Corcept Therapeutics Incorporated (NASDAQ:CORT) has reported a strong financial performance for the first quarter of 2024, with a significant 39% increase in revenue to $146.8 million compared to the previous year. The company has also raised its revenue guidance for the full year to between $620 million and $650 million. This optimistic financial outlook coincides with progress in Corcept's development programs, including positive results from their GRACE study and the anticipated submission of a new drug application for relacorilant. The company also discussed its ongoing legal dispute with Teva Pharmaceuticals, its advancements in cancer treatment studies, and its strategies to defend market share against generic competition.
Key Takeaways
- Corcept Therapeutics reports a 39% increase in Q1 2024 revenue, totaling $146.8 million.
- The company raises its 2024 revenue guidance to $620-650 million.
- Legal battle with Teva Pharmaceuticals over Korlym generic continues, with a decision expected in early 2025.
- Positive results from the GRACE study for relacorilant in Cushing's syndrome.
- Plans to submit a new drug application for relacorilant and present data at a June medical conference.
- Progress in studies for relacorilant in various cancers and dazucorilant in ALS.
- Confidence in defending market share against generics and in the potential of relacorilant over Korlym.
Company Outlook
- Raised revenue expectations suggest strong market performance and confidence in continued growth.
- Ongoing legal appeal against Teva Pharmaceuticals indicates a critical period ahead for the company's exclusivity on Korlym.
Bearish Highlights
- The potential impact of generic competition on Korlym could pose a challenge to market share.
Bullish Highlights
- Enrollment completed in four late-stage studies, indicating progress in the company's development pipeline.
- Positive Phase 2 study results for relacorilant in ovarian cancer, with ongoing ROSELLA study to replicate findings.
- Advances in treatment studies for prostate and adrenal cancers and ALS.
Misses
- No specific financial misses were discussed in the earnings call.
Q&A Highlights
- The company elaborated on its strategies to mitigate the effects of generic competition on Korlym.
- Emphasized the unrecognized nature of hypercortisolism and the potential of relacorilant as a treatment.
- Discussed the significance of the ALS functional rating scale in their Phase 2b trial for DAZALS (Remicorilant).
- Highlighted the potential of relacorilant to improve the effectiveness of immunotherapies in cancer treatment.
Corcept Therapeutics' first-quarter results and raised guidance reflect a robust financial state and promising advancements in their drug development programs. The company's focus on cortisol modulation therapies continues to show potential in treating a range of disorders, from Cushing's syndrome to various types of cancer. With the completion of enrollment in multiple late-stage studies and the upcoming submission of a new drug application for relacorilant, Corcept is poised for significant milestones in the near future. Despite the looming challenge of generic competition, the company remains confident in its strategies to defend its market share and in the superior profile of its medications. As Corcept continues to navigate its legal battle and advance its clinical trials, the healthcare market will closely watch its next moves.
InvestingPro Insights
Corcept Therapeutics Incorporated's (CORT) first-quarter earnings for 2024 have reflected positively in its financial metrics, with a notable increase in revenue and raised guidance for the year. The company's strategic focus on cortisol modulation therapies and its pipeline advancements have been pivotal in its growth. Here are some insights based on InvestingPro data and tips that may provide a deeper understanding of the company's financial health and market position:
InvestingPro Data:
- The company's market capitalization stands at $2.48 billion, indicating a substantial presence in the biopharmaceutical sector.
- Corcept's P/E ratio is currently 23.75, which aligns with the industry's competitive landscape, while the adjusted P/E ratio for the last twelve months as of Q1 2024 is slightly lower at 21.16.
- Revenue for the last twelve months as of Q1 2024 reached $523.53 million, with an impressive gross profit margin of 98.54%, showcasing the company's ability to maintain profitability.
InvestingPro Tips:
- Corcept's management has been actively buying back shares, a sign that could be interpreted as confidence in the company's future prospects.
- The company holds more cash than debt on its balance sheet, providing a solid financial foundation for ongoing and future operations.
These insights, when combined with the company's reported progress in its development programs and raised revenue guidance, suggest a strong financial position and potential for continued growth. For investors looking for a more comprehensive analysis, there are additional InvestingPro Tips available, including an assessment of the company's shareholder yield and predictions on profitability for the year. Use the coupon code PRONEWS24 to get an additional 10% off a yearly or biyearly Pro and Pro+ subscription at InvestingPro for more in-depth metrics and tips to inform your investment decisions.
Full transcript - Corcept Therapeutics (CORT) Q1 2024:
Operator: Good day and thank you for standing by. Welcome to the Corcept Therapeutics Conference Call. [Operator Instructions] Please be advised that today’s conference is being recorded. I would now like to turn the conference over to your speaker for today, CFO, Atabak Mokari. Please go ahead.
Atabak Mokari: Hello, everyone and thank you for joining us. Today, we issued a press release announcing our financial results for the first quarter and providing a corporate update. A 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 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 risks and uncertainties which may cause actual results to be materially different from those such statements expressed or implied. These forward-looking statements are described in today’s press release and the risks and uncertainties that may affect them are described in 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 first quarter of 2024 was $146.8 million, an increase of 39% compared to the first quarter of the prior year. We expect our revenue growth to continue and have increased our 2024 revenue guidance to $620 million to $650 million. Net income was $27.8 million in the first compared to $15.9 million in the first quarter of the prior year. Our cash and investments at March 31 was $451 million. I will now turn the call over to Charlie Robb, our Chief Business Officer. Charlie?
Charlie Robb: Thanks, Atabak. In March 2018, we sued Teva Pharmaceuticals to prevent it from marketing a generic version of Korlym in violation of our patents. The case was trialed in federal district court in September of last year. On December 29 of last year, the court found that Teva’s generic product would not infringe the two patents we had asserted against it. We believe the court’s verdict is wrong and have asked the Federal Circuit Court of Appeals which has appellate jurisdiction over all patent matters to reverse it. We filed our opening brief on March 11. Teva filed its responsive brief on April 22. Our reply, which will complete briefing of the matter, is due later this month. These documents are available publicly at the government’s PACER website. It’s impossible to predict exactly how long the appeal will take. The timing of oral argument and issuance of an opinion are entirely up to the Federal Circuit. Having said that, it’s reasonable to expect oral argument in the third or fourth quarter of this year and the decision early in the first quarter of 2025. If we prevail, Teva would lose FDA approval of its product, at least until the expiration of our patents in 2037. We are eager to advance this appeal. As has always been the case, we strongly believe that our position is the correct one. We are confident that the Federal Circuit, with its deep expertise in this area of the law, will agree. I’ll now turn the call over to Joe Belanoff, our Chief Executive Officer. Joe?
Joe Belanoff: Thank you, Charlie and thank you everyone for joining us this afternoon. This has been a tremendously active period at Corcept. Our commercial business is thriving and we are making substantial progress in every one of our development stage programs. In the past few weeks, we completed enrollment in 4 late stage studies and we have reached open label data from our GRACE study that takes us one step closer to submitting our NDA and bringing relacorilant to patients with Cushing’s syndrome. Our commercial growth was driven by a record number of new Korlym prescribers and a record number of patients receiving the medication. Hydrocortisolism is commonly misdiagnosed in large part because it’s frequently expressed in burdensome symptoms, hyperglycemia and hypertension, have become so common in the population as a whole. As physicians become increasingly aware that hypercortisolism is much more prevalent than previously assumed, they are screening and treating more patients for hypercortisolism than ever before. When Korlym was prescribed, we used the expertise and infrastructure that we have developed and refined over many years to support physicians and patients. This additional care helps create a life changing impact for patients who receive Korlym treatment. We have known for some time that there are large groups of patients who are far too infrequently screened for Cushing’s syndrome. The initial findings of the CATALYST study make that clear. CATALYST is the largest and most rigorous clinical study ever conducted to examine the prevalence of hypercortisolism in patients with difficult to control Type 2 diabetes. Over 1,000 patients were enrolled by leading diabetologist in the United States and 25% of these patients were found to have hypercortisolism. This is a far higher prevalence rate than is generally assumed, with potentially far reaching implications for patient care. The final results from the prevalence portion of the study presented at a keynote session at the American Diabetes Association’s Annual Scientific Sessions next month. The second portion of the CATALYST study, the treatment phase is ongoing. As the awareness and diagnosis of Cushing’s syndrome increases, we are simultaneously working to advance our proprietary selective cortisol modulator, relacorilant. Relacorilant has unique characteristics and our confidence in its efficacy and safety profile has only been increased by the open label results from the GRACE study. A pivotal trial for relacorilant GRACE has two parts. In its first open label phase, 152 patients with Cushing’s syndrome and either hypertension hyperglycemia or both receive relacorilant for 22 weeks. Patients who exhibited pre-specified improvements in either or both symptoms were given the opportunity to enter the trials randomized double-blind withdrawal phase, during which half of the patients continue to receive relacorilant and half receive placebo for 12 weeks. GRACE’s primary endpoint is maintenance of blood pressure control in the randomized withdrawal phase of the study with maintenance of glycemic control at the key secondary endpoint. Last week, we released results from GRACE’s open label phase. As I review these data here, please keep in mind this important point, because excess cortisol activity affects nearly every tissue in the body, patients with Cushing’s syndrome exhibit a wide array of signs and symptoms. Hypertension and hyperglycemia are among the most common and destructive. Patients in the open label phase in GRACE exhibited clinically meaningful and statistically significant improvements in hypertension, hyperglycemia, weight, waist circumference, cognition, Cushing’s quality of life score and other measures of clinical importance. In the open label phase of GRACE, 63% of patients with hypertension met the study’s response criteria. For the patients who entered the randomized withdrawal phase, improvements in mean systolic and diastolic blood pressure, a 12.6 and 8.3 millimeters of mercury from baseline with p-values of less than point 0.001 were observed. To ensure accuracy, hypertension was measured by 24-hour ambulatory blood pressure monitoring or ABPM, which is the gold standard for hypertension monitoring. 50% of the patients who entered GRACE with hyperglycemia, which includes patients with diabetes and patients with impaired glucose tolerance or pre-diabetes responded to relacorilant. For the patients who entered the randomized withdrawal phase, improvements in the oral glucose tolerance test or mean glucose area under the curve of 6.2 millimoles per liter, reduction in mean hemoglobin A1c of 0.7% and reduction in mean fasting glucose of 25.2 milligrams per deciliter. Oral p-values of 0.006 or less were observed. Relacorilant was well tolerated consistent with its known safety profile. Due to its unique mechanism of action which unlike Korlym does not increase patients’ cortisol levels, there were no relacorilant-induced instances of hypokalemia. In addition, no cases of drug-induced endometrial hypertrophy with or without vaginal bleeding, adrenal insufficiency or QT prolongation, which was independently confirmed, were reported. All parts of GRACE aren’t complete. Our task now is to collect, review and analyze the full dataset, including the currently blinded results of the randomized withdrawal phase and incorporated into our new drug application which we are on track to submit this quarter. We plan to present data from both the open label and randomized withdrawal phases at a medical conference in June. GRACE is not our only Phase 3 trial of relacorilant in patients with hypercortisolism. Gradient is a randomized, double-blind, placebo-controlled study in 137 patients whose hypercortisolism is caused by an adrenal tumor or adrenal hyperplasia. Patients with this etiology of Cushing’s syndrome often experience a less rapid decline, but their health outcomes are poor and include a significantly higher risk of premature death. We expect the study produced valuable data about the treatment of an etiology of Cushing’s syndrome that affects many patients. Enrollment is complete and we expect data in the fourth quarter of this year. We are also studying relacorilant as a treatment for different types of cancer mediated by cortisol activity. Our most advanced oncology program is in platinum-resistant ovarian cancer. We recently completed enrollment of 381 women in our pivotal ROSELLA study and we expect data by the end of the year. Women with platinum-resistant ovarian cancer are in urgent need of new treatment options. The goal of using relacorilant in this context is to resensitize ovarian tumors to the effects of chemotherapy by blunting the anti-apoptotic effect of elevated cortisol activity. Our successful Phase 2 trial show that women 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. Women in the intermittent relacorilant group also lived longer than those in the comparator arm, 29% of the patients who took intermittent relacorilant who are alive, 2 years after steady start versus only 14% who took nab-paclitaxel alone. Importantly, the women who received relacorilant plus nab-paclitaxel experienced no additional side effect burden compared to those who received nab-paclitaxel alone. The results from the study were published in the Journal of Clinical Oncology in June 2023 with an accompanying editorial and presented at multiple U.S. and European medical conferences. ROSELLA aims to replicate our Phase 2 study results. It’s design closely tracks our previous study. Women are randomized one to one to receive either relacorilant plus nab-paclitaxel or nab-paclitaxel alone. The primary endpoint of ROSELLA is progression-free survival with overall survival of key secondary endpoint. We are conducting this study in collaboration with leading clinicians from the Gynecologic Oncology Group or GOG in the United States and the European network of gynecological oncology trials were in GOG group in Europe and deeply appreciate their enthusiasm and support. Because of our confidence in the positive results of our Phase 2 trial, we have begun initial planning for relacorilant’s launch in oncology. The President of our Oncology division, Roberto Vieira rejoined Corcept earlier this year, is building the organization we need to help as many women as quickly as possible following approval. We are also evaluating relacorilant as a treatment for prostate cancer and adrenal cancer. Leading academic researchers and clinicians hypothesize the cortisol modulation may block an important tumor growth pathway in prostate cancer. Cortisol stimulation is thought to be 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 tumor switch to cortisol activity stimulates growth. Adding a cortisol modulator to androgen deprivation therapy could close this tumor escape route. Our collaborators at the University of Chicago are enrolling a randomized placebo-controlled Phase 2 trial of relacorilant plus Enzalutamide in patients with prostate cancer before these patients have had an initial prostatectomy. In adrenal cancer, patients’ tumors produce excess cortisol in about 50% of cases. Unfortunately, patients with this form of adrenal cancer virtually never respond to immunotherapy, because cortisol suppresses the immune system and they blunt the effectiveness of cancer therapies intended to stimulate the immune system. Our hypothesis is that adding a cortisol modulator to immunotherapies such as checkpoint inhibitors may enhance their effectiveness. We are conducting a Phase 1b trial of relacorilant plus the PD-1 checkpoint inhibitor Pembrolizumab in patients with advanced adrenal cancer, whose tumors produce excess cortisol. Our research team led by Hazel Hunt has designed a library of over 1,000 selective cortisol modulators. All of these compounds modulate the activity of cortisol, but they have distinct pharmacodynamic properties. Some are more potent in improving insulin sensitivity. Some are more potent in creating weight loss. Some get into the brain, some don’t. Some are very potent and oncologic models, some less so. One of these compounds, dazucorilant, which is highly brain penetrant has shown great promise in an animal model of ALS. We advanced dazucorilant in the clinical studies based on compelling preclinical data that showed improved motor performance and reduced neural inflammation and muscular atrophy. Our double-blind placebo-controlled Phase 2 DAZALS trial of dazucorilant recently completed enrollment. 249 patients with ALS have been randomized to receive dazucorilant for placebo for 24 weeks. The primary endpoint is based on the ALS functional rating scale. DAZALS enrolled very briskly and we expect data by year end. Finally, I will turn to our program in MASH, MASH which stands for metabolic dysfunction-associated steatohepatitis. MASH is a serious liver disorder that affects millions of patients in the United States. Cortisol modulation may serve as an effective treatment for MASH, because cortisol activity has been implicated in both the initial development and progression of this disease. Our Phase 1 dose-finding study of miricorilant on the patients who received 100 milligrams orally twice a week for 12 weeks experience a 30% reduction in liver fat and improvements in liver enzymes, markers of fibrosis and key metabolic and lipid measures just as Homa IR, serum triglycerides and LDL. Importantly, miricorilant was also very well tolerated with no apparent GI side effects. We hope to expand on these encouraging results with our MONARCH study. MONARCH is a randomized double-blind placebo-controlled bass 2b trial now actively enrolling patients with biopsy confirmed MASH. The primary endpoint of the study is reduction in liver fat with MASH resolution and fibrosis improvement in key secondary endpoints. I will conclude where I began. There has been an exceptional amount of progress at Corcept since we last met. We recently completed enrollment in four late stage trials that we expect will provide powerful evidence that cortisol modulation is a potent therapeutic mechanism in many serious disorders. This year, we expect data from our GRACE, GRADIENT and CATALYST studies in Cushing’s syndrome, our pivotal ROSELLA study in ovarian cancer, and our DAZALS study in ALS. Our clinical and development teams have worked with great urgency to complete these studies. For many of the patients in these studies, time is short. Since we launched Korlym more than 12 years ago, we have kept the needs of patients, many of whom suffered for years without proper treatment at the forefront. Our support programs are unique, comprehensive and necessary for a complex disease such as hypercortisolism. They are highly valued. While our Korlym business continues to thrive, we expect relacorilant’s improved profile and the results of our CATALYST study to cause our Cushing’s syndrome franchise to grow substantially for years to come. The results of the past quarter and all the progress on a horizon are a credit to our employees, academic collaborators and commercial partners. Collectively, we are driven by an unwavering dedication to support patients with Cushing’s syndrome and all the other disorders where cortisol modulation can make a difference. Operator, let’s proceed now to questions.
Operator: Thank you. [Operator Instructions] Our first question comes from Matt Kaplan of Ladenburg. Your line is open.
Matt Kaplan: Hey, guys. Congrats on the quarterly results. Nice quarter.
Joe Belanoff: Thank you, Matt.
Atabak Mokari: Thanks.
Matt Kaplan: Yes. Just focusing on the quarter a little bit and Korlym what are you seeing now that I guess the court has ruled that Teva doesn’t infringe your patents? Have you seen having the marketplace and any generic competition hasn’t yet?
Joe Belanoff: Yes. Now let me reintroduce to the group Sean Maduck, who is the President of our Endocrinology division and Sean will take that question.
Sean Maduck: Yes. Thanks for the question, Matt. So, as you know, Teva announced its launch on January 19. Our business is robust and continues to grow. To this point, we are not aware of losing any patients to generic mifepristone. And based on our analysis at this point, we believe generic Korlym has been available to some degree for a couple of months, but it hasn’t had any impact on our business. And something I think that’s important to just remind people of and it’s something I have said in the past, it’s that our situation is unique and not like most generic situations. We utilize one single source pharmacy that is highly staffed to distribute Korlym and the other specialty products they have. And when Korlym is prescribed both the physician and the patient receive a high level of support both at intake and ongoing from both the pharmacy and Corcept. And this is support that is tremendously valued by doctors and by patients. And for this reason, physicians who prescribe Korlym have a very strong brand preference.
Matt Kaplan: Okay, that’s really helpful. And just shifting to your pipeline and specifically, the GRACE study, given, I guess, the open label results that you have announced, can you give us a sense in how those results in terms of the effect on hypertension in these patients in hyperglycemia compare with what you have seen historically with Korlym?
Joe Belanoff: Sure, Matt. And again, I want to reintroduce Bill Guyer. Bill is our Chief Development Officer who runs all of these programs and Bill will take that question.
William Guyer: Yes, thanks, Matt. Thanks for that question. I mean, overall, we are very excited about these results, because we basically hit every endpoint across the broad range of the signs and symptoms of Cushing’s syndrome and these positive results given how clinicians will have insight into how to use a drug like relacorilant. It’s really tough to make comparisons between drugs when a drug like Korlym was launched 12 years ago with the seismic study. But when I look at the results, I see the efficacy results as very similar or even better and the safety profile as better than that of Korlym based upon what we’ve seen. When we look at the overall efficacy, we are seeing comparable efficacy, but distinctly we are seeing rapid and sustained improvement in hypertension as well as improvement in all the safety profiles, because we really haven’t seen any relacorilant-induced AEs like hypokalemia, endometrial hypertrophy, vaginal bleeding, adrenal insufficiency, or QT prolongation. So overall, we think we’ve achieved our goal of coming up with a drug that can be approvable and can improve patient lives with Cushing’s syndrome.
Matt Kaplan: Okay, that’s helpful. And then in terms of the upcoming results for the randomized withdrawal phase given I guess the 63% response rate in the hypertension and 50% in hyperglycemia, what should we be looking for and in terms of the randomized withdrawal phase?
Joe Belanoff: Bill?
William Guyer: So, in the randomized withdrawal phase, as you see in our press release and I would really point you to those patients who responded and went into the randomized withdrawal phase and you look at those graphs of that continuous decline in both hypertension and improvement in hyperglycemia endpoints. It’s those patients who will then get randomized to either continue on relacorilant or get switched to placebo. And then we are going to look for a reversal of those endpoints. And so specifically, for our primary endpoint of hypertension, we are looking for a loss of response of greater than 5 millimeters of mercury for either systolic and/or diastolic blood pressure. And then on glucose, the same things, we are looking for reversal of the improvement in the oral glucose tolerance test and all its components and reversal of the changes in hemoglobin A1c.
Matt Kaplan: Great, great. Thanks for that detail. I’ll jump back into the queue.
Joe Belanoff: Thank you, Matt.
Atabak Mokari: Thanks, Matt.
Operator: Thank you. [Operator Instructions] And our next question is coming from David Amsellem of Piper Sandler. Your line is open.
David Amsellem: Thanks. So, just a couple. First, just on Korlym and generics, can you talk about how the market might evolve to the extent that Sun and Hikma entered the market perhaps later this year and how you are thinking about your response to heightened generic competition, for instance, could you even enter with an AG of your own? So just talk to that. And then secondly, clearly there is some acceleration happening much more so than we’ve really seen for quite some time. So, is it because of CATALYST? Is it because of just greater awareness of Cushing’s just beyond what you are doing with CATALYST, just help us better understand what’s happening in the marketplace that’s driving this? Thank you.
Joe Belanoff: Sure, David. And I am going to give you over to Sean to answer that question.
Sean Maduck: So, David, thank you for the question. I think I’ll start with number three and talk a little bit of CATALYST. And just want to make it clear that we have not yet seen the impact of CATALYST this year and then it is not built into our forecast. We believe that the CATALYST results are going to increase screening for some physicians today, but ultimately, data generation takes time to translate into guidelines, which then takes time to translate to which is the medical practice and ultimately, we expect the full impact of CATALYST will be felt in 2025 and the years after that. So in terms of what drove Q1, I mean, I will reiterate something Joe said at the beginning of the call, we had more first-time prescribers, more prescriptions and more patients on Korylm than ever before. We got new patients from existing physicians and new physicians throughout the country and also we are very pleased with the results. And it’s driven by improved field execution, which we’ve seen over the last few quarters. And the investments that we have made on the marketing side, we are starting to see some results from that. But another component and you touched on it is disease awareness is increasing. And we are more confident than ever about the potential size of the Cushing’s syndrome market and then this is a multi-billion dollar market.
Charlie Robb: And then David, the only other thing I would point out is, we have seen this building now over the last five or six quarters, it really wasn’t just particularly this quarter. And I would just second what Sean said sort of the weighted evidence is now out there that this has been an under-recognized disorder. People should screen more for it. And when they screen it, they should figure out a way to treat it and it’s really organic in that way.
Sean Maduck: Right. So your next question was around sort of future market dynamics from a generic standpoint. And I’ll say – I cannot speculate on when or if other generic manufacturers may market, understand that the real process that Charlie probably touched on is still ongoing. And we don’t expect it to be resolved until the early part of next year, which is a risk. And to our knowledge, no other generic manufacturer besides Teva has received FDA approval to this point. So I’ll say just from our standpoint, we’ve been thinking about this for a long time, we have had a plan for a long time, we’ve been prepared since at least 2020 for this. So we have a plan in place. We continue to revise that plan with any new intelligence that we get. We’re continuing to invest in our Korlym business. And we are confident in our ability to both continue to grow our business today, but also defend our market share. Next question, please.
Operator: Thank you. [Operator Instructions] Our next question will be coming from [indiscernible] of Canaccord. Your line is open.
Unidentified Analyst: Thank you for taking our questions. Hi, yes. Thank you for taking our questions. My questions are regarding the ALS program. So the first part of the question is on the primary endpoint we know that it’s using the ALS functional rating scales and numerical scoring system. So I would like to ask you for your comments about, what level of change would be considered as a clinically meaningful change on that endpoint, because as we know, with the approved therapy, [indiscernible], each historical Phase 3 trial showed a drop off this score by approximately 2.5 points. And I believe that was considered as the equivalent to 4 to 5 months of survival. And then the second part of my question is, do you believe that DAZALS, Korlym who would have a chance to be approved based on the Phase 2 data, let’s assume the data is positive? Thank you.
Joe Belanoff: Yes. And I’d like again to bring Bill on the line. Bill, could you please take those questions?
William Guyer: Sure. So in relation to your first question around our primary endpoint and efficacy, so yes, you’re absolutely correct. The efficacy is the change from baseline of week 24 of the ALS functional rating scale. But we’re also, we’re looking at ALS and it’s – and DAZALS, Korlym and overall effects of patients and a long-term extend your study is going to look at survival because it’s a 3-year study. But specifics were powered at 80% to see a 2.4% difference in the ALS functional rating scale, which the researchers, clinicians and ALS experts have advised, they said you stated as being clinically relevant. As related to could this be a regulatory enabling study, yes, we believe, so at 249 patients, we designed this study from the very beginning to be a potential for regulatory enabling because ALS is a very devastating progressive disease. And the need for new medications is very high and even higher probably today. I believe that regulators would welcome new therapies that could help slow or reverse the progression of this disease. And again, DAZALS was the trial was designed specifically as a Phase 2b trial with the intention to be a regulatory enabling study.
Charlie Robb: We look at that is, I think I don’t have to really particularly remind everyone on the call, you know what an awful disease ALS is, and how there is really nothing available that works particularly well. It was – we really saw excellent preclinical data. We will find out if it translated. But yes, I think the study is of a size, that the effect is real and substantial, that has to be very interesting to regulators who I know want to bring better treatments to that disease.
Unidentified Analyst: Okay. That’s very, very helpful. And if I may, I also have a simple or straightforward question about Remicorilant in GRACE. So, for the randomized withdrawal phase data, that period of the trial is for 12 weeks. And I know we have asked you about those before, but we don’t have this trial of withdrawal Remicorilant that with Korlym. I think you stated before that the breakdowns was usually observed that four weeks to five weeks after patients stopped using that. So, I was wondering, into establishing the confidence that 12 week is long enough for us to see a difference a statistically significant difference, besides the experience with Korlym, would there be something else that we could trace back to?
Joe Belanoff: Yes. I understand the question and it’s a really, very reasonable question, I want to make sure you on the line understands of which is that is 12 weeks enough to see patients who get randomized placebo, have a loss of the very potent effect that they got in the open label phase. So, you raised a couple of points, and I want to address both of them. You are absolutely right, within Korlym, we see a rapid loss of efficacy. Sometimes you see within the first two weeks, but you often see it by four weeks or five weeks. So, certainly, that’s one reason why 12 weeks is a very reasonable guess for loss of efficacy. But we have even more evidenced now. When you look at the curves for GRACE, the rate of improvement, particularly in hypertension, you are seeing that rate of improvement in the first couple of weeks. And I suspect that this medicine doesn’t just cure patients when they come off the medicine, they had a loss of that effect. So, you are right, we have never done a randomized withdrawal study before. We can’t say with certainty that that’s enough time. But we have a very strong belief that it is and we will find out soon.
Unidentified Analyst: Okay. Great. Thank you so much.
Operator: One moment for the next question. And our next question is coming from Swayampakula Ramakanth of H.C. Wainwright. Your line is open.
Swayampakula Ramakanth: Thank you. This is RK from H.C. In terms of commercialization, with you getting ready to file the NDA based on the GRACE data, we can kind of assure ourselves the data probably is looking pretty good on the rest of the study that you are going for it. Having said that, so let’s say in a year we had this drug approved, so how are you taking on the commercial front in terms of switching patients from Korlym to Remicorilant, that’s part A of the question. Our B is, again looking at catalyst data, which has been generated with Korlym, what’s the strategy there, because again, within a year, if you have Remicorilant, do you need to do something with Remicorilant as well if you need to grab that patient population, or is this going to be a bifurcation of the market where you will let Korlym run through the diabetics and the hypertension folks, but keep the Remicorilant for the Cushing’s?
Joe Belanoff: Hey RK, let’s start off with Sean. And I may have a few comments to add at the end.
Sean Maduck: Thanks RK. So, the question in terms of switching maybe Korlym, obviously a great medication, Remicorilant will be even better. Our belief is that the Remicorilant’s efficacy and safety profile will be well received by treating physicians. And once approved, uptake will be very swift. There is no reason both the physician and the patient will want to choose them.
Joe Belanoff: So, RK look, the critical thing, and it’s something that we say every time and we say it internally, and it’s absolutely true. The main thing to understand is that hypercortisolism is an unrecognized disease in many patients who could be treated for hypercortisolism and get a lot of benefit. And that’s whether they are treated with Korlym or not. I mean again, I remind everyone that really the optimal personalized treatment is if there is a tumor that’s causing this, and you pick it out, you take out the tumor, and that’s that. And we know, unfortunately, that is not the case with many of these patients, that surgical cure either doesn’t work, or they can’t find a tumor or something like that. And that leaves them in need of medical treatment. And so the question, I will just emphasize what Sean said, Remicorilant is really a good medication, I really believe that it is a superior medication in a variety of ways to the very good effects that you get from Korlym. And I think that people will get on the catalyst information is that they need to really screen for these patients. And then that’s up to them if they ever do for it next. But I think that that people will understand that what catalyst is really proving to them is that hypercortisolism is an every single diabetology practice in the United States. And there are many patients these days who are getting optimal care for diabetes, and still have another problem that isn’t allowing it to be treated, mainly hypercortisolism.
Swayampakula Ramakanth: Fantastic. Thanks for that. And then on the adrenal cancer study, and you said that data is expected from that in mid-2024. Assuming it’s one of the cancer conferences, so what’s the thought process there that if we assume data is good, would you turn around and start a larger study right away, or do you need to kind of look at the data from other oncology indications before deciding where you want to put your money?
Joe Belanoff: Yes. Okay. Thank you for asking that question. I don’t get it that often. And so I am just going to back up a little bit to make sure everybody understands the situation of why we are in testing this. Immunotherapy, it’s changed the world and it’s fantastic. But unfortunately, it doesn’t work for even a majority of patients, I mean for those who it works, it’s fantastic. But there are many patients, unfortunately for them, it does not really work. But immunotherapy dialysis relies on your own immune system to actually capture and defeat the cancer, and that’s great, as I have said, when it works. The issue is that cortisol is your natural immunosuppressant. And so mechanistically, it’s fighting against the benefits that one gets with immunotherapy. The idea is that if you can normalize or reduce cortisol activity, immunotherapy can work significantly better. And if not related this ideas right to adrenal cancer, general cancer is just a piece of place where we can really gather some evidence, but the idea is this direction improves correct. To really look at the whole body of cancers, where immunotherapy is less than as potent as physicians think it could be. And all I can tell you is with this the first study, we have done with this, we will learn a lot from it. We will figure out what to do next. We have a lot of other things on our plate that this is really a crucial thing that we have gotten here right. I think it can be very, very meaningful to many patients.
Sean Maduck: I would like to add to that too, just to add to that, because while we are doing studies in ovarian cancer and prostate cancer and adrenal cancer, our vision really is to establish relacorilant as the agent that can really synergize with many different chemotherapy agents by adding efficacy, but not adding any toxicity. And we fully plan to explore broader applications of a drug like relacorilant in cancer throughout the lifecycle management plan. It’s been on our minds internally with the addition of our new President of Oncology, Roberto Vieira. I have been partnered in looking at all the various different types of studies and where we should be investing our research dollars in. So, you will see a more broad plan in the coming months throughout this year.
Swayampakula Ramakanth: Great, appreciate the comments. Thank you, gentlemen.
Joe Belanoff: Thanks RK.
Operator: Thank you. And one moment for our final question. And our final question of the day will be coming from Joon Lee of Truist. Your line is open.
Unidentified Analyst: Hi. This is Jeremy for Joon. Congrats on the quarter and thanks for taking our questions. Just what incrementally changed from your initial guidance inflow that led to the guidance raise range, and there is generic impact baked into the guidance. And then just quick follow-up, patients are enrolled in the double-blind portion of the study, which we will be seeing data in June. Thanks.
Joe Belanoff: Okay. I think I caught both of your questions. I am going to give the first one to Sean.
Sean Maduck: Thanks Jeremy. So, our revenue guidance will always consider all the information that we have in our best estimates going forward. And our range includes a multitude of factors including generic impact. And the range from earlier in the year to now is driven by more physicians prescribing Korlym and more patients taking Korlym.
Joe Belanoff: And the second question, I think was just that numbers question. How many…?
Unidentified Analyst: Yes, correct.
Joe Belanoff: So, how many patients were in are going to be on the randomize withdrawals set, okay, so we haven’t publicly disclosed that, but I will tell you that we have 62 patients who are in the randomized withdrawal phase of the study, and that’s what will be the basis for our trial with a mixture of those with hypertension, or diabetes and or having both.
Unidentified Analyst: Thank you.
Joe Belanoff: Okay. I think that concludes our questions. Thank you very much of course that this becomes very, very much more complex than it was years ago. And I appreciate you really trying to capture all the information that we have sent to you. See you next quarter.
Operator: This concludes today’s conference call. Thank you all for joining. You may now disconnect.
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