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spk09: Good afternoon. My name is Kathy and I'll be your conference operator for today. At this time, I would like to welcome everyone to the Ramada Therapeutics, Inc. third quarter 2022 earnings call. All lines have been placed on mute to prevent any background noise. After the speaker's remarks, there will be a question and answer session. If you'd like to ask a question during that time, simply press the star followed by the one on your telephone keypad. If you'd like to withdraw your question, again, press star one. Thank you. And Brian, Richie, you may begin your conference.
spk07: Thank you, Operator, and thank you all for joining us this afternoon. With me on today's call are Chief Executive Officer Sergio Traversa and Chief Financial Officer Maga Chinada. This afternoon, RealMata issued a news release providing a business update announcing financial results for the three and nine months ended September 30th, 2022. and filed its quarterly report on Form 10Q with the SEC. Please note that certain information discussed on the call today is covered under the safe harbor provisions of the Private Securities Litigation Reform Act. We caution listeners during this call that Romada's management team will be making forward-looking statements. Action results could differ materially from those stated or implied by these forward-looking statements due to risks, and uncertainties associated with the company's business. These forwarded statements are qualified by the cautionary statements contained in Romada's press release issued today and the company's SEC filings, including in the annual report on Form 10-K for the year ended December 31st, 2021, and subsequent filings. This conference call also contains time-sensitive information that is accurate only as of the date of this live broadcast November 10, 2022. Realmada undertakes no obligation to revise or update any forward-looking statements to reflect events or circumstances after the date of this conference call. Now, I would like to turn the call over to Sergio. Sergio?
spk03: Thank you, Brian, as always, and good afternoon to everyone. I'm pleased to welcome you to the Realmada Third Quarter 2022 Conference Call. During today's call, I will provide an update on our ongoing late-stage reliance clinical development program for REL 1017, our lead product candidate that we are currently studying as a novel treatment for patients with major depressive disorder, or MDD. Following my comment, Megha Shenouda, our chief financial officer, will review our financial results and balance sheet, and we will then take your questions. As a reminder, Reliance I and Reliance II are two ongoing Phase III sister two-arm placebo-controlled pivotal studies evaluating REL 1017-25mg as a potential adjunctive treatment for MDD. Reliance III was the Phase III two-arm placebo-controlled registrational study evaluating REL 1017-25mg as a potential monotherapy treatment for MDD. We announced top-line results last month for Reliance III in which REL 1017 was administered for 28 days to 232 subjects. The study did not achieve the primary endpoint of a statistically significant improvement in depression symptoms compared to placebo as measured by the Montgomery-Asper Depression Rating Scale, or MADRIS, on day 28. In this study, the REL1017 treatment arm showed a moderate reduction of 14.8 points at day 28 versus 13.9 points for the placebo arm. This was in higher than expected placebo response. Paradoxical results were observed in certain study sites where placebo dramatically outperformed REL1017. To better understand the paradoxical results, a post-op exploratory analysis using the bandpass method, which excludes sites with implausibly high or low placebo response was conducted. In this study, an implausibly high or low placebo response was defined as a mean decrease from baseline in Madras 10 score greater than 14 and less than 3 points. The results of the bandpass analysis showed a meaningful difference between REL1017 and placebo greater than 4.9 points on the MRAS representing a p-value below 0.05. It's important to note that while we are pleased with this statistically significant difference seen using the bandpass method, we understand that this is not sufficient to be used as an FDA submission, and we may consider planning additional studies. I want to highlight that in Reliance III, REL 1017 demonstrated very favorable tolerability and safety, confirming the results of Phase I and Phase II studies, with no opioid-like effect, no withdrawal effect, and no cytokinetic effect. While we are currently further evaluating the data from Reliance III, we believe that the primary driver behind the study not being successful was the enrollment of subjects who are not truly suffering from MDD. and responded dramatically and rapidly to placebo. As an example of this, the top enrolling center had a mean change from baseline of 23 points in the placebo group. As we approach the top line readout for Reliance 1, expected before year end, it is important to note that the high enrolling center is in Reliance 3, also recruited significantly in Reliance 1. Mitigating that to some degree is the different patient population reliance one. That is patients that are enrolled and should already be diagnosed with depression and are not responding adequately to at least one and up to three courses of antidepressant therapy. We cannot predict how this factor will balance out. Looking further ahead, we intend to apply several protocol and operational changes in the current enrolling Reliance 2 study and make certain improvement to how the trial is being conducted. We now expect top-line results from this study next year. Once we have finalized and determined how to best execute on this enrollment, we will provide a firmer timeline for top-line results for Reliance 2. Moreover, In order to be proactive and increase the likelihood of clinical success for REL1017 as a potential therapy for MDD, an indication in which two successful studies are required to achieve FDA approval, we may consider initiating new clinical trials in 2023. As we apply key learnings from Reliance 3 to improve how Reliance 2 is being conducted going forward, we focused on the four key pillars that mainly impact the success of an MDD trial. the protocol, the site selection, the patient selection, and the rating process. We will integrate our key learnings in this area into the Reliance 2 study and any possible additional study we may consider. Now, let's move on to Reliance OLS, the long-term open-label safety study that is enrolled in both rollover participants for all three PIVAPA studies, as well as de novo participants. Reliance OLS is ongoing and continues to involve participant-as-planned. Data from this long-term open-label safety study, which we now expect in first half of 2023, will be part of the planned NDA filing package. Finally, I want to emphasize that Reliance 3 was a trial-execution failure, and we remind highly confident in the potential of Rel1017 to be a safe and effective new therapy for the sweet-net-to-MDD. It is important to note that we have the financial flexibility to continue advising Proud 1017 in the clinic due to our strong balance. Maggot will review our financial in detail shortly, but we ended the third quarter with cash, cash equivalent and short-term investment of approximately $124 million. With that, I will now turn the call over to Maggot for a review of the financial. Maggot, the stage is yours.
spk06: Sure. Thank you, Sergio. Today we issued a press release announcing our business and financial results for the three and nine months ended September 30, 2022, which I will now review. For the third quarter ended September 30, 2022, total research and development expense was approximately $30.5 million as compared to $34 million for the comparable period of 2021. The decrease was primarily related to a decrease in stock-based compensation. This non-cash charge totaled $3.2 million in the most recently completed third quarter. Total general and administrative expense for the third quarter ended September 30, 2022, was approximately $8.2 million, as compared to $8.7 million for the comparable period of 2021, a decrease of approximately $0.5 million. The decrease was primarily driven by a decrease in stock-based compensation This non-cash charge totaled $5.2 million in the most recently completed third quarter. For the third quarter ended September 30, 2022, the net loss was $39.4 million, or $1.31 per basic and diluted share, compared to a net loss of $42.6 million, or $2.44 per basic and diluted share in the comparable period of 2021. The results for the nine months ended September 30, 2022. Total research and development expense was approximately $86.5 million as compared to $65.3 million for the comparable period of 2021. The increase was primarily related to an increase in costs associated with the execution of a broader clinical program for REL 1017. For the nine months ended September 30, 2022, total general and administrative expense was approximately $36.1 million as compared to $26.2 million for the comparable period of 2021. The increase was primarily driven by an increase in stock-based compensation. For the nine months ended September 30, 2022, the net loss was approximately $119.1 million, or $4.04 per basic and diluted share, compared to a net loss of $91.4 million, or $5.36 for basic and diluted share in the comparable period of 2021. As of September 30, 2022, We had cash, cash equivalents, and short-term investments of approximately $184.2 million compared to cash, cash equivalents, and short-term investments of approximately $211.9 million at December 31, 2021. As Sergio mentioned, our current cash position provides us with ample runway or approximately two years of cash. I will now turn over the call to Sergio. Sergio?
spk12: Thank you, Maggot.
spk03: Before taking your questions, I would like to share that we have on the call with us today the Reliance Program Principal Investigator, Dr. Maurizio Fava, the Chairman of Harvard's Psychiatry Department, that can answer questions regarding the REL 1017 clinical development. Thank you, Maurizio, for joining us. My pleasure. With that, I will ask the operator to open the call for questions. Operator?
spk09: Thank you. And at this time, I would like to remind everyone, in order to ask a question, please press the star, then the number one on your telephone keypad. We'll pause for just a moment to compile the Q&A roster.
spk10: And first, we will go to Mark Goodman of SVB Securities.
spk04: Thanks for taking my question. It's really on the line for Mark. Reliance One data is expected in first quarter. I'm wondering, are you making any changes to this study? What are your current plans to do with the study sites where placebo will perform the drug?
spk12: And did you talk with FDA to get an agreement for your data analysis?
spk03: Thanks. Thank you for your question. Well, the Reliance One is pretty much done. We are planning to close the database uh in the next two three weeks so we you know we expect to have data before the end of the year so it's way too late to make any change and uh now i noticed in the in the opening remark there you know there is some difference the the two factors in reliance one that could make a difference one is that the patient population is different so these are patients not naive not monotherapy the patients have been supposed to be diagnosed with depression, they have been taking at least one treatment for at least six weeks, and they have not responded adequately. So, and theoretically, and Dr. Fava can help us out on this topic, but theoretically, these patients will respond less to placebo. At the other side, the sites and the operational issues that are affected Reliance 3 are present, especially the sites that are enrolled. Large parts of the patients in Reliance 3 are also enrolled in Reliance 1. We don't know how these two factors, one is in favor, the other one may not be in favor, how they will balance themselves. But it's way too late to make any changes. We want to see what the result will look like. And sorry, can you repeat the second part of your question?
spk04: Yeah, just wondering, What's your current plan for data analysis? Is it going to be the same for, like, Reliance 3? Yes.
spk03: Yes, it's the same. We'll probably provide the band pass, but, you know, the band pass is a very good diagnostic tool, and it tells you if the product works or not. But, you know, we think that the primary analysis will be the same as Reliance 3 with all cameras.
spk12: Got it. That's very helpful. Thank you. Thank you.
spk10: And next, we'll take our question from Yar of New Suho.
spk00: Hi, guys. Thanks for taking my question. Just wanted to get a better understanding of the, I guess, the diagnostics or the tools that was used to assess the incoming patients in Reliance 3, whether the tool captured some patients who are, you know, who have been chronically depressed or, you know, are episodically depressed. They've not really established sort of like a persistent state of depression. So that's my first question. And I guess my second question is, in Reliance One, I think you said the studies have stopped and Could you tell us whether you enrolled the expected number of patients and whether the DSMB has asked you to stop the enrollment, or is it you think it's sufficiently powered, just wanted to get a better sense of what's going on there? Thanks.
spk03: Sure. Thanks for the question. Dr. Fawa, you may take the first one. You help us out a lot to analyze this data, so please go ahead. I will then answer the second question.
spk02: Go ahead. So it's a great question. I'm Maurizio Papa, the chief of psychiatry, mass general, and the principal investigator for the studies. One of the characteristics of the monotherapy trial was that patients had to be off medicines. So they had to be typically treatment-naive, never treated during the current episodes. And in addition, they had to be relatively lean for U.S. standards. That is, they had to have a BMI between 18 and 30. And we know, for example, that chronic and recurrent depression is associated with weight gain. People end up having BMIs, you know, well in their 30s. So I think that the combination of the pandemic causing stress-induced depressive episodes in individuals who do not have a prior history of depression has led to a number of individuals seeking treatment from a study because they were, you know, having trouble accessing treatment because they were not in treatment, if you wish, before. And, you know, as we see often, stress-induced and depressive episodes have a high probability of spontaneous remissions. They get better on their own. But if they get better on their own, they can get better on placebo as well. In the 301 study, we have patients who have to be on antidepressants, have to have failed to respond to antidepressants. They have to be in treatment with a psychiatrist. And so they're very likely to have recurrent forms of depression. So more bona fides. conditions, medical conditions. The challenge is that according to our DSM-5 classification, a person who develops depressive symptoms acutely meets the criteria for a major depressive episode exactly as someone who has had recurrent episodes or has chronic symptoms. So When we designed the monotherapy study, we did not factor in the impact of the pandemic on kind of the diagnosis of depression in the general population. You know, I can tell you, as the chief of psychiatry in general, we've seen a tripling of the referrals for anxiety and depression to our department. And we've seen nationally in epidemiological studies that we see a tripling of anxiety and depression. So are these diseases where we're seeing this rise of people experiencing depression or are these stress-related depressive episodes that in some ways will spontaneously resolve? The answer, we don't know the answer, but it clearly affected our hormone therapy trial. In my opinion, this should not be the issue in patients who have been, you know, under treatment with a psychiatrist, not responding to treatment. The chances of spontaneous remissions are very, very small in that population compared to patients never treated first episode, you know, caused by the pandemic.
spk03: Thank you, Marisa and Dr. Fava. And I hope that answers your question. And the second part of the question is the number of patients. The number of patients was a variable up to 350 patients, 1060. The DSMB recommended to stop the trial at the minimum number. It was 220. We exceeded a little bit that, and we are exceeding a little bit that. But don't read anything into that because the data monitoring committee may have made a recommendation for two reasons. The trial is futile, so it's not worth to proceed and add more patients that it would never be statistically significant, or the trial is already statistically significant at the 220 numbers. So, I mean, what the ADSMB recommended, it doesn't, mean anything in terms of results. No way to read if it's because the trial will be successful or the trial will not be successful. I hope that answers also the second part of your question.
spk00: Yeah, thank you very much. Thanks.
spk10: And next we go to Yatin Sanjia of Guggenheim Partners.
spk14: Hey, guys. Just a couple questions for me just to clarify it. How many of the sides that were in the monotherapy study are going to be overlapping in Reliance 1? I think previously when we had discussions with you, you seemed to imply that there is a possibility of increasing the sample size. I mean, if the study is still not done yet, why not increase the size in order to be statistically significant?
spk12: Yeah, well, thank you for the question.
spk03: And in terms of overlapping of sites, I don't have the exact number, but there is a vast, like I would say that overlapping is pretty high between monotherapy and Reliance One. The one that really matters is the sites that have a high, they enroll a lot of patients, the high-enrolling sites, and they are the ones that have this paradoxical response where placebo outperformed the drug by quite a bit, and it's kind of isolated to a few sites. So these are the ones that really could make the difference. We don't know. The sites are in Reliance 1 as well, but we don't know if the phenomena is going to be the same or not. As Dr. Faro was saying, this is different patient populations, so these sites may have different results, but we won't know it until we see it. And we discussed about expanding the enrollment in RUNCH 1. We did the SMB recommendation. If the site or if the trial is somewhat compromised, adding more patients will just expand time, cost, and probably unless we triple or double the number of patients won't make such a big difference. So it's much more productive to just see how the results look like, learn from the results, and eventually or likely start at least one new trial from scratch, applying all what we have learned from immunotherapy and what we will learn from the reliance one. So the decision was really just let's see how the data look like as the profile location is different.
spk14: Got it. And then to clarify, is the Reliance 2 already ongoing or that one is also on pause given that you first want to see what Reliance 1 is going to yield?
spk03: Well, clearly, how Reliance 1 will look like, it will have an impact on Reliance 2. For now, we are just implementing quite a bit of changes from the protocol to limiting the number of patients per site. So in changing the way the rating is done from a localized to most likely a lot less localized rating. So we are implementing these changes, but technically the trial is open. They only roll 25% roughly of the full patient population. So Reliance 2 is still a very valuable trial. the site and the similarity with Reliance 1 and 3, the sites that are affected Reliance 3, they're not in Reliance 2. And so that's already an indication, the number of patients is low. So that's a perfectly non, we don't think it's a compromise study that will continue to evolve and we expect to complete and have data sometime next year, probably.
spk12: I hope I answered your question.
spk09: And we'll move to our next caller, and that will be Andrea Tan of Goldman Sachs.
spk01: Hi, Sergio. Thanks for taking my question. Maybe you want to follow up there. Just wondering if you've been able to understand more what happened at those sites where you did observe the paradoxical results. Anything in particular that they may have been doing differently on study execution? than the other sites? And do you think additional training is maybe necessary as you look to these improvements that you were speaking about for Reliance, too?
spk03: Yeah, I would let Dr. Fava to answer that question. From my perspective, clearly additional training is needed for these sites. And then, you know, the FASTA enrollment. These sites are sites that we call them commercial sites, but they enroll patient as a base of their business so they they are not hospitals or clinics or so they're pure like uh the the size of the rotation for clinical trial and pretty much all the patients that they enrolled there have been involved coming from social media advertising so when you're all a lot of patients you're all fast and uh you know sometimes
spk02: the you know the the diagnosis is done a little bit on the on the past side but i like dr howard is really the expert of this to go more in detail yeah no it's a great question i think that you know i'm not uh certain necessarily that um that the fault was in the assessment Again, we need to consider the population that we were trying to enroll. The study specifically looked for people untreated with acute depressive episodes in the midst of a pandemic and recruited primarily through advertisement. So if I... I'm already an existing patient. I have my doctor. If I have a recurrence of my depression, I go to my doctor. I go back to the medicines I've tried before. But if I've never been treated before, I may respond to an ad. I may look at a study. So whenever you do a study that specifically looks for people who have never been treated before, who have developed symptoms acutely, don't have chronic or recurrent depression, and therefore you don't know that, you know, at least in prior episodes, have shown, you know, that they've responded only to medicines, you're likely to have what we call abnormal placebo responses. And the abnormal placebo responses are due to spontaneous remissions that may have happened, you know, at any point during the study. So the same site that may have performed terribly by enrolling these people who had depression but not recurrent Remember, we did not ask for chronic or recurrent depression. We asked for acute depression in untreated patients who are not treated by anybody. So you're looking for the best case scenario of someone who in some ways is very likely to respond to the first therapeutic intervention that they receive. You know, just interacting with people, getting out of the house during the pandemic, et cetera. Whereas in the other study, we're taking people who are in treatment, who are currently engaged, who are likely to have either chronic or recurrent depression. So it's like a different disease altogether. And so I don't know if... if I would predict that the same sites that perform badly on the immunotherapy trial are going to perform badly on the augmentation study because it's two different populations and the referral process is very different. I don't know if that addresses your question, Andrea.
spk01: Yeah, that was really helpful. As a follow-up there, I guess, to what extent do you believe the safer interview should have been able to you know, maybe mitigate some of those issues or caught people that, you know, maybe were not appropriately enrolled in the trial, or is that just the nature of the different patient populations that you're referring to that you really can't rely on the SAFER interview?
spk02: Yeah, I think that... I'm pretty confident that for, you know, the SAFER would clearly protect you from high placebo response rates in patients who are currently treated. In patients who are untreated, normally a safer interview determines what medicines you're on, is the treatment adequate, what's the treatment history, how many times have you been diagnosed, et cetera, et cetera. So the interview gives a sense of the course of illness and the confidence that you're dealing with a patient with a real disease. In a monotherapy trial of an acute episode, the question, there's no question about treatment because there's no treatment history. There's no question about course of illness because there's no requirement of chronic or recurrent. And therefore, you're in a situation of high stress, like the, you know, like the pandemic, COVID-19, you know, even an independent interview is not going to protect you against the spontaneous remissions. So I think that it's really the nature of the population that is very hard. And, you know, had those patients with spontaneous remissions had been assigned to active treatment, right, instead of the placebo in those sites where they outperformed, you know, the placebo outperformed the drug, the drug would have looked fantastic. So, you know, you often hope that randomization takes care of it. But at the level of a given site, you don't know if, you know, randomization will protect you against these spontaneous remissions. But the odds of spontaneous remissions are far greater in a monotherapy trial where you're recruiting only acute depressive episodes.
spk01: Got it. Okay. And then maybe one last question, if I can squeeze it in for you. Sergio, just wondering if you could provide more color on the additional studies that you mentioned that you're thinking of conducting. Would this be for monotherapy specifically, or is this, I guess, maybe under the condition that Reliance... Reliance One is maybe not successful and you would have to do a second phase three trial for adjunctive. Thanks so much.
spk03: Yeah, no, thank you. And look, as much as I wish, we really need, we want to see Reliance One data result before and before we make any decisions. Because moving forward, we'll probably go, continue to go into the treatment of patients that did not respond adequately to a to a treatment. And so, you know, the Reliance One data, you know, are very important and critical to understand how we will move forward. The FDA, we believe they will want to positive phase three data. So, you know, we will be planning accordingly. it's not unusual to have failed study and jnj had i believe three out of five failed studies and the first two prozac studies failed so and it hurts when it affects directly but is not very unusual so we will really base the plan based on the the first adjunctive trial results and we are planning to start at least one one more trial but we will get a lot more precise in in january after we see the 301 and we believe in December. Sorry for that, but we'll give you all the information as soon as we have more accurate plans to how to move forward.
spk01: Great. Thanks, everyone.
spk10: Thank you. And now we will move to Andrew Saive. Jeff Rees.
spk08: Hi. Thanks, and good afternoon. Thanks for the questions. It's unfortunate to see the last three, but hopefully things get better. from here. So first question is for Reliance 3, the outlier sites, what percent of all patients enrolled in Reliance 3 did these outlier sites enroll? And then what percent of patients in those outlier sites, I guess, do you think will be enrolled in Reliance 1 and Reliance 2, respectively?
spk03: Yeah, thanks, Andrew, for the question. It's a little bit difficult to answer precisely, but like roughly the site that had results that we define paradoxical where the placebo outperformed the drug for whatever reason. And they enrolled about between 25 and 30% of the patient in Reliance 3 in the monotherapy. In the first adjunctive, it's unfair to make a comparison with the same site because as Dr. Fava said, the patient population is different so this site clearly they enrolled uh 30 between 30 and 40 percent of the patients but the patient population is different and we don't know how these sites really perform the diagnostic and of the patients and uh you know it may be different we hope it's going to be different from from monotherapy but in terms of like the percent of patients was between 25 and 30 percent in monotherapy and it's going to be between I was at mid-30s, maybe a little bit more than that, in the first pre-Zero-1, the first adjunctive trial.
spk08: None of these sites is in relapsed. Oh, okay. None of the sites. Okay. And so I guess maybe a bigger picture question is, you know, is this situation of paradoxical results... Is it a common occurrence in failed depression studies or is this kind of an exception due to COVID? Just curious what your bigger picture thought is.
spk03: Yeah, Dr. Pham, can you help me out on this? You're really the expert.
spk02: Sure. So if you look at approved antidepressants, you know, all the meta-analyses have shown that about 40% of the approved antidepressants were, 40% of the trials were positive. And the 60% of those studies that were positive, typically what contributed to the lack of signal detection was an average placebo response that was excessive. So an analysis by Eugenio and Papacosta showed that when you have placebo response rates above 40%, you tend to lose the ability to detect the signal. However, the challenge for monotherapy trials is right now the current stressful situation, the economy, the pandemic situation, so forth, because it will inflate the rates of depression in the general population. And if you are simply looking at an acute major depressive episode, those patients that have in response to the stress do meet criteria. So unless you specify that you want chronic and recurrent depression in monotherapy, unless you specify that we did not do that, you're more likely to have this what we call atypical spontaneous remissions. because of the situation we're in. And, you know, I apologize, Sergio, but I have another call at 5.15, so I only have three minutes left.
spk03: Thank you. I appreciate it.
spk08: And one last one is just the cadence of the event. So it sounds like Reliance One reads out December. Would you then... meet with the FDA to kind of discuss whether you can make certain improvements to Reliance 2 following Reliance 1, depending on whatever outcome it shows, and then you get back to the street. And then what would be those certain improvements?
spk03: Yeah, and I think, thanks, Andrew. At this time, well, first of all, we really want to see the Reliance 1 results. But at this point, we don't think there is really any need to meet with the FDA because the changes planned that we are actually implementing in Reliance 2 and most likely in any other trial that we do more additional trial in the future, they are not the FDA depending. It's really purely operational. Like, I can give you some example. There are a few of them, but they're limiting the number of patients enrolled per site. Like, you know, when a site's enrolled four patients and do an audit and see how things are going to be sure that, you know, the sites, you know, perform at the maximum level. You know, we probably, we are making some change in the ratings and the decentralized rating may add maybe too much variability and we may centralize more the ratings There are quite a bit of the protocol. We are simplifying the protocol of Reliance 2 and any other potential trial. Reason being that we now have a very large amount of treated patients and safety data. So there is no need to add ECGs. And so the protocol will be more simple. So it would be also easier. for the site to involve patients. Now we can go on on all these, but these are all operational, non-FDA related changes.
spk02: Nothing else to tell. And Sergio, if 301 is positive, then we wouldn't necessarily to have make major operational changes to 302. Correct.
spk08: Okay. And just one last clarifying is none of the outlier sites are in Reliance 2. Is that what I heard you say earlier?
spk13: Correct.
spk03: Correct.
spk08: Okay.
spk03: All right. Thank you. I would not really focus on culpabilizing the site. It's more the current situation. And we'll see how Reliance 1 looks like. But it could be that these sites could have performed very well in Reliance 1. So it's more like the complexity of the all and the diagnosis and the, you know, the kind of patient and role that made most of the difference. So I would not say that these are not good sites. These are very reputable, large sites that they, it is not the first depression trial they've done. They've done many of them and they're highly qualified. So I would say it's more, you know, the kind of patients for the monetary trial that was mainly responsible. Clearly, if this size would have been limited to a single-digit patient and not to 20 plus, the impact would have been lower. But again, we'll see what 301 looks like before we make a major amendment.
spk12: Very clear. Okay, thank you.
spk10: And now we will go to Jay Olson of Oppenheimer.
spk05: Hey, Jay. Hey, thanks for taking the questions. Can you just talk about what the path forward now is to pursue monotherapy, MDD indication for REL 1017?
spk03: Yeah, thanks for the question, Jay. Look, it is an artificial, and if Dr. Fabio still wants to call my help on this, but it is really an artificial, self-created difference between adjunctive and You have seen one of the competitors that we got approval for, and treatment of FDD is a combination of two different antidepressants. And so the indication that we are pursuing is treatment of patients affected by major depression that have not responded adequately to the current treatment they are on. And the doctor will decide. if it's going to be an add-on or it will stop the non-performing antidepressant and replace with Round 1017. So we are looking for a more broader label. The trial will be done in patients that have been not performing with the current treatment, also because the diagnosis is a lot more precise and there is a lot more confidence that these patients are really affected by major depression and not by personality disorder, anxiety, or other similar depression that can be confused with major depression. If we will be successful, it's going to be like a broader label, treatment of depression.
spk05: Okay, thank you. That's helpful. And then is there any color you could provide around what percent of patients in the reliance studies have opted in to the open label extensions?
spk03: In the monotherapy, that's a good question. I don't have that number on the top of my head. MAGIT is the number.
spk06: So broadly, the numbers that we have is about 75% of patients have opted into going into the open-label study.
spk03: That's for all the trials, though, not specifically to the monotherapy.
spk05: Okay, great. Thank you. That's helpful. Thanks for taking the question.
spk03: I think we have around 600 patients in the long-term safety now.
spk12: Okay. Super helpful. Thank you. Thank you, Jake.
spk10: And now we will go to Junlei of Trist Securities.
spk13: Hi, thanks for taking my question. Do you have any data comparing the PK-PD of powder formulation to tablet formulation from other REL 1017?
spk03: Yeah, thank you, John. We will, but I believe Dr. Manfredi and the team, they look at the PK profile. There is no difference.
spk13: PK profile and the tablet, gotcha.
spk03: Yeah, well, we have the...
spk13: the the powder in solution for from the phase two data and the we look at the profile in monotherapy and the blood levels that is not different okay and uh in the press release you say that you now expect these results in 2023 uh is that referring to reliance two and if so wasn't that always the case that you you kind of expect that in 2022.
spk03: uh well yeah the the we don't you know at this point we would like not be try not to be too specific on if it is for staff second half consider that rs2 is about 25 percent enrolled but also that the focus was really really on monotherapy with a lot of effort a lot of advertising and a lot of all the energy in completing monotherapy. And so, and then Reliance 1. So Reliance 2 has always been not slowed down, but not pushed to evolve fast because we wanted to see how the other two go. So now in 2023, Reliance 2 will be the focus. And eventually with maybe another phase three similar study that, you know, we'll decide after the 301 result. So we expect we should be able to complete it within 2023. But after Reliance One data in December, we'll be a lot more specific on what the plan will be.
spk12: Right. Thank you so much. Thank you, John.
spk10: And that does conclude today's question and answer session. I would like to turn things back to Sergio for any closing comments.
spk03: Thank you all. And thank you, Dr. Fava. Thank you to the team. And in closing, I really remain grateful to the RealMada team for the continued hard work and dedication to executing what that for us is really a mission. And I would also like to extend sincere thanks to the participants and the clinical partners involved in the REL 1017 trial for the effort in advancing this important product candidate to the clinic. And we look forward to 301 data and continue to the clinical development of Respirin 17 and hopefully get it approved at some point. Thank you very much and enjoy the rest of the day.
spk10: And with that, that does conclude today's conference call. We'd like to thank you again for your participation.
spk09: You may now disconnect.
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