Corcept Therapeutics Incorporated
Q2 2017 Earnings Call Transcript

Published: 2 Aug 2017

[Operator:]

Welcome to the Corcept Therapeutics Conference. My name is Brandon and I will be your operator for today. At this time, all participants are in a listen-only mode. [Operator Instructions] Please note this conference is being recorded. And I will now turn it over to Charlie Robb. Charlie, you may begin.

[Charlie Robb:]

Good afternoon. My name is Charlie Robb. I am Corcept’s Chief Financial Officer. With me today is Dr. Joseph Belanoff, our Chief Executive Officer. Thank you all for participating in the call. Earlier today, we issued a news release giving our second quarter financial results, a corporate update and an upward revision of our 2017 revenue guidance. For a copy of this release, go to corcept.com and click on the Investors tab. Complete financial results will be available when we file our Form 10-Q. Today’s call is being recorded. A replay will be available through August 14 at 1888-843-7419 from the United States and 1630-652-3042 internationally. The pass code will be 45276605. Any statements made during this call that are not statements of historical fact are forward-looking statements subject to known and unknown risks and uncertainties that might cause actual results to differ materially from those expressed or implied by such statements. Forward-looking statements include statements regarding our financial results including our revenue guidance and expense estimates for 2017 and beyond, the anticipated contributions of our sales organization, the cost, timing and results of preclinical and clinical trials, including the trials of CORT125134 in Cushing’s syndrome and solid tumor cancers; CORT125281 in castration resistant prostate cancer; and CORT118335 for fatty liver disease and other disorders; the utility of our FKBP5 gene expression assay; the protections afforded by Korlym’s orphan drug designation for Cushing’s syndrome and our other intellectual property rights, including the composition of matter patents covering our selective cortisol modulators and patents concerning the use of cortisol modulators to treat patients with Cushing’s syndrome, triple-negative breast cancer, castration-resistant prostate cancer and other indications. These and other risks are set forth in our SEC filings, which are available at our website or from the SEC's website. We disclaim any intention or duty to update any forward-looking statements made during this call. Now, I will review our financial results. Corcept’s revenue in the second quarter was $35.6 million compared to $19.7 million in the second quarter of last year, an 80% increase. Compared to the last quarter, revenue grew 29% due entirely to increased Korlym’s sales volume as there was no price increase in the second quarter. Our fully diluted second quarter GAAP net income was $0.10 per share compared to $0.01 per share in the second quarter of 2016. Excluding the non-cash expense of stock-based compensation and implied interest on our royalty financing debt, our fully diluted non-GAAP net income for the second quarter was $0.13 per share, up from $0.03 per share in the second quarter last year. We expect our revenue growth to continue. Based on our strong commercial performance in the second quarter and our expectations for the rest of this year, we have increased our 2017 revenue guidance by $20 million to between $145 million and $155 million. Our cash and investments at quarter and increased to $67.7 million from $57.3 million at March 31, 2017. This increase is after payment of $5.7 million under our capped royalty financing. As some of you know, our royalty transaction was a source of flexible non-dilutive financing. Shortly after the launch of Korlym in 2012, we borrowed $30 million. In return, we agreed to repay $45 million, with our payments to equal, but not exceed 20% of our quarterly revenue. In July 2017, we made our final payment under this arrangement of $4.6 million. No further payments are due. Our obligations under this financing are now completely extinguished. As we have said in past calls, we believe revenue from our Cushing’s syndrome business together with our cash on hand will be sufficient to fund our planned activities which include fully funding our Cushing’s syndrome business conducting Phase 2 and Phase 3 trials of our proprietary selective cortisol modulator 125134 in both Cushing’s syndrome and solid tumor cancers conducting the Phase 1 and Phase 2 trials of CORT125281 for castration-resistant prostate cancer and the Phase 1 trial of CORT118335 and advancing into the clinic additional next-generation cortisol modulators. I will now turn the call over to Dr. Belanoff. Joe?

[Joseph Belanoff:]

Thank you, Charlie and thank you everyone on the phone for joining us. Corcept has never had a better quarter. Our revenue grew to $35.6 million, an increase of 80% from the second quarter of 2016 and 29% more than the first quarter of this year. We generated $12.6 million in GAAP net income. Excluding non-cash expenses, our non-GAAP net income was $16 million. Our cash and investments increased by $10.4 million even as our clinical development programs progressed and we paid down our royalty debt, which in July we retired completely. We have raised our 2017 revenue guidance to between $145 million and $155 million, an increase of $20 million. And we anticipate significant revenue growth in 2018, 2019 and beyond. At a superficial level, it’s easy to explain how we achieved these results. More doctors are writing the first prescriptions for Korlym and when the CLL, the medicine works writing second, third and fourth prescriptions, but I wanted to discuss the trends in medical practice that are driving this change in physician behavior. First and foremost, Korlym is effective. For almost all patients, Korlym works very well. In our pivotal trial, 87% of the patients as adjudicated by independent outside experts experienced significant clinical improvement. The positive outcomes of patients who have received Korlym since its commercial launch have been consistent with these clinical findings. Cortisol is the stress hormone. It’s secreted by the adrenal glands with a rhythm that is essential for health. It peaks just after we wake up and then falls through the day rising again just before dawn. Cushing’s syndrome is caused by a tumor that produces either excess cortisol, or ACTH, a hormone that causes the body to produce cortisol. Cortisol in patients with Cushing’s syndrome does not follow a healthy diurnal rhythm. Instead, these patients have an elevated flat cortisol curve. This is why one symptom of hypercortisolism is insomnia. Other symptoms include impaired glucose tolerance, high blood pressure, central obesity, increased fat around the neck, thinning arms and legs, weak muscles and severe fatigue. Irritability, anxiety, cognitive disturbance and depression are common. Korlym works by competing with cortisol at a glucocorticoid receptor, GR, for short. The receptor to which cortisol binds when levels are elevated. By binding to GR, Korlym turns down cortisol activity causing the symptoms suffered by Cushing’s syndrome patients to abate. Treating hypercortisolism by modulating cortisol’s activity provides important benefits. It helps to restore cortisol’s healthy diurnal rhythm. It directs treatment to the true cause of the disorder, excess cortisol activity at GR. By contrast, drugs such as ketoconazole, commonly used generic antifungal agent that lowers cortisol levels by inhibiting cortisol production, actually interferes with cortisol’s diurnal rhythm. Metaphorically drugs like this simply lower the water in the pool with no regard for cortisol’s natural rhythm. A reduction in the amount of cortisol that spills over into the urine in 24 hours, our test physicians have traditionally used to determine whether a patient with hypercortisolism has improved does not at all mean that a patient has a normal cortisol rhythm. Increasing number of physicians are realizing that using Korlym to modulate cortisol activity is often the optimum treatment for hypercortisolism. When Korlym was launched most patients received Korlym after medications intended to reduce their cortisol levels such as ketoconazole had failed. We still enroll many such patients. It is however increasingly common for physicians, particularly physicians who have used Korylm once to prescribe Korylm straightaway. Second, hypercortisolism is a serious disorder and let them [indiscernible] previously thought, physicians have become more sensitive to the dangers of hypercortisolism which is significantly more common than just the florid cases that until recently defined most doctors understanding of the disorder. Physicians increasingly understand that less severe cortisol excess, a condition until recently many doctors considered not worth treating produces detrimental symptoms. Physicians have begun screening patients who exhibit one or more symptoms of hypercortisolism such as glucose intolerance or hypertension, but who have not responded to conventional therapies for those conditions. They are discovering many patients with clearly excessive cortisol activity who may benefit from Korlym. As I mentioned a moment ago, these patients often have normal 24-hour urine – collections of urinary cortisol, a very blunt test. This cortisol activity fortunately is readily apparent with more sophisticated testing. This trend has support in the peer-reviewed literature. As I did on our last call, I referred those interested two important papers published by Dr. Diana Lopez in the Annals of Internal Medicine in August 2016. And two, one by Dr. Valentina Morelli in the Journal of Clinical Endocrinology & Metabolism in March 2014. Both researchers found significantly increased morbidity and mortality in patients with less severely excessive cortisol activity. Third, surgery cures only about half of all patients with Cushing’s syndrome. As it’s always been the case, the recommended primary treatment for a patient with Cushing’s syndrome is surgery. Finding and removing the tumor responsible for patient’s cortisol excess can produce a complete cure. Unfortunately, most cortisol or ACTH producing tumors are difficult to identify and harder to remove. An article recently published in Endocrine Practice by Dr. Eliza Geer of Mount Sinai Medical Center found that surgery, even repeated surgery attempting to resect the same ACTH producing tumor succeeds less than half the time, much less often than the 80% and higher rates claimed by some neurosurgeons and endocrinologists at leading surgical centers including her own. I stress this point, because inflated estimates of surgeries efficacy have caused many physicians and some investors to underestimate the number of patients who are candidates for Korlym. Four, Corcept’s commercial efforts target the physicians who treat most patients with hypercortisolism, community endocrinologists. When we launched Korlym, we incorrectly assumed as many physicians and investors still do that most patients with Cushing’s syndrome are cared for by physicians at leading research centers, some of whom claimed to treat 70 or more patients. Our experiences taught us that no doctor treats that many patients with Cushing’s syndrome on an ongoing basis, certainly not endocrinologists at research hospitals, no matter how expert. It is more common for these doctors to consult with the patient, refer the patient to surgery and then often incorrectly assuming that surgery succeeded lose the patient to follow-up. We are performing well because our experienced, highly skilled clinical specialists spend their time where most patients really receive their care of surgery fails in the community setting. We believe our proprietary CORT125134 now and its Phase 2 trial will greatly expand the market for cortisol modulators as a treatment for hypercortisolism. As many of you know, CORT125134 was safe and well tolerated in its Phase 1 trial where demonstrated in healthy subjects the key attribute of an effective treatment for hypercortisolism. The ability to modulate cortisol’s activity at GR by demonstrating that reverse the effects of prednisone a synthetic analog of cortisol. CORT125134 is a selective cortisol modulator that we believe will offer close benefits, but without some of Korlym’s drawbacks. Korlym modulates activity at the progesterone receptor abbreviated as PR as well as PR. In many women Korlym’s affinity for PR causes endometrial thickening and irregular vaginal bleeding, manageable side effects that patients and physicians would nonetheless strongly prefer to book – to avoid. Even more important, affinity for PR makes the active ingredient in Korlym the abortion pill, a drug that effectively modulates cortisol, but has no affinity for PR and none of the abortion pills medical and political toxicity could be distributed much more broadly than Korlym both in the United States and abroad and should be readily accepted by the physicians who currently do not prescribe Korlym. CORT12513’s Phase 2 trial is an open label single arm study that will enroll up to 30 patients and sites in the United States and Europe. We expect results in the first quarter of next year and begun planning our end of Phase 2 FDA meeting and Phase 3 study. We are also developing a plea of validated assay of gene expression that we believe will be a powerful tool for physicians diagnosing and treating patients with hypercortisolism. As I said earlier, Korlym works by reducing cortisol’s activity which is obvious to doctors as they see their patient symptoms improve. However because GR modulators like Korlym or CORT125134 do not reduce cortisol levels, the patients improving health is not accompanied by a decrease in cortisol levels. Today the test most commonly used to diagnose hypercortisolism and gauge the efficacy of treatment. Measure the amount of excess cortisol in the patient’s urine or saliva, crude proxies for excess cortisol activity that often generate inconsistent and sometimes unreliable results. Even a more sophisticated tool, the dexamethasone suppression test is not sensitive enough to always identify patients suffering from excess cortisol activity. Our hypothesis, which we have validated in healthy subjects and are now studying in patients is that expression of the gene FKBP5 is excessive in hypercortisolism and normalizes as the patient symptoms abate. If we are correct it is hard to overstate the medical advance such an assay will represent a sensitively and accurately measuring the actual cause of every Cushing’s syndrome symptom, excess cortisol activity at GR, our assay should help physicians identify patients with hypercortisolism and arrive at an optimal treatment regimen. We will achieve clear validation of our assay this quarter. Our oncology program will broaden significantly this quarter too. As many as you know in cancers whose tumors express GR such as triple negative breast, ovarian and pancreatic cancer cortisol stimulates genes that retard a apoptosis the programmed cell death as many chemotherapies are intended to provoke. Preventing the stimulation of these apoptosis suppressing genes by adding a cortisol modulator to a chemotherapy regimen should allow that regimen to achieve its optimal effect. Cortisol modulation may also help the immune system to fight cancer. There is much interest in oncologic therapies that stimulate the body’s immune system to fight the disease. Cortisol suppresses the immune system, the physiologic, well and psychological stress of cancer and its treatment raise cortisol activity above normal levels creating even greater immunosuppression. Cortisol modulators counter this effect allowing the immune system to act more potently. Cortisol modulation may also help treat castration resistant prostate cancer which is a particularly series form of the disease because androgens stimulate prostate tumor growth androgen deprivation also known as chemical castration is a common treatment for prostate cancer. Investigators at the University of Chicago have shown and Charles Sawyers group at Sloan-Kettering has confirmed that very early in treatment with the androgen receptor, antagonist enzalutamide colonies of tumor cells emerging which cortisol through it’s stimulation at GR is the primary growth factor. Combining a cortisol modulator with an androgen modulator such as enzalutamide the Astellas Medivation drug XTANDI from the outset of treatment may block this cancer escape route. University of Chicago investigators are leading an 84-patient controlled multi-center Phase 2 study of Korlym combined with XTANDI to treat patients with metastatic castration-resistant prostate cancer. The Department of Defense and the prostate cancer foundation are funding the trial. Astellas is providing XTANDI. We are providing Korlym and possess the intellectual property for the use of this combination of medications. This quarter, we will advance our proprietary selective coritsol modulator, CORT125281 as a treatment for castration-resistant prostate cancer. Preclinical results have been extremely promising. In September, we will begin a Phase 1 trial in healthy subjects to be followed in November with a trial combining the compound with XTANDI to treat patients with metastatic disease. Following the promising results of our Phase 1/2 trial of Korlym in combination with eribulin to treat patients with triple-negative breast cancer and their own extensive preclinical and clinical studies, investigators of the University of Chicago with funding from Celgene are enrolling patients in a 64-patient double-blind placebo-controlled multi-center Phase 2 trial of Korlym combined with nab-paclitaxel, Celgene’s drug ABRAXANE to treat this disease. We are providing Korlym and again possessed the intellectual property for the use of this combination of medications. We are also advancing CORT125134 to treat patients with a range of solid tumor cancers. Our Phase 1/2 trial is in its dose finding phase with expansion cohorts to open by year end. Pancreatic triple-negative breast and ovarian cancer are likely targets. I am also pleased to announce that we will begin the Phase 1 trial on one of our promising proprietary selective cortisol modulators CORT118335 this month. This compound appears to be particularly potent in the liver. In animal models, it prevents and reverses fatty liver disease and liver fibrosis. It also works well in animal models of antipsychotic induced weight gain. These disorders afflict tens of millions of people in the United States. If CORT118335’s preclinical results translate to humans, this development would constitute a major medical advance. If CORT118335’s Phase 1 trial outcome is positive, we will immediately start one or more Phase 2 trials. To sum up, Corcept had a great second quarter. Our revenues increased 80%. We raised our 2017 revenue guidance for the third time this year to between $145 million and $155 million. We generated a GAAP profit for the quarter of $12.6 million compared to $1 million in the same period last year. Our cash increased by $10.4 million in the quarter even as we advanced our clinical program and paid down our royalty debt retiring it completely in July. We continue to expect significant growth in the years ahead. We will have results of our Phase 2 trial of CORT125134 in Cushing’s syndrome a compound we believe will offer real advantages over Korlym in the first quarter next year. We have begun preparing for our end of Phase 2 meeting with the FDA and our Phase 3 trial. This quarter we will achieve clear validation of our important FKBP5 gene expression assay. Our programs to develop cortisol modulators to treat patients with castration-resistant prostate cancer continue. University of Chicago investigators are actively enrolling patients in their Phase 2 trial pairing Korlym with XTANDI. This quarter, we will start the clinical program of a proprietary compound CORT125281 to treat patients with this disease. With financial support from Celgene, University of Chicago investigators are enrolling patients in a definitive Phase 2 trial of Korlym combined with ABRAXANE to treat patients with triple-negative breast cancer. We expect to open expansion cohorts in our trial of CORT125134 to treat patients with solid tumor cancers by year end. Finally, one of our most promising compounds, CORT118335 will enter Phase 1 this month. If results are positive, we will advance it to Phase 2 for the treatment of metabolic disorders potentially including NASH and antipsychotic-induced weight gain. I will stop now to answer questions.

[Operator:]

Thank you. [Operator Instructions] And from Ladenburg Thalmann we have Christopher James. Please go ahead.

[ChristopherJames:]

Hi, Joe and Charlie. First congrats on the excellent execution this quarter. The increase is really impressive. Regarding mifepristone, could you help us maybe understand the drivers behind the surge in revenue? Is this a function of your sales force perhaps better education of endocrinologist and then maybe can you comment on the use that you are seeing in outside of Cushing’s patients, particularly in severe diabetic patients? Thanks.

[Joseph Belanoff:]

Yes, I am going to turn over the question – the bulk of your questions to Sean Maduck who runs our whole commercial area and our Korlym franchise. But I can answer your last question first we basically see very, very, very little use in anything except for Cushing’s syndrome. Sean, please go ahead.

[Sean Maduck:]

Thanks, Joe and thanks Chris for the question. I mean as Joe stated in the opening remarks, this really was organic growth driven by increased Korlym volume. We have 35 highly trained, highly skilled clinical sales specialists in the field that really are reaching more physicians on a daily basis. Because of that, there has been an increased testing as Joe referenced, which has really led to more patients being prescribed Korlym. And Korlym is a efficacious product and when physicians see the benefit that the drug has for their patients, they end up looking for more patients within their practice that could benefit. So ultimately, our first time prescribers become multi prescribers. Again ultimately, organic growth really we are seeing prescriptions from all over the country from all regions and for all patients across all geologies of Cushing’s syndrome. It really was a strong Q2 on a lot of different fronts and we don’t expect that growth to level off.

[ChristopherJames:]

Great. And then secondly, the CLIA-validated test, how do you plan to use this test commercially with either Korlym or second gen 125134?

[Joseph Belanoff:]

Chris, at this point, just the audience really understands entirely, we really are stood still figuring this out. I mean this is a very, very interesting area of science. As I said before, I think this is really an important understanding, pretty up to now, the measurements for cortisol have really had to do with the level of cortisol and bodily fluids, who cares what’s in your urine, what really matters is what’s going on at the cellular level where activity is really taking place. And our real hope for this assay is we can get a much closer measure of what’s actually going on which causes the symptoms of this really bad disease. Now, where we are really is still roughly a few steps beyond the beginning. We have really been able to validate the concept of normal people who are given prednisone and we are now in the process of testing people who actually have Cushing’s syndrome both before and after treatment. So we will see where that goes. Ultimately, where that goes commercially, we really can’t say at this point. We really are still figuring it out. It’s important to see what the science is and so forth. But I think at this point, our main focus is really getting the science right, because we think that if this really does come to pass, it’s not only breakthrough the Cushing’s syndrome, but provide some insight into how to provide a better way of diagnosis and treatment for all other endocrinologic diseases even things that Corcept itself is not working on.

[ChristopherJames:]

Got it. And then and finally, you pushed out the data for second gen to the first quarter, was this more about patient enrollment, what sort of was the logic behind that?

[Joseph Belanoff:]

I’d like to introduce the group, I think some of you know him, but maybe not all to Dr. Bob Fishman, who is our Chief Medical Officer and runs all of our clinical programs. Bob?

[Bob Fishman:]

Hi, Chris, Bob Fishman here. Thanks a lot for the questions. So yes, it is about enrollment and these are all academic sites and it took longer than expected for sites to open and get up and running and that was particularly the case in Europe. And we meet face-to-face with our investigators frequently and there are two key points that come as a result of these meetings. One is that we have a good sense of site productivity and the other is that these meetings have helped our recruiting efforts to gain traction. And in addition a number of additional sites that expressed interest in joining the study and we are adding at least 4 in the U.S.

[ChristopherJames:]

Got it. Thanks for the questions, guys and congrats again really, really impressive quarter.

[Joseph Belanoff:]

Thank you.

[Operator:]

From Bank of America we have Tazeen Ahmad. Please go ahead.

[Tazeen Ahmad:]

Hi, thanks for taking my question. So, thanks first of all for all that color on how you think the market is evolving. I just wanted to get more clarification. So are you able to potentially let us know how many docs are prescribing Korlym now, if you can’t give us the number itself, can you give us the percent change at least versus let’s say what you were seeing this time last year, in terms of your growth you definitely said it’s volume related but how much of that potentially could be from new patient growth versus patients that are already on Korlym and potentially titrating to a higher dose? And then I have a couple of follow-ups.

[Joseph Belanoff:]

Well, the answers that we have not provided specific number of doctors who have prescribed the medication as you know we think we have said in previous calls we targeted about 1,500 doctors. And certainly a greater percentage from last year of them are prescribing, but we by no means have all of them prescribe, so there are many doctors to we still expect as they begin to screen their patients more carefully that they will become prescribers in the future as well. And as for your second question, virtually all of the growth is due to new patients, almost none of it is due to titration.

[Tazeen Ahmad:]

Okay. I guess intra-quarter is there a way for us to really kind of be more aware of what your trends are, because it is very difficult to tackle a lot of these things and as you said for example, you have even been on a learning curve for some of these items one of which you said was that surgery rates aren’t as successful as we might have thought they were, I mean how are you coming to the conclusion or what do you think is the actual success rate of surgeries?

[Joseph Belanoff:]

Well, I think we have said actually from the time the Korlym was launched that we thought this would be – surgery success rate was about 50%. And I think the interesting thing is that for reasons that weren’t always clear to us that was what was believed out in the world. And I think some of it was publication bias doctors, the best doctors provided their best results and the weaker doctors didn’t publish them. But I thought what was very interesting is that as we have been out there, for the last 5 years, our original concept that was about half the patients has played out, we have never really felt like it was any different as we actually saw patients. And the interesting thing is as I said there is a very recent publication with all academic investigators which basically says, yes it is about 50% and that adds to the literature which previously show that it was about 50%, so I think there was just a real disconnect between what people were saying and what was really going on and it’s not anything new.

[Tazeen Ahmad:]

Okay. So in terms of how the differences you are seeing and uses of KOLs versus community docs, so could it be the case that community docs because they might have to treat a larger volume of patients might, when they have a patient put on Korlym immediately, put them on the higher dose, rather than titrate them up over longer periods of time, do you have any kind of feedback on that?

[Joseph Belanoff:]

Yes, I do, that’s definitely not the case. The community physician started the same dose and we actually do track that. There is – their titration curve is actually very similar to anybody else is.

[Tazeen Ahmad:]

Okay, alright. Thanks for the time.

[Joseph Belanoff:]

Sure. Thank you, Tazeen.

[Charlie Robb:]

Yes. Thanks.

[Operator:]

From Piper Jaffray, we have Charles Duncan. Please go ahead.

[Charles Duncan:]

Hi guys. First of all, thanks for taking my question and congratulations on a nice commercial quarter, also thanks for the reminder of some of the nuance differences between the cortisol modulator and synthesis inhibitor earlier in the call. I did have a couple of questions, one on Korlym 134 second generation compound, regarding Korlym, some of the questions were already asked, but I am – it looks like nice numbers, I am wondering what are some of the assumptions behind your guidance range and specifically some of the goals behind call at the lower end of the range versus the higher end of the range, what needs to happen for a good – super good performance?

[Charlie Robb:]

I am Charles, I think I just want to emphasize an important point that both Charlie and Sean made. I mean I think the language you use is the growth is entirely organic it’s just more patients. And I have said before that this is a group of physicians who unlike other physicians in other fields, oncologists as an example tend to be a little bit more cautious before they change their treatment practices, but we are actually seeing and we have seen it all year is that in some sense when herd starts to move, it really does begin to move. And our guidance to you is just that it’s guidance it has a range, because it’s unclear to us exactly where the year is going to end up. But what I can tell you and I will just use the same phrase that Sean did, it’s just not leveling off, I mean we continue to see more physicians and more – and physicians who are satisfied to write more prescriptions. And it’s a little bit hard at this point in the curve to know exactly kind of where that is and so really in some sense the difference between the low end of our range and the high end of our range really does express our uncertainty about how positive the outcome is going to be over the course of this year. But if current trend is really indicative we are just getting going.

[Charles Duncan:]

And then do you anticipate any additional price increases yet this year and can you – do you have any information on persistence or dose average dosing that you can share with us at this point?

[Joseph Belanoff:]

Well, I will give you to Charlie to ask the question about pricing.

[Charlie Robb:]

Yes. So we – pricing is something we look at every quarter. We haven’t taken a price increases since January 1, this year and we will continue to look at it. However, in formulating our guidance for the rest of the year we have not assumed any price increase.

[Joseph Belanoff:]

And I just didn’t catch, could you please repeat your second question?

[Charles Duncan:]

Do you have any information broadly on average persistence or average dosing levels for Korlym?

[Joseph Belanoff:]

I can give you sort of two different questions and I will give you some guidance to it. In the clinical study that we did, the average does at the end was about 730 milligrams. And I think at this point in time, we still run below that. Part of that is a function of more new patients and so they will start at a lower dose before they titrate up and so forth. But we worked actually very hard because we really felt that the beginning of the launch because doctors really weren’t used to this titration model that we had doctors who put people on the first dose of medication saw some modest improvement and then really didn’t do the titration, one of the real efforts that we have made as to at least titrate to the level where we saw the most efficacy and in the clinical study. and just as a reminder to you only about 20% of the patients who are on 300 milligrams in the clinical study saw that as their optimum dose. The optimum dose really range between as I have said between 600 milligrams and 900 milligrams. So that really is a portion of what we say. And again, I am sorry, Charles. I just want to make I get your next question exactly right, could you repeat it again?

[Charles Duncan:]

I think you kind of answered it, it was regarding dosing or persist?

[Joseph Belanoff:]

Okay. Yes. And the only other thing I really wanted to talk about persistence and this is important, because it’s really one of the efforts that Sean’s team made that I thought was so terrific. And it is an important medical thing, but since you have asked, I will speak to it is that we really find that the time that we have to really focus on helping patients with their medicines is in the first four months on treatment. Patients who have had high cortisol levels for long period of time when you bring those levels down, actually feel what I really describes as cortisol withdrawal, that body is not used to it. When they have surgery they feel absolutely terrible, but they can’t reverse it, surgery is just done. With medicine you can always stop taking your medicine. And we really work hard with physicians to make sure that their patient understand that that’s going to happen and in some sense it’s a sign that the medicine is really working for them, because we know that once the patient begins to see clinical improvement out in the 3-month, 4-month period, particularly they really are then reaping its benefits and stay on the medicine without an early drop off.

[Charles Duncan:]

Okay, that’s helpful. And then just shifting over to 134 quickly, you already answered a question regarding enrollment, but I am just kind of wondering if the enrollment and I think your guy mentioned that he has been meeting with people, a fair amount investigators, I am wondering if he get a sense for how the study is going and I appreciate you got to do the studies before you can really say how it’s – what the outcome is, but what’s your sense of how the piece, how enrollment is going in terms of the quality of patients and in breadth [ph] of patients. And then is it possible that the push out could do something positive for you in terms of enrolling patients that may enhance your ability to draw some conclusions from this study?

[Joseph Belanoff:]

Well. Charles, I sort of say with a smile on face, but first the most important thing I can tell you is the trial is really being conducted to its highest standards. And I think that that’s a very important thing. But I also say on the flip side of it, we have very experienced investigators. We are really convinced that of course with the inclusion criteria their following it very carefully. They are enrolling the patients who they should enroll. And so that’s not a surprise to us, that’s going on sort of as we are going along. So all I can really tell you is we are very confident. Study is being conducted appropriately and that the medicine has the effect that we anticipate that will happen, you will be able to see that.

[Charles Duncan:]

Okay. Thanks for the added information.

[Joseph Belanoff:]

Thank you. Charles. Thank you very much.

[Operator:]

[Operator Instructions] And from BioWatch News we have Alan Leong. Please go ahead.

[Alan Leong:]

So Charlie congratulations.

[Charlie Robb:]

Thanks Alan.

[Alan Leong:]

Joe you brought up the problem with ketoconazole, which is actually true with a lot of the competitive medication, they don’t allow the natural [Technical Difficulty] for cortisol levels, I am wondering if you can provide some color, the term that might present to some patients exactly in terms of the emotional well being or whatever I wonder if you can comment on that?

[Joseph Belanoff:]

Yes, I can. Thank you Alan for giving the opportunity just to expand that a little bit. I introduced this because it’s just an important scientific concept. Cortisol has a diurnal rhythm, meaning high in the morning, it falls through the day and it rises through the night and that’s very important to well-being, particularly to psychiatric well being as you know you Alan that’s the prime interest of mine. So for instance one of the symptoms that you really see in patients who have Cushing’s syndrome is very poor sleep, because their stress axis really doesn’t turn off at night. And it’s very important for one’s mental health well being to have a real needer of cortisol. And so I just think that’s a very, very important concept that if you just simply lower the level of cortisol, but it doesn’t have a diurnal rhythm you can improve some things, but there a lots of things that you don’t improve, because I think that that rhythm is actually very meaningful. And that’s really what I wanted to highlight.

[Alan Leong:]

I also want to allow you to talk about the next things in broad stroke, how much money does that take to fund your clinical trial program for the next 18 months against all the increase in revenues and working capital I guess what do you guys do with all this money?

[Joseph Belanoff:]

Okay. Well, it’s a broader question that you’re asking and I think it is actually worthwhile for the whole audience. What we have said is in some sense we are very fortunate. Our revenue growth really meets or exceeds all the things that we wanted from a clinical program at this point. And I joke about it we are not planning on paying any dividends, because we do think that as our studies get further along they become more expensive, they have larger patients. But as Charlie mentioned in his comments all the things that we will plan right now are fully covered by all the revenues that we think we are going to produce in the cash that we have on hand. So I think the broad answer to your question is expect increasing costs as we get deeper into the studies, but feel confident same degree of discipline that we provided so far on to the financial of the company, we will be providing in the future as well.

[Alan Leong:]

Thank you.

[Joseph Belanoff:]

Thank you, Alan. Well, it looks like we are out of questions here. So I really appreciate for the whole audience their time on a summer afternoon. Thank you. And we look forward to bringing you our progress next quarter.

[Operator:]

Thank you. Ladies and gentlemen, we will now conclude today’s conference. Thank you for joining. You may now disconnect.