Good afternoon, ladies and gentlemen. And thank you for standing by. Welcome to the Relmada Therapeutics Incorporated First Quarter 2021 Financial Results Conference Call. At this time all participants are in a listen-only mode. A question-and-answer session will follow the formal presentation. [Operator Instructions] Please note, this conference is being recorded. I will now turn the conference over to your host Tim McCarthy with LifeSci Advisors.

Thank you, operator. And thank you all for joining us this afternoon. With me on today’s call our Chief Executive Officer, Dr. Sergio Traversa, 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 first quarter ended March 31, 2021. 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 the 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, May 12, 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?

And good afternoon to everyone. I am pleased to welcome you to Relmada’s first quarter 2021 conference call. [Technical difficulty] update on the comprehensive development program for the end stage for the treatment of depression, the REL-1017 and the upcoming milestones. I will [Technical difficulty] for review. By the recent data that we've presented a three recent scientific conference. With that, I’ll begin with an update on RELIANCE that is the on-going statutory program [Technical difficulty] RELIANCE OLS that states for long term open-label safety study that is enrolling both rollover participants from the previous studies as well as global participants. This study are designed to evaluate REL-1017 as an adjunctive treatment for major depressive disorder MDD, and includes [Technical difficulty] more than 25 milligrams of dense and in pain that just got somebody told me that I'm breaking up. so I'll try to switch. Now it should be better. And we're saying placebo in 25 milligram or REL-1017. And both on top of standard antidepressant treatment for [Indiscernible]. We have already and successfully tried the minimum of one up to three antidepressant therapy. The primary endpoint is changing MADRS score of day 20. Key secondary endpoints include change in MADRS score of day 7, and change in CGIS the stage for severity, the score at day 28. The first phase 3 trial RELIANCE I continues to enroll as expected and additional sites are coming online nicely. In addition, we recently began enrolling participants into the second phase 3 trial RELIANCE II, which is a mirror study of RELIANCE I. Top line data from these two trials are expected in the first half of next. The RELIANCE long term open-label safety study is also underway and the rolling participant has planned. RELIANCE OLS will include both participants on the eve…

Thank you. And good afternoon, everyone. Today we issued a press release announcing our business and financial results for the first quarter ended March 31, 2021, which I will now review. For the first quarter ended March 31 2021, total research and development expense was approximately $14 million as compared to $4.5 million for the comparable period of 2020. The increase was primarily related to an increase in costs associated with the execution of a broader clinical program for REL-1017. Total general and administrative expense for the quarter ended March 31 2021 was approximately $8.4 million as compared to $5.5 million for the comparable period of 2020. The increase was primarily due to an increase in stock-based compensation. For the first quarter ended March 31 2021, we recorded a net loss of approximately $22.2 million or $1.34 for basic and diluted share, compared to a net loss of $10.7 million or $0.72 per basic and diluted share in the comparable period of 2020. On March 31 2021, the Company had cash, cash equivalents and short term investments of approximately $102.7 million compared to $117.1 million on December 31 2020. We continue to expect that this strong cash position will support us through at least the multiple data readouts we anticipate through the first half of 2022. I will now hand the call back to Sergio for further remarks on the most recent progress. Sergio?

Thank you, Chuck. The as I mentioned, I'm happy to outline the recent data that we presented in nine posters across three different medical meetings. First at the American Society for Pharmacology and Experimental Therapeutics, and [Indiscernible] preclinical, the data that confirm a lack of any neurotoxic feature that potentially linked to only lesion. This was probably not a surprise, but it's important because these, these effect has impacted the safety and development of other MDR blockers like MK-801. And these findings continue to support the consistent safety profile across preclinical and clinical studies. Next, the Society of Biological Psychiatry, we share total six posters that outline new work to understand the underlying mechanism, REL-1017. What we find was very interesting, and included additional support for a role in neural plasticity. And insight regarding its binding to NMDAR subunits, in particular the 2D subunit, which appears to explain both the lack of dissociative side effect as well as the rabid and sustained antidepressant effect. And lastly, we share the APA, the American Psychiatry Association, the data from the Phase 2 study that showed that REL-1017 demonstrated a statistically significantly rapid and sustained efficacy with large effect size, in addition to favorable safety and tolerability profile in the absence of any sign of withdrawal after ending treatment. In summary, the REL-1017 development program remained extremely active and we anticipate multiple key data results over the next 12 months. Importantly, as Chuck noted, we have a strong balance sheet driving these robust R&D efforts. And we have cash to support us through this expected data point. As always, 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 participants and clinical partners involved in the REL-1017 clinical trials for the effort in advances these important therapy through the clinic as expeditiously as possible. I do believe that now we can open up for questions and operator, you can go ahead and open the line for questions. Thank you.

Thank you [Operator Instructions] Our first question is from Andrew Tsai with Jefferies.

Thanks, good afternoon and congrats on all the progress Sergio and team. My first question is on the oxycodone study the data reading out soon. Very clear that all three doses need to be stats A versus placebo. I'm sorry, not placebo, the oxy sorry, as methadone and then similar to placebo. But can you describe just how similar as methadone should be to placebo on the vast liking score? Because from time to time, I think of a scenario where what happens if s-methadone is showing 60 to 65, for example, just outside of the typical placebo range. How would we interpret that result I guess?

Thank you, Andrew. Good afternoon, and thanks for the question. Well, look it's a good it's a key question. So oxycodone 40 milligrams, that is what we use as a competitor's is not a very high those but is high enough, that is clearly likeable by patients of people, participants, that, that like to take narcotic as a recreational drug abuse. It is a CNS drug. You we may you may expect we may expect that it's not placebo, right. You're taking benzodiazepine or you take a sleeping pill is not placebo, you feel something and if this feeling will be pleasant or not, it's very difficult to say although all the data that we have seen so far, nobody really likes it, we have people over 100 patients. And there is really no likeability at all, if you really take in Phase One, it could take a high dose like 150 milligrams, and some patient has pain and nausea. So that is not a very pleasant, very pleasant feeling. So to answer directly, your question, we -- the most important to differentiate all three doses of S-methadone from 40 mg of oxycodone. We don't expect to be very different from placebo, but also does not require that, we are similar to placebo. So I would focus everybody's attention to the obstacle, the placebo is there, just because you have something to compare, but is not we are not comparing S-methadone to, to placebo.

Right. Thank you. Yes, very good. And so my follow up question is, let's just say, data is clearly positive, completely clean. Would it be then be fair for investors to assume that the second abuse level only study versus Academy is pretty much the rest? Because you would have seen data on for example, dissociation hallucination from the oxycodone on study?

The free lancer, yes. The – I would say that, you know, I'm an old pharmacist. And I always say that drugs tend not to change the way they work in overtime. So we don't see anything that would show any dissociative or any hallucination or anything that would be like ketamine, or, like NMDA toxic effect. There is no guarantee. It's not 100% guaranteed, but it's unlikely that in a different study, that will show up as is a very different from what we see so far. So yes, the answer is yes. We, we do believe that there is a derisking component when we will see the oxycodone data.

Thank you, Sergio.

Thank you, Andrew.

Our next question is from Joon Lee with Truist.

Hi, thanks for taking our questions. I believe that DEA is on record, saying that Dextromethadone is the last addiction liability. What's the basis for that for DEA making that claim? And is that based on a specific study? And if so, what doses were used and this related to that, are you aware of DEA making similar claims about esketamine as compared to ketamine? Thank you.

Hey, Joon. Good afternoon. Thanks for the question. Yes, we actually we asked the same question to the DEA where they the data that they base the statement that S-methadone is exempt from abuse, risk and respiratory depression. And they did not do any proprietary study that is not published. They base their statement and their opinion on what is available. And there is quite a bit of literature available, including the Phase 1 that Relmada did with the single dose and multiple doses of S-methadone. So they look at whatever is available and they draw the conclusion. So that's pretty much how they did it. The comments on ketamine, MLS, ketamine, look ketamine, it is, has been on the market for quite a bit of time in few European countries as an anesthetic to replace ketamine and there's a lower dose of racemic ketamine technically pharmacologically, there is no difference between esketamine and racemic ketamine so it's pretty much the same thing, just different dose. So I would be surprised if the DEA would schedule esketamine in a different way than racemic ketamine and Johnson and Johnson which provided the perform the abuse study comparing nasal Esketamine Spravato versus intravenous ketamine and pretty much the same thing. So there was no real no real difference, esketamine is pretty much with remain the same schedule as racemic ketamine. With that said, maybe I can add one thing that ketamine and esketamine they are both scheduled three that is very different from scheduled two and there is probably more difference between scheduled two and three than any other schedule in between three, four and five and the reason being that the major worry of the FDA is not really just the abuse potential is the safety and while narcotic opioid oxycodone, Percocet, whatever is like a mood opiate agonist has that dangerous side effect that is respiratory depression that we have not seen with as methadone. Ketamine and esketamine, they don't do any respiratory depression. That's why they use in case and they use as an anesthetic because they are very safe. So that's the reason that they are in scheduled three, not because they're less abusable, then they're not caught, they you get less high with ketamine or esketamine. But because the reality is they are not. They are not very dangerous in terms of overdosing. So I hope that helps.

Yes, it's just one more thing. You, there was a pre-planned intern for the half study using ketamine, which led to sort of study premature termination, because of the lack of effect, there is similar in terms look was done for the study using oxycodone. And was there anything out of the ordinary that that you saw on a blinded basis in that study? Or that OxyContin behave as it should, based on historic data in terms of indicating the likeability?

I think yes. Now so that’s a great question. So the oxycodone study is going much faster than the ketamine because there is a lot more subject that like to abuse opioids than they like to abuse ketamine, like product. So we will have the blinded, as what I would call it like quality control, that is going to be very close to the end of the study. So fortunately, or unfortunately, it will not help much, I believe will be like probably end of May, early June. And the last patient is supposed to be out before the end of June. So we won't be able to do much in terms of taking action like we did with ketamine. With that said, ketamine, especially oral ketamine, has a history of not being like bioavailability is very valuable and not being very likable, in terms of like abuse potential, while oxycodone 40 milligram is not a very high dose, but definitely, it is much more likeable than oral ketamine 100 milligram. So we do believe that it's going to be unlikely that we will see what we saw with the ketamine study. We have seen in the qualification period where you select the participants, they have to they are tested and they have to recognize and light the control while ketamine the percent of patients that were excluded from the qualification was over 50%. The in the oxycodone study in qualification, the percent of people that are participants that they like the control, there was 40 milligram oxycodone was very high was close to the 100% that we feel more comfortable about the study. Now clearly, oxycodone is much more easier control than ketamine.

Looking forward to data. And thanks for taking our questions.

Likewise, thank you, John.

Our next question is from Yatin Suneja with Guggenheim Partners.

Hey, guys, thank you for taking my question. Just a couple on the HAP side or Human Abuse Liability Study. So I think Sergio you were just talking about the scheduling. Can you maybe help us understand how each of these studies help you from scheduling perspective? If you show a static different versus oxy and ketamine, do we know you're not going to get the same level of scheduling? And then the other part of the question is, what type of scheduling would you be okay with? Do you expect some form of scheduling with 1017? So that's the first question. I do have another follow up.

Thanks Yatin. So let me let me ask the question a little bit more expanded, expanded way so to be very, to be very clear. So the scheduling is determined by a process that involves the CSS that is the Control Substance Staff that is a piece of part of the FDA. The CSS advises the FDA, then the FDA kind of give recommendation to the DEA and the DEA makes the final conclusion all these happen after approval. The DEA has 90 days after approval to determine the scheduling. And scheduling is based on a it's called a factor analysis that includes the pharmacology, the mechanism of action, the receptor affinity, the danger, how danger is the drug and include likability, how much potential abuser like the drug, clearly the likability, it is a key factor, as well as safety, right? If you show safety by ketamine, then the FDA is clearly looking at things in a in a different way. So, to answer directly your question, if we the data that we will see, and hopefully that we hope, we will see -- they are statistically different from oxycodone on all three those as well as methadone, we cannot say for like business and FDA and DEA decision, we cannot look into the 100% certainty, but it's going to be extremely unlikely that it will be the same schedule as scheduled two. I mean could be, higher schedule, then it will depend on what the ketamine study will show. But definitely being scheduled to when you see a total statistically different score from oxycodone 40 milligrams, that I would be extremely surprising that that would happen. That's also with the whole body of data that are already available, that show like a very high safety profile. And there is no respiratory depression, and they are the most frequent or the most, like the dose limiting toxicities, nausea. And so that, that makes us pretty comfortable that if we show these results, it’s not going to be scheduled to. And to the second part of your question, what kind of what schedule we will be happy with? Well, dextromethorphan is or behind the counters, there's not even a prescription. Now we definitely do not expect as methadone first, because it's a new chemical entity, when it's very unlikely. It's impossible, it's not going to be an over the counter or anything like that. But then I believe benzodiazepine have been in the sleeping pills. And, they are scheduled four or five, if you ask me directly, and this is not the guidance of what the scheduling of -- will be, but I would say schedule four or five is pretty much the same as non-schedule, schedule three is very light, it's very benign. And there is many drugs are scheduled three, and they are prescribed very, very widely.

Got it. So…

So I would let me answer your question directly. I would be happy we scheduled three and above. I don't think commercially would make any difference. Scheduled II would be would be an issue. But we cannot hide that.

Right. Yes, very helpful. Then the other question I have is on the monotherapy study, can you maybe help us understand a little bit more in details, any particular feedback we got from the FDA, the type of patient you're going to enrol, any standard medication that is allowed? It seems like you are guiding for completion of the study, this year? Do you mean the data will become available this year? Or just maybe provide some color there? Thanks.

Yes, the sub two parts, right. The feedback from the FDA and I'm not sure I'm allowed to say anything, but let me try to phrase it in a nice way. The monotherapy protocol is very similar to the RELIANCE I and II to the add-on therapy, the only difference is the patient population they are not taking any treatment while the other one they are taking a treatment. So we are in process or with the two Phase 3 is add on therapy. And so let's put in this way we don't expect that there is anything that is particularly worried about the monotherapy. It’s the same thing. So the FDA was okay with the add on therapy. We do believe that they are okay with the monotherapy as well. I hope I answer you. The data well, yes the patient population for monotherapy is much larger than about I would say at least two to three times, the patient population will add on therapy so recruitment is we've been guided to like six, seven months. And we are planning to start before the end of this quarter that is over the next, 2, 3, 4 weeks. So we should be on time to get it done by, by your end. We are always a little cautious in terms of top line because it's always -- it takes some time to clean the data and the statistical analysis and year-end it comes around Christmas. So I'm sure you don't want to have to write in no [Indiscernible] on December 24. That would not be so. So yes, but it should be done around the year-end.

Okay, very helpful.

There is always JPMorgan, I don't know if it's going to be weird following personalities it’s always JPMorgan. It’s usually a nice stage, if we have some good data to share. But, we haven't even started so I don't want to give you any particular guidance. It is too far away to be with something specific. Just want to be around there.

Thank you.

Our next question is from Salveen Richter with Goldman Sachs.

Hi, thanks so much for taking our questions. This is Sonia on for Salveen. So at APA, you presented some data on REL-1017, where the effect was a function of percent life years since onset of MDD. Just wondering if those findings will influence the design of your monotherapy trial at all?

Thank you, Sonia. Yes, that's a very good question. The short answer is no. They with the -- the overall idea is to mimic as much as possible, the overall like standard population. So we didn't want to pre select, and we should have to stratify. We discussed it, but we should have had to stratify the patients based on how long they've been affected by depression. And you know, what's the next award but, the FDA likes to see like real world studies. So, we prefer to just do it in a standard way without stratifying. So we will enroll patients who have depression for 20 years, and patients with depression for like, two months. So that's straight answer is no, there isn't -- there was no impact on from these data. The way we read these days that have been important for one specific reason. No the NMDA antagonist, like methadone they have this feature, they are neural plastic. So they increase the functionality and the number of synapses in the brain, the communication between brain cell that is very different from SSRI, you may remember I did that I was involved in the development of Prozac for quite a bit of years for five or six years, and SSRIs, the old traditional antidepressants, they tend to be more they are symptomatic, right, they treat the symptom of depression. And if you say -- you're satisfied the patient from long term the presentation and short term depressed patient, you don't see any difference with traditional antidepressant because they don't have really a neuroplastic effect. Unlike what we have seen as methadone, that, the neuropathic effect is more evident, especially this patient were treated for a week. So if you have been depressed for 25 years, and then you get treated for a week, it's unlikely you see, like a drastic effect that you actually have seen in patients that were depressed for a shorter time. So most likely in patient that been depressed for a long time is going to take a little bit more longer treatment. And so that's we probably we may see something in the in phase three. The understanding and the learning from these data is that it is confirmed as a confirmation that an NMDA antagonist is better than they have a different mechanism and they do something different to patient with depression. So I would say in quotes and very carefully that we are looking more at disease modifying effect instead of being a symptomatic. I hope that helps.

Thank you.

[Operator Instructions] Our next question is from Jay Olson with Oppenheimer.

Oh, hey Sergio. Thank you for taking the questions and congrats on all the progress since Sage has an important catalyst coming up with data from their MDD study, can you just talk about what some of the differentiating features are for an NMDA antagonist versus a gather, Pam, and what you think would motivate MDD patients to prefer as s-methadone versus an [Indiscernible] Thank you.

Thank you, Jay. You already asked me that question. The well, there is quite a bit of differences between the allosteric modulator and the GABAA modulator like SAGE and Praxis, then NMDA channel blockers like s-methadone. So the mechanism is totally different. Although ultimately at the end, we do believe that also the GABAA modulator, they may have some influence on the NMDA process and activity, but it come from a different from a different angle, and quite a bit the opposite angle. So probably mechanistically, they're very different. In terms of activity, probably, I know what is available publicly from SAGE and from Praxis, but they tend to have a -- they are rather fast acting, but they tend to like have a shorter term efficacy profile. So they are more suitable. And this is this, what SAGE is claiming. And they definitely know a lot more than I do. But they're more suitable for episodic short term treatment of depression. And we do believe there is a market for that, too. So it's, yeah, it's a very large market. So there is enough space for drug with different profiles. So yeah, so there are quite a bit different that the bottom line is that there is very little correlation between the two different mechanism of action, different clinical profile. And we hope they all work.

Likewise, and thank you for that. I guess, since you had a number of posters that you presented at recent medical meetings, can you just talk about any feedback that you got from physicians and KOLs at those conferences?

Yes, so the -- unfortunately, we -- is not the same thing that to sit there and to hear it like the whole talking and the by the direct comments when they see the poster. So there is a little bit of guessing here, but the feedback was definitely positive. And then the, it looks like now based on data as methadone is starting to differentiate not only from racemic methadone, look, the fact that this methadone is different from an opioid, it's very clear to me, you see all the data, you have seen them as well. And also in terms of like, the other NMDA antagonists, right? Because the question that I've been, we've been asked and we asked ourselves is why has methadone even at very high doses, forget narcotic effect that that is not there, but even the hallucination the dissociation the ketamine like effect is not there, even doses that patients are healthy volunteer they cannot tolerate. And that's one is was one of the angle that was came up from this study, right that the there is a mechanism I want to go too much in detail on the earning call, but the specific activity for the sub unit 2D of the NMDA receptor, unlike ketamine that it seems more it works on the 2D but it also is as affinity for the A and B they are more related with the physiological activity of the NMDA system and the glutamate and that could explain or should explain the fact that as methadone does not have this dissociative and hallucination effect even at high doses. So, it seems that the differentiation process is moving ahead rather successfully. We are learning too, rifght. It’s not -- we saw the clinic also, we are looking of the reason that the clinic advertise looks like that. And then yes, we made good progress is really understanding how s-methadone works and it's fascinating.

Excellent, super helpful. Thank you for taking the questions.

Likewise here.

Our next question is from Marc Goodman with SVB Leerink.

Hi, this is Julian on call for Marc. Thanks for taking my question. So just prime more color on the enrollmenet of the RELIANCE trial. They're still targeting 55 sites for each study? And how should we think about the COVID impact on the clinical conduct of these trials, as the pandemic condition continues to improve? Thank you.

Thank you, Julian. And my regards to Marc. The well, let me start with the COVID impact in terms of enrolment we have not seen, especially now with the vaccine, and you have not seen really any impact of, they would slow the enrollment. And if any, then clearly, you can read that everywhere. I mean, there's been an increase in patient affected by depression, following the COVID situation. You know people had COVID, and have consequences with depression related to the aftermath of the virus, but also, the old economic situation and the old, everything that we know enough about it. So the No, there has been no impact on from the COVID situation on enrolment. It’s a bit early to, like, give exact guidance. So how we are going and we started, like three months ago, in December or January to enroll the first one. And then recently, a few weeks ago, we started enroll the second one. So it is moving the sites are the most of the sites is already in place for the for definitely for the RELIANCE I, RELIANCE II is coming very fast. So we learn from the first one. So it's been a lot more efficient in activating sites and starting to enroll patients. So so far, so good, and we don't really expect any major impact, barring catastrophic event that we that are not predictable. But the COVID definitely is not. It's not It's not an issue.

So that's very helpful. So I hope to have a quick question for SG&A. I think there was an increase in stock based compensation in 1Q? So should we expect similar levels of spending for the remainder of the year? Or is this more of a onetime payment?

I do believe that this is a question that Chuck can answer.

Yes. Yes, I am. Yes, we've had a few fluctuations, based compensation based on either folks leaving the company and their stock options being brought back in-house. But the stock based compensation expense that you saw in Q1 of this year is reasonable thread that you can expect, throughout the next few quarters.

Got it? Yes, that's very helpful. Thanks for taking the question.

We have a follow up question from Joon Lee with Truist Securities. Mr. Lee?

Sorry, I was on -- I was on mute. Sorry. And thanks for taking our follow up question. Per FDA guidance, the HAP study should be conducted and experienced recreational users with recent history in the same general pharmaceutical class, or pharmacological class. So for the HAP study using OxyContin as an active competitor, those subjects are experienced in OxyContin or oxycode on that class, not necessarily methadone, is that a fair assumption? Or is…

Oh, yes it is a fair assumption. Look methadone is used widely as a replacement for maintenance, but it's not the highly abusable opioids for a variety of reason. Two in particular, one, is that there's a long half-life so you don't have the big that you have with the oxycodone or immediate release. That's what the drug abuser or the recreational they want the high, right. If you have a slow onset it’s not something they like in particular. The second one is that racemic methadone; part of racemic methadone is dexamethasone. In dexamethasone even in NMDA and it really does not have any. We do believe that does not have a any narcotic effect. So it's not something that even recreational drug abuser they like a lot.

Okay. Thank you.

Thank you. Ladies and gentlemen, we have reached the end of the question-and-answer session. And I would like to turn the call back to Dr. Traversa for closing remarks.

Thank you operator. So thank you all for joining on the call today and we are very pleased to share the recent progress with you. As the REL-1017 clinical development program continues to advance. We're excited about the important catalysts ahead of us. And we'll keep you updated on clinical readouts and activities throughout the remainder of 2021. Thank you, again, all for joining us on the call and enjoy the rest of the day. Thank you.

This concludes today's conference. Thank you for your participation. You may disconnect your allies at this time.