Greetings. Welcome to the Relmada Therapeutics Inc. fourth quarter and full year 2020 financial results conference call. At this time all participants are in a listen only. A question and answer session will follow the formal presentation. If anyone should require operator assist during the conference, please press star zero on your telephone keypad. Please note this conference is being recorded. I will now turn the call over to your host, Tim McCarthy. 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, Dr. Sergio Traversa, Chief Financial Officer, Maged Shenouda, and Chief Accounting and Compliance Officer, Chuck Ence. This afternoon, Relmada issued a news release providing a business update and announcing financial results for the fourth quarter and full year ended December 31st, 2020. Please note that certain information discussed on the call today is covered under the safe harbor provision 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 and subsequent filings. This conference call also contains time-sensitive information that is accurate only as of the date of this live broadcast, March 23rd, 2021. 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. Good afternoon to everyone. I'm very pleased to welcome you to Relmada first ever earnings conference call. We do believe that the company has reached a maturity time that is a good time and right time to have a call. Since we expect a significant number of near-term catalysts moving forward, we intend to host update calls on a quarterly basis. The plan for today. Because this is our first earnings call and some of the people connected may not be very familiar with the company, I will begin with a brief overview of Relmada, our promising lead product candidate for the adjunctive treatment of depression, REL-1017, and the large market opportunity that we are targeting. I will then turn the call over to Maged for his review of our financials. After that, I will provide an update on our most recent accomplishment and a review of upcoming milestones and do my best to leave as much time as possible for your questions. As a brief background on how we arrived at this critical point in our corporate evolution. Relmada is a late-stage central nervous system, CNS, company focused on the development of REL-1017, which has the potential to address the significant unmet medical needs of major depressive disorder, MDD. There are about 17 or more million people in the U.S. that are affected by MDD. They have limited, safe, and effective therapeutic options. A standard antidepressant can take up to four to six weeks to show efficacy and up to 65% of the patients do not respond or do not respond well to their first antidepressant treatment. There are about 30% of the patients that don't respond up to four different antidepressant treatments. REL-1017 is being developed as a new chemical entity that's orally administered as a once-daily pill. We have patent protection up to 2033 with additional patents filed that could extend exclusivity to 2038 and beyond. We have over 50 issued and filed patents for REL-1017 and Fast Track designation for the adjunctive treatment of MDD. Based on the novel mechanism of action and phase II data that showed statistically significant rapid and sustained antidepressant effect with a favorable safety and tolerability profile, we do believe that REL-1017 has the potential to be the first FDA-approved antidepressant for the adjunctive treatment of MDD. In the phase II study, REL-1017 achieved statistical significance compared to placebo on all evaluated efficacy measures. Specifically, there was solid effects we observed on the MADRS scale. That is a well-established measure of the severity of depression with p-value below 0.03, and the large effect size, 0.7 up to one from day four to day 14. The extended efficacy up to 14- days was well beyond the seven days of dosing in the study, and it may suggest a potential neuroplastic and synaptogenic effect. Very importantly, there were no notable adverse events observed in the trial, with no evidence of treatment-induced dissociative, psychotomimetic, or opioid withdrawal symptoms. In December last year, we initiated RELIANCE I. That is the first trial in our phase III program of REL-1017 for the adjunctive treatment of depression. I will review the ongoing phase III program and discuss the upcoming milestone shortly. Before I do that, I will turn the call over to Maged for his review of the financials. Maged, it is all yours. Thank you, Sergio, and good afternoon, everyone. Today we issued a press release announcing our business and financial results for the fourth quarter and full year ended December 31, 2020, which I will now review. For the fourth quarter and year ended December 31, 2020, total research and development expense was approximately $14.9 million and $36 million respectively, as compared to $1.6 million and $7.9 million for the same periods in 2019. The increase was primarily related to an increase in costs associated with the execution for a broader clinical program for REL-1017. Total general and administrative expense for the fourth quarter and year ended December 31, 2020, was approximately $6 million and $24.9 million respectively, as compared to $2.9 million and $7.2 million for the same periods of 2019. The increase was primarily due to an increase in salaries and stock-based compensation. For the fourth quarter and year ended December 31, 2020, we recorded a net loss of approximately $20.8 million, or $1.28 per basic and diluted share, and $59.5 million or $3.81 per share, basic and diluted respectively, compared to a net loss of $4.5 million or $0.40 per basic and diluted share, and $15 million or $1.62 per basic and diluted share in the same periods of 2019. At December 31, 2020, the company had cash equivalents, and short-term investments of $117.1 million, compared to $116.4 million at December 31, 2019. We expect a strong cash position to support us through at least multiple data readouts we anticipate through the first half of 2022. I will now hand the call back to Sergio for additional remarks. Sergio? Thank you, Maged. As we had the recent announcement, I believe last week, I would like to start with an update on the human abuse potential or HAP studies. We recently announced that we early discontinued Study 120, which was assessing REL-1017 liking versus oral ketamine as an active control. As a pre-planned and blinded analysis of the initial study completers, while representing approximately 20% of the planned 40 patients, showed that a large percentage of these patients did not separate oral ketamine from placebo, which we believe was due to the poor bioavailability of oral ketamine. Very important, no dissociative or psychotomimetic events were observed in any of the treated subjects in all arms. To avoid futility, we discontinued this study and we will submit a new study design protocol to the FDA within the next month and proposing intravenous ketamine as an active comparator that has a very good and established history as an effective positive control. We anticipate the top-line data from the IV ketamine control study by the end of this year. Again, we would like to underscore that neither in the discontinued study nor in the previous clinical studies in our program or historically in existing literature, esmethadone has been associated with any psychotomimetic autoimmunogenic effect and we are encouraged by the confirmatory effect of these results. The HAP study 124 that is comparing REL-1017 to oxycodone continues as planned, and we will expect top-line data from this study by the end of the second quarter. This HAP study will be important in supporting the NDA submission for REL-1017, specifically for the FDA evaluation and the DEA determination of scheduling. It will also represent an important opportunity to add to the existing strong body of literature that clearly differentiates REL-1017 from methadone and any perceived association with dissociative symptoms or opioid effect. I will now share the key aspect of RELIANCE. It is our phase III program for REL-1017. The pivotal studies, RELIANCE I and RELIANCE II, consist of two sister two-arm placebo-controlled trials that include 364 patients per study across 55 sites. These studies will evaluate 25 -milligrams of REL-1017 and placebo on top of the patient's existing antidepressant treatment. These are patients who have failed to respond to minimum one up to three previous courses of antidepressant therapy in the current depression episode. The primary endpoint of this trial is change in MADRS score at day 28. Key secondary endpoints include change in MADRS score at day seven and CGI-S score at day 28. We believe that our phase III program is optimized to reduce the placebo effect risk based on the design, it's a two-arm study, the strong focus on site selection and their training, and the multiple levels of screening to ensure accurate patient diagnosis. Our first phase III trial, RELIANCE I, is enrolling as expected, and sites have come online nicely. We continue to anticipate the top-line data from RELIANCE I in the first half of 2022. The second phase III trial, RELIANCE II, is a mirror study of RELIANCE I and is expected to begin immediately. Data from this trial top-line are also expected in the first half of next year. RELIANCE-OLS, the open label safety study, began recently, and it is enrolling patients. This trial includes patients from RELIANCE I, RELIANCE II, but also de novo patients. We are also on track to initiate our study evaluating the use of REL-1017 as a monotherapy for MDD in the second quarter. We are currently evaluating options for this study design, and we will provide greater details once this is finalized. As you have just heard, it is an extremely busy clinical development period at Relmada, with several key data readouts over the next three to 15- months. Importantly, as Maged had highlighted, we have a strong balance sheet with enough cash to support us through all of these expected data points. I would like to take a moment to express my gratitude to the Relmada team for their hard work and dedication to executing on our mission. I would also like to extend my sincere thanks to the patients and clinical partners involved in the REL-1017 clinical trials for their efforts in advancing this important therapy through the clinic as expeditiously as possible. With that, we will now open the call for questions. Thank you. Operator, can you please open up for questions? Absolutely. At this time, we will be conducting a question and answer session. If you would like to ask a question, please press star one on your telephone keypad. A confirmation tone will indicate your line is in the question queue. You may play star two if you would like to remove your question from the queue. For participants using speaker equipment, it may be necessary to pick up your handset before pressing the star keys. Our first question comes from Andrew Tsai with Jefferies. Please go ahead. Andrew, your line is live. Oh, hey. Good afternoon. Thanks for taking my questions, and congrats on all the progress, guys. maybe for those in the audience, help us understand, remind us at a high level. You have these two abuse liability studies reading out fairly soon. remind us, what would you like to see on the VAS liability scores for both of these studies? What would positive data be like as we think about the three 1017 doses versus the two comparators versus placebo? Just maybe talk us through that, and I have a follow-up. Thanks. Sure. Thank you, Andrew. Maged, you want me to take this? Sure. Very top-down. These are not very complicated studies. If you look at every study, the data point that we expect and that people should look at as soon as the data are available is each of the three different doses of REL-1017 or esmethadone, 25 - milligrams, 75 - milligrams, and 150- milligrams, will have to be statistically different from the control. In this case, it's 40- milligrams of oxycodone and the ketamine IV in Study 120. This is really the two things that matter. One thing that I would like to clarify as a question that we have been asked some time or frequently. Esmethadone to be scheduled or non-scheduled, it does not need to be the same as placebo. It is an antidepressant. It is a CNS active drug. It's possible, and easily possible, that it will differ from placebo. If you take many of CNS active drugs, they're not placebo. The key point is that there has to be statistical significance from control. I hope I answered your question. Thanks. That very clear, Sergio. Thank you. My second question is, I don't know if you thought this through, but for the oxycodone study that's reading on Q2, I guess what would be some AEs of interest that would indicate euphoria, for example? Can we expect those AEs to be disclosed in the upcoming top-line data beyond just liability scores? Basically, I'm just wondering, how are you thinking about sharing the top-line results when it happens? Thanks. It's a good question, Andrew. We'll decide when we see the data, but top line, usually you receive really just very limited information. That's the one that matters. Then a few weeks later, you receive the more detailed data. I assume if there is anything notable, the data will be provided to us, and of course, we will disclose it. Ultimately, what really matters is the VAS score and the statistical significance. We have treated many patients with esmethadone now, and we know how the profile looks like pretty well. We have phase I, phase II. Understood. Profile. Yep. Thank you, guys. Appreciate it. Thank you, Andrew. Next question comes from Marc Goodman with Leerink. Please go ahead. Yes, just to confirm a few things. One is when the oxy data comes out, that will be a press release. You're not waiting for the ketamine data since now they're both not coming out near the same timeline, right? Is that true? Yes, Marc. Good afternoon, by the way. Yes, it's absolutely true. Reason being that the oxycodone data is by far more. They're both material, but the oxycodone is. Right. far more important than-. Right. I'm just making sure that we will get that press release whenever it is in the second quarter. Secondly, on oxy, the HAP study. Your view is that none of the doses can be relatively like oxy, right? I mean, the 150 can't be like oxy, even though it's multiple times the 25 that you're going to be using in the real world, right? Correct. Look, this is not really a tossing-a-coin kind of trial. We have 13 patients treated with 150 in phase I. None of them showed any opioid-like effect or oxycodone-like effect. We have 21 patients in the phase II. That was the 5- milligram arm that as a loading dose, they took 100. None of them showed any opioid-like, oxycodone-like effect. We do have enough evidence that even the 150 does not have any, even close to what the effect of oxycodone can be. Of course, we have to show it in a control study. We have quite a bit of evidence already out there. Lastly, any update on enrollment? How many sites are up and running for RELIANCE I? That's it. Thank you. Yeah, you caught me on that. It's evolving very quickly. I don't have the exact number. Maged, do you know? We are getting close to all site involvement because we will start very soon RELIANCE II. We wanted to wait to have RELIANCE I well up and running before to start the second one. I don't have the exact number, but it's close to having all of them up and running. Thank you. Next question. Thank you, Marc. Joon Lee with Truist Securities. Please go ahead. Hi. Thanks for taking our questions and thanks for the updates. For the upcoming human abuse potential study, has there been a similar pre-planned analysis for the HAP study using oxycodone as an active comparator, as what was done for the ketamine study? If so, was oxycodone arm behaving as they should be, based on the historic data? Also, what's the explanation for the oral ketamine not separating from the placebo in your ketamine HAP study? I have a follow-up. Thank you. Okay. The first one is if the quality control. Yes. The answer is yes. Usually everybody, I think, usually does a blinded quality control data just to be sure that there is nothing unexpected or nothing weird about data. It's mostly done for safety. We have seen that with oral ketamine, it was also looking at utility that is not very complicated to understand. After five arms, there was no likability at all, and one of the five arms, or even it was blinded, but it has to be ketamine because every patient takes every arm. It was pretty straightforward that there was an issue with the ketamine not behaving as a control, a valuable control. We have not done it yet. The oxycodone study started a couple of months after the ketamine study. The only reason being that the site that is doing it, they need a little bit more time to get up and running. They were busy with other things, we had to wait a couple of more months. At some point, we'll do the analysis, but if there is nothing notable, we will not even know it, that it happened. They only will notify us if something that will show that there is any unexpected effect or side effect or anything like it happened with ketamine that said, "Look, this thing doesn't look it's going the right direction. Thank you. You were alerted because the ketamine arm didn't separate from placebo by whoever was conducting the study. For the oxycodone HAP study using oxycodone, you don't know. You won't know if there's no real issue with the study. Right. We will only be notified if there is the material that we need to know. Okay. It can be only side effects or something safety or something that make the study will not generate any valuable, useful results like ketamine. Right. Following up on Marc's question, if the 150 arm or any one of the dosing arms actually does not separate from the active comparator statistically, do you automatically get a Schedule II, or what's the sort of decision tree after that? The ideal situation, it would be as you described, none of the doses are likable. If one of the doses happened to be likable, what's the process? That's a great question, Joon. We are not hiding that the abuse liability of the result of the study is important, but it's not the only factor that will determine the scheduling or non-scheduling of esmethadone. There are eight factors that the FDA considers when they determine the recommendation for the DEA. One is abuse liability, and it's very important. If you don't like something, it's more difficult, you abuse it or you get dependent on it. There are other factors. Look, the FDA at the end, the real focus is on safety. The reason that the oxycodone or the opioids, they are a lot more under scrutiny and the focus of the FDA is not because they're more abusable than ketamine or than alcohol or the PCP. It's because they're dangerous, right? If you overdose an opioid, say, you can have respiratory depression and unfortunately you can have some serious consequences. If you overdose ketamine, it happened, but you fell asleep or it's used as an anesthetic specifically because it does not give respiratory depression. The dangers or the potential risk is a very important factor in determining the schedule. That's why ketamine is Schedule III, not because it's less abusable than oxycodone. It's because it's less dangerous than oxycodone. There are eight of these factors. Likability is one, and then you have dangers, the history, the pharmacology, and so on. Clearly likability is important. To answer directly your question, if by chance one of the doses of esmethadone will not separate statistically from 40 mg of oxycodone, then it will depend on the FDA overall analysis and how they will consider the other factors. Consider that esmethadone in the past has been tested at 900- milligrams and nothing happened. People did not like it and nothing experienced any serious side effects. 900- milligrams is 36 times, I believe, is nine times four is 36 times the therapeutic dose. Definitely we feel comfortable that safety is not the major potential risk for esmethadone. Yeah. Of course. It's not an automatic Schedule II if one of the doses. No. happens. Correct. I get it. That's helpful. Okay. Next question, Yatin Suneja with Guggenheim Securities. Please go ahead. Hey, guys. This is Eddie on for Yatin. Thanks for taking the question. Just, you talked about for RELIANCE I on sort of the checks, the screening, multiple levels of screening that you're taking. Can you just talk a little bit more about these steps and how you're ensuring that you're not enrolling professional patients? What would be a placebo range for the MADRS improvement that would give you confidence that you had a proper screening process? I have a follow-up on the human study. Great. Let me take this one. How do we avoid or we reduce the risk of having non-depressed patients in the phase III in RELIANCE? Besides the two arms that is easier to, the placebo effect is lower than multiple arms, specifically for the patient selection. One point that we like to make, we are being advised by our advisor that the major risk in running a phase III trial for depression is actually the patient selection, because it's also connected with the placebo effect. We have multiple screening. The site select, they screen the patient, and they propose that the patient meet the criteria to be enrolled in the study. We have the CRO themselves. They will review the data, and they will evaluate if there is any risk of having this patient may not be depressed, may have some other issue or maybe a personality disorder. The data also seen by, I believe our CMO and for the safety control. Clearly, there is an opinion here. Probably the most important of the steps beyond these three steps is the review done by a group. Maged, can I say the name? Yes. It's CTNI. It's a group that was, I believe was not from MGH or Harvard. What they do, they re-diagnose the patient. Only the sites and CTNI, they have a contact directly with the patient. It's a phone interview, and they administer a different scale. It's not Hamilton, it's not MADRS. They administer a scale called SAFER. That is considered more the patient as an entity, right? For example, they look at the history of the patient, has been depressed in the past. There has been an event that has generated the current episode of depression. It gives a little bit more complete picture. They have the last say on the patient if it is suitable for the trial or not. We have four different layers, of which the last one, the CTNI, we do believe it's effective. We use it in phase II and you have seen the results. It was pretty well done. Pretty effective, by the way. I hope I answered. Yeah, no, that's great. Thank you for that color. For the ketamine abuse liability studies, can you just give a little more logistics on how they run a trial with multiple different routes of administration? Will the placebo also have to be IV, or how does that work in terms of making sure the patients are giving an accurate comparator if they're getting oral versus IV drugs? Thanks. Yes. The answer is yes. There's going to be a IV placebo and a IV oral. Okay. Thank you. Next question, Jay Olson with Oppenheimer. Please go ahead. Oh, hey guys. Congrats on the progress, and thank you for taking my questions. I was curious about the startup activities that remain to be completed before initiating the RELIANCE II second pivotal trial, and also the phase II monotherapy trial, and whether or not you expect to initiate the phase II monotherapy trial before or after RELIANCE II starts. Yeah. Maged is really helpful in looking at the operation as entirety. Maged, do you want to take this? Sure. He'll be closer. Thanks. Thanks, Sergio. Thank you, Jay, for the question. With regard to RELIANCE II, I can safely say that we're close to initiating that study. I think most of the operational pieces are in place right now. We're not quite there yet. Look for that to officially start kickoff shortly. Can you repeat the second question, Jay? I was wondering for your phase II monotherapy trial, what remains to be done before you can initiate that study, and should we expect that before or after RELIANCE II initiates? Yeah, I'll answer the second question first. Expect that after RELIANCE II starts. We still have a fair amount of work. We've completed the protocol. We've submitted it to the FDA. We're about to submit it to the FDA. We have also selected a CRO. I think a lot of the pieces are coming together. Our expectation remains that we'll start that study by the end of the first half. Oh, okay. Great. Thank you. Are there any details about the study design for the monotherapy study that you could share with us? I think we're not quite prepared to do that yet. Give us some time and we'll be able to give you a more full characterization of the study. You can expect it to be very similar to the RELIANCE I and RELIANCE II studies in that it'll be two arms, placebo versus 25- milligrams of REL-1017 de novo patients. Beyond that, we're not ready to disclose number of sites and such, and any limitations on patient selection. Okay. Got it. We'll look forward to it. Jay, the biggest difference is going to be the patients, adjunctive treatment versus monotherapy. That's going to be the difference. Okay. Got it. Thank you again for taking the questions. Thank you. Pleasure, Jay. Once again, if you would like to ask a question, please press star one on your telephone keypad. Our next question comes from Salveen Richter with Goldman Sachs. Please go ahead. Hi, everyone. Thanks for taking the question. This is Andrea in for Salveen. Sergio, maybe a question for you, just based off of what you saw from the oral ketamine study. Understand the positive control didn't separate here, but does this give you any increased confidence in the profile of REL-1017, and what you might expect to see versus the oxy? Good afternoon, Andrea, and thanks for the question. Yes, with the limitation that was a blinded analysis, we don't know who took what, they all took all arms. We have seen no evidence of dissociation, hallucination, delirium, and out-of-body experience in any of the patient that's been reviewed. That was 20% of the planned total. It clearly, esmethadone did not show anything because even blinded, there was no sign of this in any of the arms. Yes, it gave us a good level of confidence that the profile confirms what we have seen historically in the literature, that we have seen in phase I and in phase II. Clearly, we have to prove it, we see it's a little bit unlikely that a drug will behave differently in two similar studies, just with a different control arm. I mean, nobody liked it or nobody has experienced anything that could be likable in the ketamine study. It's always possible, but we see it as unlikely that will change totally behavior. Yes, the answer is yes. It supported the confidence that we have that esmethadone is not a likable compound. Okay, I would like to turn the floor over to Sergio for closing comments. Okay. Well, thank you, operator. Thank you, all of you, for joining our call today. It was our first one, so it will be remembered. We look forward to the year ahead, and we'll provide further update throughout 2021. Thank you all again, and hope you will enjoy the rest of the day. This concludes today's teleconference. You may disconnect your lines at this time, and thank you for your participation. Thank you.