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spk05: Good day and welcome to the Corset Therapeutics conference call. At this time, all participants are in a listen-only mode. After the speaker's presentation, there will be a question and answer session. To ask a question during the session, you will need to press star 1-1 on your telephone and you will then hear an automated message advising your hand is raised. To withdraw your question, please press star 1-1 again. Please be advised that today's conference is being recorded. I would now like to hand the conference over to your speaker today, Adibak Mokhari, CFO. Please go ahead.
spk11: Hello, everyone. Good afternoon, and thank you for joining us. I'm Adibak Mokhari, CoreSep's Chief Financial Officer. Today, we issued a press release announcing our financial results for the second quarter and providing a corporate update. The copy is available at CoreSep.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 at the Investors Past Events tab of our website. Statements during this call, other than statements of historical facts, are forward-looking statements based on our plans and expectations that are subject to risks and uncertainties which might cause actual results to differ materially from those such statements express or imply. These forward-looking statements are described in today's press release and the risks and uncertainties that may affect them are described in the press release and in our annual report on Form 10-K and our quarterly reports on Form 10-Q. Please refer to those documents for additional information. We disclaim any intention or duty to update forward-looking statements. Our revenue in the second quarter of 2023 was $117.7 million. an increase of 14% compared to the second quarter of last year. To reflect that growth, we are raising our 2023 revenue guidance again to a range of $455 to $470 million, up from $435 to $455 million. Net income was $27.5 million, or 25 cents per share, in the second quarter, compared to $27.4 million, or 24 cents per share, in the same period last year. Our cash and investments of $363.3 million at June 30th reflects the purchase of 6.6 million CourseUp shares for $145.4 million during the quarter. I will now turn the call over to Charlie Roth, our Chief Business Officer, to provide a legal update. Charlie?
spk07: Thanks, Adam. In March 2018, we sued Teva Pharmaceuticals and Federal District Court to prevent it from marketing a generic version of Coralum in violation of our patents. Trial is set to begin next month on the 27th of September. As a reminder, Teva cannot dispute the validity of two patents we are asserting against it, 214 patent and the 800 patent, which concern the safe co-administration of Coralum the commonly prescribed class of drugs known as strong CYP3A inhibitors. Issues determinative of these patents' validity were decided in our favor when TEVA lost the post-grant review challenge it initiated at the Patent Office. TEVA's only defense with respect to these two patents is that its proposed products would not infringe them, a position we believe has no legal or factual support. The 214 and ANR patents are two of the four patents we are asserting against TEVA. As I said last quarter, and in all of the calls we've held since this litigation began, we are supremely confident in the strength of our case. We are happy that our trial date is approaching. We look forward to our day in court. Why? Because the law and the facts are on our side. I'll now turn the call over to Dr. Joseph Belanoff, our Chief Executive Officer.
spk10: Joe? Thank you, Charlie. The strong results of our commercial business in the second quarter reflect the early return on our substantial investment to stimulate physicians to both better recognize and treat hypercorrosolism. In the second quarter, we saw a continued increase in the number of patients receiving Coralum and the number of physicians prescribing the medication. The business translation of more patients benefiting from Coralum treatment is a new record high in our quarterly revenue. We expect our growth to continue. Quorum is an excellent treatment for patients with Cushing syndrome, and there are many eligible patients who have yet to receive it. Leading endocrinologists increasingly believe that there are considerably more patients with Cushing syndrome than was once assumed. Results of our ongoing CATALYST study will likely provide further evidence to bolster this belief and, equally likely, will lead physicians to begin to identify and provide effective treatment for a large group of patients with hypercortisone whose disease currently goes undiagnosed. We are confident in the growth potential of our Cushing Syndrome business and are raising our 2023 revenue guidance range again, this time to $455 to $470 million. We're also very excited by the potential of our clinical development programs. Since inception, our research and development efforts have built on the hypothesis that cortisol modulation can be a powerful therapeutic mechanism in many serious disorders. Our proprietary compounds modulate cortisol's effects by binding to the glucocorticoid receptor, or GR, the receptor which is activated when cortisol levels are high. They do not bind to the progesterone receptor and don't cause some of Quorum's, our approved products, most serious off-target effects. Interestingly, while our compounds modulate cortisol activity, without modulating progesterone's activity, they are not identical. Some cross the blood-brain barrier, others do not. Some perform best in models of solid tumors, others are more potent in models of metabolic disease. Some appear to be tissue-specific, others have more global effects. These diverse qualities allow us to study a wide variety of disorders. Currently, we are conducting programs with three of our proprietary selective cortisol modulators, Reliquaryland, Dazucoryland, and Miracoryland in ovarian, adrenal, and prostate cancer, ALS, NASH, and of course, Cushing syndrome. We have additional compounds in clinical and preclinical development. In the next 12 months, we expect data from our GRACE, GRADIENT, and CATALYST studies, submission of an NDA for Reliquaryland and Cushing syndrome, completion of enrollment of our Rosella and Dazzle studies, and initiation of a Phase IIb trial of miracoralin in patients with NASH. This is a very exciting time for CORSEPT. We are evaluating relacoralin for the treatment of hypercortisolism in two Phase III trials, GRACE and GRADIENT. Relacoralin is a selective cortisol modulator. Like CORLA, it achieves its effect by competing with cortisol at the glucocorticoid receptor. Unlike coralline, it does not bind to the progesterone receptor, PR for short, and so does not cause PR-related side effects, including termination of pregnancy, endometrial thickening, and vaginal bleeding. By a different mechanism, relacoralline also does not cause hypokalemia, low potassium, a serious side effect experienced by 44% of patients in coralline's pivotal trial. Coralline-induced hypokalemia is a leading cause of coralline discontinuation. Relacoralin's Phase II efficacy and safety data were compelling. Patients experienced meaningful improvements in hypertension and glucose control, as well as in a variety of other signs and symptoms of Cushing syndrome. There were no relacoralin-induced instances of endometrial thickening or vaginal bleeding, and no drug-induced hypokalemia. The trial results were published in Frontiers in Endocrinology in July 2021. With enrollment in GRACE completed, We are focused on finishing the trial and preparing our NDA, which we plan to submit in the second quarter of 2024. Relichloroquine has tremendous promises of treatment for patients with all etiologies of endogenous Cushing syndrome, and we are eager to make it available. Our second phase three trial in hypercortisolism, Gradient, is studying relichloroquine's effects in patients whose Cushing syndrome is caused by an adrenal adenoma or adrenal hyperplasia. Patients with this etiology of Cushing syndrome often experience a less rapid decline, but their health outcomes are poor, including a higher risk of premature death. While we do not expect our NDA and Cushing syndrome to depend on data from Gradient, we do expect the study to produce valuable data about an etiology of Cushing syndrome that affects many patients whose hyperchlorosilism frequently goes undiagnosed and untreated. I'm pleased to announce that our CATALYST study is progressing ahead of schedule. CATALYST is a 1,000-patient phase 4 trial examining the prevalence of hypercortisolism in patients with difficult-to-control type 2 diabetes. Patients diagnosed with hypercortisolism in the CATALYST study may choose to enter a randomized double-blind placebo-controlled study of CORAL-UP. Many independent studies conducted over the last 15 years have found that the prevalence of hypercortisolism in patients with type 2 diabetes is substantially higher than in the general population. The most prominent diabetologists in the United States help us design and are participating in CATALYST, which will be the largest study of its kind. We have received very positive feedback from leading endocrinologists regarding this study and expect a complete enrollment in the fourth quarter, a bit ahead of our previous estimate. Our oncology program is testing three anti-cancer mechanisms, first postulated by investigators at the University of Chicago and later confirmed by other prominent researchers. One mechanism is increasing apoptosis, the program's cell death that chemotherapy is meant to induce in solid tumors. Cortisol works against the beneficial effect of chemotherapy by suppressing apoptosis. In our successful controlled phase 2 trial in women with platinum-resistant ovarian cancer, the addition of our selective cortisol modulator relacoralin enhanced the effect of chemotherapy, likely by blunting cortisol's anti-apoptotic effect. Relacoralin provided meaningful benefit to many of the women in our study. While these women's disease had progressed on two or more previous lines of treatment, including previous taxanes, Relacoralin appeared to resensitize the disease to chemotherapy's beneficial effects in some women. Those who received relacoralin intermittently, the day before, the day of, and the day after they received napaclitaxel, exhibited a statistically significant improvement in progression-free survival and duration of response compared to the group who received napaclitaxel monotherapy. Women in the intermittent relacoralin group also lived longer than those in the comparator arm. with a p-value that approached statistical significance. Our analysis to date indicates that 29% of the patients who took intermittent relucoralin were alive two years after study start, versus only 14% who took napaclitaxel alone. Just as important, the women who received relucoralin plus napaclitaxel experienced no additional side effect burden compared to those who received napaclitaxel alone. The results from this study were recently published in the prestigious Journal of Clinical Oncology. Results have also been featured in podium presentations at the 2021 and 2022 European Society for Medical Oncology, ESMO meeting, and at the 2022 American Society of Clinical Oncology, ASCO, annual meeting. Rosella, our confirmatory pivotal phase three trial in platinum-resistant ovarian cancer, is enrolling patients. Rosella's design closely tracks our Phase II study, and its goal was simply to replicate our positive Phase II results in a larger group. Planned enrollment is 360 women, randomized one-to-one to receive the urelacoralin plus napaklitaxel or napaklitaxel alone. The primary endpoint is progression-free survival, with overall survival a key secondary endpoint. We are conducting this study in collaboration with leading clinicians, from the Gynecological Oncology Group in the United States and the European Network of Gynecological Oncology Trials Group in Europe. We are on track to complete enrollment by the end of the year. Leading gynecological oncologists have told us that, in their view, relicoralin's potential benefit, improved progression-free and overall survival without increased side effect burden, would constitute an important medical advance and that reliquarylin plus nabpaclitaxel has the potential to become a new standard of care in women with platinum-resistant ovarian cancer. The second mechanism by which cortisol modulation may prove useful is by blocking an important tumor growth pathway. Cortisol stimulation is a major reason why patients with prostate cancer treated with the widely prescribed androgen receptor antagonist enzalutamide eventually experience resurgent disease. Deprived of androgen stimulation, their tumor switched to cortisol activity to stimulate growth. Our hypothesis is that adding a cortisol modulator to androgen deprivation therapy will close this tumor escape route. Our collaborators at the University of Chicago plan to begin a randomized placebo-controlled phase 2 trial of relicoralin plus enzalutamide in patients with prostate cancer before these patients have had an initial prostatectomy this quarter. A third therapeutic mechanism seeks to treat tumors by enhancing the body's immune response. Cortisol suppresses the immune system, which may blunt the effectiveness of cancer therapies intended to stimulate the immune system. Our hypothesis is that adding a cortisol modulator to immunotherapies, such as checkpoint inhibitors, may enhance the effectiveness of these therapies. We are conducting a Phase Ib trial of relacoralin, plus the PD-1 checkpoint inhibitor pembrolizumab in patients with advanced adrenal cancer whose tumors produce excess cortisol. Pembrolizumab is rarely effective as monotherapy in treating this form of adrenal cancer. ALS, commonly known as Lou Gehrig's disease, is a devastating illness with an urgent need for better treatment. Dazzles, Our 198-patient randomized double-blind placebo-controlled phase 2 trial of dazocoralin in patients with ALS is briskly enrolling patients. Dazocoralin is a selective cortisol modulator that has shown great promise in animal models of ALS, improving motor performance and reducing neural inflammation and muscular atrophy. We are conducting this important study in collaboration with TRICALS, a leading ALS academic consortium in Europe. We recently added clinical trial sites in the United States and are on track to complete enrollment in DASLs by early next year. Finally, I'll turn to our program in NASH, a serious liver disorder that afflicts millions of patients in the United States. Miracorlent, an oral medication, continues to demonstrate great promise as a treatment for NASH. In our prior NASH studies, Patients who received 600 milligrams or 900 milligrams of miraclorib daily exhibited large, rapid reductions in liver fat, but also substantial, albeit transient, elevations of the liver enzymes ALT and AST. The improvements in liver fat in these patients was greater and occurred much more rapidly than we had expected and is rarely seen over any period of Our ongoing Phase 1b dose-finding study, which evaluated a range of doses and dosing schedules of mirocloralin, found that patients who received just 100 milligrams of mirocloralin orally twice a week for 12 weeks experienced an approximately 30% reduction in liver fat and showed improvements in liver enzymes and markers of liver disease. These patients also experienced improvements in key metabolic and living measures such as HOMA-IR, serum triglycerides, and LDL. Importantly, Miracorla was very well tolerated. We plan to submit these results for presentation at a scientific conference and will initiate a phase 2B trial in the fourth quarter. In conclusion, we are extremely optimistic about the future of Corset. Our Cushing Syndrome business has tremendous growth potential and generates substantial profits even as we invest in our advancing development program. We are again raising our revenue guidance for this year and anticipate growth for years to come. Our catalyst study holds great promise as the data generated will help physicians to improve the screening and treatment of patients whose difficult-to-control diabetes is caused by hypercortisolism, a population whose Cushing syndrome frequently goes undiagnosed. For these patients, hypercortisolism is their disease, and diabetes is a symptom of their hypercortisolism. Our development programs are generating increasing evidence that validates our long-held belief that cortisol modulation has the potential to treat a wide range of diseases. Reducing cortisol activity is a straightforward and effective way to treat Cushing syndrome and can offer substantial benefits to patients with other serious disorders. Ovarian cancer, ALS, and NASH are current examples, but there will be others. In addition to relacoralin, dazocoralin, and miracoralin, we have many other proprietary selective cortisol modulators in our portfolio with potentially very different clinical attributes. In the next 12 months, we will see data from our GRACE, GRADIENT, and CATALYST studies in Cushing syndrome. We'll submit relacoralin's NDA in Cushing syndrome, and we'll complete enrollment in large controlled studies of platinum-resistant ovarian cancer and ALS. We will also begin a Phase IIb study in patients with NASH. As I said, this is an exciting time for Core Set. I thank our dedicated creative employees and loyal investors for making that possible. I'll stop here for questions.
spk05: Thank you. At this time, we will conduct the question and answer session. As a reminder, to ask a question, you will need to press star 1 1 on your telephone and wait for your name to be announced. To withdraw your question, please press star 1-1 again. One moment while we compile the Q&A roster. Our first question comes from the line of Matt Kaplan with Lattenberg. Your line is open.
spk02: Hi, good afternoon, and thank you for taking the question, and congrats on a strong quarter. Thanks, Matt. You're welcome. Can you give us some sense in terms of What drove the revenues in the second quarter and your confidence in increasing your guidance for this year as well?
spk10: Sure, Matt. I'm just going to reintroduce to the group Sean Duke, who is the president of our endocrinology division and runs our Cushing syndrome business.
spk01: Hey, Matt, thanks for the question. And I'll just start by saying we're very pleased with the results. Your question was what drove it. It was driven by improved access and improved field execution. And we're starting to see some early returns from our investments. Many of our investments have been on expanding the field and working to get our field more productive and efficient. So through that process this quarter, we've added both new patients and new prescribers, and we have more patients taking Corlum than ever before. Disease awareness continues to increase. And really, we're more confident than ever about the potential size of the Cushing Center market. And for the remainder of the year, I mean, at this point, our belief is just a fraction of hypercortisol patients have been identified and treated. And over the coming months and quarters, there's going to be many more.
spk02: Okay, that's helpful. And just looking at your pipeline with grace and gradient, grace completing enrollment and gradient to complete in the near term, Can you help us set expectations in terms of what to expect from Grace and Graydon as they read out perhaps next year?
spk10: Yes. Let me introduce you again to Bill Geyer, who runs all of our development here as the Chief Development Officer.
spk12: Bill, comments? Great. Thank you, Matt, for that question. So as we have now completed enrollment for the GRACE trial, the investigators and we are very excited because of that. And now we're in the plans of submitting that NDA. And we've actually been working on that NDA since last year. And as we collaboratively work with the FDA, We're going to be working on developing and submitting all of our studies so that the NDA will include many different studies. It'll include the full phase two data from a safety and efficacy perspective, the GRACE study from a safety and efficacy perspective, the gradient trial from a integrated safety perspective, as well as our long-term extension study, which has been ongoing for over five years. And we have patients on relicorlin for doing well over five years. And then we're also going to include many other new recently presented and published data that I think we're going to be excited to include in the NDA. One of those being, we just completed a thorough QT study where we evaluated the heart's QT interval and looked at relic correlate, and it saw no effects on the QT interval. And that would make this the only drug in Cushing syndrome that does not affect the QD interval. So that's exciting news as we have completed that study. We've also seen published preclinical research citing how relacorlin can uniquely shrink to uterine tumors in tissue cultures. And with those tumors, we've also seen two published case reports highlighting similar clinical benefit of relacorlin in patients. This is a differentiating factor because mipipristone was also used in those preclinical studies and saw no change in pituitary tumors. And then finally, we just presented new data from our phase two trial looking at coagulopathy parameters, which was important because Cushing syndrome patients are high risk for developing hypercoagulopathy events, and relacorlin showed no effects on those coagulopathy patterns. And that would be, again, the only drug in the Cushing syndrome space to have no effect on hypercoagulopathy patterns. All of this data makes me confident in the benefit Reliquary can bring to patients and confident as we proceed towards our NDA in the next coming year.
spk02: Great. And just a quick follow-up on that. Where are you with the manufacturing? Is manufacturing at all a rate-limiting step?
spk10: Manufacturing is not a rate-limiting step, Matt. We'll certainly be ready to have commercial supply when and if our NDA is approved.
spk02: And one last question for me, and then I'll jump back in the queue. The CATALYST study, you know, moving ahead of plans, do you have a sense in terms of, based on the design of this study, what percentage of patients that you're screening have hypocorticalism in this difficult-to-treat type 2 diabetes patients?
spk10: Yes, Matt, I understand the question. I'm going to hand you back to Bill.
spk12: So Catalyst is building on a tremendous amount of research already generated with multiple different studies, and I can cite all the studies and send you all the references. Many of those studies are in hundreds of patients, and in those independent studies over the past 15 to 20 years, we found that hypercortisolism is higher than the normal general population. And I would guesstimate it to be around, when you look at the average for those studies, it's about 10 to 20% for those patients who have difficult to control diabetes. And with Catalyst, this would be then that landmark study because it is the largest study of its kind, evaluating 1,000 patients to evaluate those with type 2 diabetes who are difficult to control. And we're doing a simple test of just one DST. You know, all of our investigators are part of this, are highly motivated by this, and that's why screening is ahead of schedule. And thus far in the catalyst study, even though it's early, I would say that the results so far are mirroring what we've seen in past published studies.
spk02: Great. Great. Thanks for the added color, guys. Thank you, Matt.
spk05: One moment for our next question. Our next question comes from the line of Edward Nash with Canaccord. Your line is open.
spk03: Hi. Thanks for taking the call. And yes, congrats, guys, on such a strong quarter. Really, really great. I do have two to ask you. And I guess this goes in the same vein of it being a really strong quarter and just the additional input in the sales effort truly kind of does what you've attributed that to. But I see that the European Society of Endocrinology has updated their practice guidelines on the treatment of adrenal insensitilomas. And I just wanted to find out what the – what the implications are there. I think it's been a while since these have been updated, so just want to kind of better understand what the implications could be there for usage of corallum.
spk10: Good, Edward. Thank you for the question, and I'm going to direct it to Sean again.
spk01: Yeah, Ed, thanks for the question. And just adding on Bill, it just There's study after study after study. There's been mounting evidence over time that this illness is more prevalent. And these European guidelines that were just updated are just another example of the evolution of the mindset around hypercortisolism. Endocrinologists recognize that hypercortisolism is more prevalent than once thought. And what these guidelines do is that they encourage physicians to look harder for the disease, which is great. The guidelines also highlight the use of the relatively simple dexamethasone suppression is going to support increased screening. So these guidelines will influence and increase both screening and diagnosis of hypercortisol in patients.
spk03: Great. Thank you.
spk07: Thank you, Edward.
spk05: One moment for our next question. Our next question comes from the line of David Amsalem with Piper Sandler. Your line is open.
spk13: Thanks. So just have a few. First, I wanted to ask a couple on miracoralin in NASH. I know you're going to have data at an upcoming medical meeting, but just thinking about the Phase 2b, can you just talk about the contours of the design of that trial? I'm assuming we're going to have liver biopsies in this trial, and is this something where you're thinking about is uh more of a phase two slash three and um or is this something where uh we should think about it as you're still going to have to do a full phase three program uh beyond this phase to be that's number one number two is as you think about americorl and um strategically is this something that you're going to look to partner down the road is this something that you're going to look to keep and commercialize and Where does it fit in the broader business, particularly given the comments about other cortisol modulators that you're looking at that you haven't disclosed? Thanks.
spk10: Yeah, thanks, David. And then two questions I think I understand. Bill, would you first describe these to be your equivalent study, and then I'll describe, I'll discuss the business possibilities.
spk12: Absolutely. Hey, thank you for that question. So as we progress towards our Phase 2B program, let me back up a little bit. One, we just completed a great advisor board at the EASL Conference, which is the European Conference for the Study of Liver Disease. And we met with the top hepatologists in the world who have done research for every molecule in the NASH phase for the past decades. And I've known them for many decades as well. And as we reviewed all the Phase 2A data from our original study and all the Phase 1B data, They were really impressed with that, and they helped guide us in designing our phase 2b trial. And so that was really encouraging as we move forward. And so that phase 2b trial right now as our study is a biopsy-confirmed NASH study in patients with NASH. This study will be a double-blind placebo-controlled trial evaluating 150 patients randomized to miracolin 100 milligrams twice weekly or placebo for 48 weeks. This is intended to be a Phase IIb study, and based upon those results, we will then progress and design a Phase III trial.
spk10: And, David, you know, the second question is an interesting one, and I just, for a variety of reasons, particularly for those who follow CORSEP for a long time. I mean, as you know, most of the things, starting with Cushing syndrome that we've worked on, have been orphan diseases, niche markets, you know, very obvious clinical need, but to a relatively small group of patients. NASH is, of course, a different story. The number of people in the United States with fatty liver disease is very large, and a sizable percentage of them have NASH, which progresses to worse things than that. So it's a big market. I don't know if the older term primary care market is the right way to describe it, but there's certainly a market with many, many patients in it. Now, it's a good question, and one that we've thought about a lot. This is something that we can do where will we need to partner? I don't really know the answer to that at this point in time. But what I will tell you is that we are not in need of anyone else's money to support the development plan. So if we decide that commercialization is better with a partner, we'll go in that direction. But I think we're really in the lucky space because of our profitable business and our long-term profitable business that we can take this as far as we want. And should we partner, we'll be at a place where it's, clearly advantageous for us to do so. And, you know, I'll end it with a simple answer. That decision has not yet been made.
spk13: Okay. That's helpful. If I might sneak in an additional question, just on Catalyst, as you get learnings from the study and, you know, particularly the answers that that you're looking for, which is the Cushing syndrome and hypercortisolism is more prevalent and raising awareness among diabetologists. Do you think about calling on a sizable group of diabetologists in your rollout and broader commercialization of Relicoralent? In other words, is this going to be a bigger, splashier, more expensive, wider launch into a wider group of physicians. Thanks.
spk01: Sean? Yeah, no, thank you for the question. And look, we're in the process of really working through that now to understand what the most effective way will be for us to launch relacorlin. We do recognize that these patients are in more than just endocrinology practices. Diabetologists in general are endocrinologists, but there's cardiologists. showing up in some primary care offices sort of throughout the country. So we are right now are working on trying to figure out scalable ways that we can get this message to physicians that they can be educated.
spk10: Yeah. But just I appreciate the question, David, particularly because we have been thinking about that. You know, I think at some point, you know, maybe a decade ago, we thought that the patients with Cushing syndrome were likely to be treated by really a very, very small number of endocrinologists. We do not think that is true anymore. We think they're distributed to a much larger group. And making sure that these patients get to optimum treatment is really, that's our ethos. That's what we really want to get to. So how it translates to practical matter is absolutely on our mind. Thanks a lot. Thank you, David.
spk05: One moment for our next question. Our next question comes from . Your line is open.
spk04: Hi. Afternoon, everyone. So a couple from me, maybe on tagging on a question about your revenue guidance for a second. I was curious, what are some of the pushes and pulls that could get Coraline revenues closer to the higher end or the lower end of this range, in your view?
spk01: Sean, please take that. Yeah, thank you for the question. Our guidance is pretty simple. It's driven by the number of patients on medicine. We have more patients taking Coraline than ever before, and we expect that there will be more in the future. We have a number of initiatives underway, and we're expecting them to impact the second half of the year. So the more patients that are prescribed Coraline, the higher the end of the range it will be. If it's a little bit fewer, it'll be on the work.
spk10: It's really as simple as that. There aren't other factors besides the number of patients that are really very appreciable.
spk04: Got it. Okay. And wanted to ask a bit about your field force. So I know you've reached the target of 60. Are you thinking of possibly expanding that later this year or maybe into next year? And what type of launch metrics are you looking for to help you make that kind of decision?
spk01: Sean, please. Yeah, it's a great question. I'll start by saying we're always evaluating the effectiveness of the team and looking to see what is the appropriate size. I think stepping back in time a little bit, through the pandemic, we felt that it was very important for us to maintain the stability of that team. But over the last year, we've taken a very hard look, and that's where we've made changes. We've strengthened and streamlined our training program. The goal is making our current clinical specialists more productive. and our newer clinical specialists more productive more quickly. And we've also, as you just alluded to, added top talent to the team. So in terms of the current size of the team, we're actually currently in the mid-50s, and we are continuing to add clinical specialists throughout the country. Right now, our target is 60, but we're unlikely to stop there. If we can continue to find top talent, we will be adding it to the team. And as we continue to evaluate what the future looks like, we'll determine if we need to go beyond that.
spk04: Got it. Thanks. Thank you, Rowana.
spk05: One moment for our next question. Our next question comes from the line of Jun Li with Truist. Your line is open.
spk06: Hi. I'm from the Strong Quarter, and thanks for taking our questions. I'm particularly intrigued by your phase four catalyst study of quality and difficulty to treat diabetics. How are you making the determination of hypercortisone and advancing them to the randomized portion of the trial? And how deployable is that screening for hypercortisone by generalists and endocrinologists who treat diabetics? And lastly, what is the endpoint in the randomized portion? And is a positive result there sufficient to get a labeled indication for diabetics? And I will follow.
spk10: Yeah. Well, June, first, welcome or welcome back. Nice to hear from you. And I think that Phil has best got his arms around, I think, all of that information. So I'm going to turn it over to him.
spk12: So thanks for the question. So when we look at Catalyst, we designed it specifically, again, and collaboratively with top diabetologists and coronologists to make this as simple and easy as possible. And it's now aligned with the guidelines, as we spoke about earlier. We've just deployed a simple test of one DST, a dexamone suppression test, and looking for those patients with a DST greater than 1.8. Those are the patients who are then positive, who then can qualify and be screened for or enrolled into the randomized placebo-controlled trial of Coraline. In that trial, the primary endpoint is just to look at a difference between glucose control between Coraline and that of placebo. and that will be our primary endpoint. And related to will it change the label of corallum, it's already consistent with a label of corallum, because when you look at the corallum indication, corallum is indicated to control hyperglycemia secondary to hypercorvizalism in adult patients with endogenous Cushing syndrome who have type 2 diabetes.
spk10: Wow, excellent. Thank you. And... I think you asked just another small question, which was, is the dexamethasone depression test something that doctors in mutual practice can undertake? The answer is yes. It's not a hard test to run.
spk06: Great. Thank you. So if Catalyst is positive, then would you need to run a trial using reliquarolent in difficult-to-treat diabetics to get the similar use commercially? And if not, Either way, actually, would dosing be different or some aspect of the drug be different between the Cushing's patients and diabetics to maybe get different pricing given the different opportunities?
spk10: I just want to make sure to clarify this. All of these patients' disease is hypercortisolism, and diabetes or glucose intolerance is secondary to their hypercortisols. It is what is causing their hyperchorosolism. So in some sense, there's no difference except for degree of illness between these patients. And some of them actually can be quite ill. So I just want to make that distinction. This is not diabetes in general. These medicines, whether it's chloralom or relachlorolin, are not for diabetes in general. They're for the treatment of hyperchorosolism, where diabetes appears as a prominent manifestation of hyperchorosolism.
spk12: And then to answer your question about would we use relacoralin, I see no reason to repeat this study. I see this catalyst as a landmark study that would easily apply to relacoralin. And I'll remind you, relacoralin, we're looking for an indication, a full indication for hypertension and diabetes, not just diabetes.
spk06: Great. Looking forward to the progress in beta. Thank you.
spk07: Thank you, Jim.
spk05: One moment for our next question. Our next question comes from the line of Swayam Pakula with HC Reinright. Your line is open.
spk08: Thank you. This is RK from HC Reinright. Good afternoon, Joe. Hi, RK.
spk00: Hi, RK.
spk08: Most of my questions have been answered, but I have a quick question on clinical data expectations for the rest of this year.
spk10: I'm sorry, I didn't quite understand your question, RK. I apologize.
spk08: So I'm just trying to understand what sort of clinical data could we expect in this year, you know, from here to the end of the year?
spk10: Yeah, I'm going to turn you over. Now I understand your question. Bill, would you please answer that?
spk12: So as I look at all of the studies that are ongoing, the one study that I could see that we are planning to submit to a conference in the fourth quarter of this year would be the NASH Phase 1b data. And so that is our plan to present that data hopefully at that conference. Catalyst will be close. You know, we're ahead of schedule. I would say it's probably first quarter of next year, but it could, we could see results from the screening and prevalence study later this year in December.
spk10: Yeah, I'm just going to underscore that. I think what you can count on is the Phase 1b results in NASH. We will have that. But everything else falls into the next year, often the early part of next year, but in 2024. Thank you. You're welcome.
spk05: One moment for our next question. Our next question comes from the line of Alan Leong with BioWatch. Your line is open.
spk09: Hey, everyone. Glad to be here, and congratulations on the ongoing work.
spk10: Well, Alan, it's wonderful to hear you. What might we help you with today?
spk09: Well, I have a few questions, and thank you for your generosity in having me. What can you tell us about the dynamics of safety and efficacy and live with that with no comment? What have you learned? And you just speculate that liver impairment level is a significant covariance.
spk10: I apologize. It's a poor connection. Could somebody read Alan's question? I couldn't hear him.
spk00: I'm sorry.
spk10: I really apologize, Alan. I really just couldn't hear you.
spk09: Oh, sorry about that. Yeah, I'm using these earbuds. Yeah. Is this better?
spk07: Yes.
spk09: Okay. What can you tell us about what you've learned about the dynamics of near-equivalent with safety and efficacy and liver fat? Okay.
spk10: I'm just going to repeat the question. Yeah. The question was, what have we learned about the dynamics of near-equivalent in terms of that? Bill, could you please talk to that?
spk12: Key pieces there, you know, we've reviewed the, you know, phase 2A data, again, using 600 and 900 milligrams. We saw those dramatic liver fat reductions in a month corresponding with rises in liver enzymes. And that's what allowed us to then explore various lower doses and different dosing regimens in phase 1B. And as we have studied various different dosing regimens, we really have determined it's the rapidity of the liver fat reductions. And we confirmed that when we reviewed all the data with our top advisors just about a month ago. And we've determined that that liver fat, rapid reduction in liver fat is tied to that rise in increasing free fatty acids, which then causes mitochondrial dysfunction, which then in turn causes that liver enzyme irritation and elevation. And that's key because what we also saw is as the liver is trying to metabolize all those free fatty acids, it actually can metabolize those because we're not seeing any dumping of fat into the bloodstream. Because in our study, we're seeing lowering effects on triglycerides, LDL, and BLDL. But importantly, we also saw that if we can slow that down, and we saw that with the 100 milligram twice a week dose, that when we slow that down, we see a steady decline up to 12 weeks And we saw that 30% reduction in liver fat with no rises in ALT or AST. We actually saw decreases in those liver enzymes. And so that's really what we have learned. And we've done many analysis looking at the slope of decline, percentage of decline. It all matches up that it really is tied to the rapidity of liver fat reduction. And we believe we've solved that problem, which is why we're going to Phase IIb.
spk09: Next set of questions. Of the following three programs, which do you think has the greatest gap in understanding from your audiences? You kind of go there and you go, wow, we have a little chasm in education to do. Feel free to split the investor community versus the life science specialist. Ovarian cancer versus, go ahead.
spk10: Yeah, no, I just want to repeat your question as I understand it, which is, you know, of our programs, which do we think is sort of least recognized by the investor community? And if that's essentially a distillation of your question, I get it, because I think one of the things that's surprising, I think, to people until they really dig into the science, and as you know, you know, sort of a recovering academic, so I'm really all about the is how broad a platform cortisol modulation is. Cortisol goes into every tissue in the body, so it really has the potential to affect many disease states. And it's, in some sense, obvious why a drug like Coralum or Relacoralum would be effective in Cushing syndrome. I think it's initially a little less obvious why it might be effective in a neurologic disease like ALS or a disease like cancer. variety of cancers. But I think that the interesting thing for us is that there are individual investors who seem to appreciate kind of individually parts of the story. But I think that there are few, and I think this is going to change over time, who really understand the global application of cortisol modulation to the whole platform. So I don't think it's a question of any individual program particularly being unrecognized. I think that it's just that some people recognize one program, some people recognize another program. And I'm really hoping to see over time is that people can actually connect all of those things because they really are connected. And I'll give you just one sort of personal example from that is that, you know, every four years we conduct a conference with all of our collaborators. As you know, we have many academic collaborations in any given time, 35 or 40 of them. And they're all over the world, and they're preclinical, and they're clinical. And we bring those people together, as you said, one time. And many times, they're unaware of the other work that people are doing, even though they're all working in cortisol modulation. It's our mission to make sure that people really understand this entire platform. And I hope that, as I said, even investors, who I know are busy people, really take the time to appreciate the global potential of these programs.
spk09: Well, thank you very much. The future is bright for both of us. Thanks.
spk10: Okay. Thank you very much, Alan. And I think with that, we're out of questions. So I look forward to talking to everybody three months from now and hope you enjoy the rest of your summer.
spk05: Thank you for your participation in today's conference. This does conclude the program. You may now disconnect.
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