Corcept Therapeutics Incorporated

Q2 2022 Earnings Conference Call

8/3/2022

spk04: Good day and thank you for standing by. Welcome to the Corsair 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 1 1 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, Adubak Mukherjee, CFO. Please go ahead.
spk14: Good afternoon, and thank you for joining us. I'm Adubak Mukherjee, Corset'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 corset.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 investor's past events tab of our website. Statements during this call, other than statements of historical fact, are forward-looking statements based on our plans and expectations that are subject to risk 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 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 to $430 million. Net income was $27.4 million, or 24 cents 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 of 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, provide an update on our litigation with generic manufacturers Teva and Hikma Pharmaceuticals. Charlie?
spk02: Thanks, Padamak. There's a little report this quarter. As many of you know, Teva is seeking to market a generic version of Coraline 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 the procedure known as a post-grant review, or PGR, and lost, it can no longer challenge the 214 patent's validity in district court. TEVA's only defense to our summary judgment motion is that its proposed product would not infringe a position we believe has no legal or factual support. The court decides the pending summary judgment motions in our favor. Teva would be barred from marketing generic corlum until 2037, when the 214 patent expires. 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, HICMA Pharmaceuticals in the same federal district court that is hearing our case against Teva. The court originally set a fact discovery deadline on 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 HICMA, 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?
spk11: Thank you, Charlie. Our Cushing Syndrome business is built on a solid foundation, a life-saving medication promoted by a commercial team that puts the interests of patients first. Our strong second quarter results reflect this. As the country gets closer to resuming a pre-pandemic way of life, physicians will experience fewer challenges identifying, diagnosing, and optimally treating their patients, especially those with a complex disorder such as Cushing Syndrome. Leading endocrinologists increasingly believe that there are substantially more patients with Cushing syndrome than was once assumed. For many of these patients, core illness is an excellent treatment. We reiterate our 2022 revenue guidance of $400 to $430 million. We are extremely optimistic about our clinical development programs. We believe cortisol modulation has the potential to treat many serious diseases. 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 non-alcoholic steatohepatitis, or NASH. Our portfolio of more than 1,000 proprietary molecules together with funds provided by our commercial success, will allow us to further broaden our lines of inquiry. 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 Quorum's, our approved products, most serious off-target effects. Interesting 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 vested 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 syndrome. We plan to start a phase two trial in patients with ALS this quarter and have additional compounds in phase one and preclinical development. Our Cushing 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 the selective cortisol modulator relacoralin 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, relacoralin appeared to resensitize some of them to chemotherapy's beneficial effects. In addition, the women who received relacoralin plus chemotherapy experienced no additional side effect burden compared to those who received chemotherapy alone. Reliquarylin provided meaningful benefit to many of the women in our study. Those who received reliquarylin intermittently, the day before, the day of, and the day after they received napaclitaxel, exhibited a statistically significant improvement in progression-free survival and duration of response compared to the group who received napaclitaxel monotherapy. While our study was not powered to show a difference in overall survival, or OS, compared to NAP haplotaxel monotherapy, women in the intermittent relacoralin 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 this study were featured in podium presentations at the September 2021 European Society for Medical Oncology, ESMO, Congress, and at the 2022 American Society of Clinical Oncology, ASCO, annual meeting. As we announced last month, we have started our pivotal phase three trial in platinum-resistant ovarian cancer, which we have named Rosella. Planned enrollment is 360 women randomized one-to-one to receive either relichloroquine plus napaclitaxel or napaclitaxel 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 Oncology 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 relacorlin intermittently was 7.3 months compared to 3.7 months for the women who received napaclitaxel alone with a hazard ratio of 0.40. Their median OS was also significantly longer, 17.9 months compared to 12.6 months with a hazard ratio of 0.38. Our goal in Phase 3 is simply to replicate our positive Phase 2 results. Leading gynecological oncologists have told us that, in their view, relucoralin's potential benefit, improved survival without increased side effect burden, would constitute an important medical advance, and that relucoralin plus napaclitaxel 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 the 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 hexacorylate combined with enzalutamide in men with castrate-resistant prostate cancer. Investigators at the University of Chicago, led by Professor Russell Smolowitz, completed a similar study of relacorylate combined with enzalutamide. dosing regimen. We have decided to proceed with a randomized placebo-controlled phase 2 trial of relacoralin plus enzalutamide in patients with prostate cancer in collaboration with Dr. Smolowicz at the University of Chicago. Patients in Professor Smolowicz's planned study will be treated with either enzalutamide or relacoralin 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 relichloroquine 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. quality of cortisol that likely blunts the effectiveness of therapies intended to enhance the body's immune response. We're conducting an open-label phase 1B trial of relacoralin plus the PD-1 checkpoint inhibitor pembrolizumab, Merck's drug Keytruda, in patients with advanced adrenal cancer whose tumors produce excess cortisol. These patients suffer the effects of adrenal cancer and Cushing syndrome, a usually quickly lethal combination. Pembrolizumab is rarely affected in treating this form of adrenal cancer. We believe that excess cortisol by suppressing the immune system may be counteracting the intended effects of Pembrolizumab, which is to stimulate the immune system. Our trial is evaluating whether reliquorolin can treat these patients' Cushing syndrome by reducing excess cortisol activity and by reversing cortisol-induced immune suppression allow Pembrolizumab to achieve its full cancer-killing effect. We plan to enroll 20 patients at sites across the United States. The primary endpoint of the study is objective response rate, with secondary endpoints including progression-free survival, duration of response, and overall survival. 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 Miracorland, Gratitude and Gratitude II, in patients with antipsychotic-induced weight gain, a serious and widespread disorder. In the United States, six 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 seeks to build on the positive data from our study of mirror correlates in healthy subjects. In 2020, we completed a trial in which 96 healthy subjects received olanzapine and either 600 milligrams of miracoralin, 900 milligrams of miracoralin, or placebo for 14 days. Subjects who received miracoralin gained significantly less weight than those who received placebo. They also exhibited a smaller increase in triglycerides and in the liver enzymes ALP 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 miracoralin 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 miracoralin or placebo for 12 weeks. Gratitude 2 is testing miracoralin 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 Miracorland or placebo for 26 weeks. While the primary endpoint in both studies is reduction in body weight, it is important to stress that measures of metabolic activity will be examined that are equally important to patient health. Improvement in lipids, glucose control, and markers of liver health would be highly desirable outcomes. These studies will produce important data in many areas. Dosing of patients in both trials is complete. We look forward to results by year-end. Miracoralent 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 Miracoralent 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 miracoralin 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 miracoralin'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 miracoralin caused their excess fat to be metabolized immediately. within the liver. Our current phase 1B dose-binding 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 reliquarolin, our plant's successor to quarolin for the treatment of hypercortisolism, in two phase 3 trials, GRACE and GRADIAN. Relacorolin is a selective cortisol modulator. Like corolla, it achieves its effect by competing with cortisol at the glucocorticoid receptor. Unlike corolla, 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, relacorolin also does not appear to cause hypokalemia, low potassium. serious side effects experienced by 44% of patients in corallum's pivotal trial. Corallum-induced hypokalemia is a leading cause of corallum discontinuation. Relacorallin'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 syndrome. There were no relacorallin-induced instances of endometrial thickening or vaginal bleeding, and no drug-induced hypokalemia. The trial results were published in Frontiers in Endocrinology last year. Grace has a planned enrollment of 130 patients with any etiology of Cushing syndrome and has a randomized withdrawal trial design. All patients initially receive relacoralin for 22 weeks. Those who meet response criteria are randomized to continue treatment with relacoralin 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 syndrome, which we expect to submit in the second half of 2023. Our second phase three trial, Gradient, is studying relic-correlance effects in patients whose Cushing syndrome is caused by an adrenal adenoma or adrenal hyperplasia. Patients with this etiology of Cushing syndrome often experience a less rapid decline, but their health outcomes are poor. Gradient is the first controlled study in patients with this type of Cushing syndrome. While we do not expect our NDA in Cushing syndrome to depend on data from Gradient, we do expect that its findings will improve the care of these increasingly recognized patients. Gradient, a randomized placebo-controlled study, has a planned enrollment of 130 patients. Finally, a word about Dazucoralant, 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 Dazucoralant in ALS, which we have named DAZLS, D-A-Z-A-L-S. This study is being shepherded by TRICALS, a leading ALS academic consortium in Europe. To sum up, our second quarter commercial results were strong and we expect growth to continue as pandemic conditions recede. We have reiterated our 2022 revenue guidance of $400 to $430 million. Our development programs continue to generate evidence validating our long-held belief that cortisol modulation has the potential to treat a wide range of diseases. Reducing cortisol activity is a straightforward way to treat Cushing syndrome. What now appears clear is that excessive cortisol activity affects other very important diseases and can be improved by cortisol modulation. 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. And in addition to relacoralant, miracoralant, and dasacoralant, we have many individually distinguishable cortisol modulators with clinical potential. Corecept is steadily advancing. I thank our dedicated creative employees and loyal investors for making this possible. I'll stop here for questions.
spk04: As a reminder, to ask a question, you will need to press star 1 1 on your telephone. Please stand by while we compile the Q&A roster. And our first question comes from the line of Matt Kaplan with Leidenberg. Your line is now open.
spk03: 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 patients, ovarian cancer patients in the U.S., and how many of those are platinum resistant and would be targets for your treatment?
spk11: Yeah. Thanks, Matt. Thanks very much for the question. So first, you know, I just want to point out, I know you know this to the whole group, that the group of platinum resistant patients are a subgroup of 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.
spk03: Okay, great. And with the Phase III trial, can you help us understand kind of the timeline for that program?
spk11: Yes. In fact, I'm going to try something that, you know, I'm really bad at technology, but Bill Geyer, our chief development officer, is in Europe and on the line. And Bill, if you can actually hear me and answer, I'd like to take that question.
spk12: Yes. Thank you very much for that question. So, yes, the Rosella study is open, and we're actively working with sites to enroll patients as soon as possible. We're also actively working with adding additional sites from around the world. When I look at this trial with our estimates, the study will take us about 12 to 14 months to enroll the study and about 12 months to accrue the data. So about two years from now, we should see results from the Rocella trial.
spk03: And then 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, specifically frontline ovarian cancer and combination as well?
spk11: 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. And we are certainly taking a very close look at that. In fact, really top of our list. And I hope to really be able to update you on how we're thinking about that in coming calls.
spk03: Thanks.
spk01: Thanks for taking the questions. Thanks, Matt. Thanks, Mitch.
spk05: And your next question comes from the line of Dennis Ding.
spk04: Let's chat, please. Your line is now open.
spk09: 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 that came from patients who are new to Cortland, and how much came from patients who couldn't take the drug before because of COVID but are getting back onto it. And then 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.
spk11: Okay, thank you, Dennis, and glad to hear from you. I'd first like to reintroduce our group to Sean Duke, who is the president of our endocrinology division, and really handling all responsibilities, including the commercial responsibilities for Coral.
spk10: Dennis, yeah, thanks for the question. I thought I would start just first off by pointing to remind everyone that Q1 is typically slightly depressed, right, because of all the insurance issues. 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, we're very pleased with the second quarter. I want to 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's ability to meet with physicians. Again, both of those are key drivers, and in the second quarter, we did see some improvement in both of those areas, and that led to more patient position interaction, more course of position interaction, which led to more new patients being prescribed and more new prescribers actually coming on board. So I would say those two are the main drivers of the change, new patients and new prescribers. 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. Telemedicine now, medical practices are closing their doors, in some cases, to pharmaceutical representatives, and that creates operational hurdles that are not just course of specific, right? These are industry-wide. And what our commitment is, is we have worked hard to find new ways to operate 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.
spk11: And Charlie, would you like to answer the second question, please? Sure.
spk02: Hi, thanks for the question. The short answer is there's no updates with respect to the DOJ subpoena, but before I elaborate a little bit on that, let me give background for folks who might not be as familiar. Folks may recall that back in 2018 or so, we suffered some short seller attention in the tax that we pushed through, of course, but there were a couple of lingering consequences of that. One was this Here is class action that we are grinding through right now. And the other, I believe, is this DOJ inquiry where they requested a whole bunch of documents concerning our commercial business. Now, our approach to this, beyond obviously cooperating with the DOJ, is to give them as much information they want faster than they can actually absorb it, just because We want to get all the information in front of them so that we can move through this. We think 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. And I stress that just because it's a little unusual. I think the typical strategy is just to delay, delay, delay. We see no point in doing that. We know 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 and faster than expected. We're doing that. But other than that, that's all I can report because that's all I know. So, 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.
spk01: Thank you, Dennis.
spk04: And your next question comes from the line of Michael Convente from CannaVacord. Your line is now open.
spk13: Hello, this is Michael on for Edward. Congrats on the quarter. I have two quick questions. So for the Phase 3 Rosella trial, can you remind us what led to choosing the nabpaclitaxel of the active chemotherapy control, which does match the Phase 2 trial, by the way? But I remember the initial phase three design a lot for investigator choice. So what, as you launched that last month, what led to that change?
spk11: Yeah, no, I understand the question. And Bill, if you're out there, would you please answer that?
spk12: Yeah, that's, thank you very much for the question. So it's a really easy decision to make. As we were looking at the phase three study design and working with the GOG, the gynecological oncology group, as well as NGOT, we had thought of and come up with many different iterations of the phase three design. And the first one that you had mentioned was investigator choice. But after we got very positive and supportive comments from the FDA, we then looked at other analyses around prior bevacizumab use, as well as patients who had one to three prior lines of therapy and patients who had excluded, where we excluded primary platinum refractory patients. Looking at that analysis, we then decided to repeat the phase two study because we saw unprecedented results where, as Joe had indicated, we saw an overall 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 two and a half months of duration of response with a hazard ratio of 0.29. So looking at those phase two results and talking and working with the FDA, we felt it was simplest to just repeat the phase two trial in our phase three study design. And the FDA agreed with that as well. So that was the simplest path to moving forward as quickly as possible. And it was a very simple and easy path for us to follow.
spk11: Yes. And I'll just add one comment to that, because I think you asked specifically about why we went from dealer's choice to napaclitaxel alone. Now, just to remind everyone, our Phase 2 study was with napaclitaxel alone, and the overall feedback we got, including the regulatory feedback, was that that was a very easy-to-understand result, and if replicated, it would be very easy to understand as a Phase 3 result.
spk13: Perfect. Thank you. And just one additional quick one, kind of on some of your earlier stage programs. So you recently, or you just announced you launched or are planning to launch in prostate cancer, and you're using enzalutamide, which is brand name Xtendi. Those patients tend to have, which they do great actually, they tend to have a median OS of around 18 to 32 months, which is quite a long time for a trial. So can you discuss perhaps the timelines for this newly initiated trial? How long do you think you'll need to run a trial to see a benefit of relic correlant? 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?
spk11: Yeah. No, I'm really glad that that caught your attention because it's a very interesting program. It's really just beginning. And just a couple things to remind the group. This is, you know, we're using relacoralin. We had a choice between relacoralin or hexacoralin. And the person who led the relacoralin study in previous study in dose binding in this group, Russell Small, which is the University of Chicago, is actually going to be leading this study as well as an investigator study, as a grant-funded study. So the timing is a little bit more opaque to us, although I know he's very anxious to get going with it. Everything that he said is, in fact, true. It's been very nice to see, because of Enzalutamide's real success, that patients with prostate cancer have received a lot of benefit that was really unthinkable 15 years ago. And 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. So I'll remind you again, this is a study that he had great interest in us, that he has now gotten funded, to look at patients pre-prostatectomy. Obviously, that's about as early as you can get. That's before diagnosis and even surgery. It does seem like enzalutamide actually has real benefit for those patients in the long run. We think that adding relacoralin to that to shut off really a tumor escape route will have even greater benefit. But the timelines for it at this point in time are a little uncertain to us. But it will be some time. You know, you're absolutely right. This is not like an end stage disease where, you know, 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.
spk13: Super. Thank you.
spk04: Your next question comes from the line of Greg Fraser from Truist. Your line is now open.
spk15: Good afternoon, folks. Thanks for taking the questions. First one on Corland. You had good year-over-year growth in sales. The trajectory doesn't appear to have been impacted so far by the newest entrance 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 Corland.
spk11: Yeah. Greg, I'm going to pass you back over to Sean.
spk10: Yeah, Greg, thanks for the question. No, we have not seen an impact from the competition, and we're pleased that more patients or more companies are out there educating physicians on hypercortisolism, and obviously guidelines and proper screening as this will continue to help patient care.
spk15: 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?
spk11: Yeah, in fact, let me give you back over to Bill again, who seems to be working. Go ahead, Bill.
spk12: Yes, yes, thank you for that question. So, 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 Relacorla can bring to their patients. You know, we've completed a few investigator meetings in the U.S. and Europe, and each of the investigators really reiterated their excitement and enthusiasm for rel-correlant and their unwavering need and desire to help us enroll this study expeditiously. So based on all of our interactions with investigators, we feel that we are still on track.
spk15: Very good. And then on the prostate cancer program, can you comment on any efficacy signals that were seen in the phase one study? Thank you.
spk11: Yeah, I just... 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. So I don't think that there's really much efficacy data that I can relate to you for things that you could draw forward from. I think that all of the results, again, in the investigator study will be presented at a conference. as we will as well. But I just want to remind the group that whatever one sees there, reminding that this is really a safety and tolerability study and to give us an indication from where to go next.
spk01: Got it. Thanks for taking the questions.
spk04: And your next question comes from the line of RK from HC Wainwright. Your line is now open.
spk06: Thank you. Good afternoon, gentlemen. It looks like 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? And if it does, at what point is the interim look going to be?
spk01: Bill, could you take that question?
spk12: Sure, I'll take that question. No, we do not have an interim look into this study. The primary endpoint is PFS. And so when we hit our predefined PFS numbers, that's when we will read out the study. And our secondary endpoint is overall survival. So at this point in time, there is not an interim look designed for the Rosella study.
spk06: Okay, thank you. And then on the DASL study in ALS, trying to understand how DASL core length, I guess, works. And also, does this drug have any efficacy in other movement disorders or neuromuscular disorders such as MS and Parkinson's.
spk11: Yeah, you know, I'm glad you asked that. It's a little more scientifically far field than I usually get in conference calls, but, you know, R.K., you know me. I could talk about this for a long time. So the bottom line is it's been known for quite a while. that there are neuromuscular diseases, and ALS is a good example where you have aberrant cortisol activity. Cortisol levels are higher, people lose their diurnal rhythm, and there really has been a thought that this contributes to disease progression. What really got us interested in ALS specifically is there's a good animal model of ALS. It's obviously not exactly the same as ALS, but it's one that's been used for a very long time called the wobbler mice. In some sense, it sounds sort of like what it is. These are animals which really lose their coordination and may manifest similar symptoms to what people do who have ALS. They have the same cortisol issues that people do as well. I guess almost half a dozen publications have been shown that desk coral and GR modulation really changes that. You know, in the animals, at least, not only do the animals slow their decline in their neurologic symptoms, they actually improve over a period of time. So, of course, not everything in animals translates to people. It would be wonderful if that actually did translate to people. But the bottom line is there's really a good reason to give it a try. I've said it before, ALS is kind of, you know, As much as we have one, the Mount Everest of medical maladies, terrible problem. And if we could offer these patients anything that resembled the results that we saw in animals, that would be a wonderful thing. 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 happened to just coincidentally be talking to an investigator today who was interested in looking at GR modulation in Parkinson's disease. So as you know, psychiatry and neurology have been my interests for a very long period of time. These are very difficult areas in which to show progress, but I do think that we will be enlarging our programs in this area and hopefully ultimately be able to offer patients And we actually have preclinical investigators who are studying hunting disease at this point. I happen to just coincidentally be talking to an investigator today who is interested in looking at GR modulation in Parkinson's disease. So, you know, as you know, psychiatry and neurology have been my interest for a very long period of time. These are very difficult areas in which to show progress. But I do think that we will be getting be enlarging our programs in this area and hopefully ultimately be able to offer patients something they clearly cannot get today.
spk06: Thank you for that. And then in the gratitude studies where the data is expected by the end of this year, so what are the next steps in those development programs in terms of, you know, when you could initiate of this year? So what are the next steps in those development programs in terms of, you know, when you could initiate late-stage trials in looking at antipsychotic-induced rate gain?
spk11: 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. We could do it in animals, and we have real hopes in these studies, but I just thank our internal staff and our investigators for actually getting this all enrolled and up to the point where we're going to see results. I think, as I said before, I just wanted 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. And 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, you know, my general answer would be it's going to be results dependent on sort of what we have to do next. But if you go to the extreme end of a result that's extremely clear and easy to interpret, I'm certain that we will begin a late-stage study next year. I really don't want to promise that. I haven't seen the results yet. But certainly, if the path is straightforward, that's where we'll go. But first, the results.
spk06: Thank you. Thanks for taking all my questions.
spk01: Sure.
spk04: And your last question comes from the line of Alan Long with BioWatch News. Your line is now open.
spk07: 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 know 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?
spk11: You know, Alan, I really apologize. It was static in the line and I couldn't hear your question. Would you mind repeating it?
spk07: Sure. My readers noted that your ALS trial design, it's not what they would claim, a toe-dipping tentative phase 2A pilot. But it's a larger, well-controlled design. What motivates the commitment to a stronger design?
spk11: Yeah, I really, okay, I heard it that time, Alan, and I really do appreciate that question. So I'm going to 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 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 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 kind of sadly people only have one shot at a trial, that you actually have to be able to present to them something that has a legitimate chance to actually providing real benefit. And 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 the very experienced group of investigators believed 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. And so we really wanted to get to the point where we used their time and our time the best and presented a result that actually is going to be the most dispositive about where we stand.
spk07: Great. Thank you. And then with the prostate, upcoming prostate cancer study, you stayed with relacoralin rather than hexacoralin. And as I recall, relacoralin has excellent GI blocking properties, while hexacoralin, if I'm not mistaken, had some interesting tissue penetration. Is that correct? And can you provide some color on the advantages that you think propel relacoralin as your drug candidate?
spk11: Yeah. The first thing I'd say is it's a pretty close call. You know, it's sort of funny, you know, this is, we actually sat down at the very beginning of these two studies, and we got first choice, and we picked Exacoralin. And Dr. Smolowitz got second choice, and he got Relacoralin. So I clearly got it wrong there. The results were pretty similar. I actually found that Relacoralin has a little bit better tolerability. It's a little bit easier drug to manufacture. And in addition to that, We know a lot more about it. You know, since that study began, we've studied lots of people with reliquarylin. We know pretty much how it acts. So hexaquarylin is not going to zero. It's going to be on the shelf right now. We just tried to be as objective as we could, and we thought the prospects were better with reliquarylin. And just, you know, I'll just fill in one that you have a good memory. In the preclinical models, although both relichloroquine and hexachloroquine work well, hexachloroquine actually did work a little better in the preclinical models. But it highlights the point that I made before, which is that you do your best to translate from animal studies, but it's not lockstep. And we just have to go with where the data showed us the best results.
spk07: And lastly, this question might be for Sean. I keep asking this. How much increasing hub-hub are you hearing out there or getting requests for treating Cushing's that's really abnormal or less severe Cushing's. And related to that are the results for Gradient being released about the same time as Grace. So it's really two in one, two related questions.
spk10: Yeah, that is a good question, Alan. I'll pass over to him. Yeah, thanks for the question, Alan. Look, corallum is prescribed for all etiologies of Cushing's. for pituitary patients all the way through to the adrenal patients. And over time, we've seen more and more patients overall be prescribed for all of those respective etiologies. So 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, Jo, if there's any more.
spk11: Yeah, no, I think it... 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? And in order to answer that, I just really have to give the whole group some context. You know, 15, 20 years ago, it really wasn't appreciated. how many patients there were, and again, still a rare disease, but more than people thought, who had hypercorrosolism, Cushing syndrome, caused by adrenal tumors. And probably a decade ago, we really started to see that that was a real group. But what's happened over the last decade is that data has really filled in. Now, there is no doubt there are many patients who have hypercortisolism caused by adrenal tumors that have previously been ignored, had bad outcomes, are largely untreated. And that's the group that actually Radiant Study focuses on. Now, we'd 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. So we think that the field is very, very interested in what's really kind of the standard double-blind study. We'll see what the results will be. Patients ranging from the best places. Maybe the point that I'll leave you with is that what was once really sort of tossed off as not really very important is no longer tossed off. In publications ranging from the best places to the Mayo Clinic, it's now very clear that the group of patients with adrenal adenomas is both sizable and is very adversely affected by their hypercortisolism.
spk07: Thanks. Looking forward to the rest of the year.
spk11: Thank you, Alan. I think that... That wraps us up here. So thank you, everybody. I hope you have a great rest of the summer, and we'll look forward to talking to you in three months.
spk04: This concludes today's conference call. Thank you for your participation. You may now disconnect.
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