Corcept Therapeutics Incorporated (CORT) Earnings Call Transcript & Summary

Good morning. Welcome to Corcept's Ovarian Cancer Program Update. I'm Atabak Mokari, Corcept's Chief Financial Officer. I want to begin by thanking those of you joining us virtually as well as a big thank you to those of you joining us here in New York. We are delighted to host this event to highlight one of our important clinical development programs. Statements during this meeting, other than statements of historical fact, are forward-looking statements based on our plans and expectations that are subject to risks and uncertainties, which might cause actual results to differ materially from those such statements expressed or implied. These forward-looking statements are described in our press release that was issued yesterday, and the risk and uncertainties that may affect them are described in our annual report on Form 10-K and our quarterly reports on Form 10-Q. Please refer to those documents for additional information regarding these forward-looking statements and the factors that may affect them. We disclaim any intention or duty to update forward-looking statements. We have a full agenda today. Our CEO, Joe Belanoff, will begin with the company overview. Next, our Chief Development Officer, Bill Guyer, will provide an overview of our oncology program. And then we're honored to be joined today by Dr. Thomas Herzog, a renowned gynecological-oncologist, who will review the ovarian cancer treatment landscape, our Phase II trial results and our upcoming Phase III trial. Following some concluding remarks by Bill, we will proceed to a Q&A session, which I will moderate. [Operator Instructions] For those of you joining in person, please submit your questions via the note cards provided and we will collect them from you. [Operator Instructions] I will now turn the meeting over to our Chief Executive Officer, Dr. Joseph Belanoff.

Thank you. It's really nice to see everybody in a room together. It has not happened. And I was saying before, I actually -- I'm not sure the last time I wore the suit. I'm just glad it still fits. But thank you really for coming. And I've been tasked with really talking about the company as a whole, and I'm going to do it briefly because we have lots of interesting information to go, but I think it really does help to sort of set the context for everything else that you're going to hear today. So Corcept, as I've said to those of you who know me for a long time, that even the name tells you what we do: cortisol and receptor. Cortisol is everything that we think about. Sometimes people will ask us, are you an oncology company, an endocrine company, a psychiatric company, neurologic company? And the answer to that is, well, we're none of those specific things. You can't put us in any of that cubbyhole. But what ties it all together is diseases which are affected by cortisol and our drugs, which modulate the effects of cortisol. Cortisol, of course, is a critical hormone, central for life. Absence of cortisol leads to death. It's produced by adrenal glands. Anyone who wants to know where that is, renal is another word for your kidney. They're just above your kidney. It's got an interesting thing, which is a diurnal variation, meaning it's high in the morning, it drops through the day, rises through the night. So all of you here are pretty much wide awake and alert because your cortisol is ready to go. It's top level for the day. And a critical thing is that it binds to virtually every organ of the body. There are receptors for cortisol almost everywhere. And so when you have a problem with cortisol, it can manifest itself in many different ways. And I'm going to talk about a few diseases, very few. But we're going to get to ovarian cancer in a second. But just keep in mind sort of as you think about this that our platform is really very, very broad. And those of you -- and I know in the room, there are some who've been investors for a very long time, you understand how we're really getting to all of those diseases. And this is a particularly exciting year because many of the things will read out this year, of which ovarian cancer is just the first. All of our compounds do a specific thing. They modulate activity at the receptor for cortisol, which is the glucocorticoid receptor. That's an important distinction from -- they don't lower the level of cortisol. Essentially, like, they're the dimmer on your light switch. They can turn down to varying degrees cortisol activity. They're all competitive antagonists. And our second-generation compounds really are very specific to cortisol. Now I'll mention her a couple of times today, but there really is a person who is responsible for all of our second-generation compounds. That's Hazel Hunt, our Chief Scientific Officer. Hazel usually resides in England. And for our afternoon conference calls, it's kind of late, so she doesn't participate in many of them. But she actually came over here today, and I'm sure all of you will have a chance to meet her as the day goes along. Now here is something that's very important. When we tasked Hazel -- actually, someone was teasing me about it before. I'm going to show you a little scientific diagram in a second. We have a great first-generation compound. We call it Korlym. It works very well to modulate cortisol, but it also antagonizes the progesterone receptor. It is, in another form, used to terminate early pregnancy. And we really tasked Hazel with seeing if we could separate those activities. That was a very difficult thing. Many companies have tried before. Hazel tried, but ultimately she succeeded. But an important thing to really understand, a very important thing, is that even though all of our compounds modulate cortisol, they are not identical from -- to each other. They have different qualities. And I say it at every single quarterly call, some are better at creating insulin sensitivity. Some are better at creating weight loss. Some are active in the oncologic models, some are not. So you cannot think of them as a compound. They really are very different from one another in important ways, which has actually created a great opportunity for us because instead of bringing one compound forward, over time, we will bring many compounds forward because of the specific activities that they have. So just -- I'll do this just very quickly. Korlym, progesterone cortisol, you can see they awful -- they look an awful lot alike because they all share the steroid portion of their molecule, which is the 4 rings there. Korlym is a competitive antagonist, but it's just as much an antagonist as the progesterone receptor as the cortisol receptor. What Hazel did, which is really pretty amazing, is she created a library of compounds, more than 1,000 of them now that are in 3 different structural series. And all of them are very potent in modulating cortisol activity, and none of them touch the progesterone receptor at all. So the primary thing of getting rid of the quality of producing termination of pregnancy by blocking the progesterone receptor and the other medical effects, which happened through the progesterone receptor, are really absent. But again, I'll make the point that they are not identical. Here's just -- you can see relacorilant, which is the drug we're going to talk about today, and Korlym. They look different. There are structural reasons why relacorilant antagonizes the glucocorticoid receptor and not the progesterone or any other receptors. But even you, sort of sitting here, can see they're not the same molecules. It's a bigger molecule. It's not a steroid, and it's -- and those qualities actually are shared amongst our -- all of our second-generation compounds. Now here's the most complicated slide I'm going to show you. I'm not going to spend much time on it. But what this really tells you is -- I think it's a fallacy for people to think of this as a simple sort of lock-and-key system. What happens actually in this system is that whatever you have, either the drug or cortisol, binds to the receptor. The receptor and ligand together translocate to the nucleus. They sit on the DNA. And then a whole host of cofactors, repressors, stimulators actually join the party. And they join the party in very different ways with different compounds. And this is really -- this is an actual readout of the co-regulators. But the important thing to really get from this slide is that they're not the same. Mifepristone is not the same as CORT125134, which is relacorilant. And it's certainly not the same as compounds below it or cortisol. And if you want to know what happened to the other compounds, names you have not heard, in various ways, they were inferior. So it's not just that relacorilant is better than mifepristone in ways that we think is important. It's better than other compounds that actually we created. But the point again is not the same. These compounds have important differences in actuality in the clinic. Okay. This, I'm going to go through really very briefly. Again, those of you who know Corcept know this well. We are an unusual biotech company. We actually make money and have for many years. And we actually pay for all of our research from that money. We're a business in some sense like our parents would understand. We make money every day, and we plow it back into our own research, where we think we can go forward. The platform is large and rich. This is just the first readout. There are many other diseases you're familiar with, liver disease, psychiatric diseases, neurologic diseases, where we're working. And here's an important thing. And I really, again, want -- like with Hazel, want to give a shout-out. We're really built on the back of doing collaborative academic research and have for many years. It's an unusual thing for a pharmaceutical company really to do. I know the downsides, but we've had tremendous upsides. It's been a great farm system for us. And I really want to give credit to the founders of what we're going to talk about today, which is the University of Chicago. This was their research 15 years ago. We were able to bring it in-house and make it go more quickly. But it was really their founding idea that cortisol modulation might be affected in certain cancers, including ovarian cancer. This is just a brief chart of our revenues and cash and so forth. Again, you've seen this before. And what you've really seen in our commercial business is growth really since inception. During the pandemic year, it sort of moderated. But we're back on to, I think, what is going to be a very good year of growth. And this is just sort of the readout for this year. I put this slide in here just so you will understand that it's the end of March, and this is a very important readout you're going to get today. But things are going to occur all through the year, both in Cushing's syndrome, oncology or metabolic diseases and as we'll mention later, we even have a neurologic disease, ALS, where we're starting this year. So all the things I've talked to you about for years are really starting to come to fruition at this point in time. And this is -- last slide for me, and I know there's plenty on here, and that's intentional. We probably have 35 different academic collaborations at any given point in time, half in the United States, half outside of the United States, half preclinical, half clinical that we support. And it really has operated as a way to develop this entire platform. And obviously, we're going to spend all our time the rest talking about oncology. But keep in mind, as the year goes along, that you're going to see results from metabolic -- you'll see something that will come out of psychiatric issues. And that's just going to continue indefinitely into the future. So thanks for your patience and your interest in all this. I think it's actually a very important part of clinical medicine. All right. I'd like to introduce you next to Bill Guyer. Bill is our Chief Development Officer. He's responsible for all of the things that you just saw in bringing them forward. And he has a few comments to make specifically about ovarian cancer and oncology.

Great. Thank you, Joe. And I want to reiterate as well, it's so great to be here live. It's been 2 years of pandemic, and it's so good to see New York back. This is one of my best cities to visit in all of the world. But it's truly a pleasure to be here today to talk about Corcept's mission to really improve patient lives through cortisol modulation. And when I look at why I joined Corcept about 8 months ago, it really was everything that Joe had just talked about. I dug deep into the science preclinically of all the work Hazel had done, looked at the pipeline. And I was excited with the potential that I could see of meeting unmet medical needs through the SGRMs, which are the selective glucocorticoid receptor modulators, across many different diseases. I was excited in seeing what we're doing in endocrinology, metabolics, neurology, but also oncology. And today, we're going to talk about our efforts in oncology with a specific focus on ovarian cancer. Now we believe we can have a positive effect for patients based upon research like this. Cortisol modulation has the potential for a broad impact across many different tumor types. And here's research looking at 20 different tumor types. And in this evaluation, they looked at the GR expression in these tumor types through a validated assay and measuring the H-score. Now the H-score has a range of 0 to 100, and it really measures the intensity of the GR activity. H-scores greater than 100 are defined as having high GR expression. And as you can see on this slide, all of these 20 tumor types had GR expression. But the vast majority actually had high GR expression. Now you also see on the graph that there's a range for that H-score. Now that range can be influenced by a few things, one of them being the stage of the cancer because as cancers continue to progress, that H-score typically will increase, which means GR expression will typically increase as well. We believe based upon this research, with selective glucocorticoid receptor modulators, we can have a positive impact not only on ovarian cancer but, hopefully, on many of these cancers listed here. We also believe that this is validated through research from 2 different academic centers that collaborated, and this is from the Oregon Health & Science University as well as the University of Southern California, which is my alma mater. And in this study, they evaluated 341 women who had ovarian cancer. And at the time of debulking therapy, they took samples of those tumors, and they evaluated GR expression, very similar to the previous study that I showed. And they look to see those who had GR expression and high GR expression. About 40% of these women had high GR expression. And as you can see here, those with high GR expression had a significantly lower progression time. And therefore, we saw that we could have potentially a positive impact not only on those with high GR expression, but we believe we can have a positive impact on anybody with GR expression. Those 2 research studies as well as many others really informed our Phase I study design, where we looked at not only ovarian cancer but also other solid tumors. And we were looking at signal seeking, basically evaluating relacorilant in various different doses and also dosing schedule. This was the first time we had studied intermittent versus that of continuous relacorilant. And we also studied various different doses of nab-paclitaxel in combination with relacorilant. And as you can see on this slide, we see a longer duration of therapy for many of these patients. And overall, about 1/3 of the patients had a response. And of note as well, the median time for progression-free survival was about 4.6 months. And as you hear from Dr. Herzog coming next, that's very similar to what we're seeing in Phase II and, I think, very predictive of what we see in Phase II. In addition to that, we also looked at other solid tumors. And when you look at all these other solid tumors, we saw actually the majority of them responded to relacorilant plus nab-paclitaxel. Of note as well, the very bottom, the vulvar squamous cell carcinoma patient is still alive today about 3.5 to almost 4 years later. All of this research as well as many other research really informed our oncology pipeline and where we are today. And we're taking a very focused and methodical approach to our oncology pipeline. But I hope to see this expand rapidly in the coming months to years. We've got 3 different mechanisms of action that we're focusing on, the first being apoptosis and trying to restimulate chemosensitivity. And that is relacorilant in combination with nab-paclitaxel in advanced, platinum-resistant ovarian cancer, currently in Phase II, soon to be Phase III as you'll hear today. The second mechanism of action is to block a growth pathway. When you use a drug like XTANDI or enzalutamide that's an androgen receptor antagonist, cortisol can get upregulated, and that can help stimulate prostate cancer growth. We're hoping to block that by using either 2 different drugs: one is the Phase I study of relacorilant plus enzalutamide, and that's being done at the University of Chicago as an investigator-initiated study; and the second one is at the bottom, which is exicorilant, which is another selective glucocorticoid receptor modulator. And that's being also studied as a Corcept-sponsored trial, a Phase I/IIa study. We're going to get the results for those studies in the second quarter this year, and that will help guide us on our next path forward in prostate cancer. And then finally, the third mechanism of action is around immunosuppression. And as all of you know, cortisol is an immunosuppressant. And if we can block that, we can hopefully help resensitize a drug like KEYTRUDA, which is a checkpoint inhibitor, to help really boost that result in adrenal cancer. But since we're here today to talk about ovarian cancer, I wanted to dig a little deeper on that mechanism of action. And when we say cortisol modulation may enhance and/or restore chemosensitivity, what does that mean? When we talk about apoptosis, what does that mean for cancer? So apoptosis is the tumor killing effect that chemotherapy is meant to stimulate. That's the programmed cell death that you're trying to help stimulate and therefore, kill that cancer. Unfortunately, though, cortisol increases expression of antiapoptotic genes, such as SGK1 as well as others. But that's the main gene we typically evaluate. We're using relacorilant as a selective cortisol modulator to compete with cortisol at the GR and hopefully, therefore, enhance and to restore chemotherapy sensitivity to a drug like nab-paclitaxel, but we hope to be more drugs beyond just nab-paclitaxel. So all of that got us to the point of Phase II and now going into Phase III. And it gets us to the point of where I'd like to introduce our special speaker, Dr. Thomas Herzog. Now Dr. Herzog is the Deputy Director of the University of Cincinnati cancer unit. He's a Professor of Obstetrics and Gynecology at the University of Cincinnati College of Medicine. And he's also on the Board of Directors for the Gynecologic Oncology Group, also known as the GOG. It's been a pleasure to work with him over the past few months, especially around his expertise in clinical trial design and regulatory strategy experience. He as well as all the GOG Partners have really helped us better understand the Phase II results and have been instrumental in helping us design our Phase III trial over the past months. And he'll be critical as we interact with regulators moving forward. So Dr. Herzog, please, welcome.

Bill, thank you very much. It's a pleasure to be with you this morning and talk about this exciting platform. I echo the sentiments of being live and in person. We just had a big meeting in Phoenix for Society of Gynecologic Oncology. Some people were complaining that their feet hurt after about 3 or 4 days from dress shoes that hadn't been worn for -- probably all new dress shoes, and a couple of colleagues were actually wearing flip-flops, believe it or not, with their suit on the last day. So we're avoiding that at least this morning. Bill, thank you for the kind introduction. I don't think even my mom would say that many nice things about me. So I'm very grateful. And it's the difference between a Zoom meeting. Nobody says those things at a Zoom meeting. So it's great. Thank you. Well, it is my pleasure to be here this morning and talk a little bit about the ovarian cancer landscape. We'll spend a couple of seconds talking about that and then to really get into -- you've heard the background and the why this should or could work, and we'll talk about some real data, which is always much more exciting. So I get the opportunity to really, I guess, be the main meal, if you will. So I'm excited about that. Hopefully, the questions are dessert, right? So we'll do that after this. So this is a success story if we look at the prevalence of disease. So in the last couple of decades, we have more women alive with ovarian cancer than we've ever had. And they are receiving more and more lines of therapy. We think -- looking at the literature, with so few studies showing an OS advantage, we really think that it's been the cobbling together of these progression-free survivals that has increased the lifespan for these women. Note that we're not curing a whole lot more women than what we did 2 decades ago. That's the unfortunate thing so far. Now we have some new things that are in the arena, and that may change based on even some of the frontline data that we have with some of the parts and so forth. But right now, we think this increase in the prevalence has really been due to those cobbling together of those PFS gains from individual, different types of drugs that we can introduce that have unique mechanisms of action. The other thing that's interesting is that I think people forget how many cases of ovarian cancer are really out there. And I think this shows it well. So although the mortality has decreased slightly -- mortality overall, say, if you look at 10 years, hasn't changed very much. Our 5-year mortality has changed significantly. So we've been able to push out median survival beyond 5 years for even those women with advanced ovarian cancer. And I think that's very important. When we think about the ovarian cancer journey for the patient, it's a devastating disease. I was in clinic yesterday and saw multiple patients with ovarian cancer. And unfortunately, most patients have high-grade serous cancers, which is the majority of the tumors that we see, present with advanced stage disease. So almost 3/4 of the patients present with stage III or stage IV disease, meaning the disease is out of the pelvis when the cancer is diagnosed. Of those patients, up to 70% to 80% of those will recur at some point. So the majority of patients with advanced ovarian cancer, unfortunately, will have recurrent disease. It's just a question of when, not if. So if we look at frontline treatment, that consists of aggressive surgical cytoreduction, either upfront or in a neoadjuvant fashion where we give several cycles of chemo, and then we then treat them with maintenance bev, maintenance PARP, no maintenance or combination bev-PARP, largely based on molecular markers and signatures and the presenting symptoms. They then, unfortunately, as I said, recur. And we use a dichotomous break between 0 to 6 months and greater than 6 months to define those patients that are platinum-sensitive when they recur more than 6 months or platinum-resistant when they recur within 6 months at the time of having received platinum. So we often have patients then that will recur more than 6 months, and we label them platinum-sensitive. They're generally treated with platinum-based regimens again. And maintenance is an option as well in those patients. Unfortunately, we have a number of patients, however, who will recur first time as platinum-resistant. You'll see a term up here, platinum-refractory. I should explain that and define that because you'll see it on some of the slides as we go through the presentation. So technically, platinum-refractory disease is a disease that actually grows during primary treatment. And these are the worst of the worst patients in that. It's a small percentage. The good news about ovarian cancer is that it's a relatively chemosensitive disease. That's why, unlike other -- some other solid tumors that you see, you see patients that are on their fourth, fifth, sixth line of therapy because they often respond or at least have stable disease on treatment. So how do you get to be platinum-resistant? Again, you recur within 6 months. And that could be primarily, meaning after frontline therapy, or it could be secondarily, after you've received treatment for platinum-sensitive disease. The point is that the majority of patients, almost all are platinum-resistant at some time in their natural history of ovarian cancer, especially those that present with advanced stage disease, which again is the vast majority of patients. So what does this look like from a numeric standpoint? We have over 21,000 new cases projected for this year with over 14,000 deaths. It gives us about 20,000 drug-treatable patients per year in the platinum-resistant ovarian cancer space. So platinum resistance occurs in virtually all patients, as I've said, and the therapy options that we have, I think everyone is familiar with those. Most of them are either single-agent chemotherapies such as paclitaxel, pegylated liposomal doxorubicin or topotecan, which are the FDA-approved agents, and that can be alone or in combination with bevacizumab. And then, of course, we have other drugs that are compendium-listed such as gemcitabine, nab-paclitaxel. And in terms of, again, looking at the numbers, the outcomes we see with most of these regimens is a progression-free survival median of about 3 to 4 months. Response rate is generally under 15% if these drugs are used alone, a little bit higher if we add bev in at the time. And overall survival is under 1 year for these regimens. We have data, as I mentioned, with nab-paclitaxel. We -- this is a nanoparticle, albumin-bound paclitaxel. So it's a different formulation than what we see with paclitaxel itself. And there is data. We've done a study within the GOG. It was done within our GOG 126-Q, which is platinum-resistant disease. And it's referenced there, Dr. Coleman. And you can reference that as to baseline type of response data that you see. The one thing I would point out in that study that's important is that those patients were all on their first recurrence. So cross-trial comparisons are always dangerous. Of course, we know that. But they're even more dangerous when the entry criteria are different. So keep that in mind. So a little bit better group, if you will. So as we look at this, what are our options? Well, there's really 4 options, right? There's -- you can always go on to a clinical trial. But many patients don't qualify for a clinical trial, don't want to go on to a clinical trial. I'm at an academic center. We try very hard to get these patients on the clinical trials because we don't have a lot of great options that are the standard of care currently for platinum-resistant disease. So these are the 3 options that we do have, single-agent chemotherapy that I just alluded to. You could do those agents and others with bevacizumab or, in some cases, PARP inhibitors. I'm going to talk a little bit about each of these. So the strengths of the single-agent chemo is that we have multiple agents to choose from. It's kind of like having a lot of quarterbacks on a team that are starters. They say if you have 3 quarterbacks or 2 quarterbacks that are your quarterback, you don't have a quarterback. This is kind of where we are with platinum-resistant disease. Key limitations are the efficacy just isn't what it should be. And this is why we have such a great unmet need in terms of drug development in this platinum-resistant space. So we need more efficacious drugs with longer durations of response. We also have to look at the patient in this setting. And I think that we're really trying to palliate symptoms at this point. Quality of life is very important. And we sort of have to keep that in mind as we treat these patients. But having chemo, it does improve the overall response rate and the PFS. I think the AURELIA trial does a nice job of illustrating that. It's very good at -- when you add the bevacizumab in, it's very good at managing ascites, large-volume ascites as well as pleural effusions. Downside is that, although rare, the side effects are quite severe. We can see GI perforations, severe hypertension, proteinuria and thromboembolic events. And some of those can even be fatal, especially the GI perforations. And bevacizumab has had an amazing journey in ovarian cancer. It has multiple approvals. It has always consistently hit its PFS benchmark for improvement, but it has not been able to improve survival in any of the studies heretofore. PARP therapy. I've sung the praises earlier about maybe even changing the landscape a little bit of ovarian cancer in terms of outcomes. We'll have to wait and see. But very promising in those who have molecular signature, predicting response in those with homologous recombination deficiency. So we're seeing excellent efficacy. Do recall though that PARPs were originally developed in platinum-sensitive maintenance and in this space, with third-line-and-beyond recurrences. So we do have data in this space. So that's encouraging. It's oral, which is great unless the patient has any GI issues. The only problem, though, is that most of the patients with the molecular signature most likely to benefit from PARP inhibition will have already been treated with a PARP at least once, if not twice. So I think you're going to see less and less PARP use in this space because we're now using it in frontline and very aggressively in platinum-sensitive recurrence. So I think that it won't be such a great option for us anymore because PARP after PARP after PARP data, it just doesn't exist. So now the exciting part. We get to talk about the randomized Phase II study of relacorilant that was performed in this platinum-resistant ovarian cancer space. So this space where we have very few great options available. And this was, as I said, a randomized Phase II study, which I think was very well done in the sense that good numbers of patients with approximately 60 in each cohort, randomization was 1:1:1. The patients had to have measurable or evaluable disease. And they had to have -- they were allowed to have up to 4 prior lines of therapy. You can see here the intermittent relacorilant is in the green there. And you can see the schedule and the dose there. So the relacorilant was given at 150 milligrams po. And the nab-paclitaxel was given at 80 milligrams per meter squared intravenously on day 1, 8 and 15 of a 28-day schedule. So the relacorilant was given on 2 days initially, then given the day before, the day 8 dose given on -- day 8 dose of the nab-paclitaxel and then the day after. And then that pattern -- and then the same thing on day 15, around day 15 and then on day 28. It was given and then you repeat. And the day 28 was actually starting a new cycle. That's the day before, if you will, of a 29-day cycle. So if you go out 7, 1, 8, 15, 22, 29, you can sort of understand then the pattern. The nab-paclitaxel, again, the dose is 80 milligrams per meter squared. Notice that the comparator arm, the nab-paclitaxel dose, was 100 milligrams per meter squared intravenous. That's in the purple. And the reason is -- given on the same schedule, the reason the dose is lower in the combination is because the relacorilant actually decreases hepatic clearance of the nanoparticle albumin-bound paclitaxel. So the preclinical data, pharmacokinetics and pharmacodynamics indicated that a lower dose would be optimal. If you look at the continuous arm, this was where the relacorilant was given every day and then the nab-paclitaxel was given on the same schedule. And essentially, so the nab-paclitaxel was given on the same schedule in all the arms. Just the dose was different in the relacorilant arms, so in both intermittent and continuous. Now the blue will go away in the sense of -- I'm going to show you data throughout. But there was not a real difference between the comparator arm and the continuous arm. So the arm that was carried forward, which is precisely what a Phase II -- randomized Phase II trial is designed to do, is to pick the winner for your Phase III trial. And so this was done very well and by the book, if you will, in terms of selecting the intermittent arm to carry forward. And so we'll show you that data, and we'll drop some of the curve so it's a little bit clearer as we go through. So if you see the blue curve is disappearing, it's not that we're trying to hide them. It's because we're trying to make it clear what you're really going to be using carrying forward between the intermittent and the comparator arms. Now the primary endpoint of this trial was progression-free survival as determined by investigator using RECIST 1.1. Key secondary endpoints included response, duration of response, overall survival and safety data. Baseline characteristics are shown here, well balanced between the 3 cohorts. If we concentrate on the intermittent versus comparator, you see that the number that are platinum-refractory was higher in the intermittent arm. And remember, these are tougher patients to treat. So most studies that are designed especially for registration don't allow these patients into the trial. And so you had over 10% versus under 2% in the comparator arm. So I think as someone assessing this data, that's helpful when -- if it were the other way around and the intermittent arm did better, I think someone would say, "Well, maybe it's because you had a better group." In this case, I think the argument would be quite the opposite that you had the tougher group actually in the experimental arm, which was the intermittent versus the comparator. Patients. How many of these have prior taxanes? If you're thinking about where you're using a taxane-based therapy as the comparator, virtually, all of these patients had that. If you look at the number that -- again, that do worse, we know a number of lines of therapy indicates the lower response rate, lower PFS and lower overall survival, you see here that fairly well balanced between the two in the comparison there. So get to the punch line here. This is the progression-free survival as determined by investigator between all 3 of the cohorts. And we'll drop out the continuous there for you to see the intermittent versus the comparator there and median was 5.6 months versus 3.8 months with a hazard ratio of 0.66. P value was 0.38, so highly statistically significant. And you can see those curves stay apart there. No banana sign there. They're still staying apart. This is looking at the sensitivity analysis. And these are always fun to look at, right, for all the different subgroups and so forth. And I think from my perspective, it's always better when all the patients benefit and you don't have a bunch of the lines, the point estimates line to the right of unity there, favoring the experimental arm. It's quite the opposite here. You can see that almost all the points are favoring the intermittent relacorilant arm. There's a couple that are right near unity. But you don't see anything that really favors the experimental regimen in any way. So it's consistent throughout the subgroups with all the patients that you see there. And even the confidence interval there does not cross 1. And again, remember, this is a Phase II. So your numbers are not as robust as what you would have with the Phase III, where those confidence intervals would be much tighter. You can see here, if you take out the platinum-refractory, those patients -- if you look at those patients, they actually did quite well on this particular study. If you look here, if you look at the progression-free survival, when you remove those patients, and the reason why we're going to show this curve is because that is the plan for the Phase III. So what we're trying to do is tell you what would the population of the Phase II look like going into Phase III if you took out the patients that were primary platinum-refractory and if you took out those that had greater than or equal to 4 prior lines of therapy. And as you can see here, that the hazard ratio gets even better. We can knock out the continuous arm. And you can see, while the median doesn't change, the hazard ratio is now 0.58. Your P value is even more impressive at 0.16. These are the swimming -- or swimmer plots here for the 3 cohorts. And what I think is important on this is looking at the median duration of response. So you're looking at 5.6 months versus 3.7 months. We'll drop out the blue there. And you can see there the overall response rate similar between the comparator and the intermittent arm, but the duration of response is significantly different. So again, 5.6 versus 3.7 with a hazard ratio of 0.36 and, again, a P value that's 0.006. So -- and you can also see here how many patients are still under treatment at the data cut here when this was performed. So the arrows indicate the continuing response there. So I think it's like 7 to 2 in terms of the 2 arms. So probably not all the same with investors. But from a medical standpoint, there is a chance that this data could even be more positive as you get with those patients that are still on treatment. This is looking at the same thing. I'm looking at duration of response. When you take -- when you remove those patients that will not be included in the Phase III study, again, you see duration of response, very positive. It becomes even more positive in terms of the hazard ratio with a hazard ratio of very impressive 0.26 with a P value of 0.001. Overall survival data is now available, and this is looking at the overall survival for all 3 cohorts. And again, if we drop out the continuous here, you see that the overall survival was 13.9 months in the intermittent cohort versus the comparator being 12.2 months. Hazard ratio was an impressive 0.67. P value was 0.66 versus the nab-paclitaxel alone. Again, pretty impressive curves. They almost come together towards the median there, just below the median. And then they're really apart for most of the time there. Again, sensitivity analysis looking at the overall survival, very impressive, again, in terms of the distribution of these different subgroups. If we look at all patients, again, we're seeing the same pattern as what we saw in the PFS sensitivity analysis. And here, if we take out the platinum-refractory -- or if we look at the platinum-refractory again, you see that those patients did very well in this group as you can see. So again, if we'd look at the overall survival curves and we remove those patients that are not going to be in the Phase III study that's planned, you'll see that the difference is the medians are the same, but the hazard ratio becomes even more impressive at 0.52, P value is 0.01. And again, very impressive curves in terms of how they stay apart. So this is looking at the overall data for all the patients in summary. And I've already shown you all this. I'm not going to read it all back to you here. But from my standpoint, it's consistent throughout the study of looking at the primary and key secondary endpoints with a benefit for those that received the intermittent relacorilant plus nab-paclitaxel versus nab-paclitaxel alone. And so these are the P values and the hazard ratios. And then if you look -- if there's any key hazard ratios you want to pay attention to, you can sort of see how they change more favorably when, again, you look at the criteria that you would use for eligibility for the Phase III trial. And that's what's shown here. So again, even more impressive when you look at these comparisons between intermittent comparator for those that are going to be eligible for our Phase III trial. Safety and tolerability. This is all in line with what we would expect from nab-paclitaxel. It appears to me that, clinically assessing this, most of the toxicity, if not all, essentially is coming from the nab-paclitaxel. So no big surprises here. In general, what we saw was that the regimen was extremely well tolerated. Any variances here, I think, are just due to some small numbers. If you want to make it a little clearer, we can compare the intermittent versus the experimental arm there -- intermittent versus the control arm, rather. And you can see here, most everything was the same. Even the fatigue in that, I think, is probably just a handful, a couple of patients that changed that around. So when I look at this data in totality from this program, I do think that cortisol modulation appears to be a promising platform moving forward in terms of oncology therapeutics. Study is the first randomized, controlled Phase II trial, relacorilant plus nab-paclitaxel in patients with platinum-resistant ovarian cancer. Primary peritoneal and fallopian tube cancers are also included in this group. We group those together conventionally. So nothing new about how that was done. That's the convention that we use. Under the umbrella of ovarian cancer, we include those diseases as well. This was a heavily pretreated group, as I said, with 4 lines of prior therapy. And still, substantial benefit was observed. And irrespective of which endpoint we used, in all patients, intermittent relacorilant plus nab-paclitaxel improved progression-free survival, duration of response compared to the control arm. Either -- an even greater differential is seen when you exclude the patients, again, who we are not planning on enrolling on the planned Phase III trial. No additional side effect burden was observed when we looked at the safety and adverse events from this study. And I'm going to tell you about the Phase III trial that is planned. And we -- and the hope is to get it started second quarter of this year. So this is the design of the Phase III. Notice it's working. So I don't know how much is going to change, but hopefully not a whole lot because I think it's pretty well designed. GOG Partners -- by full disclosure, I'm on the Board of GOG Partners and Associate Director for GOG Partners. I was -- been very involved in the design of this trial. I think we understand the regulatory landscape in ovarian cancer very well. And our colleagues at -- in ENGOT in Europe were also involved in the trial. And I'm actually on the Liaison Committee between GOG Partners and ENGOT. It's been a very good relationship. But leadership from both those groups was involved in the design of this trial. And I have to comment that Corcept has been very receptive to our advice. And sometimes, the advice wasn't delivered as tactfully as it could have been by some of our members. But I want to applaud -- some of the companies I've worked with through GOG have not been as willing to take our advice, and that hasn't always resulted well in terms of regulatory success. But that's another story. Target enrollment for this study is 360 patients. And the histology is going to include high-grade serous and grade 3 endometrioid epithelial ovarian cancers, which is the majority of patients with epithelial cancer. So you're over 80%. So it's going to be a high number that would be eligible based on histology. Those that obviously are platinum-resistant, so they progressed within 6 months of the last dose of platinum therapy. And again, I've said it over and over, who we're excluding. We're getting rid of the patients that are platinum-refractory. And one of the things people say, "Well, they look pretty good on the Phase II sensitivity analysis," and I agree. You could almost argue that's also an unmet need. The problem with platinum-refractory, though, is sometimes we're not even dealing with ovarian cancer. Remember, we get into opening the abdomen. And very often, there's disease everywhere. And they get treated with a regimen for ovarian cancer. And molecular studies get sent off and signatures and so forth and then start having some rectal bleeding. Eventually, you get a colonoscopy. And lo and behold, it gets reclassified as a colon cancer or something like that. So remember any irritation of the peritoneal cavity can cause the CA-125 to go up. So that's part of the reason why you don't really want platinum-refractory on your studies because some of those patients can sneak in and once they're on study, intention-to-treat analysis. They're in your data set and you have to live with that inclusion. So that's another reason to take those patients out. And then we have good data. I would reference Ronnie Alvarez' study. I was an author on that paper as well, where we really used to look at just platinum resistance and platinum sensitivity. But we now understand that we need to better homogenize our population by looking at other things such as was done with the Phase II. We know the molecular signature. Line of therapy is something that's new, and this also acknowledges histology. So when we put all those together, we have a better understanding of who these patients are and what their expected outcomes are. And so we can design the study statistically with more precision when we better understand that. So it's another reason to remove the heterogeneity of getting these patients out over 4 lines. Primary endpoint for this study will be progression-free survival, but this time instead of by investigator, it will be by blinded, independent central review. Key secondary endpoints will include overall survival. This is the randomization. So you're going to be -- the patient would then be randomized to relacorilant plus nab-paclitaxel or investigator's choice chemotherapy. And I'll go over those options in a second. So very similar or the same essentially as the Phase II in the intermittent is that you have the relacorilant at 150 milligrams po. The nab-paclitaxel, again, given at 80 milligrams because of the reduced hepatic clearance. And you can see the schedule there. Schedule is exactly the same, and the doses are the same. So another thing that I see some folks do is they make some significant changes between Phase II and Phase III, which I think is always a dangerous thing to do. Investigator's choice chemotherapy: pegylated liposomal doxorubicin at the community standard dose of 40 milligrams per meter squared; paclitaxel weekly at 80 milligrams per meter squared on a 1, 8, 15 schedule of 28 days; topotecan given at either a daily times 5 or a weekly schedule. And you see 2 choices there that are available. And then the same control arm with the same schedule that was used in the Phase II with the nab-paclitaxel. So physicians can choose amongst these 4 different drugs -- or what, 3 different -- 4 different drugs and 5 different options, if you will, because the topotecan has 2 different schedules that they could choose amongst. So I think this lays out the study very well. And I think that the thing that is important is that the -- when we look at the use of growth factors, G-CSF was used in the -- all the patients on the intermittent arm in the Phase II. Because of the tox profile that was seen in terms of side effects and so forth, neutropenia, the decision has been made to allow that to be at the investigator's discretion, which was what was done in the nab-paclitaxel-alone arm or the control arm. So it will be equal for both of those. So any of these, if the investigator wants to use it, they can use it. But it's not mandatory in any of the arms in this study, including the experimental arm. This is my final slide. The reason I put this up here is many people always inquire as to why -- how do you choose the primary endpoint on the these trials and is PFS going to carry the water from a regulatory standpoint or not. And in my opinion, it will. PFS is subjective. It's not as objective as overall survival. The problem with overall survival is that -- what I said is we're going to use slightly earlier lines of therapy. Many of those patients will go on to get other active treatment. So the problem then is you have other active treatment that confounds the ability to see the benefit of the regimen. But as you saw in Phase II, OS curves look pretty good. Hopefully, with more patients, that endpoint would be met as well, but that just remains to be seen. But the primary endpoint, in my opinion, should be bigger. And this is a paper that a lot of my colleagues and I, and you can see some -- Rich Pazdur from the FDA and some of the other folks from the FDA wrote from an ovarian cancer workshop back in 2017. We just had another workshop on accelerated approvals in December of this year that we did. And so we've had a lot of interactions with the FDA. And we feel that this is consistent with their review in this particular space. So I want to thank you so much for allowing me to deliver the fun part of the talk and go over the data. And again, I appreciate you all coming this morning to hear the data. Thank you.

Thank you very much, Dr. Herzog. Very well done. Really appreciate that. So in conclusion, when we look at cortisol modulation, we believe it has a significant potential across the broad range of oncology products, oncology areas, especially ovarian cancer. And when we look specifically at ovarian cancer, we believe, based upon the preclinical Phase I and Phase II results, relacorilant is a differentiated product in platinum-resistant ovarian cancer. And a few things I just want you to take home today is we've seen meaningful efficacy improvements across PFS, duration of response as well as overall survival. But the key thing is, while Dr. Herzog showed you various different data cuts, this study was powered on PFS. And even though we looked at data cuts, we hit our overall progression-free survival endpoint. And that's a key piece to take away. While we looked at various different endpoints, that was just exploratory to see how this drug was operating across many different avenues. When we look at the addition of nab-paclitaxel with relacorilant, we saw no additional side effect burden. I think that's key as well because a patient cannot see the efficacy benefit if they cannot tolerate the drug that you're giving them. And so to me, that gives you overall effectiveness. And when we look at the trial, our Phase II trial, we actually had patients staying on therapy longer in the intermittent arm than any of the other arms, the comparator arm or even the continuous arm. And I think that speaks to the side effect profile of adding no additional side effect burden. And then finally, when we talk about convenient administration, and when Dr. Herzog took you through the intermittent dosing, the key thing I want you to take away from is really that we're giving a high dose when it matters the most. So we're giving a higher dose of relacorilant at 150 milligrams and when it matters the most, meaning we're giving it before, during and after that of when nab-paclitaxel is administered. And so with that, we hope that as we go into Phase III, if we're able to replicate what we've seen preclinically, which was predictive of what we saw in Phase I, which was to me predictive of what we saw in Phase II, if we can see those same results in Phase III, we're going to see really unprecedented results for these women with ovarian cancer. So where are we going to go to next, our future opportunities, we plan to move forward in earlier lines of ovarian cancer after we start the Phase III study in the second quarter of this year. We also plan to look at other tumors, as I showed you in the preclinical data, combinations with nab-paclitaxel in many other tumor types. We're going to look at other combinations with other chemotherapies in these other tumor types. As well, we're going to look at combinations with other antitumor agents. I showed you KEYTRUDA plus relacorilant. We're going to look at other opportunities for other cancer agents. So with that, I'd like to now bring up Atabak. And I'd also like to bring up Hazel and Dorothy as we take questions from all of you. So thank you all very much.

All right. Great. For the Q&A session, we're joined by Hazel Hunt, Corcept's Chief Scientific Officer; and Dorothy Nguyen, our -- Corcept's Senior Medical Director leading our ovarian cancer program. So thank you for submitting your questions. We will get to as many as we can, and we will consolidate similar questions for the interest of time. So let's begin.

First question is with an approximately 2-month improvement in overall survival and progression-free survival, is that clinically meaningful? Tom, do you want to take that?

Sure. Yes. It's a very good question. Obviously, from a regulatory standpoint, this would be a review issue. I think that one thing that is important to understand is that PFS is a very small part of the curve. So when you're comparing Kaplan-Meier curves, to me, the more meaningful parameter is the hazard ratio. And the hazard ratios were very impressive, irrespective of which endpoint you looked at. So obviously, what the assessment cycles are -- the number of -- all those things play a role in terms of the regulatory review. But the other big thing that plays a role is what's the toxicity of the experimental compound. In this case, at least the OS signals are that it's very minimal with no increased burden for the patient symptomatically. So I think with that profile, yes, I think it's very potentially approvable.

Tom, I think, just accidently said one. What he's saying is that the median is just a single point. And I think that see people sort of don't get -- it's not even really a numerical median. It's where it crosses the 50% line, whereas the hazard ratio describes all the data, the entire curve. So theoretically, you can imagine 2 curves were identical to the median. And the median change would be nothing. There'd be no difference. And then all -- one in one group lived and all the other ones died, it's still a median that was identical, but the hazard ratio would be dramatically different. So I think that, that's really, for somebody who's looking at the whole data set, the critical thing to look at.

Okay. So next question is, what is the regulatory path forward? Have you had an end of Phase II meeting with the FDA?

Bill?

Great. Thanks for the question. So we've submitted our end of Phase II meeting request. And we're eager to meet with the FDA as soon as possible. We feel excited with all the data that Dr. Herzog has shown you plus more in the full meeting package. And we plan that the FDA should be just as excited as we are to discuss the data.

Okay. And a follow-on question to that. Have you considered submitting this package for approval now? What is the likelihood of receiving accelerated approval?

Well, that will be left up to discussions with the FDA. So we feel very excited about the data. And that will be part of the discussion when we talk with the FDA.

Yes. And I'll just [ add in there ] because this is something that we've been talking about now almost for a year since the progression-free survival data. And I've said what I'll say exactly again. Our anticipation is we're going to be doing a Phase III study. It's up on clinicaltrials.gov. And that's what we think is going to require to get to approval. We're very optimistic about that, but that's our expectation. And I want to make sure that investors have the same expectations consistent with what we have. That said, we're going to have an interesting conversation with the FDA in the near future.

Okay. Next question is how do the results of the nab-paclitaxel-only arm look relative to what you would have expected?

Tom?

Yes. They're very in line. If you look at the Coleman data, I think the response rate on the 126 study was 23%. Similar -- the actual -- the PFS in this study with what I would consider more unfavorable population based on the number of lines of therapy and allowing platinum-refractory in would actually be better. I think there was, what, 4.3 months?

4.6.

4.6, and ours was 5.6. So not trying to, again, cross-trial comparison, but it was at least as good or better. So I think -- and the control arms were consistent. So I think overall that there were no concerns raised about the control arm under -- or overperforming.

Okay. And I guess a follow-on question to that, and you talked about the investigator's choice as the comparator arm in the Phase III. But can you talk a little bit more about the rationale for that versus nab-paclitaxel alone?

Yes. And one other thing I'd add about having the nab-paclitaxel in the randomized Phase II as well as a choice in the randomized Phase III is this is a very strong comparator. So if you look at the AURELIA data, again, you'll see that -- how badly some of those drugs performed. Topotecan, I think, was under 5%. And then you added bev, and it went up. But we're looking at drugs that are approved that, really, in our larger Phase III trials, you can look at an immune study, JAVELIN 200, and look at how PLD performed, I think it was 8%. So we're looking at nab-paclitaxel as being at least as good as paclitaxel, which was, by far, the strongest in the AURELIA trial, which led to approval in that setting with bev in that space for platinum-resistant disease for the bev approval. And then if you look at Tillman's data, which admittedly was given along with bev in a straight Phase II, and then the Rob Coleman data from the GOG, you see that there was really very good performance of the nab-paclitaxel, really even outdoing the weekly paclitaxel. So it's a very strong comparator. And I think that's important to point out. As far as why you design a trial with physicians' choice, it really helps enrollment tremendously. So remember, many of these patients have had different journeys to get to this point for their recurrent. Some came through platinum-sensitive, some primarily recurred. Some of them had -- they got something else. They receive weekly paclitaxel, for example, maybe with bev. And then now they're on your study. Well, they wouldn't be eligible if you just made it a weekly paclitaxel study because the peripheral neuropathy and all those things are cumulative. So it gives you the ability as a clinician to choose what is best for the patient. And the patient doesn't want to go on something that she just failed 3 months ago. So it really helps enrollment tremendously. And I think it allows you to make the best choice for the patient based on their toxicity from prior treatments and what's going to be in her best interest. So I really like the -- you have to limit it somewhat as was done here. But I think you can't have -- do whatever you want, but you have to put up standard of care treatments. And I think the trial design addresses that very well.

Let me just make just one summary point because I think that's all very important information that you heard. Nab-paclitaxel in our study as a single arm performed as, I think, better than any other single-arm treatment that you can find in the literature. And so that's your baseline to compare to what happened with relacorilant. It wasn't being compared to a drug that had an 8% response rate. It was the strongest drug, which was available. And I think that offering it again for all the reasons Tom is talking about, I think, is very important with the whole group. But I think you have to consider the results in that context.

Next question is you mentioned excluding primary platinum-refractory patients from the Phase III. Can you define that more? What does that patient population look like? And I know you discussed some about why you're excluding it.

Yes. I alluded to it during the talk in that, first of all, it's a very difficult patient to be able to treat because they generally don't respond well to most anything. And occasionally, they're admixed with even cancers of another origin, upper GI tract or lower GI tract, for example. And so most studies, from a regulatory standpoint, do exclude them to try to make the population more homogeneous, which the regulatory agency prefers.

Okay. Next question is about -- how do you think about the level of GR expression as a prognostic factor and potentially as a guide for treatment?

Yes. I'll take that. So this goes back to one of the slides that Bill showed, which is something we've talked about before. Not all tumors have the glucocorticoid receptor on them. In fact, you could see sort of the end of the chart some which had very little. Ovarian cancer does have glucocorticoid receptors. And as you get deeper into treatment, it actually has more glucocorticoid receptors. It's upregulated as you go through various cycles. Now an -- before I answer your question directly, I think that a really important thing, and I just don't want it to get lost here, Tom made the point, but I'll make it again, which is the entire group separated. I mean that's a really unusual thing in Phase II studies. And believe me, I've been part of Phase II studies where essentially, the egg is rotten but you're looking for the part that somehow isn't. This was not the case. All the people separated regardless of their various characteristics going in. And so the Phase III study is, in some sense, just literally looking to replicate that result in a larger group of patients. Now it is true that the people in this study who had the highest GR expression, H-score is greater than 100, did better than those who did. But all of them did well. And we're not going to use that as an exclusion criteria going into the Phase III study because we think that all patients with platinum-resistant ovarian cancer have the chance to benefit from relacorilant addition. We will keep track of it because from a research point of view, it's an interesting thing. But all patients with platinum-resistant ovarian cancer who've had multiple treatments will be eligible for the Phase III study.

Okay. Next question is, can you comment on what is the time line for completing the Phase III study, including completing enrollment and data availability?

Bill?

So the timing, we hope to enroll the study within a year and then run the study for approximately a year. So it's about a 2-year time frame. And we've got equal number of sites in the U.S. and Europe. It's 40 sites in each, U.S. and Europe, so a total of 80 sites. And it's going to be, as I've told, both European investigators as well as U.S. investigators. While it's equal in both geographies, it's competitive enrollment. And so those who enroll the fastest, we would appreciate the most.

And just one thing to add because Tom is a little modest about this. I mean the Gynecologic Oncology Group, where he's on the Board, in the United States is the group that does ovarian cancer studies. They are the group that brings things forward to the FDA. And they took on this study and, I'm confident, will really shepherd it through. And the equivalent is true in Europe. Our Phase II study was a terrific effort led by Dorothy, but I'll joke a little, she did it herself. We had no kind of institutional help with that, and it still enrolled quite well. If you remember in the pandemic, enrolled about a quarter quicker than we thought it was because I think as doctors saw the results, they entered patients more rapidly. We're hoping that those time lines really are exactly what he says they are.

Okay. The next question is, how did you arrive at the number of patients for the Phase III trial? What are your powering assumptions, et cetera?

Dorothy, would you like to answer that?

How did we arrive at the number of patients?

Power assumptions.

Power assumptions. We're powering the study to evaluate progression-free survival. And that power is 80% to 90%. And then we have the OS as a secondary -- primary secondary endpoint.

Yes. So it's -- my recollection is based on the results of the Phase II study, this is 90% powered for progression-free for survival. Is that correct, Bill?

That's correct, with a hazard ratio of 0.7.

Yes. With hazard ratio of 0.7.

It's gated hierarchical.

Hierarchical gating, meaning that the PFS, we evaluate it first. And then we will look at the key secondary endpoint first of overall survival, which are important for regulators.

But even though PFS, just let me add, is -- again, if we're able to replicate what we saw in Phase II and Phase III across all of those parameters, PFS, DOR and OS, we'll see significant, again, unprecedented results if we're able to replicate that.

Okay. The next question is, is the safety profile of treatment regimens in this patient population, an important factor?

Tom?

Absolutely. So again, if you think about what the goals are of treating someone with platinum-resistant disease, it's to keep them alive for as long as possible. The quality of life becomes a very important parameter that we follow, and it affects our choice of treatment. So that's why this platform is particularly appealing in this patient group, where you have a drug that you add on to another agent that doesn't cause additional symptom burden. So safety and toxicity are key parameters.

And I guess a follow-on question to that is, how do you -- the safety profile of this combination, relacorilant plus nab-paclitaxel, how does that look relative to alternative treatments that you use?

Yes. It looks really favorable. This is -- if approved, this is a regimen that I would use and I know my colleagues would use.

Okay. Next question is how should we interpret that the overall response rate was similar in the -- across the different treatment arms relative to the comparator?

Tom, you can answer -- I'll answer. I mean it's a very high overall response rate. I mean if you caught what Tom was talking about, in this group of patients with multiple lines of treatment, you often see single-digit response rates. So having about 1/3 of the patients respond really across all lines is really saying something. I mean the comparator arm did extremely well in this study as well. I think really critical thing that was interesting, and it appeared last year but really held up, is that of those who respond, the duration of response for the people who got relacorilant is substantially greater. And that actually is why the curve separate because the people who do respond, respond for much longer. Now I wish I could say -- and I've thought about this a lot over the last year, a priori, who are they going to be? But unfortunately, we don't really have a signature for that. But consider sort of the value proposition, and as Tom's talked about here. You have a medicine, which is really not adding side effect burden. And your value proposition is sort of tails, you tie; heads, you win. Like why wouldn't I -- as a patient, why wouldn't you consider a treatment where you have the possibility to be in that group that has the long duration of response? Otherwise, you're just in a standard group without actually medical cost.

Let me add one more point to that, too, because that was a great answer. But I would again remind you, ORR was a secondary endpoint. Our primary endpoint was PFS, and we powered the study on PFS. Some studies in Phase II powered on ORR, overall response. But we did not -- we powered it on PFS, and we hit that primary endpoint in our Phase II study for all patients.

Okay. The next question, how do you think relacorilant fits into the current treatment landscape, in particular, relative to single-agent chemotherapies, Avastin and the PARP inhibitors you mentioned earlier?

Tom, would you like to take that?

Yes. I just sort of alluded to that when we were talking about the adverse events and the safety profile. But again, this is a regimen that if it performs as it did in the Phase II, it's going to be something that will be welcomed into the G1 oncology treatment community. The therapeutic index of this drug looks very favorable. And I think that it would be a welcome addition to the landscape, especially with the activity. You mentioned the response rate but also the duration of response, which is really important. We didn't really get into the concept of stable disease as well. And that can be looked at further in terms of total clinical benefit, which is a secondary endpoint of the Phase II. But based on the mechanism of action and sort of what we're seeing with those durations of responses, I would predict there'll be significant clinical benefit. But obviously, we need to see that in the Phase III data.

I mean I want to add -- I would echo that. And also, you have to realize that not all patients, given what Tom described with regard to the side effect profile, would be eligibly to get bevacizumab. And because the PARP inhibitor therapy has evolved to come earlier, many patients in this setting would have already had PARP and would not likely have a choice to be receiving PARP.

It's a really good point, Dorothy. It's just that the PARPs just aren't used in this space any longer because the patients with the molecular signature that would respond, again, would have received at least 1 line and probably 2 lines by the time they get to this point.

Okay. Next question is how big is the market opportunity in the U.S. for the expected Phase III patient population?

Yes. I think that Tom's slide is accurate. I mean it's 20,000 to 25,000 patients is really this population in the United States.

Okay. It looks like 2 more questions. So the key learnings -- can you share your key learnings from the Phase II study on patients that can benefit from relacorilant? In particular, is there an opportunity to move to earlier lines of treatment as it seems that as you have progressive lines of treatment, you become more chemo-insensitive.

I'm going to pass it over to Tom in a second, but I just want to make sure everybody understands. I mean we have a -- we're going for our first approval in oncology. And we have a circumscribed population where we think we can provide real benefits. So that's who we're studying right now. But Tom, I'm glad to have you speculate as to where potentially there may be other uses beyond that.

Yes. Purely speculative because I'm not inside your brain, and I don't know what you're going to do. But I would suspect that if the Phase III is positive, that you would want to look at using it in earlier lines of therapy. It would just make sense, especially as it looks so far, the safety and adverse event profile would favor putting it in combination. And so you may be able to combine with frontline regimens and platinum-sensitive regimens and so forth. So it's a very appealing asset from that standpoint, again, because it doesn't add toxicity.

Okay. And our last question is, given that there's a high level of GR expression in many solid tumors and activity that you've seen in other tumor types, what's next for you?

Bill?

We're currently also in prostate cancer and we're in adrenal cancer. As I looked at my first slide of all the different cancers that have GR expression, we're taking a look at all of those in a prioritized fashion to really evaluate internally where we believe we can have the greatest result and meet the highest unmet medical need for patients. And so that's a -- it's a deep discussion internally. But yes, we will be picking a few more out of that list of solid tumors to move forward with. Which one today, I cannot speak to, but there will be others.

Okay. Great. Well, thank you for joining us today for a very productive update on our ovarian cancer program. Please reach out to us with any follow-up questions. Have a great day.

Thank you.

Thank you.