Q3 2021 Corcept Therapeutics Inc Earnings Call

Unknown Executive: of clinical trials during the COVID-19 pandemic and to generate sufficient revenues to fund our commercial operations in the moment Availability of competing treatments, including generic versions of, our ability to obtain acceptable prices or adequate insurance coverage and reimbursement risks related to the development of our product candidates, including their clinical attributes, regulatory approvals, mandates, and oversight, and other requirements, and the scope and protective power of our intelligence. These and other risks are set forth in our SEC filings, which are available at our website and the SEC, On this call, forward-looking statements include those concerning the safety, efficacy, and other clinical and commercial attributes of Ralecoorline, Exichicorline, Miracorlin, Corp, and our other selective cortisol modulators for the treatment of patients with solid tumors, liver disease, hypercortizomes, anti-psychotic-induced weighting, amyotrophic lateral sclerosis, or ALS, and other disorders.

That are subject to risks and uncertainties, which may cause actual results to differ materially from those such statements expressed or implied.

These risks and uncertainties include but are not limited to our ability to operate our business and achieve our goals and conduct our clinical trials during the COVID-19 pandemic.

Generate sufficient revenues on their commercial operations from home programs.

Our ability of competing treatments, including generic versus equipment.

Billy to obtain acceptable prices or adequate insurance coverage and reimbursement requirements.

Risks related to the development of our product candidates, including their clinical attributes regulatory approvals mandates and oversight and other requirements and the scope and protective power of our intellectual property.

These and other risks are set forth in our SEC filings, which are available at our website and the SEC's website.

On this call forward looking statements include those concerning the safety efficacy and other clinical and commercial attributes umbrella Cortland extra coil Milacron Court filings, we had 176 and our other selective cortisol modulators for the treatment of patients with solid tumors hybrid Z Hypercard insourcing antipsychotic induced weight.

Amyotrophic lateral sclerosis, or ALS and other disorders.

The progress enrollment timing design and results of our clinical trials, our revenue guidance cash flow and expected growth.

The impacts of the COVID-19 pandemic on our commercial operations National performance clinical development programs as well as on physicians payers and patients and our anticipated financial performance and clinical development activities. After the COVID-19 pandemic is control.

The timing cost and outcome of litigation, including our lawsuits against Teva and Hikma pharmaceuticals.

Unknown Executive: The progress, enrollment, timing, design, and results of our clinical, Our revenue guidance, cash flow, and expected growth. The impact of the COVID-19 pandemic on our commercial operations, the national, clinical development programs, as well as on physicians, payers, and patients, and on our anticipated financial performance in clinical development activities after the COVID-19 pandemic The timing, cost, and outcome of litigation, including our lawsuits against Teva and Hickma Pharmaceuticals, have its appeal of its defeat in the post-grant review or PGR before the patent trial and appeals board of PTAM, and may include other forward-looking statements during the We disclaim any intention for duty to update forward looking, Our revenue in the third quarter of 2021 was $96.1 million compared to $86.3 million in the third quarter of 2020, an increase of 11% Third quarter of 2021 GAF net income was $30.5 million compared to $21.6 million in the same period, Non-Cabinet income, which excludes non-cash expenses related to stock-based compensation and the utilization of deferred tax assets together with related income tax tax tax was $37 million in the third quarter compared to $30 million in the same period line.

Kevin its appeal of its defeat the post Grant review, our PTR affording the patent trial and Appeals board of P. Tab and May include other forward looking statements during the course of the call.

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

Yes.

Our revenue in the third quarter of 2021 was $96 1 million compared to $86 $3 million in the third quarter of 2020, an increase of 11% third.

<unk> third quarter 2020 one's GAAP net income was $30 5 million compared to $21 $6 million in the same period last year.

Non-GAAP net income, which excludes noncash expenses related to stock based compensation and the utilization of deferred tax assets together with related income tax effects was $37 million in the third quarter compared to $30 million from the same period last year.

We have tightened our 2021 revenue guidance of 300 to $365 million to $375 million.

Compared to previous guidance of $355 million to $385 million.

Our cash and investments totaled $495 2 million at September 30, an increase of $23 $6 million from June 30.

The balance at September 30 reflects the repurchase of $28 million for common stock in the third quarter $1 2 million shares pursuant to our share repurchase program and about 200000 shares in connection with the net exercise of employee stock.

Over the term of the share repurchase.

Share repurchase program, we purchased $4 3 million shares of our common stock at a cost of $98 $2 million.

And now Charlie Robb, our Chief business Officer will provide a legal update.

Thanks and have it back in.

In March 2018, we sued Teva in Federal District court to prevent it from marketing and generic version of Korlym in violation of our patents trial was originally scheduled to start in February of this year. Although that date was vacated by the court a new trial date has not been set.

In April the court granted us permission to file for summary judgment regarding tevis infringement of our two one for Pat.

Haven't responded by filing an sone summary judgment motion with respect to the same pattern.

Unknown Executive: We have tightened our 2021 revenue guidance of $300 to $365 to $375 million compared to previous guidance of $355 to $385 million. Our cash in investments totaled $495.2 million on September 30th, an increase of $23.69.69 on June 30. The balance of September 30th reflects the repurchase of $28 million of common stock in the third quarter, 1.2 million shares pursuant to our share repurchase program, and about 200,000 shares in connection with the net exercise minimum.

Summary judgment is a procedure whereby courts can decided case without holding a trial. We believe the court has all it needs with respect to the 214 patent to decide the case in our favor having lost its action before the P tap, which I will talk about more in a minute COVID-19 can no longer challenge the 214 patents validity in the disc.

<unk> Court case, Kevin can only argue that its proposed product would not infringe physician. We believe has no legal with factual support.

The court granted our motion we will have won the case Teva would be banned from marketing generic korlym until 2037, 2% and four patent expires. The court ruled in <unk> favor. We will proceed trial sometime next year. There is at present no timetable for the court's summary judgment ruling.

Trial date, and no scheduled for any trial related activities.

In parallel with the district court action tailored to the petition that <unk>.

Unknown Executive: Over the term of the share we purchase program, we purchased 4.3 million shares of our common stock at a cost of $98.2 million. And now Charlie Rob, our Chief Business Officer, will provide legal counsel. Charlie?

Federal Circuit Court of appeals to reverse its P tap loss, which I referred to earlier the request. We believe has no merit.

Briefing is complete and the court heard oral argument on October 5th we expect a decision in the next quarter or two.

Gary Charles Robb: Thanks, Adamacher. In March 2018, we sued Teva in federal district court to prevent it from marketing a generic version of Coralum in violation of our patent. Trial was originally scheduled to start in February of this year, although that date was vacated by the court. A new trial date has not yet been set. In April, the court granted us permission to file for summary judgment regarding Teva's infringement of our 214 patent. Tema responded by filing its own summary judgment motion with respect to the same patent. Summary judgment is a procedure whereby courts can decide a case without holding a trial.

On March 12, we sued another anthem filer Hikma pharmaceuticals, and the same federal District Court that is adjudicating, our case against Teva and the Hikma case. According to set the fact discovery deadline of July one 2022 next year nothing is scheduled after that.

With respect to both Teva and Hickman Hickman.

Confident in the strength of our lead position.

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

Thank you Charlie.

The strong growth of our commercial business in the third quarter reflects the continued easing of Covid related public health restrictions.

This is enabled physicians to see their patients more frequently improving their ability to diagnose and treat patients with cushings syndrome.

The business translation of more patients benefiting from Korlym treatment is a new record high in our quarterly revenue.

Gary Charles Robb: We believe the court has all it needs with respect to the 214 patent to decide the case in our favor. Having lost its action before the PTAB, which I will talk about more in a minute, Teva can no longer challenge the 214 patent's validity in the district court. Teva can only argue that its proposed product would not infringe. The position, we believe, has no legal or factual support.

We expect our growth to continue as pandemic conditions recede leading.

Leading endocrinologist increasingly believe that there are substantially more patients with cushings syndrome and listen once assume.

For many of these patients Korlym is an excellent treatment.

We remain very optimistic about the future of our Cushings syndrome business.

It is built on a strong foundation and effective lifesaving medication promoted by a dedicated commercial team puts the interest of patients first.

Our clinical development programs are another cause for optimism.

We have created a library of more than 1000 proprietary cortisol modulators, many of which are attractive candidates for development.

Gary Charles Robb: If the court grants our motion, we will have won the case, and Teva would be banned from marketing generic Coralum until 2037 when the 214 patent expires. If the court rules in Teva's favor, we will proceed to trial sometime next year. There is at present no timetable for the court's summary judgment ruling, no trial date, and no schedule for any trial-related activity.

Like Korlym these compounds find strongly to the glucocorticoid receptor GR.

Unlike korlym they have no affinity for the progesterone receptor and so no costs on our Korlym is most serious off target effects.

Beyond sharing the qualities strong cortisol modulation and not procurement.

<unk> receptor <unk>.

Preclinical and clinical testing have shown that our molecules behave differently from one another in important ways. Some cross the blood brain barrier others do not some perform best in models of solid tumors, others are more potent models metabolic disease, some appear to be tissue specific while others have more global effects.

Gary Charles Robb: In parallel with the district court action, Teva petitioned the Federal Circuit Court of Appeals to reverse its PTAB loss, which I referred to earlier. The request, we believe, has no merit. Briefing is complete, and the court heard oral argument on October 5th.

These diverse qualities have allowed us to initiate clinical trials.

My variety of disorders, including ovarian adrenal in prostate cancer anti psychotic induced weight gain and nonalcoholic <unk> hepatitis or Nash and of course Cushing syndrome.

Gary Charles Robb: We expect a decision in the next quarter or two. On March 12th, we sued another and a filer, Hickma Pharmaceuticals, in the same federal district court that is adjudicating our case against Teva. In the Hickma case, the court has set a fact discovery deadline of July 1st, 2022 next year. Nothing is scheduled after that. With respect to both Teva and Hickman, we are competent on the strength of our legal department. I'll now turn the call over to Dr. Joseph Belinoff, our chief executive officer. Joe?

We are also planning to start phase two trial in patients with ALS in the first quarter of next year and have additional compounds in phase one in preclinical development.

<unk> commercial success has provided the funds to advance all of these programs.

Before I provide an update on our development programs I'd like to introduce you to Bill Dyer, who recently joined us to lead our clinical development activities Bill experienced tremendous success over his 20 year career at Gilead and we have already benefited from his expertise and leadership will joins us on this call and will be available during <unk>.

The Q&A session.

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

Joseph K. Belanoff: Thank you, Charlie. The strong growth of our commercial business in the third quarter reflects the continued easing of COVID-related public health restrictions. This has enabled physicians to see their patients more frequently, improving their ability to diagnose and treat patients with Cushing syndrome. The business translation of more patients benefiting from Coralum treatment is a new record high in our quarterly revenue. We expect our growth to continue as pandemic conditions worsen.

One mechanism is increasing the pop ptosis.

<unk> is the programmed cell death that chemotherapy is meant to induce.

Suppresses a pop tests in.

Our successful trial in women with advanced ovarian cancer edition of the selective cortisol modulator <unk> correlate enhance the effects of chemotherapy likely by blunting cortisol anti apoptotic effect.

Joseph K. Belanoff: Leading endocrinologists increasingly believe that there are substantially more patients with Cushing syndrome than was once assumed. For many of these patients, Quorum is an excellent treatment. We remain very optimistic about the future of our Cushing Syndrome business because it is built on a strong foundation, an effective, life-saving medication promoted by a dedicated commercial team that puts the interests of patients first. Our clinical development programs are another cause for opt-ins.

The results presented at the recent European Society for medical Oncology ESMO Congress clearly demonstrate the best benefit experienced by the women who received rolla Cortland.

Delayed disease progression without increased side effect burden.

As a reminder, our phase II trial is a controlled multicenter study of 178 women with platinum resistant ovarian cancer, who are randomized to one of three treatment arms.

Joseph K. Belanoff: We have created a library of more than 1,000 proprietary cortisol modules, many of which are attractive candidates for development. Like Corlum, these compounds bind strongly to the glucocorticoid receptor, or GR. Unlike Coralum, they have no affinity for the progesterone receptor and so don't cause some of Coralum's most serious off-target effects. However, beyond sharing the qualities of strong cortisol modulation and not perturbing the progesterone receptor, preclinical and clinical testing have shown that our molecules behave differently from one another in important ways. Some neurons cross the blood-brain barrier; others do not.

Women received a higher dose umbrella cortland on the day before the day of and the date after they received Nab Paclitaxel we call. This the intermittent arm.

58 women received a lower daily realm, korlym dose in combination with Nab Paclitaxel, we call. This the continuous <unk> and.

60 women receive Nab paclitaxel alone the comparator arm.

Trial's primary endpoint was progression free survival or PFS.

The women who participated in our study, we're very ill, including platinum refractory patients.

All had experienced disease progression. Despite prior lines of therapy. The median number of prior treatments.

It's clear that rail Korlym provided benefit to many of these women those.

Those are received rather cortland intermittently exhibited statistically significant improvement in PFS compared to the group that received Nab Paclitaxel monotherapy.

Joseph K. Belanoff: Some perform best in models of solid tumors, while others are more potent models of metabolic disease. Some appear to be tissue specific, while others have a more global effect.

They're hazard ratio was <unk> 66, with a P value of 0.038.

Joseph K. Belanoff: These diverse qualities have allowed us to initiate clinical trials for a wide variety of disorders, including ovarian, adrenal, and prostate cancer, antipsychotic-induced weight gain, non-alcoholics, the out of hepatitis or Nash, and of course, Cushing's. We are also planning to start a phase two trial in patients with ALS in the first quarter of next year, and have additional compounds in phase one and preclinical development. Horlam's commercial success has provided the funds to advance all of these Before I provide an update on our development programs, I'd like to introduce you to Bill Geier, who recently joined us to lead our Clinical Development Act. Bill has had tremendous success over his 20-year career at Gilead, and we have already benefited from his expertise and leadership. Bill will join us on this call and will be available during the Q&A session.

The median PFS was five six months, one eight months longer than the net pack paclitaxel monotherapy groups, which was $3 eight months.

The women in the intermittent arm also experienced a statistically significant improvement in their duration of response relative to those in the comparator arm five six months versus three seven months with a hazard ratio of 0.36 and a P value of 0.006.

While the overall survival or OS data collection had accumulated only 63% of the target of 120 events at the time of the database cut off the women in the intermittent arm experienced a median OS of 12 nine months compared to $10 four months in the comparator arm.

Safety and Tolerability in the two groups where comparable.

We expect that the primary analysis of the OS data for this study will be available in the first quarter of next year.

Joseph K. Belanoff: Our oncology program is testing three anti-cancer mechanisms, first postulated by investigators at the University of Chicago and confirmed by other prominent research. One mechanism is increasing apoptosis. Apoptosis is the programmed cell death that chemotherapy is meant to induce. Cortisol suppresses apoptosis.

Based on the statistically significant and clinically meaningful results. We've received extremely positive feedback from leading gynecological oncologist regarding the promise of <unk> as a potential treatment for women with this dire disease there.

The premise is simple and powerful delay.

Delay disease progression without increased side effect burden is an important medical advance.

Joseph K. Belanoff: In our successful trial in women with advanced ovarian cancer, addition of the selective cortisol modulator relicorillant enhanced the effect of chemotherapy, likely by blunting cortisol's anti-apoptotic effect. The results presented at the recent European Society for Medical Oncology, ESMO, Con, clearly demonstrate the benefit experienced by the women who received reliquor. Delayed Disease Progression without increased side effect burden. As a reminder, our phase two trial is a controlled multi-center study of 178 women with platinum-resistant ovarian cancer who are randomized to one of three treatment arms. 60 women received a higher dose of broilicorolent on the day before, the day of, and the day after they received napalachl. We call this the intermittent.

We are planning to meet with the FDA in the coming months to discuss the optimal path forward.

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

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

Deprived of androgen stimulation near tumors switched to cortisol activity stimulate growth.

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

We are conducting a dose finding study of our selective cortisol modulator extra cortland combined with <unk> in men with castration resistant prostate cancer and expect to select an optimum dose by the end of this year.

Joseph K. Belanoff: 58 women received a lower daily rel-chlorant dose in combination with napalaxal. We call this the continuous R. And 60 women received napalotaxil alone, the comparator. The women who participated in our study were very ill, including platinum refractory patients, all of whom had experienced disease progression despite prior lines of therapy. The median number of prior treatments was three.

Third oncologic mechanism recognizes cortisol suppression of the immune system.

<unk> likely lunch the effectiveness of immunotherapy.

We are conducting an open label phase one b trial umbrella Korlym plus the PD, one checkpoint inhibitor <unk> 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 are usually quickly lethal combination.

Joseph K. Belanoff: It is clear that Reliclorolent provided benefit to many of these patients. Those who received Reliclorolent intermittently exhibited a statistically significant improvement in PFS compared to the group that received napactylenotachyl. Their hazard ratio was 0.66 with a p-value of 0.038. Their median PFS was 5.6 months, 1.8 months longer than the NAPPactyl monotherapy groups, which The woman in the intermittent arm also experienced a statistically significant improvement in her duration of response relative to those in the comparator.

<unk> is a map is rarely effective as monotherapy in these patients. We believe that these patients cortisol excess maybe countering the intended effect September one is about which is to stimulate the immune therapy. So just let me say that a little bit more briefly cortisol suppresses the immune system.

Therapy increases the activity of the immune system.

By dialing back cortisol activity, we think that the immunotherapy may become significantly more effective.

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

Joseph K. Belanoff: 5.6 months versus 3.7 months, with a hazard ratio of 0.36 and a p-value of 0.006. Additionally, while the overall survival, or OS, data collection had accumulated only 63% of the target 120 events at the time of the database cutoff, the women in the intermittent arm experienced a median OS of 12.9 months compared to 10.4 months in the comparator arm. Safety and tolerability in the two groups were comparable. We expect that the primary analysis of the OS data for this study will be available in the first quarter of. Based on these statistically significant and clinically meaningful results, we have received extremely positive feedback from leading gynecological oncologists regarding the promise of Rhella Coraline as a potential treatment for women with this dire disease. Their premise is simple and powerful.

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

I'll now turn to our programs in metabolic disease and the recent findings of our proprietary selective cortisol modulator <unk> correlate in patients with Nash are serious liver disorder.

Patients who received <unk> in our phase II trial exhibited large rapid reductions in liver fat, but also substantial transient elevations of liver enzymes Alt and AST.

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

As a reminder, the trial's primary endpoint was a 30% reduction in liver fat. After 12 weeks of treatment in fact patients exhibited reductions in liver fat ranging from 38, 5% to 73, 8% after receiving mirror Portland for just one month.

Joseph K. Belanoff: Delayed disease progression without increased side effect burden is an important medical advance. We are planning to meet with the FDA in the coming months to discuss the optimal path. A second mechanism by which cortisol modulation may prove useful is by blocking an important tumor growth path Cortisol stimulation is a major reason why patients with metastatic prostate cancer, treated with the widely prescribed antigen receptor antagonist enzalutamide, eventually experienced resurgent disease. Deprived of androgen stimulation near tumors, they switch to cortisol activity to stimulate growth. Our hypothesis is that adding a cortisol modulator to androgen deprivation therapy will close this tumor escape.

It maybe the rapidity of mirror correlates fat, reducing effect caused <unk> to rise.

One way is the liver shed just slippage is by metabolizing them into fatty acids, which an excessive amounts irritate deliver.

Interestingly liver levels of serum lipids in these patients did not increase with treatment providing support for the idea that in Europe.

The excess fat in the liver being rapidly metabolized immediately within the liver.

We will present these rules results at the American Association for the study of liver disease.

AA Sld's meeting later this month.

The presentation is now available in the publications section of our website.

Our recently initiated phase <unk> dose finding trial in patients with presume Nash will evaluate mirror korlym can produce significant reductions in liver fat without causing liberty irritation.

Joseph K. Belanoff: We are conducting a dose-finding study of our selective cortisol modulator, exoclase, combined with Enzaludamide in men with castration-resistant prostate cancer and expect to select an optimum dose by the end of. The third oncologic mechanism recognizes cortisol suppression of the immune system, a quality that likely blunts the effectiveness of immunotherapy.

We're also evaluating <unk> as a potential treatment for patients with another serious and widespread disorder anti psychotic induced weight gain in.

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

Joseph K. Belanoff: We are conducting an open-label phase 1b trial of abrelichlorin plus the PD1 checkpoint inhibitor, Pembrolysmap, Merkstra, Ketruda, 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; Pemblelizamab is rarely effective as monotherapy in these patients. We believe that these patients' cortisol excess may be countering the intended effects of Pembrolyzebab, which is to stimulate immune therapy. So just let me say that a little bit more briefly.

While these drugs are very effective the exact steep price in the form of rapid and sustained weight gain which leads to cardiovascular and metabolic disease.

Average life expectancy of patients in the United States, who chronically take anti psychotic medication is decreased by 20 years frequently due to increased cardiovascular events, such as heart attacks strokes.

We are conducting two double blind placebo controlled phase II trials, a mirror correlate in patients with this disorder.

Gratitude and gratitude.

These trials seek to build on the positive data from our study of mirror Korlym in healthy subjects.

Last year, we completed a trial in which 96 healthy subjects received olanzapine and either 600 milligrams of New York Cortland 900 milligrams of Euro correlate or placebo for 14 days.

Joseph K. Belanoff: Cortisol suppresses the immune system. I mean, you know, therapy increases the activity of the immune system. And by dialing back cortisol activity, we think that the immunotherapy may become significantly more effective. Our trial is evaluating whether RELAchlorin can treat these patients' Cushing Syndrome by reducing cortisol activity and, by reversing cortisol-induced immune suppression, allow peperalizumab to achieve its full cancer-killing effect. We plan to enroll 20 patients at five sites in the United States. The primary endpoint is objective response rate, and secondary endpoints include progression-free survival, duration of response, and overall survival.

Subjects, who received mirror korlym gained significantly less weight than those who received placebo. They also exhibited a smaller increase in triglyceride and in <unk> and ASD, which typically exhibit sharp transient increases startup of Olanzapine therapy.

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

The gratitude trial is evaluating whether mirror korlym can reverse recent antipsychotic induced weight gain.

100 patients with schizophrenia or bipolar disorder, we will receive in addition to their established Joseph anti psychotic medication, either 600 milligrams of <unk> or placebo for 12 weeks.

Gratitude is being conducted at 30 centers in the United States.

Our gratitude two study is testing mirror korlym as a treatment for long standing antipsychotic induced weight gain.

Joseph K. Belanoff: I will now turn to our programs in metabolic disease and the recent findings of a proprietary selective cortisol modulator, Muracorillin, in patients with Nash, a serious liver disorder. Patients who received Miracorillin in our Phase 2 trial exhibited large, rapid reductions in liver fat but also substantial transient elevations of the liver enzymes, ALT, and AO. The improvement in liver fat in these patients was greater and occurred much more quickly than we had expected and is rarely seen over any period of treatment.

Hundred 50 patients with schizophrenia will receive in addition to their established Joseph anti psychotic medication, either 600 milligrams or 900 milligrams of mirror correlate or placebo for 26 weeks.

Gratitude two is being conducted 35 centers in the United States. The primary endpoint in both studies is reduction in body weight other.

Other important measures of metabolic activity will also be examined.

We expect to complete enrollment and gratitude to by the end of this year and in gratitude in mid 2022.

As many of you know <unk> is our planned successor to Korlym for the treatment of hyper cortisol.

We are evaluating it in two phase III trials Grace.

Joseph K. Belanoff: As a reminder, the trial's primary endpoint, 30% reduction in liver fat after 12 weeks of treatment. In fact, patients exhibited reductions in liver fat ranging from 38.5% to 73.8% after receiving Miraclorland for just one month. It may be that the rapidity of Maricloral and its fat-reducing effect caused ALT and AST to rise. One way the liver sheds its lipids is by metabolizing them into fatty acids, which in excessive amounts irritate the intestine. Interestingly, levels of serum lipids in these patients did not increase with treatment, providing support for the idea that Murroporal leads to the excess fat in the liver being rapidly metabolized immediately within the We will present these results at the American Association for the Study of Liver Disease (AASLD) meeting later this The presentation is now available in the publication section of our website.

And gradient.

Like all of our proprietary molecules rella Korlym is a selective cortisol modulators like korlym. It achieves its effect by competing with cortisol at the glucocorticoid receptor.

Unlike korlym it does not bind to the progesterone receptor PR for short.

Is not the abortion pill and it does not cause other PR related side effects, including endometrial thickening and vaginal bleeding.

By a different mechanism rella correlate also does not appear to cause hypokalemia low potassium serious side effects experienced by 44% of patients in <unk> pivotal trial.

Korlym induced hypokalemia is a leading cause of korlym discontinuation.

Relative Orleans phase II efficacy and safety data were strong.

<unk> 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 relic orland.

Incidence of endometrial thickening or vaginal bleeding and no drug induced hypokalemia.

The trial results were recently published and frontier and endocrinology.

Joseph K. Belanoff: Our recently initiated Phase 1B dose-finding trial in patients with presumed Nash will evaluate if Miracoralin can produce significant reductions in liver fat without causing liver irritation. We are also evaluating Mira Correlant as a potential treatment for patients with another serious and widespread disorder. Antipsychotic-induced weight gain. In the United States, 6 million people take antipsychotic medications, such as Lanzapine and Risparodone, to treat illnesses including schizophrenia, bipolar disorder, and depression. While these drugs are very effective, they exact a steep price in the form of rapid and sustained weight gain, which leads to cardiovascular and metabolic disease. The average life expectancy of patients in the United States who chronically take antipsychotic medication is decreased by 20 years, frequently due to increased cardiovascular events such as heart attacks and stroke.

Our Grace trial has a planned enrollment of 130 patients with any etiology of Cushing syndrome.

As a reminder, grace has a randomized withdrawal trial design.

All patients receive <unk> for 22 weeks in an open label phase.

Those who meet response criteria for improvement in glucose control hypertension, where both are randomized to continue treatment with <unk> or placebo for 12 weeks, while the pandemic has and continues to impact the execution of this trial, we and our investigators are eager to take rates to the finish line we.

Grace to serve as the basis for our NDA submission in Cushings syndrome, which we remain on track to submit in the second quarter of 2023.

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

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

Radian has a planned enrollment of 130 patients and is being conducted at many of the sites participating in Grace.

Joseph K. Belanoff: We are conducting two double-blind placebo-controlled base two trials of Miraquarellent in patients with this disorder, gratitude, and gratitude too. These trials seek to build on the positive data from our study of Miraquarellent in Healthy Subjects. Last year we completed a trial in which 96 healthy subjects received a lancepine and either 600 milligrams of Myrochorland, 900 milligrams of Myroborin, or placebo for 14 days. Subjects who received Miracorillant gained significantly less weight than those who received placebo. They also exhibited a smaller increase in trichlycerides and an ALT and AST, which typically exhibit sharp transient increases at the start of Alansapine therapy.

<unk> is the first controlled study in patients with this type of Cushing syndrome.

We do not expect our NDA in Cushing syndrome.

It depend on data from gradient, we do expect that its findings will help improve the care of this increasingly recognize these increasingly recognize patients.

Finally, a brief word about woodland three $1 76, which has shown promise in animal models of Eos, we are in discussions with leading clinicians and the FDA regarding our development plans and plan to initiate the phase II trial by early next year.

While the pandemic dampened our commercial results for more than a year, our business is growing as pandemic conditions improve and remember even in the most challenging periods of the pandemic, our commercial business generated more than enough cash to fund our advancing development activities. We.

Joseph K. Belanoff: A paper describing these results was recently published in the Journal of Clinical Psychopharmacology. The Gratitude trial is evaluating whether Miracorillant can reverse recent antipsychotic effects. 100 patients with schizophrenia or bipolar disorder will receive, in addition to their established dose of antipsychotic medication, either 600 milligrams of Miracoralin or placebo for 12 weeks. Gratitude is being conducted at 30 centers in the United States.

We believe cortisol modulation can help treat many serious disorders korlym for patients with Cushings syndrome is one example of cortisol modulations benefit.

The data generated by our ovarian cancer Nash and anti psychotic induced weight gain programs provide increasing proof of cortisol modulations broad work.

Currently our oncology program is evaluating two of our proprietary cortisol modulators in three tumor types ovarian prostate and adrenal.

Our metabolic program is following up encouraging clinical data in Nash and anti psychotic induced weight gain.

We continue to enroll patients in our phase III trials umbrella correlate in Cushing syndrome.

Joseph K. Belanoff: Our Gratitude study is testing Mira Corollant as a treatment for longstanding antipsychotic-induced 150 patients with schizophrenia will receive, in addition to their established dose of antipsychotic medication, either 600 milligrams or 900 milligrams of miracle corollant or placebo for 26 weeks. Gratitude Two is being conducted at 35 centers in the United States. The primary endpoint in both studies is reduction in body weight; other important measures of metabolic activity will also be examined. We expect to complete enrollment in Gratitude 2 by the end of this year and in gratitude in mid-2020.

Early next year, we plan to start a phase II trial using another of our proprietary compounds <unk> hundred $1 76 to treat patients with ALS and more proprietary early stage compounds to advance towards the clinic.

This is an exciting time at <unk> and I'd like to thank our employees for their tremendous effort and dedication.

In the coming months, we plan to expand our teams to support what we believe is an increasingly broad and strong pipeline.

Stop here for questions.

Yeah.

Thank you speakers, ladies and gentlemen, as a reminder, if you have a question at this time. Please press Star then the number one key on your Touchtone telephone one for Dan You May Press Star one to ask a question. Please standby while we.

Compile the Q&A roster.

Okay.

Your first question is from Chris Howerton of Jefferies. Your line is open.

Excellent. Thank you very much for taking the questions.

Joseph K. Belanoff: As many of you know, Relicorland is our planned successor to Corallum for the treatment of hypercorrhazolysis. We are evaluating it in two phase three trials, grace and gradient. Like all of our proprietary molecules, Relicorland is a selective cortisol module. Like Coralum, it achieves its effect by competing with cortisol at the glucocorticoid receptor.

I would agree a lot going on Joe and an exciting time for the company.

If you hear me.

Thank you and.

Two questions I suppose for me, one would be as you're kind of seeing.

The Hayes from the pandemic clearing and obviously the acceleration as you indicated.

What what do you think are going to be the key drivers for the commercial business in Cushings next year.

Any thoughts on things like sales projection guidance or what the key drivers are.

Joseph K. Belanoff: It does not bind to the progesterone receptor, PR for short; it is not the abortion pill, and it does not cause other PR-related side effects, including endometrial thickening and vascular bleeding. By a different mechanism, Relicorrelant also does not appear to cause hypokalemia, low potassium, a serious side effect experienced by 44% of patients in Coralum's pivotal trial. Coralum-induced hypokalemia is a leading cause of corralum discontinuation. Relical Orleans' phase two efficacy and safety data were strong.

You guys are looking forward to from a commercial perspective next year.

The second question that I would have is that like how do you anticipate.

The overall survival data from the ovarian cancer cohort I think it's from the phase two how will that impact.

The ultimate design and do you believe there is still any opportunity for an accelerated approval using an alternative endpoint outside of OS. Thank you.

Thanks, Chris I think we've got both of those questions.

To save my voice, a little bit I'm going to pass you over to even ahead of our commercial group, our Chief commercial officer, Shawn with Duke to answer the first question Hey, Chris Thanks for the questions.

Joseph K. Belanoff: Patients experienced meaningful improvements in hypertension and glucose control, as well as a variety of other signs and symptoms of Cushing syndrome. There were no RELA Coral-induced incidence of endometrial thickening or vaginal bleeding, and no drug-induced hypokalemia.

In terms of 2022, and we expect that growth will continue we do not provide guidance at this time and we will provide guidance early early next year for 'twenty two numbers.

In terms of what the drivers of growth will be.

Stepping back a little bit of Joe talked about the pandemic sort of lifting and what we know is the <unk>.

Joseph K. Belanoff: The trial results were recently published in Frontiers and Interchronology. Our Grace trial has a planned enrollment of 130 patients with any etiology of. As a reminder, Grace has a randomized withdrawal trial design. All patients receive relicorolins for 22 weeks in an open-label phase. Those who meet response criteria for improvement in glucose control, hypertension, or both are randomized to continue treatment with relicorol or placebo for 12 weeks. While the pandemic has and continues to impact the execution of this trial, we and our investigators are eager to take grace to the finish line.

Physician visits matter right for both patients and our clinical specialists have been during the pandemic. Those all went to zero at the beginning of this year and sort of increasingly throughout the year as restrictions have eased things have opened up in patients who have gone back to senior positions.

And we've been able to actually interact with physicians and as a result, we've seen more patients are being prescribed korlym. So things have started to return to normal and we're optimistic that that improvement is going to continue but so let's say if we're going to we're not there yet.

Or were there we're not there yet the reality is that some things may never return to how they were pre pandemic. So in terms of next year. One thing we've done very diligently methodically over time has looked at sort of our salesforce and potentially increasing the size. If we believe there's opportunity to get to a more positions.

Joseph K. Belanoff: We expect grace to serve as the basis for our NDA submission in Cushing Syndrome, which we remain on track to submit in the second quarter of 2021. Our second phase three trial, gradient, is studying relicorolence 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 ultimately, their health outcomes are poor. Gradyon has a planned enrollment of 130 patients and is being conducted at many of the sites participating in Grace.

We started with 15 at launch our 50 today and we're planning to get to.

<unk> 60 by next year.

Just to be clear it takes time to find the right territory that makes sense. It takes time to find the right talent and then it takes time to get that clinical specialist are trained up to a place where they can be effective.

In the field, so I wouldn't expect.

The extra 10 heads to start providing value early next year, but throughout the year, we would expect to see.

Some ramp up from that so we're really we're continuing to explore ways that we can continue to educate on disease education and on Korlym and enrich as many physicians as we possibly can and just to sum it up I mean, we have more physicians were prescribing physicians than we've ever had.

We've got more patients on Korlym, perhaps so we would expect to continue that trend into next year.

Joseph K. Belanoff: Gradyin is the first controlled study in patients with this type of Cushing. Well, we do not expect our NDA and Cushingson depend on data from creating. We do expect that Gradyin's findings will help improve the care of these increasingly recognized patients. Finally, a brief word about court 113-176, which has shown promise in animal models of ALS. We are in discussions with leading clinicians and the FDA regarding our development plans and plan to initiate a phase two trial by early next year.

And I'd like to now introduce all of you to Bill Guyer goes our Chief Development Officer recently from a long successful career at Gilead and I would like to have him answer. The question on your second question, Chris related to our ovarian cancer setting great. Thank you. Thank you Joe and thank you for that question.

<unk> was around OSA I do want to kind of bring you back to.

At the beginning of the trial with our Phase II study, we met our primary endpoint and we're very excited that we met our primary endpoint because we saw a statistical significant improvement in progression free survival and duration of response by approximately two months.

And the good thing is for that Phase II study. We saw overall results that were very strong and we didn't have to look at subgroups to see a response for <unk> plus Nab Paclitaxel. So I think that's a very positive piece and.

Joseph K. Belanoff: While the pandemic dampened our commercial results for more than a year, our business is growing as pandemic conditions improve. And remember, even in the most challenging periods of the pandemic, our commercial business generated more than enough cash to fund our advancing development activities.

After the presentation that Joe mentioned at ESMO, we've had many conversations with gynecological experts around the world and they are just as excited with those primary results from our phase III study.

Upon those results we are active in planning with meeting with the FDA and we will talk about the most relevant information to come away with Optum.

Joseph K. Belanoff: We believe cortisol modulation can help treat many serious disorders. Coraline for patients with Cushing Syndrome is one example of cortisol modulation being better. The data generated by our ovarian cancer, Nash, and antipsychotic-induced weight gain programs provide increasing proof of cortisol modulation's broad work. Currently, our oncology program is evaluating two of our proprietary cortisol modulators and three tumor types, ovarian, prostate, and adrenal. Our metabolic program is following up encouraging clinical data in Nash and antipsychotic-induced weight gain week.

Optimal design for our path forward.

When it comes to OS.

Evaluating OS.

And at the time when we did the first data cut we had 63% of OS events and at that time, we saw a trend towards an improvement of about two five months and I think that's also very positive.

But yet the good thing is that women are living longer in this trial and that's the ultimate goal of hopefully what we can achieve with <unk> plus Nab paclitaxel.

We will report.

Next analysis, when we hit that final data cut of 120 events.

We are actively planning for a phase III study and we plan to move forward and we're working with a leading organization called <unk>, which is the gynecological oncology group and as we've worked with them. They're very excited about the results as well and are actively working with us to help guide us for a path forward.

Joseph K. Belanoff: We continue to enroll patients in our phase three trials of REL Coralant and Cushing. Early next year, we plan to start a phase two trial using another of our proprietary compounds, Court 113176, to treat patients with ALS, and more proprietary early-stage compounds are advanced toward the clinic. This is an exciting time at Corset, and I'd like to thank our employees for their tremendous effort and dedication. In the coming months, we plan to expand our teams to support what we believe as an increasingly broad and strong pipeline. I'll stop here for questions. Thank you, speakers.

Related to.

Our phase III study or any other path forward with the FDA.

Thank you Bill and Chris.

I know I'm sort of the import of your question.

Look.

I think everyone should get a say before us here at previous calls that your expectation should be.

The phase III study certainly our expectations, we're setting up to do that with data will come along over the next few months and we will have conversations with the FDA.

Go from there and of course alert.

Things are settled down.

Okay.

Alright, well.

Nice to meet you Bill and thanks, a lot for answering my questions.

Thanks, Chris.

Your next question is from Matt Kaplan with Ladenburg Thalmann. Your line is open.

Operator: Thank you, speakers. Ladies and gentlemen, as a reminder, if you have a question at this time, please press star, then the number one key on your touchstone telephone. Once again, you may press star 1 to ask the question. Please stand by while we compile the Q&A list. Your first question is from Chris Howardson of Jeffries. Your line is open.

Hi, Thanks for taking the questions and congrats on the strong quarterly results.

Just wanted to I guess.

And the development programs, you mentioned AOS and plans.

Plans for 11316176 can you give us a little bit of.

In terms of the mechanism of action and why do you think.

Court with this molecule could play a role in AOS.

Yeah.

Let me, let me take that question, because again to provide a little bit of context, one of the things that really from the beginning.

Chris Howardson: Excellent. Thank you very much. I would agree there is a lot going on, Joe, and an exciting time. So for me, thank you. And two questions, I suppose, for me. One would be, as you're kind of seeing the haze from the pandemic clearing and, obviously, the acceleration, as you indicated, what do you think are going to be the key drivers for the commercial business in Cushing? Next year, you know, any thoughts on things like sales projections, guidance, or what the key drivers are, you know, that your guys are looking forward to from a commercial perspective next year? The second question that I would have is that, you know, how do you anticipate the overall survival data from the ovarian cancer cohort? I think it's from phase two.

But of course that we did a little bit differently than other pharmaceutical companies as we have always had extensive academic collaborations.

Yes.

Throughout the world happened, the United States have outside of the United States have preclinical clinical and frankly it was the only way I thought we could get to the really broad platform of cortisol modulation and just before I answer your question about AOS, everyone should understand that the initial data for the oncology.

Programs that we have came out of a long term collaboration with the University of Chicago.

<unk>.

The programs that we have in metabolic disease, particularly in Nash came out of a long term collaboration that we have with the university of Leiden, The Netherlands and would have really provided for US was a great farm system peak not all research works out, but when it does work out we're able to move it back in house and make it go much more quickly now.

One of our collaborating researchers is actually in <unk> in Argentina long term.

S investigator.

Fortunately as I know you know, Matt it really hasn't been much success in ALS.

Chris Howardson: How will that impact, you know, the ultimate design? And do you think there's still any opportunity for an accelerated approval using an alternative endpoint outside of OS? Thanks, Chris. I think we have both of those questions.

But any event and working with sort of a standard animal models in.

<unk>, he really was able to show that cortisol modulation.

And specifically.

And he has ideas are really where it's working in the brain in these animal models not just slowed the deterioration of AOS, but at least in the period for which he studied the animals actually improved thanks that actually clinically improved the animals and it also from a pathological point of view increased their muscle fiber strength and muscle function.

Sean Maduck: And to save my voice a little bit, I'm going to pass you over to the eminent head of our commercial group, Chief Commercial Officer Sean Madoot, to answer the first question. Hey, Chris, thanks for the questions. In terms of 2022, we expect that growth will continue. We do not provide guidance at this time, and we'll provide guidance early next year for our 22 numbers. You know, in terms of what the drivers of growth will be, you know, stepping back a little bit, Joe talked about the pandemic sort of lifting, and what we know is that physician visits matter, right, for both patients and our clinical specialists. And during the pandemic, those all went to zero.

So it's very intriguing finding now is like Mount Everest I mean that is not an easy not decline. It's a dire need many many companies have tried to work on it and all I can really tell you at this point is the best evidence for the success are these successful animal testing, which didn't haven't repeated several times.

And as.

But cindy the articles where you can find themselves have now all been published in peer reviewed journals. So we will see what I can tell you is that there is a group of investigators who are very interested in this mechanism. We're very interested in taking it forward.

We're very excited to give it a try.

It's a difficult area to work in but wouldn't it be cool if we can actually provide some help for these patients.

Sure that's helpful.

Sean Maduck: At the beginning of this year, and sort of increasingly throughout the year, as restrictions ease, things have opened up, and patients have gone back to their physicians, and we've been able to actually interact with physicians. And as a result, we've seen more patients being prescribed corals. So things have started to return to normal, and we're optimistic that that improvement is going to continue. But I just want to state, you know, we're not there yet. You know, we're part way there; we're not there yet. The reality is that some things may never return to how they work.

And then.

Secondly in terms of.

Castrate resistant prostate cancer.

Program.

What are the next steps after you select the optimal dose is that is that movement into phase III.

I think it's actually moving into phase II, I think really at that.

This is really a phase <unk> study I just wanted to remind again that you may know this but the whole audience that.

Its really an intriguing idea it has very good science behind it at a great places and it basically is as I said before it's blocking a critical escape pathway for men, who are receiving androgen modulation, but it's no longer effective.

Sean Maduck: So in terms of next year, you know, one thing we've done very diligently, methodically over time is look at sort of our sales force and potentially increase the size if we believe there's an opportunity to get to more positions. And, you know, we started with 15 at launch. We're at 50 today, and we're planning to get to around 60 by next year. And just to be clear, you know; it takes time to find the right territory. That makes sense. It takes time to find the right talent.

That's the concept the other practical point I want to remind everyone is that we are running a study with <unk>, which is one of our cortisol modulators. The University of Chicago is actually running a very similar study with <unk>.

And we expect that both of these to approach kind of their dose finding finish line about the same time towards the end of the year and then we will make a selection as to which of those compounds to bring forward into phase II.

Okay.

That's helpful. Thank you and then last question in terms of.

Korlym you had great success.

Third quarter.

Sean Maduck: And then it takes time to get that clinical specialist trained up to a place where they can be effective in the field. So I wouldn't expect, you know, the extra 10 heads to start providing value early next year, but throughout the year, we'd expect some ramp-up from that. So we really are continuing to explore ways that we can continue to educate on disease education and on Coralum and reach as many physicians as we possibly can.

What do you what are you seeing.

In the fourth quarter early on here in terms of are you seeing continuing that momentum in terms of new patient adds in stock.

Yes, we.

We don't comment on quarters and progress, but we see I think I think I'm, okay, saying to you we see no diminution of the trend we've previously seen.

Okay.

Thank you.

Thanks again for taking the questions.

Your next question is from Covina Man of Bank of America. Your line is open.

Sean Maduck: And just to sum it up, I mean, we have more physicians, more prescribing physicians than we've ever had, and we've got more patients. So we expect to continue that trend. And I'd like to now introduce all of you to Bill Geier.

Hi, Good afternoon, guys. Thanks for taking my questions.

A couple on Korlym, if I could can you give us a little bit more detail.

About what the contribution of price and volume were to growth this quarter.

Okay.

So I mean, so we took a 5% price increase in March 1st of last year or beginning of this year.

William Guyer: Bill is our chief development officer, recently from a long and successful career at Gilead. And I'd like to have him answer your second question, Chris, related to our, Great, thank you. Thank you, Joe, and thank you for that question.

And I guess, yes go ahead.

I was going to say, it's from a year on year growth perspective around 60% of the growth.

What's due to volume and 40% database.

I guess as this year has progressed has that contribution from volume increase.

Despite the Covid headwinds.

William Guyer: So while your question was around OS, I do want to kind of bring you back to at the beginning of the trial, with our phase two study. And we're very excited that we met our primary endpoint because we saw statistically significant improvements in progression-free survival and duration of response by approximately two months. And the good thing is that in that phase two study, you know, we saw overall results that were very strong, and we didn't have to look at subgroups to see a response for Relicorent Plus and Apalaxel. So I think that's a very positive piece.

Yes.

Yes.

As <unk> as Shawn mentioned earlier, we now have more patients taking korlym that have ever taken it and more physicians prescribing.

Okay.

And if I guess, we can move on to two ovarian cancer for for your trial design for phase three.

Are you expecting that you will only have to do one phase III study or would there be a need for Q.

And Dave do you have an official under phase two meeting with FDA before designing the study as it stands now.

Well. Thank you for that question. This is <unk>. So we are actively planning to meet with the FDA and when we have all the information to have that discussion we will within the next few months as I think Joe said at this time, we are planning on a phase III trial, that's looking at the intermittent dose because that's where we saw the most successful.

William Guyer: And, you know, after the presentation that Joe mentioned at ESMO, we've had many conversations with gynecological experts around the world, and they're just as excited about those primary results from our phase two study. Based on those results, we are actively planning a meeting with the FDA, and we'll talk about the most relevant information to come away with an optimal design for our path forward. When it comes to OS, we're evaluating OS. And at the time when we did the first data cut, we had 63% of OS events. And at that time, we saw a trend towards an improvement in OS in about two and a half months.

<unk> dose umbrella Korlym plus Nab Paclitaxel, we plan on doing a controlled study and Thats a controlled study versus an investigator's choice of treatment.

While that study will be larger than our phase II study, we basically just want to replicate the great results. We saw in phase two where we saw statistically significant improvement in PFS as.

As well as duration of response.

So we're going to actively work as I said earlier with a leading organization here in the United States that has a global connection is called the <unk> the gynecological oncology group and they're collectively just as excited as we are if not actually sometimes more excited than we are to progress. The study forward and to also help us with.

William Guyer: And I think that's also very positive. But the good thing is that women are living longer in this trial, and that's the ultimate goal of, hopefully, what we can achieve with Relicorla Plus NAPAC. We will report the next analysis when we hit that final data cut of 120 events. We are actively planning for a phase three study, and we plan to move forward, and we're working with a leading organization called GOG, which is the Gynecological Oncology Group.

With the FDA and other regulators.

And so just I'm just going to sum up because it was in there too.

Our expectation as a single study.

Right, because I was assuming that because of the anthem that need that that should be.

Sufficient so thanks for confirming okay. Thanks, guys.

Youre welcome.

Your next question is from the line of Arthur.

H C. Wainwright your line is open.

Hey, good afternoon gentlemen.

Okay. Yeah. Thanks for taking my question, So I guess.

I want to touch on the Nash Phase <unk> study for the <unk> could.

William Guyer: And as we've worked with them, they're very excited about the results as well and are actively working with us to help guide us for a path forward related to the Phase 3 study or any other path forwards with the FDA. Thank you, Bill. And Chris, you know, I know sort of the import of your question. And look, I think everyone should get, I'll say before I've said here on previous calls that your expectation should be a phase three study.

Could you guys give us more color on the study design.

The patient inclusion criteria.

And.

When could we expect initial data from that study.

Yeah, Great Great question and as I answered the question on me back you up a little bit because.

<unk> with Nash have lived with that disease and progressed over decades. They typically start with non alcoholic fatty liver disease, and then progressed to Nash, where they have fibrosis and sometimes progressed to cirrhosis.

William Guyer: Certainly, our expectation, we're setting up to do that. But data will come along over the next few months, and we will have conversations with the FDA and go from there. Of course, we will alert you as soon as things are saying. Okay, all right, well, nice to meet you, Bill, and thanks a lot for answering the question.

And the goal is to reverse that liver fat accumulation and reverse fibrosis over time and it's common in Nash development programs to achieve those goals over the course of the year and in our phase two study and again I'll get to your answer on phase one b, but I got to remind you of the phase II study that.

Joe had talked about what we saw really was with mere cortland unprecedented results for.

Fat fat loss, when we looked at <unk> 600 milligrams.

<unk> 900 milligrams, we saw.

Reductions in liver fat from 40% to as much as 75%, we actually saw one patient have complete resolution of liver fat in just four weeks.

Chris Howardson: Your next question is from Matt Kaplan of Ladenburg, Thalman. Your line is open.

Matthew Lee Kaplan: Hi, thanks for taking the questions and congratulations on the strong quarterly results. I guess, in your development programs, you mentioned ALS and your plans for 113-176. Can you give us a little bit of detail in terms of the mechanism of action and why you think, quote, this molecule could play a role in ALS? Yeah, Matt, Matt, let me take that question.

And that resulted though unfortunately with a consequential rise in <unk>.

And so as we look at those endpoints.

We're trying to now design that phase <unk> study, which we have done so and that has started and we're actively recruiting that study in that phase <unk> study is going to have four different cohorts looking at lower doses of mere cortland.

Starting at 150 milligrams 300 milligrams and.

450 milligrams as well as a dose escalation scheme is one of our cohort starting at 150 milligrams and up to a maximum dose of 600 milligrams in each cohort is gated by an evaluation of safety and efficacy every four weeks and we will continue up to 16 weeks.

Joseph K. Belanoff: Again, to provide a little bit of context, and one of the things that, really, from the beginning of Corset, we do a little bit differently than other pharmaceutical companies is we have always had extensive academic collaborations, you know, really throughout the world, half in the United States, half outside of the United States, half preclinical, half clinical. And frankly, you know, it was the only way I thought we could get to the really broad platform of cortisol modulation.

Is an open label trial. So we'll look at the safety and efficacy results as they come in for each cohort and we'll plan accordingly, as we interpret those results.

Okay. Thanks for that color. So I just wonder so for the endpoint evaluation.

You guys tend to use the image there or is there any biopsy involved for the for that study.

No biopsy is involved in this study we're using MRI PD FF, which is a MRI version to look at labor faster than and that's what we did in the phase II study as well.

Joseph K. Belanoff: And just before I answer your question about ALS, you know, everyone should understand that the initial data for the oncology programs that we have came out of a long-term collaboration with the University of Chicago, and the programs that we have in metabolic disease, particularly in Nash, came out of a long-term collaboration that we had with the University of Leiden in the Netherlands. And you know, what it really provided for us was a great farm system. Not all research works out, but when it does, we're able to move it back in-house and make it go much more quickly.

Okay. Thanks, and then we could expect the initially it upfront in nexium appropriate.

As I said, we're going to be looking at the data for each cohort and Theres four.

Four we gates and so we'll be looking at that data as it comes along it's basically a six month trial.

So but internally of course that we will be seeing the data as it comes in on a regular basis.

Okay. Thank you and then my next question is regarding the.

The capital allocation. So we almost have bidding cashing hand beside the internal pipeline development are you guys contemplating any business development targeted just curious thanks.

Joseph K. Belanoff: And one of our collaborating researchers is actually in Buenos Aires, in Argentina, a long-term ALS investigator. Fortunately, as you know, Matt, there really hasn't been much success in ALS ever. But in any event, in working with sort of standard animal models of ALS, he really was able to show that cortisol modulation, and specifically, you know, I mean, he has ideas of really where In these animal models, it not only slowed the deterioration of ALS, but at least in the period for which he studied the animals, it actually improved things. It actually clinically improved the brain. animals, and it also, from a pathological point of view, increased their muscle fiber strength and muscle function.

Or is there a thought about thanks for the question.

We are cognizant of our large cash position and regularly evaluate our capital allocation alternatives.

No nothing new or new updates to report at this time.

Yes.

Yes.

Just to underscore that though yes, we really are aware up on how successful the business is shut in and run has been we're continuing evaluating where we like to put the cash we don't need where our clinical programs. Obviously, that's the first priority. So it is a.

An active topic really at all points and.

Should we have updates you will be.

Right on the list to know thank.

Thank you Arthur Thanks for the question.

Sounds great. Thank you. Thank you for taking my question.

Yeah.

Your next question is from <unk> <unk> Your line is open.

Joseph K. Belanoff: So it's a very intriguing finding. Now, you know, ALS is like Mount Everest. I mean, that is not an easy mountain to climb.

Thanks for taking my questions, Joe Charlie add back Sean Good to hear from you and we are pleased to make your acquaintance congratulations on the quarter.

Joseph K. Belanoff: It's a dire need. Many, many companies have tried to work on it. And all I can really tell you at this point is that the best evidence for the success is these successful animal tests, which have now been repeated several times. And as, We've got to send you the articles, or you can find them yourselves, have now all been published in peer-reviewed journals. So we'll see.

I'll refer back to something that was mentioned earlier.

More patient Cushing has been previously thought I wonder if I can have some color on this reflected more.

The severe patients the classic case.

For patients or is it the.

Endocrinologists are.

Again, we don't want them less severe cases.

Yeah. Thanks, Alex This is Sean ill answer that and Joe Please add any color that you'd like to but I want to talk a little bit about sort of the historical data around this disease. So the population data.

Joseph K. Belanoff: What I can tell you is that there's a group of investigators who are very interested in this mechanism. We're very interested in taking it forward. We're very excited to give it a try. It's, you know, it's a difficult area to work in, but wouldn't it be cool if we could actually provide some help for these patients? Sure, that's helpful.

Referenced in his better operating years suggest that the prevalent patient population is around 20000 patients a year half of whom are cured by surgery I think something thats important to note about that data and you just touched on it is that 70% of those patients.

I have cushings disease and for those that aren't as familiar with <unk> patients with disease, but two or three origin.

What's happened really over time.

Matthew Lee Kaplan: And then, secondly, in terms of the cat-rate-resistant prostate cancer program, what are the next steps after you select the optimal dose? Is that movement into phase three? I think it's actually moving into phase two. I think that really, at that point, you know, we're really just a phase one piece study. I just want to remind, again, Matt, you may know this, but the whole audience, that it's really an intriguing idea.

Most recently I would say in the last five plus years as Theres really mounting evidence showing that there may be more patients with adrenal hydrocortisone was pretty good.

And then there really is a large amount of a bit of a resurgent multiple publications, which we'd be happy to share that.

Support this so there's not 1 million paperboard was lowest in patients. This is a startup still a rare disease, but could there be 30 or 40000, yes.

Wouldn't surprise me, if there were and as education increases physicians are screening more awareness is being raised.

I think we will see that evolve over time and there'll be a better understanding of what this market looks like.

Joseph K. Belanoff: It has very good science behind it from great places, and it basically is, as I said before, it's blocking a critical escape pathway for men who are receiving antigen modulation, but it's no longer effective. So that's that's the constant. The other practical point I want to remind everyone is that we are running a study with exa corollent, which is one of our cortisol modulators. The University of Chicago is actually running a very similar study with reliquid.

No I have nothing to add go ahead.

I suspect the gradient trial of diabetes.

Yes, it's really Alan very nice to be able to do that is the first controlled study in patients with this specific form of Cushing syndrome.

We were able to do it in the standard kind of double blind fashion because many of these patients are not treated at all for their hyper cortisol or at this point they are treated with seven different medications for seven different symptoms. So I'm really looking forward to add that to the scientific literature and hopefully be helpful. In clinical care very quickly.

Joseph K. Belanoff: And we expect that both of these to approach kind of their dose-finding finish line about the same time towards the end of the year. And then we will make a selection as to which of those compounds we will bring forward.

Yeah.

Got a couple more questions, but they tend to be more.

More philosophical and one follow up on Matt Kaplan question on.

103 176.

Really.

Matthew Lee Kaplan: And that's helpful. Thank you.

Portfolio, maybe apply the CNS in neuromuscular disease.

Matthew Lee Kaplan: Last question in terms of Coralum, you had great success in the third quarter. What are you seeing in the fourth quarter early on here in terms of, are you seeing continuing that momentum in terms of new patient ads? You can start. Yeah, you know, we don't comment on quarters in progress, but we see, I think I'm okay saying to you, we see no diminution of the trend we have. Thank you. Thanks again for taking the time to answer my question.

Im watching the.

Cortisol dysregulation in metabolic problems a prominent pacer.

Yeah.

I'd like to see the drug to be successful with that.

Mechanism.

But I look at your.

Got it that's all it does help mitigate their metabolic problems.

Huge.

I don't know.

For color on it.

I'll give you.

I gave you the five hour version.

Yeah.

Please go ahead.

Maybe I'll shorten it up for you look.

As you know Alan on the psychiatrist by training I think the brain is the most sensitive organ in the body to hormonal dysregulation, specifically cortisol dysregulation, but historically psychiatric and neurologic studies have been among the most difficult to do and as you know many.

Kazin Ahmad: Your next question is from Kazin Ahmad of Bank of America. Your line is open.

Kazin Ahmad: Hi, good afternoon, guys. Thanks for taking my questions. Sure. A couple on Coralyn. Can you give us a little bit more detail about what the contribution of price and volume was to growth this quarter?

Large companies have foundered in that area and programs have been cut and so on and so forth and so.

Unknown Executive: So, I mean, we took a 5% price increase on March 1st of last year, or the beginning of this year.

I have a great intellectual interest in going in that area.

Think there is tremendous need and possibility I know as you know there is a.

Unknown Executive: And I guess, yeah, go ahead.

Unknown Executive: I was going to say that from a year on your growth perspective, around 60% of the growth was due to volume, and 40%

We have a study now push dramatic stress disorder, that's being run by the.

VA theres good animal data in another neurological disease Huntington's disease, So I'm really hoping that.

Unknown Executive: And I guess as this year has progressed, we have had that contribution from volume increase despite the COVID headwinds.

And sort of the five to 10 years zone, we will really be back in a serious way into CNS disorders.

Unknown Executive: Yeah, as Tazian, and Sean mentioned earlier, we now have more patients taking Coralum than have ever taken it before,

It would really be wonderful to give some help to this patients cortisol modulation.

Has lots of good reasons to give it a try so sort of one thing at a time, we have a very full plate as it is but I do think that over time, we will be feathering in CNS disorders, as we have more information so cross your fingers.

Kazin Ahmad: Okay, and if, I guess we can move on to ovarian cancer. For your trial design for phase three, are you expecting that you will only have to do one phase three study, or will there be a need for two? And did you have an official phase two meeting with FDA before designing the study as it stands now?

They will have a full dinner.

And that's why I call. It and you can see the clinical Grace quick hitting in the portfolio expanded very interesting for a small company and yet you are opening up.

Two new drugs to the clinic.

Is this what you envision as a game plan of growing clinical portfolio.

William Guyer: Well, thank you for that question. This is Bill Kair.

William Guyer: So we're actively planning to meet with the FDA, and when we have all the information to have that discussion, we will within the next few months, as I think Joe said. At this time, we're planning on a phase three trial that's looking at the intermittent dose because that's where we saw the most successful dose of relicorlin plus an apactyl. We plan on doing a controlled study, and that's a controlled study versus an investigator's choice of treatment.

Hey.

Fatter than today.

Still hope reintroduced that your drug roughly every year.

That really is the goal and cortisol modulation is a very broad and important.

It's a very important.

Horton platform.

And we don't want to overstep, we really think very hard about what we can actually get done yes, I really do think that's a fair statement of our goal which is to add a comp had a year and if the evidence is therefore to add a disorder of year cant.

Can't promise that that's going to be the case will follow the evidence where it goes but I think that we're really onto something I think the cortisol modulation is a big area and we're first.

William Guyer: While that's a controlled study, we plan on doing a controlled study that will be larger than our phase two study, we basically just want to replicate the great results we saw in phase two, where we saw statistically significant improvements in PFS, as well as DOR, duration of response. And so we're going to actively work, as I said earlier, with a leading organization here in the United States that has a global connection.

Thanks for answering my questions, but I hope that comes true Youre kind of interesting it's an interesting situation.

Small companies are trying to.

Great great.

Great.

Large portfolio, thanks, and good luck.

Yeah, and we're not as small as we used to be Alan you remember that right.

[laughter].

So a little bit Dave.

William Guyer: It's called the GOG, the Gynecological Oncology Group, and they're collectively just as excited as we are, if not actually, sometimes more excited than we are to progress this study forward and also help us with the FDA and other regulations. But, and so just, I'm just going to sum up because it was in there to see in weeks, our expectation is a single study. Right.

Alright, well listen I'm going to stop here, great to talk to all of you. Obviously as we have news we will put it out otherwise we'll talk to all of you next quarter.

Hope Hope hope you enjoy what's left of the fall and the early winter talk to you soon bye bye. Thanks.

Thanks.

Thank you speakers, ladies and gentlemen. This concludes today's conference call. Thank you all for joining you may now disconnect.

Okay.

Okay.

[music].

William Guyer: Right, because I was assuming that because of the underlying need, that should be sufficient. So thanks for confirming. Okay, thanks guys.

Kazin Ahmad: Your next question is from the line of Arthur Hay of H.C. Wainwright. Your line is open.

Arthur He: Good afternoon, this is the answer for RK. Thanks for taking my question.

Arthur He: So I guess I want to touch on the Nash Face 1 study for Maricorin. Could you guys give us more color on the study design and as well as the patient inclusion criteria? And when could we expect initial data from that study? Yeah, great question.

William Guyer: And as I answer that question, let me just back you up a little bit because, you know, patients with Nash have lived with that disease for decades. You know, they typically start with non-alcoholic fatty liver disease and then progress to Nash-related cirrhosis, where they have fibrosis and sometimes progress to cirrhosis. And the goal is to reverse that liver fat accumulation and reverse fibrosis over time. And it's common in Nash development programs to achieve those goals over the course of a year.

William Guyer: And in our phase two study, and again, I'll get to your answer on phase 1B, but I've got to remind you of the phase two study that Joe talked about. What we saw really was with Miracorrelant, you know, unprecedented results for fat loss. When we looked at Miracorlant 600 milligrams and or 900 milligrams, you know, we saw reductions in liver fat from 40% to as much as 75%. We actually saw one patient have complete resolution of liver fat in just four weeks. And that resulted, though, unfortunately, with a consequent rise in ALT and ASP.

[music].

William Guyer: And so as we look at those endpoints, we're trying to now design that phase 1B study, which we have done, and it has started, and we're actively recruiting for that study. And that phase 1B study is going to have four different cohorts looking at lower doses of mirror correlates, starting at 150 milligrams, 300 milligrams, and 450 milligrams, as well as a dose escalation scheme in one of the cohorts, starting at 150 milligrams and up to a maximum dose of 600 milligrams.

William Guyer: And each cohort is gated by an evaluation of safety and efficacy every four weeks, and will continue up to 16 months. This is an open-label trial, so we'll look at the safety and efficacy results as they come in for each cohort, and we'll plan accordingly as we interpret them. Thanks for that color. So I just wonder, so for the endpoint evaluation, are you guys trying to use the image, or is there any biopsy involved in the NAC study? No biopsies involved in this study.

William Guyer: We're using MRI PDFF, which is an MRI version to look at liverfast within. And that's what we did in the phase two study. Okay, thanks. And we could probably expect the initial data from next year, probably. As I said, we're going to be looking at the data for each cohort, and there are four, you know, four-week gates, and so we'll be looking at that data as it comes along. It's basically a six-month trial.

Arthur He: So, but internally, of course, we'll be seeing the data as it comes in on a regular basis. Okay, thank you. And my next question is regarding capital allocation. So with the almost half-billing cash in hand, besides their internal pipeline development, are you guys contemplating any business development targets? Just curious. Hi Arthur, it's Otabak.

Atabak Mokari: Thanks for the question. We are cognizant of our large cash position and regularly evaluate our capital allocation alternatives, but we have nothing new or new updates to report. Yeah, just to underscore that, though we really are aware of how successful, you know, the business of Sean and Run has been, we're continuing to evaluate where we would like to put the cash we don't need for our clinical programs. Obviously, that's the first priority. So it is an active topic, really, at all points.

Joseph K. Belanoff: Should we have updates, you will be, you know, right on the list. Thank you, Arthur. Thanks for the question. Sounds great. Thank you. Thank you for taking my question.

Arthur He: Your next question is from Alan Leong of Biowatch. Your line is open.

Alan Leong: Thanks for taking my questions. Joe, Charlie, Outback, and Sean, good to hear from you. And Bill, pleased to make your acquaintance. Congratulations on the quarter.

Sean Maduck: I want to refer back to something that was mentioned earlier. More patients have Cushing's than previously thought. I wonder if I can have some color on this, just reflecting more severe patients, the classic case, patients are, or is it the endocrinologists are getting to lump in less severe cases? Yeah, thanks, Alan. This is Sean.

Sean Maduck: I'll answer that, and Joe, please, in any color that you'd like. But I want to talk a little bit about some of the historical data around this disease. So the population data that is often referenced and has been around for many years suggests that the prevalent patient population is around 20,000 patients a year, half of whom are cured by surgery. I think something that's an important note about that data, and you just touched on it, is that 70% of those patients have Cushing's disease.

Sean Maduck: And for those that aren't as familiar with the illness, that is, patients with a disease of pituitary origin. And what's happened really over time, and most recently, I would say in the last five plus years, is that there is really mounting evidence showing that there may be more patients with adrenal hypercortizolism than previously thought. And there really is a large amount of independent research and multiple publications, which we'd be happy to share

Sean Maduck: So, you know, there's not a million hypercortizome patients. I mean, this is still, still a rare disease. But could there be 30 or 40 thousand? Yes, it wouldn't surprise me if there were, and as education, you know, increases, positions are screening, more awareness is being raised. I think we'll see that evolve over time, and there will be a better understanding of what this market actually looks like. No, I had nothing to add.

[music].

Sean Maduck: I was going to say, I suspect your gradient trial is going to be key. Yeah, it's really, Alan, very nice to be able to do that. That is the first controlled study in patients with this specific form of Cushing Syndrome. And, you know, we're able to do it in the standard kind of double-blind fashion because many of these patients are not treated at all for their hypercorrosolism, which is treated with seven different medications for seven different symptoms.

Sean Maduck: So I'm really looking forward to adding that to the scientific literature and hopefully being helpful in clinical care very quickly. Got a couple more questions, but they tend to be more fellow softco. I want to follow up on Matt Kaplan.

Alan Leong: Kaplan's question on court,

Alan Leong: Court 113176, but really on how your portfolio may be applied to CNS and, you know, muscular diseases. Because I'm watching this, and cortisol dysregulation and metabolic problems are prominent in these, I'd like to see the drugs be successful at CNS mechanisms, but it's still not yet, but I look at your drugs, and if all they did was help mitigate their metabolic problems, that's, you know, huge. Oh, I don't know if you have any color on it.

Joseph K. Belanoff: I'll give you, I can give you the five-hour version of that. You know how I'll shorten it for you. You know, look, as you know, Alan, I'm a psychiatrist by training. I think the brain is the most sensitive organ in the body to hormonal dysregulation, specifically cortisol dysregulation. But historically, psychiatric and neural and biological studies have been among the most, do. And as you know, many large companies have failed in that area, and programs have been cut and so on and so forth.

Joseph K. Belanoff: And so, you know, I have a great intellectual interest in going into that area. I think there's tremendous need and possibility. We have a study now in post-traumatic stress disorder that's being run by the VA. There's good animal data in another neurologic disease, Huntington's disease.

Joseph K. Belanoff: So I'm really hoping that in sort of the five to 10 year zone, we will really be back in a serious way to CNS disorders. It would really be wonderful to give some help to those patients, and cortisol modulation has lots of good reasons to give it a try. So sort of one thing at a time; we have a very full plate as it is, but I do think that, over time, we will be feathering in CNS disorders as we have more information. So, cross-year-old.

Joseph K. Belanoff: You do have a full dinner plate, and that's what I call it. And you can see the clinical pace quickening and the portfolio expanding. Very interesting for a small company, and yet you're opening up, and buying two new drugs into the clinic. Is this what you envisioned as a game plan, a growing clinical portfolio in play, but even fatter than today? Are you still hoping to introduce a new drug roughly every year?

Joseph K. Belanoff: That really is the goal, and cortisol modulation is a very broad and important topic; it just is a very important platform. And we don't want to overstep. We really think very hard about what we can actually get done. But yes, I really do think that's a fair statement of our goal, which is to add a compound a year. And if the evidence is there for it, to add a disorder a year. But I can't promise that that's going to be the case. We'll follow the evidence where it leads, but I think that we're really on to something. I think cortisol modulation is a big area, and we're first.

Alan Leong: Keith, thanks for answering my questions. I hope it comes true. You're kind of interesting; it's an interesting situation being such a small company but trying to create a trade and execute a large portfolio.

[music].

Joseph K. Belanoff: Thanks and good luck. Yeah, and we're not as small as we used to be, Alan. You can remember that, right? Thank you. Move over the days. All right. Well, listen, I'm going to stop here. It was great to talk to all of you. Obviously, as soon as we have news, we will put it out. Otherwise, we'll talk to all of you next quarter. And, you know, I hope you enjoy what's left of the fall and the early winter. Talk to you later.

Operator: Thank you, speakers. Ladies and gentlemen, this concludes this conference call. Thank you all for joining. You may now disconnect.

Operator: and so on the way. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you, and and and Thank you. Thank you, and so on the Thank you, and so on the same.

Operator: Thank you. Thank you. Thank you. Thank you, and and Thank you. Thank you. Thank you.