Corcept Therapeutics - Earnings Call - Q1 2020
May 4, 2020
Transcript
Speaker 0
Our commercial business for the rest of the year. The risks COVID-nineteen poses to patients with Cushing syndrome are likely to increase demand for Korlym. At the same time, restrictions imposed by state and local governments, hospital and individual medical practices make it very difficult to work with physicians in person. Some of the imaging centers and laboratories physicians use when diagnosing patients with Cushing's syndrome and titrating to an optimum dose of Korlym are closed. Many patients are hesitant to leave their homes even to visit the doctor.
These factors are likely to reduce the rate at which new patients are introduced to Korlym and make it more difficult for physicians to monitor patients following dose titration. However, as physicians and patients adapt to a world in which COVID-nineteen is endemic, as they are beginning to do, the impact of these factors may diminish. We reaffirm our 2020 revenue guidance of $355,000,000 to $375,000,000 based on our strong first quarter results and our best estimate of how the factors that determine our revenue, pandemic related and otherwise, will evolve over the coming months. As many of you know, we are conducting a Phase III trial of relacorilant, our planned successor to relacorilant as a treatment for patients with Cushing's syndrome. The trial is known as GRACE.
Our goal for GRACE is to confirm the positive efficacy and safety findings of relacorilant's Phase II trial in which patients exhibited meaningful improvements in glucose control and hypertension to Cushing's syndrome's most pernicious manifestations as well as an important secondary endpoints without instances of Korlym's significant off target effects. Our poster presentation of relacorilant's Phase II results can be found at the Investors Past Events tab of our website. We believe relacorilant will constitute a major medical and commercial advance. While its Phase II efficacy data are comparable to Korlym's at the same time points in Korlym's pivotal trial, relacorilant promises to offer significant safety benefits. Korlym's affinity for the glucocorticoid receptor, GR for short, makes it a highly effective treatment for patients with Cushing's syndrome.
Unfortunately, Korlym is not selective for the GR. It also binds to the progesterone receptor, which causes endometrial thickening and vaginal bleeding in many women regardless of age and requires Korlym's label to carry a black box warning, the most serious medication warning required by the FDA for termination of pregnancy. By a different mechanism, Korlym causes hypokalemia, low potassium, a manageable potentially serious side effect that was experienced by forty four percent of patients in Korlym's pivotal trial and is a leading cause of discontinuation in patients taking the medication. Unlike Korlym, relacorilant is a selective GR modulator with no affinity for the progesterone receptor. It does not cause endometrial thickening or vaginal bleeding.
It is not the abortion pill. In addition, we saw no instances of drug induced hypokalemia in relacorilant Phase I or Phase II studies. These are side effects physicians and patients would strongly prefer to avoid. The COVID-nineteen pandemic has slowed the pace of enrollment in GRACE and delayed the opening of the last few of our planned 65 clinical trial sites. As public health restrictions ease, we expect our remaining sites to open and full enrollment to resume this fall.
We now plan to submit our NDA in the 2022. This quarter, we will start a Phase III study of relacorilant in patients whose Cushing's syndrome is caused by an adrenal adenoma or adrenal hyperplasia. The study is called GRADIENT, G R A D I E N T. It will be the first randomized double blind placebo controlled trial in patients with this etiology of Cushing's syndrome. GRADIENT has a planned enrollment of 130 patients at 60 sites in The United States and Europe.
Participants will receive either relacorilant or placebo for six months with the primary endpoints being improvements in glucose metabolism and hypertension. Many of the investigators for GRACE will also participate in GRADIENT. GRADIENT is part of our investment in the development of relacorilant to treat patients with hypercortisolism. It is not a required part of relacorilant's NDA. Our goal is simply to help inform and improve the treatment of patients with this type of Cushing's syndrome.
Our poster presentation, Gradient's design, is available at the Research and Pipelinepublications tab of our website. An abstract is also available in the AprilMay supplemental issue of the Journal of the Endocrine Society. I will now turn to our oncology program, which is examining three potential mechanisms by which cortisol modulation may benefit patients. Cortisol activity suppresses apoptosis, the program cell death chemotherapy is meant to cause in tumors that express the GR. We are testing whether adding our selective cortisol modulator relacorilant to chemotherapy will blunt cortisol's anti apoptotic effect, thereby allowing chemotherapy to achieve its full cancer killing potential.
Our goal is to confirm the striking data we presented at ASCO last year, where we reported results from our open label trial of relacorilant plus nab paclitaxel, siltiene's chemotherapy drug Abraxane. In our study, seven of twenty five patients with metastatic pancreatic cancer and five of eleven patients with advanced ovarian cancer achieved durable disease control, meaning their tumors either shrank or ceased growing for sixteen weeks or longer. The duration of benefit in some patients was eye catching. Two patients with metastatic pancreatic cancer exhibited tumor shrinkage for more than fifty weeks. One patient with ovarian cancer exhibited tumor shrinkage for sixty five weeks.
The tumors in all of these patients had progressed during multiple lines of prior therapy, including therapy with taxanes. A poster presentation of these results is available at the InvestorsPast Events tab of our website. Last year, we began a controlled Phase II trial of relacorilant plus nab paclitaxel in patients with metastatic ovarian cancer with a planned enrollment of 180 patients at 25 sites in The United States and Europe. Primary endpoint is progression free survival with secondary endpoints including overall survival and duration of benefit. Despite challenges arising from the COVID-nineteen pandemic, we continue to expect results of this study during the first half of next year.
This quarter, we will start a Phase III trial of relacorilant in combination with nab paclitaxel in patients with metastatic pancreatic cancer, a disease with a dire prognosis. This trial will be called RELIANT, r e l I a n t. RELIANT will be an open label trial in which eighty patients receive relacorilant plus nab paclitaxel with the primary endpoint being the objective response rate assessed by RECIST criteria. We plan to perform an interim analysis on data from the first 40 patients. We believe sufficiently positive results could support accelerated approval.
RELIAM will be conducted at 30 sites in The United States. Cortisol modulation may also benefit patients by bolstering their immune response. Cortisol is the body's natural immunosuppressant. This effect is often beneficial. It helps to prevent, for example, autoimmune disorders such as rheumatoid arthritis.
In patients with cancer, however, cortisol activity suppresses the ability of the immune system to recognize and destroy tumor cells. It also blunts the cancer killing attributes of immunotherapeutic agents such as checkpoint inhibitors. Next quarter, we are starting an open label Phase Ib trial of relacorilant plus the PD-one checkpoint inhibitor pembrolizumab, Merck's drug Keytruda in twenty patients with metastatic or unresectable adrenocortical cancer. Because their tumors produce cortisol, these patients also have Cushing's syndrome, which cortisol modulation can treat. Our trial will examine whether relacorilant can, in addition to treating Cushing's syndrome in these patients, specifically help immunotherapy achieve its maximum effect by reducing the immunosuppressive effects of excess cortisol activity.
Finally, cortisol modulation may benefit patients with castration resistant prostate cancer. Androgen stimulates the growth of prostate tumors, which is why androgen receptor antagonism with medications such as enzalutamide, Pfizer's drug Xtandi, our standard therapy. More recently, researchers at the University of Chicago and Sloan Kettering have shown that when colonies of prostate cancer cells are exposed to enzalutamide, growth is stimulated by cortisol activity at the GR. Our hypothesis is that a regimen combining a cortisol modulator with an androgen receptor antagonist will block this tumor escape route. Our selective cortisol modulator, exicorilant, is potent in animal models of castration resistant prostate cancer.
By the end of this year, we expect to select the optimum dose of exicorilant in combination with enzalutamide to bring forward in a controlled Phase II trial. In addition, a dose finding trial of relacorilant plus enzalutamide is being conducted by investigators at the University of Chicago.
Speaker 1
I will conclude with an
Speaker 0
update of our program in metabolic disorders. As many of you know, we are developing our selective cortisol modulator, miricorilant, for the treatment of antipsychotic induced weight gain and nonalcoholic steatohepatitis, or NASH. Millions of patients rely on medications such as olanzapine to treat diseases such as schizophrenia and bipolar disorder. Unfortunately, these drugs cause serious metabolic abnormalities, including rapid weight gain and lipid disorders in nearly everyone who takes them. Patients are forced to make a terrible bargain, treat one dangerous disease but at the cost of acquiring another.
Heart disease and stroke, not suicide, are the leading causes of death in patients taking antipsychotic medications. We conducted two double blind placebo controlled trials in healthy subjects in which mifepristone reduced weight gain cost by taking olanzapine or risperidone. Our results were published in the journals Advances in Therapy and Obesity. Unfortunately, we could not advance mifepristone further for this indication because mifepristone's quality as the abortifacient disqualify it as a treatment for common disorders. Miracorilant can be advanced because it is a selective cortisol modulator with no affinity for the PR.
It is not the abortion pill and if approved could be widely distributed. Miracorilant is more effective than nipipristone in animal models of antipsychotic induced weight gain. And now our completed double blind placebo controlled Phase Ib study in healthy human subjects has demonstrated that miricorilant is active in reducing antipsychotic induced weight gain in humans. In the first part of our Phase Ib trial, 66 healthy subjects received olanzapine and either six hundred milligrams of miricorilant or placebo for fourteen days. Participants who received miricorilant gained less weight than those who received placebo.
In addition, liver enzymes, markers of liver damage, increased less in patients who received miricorilant suggesting that miricorilant has protective effects in the liver. In the second part of our trial, 30 healthy subjects received olanzapine and either miricorilant at nine hundred milligrams or placebo for fourteen days. The results confirm our findings from the first part of the study. Patients receiving miricorilant gained less sharply elevated liver enzymes than subject who received placebo. No side effects, other than those commonly seen with olanzapine, were seen with either dose of miricorilant.
In fact, we plan to investigate considerably higher levels of miricorilant exposures in future studies. The full results of our Phase Ib study will be published later this year. Our double blind placebo controlled Phase two trial of miricorilant called GRATITUDE to reverse recent antipsychotic induced weight gain is in progress. In the study, one hundred patients with schizophrenia will continue to receive their established dose of antipsychotic medication and either six hundred milligrams of miricorilant or placebo for twelve weeks. GRATITUDE will be conducted at approximately 20 centers across The United States.
While the COVID-nineteen pandemic has effectively suspended new enrollment in this trial, we are confident enrollment will resume as public health restrictions ease. There has been no delay in our plans to start by year end, a placebo controlled double blind Phase II trial in patients with longstanding antipsychotic induced weight gain. In this trial, we plan to test the formulation of miricorilant that we believe will be achieved significantly higher exposures of miricorilant then will be reached in the GRATITUDE trial, which again is examining the reversal of recent antipsychotic induced weight gain. Finally, in the first quarter of next year, we plan to start a double blind placebo controlled Phase II trial of miricorilant in patients with NASH, a serious liver disorder that afflicts millions of patients. In animal models, miricorilant prevents and reverses both fatty liver and liver fibrosis, which are precursors of NASH.
We also intend to test our new more potent formulation of miricorilant in this study. In conclusion, Corcept had an outstanding first quarter of revenue and profits. We increased our balance of cash and investments to $349,000,000 We have no debt. The COVID-nineteen pandemic has slowed enrollment and site activation in GRACE, our pivotal Phase III trial of relacorilant to treat patients with Cushing's syndrome. We now plan to file our NDA in the 2022, two quarters later than we had originally planned.
We now expect to start GRADIENT, our Phase III trial of relacorilant in patients with adrenal Cushing syndrome this quarter. We expect to we continue to expect results of our controlled Phase II trial of relacorilant plus mab paclitaxel to treat patients with metastatic ovarian cancer in the first half of next year. This quarter, we plan to start a Phase III trial called RELiONT of relacorilant plus nab paclitaxel in patients with metastatic pancreatic cancer. We believe sufficiently positive results in RELiANT will support accelerated approval. Next quarter, we plan to start an open label Phase Ib study of relacorilant combined with PD-one SHEK inhibitor pembrolizumab to treat patients with metastatic or unresectable adrenal cancer.
Finally, by the end of this year, we expect to select a dose suitable for advancement of exicorilant in combination with enzalutamide to treat patients with castration resistant prostate cancer. The second part of our Phase Ib trial of miricorilant to reduce weight gain caused by olanzapine has confirmed our earlier positive results. Our double blind placebo controlled Phase II trial of miricorilant to reduce recent antipsychotic induced weight gain is open. We expect enrollment to resume as public health restrictions loosen. We plan to start a Phase II trial of miricorilant in patients with long standing antipsychotic induced weight gain by year end as originally planned using an improved formulation of miricorilant.
We now plan to start our Phase II trial of miricorilant in patients with NASH in the first quarter of next year. I'll stop here for questions.
Speaker 2
We'll hear first today from Charles Duncan with Cantor Fitzgerald.
Speaker 3
Hi, guys. Let's see. Hopefully, you can hear me. Congratulations on a very good quarter and the recent IP update, Charlie and Joe.
Speaker 0
Thank you, Charles.
Speaker 4
Good. You can hear me. Let's see.
Speaker 3
I had a couple of questions, from on the Korlym side and then in that pipeline. You got a ton of things going on in the pipeline, and I'm interested to explore that. But first, before I do, let me ask you a question on the commercial side. With regard to the revenue growth that you saw, could you help us understand better the contribution of demand versus say pricing and or dose in the quarter?
Speaker 0
Sure. Hey, Chad, this is Charlie. I'll answer that question. So just a little background for folks. Traditionally and historically, every first quarter, we face a headwind.
Our revenue faces a headwind due to a couple of factors, primarily the annual reauthorization process that insurers put their patients through, which results in patients receiving it sort of being essentially their insurance being suspended. We work through those issues and provide them with free free drug in the meantime and then get them back on paid drug. But our revenue takes a hit in the first quarter every year as we deal with that administrative hurdle. Also, in the first quarter, virtually all of our Medicare patients go through the Medicare donut hole, which is, of which we are obligated to cover about three quarters of that cost. So that is another deduction to our revenue.
And so as a result, sort of absent a price increase, our first quarter is typically flat or even down a little bit in terms of revenue. So so with that as sort of background, I can tell you we took a 5% revenue increase at the start of the year that I think had the effect of, for the most part, you know, kinda counterbalancing that that headwind. K? So that was the effect of a a change in price. Now the rest of the growth, I think, roughly speaking, think of it as about there were sort of two factors at play.
One is that insurance companies allowed patients some insurance companies allowed patients to refill their prescription just a few days earlier than normal. Think the thinking was in case there are logistical difficulties posed by the pandemic and say Federal Express can't deliver on time, they didn't want patients to run out of medicine. So a very small minority of our patients received refills a few days earlier than they normally would. Actually, that's about half of the growth that you saw in the quarter. Roughly, the other half, was due to improved patient adherence.
Patients just took their medicine more regularly than they normally do, and I'd describe that to certain pandemic conditions. But I think that's sort of a medical fact that perhaps, Joe, would you like to elaborate on at all? Yeah. I think that, I think everybody knows, including myself, patients don't always take, you know, their medicine every day even when they're supposed to, and there are some medications that they take, you know, sometimes only half the time, which obviously is not what their doctors intend. That's not really true with Korlym.
Patients do take the medicine pretty much on schedule, but still days are missed. We saw very little of that in this quarter because I think that patients with Cushing's syndrome, you know, understand and their doctors help them understand that they are particularly higher risk for infections. And frankly, the fear of contracting COVID nineteen, I think, added to that, adherence percentage. Now for us as a company, obviously, we think that that's a very important benefit for patients, and we hope to really maintain that idea that this is a medication that is best taken every single day that is prescribed as we go forward.
Speaker 3
Okay. That's helpful, Charlie and Joe. And given those dynamics, could you provide any granularity on, say, new patient, new diagnoses, new scripts, in the quarter? Because it, Charlie mentioned adherence. So what about, any additional patients?
Well, as
Speaker 0
you know that basically, starting in March, virtually every medical practice in the country shut down visits from medical science personal visits by medical science liaisons or clinical specialists. And I thought our commercial team really did a terrific job in instantly adopting the idea that there were some doctors who were still interested in being reached but needed to be reached remotely. We were still even able to conduct various events where doctors could gain more information remotely. And a really interesting thing, I think, is that there is a, admittedly, a small minority of doctors who I think, because of their own practices and perhaps their own personalities, actually seem to favor this remote contact as opposed to, the standard inpatient contact. Now on balance, of course, that's not the case.
I think that, it's difficult for patients to get to the doctor right now. Diagnosing Cushing syndrome involves a lot of testing. Everyone knows all those sort of things within the world. That being said, we did see new enrollments in in the quarter, not as many as we expect to see in a restriction absent time, but, but we did see new enrollments, and we and we continue to see new enrollments. And as I said, what we're really trying to do at this point in time is learn all the things that this forced experiment really did force us to learn and incorporate them as we go forward as things loosen up.
Speaker 3
Okay. That's helpful, Joe. And then if I could move on to the pipeline questions that I had, particularly with regard to relacorilant and Grace timing. I think you provided pretty good explanation the kind of impact of COVID-nineteen on that. But can you provide us more information with regard to the number of patients that are enrolled or actual number of sites up and running?
And any other work needed for the NDA in terms of, say, long term tox or manufacturing process optimization?
Speaker 0
Yes. No, I think I understand the question. And let me just provide a few more details. One, although the addition of patients to the study basically slowed to a trickle or close to zero at some points, I think it's important for everyone to understand that the patients who were on trial continued to be seen by their physicians. And so they marched their way through the study.
It was very interesting decision, you know, primarily at academic centers, which, which I think, you know, was their best compromise, was that patients who were already receiving medicine in the study should continue to receive the medications in study, but they didn't really, with everything else that was going on, want to add new patients to their caseload at that point in time. Now we have never actually given specific numbers that we have, but I think that you can add them up to understand sort of where we were and take best estimate and where it's going to end up. And we really do feel confident at this point that the '20 the date that we've now given, which is essentially a two quarter delay, really encompasses everything we need to get done. But to your specific questions, yes, the long term toxicology continued at pace. That's not an issue.
That will actually be done on what was the standard time line before. Manufacturing issues are and solutions moved along at their same pace. So really the limiting variable for the study was already going to be the final efficacy and safety results and still going to be the case.
Speaker 3
That's helpful. Last question and then I'll hop back in the queue is relative to your broader platform. You've got a lot of candidates in the clinic or soon to be. And I guess I'm kind of wondering, you've been at this medicinal chemistry for glucocorticoid receptor modulator game for a while. And when you consider the breadth of those efforts relative to other approaches you've seen, perhaps even recently or in the past, such as those by a recent IPO, could you compare and contrast your efforts versus others that have come along?
Speaker 0
Yeah. Broadly, I I can. I mean, we thought for a very long period of time, and it was basically my my research career and then my my my career course for the last twenty years that the cortisol modulation platform is an extremely important medical platform. Many diseases are affected by cortisol activity, and we really have followed the research to the places where we think they can be best served by treatment and we'll continue to do that. We still have interesting programs that are even earlier in the pipeline because cortisol goes everywhere in the body and cortisol modulation really affects many, many different diseases.
Now Chad is somebody who really has followed our research for a very long time. You knew that one of the really limiting variables was the only drug which was available for cortisol modulation was mifepristone, which by the activity it has in a different receptor, the progesterone receptor, had all of its notoriety as the abortion pill for a very long period of time. Korlym is an excellent drug for Cushing's syndrome, but it is not a selective drug. It gets to other receptors besides the glucocorticoid receptor. It affects other hormones activity besides cortisol.
It also affects progesterone and to a lesser degree androgen, where it's a modest androgen receptor antagonist. Our medicinal chemistry goal, and many had tried it before we did, was to come up with a selective cortisol modulating drug, a drug which did not touch the progesterone receptor. And it was really a real medicinal chemistry feat. She's not often on these calls because she's in England. Our lead chemist and head of research is a skilled medicinal chemist by background named Hazel Hunt.
And she really put together the original ideas as to how you could create a compound, which was a cortisol modulator but did not get to the progesterone receptor And ultimately, it was very, very successful in doing that. And our compounds are really profoundly selective for cortisol activity. They don't touch the progesterone receptor at all. And I think that's really a critical difference between that and all the other compounds which are out in the world at this point being developed. Either there are no other modulators or the modulators aren't quite as selective as ours.
They really get to more than one receptor. And I think that one of the really important I'll just I don't wanna get too esoteric with this, but, basically, a selective cortisol modulator, which is a four ring structure, a steroid, I think is very difficult to come by. It really took a novel structure, one which would fit the glucocorticoid receptor and not the progesterone receptor that really got us to selectivity. So I'll sort of leave it at that, but, I think that is a major difference between our compounds and others.
Speaker 2
We'll hear next from Tazeen Ahmad with Bank of America.
Speaker 5
Hello. Thanks for taking the question. Can you guys hear me?
Speaker 0
Yes, we can, Tazeen. Hi.
Speaker 5
Okay. Perfect. Hi, Tazeen. I just wanted to follow-up on the quarter, and congratulations on having a very strong number. Specifically, can you talk about any signs that you've seen in April?
And I'm asking only because based on the number that you used to show for 1Q, it seems like for the rest of the year, it shouldn't be too difficult for you to have a beat on your guidance.
Speaker 0
Right. So just because it was a little hard to hear you, Tazeen. I'm going to just repeat your question and make sure I got it right, which was what
Speaker 1
are
Speaker 0
we seeing in April and what is that for sort of portend for the rest of the year given the results we had in the first quarter. And I guess I would say that we've given our reaffirmed our guidance for the year, and that's and we don't give quarterly guidance or any kind of interim guidance unless we think that needs to change. And all I can say is that we looked at all of the drivers of our revenue, all the variables that we always look at. We adjusted them, as we thought appropriate for the conditions we saw and expect to see for the rest of the year and landed right back in the same place in our revenue guidance that we gave originally, and so we reaffirmed it. And that's really all the detail I can give you.
And Joe, do you want to add any any details? No. Mean, look, I'll I'll say something which is obvious but worth stating. It's very tough to predict where things are gonna be the rest of the year for anybody. You know, we really took our best crack at it.
We were very pleased to see how things went in the first quarter. We don't know what things currently in place will what the end results will be or, frankly, new things, which may come up as the year goes along. So we really did our best to come down where we thought it was, and you've heard it. We really don't have anything more to add at this point. Yes.
Speaker 5
So I guess based on what you saw for 1Q, which one of those things could still continue the rest of the year? So you did a good job of explaining, I think Charlie did this about talking about the 5% price increase to offset some of the impact that you see every first quarter. And that if I remember correctly from the earlier question about half of the remaining growth might have come from a small minority of patients getting their scripts renewed a little bit early in anticipation of maybe not being able to be as portable, meaning they can't get around as easily. Would you see that, for example, as something that would continue the rest of the year?
Speaker 0
What we've seen, this is, again, I'll just repeat it so you just, you know, for example, the insurance companies allowing patients to refill their prescriptions a few days earlier. Do we see that continuing? I think that's that's something that we have seen continued so far. But, you know, again, we insurance companies don't tell us their plans, and so we kind of took our best stab at how we thought it would behave over the rest of the year. But, you know, our crystal ball in that regard is really no better than anyone else's.
And that's you know, I just can't speak with any more certainty than that. And and to just add on the second point, that it's really, it's a good thing for patients to take their medicine every day. And we're really working hard to get that message out there, particularly in this time where they are at greater risk. Exactly what it's going to mean as time goes along, I don't know. But, it's a very important medical thing, and we hope that it continues.
Speaker 5
Okay. Fair enough. And then the last one for me, if I could squeeze it in, is how are you thinking about the sales force increase that you've been planning that previously you said could have impact starting in the second half of the year?
Speaker 0
Yes. Well, yes, thanks, because it seems like a distant time before thinking about that. But yes, we've actually filled out our sales force, you know, to some degree. Unfortunately, some of them had come on freshly as this began, and, we're using this time to for for them to go to even graduate school because we always teach our clinical specialists a lot, and this has really been an opportunity for them to have even more in-depth training. And we've really done that, which I give our training staff a lot of credit for.
How it's going they will now come online as things loosen up over time, and we're hoping they're going to make a substantial contribution, but time will tell.
Speaker 5
Okay. Thank you. I'm sorry about the bad quality.
Speaker 0
No problem. It's all right. We can hear you. Yes.
Speaker 2
And from Ladenburg Thalmann, we'll hear next from Matt Kaplan.
Speaker 6
Hey, guys. Congrats on a nice quarter. Just I guess a question for Charlie. Just wanted to dig in a little bit to from a legal standpoint, thanks for the update. What events or what moving parts could we see this year with respect to the Teva dispute?
Is it a situation where we just wait for the trial to occur next February or what should go on this year?
Speaker 0
Yes. So I think with respect to our sort of dispute with Teva, so both the district court lawsuit and the patent office post grant review proceeding that we have underway, I think that there's really the things to look for, frankly, are the ruling from the PTAB in November on the post grant review. I mean, we will be exchanging some legal briefs with Teva, which I think will be a matter of public record at the at the patent office. I think you can just go to the public records and look them up as they're filed. And then, you know, after that, we'll have our hearing, and then they will issue a decision.
So I think, really, the November decision from the patent office and, really, not nothing of sort of public note until the trial with Teva in February.
Speaker 6
Okay. Okay. That's helpful. Thanks for the detail. I guess a question for Joe in terms of pipeline and helping us think about the studies that you have or plan to start have ongoing plan to start in the oncology space.
I guess specifically in the pancreatic cancer, When should we expect potential results from that study as you get underway this quarter, the Phase III?
Speaker 0
With the caveat that we never really know what the pace of studies are going to be in are going to be till we begin them. I think that you actually, and this is really the true forward looking statement. So take it in that context. No more than that because we haven't even begun the study. I think that we will be at a point where we will have results on the first half of the study about a year after it begins.
Speaker 6
Okay. Very good. And then in terms of additional use of relacorilant in the oncology setting, I guess, the metastatic ovarian cancer study and also the combination with PD-one of them there, pembrolizumab. When do you think we should start to maybe more on some timelines there? When do you think we should see the results from those two studies?
Speaker 0
I heard the second one about the adrenal cancer study with pembro. It wasn't that. And what was the other study you're asking about, Matt?
Speaker 6
A metastatic ovarian cancer study. I guess that's the case. Metastatic ovarian
Speaker 0
So let me just give a little bit of editorial comment. It's actually been interesting. I think we said it in the press release, but while all studies were affected by are being affected by this pandemic, they're not 100% being affected the same. I think the oncology studies, all diseases are bad, but oncology is, in some sense, the tip of the iceberg of bad. And a lot of those patients have to end up going to the hospital regardless of their care.
So although the pace of enrollment, for instance, in the ovarian study, ovarian cancer study has diminished, it has not gone to zero, and we still expect that we will have results in the same timetable that we thought we would previously, which is first half of next year. As for the adrenal cancer study, very excited to get that started. Adrenal cancer, which we haven't talked much about, is really a rare cancer. Its incidence rate is very low, although it's very severe cancer, somewhat well understood. We're really excited to get going in that because those patients already get treated with Korlym for their Cushing syndrome.
We're really and second, do unfortunately poorly on immunotherapy currently. So there's really a good reason why a GR modulator, cortisol modulator might have the potential for success with these patients. And I can tell you in animal models, it looks pretty good. So again, as soon as that study gets started with the same caveat, very forward looking statements, study has not started yet, I think there's 20 patients will produce results in about a year.
Speaker 6
Great. Well, thanks a lot for taking the questions then. And good luck.
Speaker 0
Yes. No, good to talk to you, Matt.
Speaker 2
We'll hear next from Chris Howerton with Jefferies.
Speaker 7
Hey, great. Thanks so much for taking the questions. And I will offer my congratulations on a successful quarter as well.
Speaker 0
Thank you, Chris.
Speaker 7
Sure. So I guess maybe for to start off, Charlie, if you could help us think about the operating expenses moving forward for the rest of the year. There's obviously some R and D that may be starting, but unclear to me specifically what the trends are trajectory we should expect for SG and A with maybe a different operating style with respect to detailing core line?
Speaker 0
Sure. I think the way to think about it also starting with, you know, s g and a. I mean, the, you know, we have not, had to lay, you know, lay anyone off because of the pandemic. We've been able to, you know, administer the business pretty smoothly even at a distance, which is not too surprising since, you know, living in the Bay Area, you know, there's a working from home and so forth is a pretty well established practice. So we've been able to run the business smoothly.
And and just historically, if you look back at our s g and a, it tends to be pretty flat over the course of the year. So while, yes, there will be some less spending on travel and entertainment as the, you know, as the until pandemic restrictions ease, I wouldn't think that's gonna be a particularly material, difference. And I I I wouldn't spend too much time trying to guesstimate what that, reduction would be because I don't think it's gonna really matter. On the R and D side, while it is true that a sort of slower pace of site activation and slower patient enrollment will reduce our R and D expenses, again, or spread study costs out over, you know, a longer period of time. Again, I think the cost of actually, you know, enrolling and caring for a patient in a study is just a part of the overall expense.
And so while it will reduce our spending a little bit, I mean, r and d includes very significant expenditures on manufacturing work, CMC work, preclinical research.
Speaker 7
Alright. Then, you know, maybe I think obviously there's increased interest with respect to the oncology platforms and GI antagonism. So within your specific pipeline, maybe Joe, you could describe for us the important differences between relacorilant and exicorilant and what kind of the ideal settings might be for one or both of those?
Speaker 0
Well, that's an interesting question. So thanks for letting me address it. And to do that, I really want to give you some context, which I don't think I've really had a chance to provide in the past, which is, just to be blunt about it, a decade ago when we were thinking about creating selective cortisol modulators, really it was just, in fact, sort of the program was entitled nipipristone without progesterone antagonism because that's really all we were going for. We wanted to have something which wasn't the abortion pill because the medical side effects of the progesterone antagonism both in terminating pregnancy and all the other medical side effects. And many people had actually tried at that point to do it and it was not an easy thing to do.
But as I said mentioned before, Doctor. Hunt actually was able to figure that out and we were really on our way. But what was interesting about it was that she ultimately created four different series of compounds, all of which were cortisol modulators, none of which touch progesterone, a really very deep library. But initially, it was one compound we were looking for. The really interesting thing that happened was that when we started testing these compounds preclinically, all of them modulated cortisol, none of them touched the progesterone receptor, but they weren't identical.
Some were better at preventing weight gain. Some were better at creating insulin sensitivity. Some got into the brain. Some didn't get into the brain. And some were more potent in oncologic models than others.
And some of them were more specific in specific oncologic models than others. And so what really ended up happening because of that, and I think we understand it's another whole lecture we'll talk about offline if you're interested, but the bottom line was I think we really understand the science of the tissue selectivity that we didn't understand before. But the bottom line was that instead of creating just a single follow on compound, it created four or five different compounds, which might be specific for different disorders. While all of them might have effects, some of them had much more potent effects. And as you know, exicorilant in particular happens to be very potent in the prostate cancer model preclinically.
We thought even more potent than relacorilant, but we're also testing relacorilant through the investigator study that we've described.
Speaker 7
Got it. Okay. That's very helpful. Thank you, Joe. One, I hope this is a problem that you have to deal with, but when we think about Relequine in its mature stage, theoretically it could be applied to both Cushing's syndrome as well as oncology.
Strategically, how do you think about pricing and commercialization between those two settings?
Speaker 0
Well, I think that that's actually an easier one to bridge because I think that the cancers that we are talking about are really still orphan or small number cancers, not so different than the population that we see in Cushing's syndrome. So again, without any kind of, again, sort of specific study of them, I don't think there's really a lot of pricing difference between those two. Now that would be very different if we were introducing relacorilant for some mass market disease where primary care pricing would be would sort of rule the day. What's interesting is that miricorilant, the drug that we are developing for antipsychotic induced weight gain and NASH happens to be a very liver specific drug. It's a very organ specific drug and not a particularly good drug for Cushing's syndrome.
There are other things like, you've probably heard the term SERMs, estrogen modulators, which are very patient specific. Miracorilant is one as well. It is not particularly effective in Cushing's syndrome. It really is aimed at primary care disorders at a at at the standard primary care pricing. So not an issue for relacorilant and miricorilant is different.
Speaker 7
Okay. Okay. Alright. Well, that's very clear. Okay.
Well, thank you. Thanks so much for taking the questions, and I'll I'll have to
Speaker 0
take look. Talk to you, Chris. Yep. Thanks.
Speaker 2
We'll go next to Swayampakula Ramakanth with H. C. Wainwright.
Speaker 0
Hello, RK.
Speaker 4
Hi, how are you? Thanks.
Speaker 0
Thank you
Speaker 4
for taking my questions. Most of my questions on the commercial front of your story have been asked. So I just want to explore a few of these studies with you. On the GARDIENT, which is a study in patients suffering from adrenal adenoma, ends up causing Cushing's disease. So how big is this population?
And if the study that you're planning progresses as you expect it to, what would be the timeline for the data and also for filing because this probably is going to come post GRACE?
Speaker 1
Yeah. So again, let me just
Speaker 0
give a little background for this. It's been well understood for, I guess, as long as Cushing's syndrome has been understood that adrenal tumors can produce enough cortisol to really be symptomatic. What's been very interesting over the last twenty five years is that with the advances in imaging, there have been more patients discovered who have had adrenal tumors that were producing cortisol but not at the high enough level to produce really florid symptoms but still to produce real symptoms that were cause morbidity, symptoms related to glucose intolerance and hypertension and so forth. That's really become much better understood in the last ten years. Now what's interesting about that is many of these patients never really got treated for their hypercortisolism.
They get treated with seven different medications for seven different parts of their disease, but never with really a unifying diagnosis. And it's really been only in the last decade that that's true. And interest really of getting that right is important. Now a couple of interesting things. These patients as a group tend to not have severe cases of Cushing's syndrome, but they have real cases of Cushing's syndrome.
An interesting thing from study perspective is that this is a group of patients who can be studied in a double blind fashion since many of them at the current time are not being treated for their hypercortisolism with an anti cortisol agent at all. So from an ethical point of view, they can be randomized for cortisol modulating treatment like ours, like relacorilant or placebo, and do the sort of standard true double blind study. It's very difficult to do with people who have more profound Cushing's syndrome because they're giving somebody a placebo, frankly, is unethical and people are resistant to it because placebo simply just doesn't work in that disease state. Okay. Now to your specific question.
Yes, it's still an orphan group. I mean, we don't know exactly how many people actually have Cushing's syndrome caused by adrenal tumors. But and so the number really is unknown and we will find that out basically over time. But it's not an insignificant group of people and it certainly could be as many people as currently are diagnosed with pituitary Cushing syndrome.
Speaker 4
Okay. Fair enough. Thanks. Regarding the GRATICUDE study, which is the one in treating with the angiotensin atherosclerosis. Yes.
How similar is that study to the Phase 1b in terms of the study design? And if there are any differences, what sort of differences
Speaker 0
are you? I understand the question and thanks for the opportunity to clarify this. So the Phase I study, remember, is in normal healthy subjects. So these are people who are just volunteers, and they are given olanzapine for two weeks with either placebo or with miricorilant. And so they're not patients really at all.
It's a Phase I study. And what we're really trying to find out is whether the medication miricorilant was active in reducing the effects that you quickly see with miricorilant even in healthy people. So in that sense, a Phase I study where an important pharmacodynamic effect can be assessed. And we told you in that kind of study, miricorilant looked good, similar to what we had seen with mifepristone many years ago. Now the Phase II studies are really, quite different.
They're in patients and they are the one that we described, the GRATITUDE study, in patients who have gained weight recently within the last six months as an outlier thing from taking one of these antipsychotic medications. And the study is about reducing that weight. And those patients stay on their antipsychotic medication having gained the weight, then they're randomized to either miricorilant or placebo and the study result is a reduction in weight as well as looking at all the other metabolic variables which have already gone awry because of the use of the antipsychotic medication. So really what we've learned in the Phase one study was and it's a big deal. This is a medication which is active in an important mechanism.
Now comes the real test of whether it works in patients who are actually being affected by the disease.
Speaker 4
And just to follow-up on this, in this study you have an endpoint which is at the end of twelve weeks, what is the weight gain that is not I mean, well, they really don't get the weight gain, which is that and the 10 is twelve weeks. Is that good enough because these patients generally have weight gains depending on how long they have been on the dose and sometimes some of these patients are still titrating their dose as as the disease waxes and wanes. So I'm I'm just trying to understand all these
Speaker 0
So so so the patient group in this study are on stable antipsychotics, so their dose has now been titrated, but their weight gain is recent. So they started on the medication in a relatively recent period of time so that the weight gain that they've seen can be assessed not by just staying home during the pandemic virus, during the coronavirus, but specifically due to the medication. And that's what we're really trying to suss out, whether that weight gain, which we think is a direct effect of the antipsychotic medication, can be reduced with our drug.
Speaker 4
Okay. Thank you very much, Joe. Thanks.
Speaker 0
Nice to talk to you, RK.
Speaker 2
And from Stifel, we'll hear next from Adam Walsh.
Speaker 8
Hi. Thanks for taking my questions. This is Adam on for Adam. One quick question.
Speaker 0
Hi. In
Speaker 9
your tumor studies, have you seen
Speaker 8
any drug drug interactions between relacorilant and Abraxane from your clinical data to date?
Speaker 0
Yes. Yes. There is a drug drug interaction. When you use relacorilant, you need to use less Abraxane to get to the same plasma level of Abraxane. And it's due to the CYP3A4 interaction.
Speaker 8
So could this EDI be a potential problem for the combo therapy of these two drugs?
Speaker 0
Well, I'm not sure what in what sense you mean a problem. I mean, have to use less Abraxane. So I guess whoever's making Abraxane is going to make a little less money from it. But in terms of its actual medical effect, no, I think that, that commonly you have to look at drug drug interactions and I think that that's really a portion of it. But as I said, no, we really had no issue, I think, with the investigators in the study having to account for that effect.
Speaker 8
All right. Thank you.
Speaker 2
And we'll move to Allen Leong with BioWatch News.
Speaker 4
Hi, Joe. Hi, Charlie. Hello, Allen. Quarters. Yeah.
Speaker 6
Thank you.
Speaker 4
Hey. I want to ask, can you get a little more color on the say recent miricorilant phase one b trial at the higher dose? At the
Speaker 0
higher dose at nine hundred
Speaker 4
milligrams, would it create a significantly or consistently increased blood levels in patients? And if so, did you see any dose or blood level dependent patterns, Or is this kind of hard to tell because there was only a small incremental increase in the blood level?
Speaker 1
Yes. Well, what I think and
Speaker 0
I really wanted to hold this because I think this is going to be a nice publication when it comes out. I think the main thing to really glean from is, yes, we did see some increase in plasma level, and we were pleased to see that the same effect that we've seen at six hundred milligrams also was true at nine hundred milligrams. The other important effect, and I don't want this to get lost here, Alan, is that, you know, just as a prescribing doctor, you know, I mean, I I guess it's just, you know, sort of like as a doctor. I've never given a medication that has no side effects. You know, if you get a dose high enough where you're really getting maximum efficacy, you begin to create some side effects.
And we haven't seen really no side effects at this at this plasma level of miricorilant. So my sense of it is that we are not not yet at that level where we actually are getting maximum effect. What was really nice to see in this particular stage of the study with miricorilant was the same activity, which you can never take for granted, really appeared just as well the second time around.
Speaker 4
Just wanted to follow-up on the abnormal question and answer. Carl Leung and Christian syndrome, are you seeing some prescriptions go to primary care now, especially as lots of your patients are being treated? And if true, do you envision the adenomas and subindications elucidating primary care scripts? Could you provide any thoughts about that?
Speaker 0
Yes. We mostly do not see patients. In fact, almost all of our prescribers are endocrinologists. The only real exception to that is there are some areas of the country where primary care physicians in more remote areas are sort of the only game in town and they act as psychiatrists, endocrinologists and so forth to treat everywhere who goes along. No, the broader answer to your question is, no, we think this is a disease which really is best treated by endocrinologists.
They understand kind of all the ins and outs, cortisol goes everywhere, and we expect that, that's going to continue to be the case as we go forward.
Speaker 4
Well, thanks. And let me just add that, that was a knockout quarter. We're executed to help to set up the year. So great work.
Speaker 0
Well, no, thanks, Alan. And for everyone who doesn't know Alan, he's calling from the epicenter of viral contagion, and I'm glad that you're well.
Speaker 4
Thanks.
Speaker 0
Okay. Bye bye. Listen, I think that, that clears our question queue. So thank you to everybody. Please stay healthy, and we look forward to talking to you next quarter.
Speaker 2
And that does conclude today's conference. Again, thank you all for joining us.