Good day, and thank you for standing by. Welcome to the Corcept Therapeutics conference call. At this time, all participants are in a listen-only mode. After the speaker presentation, there will be a Q&A session. To ask a question during the session, you will need to press star one one on your telephone. You will then hear an automated message advising your hand is raised. Please be advised that today's conference is being recorded. I would now like to hand the conference over to your speaker today, Atabak Mokari, CFO. Please go ahead.
Good afternoon, and thank you for joining us. I'm Atabak Mokari, Corcept's Chief Financial Officer. Today, we issued a press release announcing our financial results for the second quarter and providing a corporate update. The copy is available at corcept.com. Our complete financial results will be available when we file our Form 10-Q with the SEC. Today's call is being recorded. A replay will be available at the Investors tab of our website. Statements during this call, other than statements of historical fact, are forward-looking statements based on our plans and expectations that are subject to risks and uncertainties, which might cause actual results to differ materially from those such statements express or imply.
These forward-looking statements are described in today's press release, and the risks and uncertainties that it may affect them are described in the press release and in our annual report on Form 10-K and our quarterly reports on Form 10-Q. Please refer to those documents for additional information. We disclaim any intention or duty to update forward-looking statements. Our revenue in the second quarter was $103.4 million, an increase of 13% compared to the second quarter of last year. We expect our revenue growth to continue and have reiterated our 2022 revenue guidance of $400 million-$430 million. Net income was $27.4 million or $0.24 per common share in the second quarter.
Our cash and investments increased $13.9 million in the second quarter to $382 million at June 30th. The increase in cash was $13.5 million less than it might have been due to a recent change in federal tax law. Previously, R&D expenses could be deducted from income for the purposes of calculating federal tax in the year in which they were incurred. Beginning this year, R&D expenses must be amortized over five years, which means that the tax benefit of each year's R&D spending, while unchanged in the aggregate, will now be recognized in five equal annual installments. Our cash balance on June 30th reflects the impact of this change for the first half of the year. If Congress restores the immediate deductibility of R&D spending, we will receive a tax refund.
I will now turn the call over to Charlie Robb, our Chief Business Officer, to provide an update on our litigation with generic manufacturers Teva and Hikma Pharmaceuticals. Charlie?
Thanks, Atabak. There's little to report this quarter. As many of you know, Teva is seeking to market a generic version of Korlym in violation of our patents. In March 2018, we sued Teva in federal district court. That lawsuit is still underway, although currently all is quiet. Over a year ago, we filed for summary judgment on Teva's infringement of our '214 patent. As expected, Teva responded by filing its own summary judgment motion. Summary judgment is a procedure whereby courts decide a case without holding a trial. The court has not responded to these motions. Because Teva challenged the validity of our '214 patent before the patent trial and appeals board in a procedure known as a post-grant review or PGR, and lost, it can no longer challenge the '214 patent's validity in district court.
Teva's only defense to our summary judgment motion is that its proposed product would not infringe, a position we believe has no legal or factual support. If the court decides the pending summary judgment motions in our favor, Teva would be barred from marketing generic Korlym until 2037 when the 214 patent expires. If the court rules in Teva's favor, we will proceed to trial, most probably sometime next year. There is no timetable for the summary judgment motion ruling, no trial date, and no schedule for any trial-related activities. In March 2021, we sued another ANDA filer, Hikma Pharmaceuticals, in the same federal district court that is hearing our case against Teva. The court originally set a fact discovery deadline of July 1st of this year, although that date has been vacated. No deadlines are currently scheduled for this case.
With respect to both Teva and Hikma, we are confident in the strength of our legal position. I'll now turn the call over to Dr. Joseph Belanoff, our Chief Executive Officer. Joe?
Thank you, Charlie. Our Cushing's syndrome business is built on a solid foundation, a life-saving medication promoted by a commercial team that puts the interests of patients first. Our strong second quarter results reflect this. As the country gets closer to resuming a pre-pandemic way of life, physicians will experience fewer challenges identifying, diagnosing, and optimally treating their patients, especially those with a complex disorder such as Cushing's syndrome. Leading endocrinologists increasingly believe that there are substantially more patients with Cushing's syndrome than was once assumed. For many of these patients, Korlym is an excellent treatment. We reiterate our 2022 revenue guidance of $400 million-$430 million. We are extremely optimistic about our clinical development programs.
We believe cortisol modulation has the potential to treat many serious diseases. The positive results of our phase II trial in women with platinum-resistant ovarian cancer provide serious evidence supporting cortisol modulation's broad application. This year, we will see important results from our phase II GRATITUDE trials in antipsychotic-induced weight gain and our dose-ranging study in patients with nonalcoholic steatohepatitis or NASH. Our portfolio of more than 1,000 proprietary molecules, together with funds provided by our commercial success, will allow us to further broaden our lines of inquiry. All of our compounds modulate cortisol's effects by binding strongly to the glucocorticoid receptor or GR. They do not bind to the progesterone receptor, and so don't cause some of Korlym's, our approved products, most serious off-target effects. Interestingly, while all of our compounds modulate cortisol's activity without modulating progesterone's activity, they are not identical.
Some cross the blood-brain barrier, others do not. Some perform best in models of solid tumors, others are more potent in models of metabolic disease. Some appear to be tissue-specific, others have more global effects. These diverse qualities allow us to effectively examine a wide variety of disorders. Currently, we are studying ovarian, adrenal, and prostate cancer, antipsychotic-induced weight gain, NASH, and of course, Cushing's syndrome. We plan to start a phase II trial in patients with ALS this quarter and have additional compounds in phase I and preclinical development. Our Cushing's syndrome business has funded all of these programs and will continue to do so. Our oncology program is testing three anti-cancer mechanisms, first postulated by investigators at the University of Chicago and later confirmed by other prominent researchers. One mechanism is increasing apoptosis. The program's cell death that chemotherapy is meant to induce in solid tumors.
Cortisol works against the beneficial effect of chemotherapy by suppressing apoptosis. In our successful controlled phase II trial in women with platinum-resistant ovarian cancer, the addition of a selective cortisol modulator, relacorilant, enhanced the effect of chemotherapy, likely by blunting cortisol's anti-apoptotic effect. While these women's disease had progressed on two or more previous lines of treatment, including previous taxanes, relacorilant appeared to resensitize some of them to chemotherapy's beneficial effects. In addition, the women who received relacorilant plus chemotherapy experienced no additional side effect burden compared to those who received chemotherapy alone. Relacorilant provided meaningful benefit to many of the women in our study. Those who received relacorilant intermittently, the day before, the day of, and the day after they received nab-paclitaxel, exhibited a statistically significant improvement in progression-free survival and duration of response compared to the group who received nab-paclitaxel monotherapy.
While our study was not powered to show a difference in overall survival, or OS, compared to nab-paclitaxel monotherapy, women in the intermittent relacorilant group also lived longer than those in the comparator arm with a P value that approached statistical significance. No approved therapies have demonstrated an overall survival benefit in patients with platinum-resistant ovarian cancer. The results from the study were featured in podium presentations at the September 2021 European Society for Medical Oncology, ESMO Congress, and at the 2022 American Society of Clinical Oncology, ASCO annual meeting. As we announced last month, we have started our pivotal phase III trial in platinum-resistant ovarian cancer, which we have named ROSELLA. Planned enrollment is 360 women randomized 1 to 1 to receive either relacorilant plus nab-paclitaxel or nab-paclitaxel alone. The primary endpoint will be progression-free survival with overall survival a key secondary endpoint.
ROSELLA's design closely tracks our phase II study with adjustments that emerge from constructive conversations with the FDA and leading clinicians from the Gynecologic Oncology Group in the United States and the European Network of Gynecological Oncological Trial Groups in Europe. Two adjustments warrant special notice. First, women who enroll in ROSELLA must have received prior bevacizumab therapy, which is the current standard of care in the United States for patients with platinum-resistant ovarian cancer. 59% of the women in our phase II study had received prior bevacizumab, and we expect this percentage to continue to increase in clinical practice. Second, women whose tumors have not responded at all to platinum-based treatments and those who have received more than three prior lines of therapy will be excluded.
Women in our phase II study meeting these criteria exhibited even greater differential improvement in progression-free survival, duration of response, and overall survival without an increase in the frequency or severity of adverse events. Median PFS for women who received relacorilant intermittently was 7.3 months compared to 3.7 months for the women who received nab-paclitaxel alone with a hazard ratio of 0.4. Their median OS was also significantly longer, 17.9 months compared to 12.6 months with a hazard ratio of 0.38. Our goal in phase III is simply to replicate our positive phase II results.
Leading gynecological oncologists have told us that in their view, relacorilant's potential benefit. Improved survival without increased side effect burden would constitute an important medical advance, and that relacorilant plus nab-paclitaxel has the potential to become a new standard of care in women with platinum-resistant ovarian cancer. A second mechanism by which cortisol modulation may prove useful is by blocking an important tumor growth pathway. Cortisol stimulation is a major reason why patients with prostate cancer treated with a widely prescribed androgen receptor antagonist enzalutamide eventually experience resurgent disease. Deprived of androgen stimulation, their tumors switch to cortisol activity to stimulate growth. Our hypothesis is that adding a cortisol modulator to androgen deprivation therapy will close this tumor escape route. We recently completed a dose-finding study of our selective cortisol modulator, exacorilant, combined with enzalutamide in men with castrate-resistant prostate cancer.
Investigators at the University of Chicago, led by Professor Russell Szmulewitz, completed a similar study of relacorilant combined with enzalutamide. Both studies produced acceptable dosing regimens. We have decided to proceed with a randomized placebo-controlled phase II trial of relacorilant plus enzalutamide in patients with prostate cancer in collaboration with Dr. Szmulewitz at the University of Chicago. Patients in Professor Szmulewitz's planned study will be treated with either enzalutamide or relacorilant plus enzalutamide before they have had an initial prostatectomy. Enzalutamide has been shown to have benefit much earlier in patients' treatment path than was apparent at its first approval, and we think that relacorilant has the potential to add to its benefit. The patient group that will be studied is large, as is the commercial opportunity.
A third therapeutic mechanism seeks to treat tumors by reducing cortisol suppression of the immune system, a quality of cortisol that likely blunts the effectiveness of therapies intended to enhance the body's immune response. We are conducting an open-label phase I-b trial of relacorilant plus the PD-1 checkpoint inhibitor pembrolizumab, Merck's drug Keytruda, in patients with advanced adrenal cancer whose tumors produce excess cortisol. These patients suffer the effects of adrenal cancer and Cushing's syndrome, a usually quickly lethal combination. Pembrolizumab is rarely effective in treating this form of adrenal cancer. We believe that excess cortisol, by suppressing the immune system, may be counteracting the intended effects of pembrolizumab, which is to stimulate the immune system. Our trial is evaluating whether relacorilant can treat these patients' Cushing's syndrome by reducing excess cortisol activity and by reversing cortisol-induced immune suppression to allow pembrolizumab to achieve its full cancer-killing effect.
We plan to enroll 20 patients at sites across the United States. The primary endpoint of the study is objective response rate, with secondary endpoints including progression-free survival, duration of response, and overall survival. I'll turn now to our programs in metabolic disease, which will produce important data soon. We are conducting two double-blind, placebo-controlled phase II trials of miricorilant, GRATITUDE and GRATITUDE II, in patients with antipsychotic-induced weight gain, a serious and widespread disorder. In the United States, 6 million people take antipsychotic medications such as olanzapine and risperidone to treat illnesses including schizophrenia, bipolar disorder, and depression. While these drugs are very effective, they cause rapid and sustained weight gain as well as cardiovascular and metabolic disease. The burden on patients is severe. The average life expectancy of patients in the United States who take antipsychotic medications chronically is decreased by 20 years.
These side effects also dissuade many patients from adhering to their treatment regimen. The GRATITUDE trial seek to build on the positive data from our study of miricorilant in healthy subjects. In 2020, we completed a trial in which 96 healthy subjects received olanzapine and either 600 milligrams of miricorilant, 900 milligrams of miricorilant, or placebo for 14 days. Subjects who received miricorilant gained significantly less weight than those who received placebo. They also exhibited a smaller increase in triglycerides and in the liver enzymes ALT and AST, which typically exhibit sharp transient increases at the start of olanzapine therapy. A paper describing these results was published in the Journal of Clinical Psychopharmacology last year. GRATITUDE is evaluating whether miricorilant can reverse recent antipsychotic-induced weight gain.
Patients with schizophrenia or bipolar disorder receive, in addition to their established dose of antipsychotic medication, either 600 milligrams of miricorilant or placebo for 12 weeks. GRATITUDE II is testing miricorilant as a treatment for long-standing antipsychotic-induced weight gain. Patients with schizophrenia receive, in addition to their established dose of antipsychotic medication, either 600 milligrams or 900 milligrams of miricorilant or placebo for 26 weeks. While the primary endpoint in both studies is reduction in body weight, it is important to stress that measures of metabolic activity will be examined that are equally important to patient health. Improvements in lipids, glucose control, and markers of liver health would be highly desirable outcomes. These studies will produce important data in many areas. Dosing of patients in both trials is complete.
We look forward to results by year-end. Miricorilant is also our candidate treatment for patients with NASH, a serious liver disorder that affects millions of patients in the United States. In our prior study, patients who received miricorilant exhibited large, rapid reductions in liver fat, but also substantial, albeit transient, elevations of ALT and AST. The improvement in liver fat in these patients was greater and occurred much more rapidly than we had expected, and are rarely seen over any period of treatment. Patients exhibited reductions from 38.5% to 73.8% after receiving miricorilant for just one month. To put this in perspective, recall that the trial's primary endpoint was a 30% reduction in liver fat after 12 weeks. It may be that the rapidity of miricorilant's fat-reducing effect caused the patient's ALT and AST to rise.
One way the liver sheds fat is by metabolizing it into fatty acids, which in excessive amounts irritate the liver. Lipids in the bloodstream of these patients did not increase, providing support for the idea that miricorilant caused their excess fat to be metabolized immediately within the liver. Our current phase 1b dose-finding trial in patients with presumed NASH aims to identify a dosing regimen that significantly reduces fat without causing excessive liver irritation. We expect results later this year. As most of you know, we are evaluating relacorilant, our planned successor to Korlym, for the treatment of hypercortisolism in two phase III trials, GRACE and GRADIENT. Relacorilant is a selective cortisol modulator. 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, and so does not cause PR-related side effects, including termination of pregnancy, endometrial thickening, and vaginal bleeding. By a different mechanism, relacorilant also does not appear to cause hypokalemia, low potassium. A serious side effect experienced by 44% of patients in Korlym's SEISMIC trial. Korlym-induced hypokalemia is a leading cause of Korlym discontinuation. Relacorilant's phase II efficacy and safety data were strong. Patients experienced meaningful improvements in hypertension and glucose control, as well as in a variety of other signs and symptoms of Cushing's syndrome. There were no relacorilant-induced instances of endometrial thickening or vaginal bleeding and no drug-induced hypokalemia. The trial results were published in Frontiers in Endocrinology last year. GRACE has a planned enrollment of 130 patients with any etiology of Cushing's syndrome and has a randomized withdrawal trial design.
All patients initially receive relacorilant for 22 weeks. Those who meet response criteria are randomized to continued treatment with relacorilant or placebo for 12 weeks. We and our investigators are eager to take Grace to the finish line. We expect Grace to serve as the basis for our NDA submission in Cushing's syndrome, which we expect to submit in the second half of 2023. Our second phase III trial, Gradient, is studying relacorilant's effects in patients whose Cushing's syndrome is caused by an adrenal adenoma or adrenal hyperplasia. Patients with this etiology of Cushing's syndrome often experience a less rapid decline, but their health outcomes are poor. Gradient is the first controlled study in patients with this type of Cushing's syndrome.
While we do not expect our NDA in Cushing's syndrome to depend on data from GRADIENT, we do expect that its findings will improve the care of these increasingly recognized patients. GRADIENT, a randomized placebo-controlled study, has a planned enrollment of 130 patients. Finally, a word about dazucorilant, which has shown great promise in animal models of ALS. ALS, commonly known as Lou Gehrig's disease, is a devastating disease with very modest pharmacologic treatment options. This quarter we plan to initiate a 198 patient randomized double-blind placebo-controlled phase 2 trial of dazucorilant in ALS, which we have named DAZALS, D-A-Z-A-L-S. This study is being shepherded by TRICALS, a leading ALS academic consortium in Europe. To sum up, our second quarter commercial results were strong, and we expect growth to continue as pandemic conditions recede.
We have reiterated our 2022 revenue guidance of $400 million-$430 million. Our development programs continue to generate evidence validating our long-held belief that cortisol modulation has the potential to treat a wide range of diseases. Reducing cortisol activity is a straightforward way to treat Cushing's syndrome. What now appears clear is that excessive cortisol activity affects other very important diseases and can be improved by cortisol modulation. Ovarian cancer is an excellent example, but there will be others. Later this year, we will have important data from our antipsychotic-induced weight gain and NASH studies. Our just opening multinational trial in ALS has real promise. A whole academic field in the use of cortisol modulation in alcohol and other addictions has begun. In addition to relacorilant, miricorilant, and dazucorilant, we have many individually distinguishable cortisol modulators with clinical potential.
Corcept is steadily advancing. I thank our dedicated, creative employees and loyal investors for making this possible. I'll stop here for questions.
As a reminder, to ask a question, you will need to press star one one on your telephone. Please stand by while we compile the Q&A roster. Our first question comes from the line of Matt Kaplan with Ladenburg. Your line is now open.
Hi, thanks for taking the questions and congrats on a good quarter. I guess with the initiation of your phase III study in platinum-resistant ovarian cancer patients, can you help us understand the market opportunity there? Specifically, how many ovarian cancer patients in the U.S. and how many of those are platinum resistant and would be targets for your treatment?
Yeah. Thanks, Matt. Thanks very much for the question. So first, you know, I just wanna point out, I know you know this to the whole group, that the group of platinum-resistant patients are a subgroup of patient, all patients who have ovarian cancer. It's approximated that there are somewhat above 200,000 patients in the country who have ovarian cancer, and our best estimate is about 20,000-25,000 patients who have platinum-resistant disease and about an equal number in Europe to that.
Okay, great. With the phase III trial, can you help us understand kind of the timeline for that program?
Yes. In fact, I'm gonna try something that, you know, I'm really bad at technology, but Bill Guyer, our Chief Development Officer, is in Europe and on the line. Bill, if you can actually hear me and answer.
Yes.
Mike's exact question.
Yes, thank you very much for that question. Yes, the ROSELLA study is open, and we're actively working with sites to enroll patients as soon as possible. We're also actively working with adding additional sites from around the world. When I look at this trial with our estimates, the study will take us about 12 months-14 months to enroll the study and about 12 months to accrue the data. About two years from now, we should see results from the ROSELLA trial.
Okay. Last question on the ovarian cancer. Do you think in the future that this could be an opportunity to move to earlier stages of treatment and specifically frontline ovarian cancer in combination as well?
Well, thanks, Matt. The answer to that is something we're looking at very seriously. As you know, many drugs are often approved in sort of late-line therapy and then as evidence increases and, you know, of course, with longer studies, it moves earlier in treatment. We are certainly taking a very close look at that, in fact, really top of our list. I hope to really be able to update you on how we're thinking about that in coming calls.
Great. Thanks. Thanks for taking the questions.
Sure. Thanks, Matt.
Okay. Thanks, Matt.
Your next question comes from the line of Dennis Ding with Jefferies. Your line is now open.
Hey, guys. Thanks for taking my question. Two for me. Question number one, can you give a little bit more granularity on some of the patient dynamics in Q2? Specifically, you know, how much of the sequential revenue growth was from normalization of price, how much of it came from patients who are new to Korlym, and how much came from patients who couldn't take the drug before because of COVID but are getting back onto it? My second question, can you just update us on the DOJ subpoena in terms of what we're waiting for, and just remind us what is the next step? It seems like this could be a pretty major binary event, you know, once it eventually unfolds. Thank you.
Okay. Thank you, Dennis, and glad to hear from you. I'd first like to reintroduce our group to Sean Maduck, who is the president of our endocrinology division, and really handling all responsibilities, including the commercial responsibilities for Korlym.
Dennis, yeah, thanks for the question. I thought I would start just first off by pointing to sort of remind everyone that Q1 is typically slightly depressed, right? Because of all the insurance changeovers and the volume of free drug that we give to ensure patients don't stop therapy over the course of their insurance reauthorizations. All that being said, you know, we're very pleased with the second quarter. I wanna remind everyone of what are the key drivers of our business, and that's really a patient's ability to see their doctor in person, and then of course, that clinical specialist ability to meet with physicians. Again, both of those are key drivers.
In the second quarter, we did see some improvement in both of those areas, and that led to more patient-physician interaction, more Corcept physician interaction, which led to more new patients being prescribed and more new prescribers actually coming on board. I would say those two are the main drivers of the change, new patients and new prescribers. Again, all that being said, neither of those metrics have reached the pre-pandemic levels that we had seen before the start of COVID-19, and we're actually not sure if they ever will as an organization. There's telemedicine now, medical practices are closing their doors in some cases to pharmaceutical representatives, and that creates operational hurdles that are not just Corcept specific, right? These are industry-wide.
What our commitment is, we have worked hard to find new ways to operate in that new normal and we are continuing to do that, and I'm very confident that we will find new and creative ways to continue to reach our target audience.
Charlie, would you like to answer the second question, please?
Sure. Hi. Yeah, thanks for the question. The short answer is there's no updates with respect to the DOJ subpoena. Before I elaborate a little bit on that, let me give background for folks who might not be as familiar. You know, we... Folks may recall that, you know, back in 2018 or so, you know, we suffered some short seller attention and attacks that we, you know, pushed through, of course, but there were a couple of lingering consequences of that. One was this securities class action that we are grinding through right now. The other, I believe, is this DOJ inquiry, where they requested a whole bunch of documents, you know, concerning our commercial business. Now the...
Our approach to this, you know, beyond obviously cooperating with the DOJ, is to give them as much information they want faster than they can actually absorb it, just because we wanna get all the information in front of them so that we can move through this. We think that's our path to resolution. The truth is our friend in this case, and we are moving things as quickly as we can on our side. I stress that just because it's a little unusual. I think the typical strategy is just to delay, delay. We see no point in doing that. You know, we know there's light at the end of the tunnel, and that's what we're driving to as fast as we can. Having said that, of course, we don't control the pace of this.
All we can do is put the information out there as it's requested faster than expected. We're doing that. Other than that's all I can report because that's all I know. You know, this will be resolved at some point. We're very confident in our position. I just can't say more than that right now.
Thank you, Dennis.
Your next question comes from the line of Michael Covente from Canaccord. Your line is now open.
Hello. This is Michael on for Edward . Congrats on the quarter. I have two quick questions. So for the phase III ROSELLA trial, can you remind us what led to choosing the nab-paclitaxel as the active chemotherapy control, which does match the phase II trial, by the way. I remember the initial phase III design allows for investigator choice. What, as you launched that last month, what led to that change?
Yeah. No, I understand the question. Bill, if you're out there, would you-
Yeah.
Please answer that?
Yeah. That's. Thank you very much for the question. It was a really easy decision to make. As we were looking at the phase III study design and working with the GOG, the Gynecologic Oncology Group, as well as ENGOT, we had thought of and come up with many different iterations of a phase III design, and the first one that you had mentioned was investigator choice. After we got very positive and supportive comments from the FDA, we then looked at other analyses around prior bevacizumab use, as well as patients who had 1-3 prior lines of therapy and patients where we excluded primary platinum refractory patients.
Looking at that analysis, we then decided to repeat the phase II study because we saw unprecedented results where, as Joe had indicated, we saw an overall response rate for PFS of greater than three months with a hazard ratio of 0.40. We saw OS benefit of greater than five months with a hazard ratio of 0.38, and we saw a benefit of about 2.5 months of duration of response with a hazard ratio of 0.29. Looking at those phase II results and talking and working with the FDA, we felt it was simplest to just repeat the phase II trial in our phase III study design. The FDA agreed with that as well.
that was the simplest path to moving forward as quickly as possible, and it was a very simple and easy path for us to follow.
Yeah. I'd just add one comment to that because I think you asked specifically about why we went from dealer's choice to nab-paclitaxel alone. Just to remind everyone, our phase II study was with nab-paclitaxel alone, and the overall feedback we got, including the regulatory feedback, was that that was a very easy to understand result, and if replicated, would be very easy to understand as a phase III result.
Perfect. Thank you. Just one additional quick one, kind of on some of your earlier stage programs. You recently or you just announced you've launched or are planning to launch in prostate cancer. You're using enzalutamide, which is brand name Xtandi. Those patients tend to have, which they do great actually, they tend to have a median OS of around 18 months-32 months, which is quite a long time for a trial. Can you discuss perhaps the timelines for this newly initiated trial? How long do you think you'll need to run a trial to see a benefit of relacorilant? Would you do like an interim data cut to sort of see how it's going? Any sort of thoughts on this and this program as it finally gets off the ground?
Yeah. No, I'm really glad that caught your attention because it's a very interesting program. It's really just at the beginning. Just a couple things to remind the group. This is, you know, we're using relacorilant. We had a choice between relacorilant or exacorilant. The person who led the relacorilant study in previous study in dose finding, in this group, Russell Szmulewitz, which is the University of Chicago, is actually gonna be leading this study as well as an investigator study, as a grant-funded study.
The timing is a little bit more opaque to us, although I know he's very anxious to get going with it. Everything that you said is in fact true. It's been very nice to see because of you know, enzalutamide's real success that patients with prostate cancer have achieved a lot of benefit that, you know, was really unthinkable 15 years ago. As I said in my comments earlier, enzalutamide not just seems to work kind of at the end of line treatment, but earlier in therapy. I'll remind you again, this is a study that he had great interest to us, that he has now gotten funded to look at patients pre-prostatectomy. That, you know, obviously that's about as early as you can get. That's before diagnosis and even surgery.
Does seem like enzalutamide actually has real benefit for those patients in the long run. We think that adding relacorilant to that to shut off really a tumor escape route will have even greater benefit. The timelines for it at this point in time are a little uncertain to us. It will be some time. You know, you're absolutely right. This is not like an end-stage disease where, you know, sort of sadly, people die quickly. We'll have to look at this over a period of time, and I'll get back to you with more specifics in coming calls.
Super. Thank you.
Your next question comes from the line of Greg Fraser from Truist. Your line is now open.
Good afternoon, folks. Thanks for taking the questions. First one on Korlym. You had good year-over-year growth in sales. The trajectory doesn't appear to have been impacted so far by the newest entrant into the Cushing's market. I'm just curious if you've detected any impact so far on utilization trends or prescribing that might be related to the Korlym?
Yeah. Greg, I'm gonna pass you back over to Sean.
Yeah, Greg, thanks for the question. No, we have not seen an impact from the competition. Traditionally, we believe that more patients or more companies are out there educating physicians on hypercortisolism, and obviously, the guidelines and proper screening as this will continue to help patient care.
Got it. On the GRACE study, I know you reiterated your target for NDA submission. Can you just confirm that enrollment in the study has been progressing in line with your expectations?
Yeah. In fact, let me give you back over to Bill again, who seems to be working. Go ahead, Bill.
Yes. Yes, thank you for that question. Yes, timelines are still on track. You know, first and foremost, we're excited and focused on finishing this study, as are each and every one of the investigators because of the benefit relacorilant could bring to their patients. You know, we've completed a few investigator meetings in the U.S. and Europe, and each of the investigators really reiterated their excitement and enthusiasm for relacorilant and their unwavering need and desire to help us enroll this study expeditiously. Based on all of our interactions with investigators, we feel that we are still on track.
Very good. On the prostate cancer program, can you comment on any efficacy signals that were seen in the phase I study? Thank you.
Yeah. I mean, there really is a quick answer to that. It's really designed as a dose-finding study, obviously not in a controlled setting. I don't think that there's really much efficacy data that I can relate to you for things that you could draw forward from. I think that all of the results again, you know, in the investigator study will be presented at a conference as we will as well. I just wanna remind the group that whatever one sees there, reminding that this is really a safety and tolerability study and to give us an indication for where to go next.
Got it. Thanks for taking the questions.
Your next question comes from the line of R.K. from H.C. Wainwright. Your line is now open.
Thank you. Good afternoon, gentlemen. It looks like you had a very good quarter. Just a couple of quick questions on the pipeline front. On the ROSELLA study, does the study have an interim look? If it does, at what point is the interim look going to be?
Bill, could you take that question?
Sure, I'll take that question. No, we do not have an interim look into the study. The primary endpoint is PFS. When we hit our predefined PFS numbers, that's when we will read out the study. Our secondary endpoint is overall survival. At this point in time, there is not an interim look designed for the ROSELLA study.
Okay, thank you. Then on the DAZALS study in ALS, trying to understand how dazucorilant, I guess, works and also, does this drug have any efficacy in other movement disorders or neuromuscular disorders such as MS and Parkinson's?
Yeah. You know, I'm glad you asked that. It's a little more scientifically far afield than I usually get in conference calls, but you know, RK, you know me, I could talk about this for a long time. The bottom line is this. It's been known for quite a while that there are neuromuscular diseases, and ALS is a good example, where you have aberrant cortisol activity. Cortisol levels are higher. People lose their diurnal rhythm, and there really has been a thought that this contributes to disease progression. What really got us interested in ALS specifically is there's a good animal model of ALS. It's obviously not exactly the same as ALS, but it's one that's been used for a very long time called the wobbler mice. In some sense, it sounds sort of like what it is.
These are animals which really lose their coordination and may manifest similar symptoms to what people do who have ALS. They have the same cortisol issues that people do as well. Now, you know, in I guess, almost half a dozen publications been shown that does correlate GR modulation really changes that. You know, in the animals, at least not only do the patient. Not only do the animals slow their decline in their neurologic symptoms, they actually improve over a period of time. Of course, not everything in animals translates to people. It'd be wonderful if that actually did translate to people. The bottom line is there's really a good reason to give it a try.
I said it before, ALS is kind of, you know, as much as we have one, you know, the Mount Everest of medical maladies, terrible problem. If we could offer these patients anything that resembled the results that we saw in animals, that would be a wonderful thing. Now, your second question is also prescient because there are other neuromuscular diseases where there is cortisol aberration. For instance, Huntington's disease is one, and we actually have preclinical investigators who are studying Huntington's disease at this point. I happen to just coincidentally be talking to an investigator today who is interested in looking at GR modulation in Parkinson's disease. You know, as you know, you know, psychiatry and neurology have been my interest for a very long period of time. These are very difficult interest areas in which to show progress.
I do think that we will be enlarging our programs in this area and hopefully ultimately be able to offer patients some. We actually have preclinical investigators who are studying Huntington's disease at this point. I happen to just coincidentally be talking to an investigator today who is interested in looking at GR modulation in Parkinson's disease. As you know, you know, psychiatry and neurology have been my interest for a very long period of time. These are very difficult interest areas in which to show progress. I do think that we will be enlarging our programs in this area and hopefully ultimately be able to offer patients something they clearly cannot get today.
Thank you for that. In the GRATITUDE studies, where the data is expected by the end of this year, what are the next steps in those development programs, in terms of, you know, when you could initiate late-stage trials in looking at antipsychotic-induced weight gain?
Yeah. Well, first, we're very excited to complete these studies. No one has ever had a successful study in reversing antipsychotic-induced weight gain. You know, we could do it in animals, and we have real hopes in these studies. But I just, you know, thank our internal staff and our investigators for actually getting this all enrolled and up to the point where we're gonna see results. I think, as I said before, I just want to emphasize this point that we're not just looking at weight gain. Hopefully, we'll really see metabolic changes that will be very beneficial to these patients as well.
One thing I haven't commented on before, we may see psychiatric changes that are beneficial to these patients because we think the cortisol modulation has a chance to actually be useful in that vein, as well. Now, the answer to your specific question, I could give you know, my general answer would be it's gonna be results dependent as to sort of what we have to do next. If you go to the extreme end of a result that's extremely clear, and easy to interpret, I'm certain that we will begin a late-stage study next year. I really don't wanna promise that I haven't seen the results yet, but certainly, if the path is straightforward, that's where we'll go. First, the results.
Thank you. Thanks for taking all my questions.
Sure.
Your last question comes from the line of Alan Leong with BioWatch News. Your line is now open.
Congratulations on another good quarter.
Hi, Alan.
Hey, Joe. Although I've written about it, our readers would like to hear about your rationale behind the ALS trial design. They note that that's not a quote, "toe dipping phase to a pilot," end quote, but a larger, well-controlled design. What motivated the commitment to a stronger design?
You know, Alan, I really apologize. There was some static in the line, and I couldn't hear your question. Would you mind repeating it?
Sure. My readers noted that your ALS trial design is not what they would claim a toe-dipping tentative Phase II pilot, but it's a larger, well-controlled design. What motivates the commitment to a stronger design?
Yeah, okay, now I heard it that time, Alan, and I really do appreciate that question. I'm gonna repeat that question in case it was hard to hear for other people out in the audience. What Alan was asking is, instead of doing, you know, a small study that just looked at a specific biomarker or something like that, why are we doing essentially what is a very good sized, well-controlled study? I have to tell you, part of that is my own personal bias, which is that, you know, it's very hard to know, particularly in psychiatric and neurologic diseases, what you actually have until you do a well-controlled study with placebo.
The flip side of that is that I think particularly in a disease like ALS, where kinda sadly people only have one shot at a trial, that you actually have to be able to present to them something that has a legitimate chance to actually providing real benefit. You know, as I said before, our animal studies really were quite positive, but it was very important for us to be able to, in some sense, sell this concept to a very experienced group of investigators who believe that it had a shot. Because just to be blunt about it, if patients enter our study, they may never be able to enter another study.
We really wanted to get to the point where we used their time and our time the best and presented a result that actually is gonna be the most dispositive about where we stand.
Great. Thank you. Then with the prostate, upcoming prostate cancer study, you stayed with relacorilant rather than exicorilant. As I recall, relacorilant has excellent GI blocking properties while exicorilant, if I'm not mistaken, has some interesting tissue penetration. Is that correct? Can you provide some color on the advantages that you think propel relacorilant as your drug candidate?
Yeah. The first thing I'd say is, it's a pretty close call.
Mm-hmm.
You know, it's sort of funny, you know, this is, we actually sat down at the very beginning of these two studies, and we got first choice, and we picked exacorilant. Dr. Szmulewitz got second choice, and he got relacorilant. I clearly got it wrong there. The results were pretty similar. Actually found that relacorilant has a little bit better tolerability. It's a little bit easier drug to manufacture. In addition to that, we know a lot more about it. You know, since that study began, we studied lots of people with relacorilant. We know pretty much how it acts. Exacorilant is not going to zero. It's gonna be on the shelf right now. We just tried to be as objective as we could, and we thought the prospects were better with relacorilant.
Just, you know, I'll just fill in one detail. You have a good memory. In the preclinical models, although both relacorilant and exacorilant work well, exacorilant actually did work a little better in the preclinical models. It highlights the point that I made before, which is that you do your best to translate from animal studies, but it's not lockstep, and we just have to go with where the data showed us the best results.
Yeah. Lastly, this question might be for Sean. I keep asking you this. How much increasing hubbub are you hearing out there or getting requests for treating Cushing's that's really adenoma or less severe Cushing? And related to that, are the results for GRADIENT being released about the same time as GRACE? So it's really two in one.
Sure.
Two related questions.
Sean, Alan, I'll pass it over to him.
Yeah. Thanks for the question, Alan. Look, Korlym is prescribed for all etiologies of Cushing's, for pituitary patients all the way through to the adrenal patients. Over time, we've seen more and more patients overall be prescribed for all of those respective etiologies. I would say, you know, the understanding of this illness has increased. That's where we spend obviously a lot of our time educating physicians, and through that, we've seen some demand increase. I don't know, Joe, if there's anything you wanna add.
Yeah, no, I think that Alan, I think that maybe one of the things that you're getting at is, in some sense, what's the value of the study on adrenal adenomas, of the GRADIENT study in particular. In order to answer that, I just really have to give the whole group some context. You know, 15 years, 20 years ago, it really wasn't appreciated how many patients there were, and again, still a rare disease, but more than people thought, who had hypercortisolism Cushing's syndrome caused by adrenal tumors. Probably a decade ago, we really started to see that that was a real group. What's happened over the last decade is that data has really filled in.
There is no doubt that there are many patients who have hypercortisolism caused by adrenal tumors that have previously been ignored, had bad outcomes, are largely untreated. That's the group that actually GRADIENT study focuses on. Now, we like to be able to help any patient who has hypercortisolism, and I think that actually producing controlled results is one of the ways to really get there. We think that the field is very, very interested in what's really kind of the standard double-blind study. We'll see what the results will be. Maybe the point that I'll leave you with is that what was once really sort of tossed off as not really very important is no longer tossed off.
In publications ranging from the best places to the Mayo Clinic, it's now very clear that the group of patients with adrenal adenomas is both sizable and is very adversely affected by their hypercortisolism.
Thanks. Looking forward to the rest of the year.
Okay. Thank you, Alan. I think that wraps us up here. Thanks. Thank you, everybody. I hope you have a great rest of the summer, and we look forward to talking to you in three months.
This concludes today's conference call. Thank you for your participation. You may now disconnect.