Good afternoon. Thank you for attending today's Relmada Therapeutics, Inc first quarter 2023 earnings call. My name is Forum, and I will be your moderator for today's call. All lines will remain muted during the presentation portion of the call with an opportunity for questions and answers at the end. If you would like to ask a question, please press star one on your telephone keypad. It is now my pleasure to pass the conference over to our host, Tim McCarthy from LifeSci Advisors. Mr. McCarthy, please proceed. Thank you, operator, and thank you all for joining us this afternoon. With me on today's call are Chief Executive Officer, Sergio Traversa; Chief Medical Officer, Dr. Cedric O'Gorman; and Chief Financial Officer, Maged Shenouda. This afternoon, Relmada issued a press release providing business update announcing financial results for the three months ended March 31st, 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 of 1995. 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 31st, 2022, and subsequent filings. This conference call also contains time-sensitive information that is accurate only as of the date of this live broadcast, May 11th, 2023. Relmada undertakes no obligations to revise or update any forward-looking statements to reflect events or circumstances after the date of this conference call. I would like to turn the call over to Sergio. Sergio? Thank you, Tim. As always and good afternoon to everyone. I am pleased to welcome you to the Relmada first quarter 2023 conference call. During today's call, we will provide an overview of our ongoing Phase III program for REL-1017 in major depressive disorder. Cedric will provide a clinical review and update, and Maged will review our financial results and balance sheet. We will take your questions. To begin, as we said on our last call, based on the results from Study 301, we intend to primarily focus on REL-1017 as an adjunctive treatment for major depressive disorder or MDD. We have implemented critical changes to the ongoing Study 302, a Phase III two-arm placebo-controlled pivotal study evaluating REL-1017 25 milligrams, and we will initiate our new trial Study 304 for adjunctive MDD. Our Study 302 protocol amendment was finalized and is now being implemented across all clinical sites. The new Study 304 protocol has been drafted and will be ready for study initiation by mid-2023. The full results for REL-1017 in Study 301 reinforce that the two most important drivers for study success are recruiting the appropriate patient with true MDD and controlling for placebo response. REL-1017, unlike the conventional monoaminergic antidepressant, acts by blocking the NMDA receptor and correcting the consequences of dysregulated glutamatergic pathways believed to underlie the pathophysiology of MDD. It does not affect mood by altering neurotransmitter levels or independently of pathophysiology. It is believed that REL-1017 has no effect in the situational depressed patient, so its efficacy signal is dependent on enrolling appropriate subject with a true MDD pathophysiology and diagnosis into the trial. Since our last call, we have been focused on optimizing the design of our clinical trial for signal detection via the amendment of the Study 302 protocol and via the drafting of a new streamlined Study 304 protocol. Both resulting protocols have concentrated on recruiting appropriately diagnosed subject, controlling placebo response, and enhancing signal detection. Additionally, we have been finalizing the selection of the preferred clinical sites and have been visiting these sites as we strengthen our relationship in collaboration with them on our clinical trials. I'm also pleased to report that the open label one-year safety study for REL-1017, Study 310, is concluding with all treatment visit completed and final safety follow-up visits occurring in the next couple of weeks, therefore attaining the necessary long-term safety exposure required for the purpose of our NDA filing. We expect to release data from this study later this year. Before moving on to provide further detail on the clinical progress in our first quarter financial results, I would like to emphasize that Relmada is sufficiently funded to fully execute our plans to reach data readouts from both Phase III trials. I will turn now the call over to Cedric, our Chief Medical Officer, to go over the clinical progress in the quarter and provide an update on the plans moving forward. Cedric? Thank you, Sergio. As Sergio indicated, we've now amended our Study 302 protocol, which has been IRB approved and subjects are already being screened under this streamlined protocol. The amendment has significantly lessened the burden to both subjects and sites by reducing required time spent by subjects at the site. This was achieved by removing duplicative assessments and evaluations that were of exploratory interest. The amended protocol capitalizes on our learnings from the completed control trials and optimizes the potential for reduction in the high placebo response seen in those completed studies. As you recall, when we analyzed the results of the Study 301, which failed to meet its primary endpoint, we saw in a post-hoc analysis of subjects from verifiable versus non-verifiable sources a striking difference. Verifiably sourced patients were defined as patients who were known to the sites, such as current patients obtained from the site database, and healthcare professional referrals. All of these elements increase the confidence in these subjects having a confirmed diagnosis of MDD as contrasted with non-verifiably sourced subjects. Non-verifiably sourced subjects were those recruited through radio and TV ads, social media, via the Internet, and through recruitment agencies. We observed that reliably sourced subjects treated with REL-1017 had a change from baseline of 15.2 points on the MADRS total score at day 28 versus 11.8 points for placebo. This amounts to a 5.5 point placebo-adjusted difference with a p-value of 0.016. From this post-hoc analysis of our Study 301 data, it is clear to us that in clinically depressed patients from verifiable sources, REL-1017 has a strong signal of efficacy. In the ongoing Study 302 and the upcoming Study 304, we will require that patients coming from verified sources have documented evidence of their MDD diagnosis. We will require medical records from prospective subjects to verify MDD diagnosis and antidepressant treatment history. Additionally, as you recall, two of our highest enrolling sites in the Study 301 were particularly impacted by paradoxical data and high placebo response. When we excluded all data from these two sites, the population was reduced by only approximately 40 patients, and we saw a 4.1 point placebo-adjusted difference at day 28 on the MADRS total score favoring REL-1017. These important post-hoc learnings have allowed us to make site selection improvements and prioritize moving forward with those sites who were better able to control for placebo response. Moreover, we intend to limit the number of patients enrolled per site so no single site can have a disproportionate effect on study outcomes, as was observed in the prior controlled trials. In the ongoing Study 302, we are planning to enroll approximately 300 patients and currently expect that trial to complete in the first half of 2024. Currently, we have enrolled over one-third or over 100 patients into this study. We plan to initiate the new Study 304 in mid-2023, also with a planned enrollment of approximately 300 patients, with completion anticipated in the second half of 2024. Additionally, as Sergio mentioned, our open-label one-year safety study for REL-1017, Study 310, is concluding with final safety follow-up visits occurring over the next couple of weeks, fulfilling the long-term safety exposure requirement for our NDA filing. We expect data from this study to be available later this year. As we continue to advance our ongoing phase III program for REL-1017, we are also focused on further enhancing the trove of published and presented data in support of our promising late-stage product candidate. To this end, we have had two late-breaking posters accepted for presentation at the upcoming 2023 American Society of Clinical Psychopharmacology meeting or ASCP at the end of May. One presentation will highlight the per-protocol efficacy results from Study 301. As a reminder, this was a pre-specified analysis. Per-protocol refers to the population of patients who were treated to day 28 and did not have major protocol deviations. This pre-specified analysis resulted in the exclusion of only 29 patients compared to the full analysis set. Per-protocol comprised 198 subjects compared to 227 in the full analysis set. The change in MADRS total score from baseline at day 28 was 15.6 points for REL-1017 and 12.5 points for placebo for a placebo-adjusted difference of 3.1 points and a p-value of 0.051 approaching statistical significance. The second presentation will review the safety results from Study 301, specifically the lack of indication of abuse potential and absence of withdrawal signs and symptoms in the trial. There was no difference between REL-1017 and placebo treatment groups in terms of drug likability, abuse potential, and withdrawal effects. I will now turn the call over to Maged to review our first quarter financial results. Maged? Sure. Thank you, Cedric. Today, we issued a press release announcing our business and financial results for the three months ended March 31, 2023, which I will now review. For the first quarter ended March 31, 2023, total research and development expense was approximately $15.9 million as compared to $25 million for the comparable period of 2022. The decrease was primarily associated with the completion of Study 301 and Study 303 in late 2022. The non-cash charge related to stock-based compensation totaled $2 million in the most recently completed first quarter. Total general and administrative expense for the first quarter ended March 31, 2023, was approximately $12.3 million as compared to $13.3 million for the comparable period of 2022, a decrease of approximately $1 million. The decrease was primarily driven by a decrease in stock-based compensation. This non-cash charge totaled $9.4 million in the most recently completed first quarter. For the first quarter ended March 31, 2023, the net loss was $26.3 million or $0.87 per basic and diluted share, compared with a net loss of $39.7 million, $1.40 per basic and diluted share in the comparable period of 2022. Net cash used in operating activities for the three months ended March 31, 2023 totaled $16.5 million compared to $19.4 million for the three months ended March 31, 2022. As of March 31, 2023, we had cash equivalents and short-term investments of approximately $132.4 million compared to cash equivalents and short-term investments of approximately $148.3 million as of December 31, 2022. Based on our clinical development plan, our current cash position provides us with ample runway through the end of 2024. Of note, the conclusion of Study 310, which Sergio discussed earlier, as well as completion of certain earlier stage studies will support this expected cash runway. I'll now ask the operator to please open the call for questions. Operator. Certainly. If you would like to ask a question, please press Star followed by one on your telephone keypad. If for any reason you would like to remove that question, please press Star followed by two. Again, to ask a question, press Star one. As a reminder, if you are using a speakerphone, please remember to pick up your handset before asking your question. We will pause here briefly as questions are registered. Our first question comes from the line of Marc Goodman with SVB Securities. Marc, your line is now open. Thanks. To my question, this is really on the line for Marc. I'm just wondering, based on the current data from RELIANCE I and II, do you believe that four weeks is the right duration to move forward with another trial? Do you think a longer trial, like maybe four, five or six weeks, may have increased the separation? Thanks. Thanks for the question. It's Sergio here. Cedric, I believe the question is for you. Yeah, thanks for the question. You know, we have looked at that, looking at the trajectory of the improvements observed with drug and placebo in the completed studies, we believe that if we can control placebo response and still see the trajectory of improvement with what essentially is a rapid acting antidepressant through its N-NMDA antagonism, we think that four weeks is sufficient in order to separate and have a positive study. Also we've got agreement with the regulatory agencies to pursue a four week. We think that the best approach now is to pursue four weeks. Also when you look at the per-protocol analysis and the other post hoc analysis, per-protocol being pre-specified and the post hoc, we believe that if we can control placebo response, four weeks would be a sufficient duration. Got it. That's very helpful. Thank you. Yeah. Yeah. Thank you, Cedric. If I can add, if you look at the curve on the like the 301 data, it may be a little misleading because the placebo response in this trial was extremely high and unusual because was characterized by a very early high placebo response. Usually placebo doesn't behave like that. It should not behave like that. On a normal placebo response rate, curve, it would show that 28 days, four weeks would be like an appropriate, primary endpoint timeline. Hope we answered your question. Yeah, makes sense. Appreciate the color. Thank you for your question. Our next question comes from the line of Uy Ear with Mizuho. Your line is now open. Guys, thanks for taking my question. I have two questions. My first question is, you know, I think you said you have completed selection for sites for the Study 304 studies. Just wondering if there's any overlap with the Study 302 studies. I think you also indicated you're limiting the number of patients enrolled in each of these sites. Just wondering like, how many patients are you expecting to enroll at each of the sites? I guess with, and how many sites are there with Study 304, if you can share that. My second question is, I think previously you indicated that you would read out the data for the RELIANCE long-term safety studies in mid 2023. Now you're just saying 2023. Just wondering if there's a change. Thanks. Thank you. We, Cedric, I believe that also this question is for you. Sure. Hopefully I'll hit on all the questions here, but the first one was about the selection of sites for 304 and whether there's overlap with 302. No, because we will be starting the 304 study mid-year and mid-middle of this year, therefore 302 is ongoing, they are unique sites across the two studies. I think you said, you asked how many sites per trial, and I think approximately 50 is a good guide. In terms of number of patients per site, we're not going to... We're going to make sure that we have a cap that doesn't allow disproportionate effect of any one site, but at the same time we're not providing an arbitrary number on which to cap, but we are carefully monitoring the activities so that they don't outweigh, you know, the rest of the sites performing on the trials. I think the last question was about guidance around data from the open label. We did say middle of the year, and the study is completing by, you know, the last follow-up safety visits occurring in the next two weeks. It's just a question of how quickly we can, you know, clean the data and get it to you. I wouldn't say that we, I wouldn't say that we are changing, our expectation there because we can still meet it just as soon as we clean the data and are able to generate the outputs. I don't know, Sergio, maybe you wanna add anything there. Yeah, no, I think that's right. I mean, the study has been completed or is on its way to be completed next few weeks. You know, it's 600 plus patients, so there's a lot of data, and we want to be sure that, you know, we have a complete understanding of the data before we release. It will provide quite a bit of new data, so we want to do it appropriately. It will be some time, yeah, in the second half. Okay. Thank you. Thank you for your question. Our next question comes from the line of Andrew Tsai with Jefferies. Andrew, your line is now open. Okay, great. Thanks. Good afternoon. Thanks for taking the questions. Great job, getting things up to speed. First question is, maybe a holistic high-level question for you guys. You know, at this stage, would you say how are you balancing quality of patients and sites versus getting the data as fast as possible for investors? Are you kind of operating in such a way that you are not taking, quote-unquote, "no shortcuts" whatsoever? Just so it's a high-level question to start. Yeah, I'll give you the top-down, and Cedric can expand and, you know, give you his opinion as well. Just in light of, you know, the experience that we had with the other two studies, clearly quality is the driver. Of course, we have to consider time too because, you know, the trial, the studies have to be concluded on a reasonable amount of time. Let's put it in this way, plus minus three months, we don't think that would make a difference for investors, as long as, you know, the results of the study will be, you know, positive. Cedric, you wanna add? Yeah, I would just echo what you said, Sergio, in terms of the focus being on quality, not on speed. I think that quality sites have been selected based on what we were able to learn from those sites that did a better job at controlling placebo response versus not. Also the sites that did a better job at being able to verify confirmed diagnosis and get the right patients into the trial versus the more unverified resource patients. Also, we're applying a really rigorous eligibility review process now. As a result of that and requiring medical records, it obviously slows down the rate somewhat in making sure that we don't so cut corners here and that we really get the most appropriate patients into the studies. Right. Makes sense. Another thing just came to my mind is I think last time you showed maybe a subgroup analysis where patients, you know, how patients performed differently pre and post COVID. It made me think, what if there was a new COVID variant later this year? Knock on wood. If that were to happen, what would you do for your study? Would you kinda pause enrollment? Just would be curious to gauge your thinking here. Thank you. Yeah, Cedric, would you mind to take it? It's a very interesting question. What I can say is that obviously, post-pandemic lifting of restrictions saw a much better effect and separation for drug versus placebo. The impact of COVID-19 across numerous trials has been documented already. It wasn't just our study. It's a valid concern, but I would also say that there are other aspects in the analysis that we did, which showed a more profound effect, you know, when you considered the verified patients with confirmed diagnosis versus unverified. Even the per-protocol pre-specified analysis showed that there was good retention throughout the entire study. We had very low discontinuation rates. REL-1017 has a particularly placebo-like side effect profile. This is really in two senses. It's aided continuation through the study, and in the other sense, often trials somewhat paradoxically benefit from this aspect of functional unblinding. It would appear that patients truly cannot distinguish between drug and placebo. That's my interpretation of the data that I've been looking at. If there was a pandemic, I think we'd have to look at that closely. I'm hoping that we're past that now, and that's the importance in getting this done. The studies are up and running right now, and the new study is set to start. Let's hope we don't have another COVID pandemic. Right. Yes. Okay. Very good. Thanks for the update. Thank you, Andrew. Thank you for your question. Our next question comes from the line of Andrea Tan with Goldman Sachs. Andrea, your line is now open. Hi, everyone. Thanks for taking my question. Two for me, please. First, with respect to the open label safety study, I know you've spoken in the past about the potential to understand the real world effect of treatment through that data set, but just given that these are patients who rolled over both from the failed RELIANCE I and RELIANCE III trials, just wondering if you could help frame expectations for that data read and how they should be interpreted within that context. Then secondly, just curious if a data monitoring committee will be utilized in 302 and 304 with respect to recommending early stoppage of the studies similar to what was done for 301. Thanks so much. Thank you, Andrea, and great question. I believe, Cedric, it's, you know, to answer. Cedric. Sure. Thank you. The open label study, you're absolutely right, Andrea. It really does reflect how patients might get the drug medication in the real world, and it can provide very important information regarding response, durability, continuation, tolerability of the drug in the real world, and you have it out to 12 months, which is really nice long-term exposure. It has quite a number of subjects in the study, as you point out, some are rollover from the completed 301 and 303. Some are rollover from 302. You also have patients who came in de novo into the open label study. It also has a mix of monotherapy and adjunctive. There are numerous sort of subsets that we look forward to parsing out and being able to share with you. Again, we'll have to see what the data is and with the study completing the safety follow-ups, there'll be more to come on that. With regards to the safety, the data monitoring committee, we always both internally have a rigorous safety review process for all our trials, and we would continue to use the data monitoring committee. With regards to potentially increasing the size of the study, that's certainly on the table for us to have a look at as well. Got it. Maybe just one. Sorry. One follow-up on the considerations for increasing the study size. Maybe if you could just provide a little bit more color around that comment. Go ahead, Cedric. Well, what I was going to say was we, you know, we haven't actually given any guidance about, you know, our like, so take 304, for example. The protocol is in its final stages of development. When that's finalized, the design will be shared, and it will be up in ClinicalTrials.gov. I would be sort of hesitant to jump into detail around plans for interim analysis or upsizing the trial only because we haven't finalized design. We haven't spoken about our plans in that regard yet. I wouldn't want to prematurely comment on that. Okay. Thank you. Thank you for your question. Our final question comes from the line of Yatin Suneja with Guggenheim Partners. Yatin, your line is now open. Yeah, a few questions from me. Could you comment on your interactions with the FDA? Have you met with them and discussed these amendment to the protocol for RELIANCE II? Then, you know, you made the modification. There are patients that were added before the modification. How will the mixed data be analyzed? Just curious, the interaction or the agreement has been. Yeah. Go ahead, Cedric. Go ahead. With regards to communications with the FDA, you know, clearly, we don't comment on specific interactions with the FDA, but we do have an ongoing dialogue with the FDA. We certainly wouldn't do anything that didn't have the approval of the regulatory authorities in any of our plans or decisions moving forward. With regards to the question around the patients before and after the amendment, I mean, ultimately we will finalize the statistical analysis plan and submit that to the FDA. You know, I won't comment on the specifics of our plan, statistical analysis plan, but having run a plethora of calculations and modeling around the first 100 patients in Study 302 versus expectations and assumptions based around the subsequent 200, we feel confident that if REL-1017 has a signal for efficacy, that this can be a positive study based on our calculations. Okay. Cedric, one more, if I may. This is with regard to the onset of action. If you look at the first, very first study that was done, I mean, the onset was pretty rapid, nice separation within a week. What has changed? Like even in a subset analysis when we take all the precautions and we do a post-hoc, the onset looks a little bit slower and the curves are not similar. What's going on? Thanks. Go ahead, Cedric. Okay. Thank you. I'm really glad you asked that question because you're absolutely right. In the phase II, the week one profound improvement with drug was like 16.8 points compared to 8.8 with placebo. We saw effect sizes of the order of 0.7 - 1.0. That was an incredibly well-controlled inpatient study. Now what we do know is that, outpatient... well, going from phase II to phase III is a challenge in itself, but then also the outpatient population is a little bit more difficult to control as we have seen from the various post-hoc analysis that I've already mentioned. What is striking in 301, for example, is that the majority of the placebo response happened in the first week. Ultimately, the change from baseline with placebo in Study 301 was 12.9 points, and the vast majority of that had occurred by day seven. In looking at the protocol, we were able to see that the screening visit was very, very long. The baseline visit was long. We had a day four visit which was long, then by day seven when they came in, they were having another extensive visit on site and getting interaction with the staff. I think that what you're seeing that's different is that the placebo patients were having what maybe is best described as a full therapeutic effect. All our efforts really are focused now on minimizing site patient interaction in that crucial first week. I think that, and what I'm hopeful for is that with the new amended protocol and the new study planned, you'll see less of a significant placebo change in that first week, and it'll be more gradual. The potential for REL-1017 to seem closer to what we saw in phase II, I'm hopeful that we'll be able to isolate that effect with this careful trial design that we've implemented. Thank you, Cedric. Yatin, if I can add little bit of color. We have seen from like the data there now, we have a significant amount of data available, and REL-1017 has a like a marked effect when the patient is really affected by MDD, so really depressed patients. Looking at the data clearly it shows that in 301 and the two studies that didn't work the way we would've thought and we would've liked, there were a significant percent of patients that were affected by other, like situational depression and/or not depressed at all or. So that, you know, the data have been kind of skewed in the opposite direction because of the, you know, patient selection. We do believe that if we, like the patient enrolled is a patient affected by depression, we should see an early response similar to phase II. Got it. Very helpful. I hope we answered your question. Yeah, no, that's very helpful. One more question if I may. Maybe Maged can comment on the expenses. you know, nice control on the R&D side. Curious how to think about the next three quarters and, you know, G&A still a little bit higher? would love to understand like how that would shape up? thank you so much. Sure. Thanks for the question, Yatin. With regard to G&A, I would expect it to stay in the $2 million per quarter range for, you know, the remainder of the year. Slightly up, slightly down, but on average around that for the remainder of the year. We haven't really given R&D guidance, but you can think of the entire year as having a little bit more R&D spend on a quarterly basis in the second quarter, then the R&D spend should start to moderate in the third and fourth quarter. We're gonna have, you know, trial startup spend in the third quarter, but all of this in around, I would say, the $15 million-$16 million range per quarter. Very helpful. Thank you. My pleasure. Thanks for the questions, Yatin. Thanks, Yatin. Thank you for your question. This concludes our Q&A session for today's call. I will now pass back to the management team for any closing remarks. Thank you. Sure. Well, thank you. In summary, we remain confident that we have an approvable drug, and that we have the right plan and the team in place to optimize the chances for success. We also believe we have the most reliable site identified and know how to identify the most suitable MDD patient, patients affected by major depression. We have greatly improved our study protocols. Also as a reminder, all other preclinical and clinical and CMC pieces are in place for a successful NDA filing for REL-1017. We are sufficiently funded to fully execute on our plans for REL-1017 development. We look forward to reporting progresses with Study 302 and 304 throughout the remainder of the year. In closing, I remain grateful to the Relmada team for their continued hard work and dedication to executing on our mission. I would like to extend my sincere thanks to the participants and clinical partners involved in the REL-1017 trials for efforts in advancing this important product candidate through the clinic. Finally, we are grateful for the opportunity to continue supporting our advocacy partner in their Mental Health Awareness Month initiative this May and appreciated the chance to support the important work that they are doing. That said, big thank you to all the participants and everybody interested on the progress and on Relmada, and we'll update you the next development in real time. Thank you. This concludes today's Relmada Therapeutics Inc. first quarter 2023 earnings call. Thank you for your participation. You may now disconnect your line.