CORT - NASDAQ

Thank you for standing by, and welcome to Corcept Therapeutics conference call. [Operator Instructions] I would now like to hand the call over to Atabak Mokari, CFO. Please go ahead.

Hello, everyone. Good afternoon, and thank you for joining us. Today, we issued a press release announcing our financial results for the fourth 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-K 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 might cause actual results to be materially different from those such statements expressed or imply. The risks and uncertainties that may affect our forward-looking statements are described in our annual report on Form 10-K and our quarterly reports on Form 10-Q, all of which are available at the SEC's website. Please refer to those documents for additional information. We disclaim any intention or duty to update forward-looking statements. Our 2024 revenue was $675 million, an increase of 40% compared to the prior year. We expect our revenue growth to continue and to provide a 2025 revenue guidance of $900 million to $950 million. Net income was $141 million for the full year 2024, an increase of 33% compared to the prior year. Our cash and investments at December 31, 2024, were $603 million compared to $425 million at the end of the prior year. In 2024, we acquired $38 million of our common stock pursuant to our stock repurchase program, the net exercise of stock options by Corcept employees and the net vesting of restricted stock grants. I will now turn the call over to Charlie Robb, our Chief Business Officer. Charlie?

Thanks, Atabak. I don't have much to report this quarter. As many of you know, in March 2018, we sued Teva from -- to stop it from marketing a version of Korlym in violation of our patents. In December of last year, the trial court ruled against us. We have appealed that decision to the Federal Circuit Court of Appeals. Briefing in the matter is complete. Documents are available at the government's PACER website. And the next step is for the Federal Circuit to schedule oral argument, which is still not done. The earliest plausible date, given the court's scheduling process, is for argument in May or later. The decision is between 3 or 4 months after that. The matter of the absolute schedule, if we prevail, Teva would lose FDA approval of its product and be required to withdraw from the market until the expiration of our patents in 2037. As I've said before, we are eager to advance this appeal. We strongly believe that our position is correct, that the Federal Circuit will agree. I'll now turn the call over to Joe Belanoff, our Chief Executive Officer. Joe?

Thank you, Charlie, and thank you, everyone, for joining us this afternoon. 2024 was a great year for Corcept. Each successive quarter of 2024 brought a record number of new Korlym prescribers and patients receiving Korlym. Our rapidly increasing number of physicians now know that hypercortisolism is much more prevalent than was previously assumed. They are screening and treating many more patients than ever before. We are confident that our Cushing's syndrome business will continue to grow for years. On December 30, we submitted a new drug application for our proprietary selective cortisol modulator, relacorilant. Our NDA is based on compelling results from the GRACE GRADIENT long-term extension and Phase II relacorilant studies. Our pivotal GRACE Phase III study had 2 parts. In the trial's open-label phase, 152 patients with hypercortisolism and either hypertension, hyperglycemia, or both received relacorilant for 22 weeks. Patients who met prespecified improvements were given the opportunity to enter the trial's randomized double-blind withdrawal phase, in which half of the patients continued to receive relacorilant, and half received placebo for 12 weeks. Patients in the open-label phase of GRACE exhibited clinically meaningful and statistically significant improvements in hypertension, hyperglycemia, weight, lean muscle mass, weight circumference, cognition, Cushing's quality of life score and other important clinical measures. In the randomized withdrawal phase of GRACE, which compared patients taking relacorilant to those taking placebo, relacorilant met its primary endpoint of retaining improved blood pressure control. The odds ratio, which was the study's primary endpoint, was 0.17 with a p-value of 0.02. An odds ratio of 0.17 means that patients taking relacorilant were 6x more likely to maintain their blood pressure response compared to those taking placebo. In addition, patients who continue to take relacorilant in the randomized withdrawal phase of the study maintained or increased the broad range of other improvements in the signs and symptoms of hypercortisolism generated in the open-label phase of the study, while those who received placebo experienced a significant worsening of these signs and symptoms. Patients who completed the Phase II GRACE and GRADIENT studies were eligible to enter our long-term extension study, where they continue to receive relacorilant, or for patients in the placebo arm of GRADIENT, received relacorilant for the first time. Patients in the extension study have now taken relacorilant for up to 6 years. This group of 116 patients has exhibited additional clinically meaningful and durable cardiometabolic improvements. For instance, at week 24 of the study -- I'm sorry, for instance, at month 24 of the study, they experienced a further reduction in their systolic blood pressure of 10 millimeters of mercury, a p-value of 0.012, and their diastolic blood pressure of 7.3 millimeters of mercury, a p-value of 0.016 compared to those measurements at the time they entered the extension study. Again, please remember, these improvements were in addition to the improvements already exhibited in the Phase II GRACE or GRADIENT parent study. Relacorilant's efficacy and safety, which I will discuss in a moment, is clearly evident when one follows the clinical course of patients as they enter the Phase II GRACE or GRADIENT study, complete that study, then participate in the long-term extension study. As a group, patients exhibit rapid improvement at the start of relacorilant therapy, which maintained or continues to improve in the extension study. Patients whose relacorilant treatment is interrupted, for instance, by being a assigned to placebo in the GRACE randomized withdrawal phase, exhibit rapid improvements at the start of relacorilant therapy, then deterioration when switched to placebo, followed by resumption of improvement when relacorilant is restarted. Just as important as relacorilant's efficacy is its safety. Relacorilant has been well tolerated in all of its studies. The most common adverse events have been mild to moderate nausea, edema, pain in the extremities and back and fatigue. These symptoms are consistent with the cortisol withdrawal that patients with hypercortisolism experience following a rapid reduction in their cortisol activity, whether due to surgery that removes an ACTH or cortisol secreting tumor or at the start of medical therapy. As expected, there have been no relacorilant-induced instances of hypokalemia, endometrial hypertrophy or drug-induced vaginal bleeding, no cases of adrenal insufficiency and no instances of QT prolongation. These adverse events can have serious health consequences. Each of the currently available medications for patients with Cushing's syndrome can cause 1 or more of them. As we advance relacorilant, we continue to work at increasing physician awareness and understanding of hypercortisolism. The prevalence phase of our CATALYST study showed that 1 in 4 patients with difficult to control type 2 diabetes has hypercortisolism, a far higher rate than was assumed. In December, we completed CATALYST treatment phase, a double-blind, placebo-controlled study in which 136 patients identified in CATALYST first phase as having hypercortisolism,were randomized to receive either Korlym or placebo. The results were striking. Patients who received Korlym exhibited a large reduction, 1.47% in hemoglobin A1c, a key measure of glucose control, compared to a 0.15 decrease in patients who received placebo, a p-value of less than 0.0001. The magnitude of reduction seen in the treatment arm is especially striking, given that these patients are already receiving the best REDs treatments available, including Ozempic and Mounjaro. Another CATALYST finding is that hypercortisolism is even more common in patients who have cardiovascular disease in addition to diabetes. In a substantial group of patients in the CATALYST study, taking 3 or more medications to manage their hypertension, more than 1/3 were found to have hypercortisolism. Later this quarter, we will start our newest study, MOMENTUM, which will help establish the prevalence of hypercortisolism in patients with resistant hypertension. We are confident that increased physician awareness and understanding of hypercortisolism, combined with the advancement of relacorilant, a safe and effective therapy, will improve the lives of patients who struggle with the devastating impact of this disease. We are already seeing it. As you know, we are also studying relacorilant as a treatment for types of cancer where cortisol plays a role. We expect data soon from our pivotal ROSELLA study. In this study, 381 women with platinum-resistant ovarian cancer have been randomized on a one-to-one basis to receive either nab-paclitaxel, probably the most effective chemotherapy currently prescribed to women with platinum-resistant disease, or nab-paclitaxel plus relacorilant. For many of these patients, nab-paclitaxel or any chemotherapy has become much less useful than earlier in the course of treatment. Our expectation is that relacorilant will resensitize ovarian tumors to the effects of nab-paclitaxel by blunting the anti-apoptotic effects of cortisol activity. ROSELLA's design tracks the design of our successful controlled Phase II trial. In that study, 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 relacorilant group also live longer than those in the comparator arm. 29% of the patients who took intermittent relacorilant were alive 2 years after study start, compared to 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 monotherapy. We expect relacorilant to replicate these results. Enrollment in ROSELLA is complete. We anticipate having progression-free survival results by the end of this quarter. We are conducting ROSELLA in collaboration with leading clinicians from the Gynecologic Oncology Group, or GOG, in the United States and the European network of Gynecologic Oncology Trials or ENGOT Group in Europe and deeply appreciate their enthusiasm and support. In anticipation of a successful outcome, we have established a stand-alone oncology division so we can move swiftly after the conclusion of ROSELLA to bring relacorilant to the women who can benefit from it. Positive results will also prompt us to explore relacorilant as a treatment for earlier stages of ovarian cancer and other solid tumors that express the glucocorticoid receptor. In addition to exploring cortisol's potential to resensitize tumors to chemotherapy, we are evaluating its potential use in combination with androgen deprivation therapy. Cortisol stimulation is a major reason why patients with prostate cancer treated with a widely prescribed androgen receptor antagonist enzalutamide, eventually experience resurgent disease. Deprived of androgen stimulation, their tumor switched to cortisol activity to stimulate growth. Leading academic researchers and clinicians hypothesize that cortisol modulation can block this tumor escape route. Our collaborators at the University of Chicago are currently enrolling a randomized placebo-controlled Phase II trial of relacorilant plus enzalutamide in patients with early-stage prostate cancer before these patients have had an initial prostatectomy. Another possible role of cortisol receptor antagonist is in combination with immunotherapy. Because cortisol suppresses the immune system, it may blunt the effectiveness of cancer therapies intended to stimulate an immune response. Adding a cortisol modulator to immunotherapies such as checkpoint inhibitors may enhance their effectiveness. Following our Phase Ib trial in advanced adrenal cancer, we're deciding how best to investigate the utility of our compounds in combination with immunotherapies in other tumor types and earlier stages of cancer. One of our proprietary compounds, dazucorilant, readily crosses the blood brain barrier and is a candidate for the treatment of neurologic disorders. Based on compelling data showing improved motor performance and reduced neuroinflammation in muscular atrophy in a commonly used mouse model, ALS, we conducted a 249-patient randomized, double-blind, placebo-controlled Phase II trial of dazucorilant in that dire disease. Unfortunately, patients who received dazucorilant did not show improvement in the ALS functional rating scale, the study's primary endpoint. However, we did observe a statistically significant improvement in patient survival at week 24 of the study. No death occurred in the 83 patients who received 300 milligrams of dazucorilant, while 5 deaths occurred in the 82-patient placebo grid, a p-value of 0.02. The open-label long-term extension study is ongoing, and we expect to receive 1 year overall survival results early in the second quarter. MASH, metabolic dysfunction associated steatohepatitis, is a serious liver disorder that afflicts millions of patients in the United States alone. Cortisol activity plays a role in both the initial development and progression of the disease, and cortisol modulation may serve as a treatment. One of our proprietary molecules, miricorilant, has very potent activity in the liver. Our Phase Ib dose-finding study of miricorilant found that patients who received 100 milligrams orally just twice a week for 12 weeks experienced a 30% reduction in liver fat and improvements in liver enzymes, markers of fibrosis and key metabolic and lipid measures such as insulin resistance, serum triglycerides and LDL. The compound was also very well tolerated, with none of the GI side effects which commonly arise in patients being treated for MASH. Our randomized double-blind, placebo-controlled Phase IIb MONARCH study aims to expand on our encouraging Phase Ib results. MONARCH is enrolling 2 cohorts. In the first, 120 patients with biopsy-confirmed MASH are randomized 2:1 to receive either 100 milligrams of miricorilant twice weekly or placebo for 48 weeks. The primary endpoint for this cohort is reduction in liver fat, with biopsy-confirmed mass resolution and fibrosis improvement as key secondary end points. The second cohort has a planned enrollment of 75 patients with presumed MASH. Patients in this cohort will be randomized 2:1 to receive either 100 milligrams miricorilant twice weekly for 6 weeks, followed by 200 milligrams of miricorilant twice weekly for 18 weeks or placebo for the whole 24 weeks. In this cohort, the primary endpoint is also reduction in liver fat. As I said earlier, 2024 was a great year for Corcept. We expect even greater success for years to come. Physicians are becoming increasingly aware of hypercortisolism and its clinical consequences. We have seen that understanding translate to a long string of record quarters for new prescribers and patients receiving cortisol modulation therapy. The CATALYST results provide potent evidence to further advance the field by demonstrating that hypercortisolism is clearly much more common than previously assumed, and the treatment with a cortisol modulator is highly effective. Relacorilant's strong efficacy and safety profile positions it to become the new standard of care for patients with hypercortisolism. The positive results from our GRACE GRADIENT long-term extension and Phase II studies provide powerful support for successful relacorilant NDA and hypercortisolism. Meanwhile, our development programs continue to advance. We expect results from our pivotal ROSELLA study in ovarian cancer in just a few weeks. Our prostate cancer ALS and MASH studies are ongoing, and we plan to initiate our MOMENTUM study this quarter. We don't spend much time on these calls discussing the topic, but you should also know that we have a broad and active research portfolio, many proprietary selective cortisol modulators with potential very distinctive clinical attributes. We are comprehensively evaluating these attributes in their therapeutic applications and will advance the most promising compounds to the clinic. The problems caused by excess cortisol activity often have profoundly negative effects on patients. We are dedicated to finding new, more effective and safer treatments to help them. Operator, let's proceed now to questions.

[Operator Instructions] Our first question comes from the line of David Amsellem of Piper Sandler.

I just had a few on relacorilant. First, can you talk to when we should hear about NDA acceptance? And what are your thoughts on the potential for an ADCOM here? And is that something you're preparing for? So that's number one. And then on the ROSELLA trial, regarding the change and the endpoints or I guess, elevating overall survival to co-primary, I guess what I'm wondering is how unusual is something like that at this sort of advanced stage of the trial? And what should we make of that, number one? And then number two, can you talk to statistical penalties associated with now having a co-primary endpoint instead of a single progression-free survival endpoint?

David, thank you for the questions. And I will turn them over to the best people to answer in the company. But let me just clarify 1 small thing before we start, which is that we don't have co-primary endpoints. We have dual primary endpoints, and that's a very big difference. And Bill Guyer, when he gets to it, will actually answer that question. But the first question about the relacorilant for Cushing's syndrome NDA is, I think, best answered by Charlie Robb, our Chief Business Officer and Head of Regulatory.

Sure. So yes, thanks for the question. We submitted our NDA on December 30, as we put out in our press release, and the FDA has 60 days to sort of review it for acceptance. and that review is typically not -- it's not a sort of a preview of their substantive review for drug approval, but it's -- I'm sure all the parts of the application are there that there's sufficient data for them to review and then they can go ahead and proceed. And it's typical to receive during that 60-day period, various information requests from the agency for this data or that data, where could they find this or that piece of information. And we've been receiving that very ordinary course routine correspondence and responding to it over the past 60 days. So the process has been moving exactly as we understood it to move. And by sort of statute or regulation, the FDA is due to give us a response within 60 days. So, soon.

Okay. And the second question, Charlie, about an AdCom.

And we are not expecting an AdCom. I mean the past couple of medications for Cushing's syndrome were approved without them. Korlym was approved without one. And there's nothing about relacorilant's efficacy or safety that we think would require one. So we will be ready for it of course if it occurred. It would not bother us, but we don't expect it.

Thank you, Charlie. And now I'd like to reintroduce you to Bill Guyer. Bill is our Chief Development Officer and in charge of everything related to relacorilant's development.

Thank you, question related to ROSELLA. So first, before I answer that question, I'm really proud to share that we just reached the number of events for PFS by Vicker. And that allows us to now work with every 1 of the 120 investigators to ensure that all the data for the 381 patients are entered into the database so we can then do our analysis, and that's why we believe we will have our analysis done by the end of this quarter. So it's a very good positive thing for the ROSELLA study. Now specific to your question about the endpoint, we -- how common is this? I'd say very common because we've been actively working with regulators, both the FDA and EMA related to the ROSELLA study. And based upon their comments, we came to an agreement to have a dual primary endpoint of PFS by Vicker and OS to give us 2 shots on goal. So 2 chances for a positive study where we only need to meet 1 of them to have this be defined as a positive study. Now with that change, from a statistical point of view, the p-value for PFS by Vicker is now 0.04 and for OS is 0.01, and we are adequately powered to detect a difference for both PFS and OS. But let me come back to dual primary endpoint, what does that mean? Basically, for us to have a positive study, all we need is for 1 of them to be successful in order to declare the ROSELLA study a positive study. And once we meet that PFS by Vicker endpoint, we really don't have to wait for OS even though we expect to meet that OS endpoint. Of note also from a statistical point of view, once we meet our PFS endpoint, statistically, we can recycle that alpha where now for OS, it no longer becomes 0.01, we can now elevate that to be a p-value of 0.05. Now once we hit that PFS endpoint by the end of this quarter, we then plan to proceed with an NDA and MAA. So I see these changes are very positive for the program and very positive for women with platinum-resistant ovarian cancer.

Thank you, Bill. Thank you, David. Next question, please.

Our next question comes from Swayampakula Ramakanth of H.C. Wainwright.

I really appreciate taking questions. So a couple of questions. One on ROSELLA and the other is on CATALYST. So on ROSELLA on this dual endpoints, so how does that work? So Bill just said that if we hit the PFS endpoint at the end of the March -- at the end of March, we can file and go forward. However, if it turns negative, so what happens and -- and how long do you think we need to wait for the OS data to come through for filing? So that's question number one. And question number two on CATALYST. It's great to see continued increase of patients on Korlym and Korlym screening. Or screening patients for Cushing's syndrome. That's what I meant. In terms of utilization of the CATALYST data and the benefit of the CATALYST study, are you folks already seeing some of that either in terms of screening patients are also getting patients on the drug? And how would you start talking more about the entire CATALYST data in both the prevalence and the treatment?

Thank you, RK. I think I caught your question. The first one is best answered by Bill Guyer again. Bill, go on the ROSELLA study.

So thanks for the question, RK. So one, related to our end point. We don't plan to miss our PFS endpoint. So we do plan to hit that PFS endpoint and not have to wait for OS, as I stated before. But if we happen to miss that PFS endpoint, we do then have that second chance for a positive study with OS and we would hit OS approximately 1 year from now.

Thank you, Bill. And Sean, you -- let me reintroduce Sean. Sean is the President of our Endocrinology division. And he's really responsible for all [indiscernible] relacorilant. Sean, why don't you take the crack at the CATALYST question?

Yes. RK, thanks for the question. So in terms of CATALYST, the question of are we starting to see an impact. I would say that we start to see a small impact, recognize that there's always a delay between data generation, publication, guideline inclusion and then medical practice changes. So when we really expect to see more of an impact in the second half of this year and in the years to come. And why do we expect to see that? And that's because more data is going to be released as the year goes on. And so your question about how are we utilizing that data now, we are -- we can't speak to. And when the data is published, we'll be able to more broadly communicate the complete story of both the prevalence as well as the treatment findings to physicians.

Thank you, RK. Okay. Next question, please.

Next question comes from Joon Lee of Truist.

This is Asim Rana on for June. Just back on the ROSELLA study, I just wanted to understand a little bit better, like was there something specifically that prompted the change in the end point? And did you have buy-in from the FDA on the change? And then just on the 2025 revenue guidance, what was baked into that? Revenue was flat quarter-over-quarter. Just wondering about that.

First question, please, Bill, go ahead and why don't you answer that?

So again, for ROSELLA what prompted the change is just, again, we've been actively discussing ROSELLA with the FDA and EMA. And just through those collaborative conversations, we came in an agreement in a very positive way to elevate OS as a dual primary endpoint to give us 2 chances for a positive trial. That really is what prompted it. Just having a collaborative conversation with the FDA. So yes, they are in agreement with this change.

Okay. And Sean, the second question, please, about guidance and overall strength of the business and in endocrinology.

And I believe the question was around sort of the flat quarter. So we had a fantastic fourth quarter with a record number of patients and prescribers. And in fact, as Joe mentioned in his opening remarks, it was the best quarter we've ever had. However, our pharmacy partner had some operational challenges that impacted our Q4 revenue. So why did that happen? Well, more and more health care providers are recognizing that hypercortisolism is more prevalent than they once thought, and they're aggressively screening for it in their practices. And because of that, we experienced significant prescription growth in 2024, and the majority of that growth came in the second half of the year. Although growth is obviously fantastic. It temporarily overwhelmed the operational capabilities of our pharmacy vendor, and it took longer than expected to start patients on Korlym. Now we're confident that these issues have been identified and are being resolved, and we expect that the pharmacy will handle the amount of our business growth going forward. Things are moving in the right direction, and we have incorporated all of that into our guidance. So now in terms of the guidance, what's baked into that, and we take all factors into account. One thing that's emerged this year through CATALYST and through all the other studies that preceded it is that this patient population is understated. The old historical epi data would say that there were 10,000 of these patients, and we now know that that number is larger and the FDA agrees with us on that. So we're focused on unlocking the full potential of the market and see continued growth through the rest of this year. And I think more importantly, we see ourselves and more confident than ever that we're on track to grow our hypercortisols and business from $3 billion to $5 billion in annual revenues in 3 to 5 years. This market is expanding and it's expanding rapidly.

And I'd just like to underscore just a very important thing. It's now clear that there are many more patients with hypercortisol that were once presumed. And they are in many practices throughout the country, all large practices. And even more important, what CATALYST showed was that treating these patients with cortisol antagonist like Korlym or an upcoming relacorilant is very effective in treating patients who often have not gotten any relief from other treatments. And so that's really a very, very beneficial thing. Now we've really taken this 1 step at a time. You saw the CATALYST treatment results at the end of last year. We are going to appear in major conferences throughout this year. These findings will be in substantial publications starting soon and then going through the rest of the year, but there's many, many data points that we'll actually get out there. Now medicine changes slowly over time. Sometimes to detriment of patients. But as Sean has pointed out, we've really seen that change pick up in the second half of last year, and we think that is going to continue through this year, accelerating as the year goes along. So I think medicine is really changed by this work. And I think patient benefit will really be substantial as we go forward, and that's going to go on for an extended period of time. Okay. I don't see any more questions out there. So I'm going to call it now. Thank you very much for all listening in. As you've heard on this call, this probably will -- you will be getting other important information from Corcept in the upcoming weeks and months. So please stay tuned. Thank you very much.