RLMD (2021 - Q3)

Greetings and welcome Relmada Therapeutics Inc. Third Quarter 2021 Earnings Call. At this time, all participants are in a listen-only mode. A question and answer session will follow the formal presentation. [Operator Instructions] As a reminder, this conference is being recorded. I would now like to turn the conference over to your host, Tim McCarthy. Tim McCa

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 Accounting and Compliance Officer, Chuck Ence. This afternoon, Relmada issued a news release providing a business update and announcing financial results for the three and nine months ended September 30, 2021, and filed its quarterly report on Form 10-Q with the SEC. Please note that certain information discussed on the call today is covered under the Safe Harbor provisions of the Private Securities Litigation Reform Act. We caution listeners 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 30, 2020 and subsequent filings. This conference call also contains time-sensitive information that is accurate only as of the date of this live broadcast, November 11, 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 would like to turn the call over to Sergio. Sergio?

Thank you, Tim, and good afternoon to everyone. And we also have on the call today, Maged Shenouda, that is our CFO on top of Chuck Ence. And I am pleased to welcome you to Relmada’s third quarter 2021 conference call. On today's call, I will provide an update on the comprehensive development program for our lead product candidate REL-1017 for the adjunctive and monotherapy treatment of major depression disorder or MDD; highlight the substantial market opportunity for this compelling product candidate and review upcoming milestones. Following this, I will turn the call over to Maged Shenouda, Chief Financial Officer for a review of the financials. I will then provide a brief overview of the data that we recently presented at the Neuroscience Education Institute Conference last week. With that, I will begin to by highlighting the point that we will have data readouts in each quarter of next year. I will elaborate further on this shortly, but in summary, in the first quarter of next year 2022, we expect top-line results from our second human abuse potential or HAP study, each one assessing REL-1017 versus intravenous ketamine. Following this, in the second quarter, we anticipate top-line data from RELIANCE III, the ongoing monotherapy registrational Phase 2 trial. In the third and fourth quarters of 2022, we expect top-line results from RELIANCE I and RELIANCE II respectively. The two ongoing Phase III sister 2 arm, placebo-controlled pivotal studies. With that, I would like now to reiterate the important development on regulatory update that we provided for REL-1017 last month. To begin with the RELIANCE III, which aims to randomize 364 patients is expected to be completed in the second quarter of 2022, prior to the anticipated conclusion of RELIANCE I and RELIANCE II the adjunctive MDD studies, which I will discuss momentarily. These MDD monotherapy study is for individuals who are diagnosed with depression and are not currently taking standard antidepressant therapy. Importantly, conducting RELIANCE III is the Phase 3 study may meaningfully reduce the time for a potential approval of REL-1017 as a MDD monotherapy. In addition, in order to support potential regulatory submission seeking approval for REL-1017 as a monotherapy, as well as adjunctive treatment, the FDA confirmed that based on what is known at this time will not be required to conduct a two years carcinogenicity study of REL-1017. With an understanding that sufficient pre-clinical safety data has been generated today. The FDA also confirmed that Relmada does not need to conduct a TQT cardiac study in human to support cardiac safety in a potential regulatory submission for REL-1017. As the data provided to-date as well as the data to be generated from the Phase 3 program would be adequate to evaluate and confirm the cardiac safety profile of REL-1017. Moving on, I will now provide an update of the ongoing RELIANCE I and RELIANCE II studies, each of which would include 364 participants per study across 55 sites, as well per study. As a reminder, RELIANCE I and II are designed to evaluate REL-1017 as an adjunctive treatment for MDD and both include two arms, placebo and 25 mg of REL-1017. Both of which are in addition to a standard antidepressant for participants who have had inadequate response to a meaning of 1 and up to 3 standard antidepressant therapies. The clinical trial protocol remains unchanged with the primary endpoints being changing MADRS score at day 28 and key secondary endpoints include the change in MADRS score at day 7 and the change in Clinical Global Impression severity score at day 28, the CGIS. Both RELIANCE I and RELIANCE II are progressing with top-line data expected in the second half of next year. The RELIANCE development program also includes the RELIANCE-OLS, a long-term open-label safety study that is enrolling both rollover participants from own three pivotal studies as well as de novo participants. RELIANCE-OLS is ongoing and enrolling participants as planned. Data from this long-term open-label safety study would be part of the NDA filing package. As we look ahead to the key RELIANCE clinical program, the catalysts I outlined earlier, it is important to note that we are highly confident that we are more than sufficient powered our studies to demonstrate the desired sites and targeted degrees in MADRS score improved. Our significant, while REL-1017 demonstrated data points improving score per placebo in the Phase II trial. Moving on, our second HAP study evaluating REL-1017 versus intravenous ketamine, which has an established history as an effective positive control and is ongoing. Based on the current rate of recruitment we expect top-line results from this study in the first quarter of 2022. As a reminder, in the third quarter, we announced positive top-line results from our first HAP study, evaluating REL-1017 versus oxycodone 40 mg as an active control. As we discussed these data in length on our last two investor calls, I won’t go into too much detail here. However, I will reiterate that this study was designed in a manner that followed the FDA 2017 guidelines on the assessment of the abuse potential of drugs. Top-line results for the primary endpoint showed that all three doses of REL-1017 evaluated in recreational opioid users demonstrated a highly statistically significant difference versus the active control drug oxycodone 40 milligrams. Notably, the highly statistically significant difference was confirmed between the active control and 150 milligrams of REL-1017, which is the maximum tolerated dose and is 6x the proposed therapeutic dose. As the secondary endpoints, such as desire of taking the drug again were consistent with those of the primary endpoints demonstrated no evidence of any meaningful abuse potential. Importantly, these results are consistent with HAP study results that is seen in the drug would affect the CNS and which have been stable at classes four, five or even on schedule. I also wanted to take a moment to reaffirm the need for a new therapeutic option with a potential clinical profile than REL-1017 presents. Over 17 million individuals suffer from MDD and the current option of limited in their ability to have discussions. Current antidepressant standards have significant side-effects and can take four, six weeks to show efficacy. 65% of patients do not respond to their first antidepressant treatment and 30% do not respond to any of the current available oral treatment. Furthermore, there are only three FDA-approved adjunctive treatment for major depression disorder all of which are antipsychotics, which often can cause long-term serious side-effects. It is evident that new treatment options are needed and we believe that REL-1017 has the potential to make a difference for these patients and their care deeds as a monotherapy or adjunctive treatment. I will now pass the call over to Maged to review the financials. I we will then touch on the recent poster presentation at the recently held Neuroscience Education Institute Conference. Please go ahead, Maged.

Yes. Sure. Thank you, Sergio, and good afternoon, everyone. Today we issued a press release announcing our business and financial results for the three months and nine months ended September 30, 2021, which I will now review. For the third quarter ended September 30, 2021, total research and development expense was approximately $34 million as compared to $11.2 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 second quarter ended September 30, 2021 was approximately $8.7 million, as compared to $5.9 million for the comparable period of 2020. The increase was primarily due to an increase in personnel cost, stock-based compensation and consulting services. For the third quarter ended September 30, 2021, we recorded a net loss of approximately $42.6 million or $2.44 per basic and diluted share, compared to a net loss of $16.9 million or $1.05 per basic and diluted share in the comparable period of 2020. Turning to the results for the nine months ended September 30, 2021. Total research and development expense was approximately $65.3 million, as compared to $21.1 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. For the nine months ended September 30, 2021, general and administrative expense was approximately $26.2 million, as compared to $18.8 million for the comparable period of 2020. The increase was primarily due to increase in personnel cost, stock-based compensation and consulting services. For the nine months ended September 30, 2021, we recorded a net loss of approximately $91.4 million or $5.36 per basic and diluted share, compared to a net loss of $38.7 million or $2.52 per basic and diluted share in the comparable period of 2020. On September 30, 2021, the company had cash and cash equivalents and short-term investments of $88.1 million, which compares to $117.1 million on December 31, 2020. I will now hand the call back over to Sergio for further remarks on our most recent progress. Sergio?

Thank you, Maged. Earlier this month, I mean, in the last week, we presented a total of eight posters at the NEI Congress including three posters with new data heads resulting from post-op analysis from our Phase 2 trial. First, the post-op analysis of the dissociative symptom of depression questionnaire the SDQ, on MSED scale scores from patients treated with REL-1017 showed improvement in such scales of cognition, motivation, anxiety, its ability of the sleep function signaling the benefits from REL-1017 may extend well beyond just with improvement. These data suggest that REL-1017 may have potentially meaningful implications for patients working and social ability. The second poster included a post-op analysis of its success of MDD patients experiencing the psychiatric symptoms prior to treatment. And it showed the clinically meaningful improvement in the Abnormal Clinical Administered Dissociative States Scale Scores, which is used to measure dissociative state after REL-1017 treatment. It suggests that REL-1017 may not only be exempt from generating dissociative symptoms other NMDA antagonists but it may have to be beneficial in patients affected by such docs. Finally, like some of the current standard of care antidepressants has shown an increase in lipid metabolism abnormalities with patients with MDD at risk. A post-op analysis showed that REL-1017 did not significantly – potentially lacking in cardiovascular risk. In summary, REL-1017 developer program remains on track and we expect key data catalyst in each quarter next year. To reiterate, we expect top-line results from the second half study, this one assessing REL-1017 versus intravenous ketamine in the first quarter followed by top-line data from the RELIANCE III monotherapy trial in second quarter, in the third and fourth quarters of 2022, we expect top-line results from the RELIANCE I and RELIANCE II adjunctive trial respectively. Importantly, as Maged noted, our robust R&D initiatives are supported by a strong balance sheet. In closing, I remain grateful to the Relmada team for their continued hard work and dedication to executing on our mission. I would also like to extend my sincere thanks to the participants and clinical partners involved in the REL-1017 clinical trials for their efforts in advancing this important therapy to the clinic as expeditiously as possible. I believe, we will now open up the call for questions. And operator, can you please open up?

[Operator Instructions] Our first question is from Andrew Tsai with Jefferies. Please proceed.

Okay. Great. Thanks guys for taking my questions. I noticed at the NEI Congress, I noticed you also shared some additional secondary endpoints for the oxycodone abuse liability study. I can help it notice while that means increased a little for esmethadone on the secondary endpoints, the scores is at the medium state at 50. So, I thought that was interesting. I was wondering if you kind of talk about that. But at the same time, I just felt like, I guess, it’s part of my second question is, like did you ever find out who – what the outliers were, who scored high. What exactly high in terms of the VAS score and I guess, what were they exactly feeling to make them score higher? And then, can you confirm that they were definitely not feeling euphoric mood or anything like that, but maybe it’s because of the CNS effects. Thanks.

Well, thank you, Andrew, for the question. Look, on the data that we presented at the NEI last week, the old dataset is out for publication at some point that we published shows all the details would be there. I would just summarize that the – there was very marginal difference between primary and secondary endpoints. They are – we can say they would be very consistent and they confirm that the slight difference from placebo, that is both expected from any CNS product that affect the mood, especially even the massive dose of six times as therapeutic dose. But none of these data are inconsistent with the primary endpoints. So it’s just a confirmation. On your second question on the – the straight answer is the – we did not reach out, so we cannot reach out to the subject after they complete the study we don’t really know who they are. So, in the hands of the site, so we set the privacy. There is some question that has been asked in the various questioning and limited questionnaire that in the study. And the – we did look at the outliers without knowing who they are or why they were outliers. But what we have noticed is that, the vast majority – it’s a single-digit number of outlier. So it was not – and I’d say, it was not an extensive likeability score across the different set of subjects. There was only – I don’t remember the exact number, but it was a single-digit number of patients that’s for whatever reason they score high. That – we see that as a positive signal, because though we cannot confirm with one third. This study was not designed to the fact that to show any antidepressant effects, but over 90% of the subjects totally not feeling any likeability and only a single digit number of subjects liking the drug significantly. We can – we suspect that there was something in these patients and in these subjects that made them like it in particular bets. We can speculate that could have been the first though that was – with rather symptoms from anxiety and psychiatric, psychological symptoms and taking a massive dose of a rapid-acting antidepressant that may have felt some benefits. So, I hope I answered your questions.

Yes. Very knowledge more than I think.

Right. It is. It is.

Thank you.

Well, look, Phase 3 will answer all these questions. I look forward to the ketamine data.

Right. And speaking of the Phase 3 studies, I did have one hypothetical question is, the first Phase 3 monotherapy depression data in Q2. So, hypothetically, if it happen to show next date on efficacy, which I say it doesn’t hit day 28 or maybe it doesn’t show rapid effects, I guess, the question would be then, why should that not be a negative rate to your Phase 3 adjunct studies?

Well, first we hope that data we have confirmed what we have seen Phase 2. And the only way that that could happen, we know that the drug is Phase 2 data we outlined. So there is no doubt that it is a very, very strong efficacy signal. So that signal is not confirmed or repeated in monotherapy the only or potentially one reason could be that there is some form of synergy between a current and existing treatment even if it fails to show efficacy and as in the NMDA. So I would not read that this, by chance it doesn’t work well as a monotherapy that we can take that the adjunctive treatment would not work as well as there maybe some reason that – if you ask me to reiterate, we don’t believe that that’s the case, but domestically that I would not correlate the monotherapy directly to the adjunctive treatment because there is a difference in adjunctive that taking two drugs versus one in the monotherapy. But, to be honest, I too believe that’s not going to be the case.

Great. Thank you. Very last question, very quickly is just for the monotherapy study, can you remind us the primary endpoint day 28, I guess, what kind of minimum separation versus placebo – which would be the minimum that you would like to see? And are these assumptions then similar to the Phase 3 adjunct MDD studies? So, can you just remind us one more time? Thanks.

Yes. This one I can give you a more straight answer. The statistical plan is the same – exactly same for all the three Phase 3, the two adjunctive with the monotherapy. And it is designed to detect a delta of two point in the MADRS score versus placebo. So, if we hit two points delta, the study will be statistically significant. That’s the way the statistic has been designed, all the three studies. Now the reason that it’s two points, because rule of thumb is not like not in the FDA guidance, of course. But the rule of thumb is that, looking at all the approved products, two points as a monotherapy or even adjunctive is a clinically meaningful delta that potentially could get to an approval. There are lot of other factors with the approval, but in terms of like efficacy, I believe what Professor [Indiscernible] have published that two point delta is clinically meaningful. Therefore, it should be – it should deserve everything, saying the same, it should deserve an approval for treatment resistant therapy or depression that is not something that we are doing or we are looking at 1.5 point becomes the correspondent number for potential to getting an approval. So, we ask eight point delta. So that’s a lot of room and we wanted t be conservative. We know that Phase 3 it is more liability, more patients, more sites. So, we will be left with some room for something doesn’t go the way we like it. But if we show one-fourth of the efficacy that we have seen in Phase 2, it is still – it would still be statistically significant.

Okay. Perfect. Thank you, Sergio.

Thank you, Andrew.

Our next question is from Yatin Suneja with Guggenheim Partners. Please proceed.

Hey guys. Thank you for taking my question. Maged, good to hear your voice. Just a couple for me.

Likewise.

With regard to the RADIANCE III which has now been upgraded to Phase 3, can you just help us understand, like what exactly was the conversation with the FDA? And then, in terms of that led to it being Phase 3, but earlier you think about a Phase 2? And then, how is your filing strategy going to be? Are you going to complete all three studies and then file? Just trying to get a sense of the type of label you are hoping to get? So that, a couple questions on the RELIANCE. And then, one question on the ketamine study that you are doing. Can you just help us understand what you are doing differently in this study to make sure you do get a separation between ketamine and the placebo arm which did not happened in the first study?

Okay. Well, thank you, Yatin, first for the questions and all those insights. So the first question was what the change that the monotherapy study has become a filing or a pivotal study. Well, we did not actually have a conversation with the FDA in the sense that we send the proposal of making this Phase 3 and we waited the traditional 30 plus, 30, so the 60 days, that usually signal that the FDA does not have anything in uphold for moving with the program and that’s what we did. So, we waited until end of August and then, we didn’t hear anything again from the FDA. So, we make it the Phase 3. There was really not a lot of difference. The product was exactly the same. So there was no change or in the problem. The question is that, what has changed that make us think the lipid things instead of Phase 2. Two things, one was the feedback from the FDA on the two years carcinogenicity study and the TQT that shows that the FDA is somewhat comfortable with the safety and tolerability of the drug. And then, now the abuse HAP study in July that we do believe could have been an issue with the FDA to expand a trial to like 350 patients, all outpatients. So, we put together all these data and that we took some risk that the FDA could have said, well, you don’t have any efficacy data as a monotherapy, the safety is we know relatively comfortable, or comfortable, but there is no single data that shows that the drug has any efficacy in monotherapy although we do believe that is not very different from adjunctives. And so, that was the reason that we initially we thought about in the Phase 2 and then in Phase 3. Then we saw the FDA relatively comfortable. We had the abuse data to proceed and they are very positive and then, also some illness but it works. And so, that’s why we moved to – we make it regarding a Phase 3 filing study. The second question was…

It was on the ketamine, like the differences between the past study and this study to make sure at this time the ketamine and the placebo arm separate?

No, yes, no, that’s simply – the first failed – our unsuccessful ketamine study was – the reason was that all our ketamine, the bioavailability is very poor and it did not work as a control. But we had almost half of the patients they were taking all our ketamine. We thought they were taking placebo in the qualification part of the study. So, that would not in the study look. And now we are using an intravenous ketamine. And this, we kind of look at what Johnson & Johnson has gone with a ketamine rich product. So, I believe it’s 50 million number infusion report, I mean, that’s a kind of standard and that certainly works as a control. So, if – there is no doubt that the control will work. And the study has been progressing nicely, looking forward the data, and the regulatory, correct? Look, we have fast track. So we are planning to do a rolling NDA, usually rolling NDA you file the kind of standard with CMC. Probably, we will file the all pre-clinical package, really decided the final studies for the Phase 3 that I do believe that the – if they are not too far away one from the other. Probably we will have to file the module for the Phase 3 and the efficacy study together. And clearly there is like month one and the other, then maybe we will file whatever we have available and not wait for the RELIANCE II and III, like the plan is to do a rolling NDA. So we want the FDA to have enough time to review the more standard CMC and preclinical. So if there is anything that they would like us to do more, we will have time. We won’t delay the FDA, the filing.

Got it. Maybe one question for Maged. Can you maybe help us with the P&L? I mean, so steep rise in R&D. Just trying to get a sense how much was non-cash there? And then, how should we model that can in the half of this year and then next – this 4Q in the next year? Thank you.

Yes. Yes. So, thanks for the question, Yatin. With regard to non-cash components of R&D for the quarter, that was $11.8 million for the R&D line and $6.4 million for the SG&A line and with regard to just the remainder of the year, I would say, I am pointing you to our 10-Q which we expect to file tomorrow morning. And certainly, we are not giving guidance, but the question relates to expenses going forward and sort our ability to meet that, we believe we have sufficient funding to continue with ongoing operations for at least 12 months.

Got it. Thank you so much.

Sure.

Our next question comes from Joon Lee with Truist Securities. Please proceed.

Hi, thanks for the updates and for taking our questions. I would have thought to ask this question as the fact that it’s come up for another company that just reported data for TRD study. And given your Phase 2, also included TRD patients, I thought I ask. Did you see any suicide ideation in your trial? And I have a follow-up.

Yes. Thank you, Joon. Thank you that these questions it could – wouldn’t come. Of course, we look at the data and that has been released a few days ago. We only know what there was in the press release nothing more than that and so, the straight answer is that, no, we have not seen any suicidal ideation in any of our study. We do believe that that NMDA antagonist, the attributes, they are supposed to reduce the suicidal ideation not – if you look at there is another for our competitor that is working on a nasal form of ketamine and they are running the trial as suicidality ideation reduction. So, NMDA antagonist is there specifically they are supposed to be specifically syndicated for reduced ideation for suicide. Now, the program that showed is a side-effect, an increase in suicidality. Look it’s when you – it is a 5H2A way out of this, right? And if you remember, and I do because it was less than fifth year under development and launch of process – we have taken surge on. And the issue, one of the, it is a black box observatory. So it’s a totally different mechanism of action. And, yes, look it’s so speculative. We really don’t know, it’s 5H2A versus – so, it’s all speculative. But if there was – as mentioned, this could be one. With that said, we look into – we spoke with a few specialists. When you take such a high dose of silo IV and these are not drug abusive, right these are patients with depression. So, they don’t want to have – how to call, the cycles and they take the trip, right, it’s not something that they enjoy. If you are heavily depressed, and you have treatment resistant depression, you take a massive dose of [Indiscernible] for more than few minutes, you are totally confused. That’s why it’s an in-clinic treatment. So, if you are depressed and you are in the start of confusion, you may have some suicidality. But I would not read too much into that. Basically, that moments thoroughly and I believe it’s working, just on issues right after during the acute phase. And it’s way too early to speculate.

But your Phase 2 was also a patient monitored for two weeks, but you saw no sucidality by that being an in-patient study?

Yes. We have no, no issues with suicidality.

Okay. Okay.

We don’t expect.

And then, just follow-up question is, I was really intrigued by the posters showing symptom include but using the FDT, FDQ scale which was not stats say and we were at day 7 which was the last day of dosing. But any stat say 7 days later, what is the significance of FDQ within physician circle versus academic circles and how is that used? And why do you think it’s speculated like seven days later as opposed to the last day of dosing during the trial period or during the dosing period?

Yes. I answer the first question first. Sorry, the second question first. The patient is slower to react in the self-administered questionnaire and then, when you’d ask questions from the clinicians and so the MADRS and the PGI, they are a lot quicker to the fact – the patients are little bit more kind of they had time to go home and they realized when they went home without taking anything there, we are actually feeling better and in terms of depressant symptoms and they report that the – when they come at day 14 as a control. So, it’s not – it’s really usual that there is a slower response from the SDQ compared to MADRS and PGI just because of patients reported – and so, there is – of course, we believe is the reason that at day 14 was better than the day 7. The patient had to need some time to get used to not having depression symptoms before they are reporting that. And sorry, the –question.

Oh, no. how is it used by the physicians at the SDQ? Is it the pure of academic metric that they use?

Well, I believe it was published in Eminence Academic. So, the – I don’t know what will the FDA most likely, they look at everything, right, based on all these previous antidepressants approved. It means something. But it’s only a support for the MADRS. From another conversation with the FDA, I do believe MADRS correctly found wrong, but I do believe that they consider CGI and MADRS somewhat similar. So, we try to take it into different endpoints and think that – if you are okay with the MADRS, of course, you would be okay with the CGI. Right, so don’t play. We are not playing, but the – you said, the – they are strictly correlated. FDQ is not strictly correlated. So it has some meaning there. You have to be – get good results from the MADRS.

Thank you so much. Yes, thank you.

I hope I answered.

Yes, yes, that’s pretty good. And looking forward to other data next – every quarter next year. Thank you.

Thank you.

Our next question is from Andrea Tan with Goldman Sachs. Please proceed.

Thanks for taking the question. Sergio, the first one, just a follow-up on your comments on the plans for the rolling NDA submission. Would results from RELIANCE III support approval for monotherapy use or would you need to run a second trial to picture that indication?

Yes, I would say it’s a good question. By the way, good afternoon, Andrea. The – our opinion, so, the FDA have commented upon this. If all these three studies are positive, we do believe that one, monotherapy study would be enough to get an indication underneath. If would be the only positive study, then I don’t think that it’s going to work. So we will have to run at least another one as a monotherapy. So, that’s our current thinking.

Got it. And then, just one if you could comment on what you are seeing with enrollment in the RELIANCE I and II trials that’s delaying the timing of those readouts. And in particular, do you see this in any way reflecting commercial dynamics that could play if REL-1017 were approved?

Yes, do you mean, why it takes a little longer to complete the adjunctive. Look, this is more simple as the quality of the trial. We have a lot of lot of – we pay a lot of attention with the quality of – we really want the patients to be the first. And so, and that’s there is a pretty high selection of the patient, I mean, not selection, but we don’t know, patients will respond or not. But definitely, we want to be sure that that patient needs depressed but not have personality disorder or does not have anything that would not be an appropriate for an antidepressant treatment. And the failure rate from screening is about 50%. So, one out of two patients is not enrolled, because that’s not qualified. So, we have very stringent inclusion and exclusion criteria mostly focused on safety of course, but focus also on being sure that we don’t enroll everybody. And enrolling is very easy. If you want just to conclude the study, you can do it very, very quickly, but that’s not what we want to do. We want a study that would reflect the effects of the program, our drug and that it takes a little bit more time. The monotherapy is supposedly lot faster, because that’s in September and we see what the ramp up is. But, the inclusion and exclusion criteria are the same as an adjunctive, but the patient selection is – it is more patients as for the industry.

Got it. Thanks, Sergio.

Thank you, Andrea.

Our next question comes from Jay Olson with Oppenheimer. Please proceed.

Hey, congrats on the progress and thanks for taking the questions. Maybe just to follow-up on the recent competitors’ results in TRD. Do you see any read across from that COMPASS Pathways study for psilocybin in TRD to your own psilocybin program from Arbormentis? And can you maybe give us an update on the current status of that compound?

Yes. Sure, sure. Thank you, Jay. Nice to hear from you. Look, the prospects if there any correlations, the answer is no. The base of our program on the silo siding is go to the different forms pretty much every other competitor that works on silo siding. We are not doing anything regarding psychiatry and so, now depressant is neurodegenerative diseases and we want to leverage our expertise on the neuroplastic effect of DDNF and high rates to an agonist at the end of the castrate, pretty much results in a similar neuroplastic effect similar to an NMDA antagonist. So, we want to leverage what the – of the science in neurodegenerative diseases and we use enormously lower dose compared to the competition and works from psychiatry. And the base of that is that with that our scientist that – but it’s actually our scientist, they do not believe that you need to get hired to get like [Indiscernible] whatever effect to have a neuroplastogenic effect. So we go for much lower dose for chronic treatment and not with psychiatry and neurodegenerative diseases. So, the straight answer is, there is no correlation between what the other companies are doing, what we do. The status, we are working on manufacturing. Believe it or not if that’s the - it is not the easiest compound to produce synthetically and I don’t know, Maged, certainly – talk too much, but. We have designed and generated our own proprietary synthetic with a freedom chemist. And so, we are going through the manufacturing right now and dealing with the FDA, of course, the silo siding about the problem we are working on is to settle, easy two parts, sorry, one silo siding, the molecule, that’s one we would like if the FDA agrees, especially, because we use very low dose compared to the other players. And we would like to leverage all the safety data that is a pretty sizable package of safety for silo siding, especially at low dose. And so, definitely if the FDA agrees, then theoretically in the manufacturing will be completed then theoretically we can go straight and face to sometime probably in the second half of next year. Honestly, we are very busy – dealing with this massive safety program of REL-1017. So silo siding is going, but it is not the instruction. So that we are focusing on REL-1017 if we see the focus up to the Phase 3 data, then we will focus on silo siding, as well. But the plan is to be able to do things to – sort the things to sometimes in the second half of next year when manufacturing could be done. And the FDA – if the FDA will agree to skip, whether it’s preclinical and Phase 1 as we do believe. And the second part of the program is derivatives of silo siding is a new chemical entity. So that’s a full fledged development. So, we will start – we have synthesizing now but we will start from in vitro and I believe we are doing some animal studies now. But it’s very – through the earliest than the silo siding as the silo siding more we could. I hope that answers you.

Yes, that’s great. That’s super helpful. Thank you very much and maybe just one follow-up. Can you comment on what particular forms of neurodegeneration that you are thinking about studying when you initiate your Phase 2 trials?

Let me try. Let me try without – yes, so we are focusing on diseases where there is a damage of the nerves - of some nerves. I would say, acute damage. So – and if we are right, and silo siding is very safe and especially at the doses that we are using, potentially, it could speed up the recovery of the - of limited damage of the nerve, or speed up the recovery if there is a way to measure the recovery.

So, wouldn’t update more than that.

How should we, we are discussing with or we will discuss with the FDA, so. We want to be sure that there are in agreement of what we want to do. But that’s pretty much would be the plan. So, more acute nerve injury and so, attempting to improve the reduced damage and for improved recovery of that.

Great. That’s super helpful.

That’s an important one indication of course, it’s the acute nerve damage, it can be - it can happen for it, but I – yes.

Okay. It’s not only in the spinal cord injury or stroke?

No. Spinal cord injury, I have been involved 25 years ago and never get close to that. And not spinal cord injury.

Okay. Okay. Alright. Great. Thank you so much. I appreciate the additional color.

Thank you, Jay.

Thank you. Ladies and gentlemen, there are no further questions at this time and I’d like to turn the call back to Sergio Traversa for any closing remarks.

Thank you, operator and well, thank all of you for joining us on the call today. We are pleased to share our recent progress with you and the REL-1017 clinical development program continued to advance. W are excited about the many important catalysts that lie ahead of us in 2022 and we will keep you updated on clinical readouts and activity in the coming months. Next year is really would be the – where – we will know if we have a drug or not. And we do believe – I do believe that we do have a drug and it potentially can be a very good drug at helping a lot of people. Thank you all again for joining on the call and enjoy the rest of your day. Thank you.

This concludes today’s conference. You may now disconnect your lines at this time. Thank you very much for your participation.