Good afternoon, ladies and gentlemen, and welcome to the Relmada Therapeutics Inc. fourth quarter and full year 2023 results call. At this time, all lines are in a listen-only mode. Following the presentation, we will conduct a question and answer session. If at any time during this call you require immediate assistance, please press star zero for the operator. This call is being recorded on Tuesday, March 19, 2024. I would now like to turn the conference over to Mr. Tim McCarthy. Thank you. Please go ahead. 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, Maged Shenouda. This afternoon, Relmada issued a press release providing a business update, announcing financial results for the three and 12 months ended December 31, 2023. 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 that during this call, Relmada's management team will be making forward-looking statements. Actual 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 forward-looking statements are qualified by the cautionary statements contained in Relmada'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 31, 2023, and subsequent filings. This conference call also contains time-sensitive information that is accurate only as of the date of this live broadcast, March 19, 2024. Relmada 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'd like to turn the call over to Sergio. Sergio? Thank you, Tim, as always. Good afternoon to everyone, and welcome to the Relmada fourth quarter and full year 2023 conference call. We are continuing to make solid progress in advancing the ongoing phase III program for REL-1017 in major depressive disorder, MDD, as well as in the promising preclinical novel psilocybin program, all of which I will briefly cover today. Following this, Maged will review of our fourth quarter and full year 2023 financial results, and then we will take your questions. Let's begin with an update on the phase III program for REL-1017. As you know, Relmada is focused on developing REL-1017 as an adjunctive treatment for MDD. As previously communicated, we have made critical changes to RELIANCE II, the ongoing Study 302, a phase III, 2-arm, placebo-controlled pivotal study evaluating REL-1017 25 mg for adjunctive MDD, aimed at controlling placebo response and improving the enrollment quality. The amendment Study 302 protocol has been implemented across all our clinical sites. Enrollment continues to steadily progress, and our ability to leverage our close relationship with the study site is paying dividends. Moreover, the ongoing initiative we put in place to drive trial awareness with prospective patients are also bearing fruit. Importantly, we are evaluating the productivity of sites on a real-time basis and making changes where needed. As a reminder, we plan to enroll approximately 300 patients into RELIANCE II. Based on our current projection, we expect the enrollment into RELIANCE II to be completed in mid-2024. In our second phase III trial for REL-1017, named RELITE or Study 304, we began dosing patients during the third quarter of last year. RELITE also has a planned enrollment of approximately 300 patients that is planned to be completed by year-end 2024. To reiterate what we have said previously, like RELIANCE II, RELITE is a randomized, double-blind, placebo-controlled 4-week trial evaluating the efficacy and safety of REL-1017 as an adjunctive treatment for MDD in patients experiencing inadequate response to ongoing background antidepressant treatment. The primary endpoint of both studies is the same, is the change in the MADRS total score from baseline to day 28 as compared to placebo. I should highlight that we made significant changes to our screening and enrollment processes in order to ensure that we have patients that meet all the quality criteria. More specifically, we have instituted a comprehensive adjudication process through which we now require medical records for all patients involved in RELIANCE II and RELITE. Given this, our screen failure rate in these studies is now approximately 80% versus 50% previously in RELIANCE I and RELIANCE III, our previously completed phase III trial for REL-1017. We strongly believe that these changes will significantly enhance the probability of success of our current studies. Of note, we have completed all the necessary preclinical manufacturing and phase I studies required for a potential REL-1017 NDA filing and are now focused on execution of various pre-commercial readiness activities. Moving now to our promising preclinical novel, modified-release psilocybin program.... You may recall that at last November AASLD meeting, the liver conference, compelling clinical, preclinical data were presented in a poster presentation. These data demonstrated the beneficial effect of low chronic dose psilocybin on multiple metabolic parameters in a rodent model of metabolic dysfunction-associated steatotic liver disease or MASLD. These initial promising preclinical results support the therapeutic potential of low chronic dose of psilocybin. As we said previously, based on the data, low dose psilocybin could improve lipids and glucose with potential fewer side effects over other investigative treatment approaches such as GLP-1, glucagon, and GIP. We intend to initiate a single ascending dose phase I trial in obese patients in the first half of 2024, to define the pharmacokinetic safety and tolerability profiles for our modified-release psilocybin formulation in this population. This will be followed by a phase IIa trial to establish critical proof of concept. Data from the planned IIa study is anticipated in the first half of next year. Just to summarize our multiple upcoming key milestones over the next 12-18 months, we anticipate completing enrollment in the ongoing RELIANCE II study mid-2024, with top line in the second half. In addition, we plan to complete enrollment in the RELITE study by the end of this year. Finally, we intend to initiate the phase I clinical trial for the modified-release formulation of psilocybin in the first half of this year. Moving on, while Maged will provide a detailed review of our financials, I would like to emphasize that with current cash on hand, to take us into 2025, Relmada remains sufficiently funded to fully execute our plans to reach data readouts from both REL-1017 phase III trials, RELIANCE II and RELITE, as well as conduct the planned phase I for our modified-release psilocybin formulation. I will now turn the call over to Maged to review our fourth quarter and full year financial results. Maged? Thank you, Sergio. Today, we issued a press release announcing our business and financial results for the three and 12 months ended December 31, 2023, which I will now review. For the fourth quarter ended December 31, 2023, total research and development expense was approximately $14.8 million, as compared to $26.9 million for the comparable period of 2022, a decrease of approximately $12.1 million. The decrease was primarily associated with the completion of two phase III trials and the long-term open-label safety trial, Study 310. The research and development non-cash charge related to stock-based compensation totaled $1.8 million in most recently completed fourth quarter. Total general and administrative expense for the fourth quarter ended December 31, 2023, was approximately $12.1 million, as compared to $11.8 million for the comparable period of 2022, an increase of approximately $243,000. The increase was primarily driven by an increase in compensation expense due to higher employee-related costs. The general and administrative non-cash charge related to stock-based compensation totaled $8.1 million in the most recently completed fourth quarter. For the fourth quarter ended December 31, 2023, the net loss was $25.2 million, or $0.84 per basic and diluted share, compared with a net loss of $37.9 million or $1.28 per basic and diluted share in the comparable period of 2022. Turning to the results for the full year ended December 31, 2023. Total research and development expense was approximately $54.8 million, as compared to $113.3 million for the year ended December 31, 2022, representing a decrease of $58.5 million. Again, the decrease was primarily driven by a reduction in study costs associated with the completion of two phase III trials and the long-term open-label safety trial, Study 310. For the year ended December 31, 2023, total general and administrative expense was approximately $48.9 million, as compared to $47.9 million for the year ended December 31, 2022. Again, an increase was primarily driven by an increase in compensation expense due to higher employee-related costs. For the year ended December 31, 2023, the net loss was approximately $98.8 million, or $3.28 per basic and diluted share, compared with a net loss of $157 million, or $5.30 per basic and diluted share for the year ended December 31, 2022. As of December 31, 2023, we had cash, cash equivalents, and short-term investments of approximately $96.3 million, compared to approximately $148.3 million as of December 31, 2022. Cash use in operations for the full year 2023 was $51.7 million. Based on our current clinical development plan, our current cash position provides us with ample runway into 2025. Of note, this time period includes data readouts from both phase III trials, RELIANCE II, Study 302, and RELITE, Study 304, as well as the initiation of our planned phase II trial of our modified-release psilocybin formulation. I will now ask the operator to please open the call for questions. Operator? Thank you. Ladies and gentlemen, we will now begin the question and answer session. Should you have a question, please press star followed by the one on your telephone keypad. You will hear a three-tone prompt acknowledging your request. Questions will be taken in the order received. Should you wish to cancel your request, please press star followed by the two. If you are using a speakerphone, please leave the handset before pressing any keys. One moment, please, for your first question. Your first question comes from the line of Marc Goodman from Leerink Partners. Please go ahead. Hi, good afternoon. This is Basma on for Marc. For RELIANCE II, could you please remind us again how many patients were enrolled before the protocol amendments? And, do you expect that, due to the inclusion of these patients prior to the amendments, that there will be any source of, I would say noise or to the trial? Or were you able to go back and check the inclusion criteria? Thank you. Well, thank you. That's Sergio here. That's a great question. That'd be the previously to the amendment, we enroll about 80, 90 patients. And, and so the, as of now, I mean, they will be included in the, in the final analysis. And, like, we have noticed, if I can expand for a, for a bit, we have noticed that there was a big difference in patient enrollment when the COVID restriction were in place and, and, after the COVID restriction were lifted. So of these 80, 90 patients, about half were enrolled after the COVID restriction were lifted. So I mean, we, the data are blinded, so we don't really know how the data will look like, but we don't have any reason to believe that, right, this patient would carry any particular baggage. Also because the sites that where the issue with data was generated in the previous trials, they've never been phased in RELIANCE II. So the bottom line is that, yes, this patient will be included in the final analysis, but we don't have any particular reason to believe that would carry any particular burden on the final review. And we do have on the call Dr. Andrew Cutler, that is our special, you know, advisor for clinical development. Maybe Andrew, if you are online, you may want to expand a little bit on the question that is, right, will these patients enrolled previous to the protocol amendment carry any weight on the final results? Well, thank you very much. I'm here. Excuse me. I think it's a very reasonable question, but I'm pretty confident. I would say I'm very confident that we should be successful. The previous study really was very close to being positive. It just missed. And so you don't have to be perfect here, we just have to be better. I think the changes that have been made, particularly with respect to analyzing the quality of the sites and the protocol amendment, will make the quality of the second cohort here, which is gonna be the majority of the patients, I think will carry through. So I'm very confident that despite having some patients enrolled previously, you know, I still think we're going to be successful overall. Thank you. That's very helpful. I hope that answered your question. Yes, thank you. Thank you. And your next question comes from the line of Uy Ear from Mizuho Securities. Please go ahead. Thank you for taking my questions. So, I have a couple. So, just following up on the previous question, you know, at these sites that enroll patients previously. Could you maybe elaborate on or remind us, just like, were most of these patients referred by physicians? And, you know, were there large volumes of patients, or was it just a few patients at these sites? Yeah, so that's sort of the first question, and I'll ask a second question after that. Thanks. Yeah, sure. Thank you. Well, there were two sites that together enroll about 20% of Study 301, the adjunctive treatment study, and that they've never been present in 302. And, you know, there were a couple of issues there. We don't really know why the data of these two sites were the opposite or completely different from the other 41 sites in the trial, but, you know, just have to accept that, you know, that there was reality. But they've never been in the Study 302, and now we are limiting the number of patients enrolled for each site. So we won't have any site that will, like, make a major impact on the final numbers. So we feel confident that with these measures, what happened in the Study 301 will not happen again. Okay. Yeah, if I could add one other quick thing. Another, another modification we made was requiring medical records, to ensure that these were legitimate patients who actually were taking an antidepressant, and that was not done in the 301 study. So that's another improvement we've made. All right, thanks. And maybe, more presently, could you provide some color on maybe the proportion of patients who've been so far enrolled in RELIANCE II? And, and, you know, and maybe RELITE as well, and so... And, and after that, maybe just briefly, Maged, like, just tell us, help us think to think about how to to model the cadence of spending. Is, is it sort of relatively flattish, or would it sort of go down towards the end of the year? Thanks. Yeah, I'll take the first one. Maybe we may not want to go, like, in real details about number of patients, but, like, we passed half of the trial at the end of last year. Enrollment is progressing steadily with some variability, maybe week to week. But, you know, it's on track, and, you know, we are confident that we have top line data in the second half of this year. Like, when we get closer, we'll be a little bit more precise. But, you know, we stay with, you know, this a little bit broad guidance about second half of this year. Reason being that we are screening quite a bit of patients. I mean, I don't know, well, the number of screened patients is very large. What we have noticed with the improvement on the protocol, clearly the screening failure rate went up significantly. We were around 50% on the previous trial. I think I mentioned that before. We are now approaching 80%, so, I mean, the selectivity in enrolling patients is much higher. We did look, if I can expand on the reason why these patients are not enrolled and have been screened, and they're all legitimate reasons. So these are the patients that generated the issue in the previous trials, and definitely we don't want these kind of patients again in the new trials. So, you know, the screening process, it's going very, very well, and the screening failure for legitimate reasons, it's much higher. So we do believe that the quality is very, very good in this trial. I know, Andrew, if you want to add something. No, no, I think you've said it well. It's in line with what I said earlier. We're really trying to make sure we have the right patients, with legitimately with the illness and not patients with mild depression or who are not legitimate patients. So we're really trying to be careful about selecting the right patients. Maged, I think, the Maged, the second one is both for you. Sure. Yep, yep. So, hi, Uy. Thanks for the question. So G&A expense should, you know, follow the pattern we've had in 2023 on a quarterly basis. You know, a lot depends on enrollment patterns, but our current expectation is that R&D should tick up a little bit in the third quarter, and then, excuse me, in the first quarter, and then, again, you know, increase in the second quarter and then, you know, stay at that level through the third and fourth quarter. As you can sort of see enrollment pick up in 302 and then pick up in 304 as well. So I hope that helps. Very helpful. Thank you. Sure. My pleasure. Thank you. And your next question comes from the line of Andrew Tsai from Jefferies. Please go ahead. Hey, good afternoon. Thanks for taking my question. So, first one, I noticed in your prepared remarks, you said how you're monitoring sites in real time, making changes accordingly. So what exactly are you monitoring for, and what kinds of changes are you making on a day-to-day kind of basis? And then secondly, are there any learnings or thoughts that you might have on Sage's recent rejection for their MDD study? And sorry, not study, but the, the approval, and if there's any read-through or any lessons learned that you think you could apply to REL-1017? Thanks. Well, thank you. Thank you, Andrew, and thanks for the call. I will ask you after to repeat the second question because I didn't get it 100%. But the first question is, I think Andrew can go a lot more in detail since he has run a site for 30 years and has done many, many CNS clinical trial. But there is no magic, right? You monitor, in general, you monitor every like 3-4 patients, 4-5 patients enrolled by the site. How the blinded data they look like? Of course, they're blinded, so you don't know if they are if they are good... But you definitely can have a good understanding if there is something wrong, right? When you have data that the variability week over week of the first four weeks is one week, one week up, one week down, and you go up and down, you know, usually that's not the behavior that placebo and the drug do, right? When there is a trend, there is a trend. So that's one signal. And then, you know, the overall quality of the site, right? How, you know, the quality is documenting data. They put the data in the database. So there is no one single factor. It's the combination that can give you a sense if the site is providing, like, the service that, yeah, that we would like to. Andrew, I mean, you have done this for a long time. Do you wanna add anything? Yes. Yes, there are various quality indicators you look for, and I think we're watching, we're minding the store, much more closely here. You look for things like, are the rating scales consistent? Are they all, kind of, all moving in the same direction? You look for adherence to the protocol and what we call protocol violations, which indicates sloppiness. You know, this time we're being careful to not let, as Sergio said, any sites just kinda get off to the races and recruit too, too many patients or too fast. So there are a variety of quality indicators you look for and consistency things you look for, as Sergio said, and we're watching those. And then if there's a site that has issues, we're, we're actually, stopping their enrollment. We're trying to figure out what's going on and deciding if we wanna continue with them or not. Hope I answered your question, Andrew, and, if you don't mind to repeat the second one, because I didn't get it. Oh, perfect. You know, Sage recently had their NDA rejected for MDD, and I'm just curious if the reason behind that rejection has any bearing or read-through to your, you know, esmethadone, basically? Sergio, maybe I could help. Maybe I could help with this one. Yes, you can. Go ahead. Because I was very involved with that. It's really apples and oranges. Their paradigm was very different. It was a two-week treatment paradigm with a very different mechanism. And really, the problem was they didn't have a good story for how two weeks of treatment would hold a charge. And in their phase II study, there was a suggestion that the efficacy continued on beyond the two weeks. However, it was not well replicated in phase III, so the FDA had concerns about that. It's a very different paradigm, very different medicine. I don't see it as a compe-- you know, as an issue or anything that would influence what we're doing. Makes sense. Okay. Thank you, Andrew. Thank you very much. Thank you, Andrews. Both Andrews. Thank you. Once again, that is star one to ask a question. Your next question comes from the line of Andrea Tan from Goldman Sachs. Please go ahead. Good afternoon. Thanks for taking our questions. Sergio or Andrew, just curious if you're able to share what RELIANCE II and the RELITE studies are powered to detect, and remind us what you're assuming here for placebo response. Yeah, it's great. Thank you, Andrea, for the question. Well, we haven't filed with the FDA the final statistical plan. You usually do it at the very end. There is no advantage to doing it before. But, you know, it's a fair assumption that usually what you want to detect is a clinically meaningful effect. That, according to the expert in adjunctive treatment, is like 2-2.5 points. So the trial is designed to detect that kind of a change from placebo. And that is, right, that would be the minimum, right? We hope we can do better than that based on the phase II data, but that's a fair assumption. That would be the statistical plan. And with 300 patients involved, right, the. It's, like, it is feasible. It's realistic. Mm-hmm. And then maybe just one quick question on REL-P11 here. Just, I wanted to confirm which indication you're looking to study this in? Yes. We actually did not discuss the indication. Reason being that we don't really know exactly what kind of indication we will look at. Like, with the... We have to do phase I and, for, like, pharmacokinetic, all the parameters, the new formulations, the new concept, low dose, chronic treatment. What we can see is the effect that had on the rodent model, that according to the expert, it's somewhat relevant for what should happen in humans. And what we have seen is that, you know, there is a material decrease in body weight with no diet, with continuing the high fat, high glucose diet. So despite, like, high fat and high glucose diet, the rodent, they lost weight, not as much as a GLP-1, but enough to make it like a valuable drug to treat obesity. But at the same time, we have seen a material decrease in glucose level, like similarly, probably a little higher than metformin. And we have seen a very material effect on fatty liver and all these, like, continuing a diet with high fat, high glucose. So it kind of works on all the span of parameter metabolic symptoms so weight, glucose, and fatty liver. So I mean, the fair assumption that the indication will be a metabolic one. We haven't decided yet, and will be decided after phase II proof of concept, specifically what the indication will be. That, you know, could be like maybe not obesity by itself, but, you know, it could be also a combination with the GLP-1 and to overcome some of the limitation of the GLP-1, like muscle loss. But, you know, we need to see the data, and there is like a wide range of possibility all on the metabolic area, and that are suitable. And we'll try to do something that is, you know, a reasonably good way to get the drug approved in a relatively, you know, short amount of time. Got it. And I don't have the straight answer. Yeah, the straight answer, but that, that's where we are now, waiting for, you know, efficacy data to make the final decision where to go. Got it. Maybe just one follow-up there. Have you seen evidence to date pre-clinically that you are avoiding loss of muscle when you've tracked the weight loss in these rodents? Well, in the preclinical, we haven't seen it because we haven't looked at it. But it's a fair assumption that, right, since there is no change in diet, right, the model, the rodent don't lose weight because they stop eating or they reduce the food intake like with GLP-1. So psilocybin is 5-HT2A agonist, and it acts at the metabolic level. So pretty much it increase, you know, the metabolism of fat. So mechanistically is not really expected to have, you know, loss of muscles, unlike the GLP-1. Okay. Thanks, everyone. Thank you, Andrea. Thank you, and your last question comes from the line of Yatin Suneja from Guggenheim. Please go ahead. Good afternoon. Thank you for taking our question. This is Yatin Suneja. Following up to the previous questions, can you clarify if you already performed the real-time start tracking in the previous RELIANCE studies, or is it something that you have implemented new only now? Then I wanted to ask you about the statistical plan, if that is run by a third party or internally within the company. Thank you. Well, thank you for the question. If I understood correctly, the first question is that we did implement a monitoring of the sites in the study, in the previous studies, and the straight answer is no. And, you know, there was COVID, you know, a little bit more complicated to do it than now. And, you know, we didn't do it. So, but that's only one of the changes operational that were made in the new protocol. And so that was one, but you know, the requirement for medical record is probably the biggest one. And, and so, I mean, the whole goal, as we discussed, you know, a few times or many times, is to really enroll patients that are affected by biological depression, and they have a history. This is an adjunctive trial, so the patient has to come in, already on some antidepressant and, you know, to have access to medical and pharmacy records. It's a good proxy, to be sure that the patient is a real patient. These are things that we didn't do in the previous trial for a variety of reasons. Yeah, so, sorry, can you repeat the second one? Yeah. I was asking if the statistical plan is designed by a third party or internally within your company? Yeah, no, it is. Well, its design is a collaboration and, and so but it is, but it is we have the help of a, like, a large statistical consulting company, independent, that advise us on, you know, the statistics. Got it. Thank you. Thank you. Thank you. There are no further questions at this time. Mr. Traversa, please go ahead. Well, thank you. And in summary, we remain confident that we do have an approvable drug in REL-1017, and are excited by the potential of a novel psilocybin and derivative programs. So we look forward to reporting on progress with our pipeline in the near term, in the months ahead. And to close, I'm grateful to the Relmada team for their continued hard work and dedication to executing on our mission. And I would also like to extend my sincere thanks to the patients and clinical partners involved in the REL-1017 trials for their participation in the advancement of this promising investigational medicine in development. Thank you very much to everyone. Thank you. That concludes our conference today. Thank you for participating. You may all disconnect.