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spk01: Good day and thank you for standing by. Welcome to the CoreSAP 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 that session, you'll need to press star 1 1 on your telephone, and you'll then hear an automated message advising that your hand is raised. Please be advised that today's conference is being recorded. I would now like to hand the conference over to your speaker today, Adibak Makkari, CFO. Please go ahead.
spk09: Good afternoon, and thank you for joining us. I'm Adibak Makkari, Corsup's Chief Financial Officer. Today, we issued a press release announcing our financial results for the third quarter and providing a corporate update. A copy is available at corsup.com. Our complete financial results will be available when we file our Form 10-Q with 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 fact, are forward-looking statements based on our plans and expectations that are subject to risks and uncertainties, which might cause actual results to differ materially from those such statements 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 in our annual report on Form 10-K and in 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 third quarter of 2022 was $101.7 million compared to $96.1 million in the third quarter of last year. Net income was $34.6 million or 30 cents per common share in the third quarter compared to $30.5 million or 24 cents per common share in the same period last year. Our cash and investments at September 30th was $401.2 million, an increase of $19 million in the quarter. We expect our revenue growth to continue and have tightened our 2022 revenue guidance to $400 to $410 million. I will now turn the call over to Charlie Roth, our Chief Business Officer, provide an update on our litigation with generic manufacturers Teva and Hikma Pharmaceuticals.
spk04: Charlie? Thanks, Atabak. I have little to report. In March 2018, we sued Teva and federal districts work to prevent it from marketing a generic version of Corlum in violation of our patents. That lawsuit is still underway, although there has been no activity for more than a year. In the second quarter of 2021, we filed for summary judgment based on Teva's infringement of our 2014 patent. Teva, as expected, responded by filing its own summary judgment motion. Summary judgment is a procedure whereby courts decide a case without holding a trial. The court has not responded to these motions. Remember that Teva challenged the validity of the 214 patent that is the basis of our summary judgment motion at the patent office and lost. which means it cannot challenge the 214 patent's validity in district court. As a result, it's only defense to our summary judgment motions that its proposed product would not infringe a position we believe has no support. The court decides the pending summary judgment motions in our favor. Teva would be barred from marketing generic corral until 2037 when the 214 patent expires. The court rules in Teva's favor, we will proceed to trial. most likely sometime next year. There's no timetable for the summary judgment motion ruling, no trial date, and no schedule for any trial-related activities. In March 2021, we sued another antifiler, Hikma Pharmaceuticals. Discovery in that case is scheduled to conclude in April 2023. No trial date has been set. With respect to both Teva and Hikma, we are confident in the strength of our legal position. I'll now turn the call over to Dr. Joseph Belanoff, our Chief Executive Officer. Joe?
spk06: Thank you, Charlie. Our Cushing Syndrome business is built on a solid foundation, a life-saving medication promoted by a commercial team that puts the interests of patients first. Diagnosing and treating patients with a complex disease such as Cushing Syndrome requires frequent in-person contact with patients. Our revenue in the third quarter was affected by fewer than expected in-person interactions, as many physician practices have not returned to pre-pandemic patterns of activity. To reflect this near-term challenge, we are tightening our 2022 revenue guidance to $400 to $410 million. We remain extremely optimistic about the present and the future of our Cushing syndrome business. Corllum is an excellent treatment for patients with Cushing syndrome, and leading endocrinologists increasingly believe there are considerably more patients with Cushing syndrome than was once assumed. We are making substantial investments to improve the screening and treatment of these patients, and we are confident these initiatives will contribute to our results in the coming quarters. We are also very encouraged by the potential of our clinical development programs. Our clinical trials continue to advance and generate data supporting cortisol modulation's broad therapeutic potential. We are very excited about our most recently initiated studies, ROSELLA, our confirmatory Phase III trial in platinum-resistant ovarian cancer, and DASLs, our Phase II trial in ALS. We are also looking forward to important readouts from our two Phase II trials in antipsychotic-induced weight gain by the end of this year. Our portfolio of more than 1,000 proprietary molecules, together with funds provided by our commercial success, will allow us to further broaden our therapeutic areas of interest. All of our compounds modulate cortisol's effects by binding to the glucocorticoid receptor, or GR. They do not bind to the progesterone receptor, and so don't cause some of Quorum's approved products with serious off-target effects. Interestingly, while all of our compounds modulate cortisol's 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 in ovarian, adrenal, and prostate cancer, ALS, antipsychotic-induced weight gain, NASH, and, of course, Cushing syndrome. We are also investigating cortisol modulation's role in other disease and have additional compounds in clinical and preclinical development. Our Cushing Syndrome business has funded all of these activities and will continue to do so. 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 programs tell that the 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 some of them to chemotherapy's beneficial effects. Those who received relacoralin intermittently, the day before, the day of, and the day after they received nabpaclitaxel, exhibited a statistically significant improvement in progression-free survival and duration of response compared to the group who received nabpaclitaxel monotherapy. While our study was not powered to show a difference in overall survival or OS compared to napaclitaxel monotherapy, women in the intermittent relacoralin group also lived longer than those in the comparator group with a p-value that approached statistical significance. I remind you that, to date, no approved therapies have demonstrated an overall survival benefit in patients with platinum-resistant ovarian cancer. In addition, The women who received relacoral and plus napaclitaxel experienced no additional side effect burden compared to those who received napaclitaxel alone. The results from this study were featured in multiple podium presentations at the 2021 and 2022 European Society for Medical Oncology, ESMO, meetings, and at the 2022 American Society of Clinical Oncology, ASCO, annual meeting. Rosella, our pivotal Phase III trial in platinum-resistant ovarian cancer, is active and enrolling patients. Rosella's design closely tracks our Phase II study with planned enrollment of 360 women, randomized one-to-one to receive either relucoralin plus napaklitaxel or napaklitaxel alone. The primary endpoint will be progression-free survival, with overall survival a key secondary endpoint. We are conducting this study in collaboration with leading clinicians from the Gynecologic Oncology Group in the United States and the European Network of Gynecological Oncology Trials Group in Europe. Our goal in phase three is simply to replicate our positive phase two results. Leading gynecological oncologists have told us that, in their view, reliquarylin's potential benefit improves survival without increased side effect burden would constitute an important medical advance, and then relacoron plus napaclitaxel has the potential to become a new standard of care in women with platinum-resistant ovarian cancer. A 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 the androgen stimulation, their tumors switch to cortisol activity to stimulate growth. Our hypothesis is that adding a cortisol modulator to androgen deprivation therapy will close this tumor escape route. Next year, in collaboration with the University of Chicago, we will begin a randomized placebo-controlled phase two trial of relacorlin plus enzalutamide in patients with prostate cancer early in their course of treatment before they have had their prostatectomy. A third mechanism of cortisol modulation seeks to treat tumors by enhancing the body's immune response. Cortisol suppresses the immune system, which may blunt the effectiveness of cancer therapy intended to stimulate the immune system. Our hypothesis is that adding a cortisol modulator to immunotherapies such as checkpoint inhibitors may increase the effectiveness of those therapies. We are conducting a phase 1B trial of relacoralin plus the PD-1 checkpoint inhibitor, pembrolizumab, Merck's drug, Keytruda, in patients with advanced adrenal cancer whose tumors produce excess cortisol. These patients suffer the effects of adrenal cancer and Cushing syndrome, a usually quickly lethal combination. Pembrolizumab alone is rarely effective in treating this form of adrenal cancer. Our trial is evaluating whether relacoralin can treat these patients' Cushing syndrome by reducing excess cortisol activity and by reversing cortisol-induced immune suppression, allow pembrolizumab to achieve its full cancer-killing effect. The primary endpoint of this study is objective response rate, with secondary endpoints including progression-free survival, duration of response, and overall survival. I'll now provide an update on our ALS program. ALS, commonly known as Lou Gehrig's disease, is a devastating illness with an urgent need for better treatment. We are excited that we have initiated DAZL, our 198-patient randomized double-blind placebo-controlled phase 2 trial of dazocoralin in patients with ALS. Dazocoralin is a selective cortisol modulator that crosses the blood-brain barrier and 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, the leading ALS academic consortium in Europe. Next, I'll turn to our programs in metabolic disease, which will produce important data soon. We are conducting two double-blind placebo-controlled Phase II trials of miracoraline. gratitude, and gratitude 2 in patients with antipsychotic-induced weight gain, a serious and widespread disorder. In the United States, 6 million people take antipsychotic medications such as olanzapine and risperidone to treat illnesses including schizophrenia, bipolar disorder, and depression. While these drugs are very effective, they often cause rapid and sustained weight gain, as well as cardiovascular and metabolic disease. The burden on patients is severe. The average life expectancy of patients in the United States who take antipsychotic medication chronically was decreased by 20 years. These side effects also dissuade many patients from adhering to their treatment regimen. The GRATITUDE trial seemed to build on the positive data from our study of miracoralin in healthy subjects. In 2020, we completed a trial in which 96 healthy subjects received olanzapine and either 600 milligrams of miracoralin, 900 milligrams of miracoralin, or placebo, for 14 days. Subjects who received mericoralin gained significantly less weight than those who received placebo. They also exhibited a smaller increase in triglycerides and in the liver enzymes ALT and AST, which typically exhibit sharp transient increases at the start of olanzapine therapy. A paper describing these results was published last year in the Journal of Clinical Psychopharmacology. Gratitude is evaluating whether Miracle-Orland can reverse recent antipsychotic-induced weight gain, and Gratitude 2 is evaluating the reversal of long-standing antipsychotic-induced weight gain. While the primary endpoint in both studies is reduction in body weight, I also want to stress the importance of general improvement to the patient's metabolic health as an indication of the patient's condition being treated more fully. For example, Improvements in lipids, glucose control, and markers of liver health would be highly desirable outcomes. These studies will produce important data in many areas, and we look forward to their results by the end of this year. Miracoralin is also our candidate treatment for patients with NASH, a serious liver disease that afflicts millions of patients in the United States. In a prior NASH study, patients who received Miracoralin exhibited large, rapid reductions in liver fat, but also substantial, albeit transient, elevations of the liver enzymes ALT and AST. The improvement 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 treatment. Patients exhibited reductions in liver fat ranging from 38.5% to 73.8% after receiving miracoralin for just one month. put this in perspective, recall that the trial's primary endpoint was a 30% reduction of liver fat after 12 weeks. It may be that the rapidity of miracoral and its fat-reducing effect caused the patient's ALT and AST to rise. One way the liver sheds fat is by metabolizing into fatty acids, which in excessive amounts irritate the liver. Lipids in the blood of these patients did not increase. providing support for the idea that neurochloroquine caused their excess fat to be metabolized immediately within the liver. The goal of our Phase 1B dose-finding study in patients with NASH is to identify a dosing regimen that captures the unprecedented rotidity and magnitude of liver fat reduction without causing excessive liver irritation. Enrollment of this trial has been robust, and we plan to share its results in the first half of 2023. Finally, as most of you know, we are evaluating relacoralin, a plant successor to corallin, for the treatment of hypercortisolism in two Phase III trials, GRACE and GRADIENT. Relacoralin is a selective cortisol modulator. Like corallin, it achieves its effect by competing with cortisol at the glucocorticoid receptor. Unlike corallum, 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, relacorallum also does not appear to cause hypokalemia, low potassium, a serious side effect experienced by 44% of patients in corallum's pivotal trial. Corallum-induced hypokalemia is a leading cause of corallum discontinuation. Relacoralin's Phase II efficacy and safety data were strong. Patients experienced meaningful improvements in hypertension and glucose control, as well as in a variety of other signs and symptoms of Cushing's 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 last year. Races enrolling patients with any etiology of Cushing's and has a randomized withdrawal trial design. All patients initially receive relacoralin for 22 weeks in an open-label part of the study. Those who meet response criteria are randomized to continue treatment with relacoralin or placebo for 12 weeks. We and our investigators are eager to take Grace to the finish line. We expect Grace to serve as the basis for our NDA submission in Cushing syndrome, which we expect to submit in the second half of 2023. Our second phase three trial, GRADIENT, is studying relic oral 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. GRADIENT is the first controlled study in patients with this type of Cushing syndrome. While we do not expect our NDA in Cushing to depend upon data from Gradient, we do expect that its findings will help improve the care of those increasingly recognized patients. Gradient, a randomized placebo-controlled study, has a planned enrollment of 130 patients. To sum up, our commercial business continues to generate substantial profits even after funding all of our development programs. We are extremely optimistic about the present future of our Cushing Syndrome business, and are making significant investments to improve the screening and treatment of patients with Cushing syndrome. We are confident that these initiatives will contribute to our results in the coming quarters and expect our revenue growth to continue. Our development programs continue to generate evidence validating 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. It is now clear that excess cortisol activity affects other various serious disorders, and cortisol modulation can provide substantial benefits. Ovarian cancer is a prime example, but there will be others. Our just-open multinational trial in ALS has real promise, and we will have important data from our antipsychotic and ubiquitin studies later this year and from our NASH program in the first half of next year. The whole academic field in the use of cortisol modulation in alcohol and other addictions is open-ish. And in addition to relacoralin, miracoralin, and dasacoralin, we have many other cortisol modulators in our portfolio with potentially very different clinical attributes. CoreSept is steadily advancing across multiple fronts. I thank our dedicated creative employees and our loyal investors for making this possible. I'll stop here for questions.
spk01: Thank you. At this time, we'll conduct a question and answer session. As a reminder, to ask a question, you'll need to press star 1-1 on your telephone and then wait for your name to be announced. Please stand by while we compile our Q&A roster. Okay, our first call comes from the line of Ed Nash of Jefferies. Your line is open.
spk03: Hi, it's actually Edward Nash at Canaccord. Thanks for taking my call and I really appreciate the overall pipeline overview. I just wanted to maybe touch on a point, Joe, that you brought up at the beginning of your comments, just talking about the limited interactions that are still occurring in the doctor's offices there. And I just wanted to kind of understand, I guess, better understand that because We're clearly not in the peak of COVID anymore now, and things have relatively gotten back to normal. And it seems that a lot of the doctor's offices, if they are still doing virtual, it's because of their choice or patient's choices. So I just wanted to understand just kind of what is going to be the push to to kind of get things back to where they need to be. Are patients really having a hard time getting appointments with the endocrinologist to either for follow-up or is it a lab issue? I'm just trying to understand. I know there's a lot of moving parts, but kind of what is kind of the overall stopgap that's really causing the problem here on growth of corallum?
spk06: Yes. And I think we really do understand your question. And I just want to reintroduce you to Sean, who is the president of our endocrinology division and runs all of our commercial activities. I think he can really give you a detailed answer to that question.
spk07: Yeah, thanks for the question. And again, as Joe stated, the interactions really have not returned for us to pre-pandemic levels. And right now, we're not sure if they ever will. You know, as a company, we spend a lot of time educating on disease. And if physicians aren't aware of hyperperitonealism, they're not aware that it could be a source of their patient's comorbidities, they don't look for it or screen for it. So we worked hard and will continue to work hard to find new ways to operate what we perceive to be this new normal. And we'll continue to innovate, and I'm confident that we'll continue to find new and creative ways to reach our target audience. Part of your question was around, although we're not maybe in the height of the pandemic, some practices and health groups that maybe weren't always up to seeing clinical specialists in the past, I would say have somewhat taken advantage of the change and of the situation now and closed their doors to pharmaceutical reps, which is a shame because a lot of the newest information in science actually is delivered by industry.
spk06: Yeah, and what I really just like to answer the question, just to really give you the kind of full round, is that I agree with you. You know, when I'm out now, it seems as if that many things are back to pre-pandemic normal, although not entirely. And I think, you know, as a physician myself, I can tell you that there are many doctors whose practices have changed in character to some degree. Now, our major effort in terms of sales really always relied on particularly at the very beginning before a physician had prescribed, many in-person sessions as the doctor was educated over a period of time before they began screening. I think the reality is that while many practices in some ways have returned to normal, I think that other practices may not ever return to what was like pre-pandemic. It's really on us to figure out ways to make sure that education process continues in this new way. I'm really very confident that we have. We have very specific ideas of how to do that. But we're now accepting that this is how the world is going to be going forward, and we're going to operate from that perspective.
spk03: Great. Thanks so much.
spk01: Okay. Thank you. One moment for our next question, which comes from the line of Dennis Ding of Jefferies. Your line is now open.
spk02: Hey, guys, thanks for taking the question. Two questions for me, if I may. Number one, if you look at the business from a big-picture perspective, maybe talk about your commitment and, importantly, visibility in continuing to achieve a double-digit growth profile as we look towards 2023 and afterwards. And then number two, maybe comment on the anti-psychotic-induced weight gain trial, you're going to have some data by year end. Remind us what Levalvi showed on percent weight loss and the level of efficacy you hope to see for a phase two study. And maybe to follow up on that, what opportunities do you see outside of AIWG and NASH? And I'd be curious to get your view on the broader applicability in much larger markets.
spk06: Edward, two different areas of questioning. So let's go one at a time. The first question I'd like to, as it relates to hypercortisolism and our commercialization effort, I'd like to give you back to Sean.
spk07: Yeah, thank you for the question. And I want to remind everybody about the significant growth potential that exists in this market. I mean, there is now a substantial amount of independent research that suggests that hypercortisolism is potentially far more prevalent than previously thought. It's still a rare disease, but could there be 30,000 to 40,000 patients? Yes, and we're focused on unlocking that full potential. So despite some of these current challenges that we just went through, we're confident in our path to sustained growth. I thought I'd maybe take a minute to tell you a little bit about what a couple of those key strategies are. We talked about how access has been a challenge. So one of our physician interactions. And we're going to do that by increasing the size of our customer-facing team and the support groups around that and working to improve the productivity of that team. The second big focus area for us is really around increasing screening and referral rates by raising awareness and specialties that we believe have enriched patient populations. So I'm going to give you a couple examples. For example, number one, diabetologists see a large number of treatment-resistant diabetics. Yet, they do not routinely screen for Cushing syndrome, even though literature states that anywhere from 8% to 10% of this population may have underlying hypercortisols. As another example, radiologists frequently discover adrenal nodules during routine abdominal scans. However, those patients are often not referred to an endocrinologist for workup, even though radiology guidelines said they should be. So not all specialties are aware of hypercortisolism, and because of this, many patients go undiagnosed. And we're very focused on changing that. We're going to use various marketing channels, as Joe mentioned, to get the message out to these customers through in-person print and digital means. Not all these patients will be Portland candidates, but some will. And really, I think to sum it up, all of our strategies and tactics are focused on increasing physician interactions, raising hypercortisolism awareness,
spk06: patient screening and most importantly improving care for our proposals and patients and Dennis your second question had to do with our anti-psychotic induced weight gain program and I'm going to turn it over in a second to Bill Geyer who is our chief development officer and responsible for all the drugs to development including anti-psychotic induced weight gain but just one small point it but I think it's an important one you mentioned will Bobby and I Just a factual point is we will lobby for the prevention of antipsychotic, in fact, olanzapine-induced weight gain, not for weight loss. I think that's an important distinction. So I'll turn you over now to Bill, and he can give you an answer to your variety of questions.
spk08: Yeah, thank you very much. So regarding our antipsychotic-induced weight gain focus, it's from the Gratitude and Gratitude II studies. And yes, we will have data by the end of this year. And we expect to evaluate both of those studies individually, but also collectively, pooling the data to just make sure we fully understand all of the data from these trials. Because we really think that we've got to take a holistic review of all of the data. And as Joe had stated earlier, we want to make sure that we analyze the data, not just on the primary focus of weight gain, but also all of the other metabolic factors. And in addition, importantly, psychiatric measures. And so that's going to be our focus is to make sure that we fully understand all of that data because we believe when we produce the results and we communicate those results, we want to make sure that we're clear what we understand and therefore you understand the benefit that Mericorlin can bring to these patients.
spk06: Good. I think, Dennis, you also asked the question about the larger issue of weight, maybe weight loss in general. And I just want to make sure all the listeners know that we have no programs in weight loss as a entity. This really is about the specifics of patients who have gained weight by taking antipsychotic medications, medications like Lanzabine or Risperdal or Seroquel. That's where we're aiming right now. It's a very different program to consider for weight loss in general.
spk01: Next question, please. Yes, thank you. Our next question comes from the line of Greg Frazier of Truist, your line is now open. Greg Frazier, your line is now open.
spk05: Ah, sorry. Thank you. Thanks for taking the questions, and good afternoon. Sure. Quick follow-up on Miracorland. It sounds like you'll be, when you make the announcement, you'll be providing a lot of quantitative results from the study to help investors assess the outcome. the right way to think about it.
spk06: Yeah, I mean, these studies, as you know, are the first studies we've done with miracoralin in antipsychotic-induced weight gain or reversing antipsychotic-induced weight gain, and we think they're going to provide a very rich data set which will indicate our best path forward. Got it. Okay.
spk05: For Coralim and the guidance and the growth that's assumed in 2022, how much of the growth is driven by new patients versus price or higher average dose or changes in gross net or any other factors?
spk07: I'm going to return you to Sean for that answer. So just to clarify, the question is the forward-looking through the end of this year, that growth is driven by new patients and more tablets out the door to those patients.
spk06: And to your question about dose, Our dose rarely changes. It's been the same, you know, same average dose for many years. Got it.
spk05: Okay. I'm sorry if I missed this. I got on late, but did you comment on the competitive environment? Are you seeing any impacts from Recorla or from the more mature products? I'm curious if the other companies, maybe you're seeing other companies doing things differently than they have in the past that may be having an impact.
spk06: No, Greg, you didn't miss it, but we understand the question, and Sean will answer it.
spk07: Yeah, very similarly to how I've responded in the past on this one. We haven't seen an impact. And we're pleased, honestly, that more companies are out there talking about hypercortisone. It raises awareness, which I just mentioned is lacking in certain areas and ultimately in all the patients.
spk05: Okay. And then on grace, has patient enrollment been hitting your target?
spk08: Bill? Well, we don't typically talk about enrollment. What we talk about is our focus on submitting an NDA. And the team is focused on completing that NDA in the second half of next year. And I'm very confident that the team is working hard to meet that target of submitting that NDA. You know, we've taken, as I think I've said on previous calls, an all-hands-on-deck approach, and that continues. We're cross-functionally working with investigators, as well as working internally, not only to enroll the study, but also to start actively writing and completing the NDA today. And we are actively working on the NDA. I think we're actively working with the FDA. You know, we've completed investigative meetings in the U.S. and Europe this year, and we've made many one-on-one visits to our key investigators. And it's clear after meeting with those investigators and talking about the trial that they have an unwavering support and excitement around relic correlant and the GRACE study and are committed to completing this trial.
spk05: Have you said when you expect to enroll the last patients?
spk08: We expect to submit an NDA by the second half of 2023.
spk05: That's our focus. Yeah, understood. Okay. Thanks for taking the questions.
spk01: Thank you. One moment for our next question, which comes from the line of Alan Leong of BioWatch News. Your line is now open.
spk10: Thanks. This is Alan Leong. Hi, Alan. Yeah, I have a few fine-grained questions. Let me ask, how prevalent is NASH or fatty liver among chronic schizophrenics? And is there any collected info to infer this in the current antipsychotic-induced weight gain trial?
spk06: Yeah, your question was a little hard to hear. I'm going to repeat it, and then I'll answer the question I thought I heard, and we'll go from there. I think you were asking, is it known or do we know prevalence of NASH in patients who have chronic psychiatric illnesses and are treated with antipsychotic medications. That question is, we don't know the prevalence. I don't think anybody knows the prevalence. I don't think it's been counted in that way, but it's not zero. Without a doubt, these are patients who have overweight, and they have, in many cases, have been overweight for a real period of time. And those certainly, those two characteristics are certainly correlated with the development of fatty liver disease and NASH. So I can't answer your question quantitatively, but qualitatively, it certainly is something which exists.
spk10: Yeah, the same question for ALS patients. What do you know about ALS? metabolic syndrome in ALS patients, especially when I look at the literature, it seems like the CNF and neuromuscular patients seem to experience cortisol dysregulation. So I'd love to get your commentary on that.
spk06: Well, you know, good. Thank you for giving me the opportunity to talk about that. It's really been known for quite a while, probably 20 years, that patients with ALS have hypercortisolism. They exhibit hypercortisolism. Never really been known what to do about that or if that was, in fact, leading to their disease. But the key element for us was a very strong academic researcher who treated an animal model that It was sort of a standard animal model for ALS and found that treating them with a cortisol modulator really led to both pathological and clinical improvements. Now, how they relate to, you know, I'm not sure if the question was about whether those patients have metabolic disturbances. I know that less. In some sense, the issue of ALS is so profound that you don't see a lot of reporting of other symptoms. So I've never actually heard that question posed before, and I'm not sure I've ever seen any literature on it.
spk10: Last question. You have the MRI NASH sub-study. Would it also be able to detect fibrotic composition and structure? Because in the past, MRI detected only growth changes, but I want to make sure I haven't missed anything with very recent improvements in the MRIs.
spk06: Yeah, for that question, I'm going to give you back to Bill, who really is a NASH expert and has, you know, been in this field for many years.
spk08: Go ahead, Bill. Yeah, thank you for that question. So, for the sub-study, I mean, our focus mainly is around liver fat reduction. And the reason for that is it's been seen in most literature that when you get at least a 30% drop in liver fat reduction, that corresponds to getting improvement in fibrosis. Now, within the Phase 1B study, we're not looking at fibrosis at this time, but there were other non-invasive markers that we're going to be using and analyzing as those biomarkers to look at improvements in liver fibrosis. We will then take those learnings and apply them as we move forward to a phase two study and use those same parameters and or use liver biopsies as well. But yes, we will be gathering biomarkers to look at liver fibrosis to see if we're seeing improvements there as well.
spk10: Thank you. Looking forward to the next month.
spk06: Yeah, thank you, Alan. And thank you to everybody who's listened in. We're really looking forward to our next communication and hope you have a good rest of the week. Thank you very much.
spk01: Thank you for your participation in today's conference. This does conclude the program and you may now disconnect.
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