I would now like to hand the conference over to your speaker today, Atabak Mokari, CFO.

We think that that's our path to resolution.

I would now like to hand, the conference over to your speaker today out of block Macquarie CFO . Please go ahead.

Please go ahead.

The truth is our friend in this case, and we are moving things as quickly as we can, on our side.

Good afternoon, and thank you for joining us I'm out of Bakken Macquarie course, as Chief Financial Officer.

Today, we issued a press release announcing our financial results for the second quarter and providing a corporate update copies.

Copies available of course that dot 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 at the investors past 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 may cause actual results to differ materially from those such statements expressed or implied.

These forward looking statements are described in today's press release, and the risks and uncertainties that may affect them are described in our press release and in our annual report on Form 10-K, and our quarterly reports on Form 10-Q. Please refer to those documents for additional information we.

We disclaim any intention or duty to update forward looking statements.

Our revenue in the second quarter was $103 $4 million, an increase of 13% compared to the second quarter of last year.

We expect our revenue growth to continue and have reiterated our 2022 revenue guidance of $400 million to $430 million.

Net income was $27 4 million or 24 per common share in the second quarter our.

Our cash and investments increased $13 9 million in the second quarter to $382 million at June 30.

The increase in cash was $13 $5 million less than it might have been due to a recent change in federal tax law pre.

Previously R&D expenses can be deducted from income for the purposes of calculating federal tax in the year in which they were incurred.

Beginning this year R&D expenses must be amortized over five years, which means that the tax benefit of each year's R&D spending while unchanged in the aggregate will now be recognized in five equal annual installments.

Our cash balance at June 30 reflects the impact of this change for the first half of the year.

If congress restored the immediate deductibility of R&D spending we will receive a tax refund.

I will now turn the call over to Charlie Robb, our Chief business officer to provide an update on our litigation with generic manufacturers Teva and Hikma Pharmaceuticals Charlie.

And I stress that just because it's a little unusual.

Thanks, Pat and Mac.

Ah report this quarter.

No.

In the marketed generic version of Korlym in violation of our patents.

March 2018, we sued Teva in Federal District Court that lawsuit is still underway. Although currently all is quiet.

I think the typical strategy is just to delay, delay, delay.

Over a year ago, we filed for summary judgment on infringement of our 214 patents.

We see no point in doing that.

Um, you know, we know there's life at the end of the tunnel and that's what we're driving, to as fast as we can.

Having said that, of course, we don't control the pace of this.

All we can do is, um, put the information out there as it's requested and faster than, expected.

We're doing that.

Um, but other than that, that's all I can report because that's all I know.

As expected seven responded by filing it so in summary judgment motions.

So, you know, we'll, uh, this will be resolved at some point.

Summary, judgment is a procedure where by courts decide the case without holding in trial.

<unk> has not responded to these motions.

Because teva challenged the validity of our Q1 for patent before the patent trials and appeal.

Trial, and Appeals board and a procedure known as a post grant review or PDR and lost it can no longer challenged the 214 patents validity and district court.

So it was only defense to our summary judgment motion is that its proposed product would not infringe physician. We believe has no legal works actuals.

If the court decides the pending summary judgment motions in our favour Teva would be barred from marketing generic korlym until 2037, and the 204 patents expires court ruled in <unk> favor. We will proceed to trial, most probably sometime next year.

There is no timetable for the summary judgment motion ruling no trial date and no schedule for any proud related activities.

In March 2021, we sued another Anda filer, Hikma pharmaceuticals, and the same federal District Court hearing our case against Teva.

Originally set of fact discovery deadline of July 1st of this year, although that date has been vacated.

No deadlines are currently scheduled for this case.

With respect to both Teva and Hikma, we are confident in the strength of our legal position.

We're very confident in our position.

Atabak Mokari: Good afternoon, and thank you for joining us.

I just can't say more than that right now.

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

Atabak Mokari: I'm Atabak Mokari, Corcept's Chief Financial Officer. Today, we issued a press release announcing our financial results for the second quarter and providing a corporate update.

Thank you, Dennis.

Thank you Charlie.

The copy is available at corcept.com.

Operator: And your next question comes from the line of Michael from Canada.

Our Cushings syndrome business is built on a solid foundation a life saving medication promoted by our commercial team that puts the interest of patients first our strong second quarter results reflect this.

Michael from Canada: Your line is now open.

Our complete financial results will be available when we file our Form 10-Q with the SEC.

Unknown Speaker: Thanks, Adamak.

Hello.

As the country gets closer to resuming a pre pandemic lay up light positions will experience fewer challenges identifying diagnosing and optimally treating their patients, especially those with the complex disorders, such as Cushings syndrome.

There's little to report this quarter.

As many of you know, Teva is seeking to market a generic version of Coralim in violation of our patents. In March 2018, we sued Teva in federal district court. That lawsuit is still underway, although currently all is quiet. Over a year ago, we filed for summary judgment on Teva's infringement of our 214 patent. As expected, TEVA responded by filing its own summary judgment motion. Summary judgment is a procedure whereby courts decide a case without holding a trial.

This is Michael on for Edward.

The court has not responded to these motions.

Because TEVA challenged the validity of our 214 patent before the patent trial in appeals, board in the procedure known as a post-grant review, or PGR, and lost, it can no longer challenge the 214 patent's validity in district court.

TEVA's only defense to our summary judgment motion is that its proposed product would, not infringe a position we believe has no legal or factual support. If the court decides the pending summary judgment motions in our favor, TEVA would be barred, from marketing generic core limit until 2037 when the 214 patent expires.

If the court rules in TEVA's favor, we will proceed to trial, most probably sometime next, year.

There is no timetable for the summary judgment motion ruling, no trial date, and no schedule, for any trial-related activities.

In March 2021, we sued another antifiler, Hickam Pharmaceuticals, in the same federal district court that is hearing our case against TEVA. The court originally set a fact discovery deadline of July 1st of this year, although, that date has been vacated.

Leading endocrinologist increasingly believed there are substantially more patients with Cushings syndrome that was once assumed for many of these patients korlym is an excellent treatment.

No deadlines are currently scheduled for this case.

With respect to both TEVA and Hickam, we are confident in the strength of our legal position.

I, uh, congrats on the quarter.

We reiterate our 2022 revenue guidance of $400 million to $430 million.

I had two quick questions.

We are extremely optimistic about our clinical development programs. We believe cortisol modulation has the potential to treat many serious diseases. The positive results of our phase II trial in women with platinum resistant ovarian cancer provides serious evidence supporting cortisol modulations broad application.

Uh, so for the phase three was Bella trial, uh, can you remind us what led to choosing, the, uh, Natakla taxo of the active chemotherapy control, which does match the phase two trial by the way.

But I remember the initial phase three design a lot for investigator choice.

This year, we will see important results from our phase II gratitude trials and anti psychotic induced weight gain in our dose ranging study in patients with non alcoholic Seattle hepatitis or Nash.

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

Joe?

Joseph Belanoff: Thank you, Charlie.

Our portfolio of more than 1000 proprietary molecules together with funds provided by our commercial success will allow us to further broaden our lines of inquiry.

Our Cushing Syndrome business is built on a solid foundation, a life-saving medication, promoted by a commercial team that puts the interests of patients first.

Our strong second quarter results reflect this.

As the country gets closer to resuming a pre-pandemic way of life, physicians will experience fewer, challenges identifying, diagnosing, and optimally treating their patients, especially those with a complex disorder such as Cushing Syndrome.

Leading endocrinologists increasingly believe that there are substantially more patients, with Cushing Syndrome than was once assumed.

All of our compounds modulate cortisol effects by binding strongly to the glucocorticoid receptor GR.

For many of these patients, Quorum is an excellent treatment.

We reiterate our 2022 revenue guidance of $400 to $430 million.

Not bind to the progesterone receptor and so Dell costs on our core loans are approved products most serious off target effects.

We are extremely optimistic about our clinical development programs.

We believe cortisol modulation has the potential to treat many serious diseases.

Interesting play, while all of our compounds modulate cortisol activity without modulating progesterones activity, they're not identical some cross the blood brain barrier others do not some perform best in models of solid tumors, others are more potent in models of metabolic disease, some appear to be tissue specific.

Others have more global effects.

These diverse qualities allow us to effectively examined a wide variety of disorders. Currently we are studying ovarian adrenal in prostate cancer anti psychotic induced weight gain Nash and of course Cushings syndrome.

We plan to start a phase two trial in patients with ALS this quarter and have additional compounds in phase one in preclinical development.

Our Cushing syndrome business has funded all of these programs and we'll continue to do so.

Our oncology program is testing three anti cancer mechanisms first postulated by investigators at the University of Chicago and later confirmed by other prominent researchers.

One mechanism is increasing a pop ptosis programmed cell death that chemotherapy is meant to induce in solid tumors.

It all works against the beneficial effects of chemotherapy by suppressing a pop doses and our successful controlled phase II trial in women with platinum resistant ovarian cancer. The addition of the selective cortisol modulator rella cortland enhance the effects of chemotherapy.

The positive results of our Phase II trial in women with platinum-resistant ovarian cancer, provide serious evidence supporting cortisol modulation's broad application.

So what, um, as you launched that last month, what led to, uh, that, uh, change?

Yeah, no, I understand the question and Bill, if you're out there, um, would you please, answer that?

Yeah, that's, uh, thank you very much for the question.

So it was a really easy decision to make this.

We were looking at the phase three study design and working with, uh, the GOG, the gynecological, oncology group, as well as, and got, we had thought of and come up with many different iterations of a phase three design. And the first one that you had mentioned was investigator choice.

Likely by Blunting cortisol anti apoptotic effect.

While these women's disease had progressed on two or more previous lines of treatment, including previous Taxane rella correlate appear to re sensitize somewhat empty chemotherapies beneficial effects.

In addition, the women who received rella Cortland plus chemotherapy experienced no additional side effect burden compared to those who received chemotherapy alone.

<unk> provided a meaningful benefit to many of the limit in our study.

Those who received rella cortland intermittently.

Before the day of and the day after they received Nab paclitaxel exhibited a statistically significant improvement in progression free survival and duration of response compared to the group who received Nab Paclitaxel monotherapy.

While our study was not powered to show a difference in overall survival for Oss compared to Nab Paclitaxel monotherapy women in the intermittent <unk> group also live longer than those in the comparator arm with a P value that approach statistical significance.

No approved therapies have demonstrated an overall survival benefit in patients with platinum resistant ovarian cancer.

The results from this study were featured in podium presentations at the September 2021 European Society for medical Oncology ESMO Congress and at the 2022 American Society of clinical oncology <unk> annual meeting.

As we announced last month, we have started a pivotal phase III trial in platinum resistant ovarian cancer, which we have named rosella.

Planned enrollment is 360 women randomized one to one to receive either <unk>, plus Nab paclitaxel or Nab Paclitaxel alone.

The primary endpoint will be progression free survival with overall survival secondary endpoint, Brazil.

Zealous design closely tracks, our phase II study with.

With adjustments that emerge from constructive conversations with the FDA and leading clinicians from the gynecologic oncology group in the United States and the European network of Gynecological oncology trial groups in Europe .

But after we got very positive and supportive comments from the FDA, we then looked at other, analyses around prior Bevacizumab use as well as patients who had one to three prior lines of therapy and patients who had excluded where we excluded primary platen refractory patients.

Two adjustments foreign special notice.

Women, who enroll and rosella must have received prior bevacizumab therapy, which is the current standard of care in the United States for patients with platinum resistant ovarian cancer.

59% of the limited our phase two study had received prior Bevacizumab and we expect this percentage to continue to increase in clinical practice.

Second women, whose tumors have not responded at all to platinum based treatments and those who have received more than three prior lines of therapy will be excluded.

Women in our phase II study meeting these criteria exhibited even greater differential improvement in progression free survival duration of response and overall survival without an increase in the frequency of severity or severity of adverse events.

Median PFS for women, who received rella correlate intermittently to seven three months compared to $3 seven months for the women, who receive Nab paclitaxel alone the hazard ratio of <unk>.

Looking at that analysis, we then decided to repeat the phase two study because we saw, unprecedented results where, as Joe had indicated, we saw an overall, um, response rate for PFS of greater than, um, three months with a hazard ratio of 0.40. We saw OS benefit of greater than five months with a hazard ratio of 0.38. And we saw a benefit of about two and a half months of duration response with a hazard, ratio of 0.29.

Their median OS was also significantly longer $17 nine months compared to $12 six months with a hazard ratio of <unk> three.

H.

So looking at those phase two results and talking in, in working with the FDA, we felt, it was simplest to just repeat the phase two trial in our phase three study design. And the FDA agreed with that as well. So that was the simplest path to moving forward as quickly as possible.

Our goal in phase III is simply to replicate our positive phase two results, leading gynecological oncologists have told us that in their view relative Orleans potential benefit.

And it was a very simple and easy path for us to follow.

Swayampakula Ramakanth, Joon Lee, Atabak Mokari, Swayampakula Ramakanth, Joon Lee, Atabak Mokari, This is, you know, we're using rel-correlant.

We had a choice between rel-correlant or ex-correlant.

<unk> survival without increased side effect burden would constitute an important medical advance and that relative <unk> plus Nab paclitaxel has the potential to become a new standard of care in women with platinum resistant ovarian cancer.

Our second mechanisms by which cortisol modulation may prove useful slide blocking an important tumor growth pathway.

Cortisol stimulation is a major reason why patients with prostate cancer treated with a widely prescribed androgen receptor antagonist and <unk> eventually experienced resurgent disease.

Comprised of androgen stimulation their tumors switch to cortisol activity to stimulate growth.

Our hypothesis is that adding a cortisol modulator to androgen deprivation therapy will close this tumor escape route.

We recently completed a dose finding study of our selective cortisol modulator <unk> combined with <unk> in men with castrate resistant prostate cancer.

Investigators at the University of Chicago led by Professor Russell <unk> completed a similar study of <unk> combined with <unk>.

And the person who led the rel-correlant study in previous study in dose-finding in this group, Russell Smallwoods at the University of Chicago, is actually going to be leading this study as well as an investigator study, as a grant-funded study.

Both studies produced acceptable dosing regiments.

So the timing is a little bit more opaque to us, although I know he's very anxious to get going with it.

We have decided to proceed with the randomized placebo controlled phase II trial umbrella Cortland, plus <unk> in patients with prostate cancer in collaboration with Dr. Smaller with the University of Chicago.

Everything that he said is, in fact, true.

It's been very nice to see, because of, you know, Enzalutamide's real success, that patients with prostate cancer have received a lot of benefit that, you know, was really unthinkable 15 years ago.

Patients and professor smell it lets us plan study will be treated with either <unk> or <unk>, plus and solidified before they have had an initial prostatectomy.

<unk> has been shown to have benefit much earlier in patients treatment path and was apparent at its first approval and we think that <unk> has the potential to add to its benefit.

And as I said in my comments earlier, Enzalutamide not just seems to work kind of at the end-of-the-line treatment, but earlier in therapy.

So I'll remind you again, this is a study that he had great interest in us, that he has now gotten funded, to look at patients pre-prostatectomy.

Patient group that will be studied as large as is the commercial opportunity.

That, you know, obviously that's about as early as you can get.

A third therapeutic mechanism seeks to treat tumors by reducing cortisol suppression of the immune system.

Holly was all but likely once the effectiveness of therapies intended to enhance the body's immune response.

We are conducting an open label phase <unk> trial of <unk>, plus the PD, one checkpoint inhibitor <unk> merck's drug keytruda in patients with advanced adrenal cancer, whose tumors produce excess cortisol.

That's before diagnosis and even surgery. It does seem like Enzalutamide actually has real benefit for those patients, in the long run.

We think that adding rel-correlant to that to shut off really a tumor escape group will have even greater benefit.

But the timelines for it at this point in time are a little uncertain to us. But it will be some time.

You know, you're absolutely right.

This is not like an end-stage disease, where, you know, sadly people die quickly.

These patients suffer the effects of between cancer, and Cushing syndrome, and usually quickly lethal combination.

We'll have to look at this over a period of time.

Henry Iliza map is rarely effective in treating this form of adrenal cancer.

And I'll get back to you with more specifics in coming calls.

Thank you.

We believe that excess cortisol suppressing the immune system may be counteracting the intended effects of <unk>, which is to stimulate the immune system.

Operator: Your next question comes from the line of Greg Fraser from Truist.

Your line is now open.

Our trial is evaluating with the relic orland and treat these patients cushings syndrome by reducing excess cortisol activity and by reversing cortisol induced immune suppression allow <unk> to achieve its full cancer, killing effect.

We plan to enroll 20 patients at sites across the United States. The primary endpoint of the study is objective response rate with secondary endpoints, including progression free survival duration of response and overall survival.

I'll turn now to our programs in metabolic disease, which will produce important data soon.

This year, we will see important results from our Phase II gratitude trials in antipsychotic-induced, weight gain and our dose-ranging study in patients with non-alcoholic steatohepatitis or NASH.

Our portfolio of more than 1,000 proprietary molecules, together with funds provided by, our commercial success, will allow us to further broaden our lines of inquiry.

We are conducting two double blind placebo controlled phase II trials mirror core Lynch <unk>.

All of our compounds modulate cortisol's effects by binding strongly to the glucocorticoid, receptor, or GR.

<unk> and gratitude.

They do not bind to the progesterone receptor and so don't cause some of Quorum's, our, approved products, most serious off-target effects.

Patients with anti psychotic induced weight gain serious and widespread disorder.

In the United States 6 million people take anti psychotic medications, such as Olanzapine and risperidone to treat illnesses, including schizophrenia bipolar disorder and depression.

While these drugs are very effective because rapid and sustained weight gain as well as cardiovascular and metabolic disease.

The burden on patients and severe.

Average life expectancy of patients in the United States, who take the anti psychotic medications chronically has decreased by 20 years.

Side effects also dissuade many patients from adhering to their treatment regimen.

The gratitude trials seek to build on the positive data from our study of mirror Cortland in healthy subjects.

Interestingly, while all of our compounds modulate cortisol's activity without modulating, progesterone's activity, they are not identical.

Some cross the blood-brain barrier.

Others do not.

In 2020, we completed trial in which 96 healthy subjects received olanzapine and either 600 milligrams of mirror Orland 900 milligram severe cortland or placebo for 14 days.

Some perform best in models of solid tumors.

Others are more potent in models of metabolic, disease.

Some appear to be tissue-specific.

Others have more global effects.

These diverse qualities allow us to effectively examine a wide variety of disorders.

Who received korlym and significantly less weight and those who received placebo. They also exhibited a smaller increase in triglycerides and in the liver enzymes Alt and AST, which typically exhibit sharp transient increases at the start of Olanzapine therapy.

A paper describing these results was published in the journal of clinical Psychopharmacology last year.

Gratitude is evaluating whether mirror cortland can reverse recent antipsychotic induced weight gain.

Currently, we are studying ovarian, adrenal, and prostate cancer, antipsychotic-induced weight gain, NASH, and, of course, Cushing's Syndrome.

Agents with schizophrenia or bipolar disorder received in addition to their established Joseph anti psychotic medication, either 600 milligrams of <unk> or placebo for 12 weeks.

We plan to start a Phase II trial in patients with ALS this quarter and have additional, compounds in Phase I and preclinical development.

Our Cushing's Syndrome business has funded all of these programs and will continue to do so.

Gratitude to his testing mirror korlym as a treatment for long standing antipsychotic induced weight gain patients.

Patients with schizophrenia receive in addition to their established dose of anti psychotic medication, either 600 milligrams or 900 milligrams with Miracle, Ireland or placebo for 26 weeks.

While the primary endpoint in both studies is reduction in body weight is important to stress that measures of metabolic activity will be examined that are equally important to patient health.

<unk> and lipids glucose control in markers of liver health would be highly desirable outcomes. These studies will produce important data in many areas.

Dosing of patients in both trials is complete we look.

<unk> results by year end.

Mirror Cortland is also our Kennedy treatment for patients with Nash.

Serious liver disorder that affects millions of patients in the United States.

In our prior study patients who received <unk> exhibited large rapid reductions in liver fat, but also substantial albeit transient elevations of ALC ASD.

The improvement in liver fat in these patients was greater and incurred much more rapidly than we had expected and are rarely seen over any period of treatment.

Patients exhibited reductions from 38, 5% to 73, 8% after receiving mirror correlate for just one month.

This in perspective recall that the trial's primary endpoint was a 30% reduction in liver fat after 12 weeks.

And maybe that the rapidity of mirror correlates fat, reducing effect caused the patients PLT and ASC to rise one way to deliver ships that is by metabolizing fatty acids, which in excess of amounts irritate the liver.

It's in the bloodstream obese patients did not increase providing support for the idea that mirror cortland caused their excess fat to be metabolized immediately within the liver.

Our current phase <unk> dose finding trial in patients with presumed Nash is to identify a dosing regimen that significantly reduces fat without causing excess of liver irritation.

Results later this year.

As most of you know we are evaluating relative Moreland, our planned successor to Korlym for the treatment of hyper cortisol is in two phase III trials race in gradient.

<unk> is a selective cortisol modulator like korlym it achieves its effect by competing with cortisol at the glucocorticoid receptor.

Our oncology program is testing three anti-cancer mechanisms, first postulated by investigators at the University of Chicago and later confirmed by other prominent researchers. One mechanism is increasing apoptosis, the program's cell death that chemotherapy is meant to induce in solid tumors. Cortisol works against the beneficial effect of chemotherapy by suppressing apoptosis. In our successful, controlled Phase II trial in women with platinum-resistant ovarian cancer, the addition of the selective cortisol modulator relacorrelant enhanced the effect of chemotherapy, likely by blunting cortisol's anti-apoptotic effect.

While these women's disease had progressed on two or more previous lines of treatment, including previous taxanes, relacorrelant appeared to resensitize some of them to chemotherapy's beneficial effects. In addition, the women who received relacorrelant plus chemotherapy experienced no additional side effect burden compared to those who received chemotherapy alone. Relacorrelant provided meaningful benefit to many of the women in our study. Those who received, relacorrelant intermittently, the day before, the day of, and the day after they received napaquitaxel exhibited a statistically significant improvement in progression-free survival and duration of response compared to the group who received napaquitaxel monotherapy.

While our study was not powered to show a difference in overall survival, or OS, compared, to napaquitaxel monotherapy, women in the intermittent relacorrelant group also lived longer than those in the comparator arm, with a p-value that approached statistical significance.

Unlike korlym it does not bind to the progesterone receptor PR for short and so does not cause PR related side effects, including termination of pregnancy, endometrial thickening and vaginal bleeding by.

By a different mechanism relic also does not appear to cause hypokalemia low potassium.

Area side effects experienced by 44% of patients Korlym pivotal trial Korlym.

Korlym induced hypokalemia is a leading cause of korlym discontinuation.

<unk> phase II 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 syndrome. There were no rella correlate induced instances of endometrial thickening or batch no bleeding and no drug induced hypokalemia.

Trial results were published in frontier and endocrinology last year.

Grace has a planned enrollment of 130 patients with any etiology of Cushing syndrome, and is a randomized withdrawal trial design.

All patients initially receive <unk> for 22 weeks those who meet response criteria are randomized to continue treatment with Vela cortland or placebo for 12 weeks.

We and our investigators are eager to take race to the finish line.

We expect grades to serve as the basis for our NDA submission in Cushing Cushing syndrome, which we expect to submit in the second half of 2023.

Our second phase III trial gradient studying rella correlates effects in patients, whose cushings syndrome is caused by an adrenal adenomas or adrenal hyperplasia.

Patients with this etiology of Cushing syndrome, often experience a less rapid decline, but their health outcomes are poor.

Gradient is the first controlled study in patients with this type of Cushing syndrome.

While we do not expect our NDA cushings syndrome depend on data from gradient. We do expect that its findings will improve the care of these increasingly recognize patients.

<unk> a randomized placebo controlled study has a planned enrollment of 130 patients.

Finally, a word about <unk>, which has shown great promise in animal models of ALS.

ALS, commonly known as Lou Gehrig's disease is a devastating disease with very modest pharmacologic treatment options.

This quarter, we plan to initiate a 198 patient randomized double blind placebo controlled phase II trial of potassium Cortland and <unk> ALS, which we have named Dazzles EAC AOS.

This study is being shepherded by <unk>, a leading AOS academic consortium in Europe .

Good afternoon, folks.

Sum up our second quarter commercial results were strong and we expect growth to continue as pandemic conditions receipt, we have reiterated our 2022 revenue guidance of $400 million to $430 million.

Thanks for taking the questions.

First of all, on Coraline, you had good year-over-year growth in sales.

The trajectory doesn't appear to have been impacted so far by the newest entrant into the Cushing's market.

Our development programs continue to generate evidence validating our long held belief that cortisol modulation has the potential to treat a wide range of diseases. We.

Reducing cortisol activity is a straightforward way to treat Cushing syndrome.

It now appears clear is it excessive cortisol activity effects other very important diseases and can be improved by cortisol modulation.

Ovarian cancer is an excellent example, but there will be others.

Later this year, we will have important data from our anti psychotic induced weight gain and Nash studies.

Just opening multinational trial in ALS has real promise.

Our whole academic field and the use of cortisol modulation in alcohol and other addictions has begun.

And in addition to <unk> and Mira <unk> and <unk>, we have many individually distinguishable cordial cortisol modulators with clinical potential.

Of course that is steadily advancing.

I'm just curious if you've detected any impact so far on utilization, trends, or prescribing that might be related to, Coraline.

Greg, thanks for the question.

I think our dedicated creative employees and loyal investors for making this possible.

No, we have not seen an impact from the competition, and, truthfully, we're pleased that more companies are out there educating physicians on hypercortisolism, and obviously, guidelines and proper screening as this will continue to help patient care.

I'll stop here for questions.

Yeah.

And as a reminder to ask a question Healy Crestar one one on your telephone.

On the GRACE study, I know you reiterated your target for NDA submission.

Can you just, confirm that enrollment in the study has been progressing in line with your expectations?

Please standby alone to compile the Q&A roster.

Yeah, in fact, let me give you back over to Bill again, who seems to be working.

Okay.

And our first question comes from the line of Matt Kaplan with Ladenburg. Your line is now open.

Bill: Go ahead, Bill.

Yes, yes, thank you for that question.

Hi, Thanks for taking the questions and congrats on a good quarter.

So, yes, timelines are still on track.

No approved therapies have demonstrated an overall survival benefit in patients with, platinum-resistant ovarian cancer.

I guess with the with the.

Initiation of Phase III study in.

Platinum resistant.

Varian cancer patients can you help us understand the market opportunity there.

Typically how many patient ovarian.

Cancer patients in the U S and.

How many of those are platinum resistant and would be.

Targets for your treatment.

Yes.

Results from the study were featured in podium presentations at the September 2021 European Society for Medical Oncology, ESMO, Congress, and at the 2022 American Society of Clinical Oncology, ASCO, annual meeting.

Thanks, Matt Thanks, very much for the question.

So first.

As we announced last month, we have started a, pivotal phase three trial in platinum-resistant ovarian cancer, which we have named ROSELA. Planned enrollment is 360 women, randomized one-to-one, to receive either relacorrelant plus napaquitaxel or napaquitaxel alone. The primary endpoint will be progression-free survival, with overall survival a key secondary, endpoint. Rosella's design closely tracks our Phase II study, with adjustments that emerged from, constructive conversations with the FDA and leading clinicians from the Gynecologic Oncology Group in the United States and the European Network of Gynecological Oncology Trial Groups, in Europe.

You know, first and foremost, we're excited and focused on finishing this study as are each and every one of the investigators because of the benefit Reller-Correlate can bring to their patients. You know, we've completed a few investigator, meetings in the U.S. and Europe, and each of the investigators really reiterated their excitement and enthusiasm for Reller-Correlate and their unwavering need and desire to help us enroll this study expeditiously.

I just want to point out I know you know this to the whole group that the group of platinum resistant patients are a subgroup of patients all patients who.

Two adjustments warrant special notice.

Berrien cancer.

First, women who enroll in Rosella must have received prior bevacizumab therapy, which, is the current standard of care in the United States for patients with platinum-resistant ovarian cancer. Fifty-nine percent of the women in our Phase II study had received prior bevacizumab, and, we expect this percentage to continue to increase in clinical practice.

Second, women whose tumors have not responded at all to platinum-based treatments and those, who have received more than three prior lines of therapy will be excluded. Women in our Phase II study meeting these criteria exhibited even greater differential, improvement in progression-free survival, duration of response, and overall survival without an increase in the frequency or severity of adverse events. The median PFS for women who received Relacorlin intermittently was 7.3 months, compared to, 3.7 months for the women who received napaquitaxel alone, with a hazard ratio of 0.40. Their median OS was also significantly longer, 17.9 months compared to 12.6 months, with, a hazard ratio of 0.38.

Proximity is that they are somewhat above 200000 patients in the countries, who have ovarian cancer and our best estimate is about 2000, 25000 patients who have platinum resistant disease and about an equal number in Europe to that.

Okay great.

And with the with the Phase III trial can you help us understand kind of the timeline for.

Our goal in Phase III is simply to replicate our positive Phase II results.

So, based on all of our interactions with investigators, we feel that we are still on track.

American gynecological oncologists have told us that, in their view, Relacorlin's potential, benefit, improved survival without increased side-effect burden, would constitute an important medical advance and that Relacorlin plus napaquitaxel has the potential to become a new standard of care in women with platinum-resistant ovarian cancer.

A second mechanism by which cortisol modulation may prove useful is by blocking an important, tumor growth pathway.

Cortisol stimulation is a major reason why patients with prostate cancer treated with, a widely prescribed androgen receptor antagonist, enzalutamide, eventually experience resurgent disease. Deprived of androgen stimulation, their tumors switch to cortisol activity to stimulate growth.

For that program.

Very good.

Yes in fact, I'm going to try something.

Really got a technology, but bill Guyer, our Chief Development Officer is in Europe , and on the line and the <unk>.

Unknown Speaker: And then on the prostate cancer program, can you comment on any efficacy signals that were seen in the Phase 1 study?

Thank you.

You can actually hear me an answer.

I'll take that question.

Yes. Thank you very much for that question. So yes, there were still a study is open and we're actively working with sites to enroll patients as soon as possible. We're also actively working with adding additional sites around the world. So when I look at this trial with our estimates. This study will take us about 12 to 14 months to enroll the study.

Yeah, I just, I mean, there really is a quick, answer to that.

Our hypothesis is that adding a cortisol modulator to androgen deprivation therapy will close, this tumor escape route. We recently completed a dose-finding study of our selective cortisol modulator hexacorrelant, combined with enzalutamide in men with castrate-resistant prostate cancer.

It's really designed as a dose-finding study, obviously not in a controlled setting.

Investigators at the University of Chicago, led by Professor Russell Smolowitz, completed, a similar study of Relacorlin combined with enzalutamide. Both studies produced acceptable dosing regimens. We have decided to proceed with a randomized placebo-controlled Phase II trial of Relacorlin, plus enzalutamide in patients with prostate cancer in collaboration with Dr. Smolowitz at the University of Chicago. Patients in Professor Smulowitz's planned study will be treated with either enzalutamide, or Relacoralin plus enzalutamide before they have had an initial prostatectomy.

So, I don't think that there's really much efficacy data that I can relate to you for things that you could draw forward from.

I think that all of the results, again, you know, in the investigator study will be presented at a conference as we will as well.

But I just want to remind the group that whatever one sees there, reminding that this is really a safety and tolerability study and to give us an indication for where to go next.

Enzalutamide has been shown to have benefit much earlier in patient's treatment path and, was apparent at its first approval and we think that Relacoralin has the potential to add to its benefit.

The patient group that will be studied is large as is the commercial opportunity.

A third therapeutic mechanism seeks to treat tumors by reducing cortisol suppression of, the immune system, a quality of cortisol that likely blunts the effectiveness of therapies intended to enhance the body's immune response. We're conducting an open-label phase 1b trial of Relacoralin plus the PD-1 checkpoint inhibitor, Pembrolizumab, Merck's drug Keytruda, in patients with advanced adrenal cancer whose tumors produce excess cortisol.

These patients suffer the effects of adrenal cancer and Cushing syndrome, a usually quickly, lethal combination.

Pembrolizumab is rarely affected in treating this form of adrenal cancer.

We believe that excess cortisol, by suppressing the immune system, may be counteracting the, intended effects of Pembrolizumab, which is to stimulate the immune system. Our trial is evaluating whether Relacoralin can treat these patients' Cushing syndrome, by reducing excess cortisol activity and by reversing cortisol-induced immune suppression allow Pembrolizumab to achieve its full cancer-killing effect.

We plan to enroll 20 patients at sites across the United States. The primary endpoint of the study is objective response rate, with secondary endpoints including, progression-free survival, duration of response, and overall survival.

Got it.

I'll turn now to our programs in metabolic disease, which will produce important data soon.

We are conducting two double-blind, placebo-controlled, Phase II trials of Miracoralin, Gratitude, and Gratitude II, in patients with antipsychotic-induced weight gain, a serious and widespread disorder.

In the United States, 6 million people take antipsychotic medications, such as olanzapine, and risperidone, to treat illnesses including schizophrenia, bipolar disorder, and depression. While these drugs are very effective, they cause rapid and sustained weight gain, as, well as cardiovascular and metabolic disease.

The burden on patients is severe. The average life expectancy of patients in the United States who take antipsychotic medications, chronically is decreased by 20 years. These side effects also dissuade many patients from adhering to their treatment regimen.

The Gratitude trials seek to build on the positive data from our study of Miracoralin, in healthy subjects. In 2020, we completed a trial in which 96 healthy subjects received olanzapine and either, 600 milligrams of Miracoralin, 900 milligrams of Miracoralin, or placebo for 14 days.

University, which typically exhibits sharp transient increases at the start of a lambs, of pain therapy.

A paper describing these results was published in the Journal of Clinical Psychopharmacology last year.

12 months to accrue the data so about two years from now we should see results from the sell of trial.

Gratitude is evaluating whether miracloraline can reverse, recent antipsychotic-induced weight gain. Patients with schizophrenia or bipolar disorder receive, in addition to their established dose of antipsychotic medication, either 600 milligrams of miracloraline or placebo for 12 weeks. Gratitude, too, is testing miracloraline as a treatment for longstanding antipsychotic-induced weight gain.

Patients with schizophrenia receive, in addition to their established dose of antipsychotic medication, either 600 milligrams or 900 milligrams of miracloraline or placebo for 26 weeks.

While the primary endpoint in both studies is reduction in body weight, it is important to stress that measures of metabolic activity will be examined that are equally important to patient health.

Improvement in lipids, glucose control, and markers of liver health would be highly desirable outcomes.

These studies will produce important data in many areas.

Dosing of patients in both trials is complete. We look forward to results by year end.

Okay, and then and then.

Miracloraline is also our candidate treatment for patients with NASH, a serious liver disorder that affects millions of patients in the United States. In our prior study, patients who received miracloraline exhibited large, rapid reductions, in liver fat, but also substantial, albeit transient, elevations of ALT and AST. The improvement in liver fat in these patients was greater and occurred much more rapidly than we had expected and are rarely seen over any period of treatment.

Patients exhibited reductions from 38.5% to 73.8% after receiving miracloraline for just one month. To put this in perspective, recall that the trial's primary endpoint was a 30% reduction in liver fat after 12 weeks. It may be that the rapidity of miracloraline's fat-reducing effect caused the patient's ALT, and AST to rise. One way the liver sheds fat is by metabolizing it into fatty acids, which in excessive amounts irritate the liver. Lipids in the bloodstream of these patients did not increase, providing support for the idea that miracloraline caused their excess fat to be metabolized immediately within the liver.

Our current phase 1b dose-finding trial in patients with presumed NASH aims to identify a dosing regimen that significantly reduces fat without causing excessive liver irritation. We expect results later this year.

And then last question on the ovarian cancer.

As most of you know, we are evaluating relacloraline, our plant's successor to coralline, for the treatment of hypercortisolism in two phase 3 trials, GRACE and GRADIENT. Relacloraline is a selective cortisol modulator. Like coralline, it achieves its effect by competing with cortisol at the glucocorticoid receptor.

Unlike coralline, it does not bind to the progesterone receptor, PR for short, and so does not cause PR-related side effects, including termination of pregnancy, endometrial thickening, and vaginal bleeding.

By a different mechanism, relacloraline also does not appear to cause hypokalemia, low potassium.

Do you think in the future that this could be an opportunity to move to earlier stage two.

A Serious Side Effect Experienced By 44% Of Patients In Corlum's PITFAL Trial.

Corlum Induced Hypochylemia Is A Leading Cause Of Corlum Discontinuation.

Relocorlin's Phase 2 efficacy and safety data were strong. Patients experienced meaningful improvements in hypertension and glucose control, as well, as in a variety of other signs and symptoms of Cushing syndrome.

There were no Relocorlin Induced instances of endometrial thickening or vaginal bleeding, and no drug-induced hypokalemia.

The trial results were published in Frontiers in Endocrinology last year.

GRACE has a planned enrollment of 130 patients with any etiology of Cushing syndrome and, has a randomized withdrawal trial design. All patients initially receive Relocorlin for 22 weeks. Those who meet response criteria are randomized to continue treatment with Relocorlin or placebo, for 12 weeks.

We and our investigators are eager to take GRACE to the finish line.

Treatment.

We expect GRACE to serve as the basis for our NDA submission in Cushing syndrome, which, we expect to submit in the second half of 2023.

Typically the frontline.

Our second Phase 3 trial, Gradient, is studying Relocorlin's effects in patients whose Cushing, syndrome is caused by an adrenal adenoma or adrenal hyperplasia. Patients with this etiology of Cushing syndrome often experience a less rapid decline, but, their health outcomes are poor.

In cancer combination as well.

Gradient is the first controlled study in patients with this type of Cushing syndrome.

While we do not expect our NDA in Cushing syndrome to depend on data from Gradient, we do expect that its findings will improve the care of these increasingly recognized patients. Gradient, a randomized placebo-controlled study, has a planned enrollment of 130 patients.

Finally, a word about Dasucorlin, which has shown great promise in animal models of ALS.

Thanks, Matt.

ALS, commonly known as Lou Gehrig's disease, is a devastating disease with very modest, pharmacologic treatment options. This quarter, we plan to initiate a 198-patient randomized, double-blind, placebo-controlled, Phase 2 trial of Dasucorlin in ALS, which we have named DAZLS, D-A-Z-A-L-S. This study is being shepherded by TRICALS, a leading ALS academic consortium in Europe.

The answer to that is something we're looking at very seriously.

As you know many many drugs are often approved in late line therapy.

Evidence.

Increases and of course with longer studies to move earlier in treatment and we are certainly taking a very close look at that.

That's really top of our list and I hope to really be able to update you on how we're thinking about that in coming calls.

Thanks for taking the questions.

Great. Thanks, Thanks for taking the question.

Sure. Thanks, Matt Thanks, Matt.

And your next question comes from the line of Dennis Yang with Jefferies. Your line is now open.

Operator: And your next question comes from the line

of Arkay from HSC Wainwright.

Arkay from HSC Wainwright: Your line is now open.

Hey, guys. Thanks for taking my question.

Two for me.

Question number one can you give a little bit more granularity on some of the patient dynamics in Q2.

Specifically, how much of the sequential revenue growth was from normalization of price how much of that came from patients who are new to korlym and how much came from patients who couldnt take the drug before because of Covid are getting back onto it and then my second question can you just.

Data on the Doj subpoena in terms of what we're waiting for and just to remind us what is the next step but it seems like this could be a pretty major a binary event.

Thank you.

Okay. Thanks, Julie unfolds. Thank you.

Okay. Thank you Dennis and <unk>.

A year from your first like to introduce reintroduce our group to Sean Duke who is the president of our Endocrinology Division.

Sandy handling all responsibilities, including the commercial responsibilities.

Good afternoon, gentlemen.

Dennis Thanks for the question I thought I would start just first off by pointing to.

To remind everyone that Q1 is typically slightly depressed rate because of all the insurance changeovers and the volume of free drug that we give to ensure patients don't stop therapy over the course of their insurance reauthorization.

That being said, we're very pleased with the second quarter.

To sum up, our second quarter commercial results were strong, and we expect growth to continue, as pandemic conditions recede. We have reiterated our 2022 revenue guidance of $400 to $430 million.

It looks like we have a very good quarter.

Our development programs continue to generate evidence validating our long-held belief that, cortisol modulation has the potential to treat a wide range of diseases. Reducing cortisol activity is a straightforward way to treat Cushing syndrome. What now appears clear is that excessive cortisol activity affects other very important diseases, and can be improved by cortisol modulation.

Lung cancer is an excellent example, but there will be others.

To remind everyone of what are the key drivers of our business and that's really a patient's ability to see their doctor and person and then of course, our clinical specialists ability to meet with physicians again, both of those are key drivers in the second quarter and we did see some improvement.

Later this year, we will have important data from our antipsychotic-induced weight gain, and NASH study.

Our just-opening multinational trial in ALS has real promise.

A whole academic field in the use of cortisol modulation in alcohol and other addictions, has begun. And in addition to Relaquarelent, Miraquerelent, and Dazaquerelent, we have many individually, distinguishable cortisol modulators with clinical potential.

I'll stop here for questions.

Just a couple of quick questions on the pipeline front.

Corcept is steadily advancing.

And as a reminder, to ask a question, you will need to press star 11 on your telephone.

On the Rosella study, does the study have an interim look?

I thank our dedicated, creative employees and loyal investors for making this possible.

And if it does, at what point is the interim look going to be?

Please stand by while we compile the Q&A roster.

Bill: Bill, could you take that question?

Look in those areas and that led to more patient physician interaction more of course that physician interaction, which led to more new patients being prescribed and more new prescribers actually coming onboard. So I'd say those two are the main the main drivers of the change.

Sure, I'll take that question.

No, we do not have an interim look into this study.

The primary endpoint is PFS. And so, when we hit our predefined PFS numbers, that's when we will read out the study. And our, secondary endpoint is overall survival.

So, at this point in time, there is not an interim look designed for the Rosella study.

Okay, thank you.

And then, on the Diazell study in ALS, I'm trying to understand how diazolicor lentil works and also does this drug have any efficacy, in other movement disorders or neuromuscular disorders such as MS and Parkinson's?

Yeah, you know, I'm glad you asked that.

It's a little more scientifically far afield than I usually get in conference calls, but you know, RK, you know me, I could talk about this for a long time.

So, the bottom line is it's been known for quite a while that there are neuromuscular diseases and ALS is a good example where you have aberrant cortisol activity.

Cortisol levels are higher, people lose their diurnal rhythm, and there really has been a thought that this contributes to disease progression.

What really got us interested in ALS specifically is there's a good animal model of ALS. It's obviously not exactly the same as ALS, but it's one that's been used for a very long time called the wobbler mice.

In some sense, it sounds sort of like what it is.

These are animals which really lose their coordination and may manifest similar symptoms to what people do who have ALS.

And they have the same cortisol issues that people do as well.

And now, you know, in I guess almost half a dozen publications, it's been shown that DETS, CORAL, and GR modulation really changes that.

In the animals, at least, not only do the animals slow their decline in their neurologic symptoms, they actually improve over a period of time.

The prescribers again all of that being said.

So, of course, not everything in animals translates to people.

It would be wonderful if that actually did translate to people.

But the bottom line is there's really a good reason to give it a try.

Neither of those metrics have reached the pre pandemic levels.

I've said it before, ALS is kind of, you know, as much as we have one, you know, the Mount Everest of medical maladies, terrible problem.

And if we could offer these patients anything that resembled the results that we saw in animals, that would be a wonderful thing.

C before the start of COVID-19, and we're actually not sure if they have a role as an organization.

Medicine now.

Practices are closing their doors in some cases the pharmaceutical representatives.

Creates operational hurdles that are not just for some specific rate. These are industry wide and what our commitment as we have worked hard to find new ways to operate in that normal in <unk>.

Our continuing to do that I'm very confident that we will find new and creative ways to continue to reach our targets.

Now, your second question is also prescient because there are other neuromuscular diseases where there is cortisol aberration.

And Charlie would you like to answer the second question. Please sure.

For instance, Huntington's disease is one.

And we actually have preclinical investigators who are studying Huntington's disease at this point.

I happen to just coincidentally be talking to an investigator today who is interested in looking at GR modulation in Parkinson's disease.

So, you know, as you know, psychiatry and neurology have been my interest for a very long period of time.

Hi, yes. Thanks for the question. The short answer is there's no updates with respect to the Doj subpoena, but before I elaborate a little bit on on that let me give background for folks who might not be as familiar.

Folks may recall that back in 2018, or so we suffered some sort.

Short seller attention in the tax that we pushed through a course, but but there are a couple of lingering consequences that one was this securities class action that we are.

Grinding through right now and the other I believe is this Doj inquiry.

These are very difficult areas in which to show progress.

But I do think that we will be enlarging our programs in this area and hopefully ultimately be able to offer patients.

And we actually have preclinical investigators who are studying Huntington's disease at this point.

I happen to just coincidentally be talking to an investigator today who is interested in looking at GR modulation in Parkinson's disease.

So, you know, as you know, psychiatry and neurology have been my interest for a very long period of time.

They requested a whole bunch documents concerning our commercial our commercial business.

These are very difficult areas in which to show progress.

But I do think that we will be enlarging our programs in this area and hopefully ultimately be able to offer patients something they clearly cannot get today.

Yes.

Our approach to this beyond obviously cooperating with the Doj is to give them as much information they want faster than they can actually absorb it just because we want to get all the information in front of them. So that we can move through this we think thats our.

Thank you for that.

And then in the gratitude studies where the data is expected by the end, of this year, so what are the next steps in those development programs in terms of, you know, when you could initiate of this year?

So what are the next steps in those development programs in terms of, you know, when you could initiate late-stage trials in looking at antipsychotic-induced weight gain?

Yeah.

<unk> solution. The truth is our friend in this case and we are moving things as quickly as we can on our side and I stress that just because it's a little unusual I think the typical strategy is just to delay delay delay we see no point in doing that.

We know Theres light at the end of the tunnel and that's what we're driving to as fast as we can having said that of course, we don't control. The pace of this all we can do is put information out there as it is requested.

And faster than expected we're doing that.

But other than that that's all I can report because thats all I know so well.

This will be resolved at some point, we're very confident in our position.

Well, first, we're very excited to complete these studies.

Can't say more than that right now.

Thank you Dennis.

And your next question comes.

Operator: And our first question comes from the line of Matt Kaplan with Lattenberg.

No one has ever had a successful study in reversing antipsychotic-induced weight gain.

Comes from the line of Michael <unk> from Canaccord. Your line is now open.

Matt Kaplan: Your line is now open.

You know, we could do it in animals, and we have real hopes in these studies, but I just, you know, thank our internal staff and our investigators for actually getting, this all enrolled and up to the point where we're going to see results.

Hi.

Thanks for taking the questions, and congrats on a good quarter.

I think, as I said before, I just wanted to emphasize this point that we're not just looking at weight gain.

Hello, This is Michael on for Edward.

Hopefully, we'll really see the follow-up changes that will be very beneficial to these patients as well, and one thing I haven't commented on before, we may see psychiatric changes that are beneficial to these patients because we think that cortisol modulation has a chance to actually be useful in that vein as well.

I really don't want to promise that.

I guess with the initiation of your phase three study in platen-resistant ovarian cancer, patients, can you help us understand the market opportunities there, specifically how many patients, ovarian cancer patients in the U.S. and how many of those are platen-resistant and would be targets for your treatment?

Now, the answer to your specific question I could give you, you know, my general answer would be it's going to be results dependent on sort of what we have to do next, but if you go to the extreme end of a result that's extremely clear and easy to interpret, I'm certain that we will begin a late-phase study next year.

I haven't seen the results yet, but certainly, if the path is straightforward, that's where we'll go, but first, the results.

Unknown Speaker: Yeah.

Thank you.

Congrats on the quarter two quick questions.

So for the first three rosella trial can you remind us what led to choosing the Nab paclitaxel as the active chemotherapy control, which does match the phase II trial by the way, but I remember the initial phase III design a lot for investigator choice so what.

Thanks, Matt.

Thanks for taking all my questions.

Sure.

Operator: And your last question comes from the line of Alan Long with BioWatch News.

As you launched that last month, what led to that change.

Alan Long: Your line is now open.

Yes, no I understand the question and Bill Youre out there would you please answer that.

Thanks very much for the question.

Congratulations on another good quarter.

Yes. Thank you very much for the question. So it's a really easy decision to make this we were looking at the phase III study design and working with the Doj Gynecological oncology group as well as and got we had thought of and come up with many different iterations of the phase III design and the first one that you had mentioned with investigator choice but.

Hi, Alan.

Although – hey, Joe.

Although I've written about it, our readers would like to hear about, your rationale behind the ALS trial design. They notice – they note that that's not a, quote, pill-dipping phase to a pilot, unquote, but a larger well-controlled design.

So first, you know, I just want to point out, I know you know this to the whole group, that, the group of platen-resistant patients are a subgroup of all patients who have ovarian cancer. It's approximated that there are somewhat above 200,000 patients in the country who, have ovarian cancer, and our best estimate is there are about 20,000 to 25,000 patients who have platen-resistant disease, and about an equal number in Europe do that.

What motivated the commitment to a stronger design?

Okay.

You know, Alan, I really apologize.

Great.

It was static in the line, and I couldn't hear your question.

After we got very positive and supportive comments from the FDA. We then looked at other analyses around prior Bevacizumab view as well as patients who had one to three prior lines of therapy and patients who had excluded where we excluded primary platinum refractory patients.

Would you mind repeating it?

Sure.

And with the phase three trial, can you help us understand kind of the timeline for that, program?

Looking at that analysis.

We then decided to repeat the phase II study because we saw unprecedented results where as Joe had indicated we saw overall.

Yes.

Joseph Belanoff: In fact, I'm going to try something that, you know, I'm really bad at technology, but, Bill Geyer, our chief development officer, is in Europe and on the line.

Response rates for PFS of greater than three months with a hazard ratio of <unk> four zero, we saw OS benefit of greater than five months with a hazard ratio of <unk> 38, and we saw a benefit of about two five months of duration of response, but the hazard ratio of <unk> nine so looking at those phase II results.

And Bill, if you can actually hear me and answer, I'd like to take that question.

William Guyer: Yes.

Thank you very much for that question.

And so, yes, the ROSELLA study is open, and we're actively working with sites to enroll, patients as soon as possible. We're also actively working with adding additional sites from around the world.

So, when I look at this trial with our estimates, the study will take us about 12 to 14 months, to enroll the study, and about 12 months to accrue the data.

So, about two years from now, we should see results from the ROSELLA trial.

My readers noted that your ALS trial design, it's not a, what they would claim, a pill-dipping tentative phase to a pilot, but it's a larger well-controlled design.

Okay.

What motivated the commitment to a stronger design?

And then last question on the ovarian cancer.

Yeah.

And talking and working with the FDA. We felt it was simplistic to just repeat the phase II trial in our phase III study design.

Do you think, in the future, that this could be an opportunity to move to earlier stages, of treatment, specifically frontline ovarian cancer and combination as well?

I really – okay.

The FDA agreed with that as well so that was the simplest path to moving forward as quickly as possible and with a very simple and easy path for us to follow.

Yes, and I understand one comment to that because you asked specifically about why we went from dealers choice too.

Nab Paclitaxel alone just to remind everyone. Our phase II study was with Nab Paclitaxel alone and overall feedback we got including regulatory feedback was that that was a very <unk>.

Do you see to understand result, and if replicated would be very easy to understand as the phase III results.

Perfect. Thank you and just one additional quick one kind of on some of your earlier stage programs. So you recently just announced we've launched or are planning to launch.

In prostate cancer.

We were delighted with this brand name attended those patients tend to have great actually they tend to have a median OS of around 18% to 32 months, which is quite a long time for a trial. So can you discuss perhaps the timelines for this newly initiated trial, how long do you think you'll need to run a trial to see a benefit of <unk> correlates what you do like an interim.

Data cut.

And sort of see how it is going any sort of thoughts on this.

Program is it finally gets off the ground.

Yes, no I'm really glad that that caught your attention because it's very interesting program. It's really just the beginning and just a couple of things to remind the group.

This is.

We're using real Korlym, we had a choice between quarter Warner extra Korlym and the person who led the <unk> study in previous study and just finding in this group on Russell small, which is the university of Chicago is actually going to be leading this study as well as an investigator study is a grant funded.

So the timing is a little bit more opaque to us although I know he's very anxious to get going with it everything that you said is in fact true it's been very nice to see because of <unk> and Hulu divides real success that patients with prostate cancer have achieved a lot of benefit.

It was really unthinkable that 10 years ago, and as I said in my comments earlier and dilutive might not just seems to work kind of at the end of the line treatment earlier in therapy. So I'll remind you again. This is a study that he had great interest to us that he has now got funded to look at patients pre prostatectomy, obviously, that's about as early as.

You can get that's before diagnosis and even surgery does seem like <unk> actually has real benefit for those patients in the long run we think that adding really correlate to that to set up really a tumor escape will have even greater benefit but the timelines for it at this point in time are a little uncertain to us, but it will be some time.

Youre absolutely right. This is not like an end stage disease, we're seeing sort of SaaS people die quickly we'll have to look at this over a period of time and I will get back to you with more specifics incoming calls.

Different thank you.

Well, thanks, Matt.

Okay.

The answer to that is something we're looking at very seriously.

Now, I heard it that time, Alan, and really do appreciate that question.

Your next question comes from the line of Greg Fraser from Cowen. Your line is now open.

Good afternoon folks thanks for taking the questions.

As you know, many drugs are often approved in sort of late-life therapy, and then as, evidence increases and, you know, of course, with longer studies, it moves earlier in treatment.

So I'm going to repeat that question in case it was hard to hear for other people out in the, audience.

And we are certainly taking a very close look at that.

In fact, really top of our list.

First of all on Portland.

You had good year over year growth in sales the trajectory doesn't appear to have been impacted so far by the newest entrant into the Cushing market I'm. Just curious if you detected any impact so far on utilization trends or prescribing that might be related to the core lab.

And I hope to really be able to update you on how we're thinking about that in coming calls.

Yes, Greg I'm going to pass you back over to Sean Yeah, Greg. Thanks for the question no. We have not seen an impact from the competition and traditionally we're pleased that more patients are more companies or other educating physicians on hydrocortisone.

Thanks.

Thanks for taking the questions.

And obviously the guidelines.

Screening is this will continue to outpatient care.

Got it on the Grace study I know you reiterated your target for NDA submission can you just confirm that enrollment in the study has been progressing in line with your expectations.

Operator: And your next question comes from the line of Dennis Ding.

What Alan was asking is, instead of doing, you know, a small study that just looked at a specific biomarker or something like that, why are we doing essentially what is a very good-sized, well-controlled study?

Let's check please.

Yes in fact, let me give you back over to Bill again seems to be working go ahead Bill yes, yes. Thank you for that question. So yes timelines are still on track.

Dennis Ding: Your line is now open.

Hey guys, thanks for taking my question.

First and foremost we're excited and focused on finishing finishing this study is as our each and every one of the investigators because of the benefit roller correlate can bring to their patients. We've completed a few investigator meetings in the U S and Europe and each of the investigators really reiterated their excitement enthusiasm for rail Cortland and <unk>.

Two for me.

Question number one, can you give a, little bit more granularity on some of the patient dynamics in Q2?

Specifically, you know, how much of the sequential revenue growth was from normalization of price?

How much of that came from patients who are new to Cortland? And how much came from patients who couldn't take the drug before because of COVID but are getting back onto it?

Wavering.

Need and desire to help us enroll the study expeditiously so based on all of our interactions with investigators.

And then my second question, can you just update us on the DOJ subpoena in terms of what we're waiting for?

We feel that we are still on track.

Very good and then on the prostate cancer program can you comment on any efficacy signals that we're seeing in the phase one study. Thank you.

And just remind us what is the next step?

Yes.

I mean really there really is a quick answer to that is really designed as a dose finding study obviously not in a controlled setting so.

I don't think that Theres really much efficacy data that I can relate to you.

For things that you could draw forward from.

I think that all of the results again in the investigator study will be presented at a conference as we as we will as well, but I just wanted to remind the group that whatever one sees there reminding that this is really a safety and Tolerability study and to give us an indication for where to go next.

Got it thanks for taking the questions.

And your next question.

Comes from the line of RK from H C. Wainwright. Your line is now open.

It seems like this could be a pretty major binary event, you know, once it eventually unfolds.

Thank you.

Good afternoon gentlemen.

It looks like a very.

Very good quarter.

Just couple of quick questions on the pipeline front on the <unk> study.

Thank you.

Do you does the study.

Okay, thank you, Dennis.

Tim book.

And.

If it does at what point you think.

Greg.

Bill could you take that question.

Sure I'll take that question no. We do not have an interim look into this study the primary endpoint is PFS and so when we hit our pre defined PFS.

Numbers Thats, when we will read out the study and our secondary endpoint is overall survival. So at this point in time, there is not an interim look designed for the rest of our study.

Okay. Thank you.

And then on.

<unk>.

The <unk> study.

Yep.

Yes.

Im trying to.

Understand.

<unk>.

Ill pass on.

That is on our core land package.

Works and also.

That's this drug have any efficacy.

The.

Other movement disorders, neuromuscular disorders, such as Parkinsons.

And glad to hear from you.

Yes.

Joseph Belanoff: I'd first like to introduce, reintroduce our group to Sean Maduck, who is the president of our endocrinology division and really handling all responsibilities, including the commercial responsibilities for Corl.

I'm glad you asked that it's a little more scientifically our field and I usually get in conference calls.

I can talk about this for a long time.

So the bottom line, it's been known for quite a while that they are a neuromuscular diseases. In ALS is a good example, where you have abrin cortisol activity cortisol levels are higher people lose their diurnal rhythm and there really has been a thought that this contributes to disease progression.

What really got us interested unless specifically is there is a good animal model of AOS. Its obviously not exactly the same as AOS, but it's one that it's been used for a very long time called Wadler mice.

It sounds sort of like what it is these are animals, which really lose their coordination and may with manifest similar symptoms to what people do have pls and they have the same cortisol issues that people do as well and it's now.

And I guess almost half a dozen publications can shed on that.

Desk Korlym GR modulation.

Really changes that.

In the animals at least not only the patient did not only to the animals slow their decline and their neurologic symptoms. They actually improve over a period of time. So of course not everything in animals translates to people who would be wonderful if that actually did translate to people, but the bottomline is this really a good reason to even try I've said it before.

POS is kind of.

As much as we have won the Mount Everest.

Medical maladies terrible problem and if we can offer these patients anything that resembled the results that we saw in animals that would be wonderful thing and your second question is also prescient because there are other neuromuscular diseases, where there is cortisol.

Aberration for instance, Huntington's disease is one and we actually have preclinical investigators who are studying huntington's disease at this point.

I happened to just coincidentally be talking to an investigator today, who is interested in look each GR modulation in Parkinson's disease. So.

As you know psychiatry and neurology have been my interest for a very long period of time is a very difficult interest area.

He is in which to show progress, but I do think that we will.

Pete enlarging our programs in this area and hopefully ultimately be able to offer patients.

And we actually have preclinical investigators who are studying huntington's disease at this point.

I happened to just coincidently be talking to an investigator today, who is interested in look each GR modulation in Parkinson's disease. So.

As you know psychiatry and neurology have been my interest for a very long period of time. These are very difficult interest areas in which to show progress, but I do think that you will be.

Beat enlarging our programs in this area and hopefully ultimately be able to offer patients something that clearly cannot get today.

Thank you for that.

And then the gratitude studies.

The data is expected by the end of this year.

So what's what are the next steps in those development programs.

In terms of.

When your coordination of this year.

<unk>.

So what's what are the next steps in those development programs.

In terms of.

When you could initiate.

Trials.

And looking at.

Anti psychotic induced weight gain.

Yes.

First.

We're very excited to complete these studies no one has ever had a successful study in reversing anti psychotic induced weight gain.

We could do it in animals, and we have real hopes in these studies, but.

But I just think our internal staff and our investigators for actually getting this all enrolled and up to the point, where we're going to see results.

I think as I said before I just want to emphasize this point that we're not just looking at.

Hopefully, we'll really significant changes that will be very beneficial to these patients as well and one thing. We haven't commented on before we make some psychiatric changes that are beneficial to these patients because we think that cortisol modulation has chance to actually be useful in that vein as well now the answer to your specific question Ike.

I'd give you.

My General answer would be it's going to be results depend on us sort of what we have to do next but if you go to the.

Extreme and as a result, it's extremely clear.

And easy to interpret I'm certain that we will begin a late stage study next year I really don't want to promise that I haven't seen the results yet, but certainly it's a path to straightforward that's where we'll go.

First the results.

Thank you thanks for taking all my questions.

Dennis, yeah, thanks for the question.

Sure.

Okay.

I thought I would start just first off by pointing, to remind everyone that Q1 is typically slightly depressed, right, because of all the insurance changeovers and the volume of free drug that we give to ensure patients don't stop therapy over the course of their insurance reauthorizations.

And your last question comes from the line of Alan laws.

<unk> Your line is now open.

All that being said, you know, we're very pleased with the second quarter.

Congratulations on another good quarter.

I want to remind everyone of what are the key drivers of our business.

Hi, Alan.

Joe.

Although ive written about it our readers will like to hear about your rationale behind the Lf trial design.

To be noted.

Hello, dipping phase Iia pilot.

While there are larger well controlled design.

Motivated the commitment to a stronger design.

Uh huh.

And that's really a patient's ability to see their doctor in person.

I really apologize there was static in the line and I Couldnt hear your question would you mind repeating it.

Sure.

My record, Florida, that's trial design.

<unk>.

They will claim a pro.

Tentative phase two a pilot, but it is the larger well controlled design what motivate the curtain.

Stronger design.

Yes, I would really okay now I heard at that time.

And I really do appreciate that question and so im going to repeat that question in case. It was hard to hear for other people out in the audience, what Alan was asking it instead of doing.

Small study that just looked at a specific biomarker or something like that why are we doing essentially what is a very good sized well controlled study and I have to tell you a part of that is my own personal bias, which is debt.

And I have to tell you, part of that is my own personal bias, which is that, you know, it's very hard to know, particularly in psychiatric and neurological But it was very important for us to be able to, in some sense, sell this concept to a, very experienced group of investigators who believe that it had a shot.

It's very hard to know, particularly in psychiatric and neurologic diseases. What you actually have until you do a well controlled study.

Study with placebo.

And the flip side of that is that I think particularly in a disease like.

We're kind of sadly people only have one shot at a trial that you actually have to be able to present to them something that has a legitimate chance to actually providing real benefit.

As I said before our animal study is really quite positive, but it was very important for us to be able to sunset sell this concept and very experienced.

The investigators believe that had a shot because just to be blunt about it.

Because just to be blunt about it, if patients enter our study, they may never be able to, enter another study.

Patients enter our study they may never be able to enter another.

So we really wanted to get to the point, where we use their time and our time with guest and presented a result that actually is going to be the most positive about where we stand.

And so, we really wanted to get to the point where we used their time and our time the, best and presented a result that actually is going to be the most dispositive about where we stand.

Great.

Okay.

Thank you.

Thank you and then with the prostate upcoming prostate cancer study with <unk>.

And then, of course, that clinical specialist's ability to meet with physicians.

And then with the prostate, upcoming prostate cancer study, you stayed with Rilocorlant, rather than Exocorlant. And as I recall, Rilocorlant has excellent GI blocking properties, while Exocorlant, if I'm not mistaken, had some interesting tissue penetration.

With thriller Cortlandt, rather than Korlym.

Again, both of those are key drivers.

I recall ROIC has excellent job walking the property as well as the correlate if im not mistaken has some interesting tissue penetration is that correct and can you provide some color on the advantage.

Is that correct?

And can you provide some color on the advantages that prevent, that you think propel Rilocorlant, as a drug candidate?

Yes.

You think propelled rella korlym as a drug candidate.

Yeah.

Yeah. The first thing I'd say is a pretty close call on you.

The first thing I'd say is it's a pretty close call.

You know, it's sort of funny, you know, this is, we actually sat down at the very, beginning of these two studies, and we got first choice, and we picked Exocorlant.

It's sort of funny this is.

We actually sat down at the very beginning of these two studies and we got first choice would be picked extra cortland and.

And Dr. Smolowitz got second choice, and he got Rilocorlant.

<unk> got second choice and he got relative borrowing so clearly got it wrong there.

So, I clearly got it wrong there.

The results were pretty similar.

<unk> were pretty similar actually found with Korlym.

I actually found that Rilocorlant has a little bit better tolerability.

Our tolerability, it's a little bit easier drug to manufacture and in addition to that.

It's a little bit easier drug to manufacture. And in addition to that, we know a lot more about it.

We know a lot more about that study began studying lots of people with <unk>, we know pretty much how it at.

You know, since that study began, we've studied lots of people with Rilocorlant. We know pretty much how it acts.

So, Exocorlant is not going to zero.

<unk> is not going to zero, it's going to be on the shelf right. Now we just tried to be as objective as we could and we thought the prospects were better with relic correlate and just I'll just filling one that you have a good memory in the preclinical models, although bulk railroad Carlin and ex Korlym worked well extra correlate.

It's going to be on the shelf right now.

We just tried to be as objective as we could, and we thought the prospects were better with, Rilocorlant.

And just, you know, I'll just fill in one, that you have a good memory.

In the preclinical models, although both Rilocorlant and Exocorlant worked well, Exocorlant actually, did work a little better in the preclinical models.

Actually did work a little better in the preclinical models, but it highlights the point that I made before which is that you do.

But it highlights the point that I made before, which is that you do your best to translate, from animal studies, but it's not lockstep, and we just have to go with where the data showed us the best results.

Your best to translate from animal studies, but it's not lock step and we just have to go with where the data showed us the best results.

Yeah.

And lastly, this question might be for Sean.

Lastly.

This question might be for Sean I keep asking you. This.

I keep asking this.

How much increasing hub hub are you hearing out there or getting requests for treating, cushions that's really abnormal or less severe cushion?

How much increasing how.

Are you hearing out there or digging request score for treating <unk>.

Krishna.

That's really.

Either normal or less severe Christian.

And related to that, are the results for gradients being released about the same time as grace?

And related to that are the results for gradient being released.

About the same time, it's great.

So, it's really two in one.

That's really clear and just a quick related question on Alan Passover.

Yeah, that is a good question, Sean.

Sean Maduck: Alan, I'll pass it over to him.

Pass over to him okay. Thanks for the question Alan.

Yeah, thanks for the question, Alan.

Okay.

Corallum is prescribed for all etiologies of cushions, for pituitary patients all the, way through to these renal patients.

Korlym is prescribed for all ideologies of Krishna for pituitary patients all the way through to the renal patients and over time, we're seeing more and more efficient overall.

And over time, we've seen more and more patients overall be prescribed for all of those respective, etiologies.

Be prescribed.

Or for all of those respective geologist so I would say.

So, I would say...

The understanding of this illness has increased.

The.

Understanding of this comment is increase Thats, where we spend on obviously one of our time educating physicians and through that we've seen some demand increase jokers, yes, no I think.

That's where we spend, obviously, a lot of our time, educating physicians, and through that, we've seen some demand increase.

I don't know, Joe, if there's anything you want to add.

Joseph Belanoff: Yeah, no, I think that, Allen, I think that maybe, one of the things that you're getting at is, in some sense, what's the value of the study on adrenal adenomas, of the gradient study in particular?

Alan I think that may be one of the things that you are getting at is.

What's the value.

The study unintentional adenomas the gradient study in particular and in order to answer that I, just really have to keep the whole group's some context.

And in order to answer that, I just really have to give, the whole group some context.

You know, 15, 20 years ago, it really wasn't appreciated, how many patients there were, and again, still a rare disease, but more than people thought, who had hypercorazolism, Cushing syndrome, caused by adrenal tumors.

15, 20 years ago, it really wasn't appreciated how many patients there were and again, it's still a rare disease, but but but more than people thought who had hyper cortisol Cushing syndrome caused by adrenal tumors and probably a decade ago, we really started to see that that was a.

And probably a decade ago, we really started to see, that that was a real group.

A real group, but what's happened over the last decade is that data is really filled in now there is no doubt there are many patients who have hydrocortisone. Some caused by entry on tumors that have previously been ignored had bad outcomes are largely untreated and thats the group that actually.

But what's happened over the last decade, is that data has really filled in. Now, there is no doubt that there are many patients, who have hypercorazolism caused by adrenal tumors that have previously been ignored, had bad outcomes, are largely untreated.

And that's the group that actually, gradient study focuses on.

Radiant study focuses on now.

Now, we'd like to be able to help any patient, who has hypercorazolism, and I think that actually producing controlled results is one of the ways to really get there.

We'd like to be able to help any patient who is hyper cortisol lesson and I think that actually producing control.

<unk> is one of the ways to really get there. So we think that the field is very very interested in whats really kind of a standard double blind study, we'll see what the results will be patients ranging from the best places maybe the point that I'll leave you with is that what was once really sort of cost off as.

So we think that the field is very, very interested, in what's really kind of the standard double-blind study.

We'll see what the results will be.

Patients ranging from the best places, maybe the point that I'll leave you with is that what was once really sort of tossed off as not really very important is no longer tossed off. In publications ranging from the best places, to the Mayo Clinic, it's now very clear that the group of patients with adrenal adenomas is both sizable and is very adversely affected by their hypercorazolism.

Thanks.

Not really very important is no longer tossed up and publications ranging from the best places to the Mayo clinic, It's now very clear that the group of patients with adrenal adenomas as both sizable and its very adversely affected by their hyper cortisol with them.

Thanks.

Looking forward to the rest of the year.

Looking forward to the rest of the year.

Okay. Thank you Alan.

Thank you, Alan.

I think that.

Operator: I think that wraps us up here.

That wraps this up here. So thanks. Thank you everybody I hope you all have a great rest of the summer and we look forward to talking to you in three months.

So thanks.

Thank you, everybody.

I hope you have a great rest of the summer, and we'll look forward to talking to you in three months.

Yeah.

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

This concludes today's conference call.

Operator: Thank you for your participation.

You may now disconnect.

Okay.

The conference will begin shortly to raise your hand during Q&A you can dial one one.

And in the second quarter, we did see some improvement in both of those areas. And that, led to more patient-physician interaction, more core set physician interaction, which led to more new patients being prescribed and more new prescribers actually coming on board. So I would say those two are the main drivers of the change, new patients and new prescribers.

The conference will begin shortly.

Again, all that being said, neither of those metrics have reached the pre-pandemic levels, that we had seen before the start of COVID-19.

And we're actually not sure if they ever will as an organization.

There's telemedicine now.

To raise your hand during Q&A, you can dial star 11.

[music].

Thank you.

[music].

Medical practices are closing their doors in some cases to pharmaceutical representatives.

Operator: Swayampakula Ramakanth, Joon Lee, Atabak Mokari, Sean Maduck, William Guyer, Corcept Therapeutics Inc, Unknown Attendee, Swayampakula Ramakanth, Joon Lee, Atabak Mokari, Sean Maduck, William Guyer, Corcept Therapeutics Inc, Swayampakula Ramakanth, Joon Lee, Atabak Mokari, Sean Maduck, William Guyer, Corcept Therapeutics Inc

And that creates operational hurdles that are not just HRSA-specific, right?

These are industry-wide.

And what our commitment is, is we have worked hard, to find new ways to operate in that new normal.

And we are continuing to do that.

And I'm very confident that we will find new and creative ways to continue to reach our target audience.

Unknown Speaker: And Charlie, would you like to answer the second question, please?

Sure.

Hi, Ed.

Thanks for the question.

The short answer is there's no updates with respect to the, DOJ subpoena.

But before I elaborate a little bit on that, let me give background for folks who might not be as familiar.

[music].

[music].

Folks may recall that back in 2018 or so, we suffered some short-seller attention and attacks that we pushed through, of course. But there were a couple of lingering consequences of that. One was this securities class action that we are grinding through right now.

And the other, I believe, was this DOJ inquiry, where they requested a whole bunch of documents concerning our commercial business.

Now, the, um, the, the, our approach to this, you know, beyond obviously cooperating with, the DOJ is to give them as much information they want faster than they can actually absorb it just because we want to get all the information in front of them so that we can move through this.