CORT (2021 - Q1)

Good day, and welcome to the Corcept Therapeutics Conference Call. Today's conference is being recorded. At this time, I'd like to turn the conference over to Atabak Mokari. Please go ahead. Atabak M

Good afternoon. I'm Atabak Mokari, Corcept's Chief Financial Officer. Today, we issued three press releases, one announcing the positive outcome of our 178 patients Phase 2 trial of relacorilant in combination with nab-paclitaxel to treat patients with platinum-resistant ovarian cancer. Second, announcing markedly decreased liver fat in patients in our Phase 2 trial of miricorilant as a potential treatment for nonalcoholic steatohepatitis or NASH, and the third, providing a clinical update and announcing our financial results for the first quarter. Copies of all of these are available at corcept.com. Our complete financial results will be available when we file our Form 10-Q with the SEC. Today's call is being recorded. A replay will be available on the Investors past events tab of our website.

Thanks, Atabak. In March 2018, we sued Teva Pharmaceuticals in Federal District Court to prevent it from marketing a generic version of Korlym in violation of our patents. Originally, trial was set to start February 2, 2021. Last quarter, the court vacated that date and ordered the parties to be ready for trial by March 17th. The court then vacated that date well. We expect to complete discovery by the end of this month. No trial date or trial ready date has been set. Last month we asked the court to issue an order known as summary judgment deciding the case in our favor. Summary judgment is a procedure whereby judges can decide the case without holding a trial. In the court where we have sued Teva, a party needs the court's approval even to request summary judgment. We receive that approval in March. We filed our motion on April 8th basing it on only one of our patents, the 214 patent. Having agreed to hear our summary judgment motions, the court will consider the brief submitted by us and Teva briefing will be complete in June 9th and will then review the material facts of our dispute.

Thank you, Charlie. Before I turn to our recent clinical developments, I want to underscore a point Atabak made about our financial results. Pandemic-related public health measures and the steps both physicians and patients have taken to reduce their risk of infection have made it very hard for our business to grow. Diagnosing and treating patients with complex disease such as Cushing's syndrome requires frequent close in-person contact. Since March of last year, this level of contact was impossible. Only now and not everywhere and not fully our contact starting to move toward their pre-pandemic state. We are confident conditions will continue to improve.

Thank you. And we'll go first to Chris Howerton of Jefferies.

Great, wonderful. Thanks so much for taking the questions and congratulations on certainly the ovarian cancer data, great results there. So maybe just a -- yes, of course. So maybe just a couple of questions from me. First on that program itself with the -- maybe if you could give us just some of your initial thoughts in terms of what the Phase 3 trial might look like there. And I guess is there any opportunity whatsoever to have a discussion with the agency to say, look, these are clinically meaningful data, is there any opportunity for an accelerated approval? So I guess that's one general question or I suppose two is there. A quick one for Charlie on the legal update, just wanted to clarify with respect to the PGR that Teva can no longer challenge the validity. Is it all arguments of validity or just those that were used during the PGR proceeding? And then the final question just relates to the commercial business, obviously, I think the discussion around dose titration and getting the right new patients to the right dose certainly makes a lot of sense. And I just wanted to check in on some of the status of existing patients, if there is any kind of changes with respect to discontinuation rates. Thanks.

Hey, Chris. Thank you very much for all those questions and I'll take a breath just for a second and I'll assign these questions to various members of the executive team right here and then I'll come back at the end. So first let's take your patent question to Charlie.

Yes. Hi, Chris. Teva is barred from using in District Court any arguments it raised or could have raised before the patent office and that's actually quite a high standard. It can't just be, well, we didn't argue this because we didn't think of it at the time, but now we've thought of it. So we'd like to throw it out there. They have to have essentially a very good reason. And the classic example would be they just, they learned something from discovery in the litigation that they did not know at the time of PGR. But in our case, discovery was over before the PGR was over, so nothing. So I think that they've got this very limited path and they will not be able to chance the validity in District Court.

The question you asked, Chris, I'll let Andreas Grauer, our Chief Medical Officer answer that. Andreas will be able to answer it, which is potential design for the Phase 3 study.

Yes, thank you for the question. And obviously that is what we are working on very hard right now. We will compare the combination of relacorilant and -- of relacorilant nab-paclitaxel and I think we will look at the intermittent dose that based on the data that we have seen, it seems to be the more effective use of relacorilant in this particular tumor type. And we'll have to figure out what the best competitor to that is. Most likely I think we will pick paclitaxel. That makes a lot of sense as a competitor in a large Phase 3 trial. Alternative considerations are we might look into a dealer's choice competitor where we would give investigators the opportunity between a number of established standard and approved treatments for this condition. Size will have to be figured out dependent on the expected overall survival benefit that we'll be looking for and that is obviously also a key factor for the ongoing trial that we're still waiting for. It's not getting planning, but it will get the launch of our Phase 3 trial to see the overall survival data from this study.

And Chris, let me handle your other question, which of course is obviously intriguing one. So, as Andreas just said, we're already in really the hot up -- the serious stage of planning for a Phase 3 study and your question was, is it possible that the data would be sufficient to actually at the end of this study, the results I'll have to take that to the FDA to submit an FDA, that's just submit an NDA. And I'll give you the top line answer to that question is, it's a slim possibility. Our really our expectation is that we will have to do a Phase 3 study. But let me give you a little bit more color on that, it's highly likely that the primary endpoint for Phase 3 study and in fact for approval is overall survival. And we're very pleased obviously with the statistically significant improvement in progression-free survival, overall survival is still being determined at this point. But -- and I'll leave it at this because obviously that data will come out toward the end of the year and we want to release other data as we have it. We like what we're seeing. I -- we promise nothing at this point, but I can imagine an unusual circumstance where that data on overall survival was so strong that it could lead to a discussion with the FDA at that point. I don't want anybody to count on that. I think it's not the likely direction, but yes we are thinking about that in the same way that you. The last question you asked were commercial questions, Chris. And I'm going to push this over to Sean Maduck, who is our Chief Commercial Officer.

Hi, Chris, and thanks for the questions. Your question was a two-part one. One was around for discontinuation of existing patient base, is there -- have we seen a change there, and the answer to that is no. And your next question was around titrations, so I thought I'd spend a minute talking about to what success looks like and what we need for us to call it growth. There's really three key factors that were affected by the pandemic. One is this core sensibility to educate doctors on hypercortisolism and Korlym. Two would be a doctor's ability to actually see their patients multiple times for an extensive work-up prior to a diagnosis. And then the last one being once a patient actually starts Korlym, the frequent follow-up that's required with their physician to monitor progress and to guide appropriate titration. And with new patients that have come on during the pandemic that's something that's really been a challenge. News patients have either not titrated or titrating at a much more slow rate to get to the optimal dose and again directly related to durability to see their position with the appropriate frequency or even their access to labs or the willingness to go and get labs that they may need to do so. So in time as things open back up, we believe that titration will catch up, but for the time being, in aggregate, this has decreased our average overall dose.

Okay, OK. Well that -- first of all, thanks for shimmering me on my questions and I'll hop back in the queue. Thanks again.

Thank you, Chris.

We'll go next to Arthur He of H.C. Wainwright.

Hello, Arthur.

Hey, good afternoon, gentlemen. Congratulations on the ovarian data. And I just want to -- so at which venue could we expect the overall survival data for the informative study?

I'm sorry, I didn't quite hear the question, which submitted.

Where we are going to...

Which venue we will -- yes, at this point in time, the answer is first, overall survival is likely to take some amount of months from here. We will get other data before we actually get the final overall survival data. And all I can tell you is that we will present this to conferences as quickly as we can just depending on conference deadlines. So we're really examining that as we go forward here, but whatever we receive in any kind of bolus of things, we will send out to a conference and present it there. I can't say with certainty which ones yet.

Okay, that's great, thanks for that. And my second question is regarding to the NASH study. So I just wondering beside the trends in ALT and AST elevation, is there any other safety signal observed in these four patients?

I'm going to give you get back to Andreas Grauer.

Yes, no, that was the safety signal that we did observe and which obviously -- that was what we had seen first, right. That's why we stopped dosing and halted the trial. The benefit that we observed that came after, because we did a thorough investigation of all aspects of what happened to these patients. And quite frankly, we were surprised to see such an improvement in liver fat so quickly and we shared that with some of our advisors and they were surprised. They had never seen something like -- quite like that before, which again encouraged us to say what we really want to try to figure out how we can find a sweet spot and find the dose or schedule of giving this drug in a way that is both effective and safe.

But, Arthur, the short answer to your question is, we did not see anything besides elevated liver function tests at the time that we halt the dosing.

That's great. And just follow up on the efficacy similar-wise, the fat reduction is really impressive. I just curious, have you guys manage that or just take a look at the fibrosis for these patients?

Yes, no. So they -- first of all, this was a non-invasive. So this was a -- was not a biopsy trial. So we didn't look at fibrosis in this particular trial. We also did not repeat, like for example of a fibroscan measurement. The MRI data is really the only thing that we have. Seeing a change in fibrosis within four weeks, which was the treatment duration for most of these patients would be absolutely unexpected but we wouldn't know, we didn't know.

But just, Arthur, for comparison, in almost all of the studies, the issue, this threshold number is 30% in terms of fat reduction is presumed to -- and actually there's studies which show really correlates with reduction in NASH, in fibrosis and NASH. And that's how we incent our 30% target and that's how like others did the same thing. So I'm just going to reiterate what Andreas said, it was really extraordinary to see after such a short period of time that these patients to have much greater in some cases reduction back then 30% and so it's really a potent medication. Now we really have to figure out how to harness it.

Okay, that's great. Thank you very much for taking my question.

And we'll move to our next question from Tazeen Ahmad of Bank of America.

Hi, good afternoon, guys. Thanks for taking my question and congrats as well from me on the ovarian data. To go back to...

Thank you, Tazeen.

If you go back to Korlym for one second, you've talked in-depth about all of the ways in which COVID has impacted sales and that is consistent with what we are hearing from other companies across multiple indications. I am curious to know if you're getting any feedback from your sales force on if they're seeing any kinds of competitive risk from the retro drug that recently launched and is just feedback from a non-quantitative aspect we will be curious to hear your thoughts on that. And then I have a couple of follow-ups.

Sure, Tazeen. I'm going to pass you back to Sean who really runs all of the Korlym business.

Yes, thanks, Tazeen, for the question. Short answer is no, we're not seeing an impact on our business from Isturisa of specifically what you're referencing, not seeing virtually any impact on our existing base and we continue to add patients to our Korlym at our expected rate. I just want to remind everybody on the call that Isturisa is actually approved for Cushing's disease which is a subset of Cushing's syndrome and Korlym of course is approved for broader symptom, which encompasses all etiology businesses.

Okay. And then while we're on the topic, you had mentioned some factors to highlight including getting doctors educated about Korlym. Now for a drug that has been on the market, it's a relatively mature drug, what percent of the doctor population, targeted doctor population do you think is still yet to be fully educated on the benefits of the drug?

Yes. So I mean we have -- we reach out to as best we can sort of all endocrinologists within the country. I mean, ultimately, we believe that every one of them could potentially have a patient with Cushing syndrome. We target list of 1,500 to 2,000 with greater frequency, but there are many that have yet to prescribe. So there is real opportunity within the existing endoncronology base to write their first prescription approval.

Yes. And what I'd add to that, Tazeen is, as Sean said, we focused on about 1,500 to 2,000 of about 7,000 or 8,000. But as -- I know this that most endocrinologists these days are diabetologists, they not really looking in other things like Cushing's syndrome. But we now actually think that in fact as a result of peer-reviewed publications and more looking at this is that some of those diabetologists would not previously taken Cushing's syndrome is something that they really want to take a look at are starting to do that. And that would -- that's what makes us hopeful that we can reach all of the patients who have Cushing's syndrome as opposed to the fraction we've reached so far.

Okay, cool. Thank you. And then maybe one question on the RELIANT study if I could. You are going to have this interim read of 40 patients. What is the bar of efficacy that we should be looking for? And could you potentially file after that interim read?

I am going to pass you to Andreas in a second, but I guess could is a pretty broad term. It is definitely not our expectation that that would be possible to file after just these 40 patients. And the bar, I think as we've mentioned in previous calls, what you compare it to is 0% response rate and something like above 20% it's something that everyone would say, well, that must be your medicine. If it's 10% to 20%, you have to think about there is something going on. And if it's below 10%, it's hard to know whether that's different than what you had ordinarily expect. And we're very interested in seeing now -- if we were sort of pick the Great White Well of cancers, I mean pancreatic cancer is terrible and metastatic cancer pancreatic cancer is really terrible. So we'll just have to wait and see where that is.

Yes, I asked that already because of the undermet need. Okay, thank you.

No, no. Right. And then of course is the other side of is the bar is lower, of course, because of that.

Will go next to Matt Kaplan of Ladenburg Thalmann.

Hi, good afternoon. Thanks for taking the questions. And yes, and my congrats to the ovarian cancer top line results here. I just wanted to dig in a little bit to the differences that you're seeing in the dosing regimen and what to make of those? I guess maybe how many patients in the hundred milligram daily dose were up titrated 150 milligrams in the study?

Matt, I'm giving your question over to Andreas.

Yes. So overall 30% of the patients in the hundred milligram dose for up titrated, not all of them to 150, about two-thirds of the one that were up titrated, were up titrated to 150. So that, those are the exact data.

Yes. The other thing and Matt, maybe if this is a longer answer sort of take it offline. There is a theory as to why intermittent dosing actually might be effective in terms of the glucocorticoid receptor genes that that are sort of needed at that zone and of course treatment is always the combination of efficacy and potential for adverse events. And so there is a real theory behind intermittent dosing. It wasn't just a random event. And it was interesting to see that, in fact it was both superior at this point to every day therapy at a lower dose and then it was superior to the background therapy with statistics.

And then in this study, what's your sense in terms of the overall response rate that you're seeing. And was there a differentiated overall response rate and the choosing arms?

Right. So I don't want to give too much information because from one of our early questions, we don't want to spoil our chance to present this at important conferences and so really want a limit as to what we materially have to talk about, but I can give you a general answer to that question. Which is that the overall response rate -- and I say this without specific numbers was relatively the same among the crews, but what was really different was the duration of response to those who responded and that's where the separates.

Okay, Thanks. And just shifting gears to take GRACE, the GRACE study for Cushing syndrome. Well, what's your sense in terms of enrollment there, is it starting to accelerate now, as we're turning the corner in the pandemic here hopefully way, at least in some parts of the world? Are you seeing an acceleration in enrollment?

I think we -- enrollment starts to pick up again and the winter was pretty disappointing for us, but now in the spring, we're seeing signs of progress, both in the U.S. and in Europe and Europe obviously somewhat slower than in the U.S. So we're positive and hopeful that we can deliver what we told you we are planning to deliver.

Yes. And just to underscore that just again, I know, this Matt coz' you follow us through for a long time, but those, you don't. This is to some degree a Euro-centric study. We expect in the end, our overall enrollments should probably be -- I don't know 70% European that's what it was in this Phase 2 study. So to a bit more of a wildcard. But the general answer as you know is things are getting better. And we're at this point completely hopeful that we will keep our current timeline.

Okay, great. And then last question, in terms of relacorilant, the increase in liver enzymes, liver function tests that you're seeing in the NASH study. Can you talk about what you're seeing kind of across the board in general with relacorilant and other indication other patient populations? Are you seeing any indications of liver enzyme increases?

Hey, Matt I just want To clarify one thing, the drug in the NASH study

Oh, that's miricorilant, yes.

Miricorilant, relacorilant doesn't -- has never produced any of these that type particular issue. But I'll leave you to Andreas here to answer the question related to miricorilant.

Yes, so for miricorilant again we've seen this elevation of liver enzymes in the NASH study. And interestingly, we've seen it in the patients that have shown the massive reduction in liver fat. So our best assumption at the moment is that those two events are related and maybe we're simply resolving the liver fat too much too quickly, and we'll have to slow down the effect in order to make this palatable for the liver as a long-term benefit. In our antipsychotic induced weight gain studies where we are using the same doses that we have initially used in NASH, we are not seeing these changes and therefore there seems to be a true influence of the underlying disease on the side effect profile that we're observing.

Thanks, Matt.

Thanks, thanks.

And we'll hear next from Alan Leong of BioWatch News.

Hi, there. Congratulations.

Thank you, Alan.

Going to the NASH trial, when you had this amount of fat reduction. Did you see a global in the body? I know it was only one month but are you seeing overall weight reductions? And if you were able to even give any inferences on fat reductions and the other organs?

So Alan is this a personal question? Yes. Yes, in a month. Andres can tell you if he even looked at that though, but we were not expecting general weight loss. Do you have an answer to that?

Well especially in our inflow for patients right, where we wouldn't have any

But it's an interesting question. And we will look at that out.

Yes, I'm trying to go on the side door antipsychotic weight gain. Let's take antipsychotic weight gain and any you can service any of them that signals were slight, is the current thinking of that the consumption of antipsychotic puts a break on how much fatty acid gets your waist?

Yes -- I hope everyone heard that because it sort of an intriguing idea. So I'm just going to settle out. And then I'll give you my opinion that somehow antipsychotic medications are protective against this, probably not as probably not the case. I think it is coincidental, but I want to underscore what Andreas said even a bit more than I might have thought, I have learned about this that NASH is really a different disease, in the sense that the patients with NASH hepatitis is its own real problem, you already have people who have inflammation and so perhaps that's what makes the diseases really different. And we're still studying about that because Andreas is really giving you kind of more global response to it. As I said, I don't think it's the anti-psychotic medication. I think it's just the underlying group of patients are not as identical as one might have thought.

That's helpful. Last question, on ovarian cancer, anything stick out for the responders, for example was the number of prior treatments show any separation of the curves? Or whether they had been on Avastin before or not?

As you always do you push me to the end of the map to be released. Okay.

I understand. This is a wonderful time. Thanks for having me ask the questions. Looking forward to what's happening in the next, over the next several months. Thank you.

That's very nice of you. Thank you, Alan. And so with that we have used an hour of your time. Thank you, very excited about what we've seen today. As I mentioned before, I really do think that this is the most important results we've had since the pivotal trial in Korlym that was eight years ago. So this is a big day for us and we're very glad to answer any more questions offline, very glad to update you as the year goes along. Thank you.

And so, ladies and gentlemen, that does conclude this call. We would like to thank you for your participation. You may now disconnect.