Full Year 2023 Relmada Therapeutics Inc Earnings Call

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Operator: Good afternoon, ladies and gentlemen, and welcome to the Relmada Therapeutics Inc. fourth quarter and full year 2022 results call. At this time, all lines are in a listen-only mode.

Good afternoon, ladies and gentlemen, and welcome to the real Magic Therapeutics, Inc. Fourth quarter and full year 2022 results call. At this time all lines are in a listen only mode.

Operator: Following the presentation, we will conduct a question and answer session. If at any time during this call you require immediate assistance, please press star zero for the operator. This call is being recorded on Tuesday, March 19, 2024. I would now like to turn the conference over to Mr. Timothy McCarthy. Thank you.

During the presentation, we will conduct a question and answer session.

Any time during this call ill be quite you need assistance. Please press star zero for the operator. This call is being recorded on Tuesday March 19, 2024, I would now like to turn the conference over to Mr. Tim Mccarthy. Thank you. Please go ahead.

Timothy McCarthy: Thank you, operator. And thank you all for joining us this afternoon. With me on today's call are Chief Executive Officer Sergio Traversa and Chief Financial Officer Maged Shenouda. This afternoon, Relmada issued a press release providing a business update and announcing financial results for the three and 12 months ended December 31st, 2023. Please note that certain information discussed on the call today is covered under the Safe Harbor provisions of the Private Securities Litigation Reform Act. 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.

Thank you operator, and thank you all for joining US. This afternoon with me on today's call are Chief Executive Officer, Sergio to reverse that and Chief Financial Officer magazine do it.

This afternoon <unk> issued a press release, providing a business update announcing financial results for the three and 12 months ended.

Remember 31 2023 please.

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 very modest 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 Companys business.

Timothy McCarthy: These forward-looking statements are qualified by the cautionary statements contained in Relmada's press release issued today and the company's SEC filings, including in the annual report on Form 10-K for the year ended December 31, 2023, and subsequent filings. This conference call also contains time-sensitive information and is accurate only as of the date of this live broadcast, March 19th, 2024. Relmada undertakes no obligation to revise or update any forward-looking statements to reflect events or circumstances after the date of this conference call. Now, I'd like to turn the call over to Sergio. Sergio?

These forward looking statements are qualified by the cautionary statements contained in Rome modest press release issued today and the Companys SEC filings, including in the annual report on Form 10-K for the year ended December 31 2023 filings.

Violence.

This conference call also contains time sensitive information that is accurate only as of the date of this live broadcast March 19 2024.

<unk> undertakes no obligation to revise or update any forward looking statements to reflect events or circumstances. After the date of this conference call now.

Now I would like to turn the call over to Sergio Sergio.

Sergio Traversa: Thank you, team, as always. Good afternoon to everyone and welcome to the Relmada fourth quarter and full year 2023 conference. We are continuing to make solid progress in advancing the ongoing phase three program for RELM 1017 in major depressive disorder, or MDD, as well as in the promising preclinical novel psilocybin program, which I will briefly cover today.

Thank you team is always good afternoon to everyone and welcome to the <unk> fourth quarter and full year 2023 conference call.

We have continued to make solid progress in advancing the ongoing phase III program for route 10, 17 in major depressive disorder MTV.

As well as in the promising preclinical novel Silo siding program.

All of which I will briefly cover today.

Sergio Traversa: Following this, Maged will review our fourth quarter and full year 2023 financial results, and then we will take your questions. Let's begin with an update on the phase three program for rail transfer. As you know, Relmada is focused on developing REL1017 as an adjunctive treatment for MDT.

Following these magnet will review.

Our fourth quarter and full year 2023 financial results and then we will take your questions.

Let's begin with an update on the phase three program for <unk> as you know <unk> focuses on developing 10 17 is an adjunctive treatment for M D.

Sergio Traversa: As previously communicated, we have made critical changes to Reliance 2, the ongoing study 302, a phase 3, two-arm placebo-controlled pivotal study evaluating RELTEN17 25 mg for adjunctive MDD aimed at controlling placebo response and improving enrolment quality. The Amendment Study 302 Protocol has been implemented across all our clinical sites. Enrollment continues to steady progress, and our ability to leverage our close relationship with the study site is paying dividends. Moreover, the ongoing initiative we put in place to drive trial awareness with prospective patients is also bearing fruit. Importantly, we are evaluating the product video site on a real-time basis and making changes where needed.

As previously communicated we have made critical changes to reliance to the ongoing study three zero to a phase III two arm placebo controlled pivotal study evaluating <unk> and 17 25 milligram for adjunctive NBD aimed at controlling.

Placebo response, and improving the enrollment quality.

The Amendment study three or two profitable has been implemented across all our clinical study sites.

Enrollment continues to steadily progress and our ability to leverage our close relationship with the study site is paying dividends.

Moreover, the ongoing initiative, we put in place to drive trial awareness with prospective patients are also bearing fruit.

Importantly, we are evaluating the product P video site on a real time basis, and making changes where needed.

Sergio Traversa: As a reminder, we plan to enroll approximately 300 patients into Reliance. Based on our current projections, we expect the involvement in Reliance 2 to be completed in mid-2020. In our second phase three trial for REL 1017, named Relight, or study 304, we began dosing patients during the third quarter of last year. Relife also has a planned enrollment of approximately 300 patients that is planned to be completed by year-end 2024. To reiterate what we have said previously, like Reliance II, Reliance is a randomized, double-blind, placebo-controlled four-week trial evaluating the efficacy and safety of REL1017 as an adjunctive treatment for MDD in patients experiencing an inadequate response to ongoing background antidepressant treatment.

As a reminder, we plan to enroll approximately 300 patients into reliance too.

Based on our current projections, we expect the involvement into July as two to be completed in mid 2024.

In our second phase III trial for <unk> thousand 17 named re light or studied 304, we begin dosing patients during the third quarter of last year.

<unk> also has a planned enrollment of approximately 300 patients that is planned to be completed by year end 2024.

To reiterate what we have said previously like rely as to realize is a randomized double blind placebo controlled four week trial.

Evaluating the efficacy and safety of <unk> 17, as an adjunctive treatment for MTBE in patients experiencing inadequate response to ongoing background antidepressants.

Sergio Traversa: The primary endpoint of both studies is the change in the Madras total score from baseline to day 28 as compared to placebo. I should highlight that we made significant changes to our screening and enrollment processes in order to ensure that we have patients that meet all the quality criteria. More specifically, we have instituted a comprehensive adjudication process through which we now require medical records for all patients enrolled in Reliance II and Reliance.

The primary endpoints of both studies is the pain is the change in the mattress total score from baseline to day 28 as compared to placebo.

I should highlight that we've made significant changes to our screening and enrollment processes in order to assure that we have patients that meet all the quality criteria.

More specifically, we have instituted a comprehensive adjudication process through which we now require medical records for all patients involved he really has two and reliable.

Sergio Traversa: Given this, our screen failure rate in these studies is now approximately 80% versus 50% previously in Reliance 1 and Reliance 3. Additionally, our previously completed Phase 3 trials were well 1070. We strongly believe that these changes will significantly enhance the probability of success of our current study. [inaudible] We have completed all the necessary preclinical, manufacturing, and phase one studies required for a potential RELM 1017-NDA file, and are now focused on execution of values for pre-commercial readiness. Moving now to our promising preclinical novel, the Modified Release Psilocybin Program. You may recall that at last November's AASLD meeting, the Lever Conference, compelling preclinical data were presented in a poster presentation. These data demonstrated the beneficial effect of low-chronic-dose psilotyping on multiple metabolic parameters in a rodent model of metabolic dysfunction associated with steatotic liver disease, or MASLD.

Given this our screen failure rate in these studies is now approximately 80% versus 50% previous day, one and really as to meet our previously completed phase II trials for route 10 17.

We strongly believe that these changes will significantly enhance the probability of success of our current status.

I would note.

We have completed all the necessary preclinical manufacturing and phase one studies required for a potential 10, 17 98 filing and are now focused on execution of values pre commercial readiness activities.

Moving now to our promising preclinical NOLA modified release silo saving program.

You may recall that at last November.

A a S. L D meaty believer Congress compelling pre nickel preclinical data were presented in a poster presentation.

These data.

Demonstrated the beneficial effect of law chronic low crawling those titles typing on multiple metabolic parameters in a rodent model metabolic dysfunction associated stay at Arctic lever disease or M. A S. L D.

Sergio Traversa: These initial promising preclinical results support the therapeutic potential of low chronic doses of psilocybin. As we said previously, based on this data, low-dose psilocybin could improve lipids and glucose with potential fewer side effects over other investigative treatment approaches, such as GLP-1, glucagon, and GIP. We intend to initiate a single ascending dose phase one trial in obese patients in the first half of 2024 to define the pharmacokinetic, Safety, and Tolerability Profiles for our Modified Release Psilocybin Formulation in this population. This will be followed by a Phase 2A trial to establish critical proof of concept. Data from the Plan 2A study is anticipated in the first half of next year. Just to summarize the multiple upcoming key milestones over the next 12-18 months. We anticipate completing involvement in the ongoing Reliance II study mid-2024, with top line in the second half. In addition, we plan to complete involvement in the real-life study by the end of the year. Finally, we intend to initiate a phase one clinical trial for the modified release formulation of psilocybin in the first half of. Moving on.

These initial promising preclinical results support the therapeutic potential of low chronic dose of silo siding.

As we said previously based on the data these data logos, Tyler I'd be could improve lipids and glucose with potential fewer side effects over other investigating treatment approaches such as G. L. P. One gook adult and G IP.

We intend.

To initiate a single ascending dose phase one trial in obese patients in the first half of 2024 to defy the pharmacokinetic safety and Tolerability profile or our modified release silos IV formulation in this population.

This will be followed by a phase Iia trial to establish clinical proof of concept.

Data from the plant to a study is anticipated in the first half of next year.

Just to summarize of our multiple upcoming key milestones over the next 12 18 months.

We anticipate completing involvement in the envoy and reliance do study mid 2024 with top line in the second half.

In addition, we plan to complete enrollment in the real life study by the end of this year.

Finally, we intend to initiate a phase one clinical trial for the modified release formulation of <unk> in the first half of this year.

Moving on to.

Sergio Traversa: While Maged will provide a detailed review of our financials, I would like to emphasize that with current cash on hand... to take us into 2025, Relmada remains sufficiently funded to fully execute our plans to reach data readouts from both REL 1017 phase 3 trials. Reliance on you and Reliance, as well as conduct the planned phase one for our modified. [inaudible] I will now turn the call over to Maged to review our fourth quarter and full year financial results. [inaudible] Thank you, Sergio.

Slide <unk>, we provide a detailed review of our financial I would like to emphasize that with current cash on hand.

To take us into 2025.

That remains sufficiently funded to fully execute our plans to reach data readouts from both real time 17 phase II trials reliance who are we liked as.

As well as from the planet Phase one four hour modify rudi's Silas IV formulation.

I will now turn the call over to Maggie to review, our fourth quarter and full year financial results.

<unk>.

Thank you Sergio today, we issued a press release announcing our business and financial results for the three and 12 months ended December 31, 2023, which I will now review.

Maged S. Shenouda: Today we issued a press release announcing our business and financial results for the three and 12 months ended December 31, 2023, which I will now review. The fourth quarter ended December 31, 2023.

For the fourth quarter ended December 31, 2023, total research and development expense was approximately $14 $8 million as compared to $26 $9 million for the comparable period of 2022, a decrease of approximately $12 $1 million.

Maged S. Shenouda: Total research and development expense was approximately $14.8 million, and it was compared to $26.9 million for the comparable period of 2022, a decrease of approximately $12.1 million. The decrease is primarily associated with the completion of two phase three trials and the long-term open label safety trial study 310. The research and development non-cash charge related to stock-based compensation totaled $1.8 million in the most recently completed fourth quarter. Total general and administrative expense for the fourth quarter ended December 31, 2023, was approximately $12.1 million, as compared to $11.8 million for the comparable period of 2022, an increase of approximately $243,000. The increase was primarily driven by an increase in compensation expense due to higher employee-related costs.

Decrease was primarily associated with the completion of two phase III trials and the long term open label safety trial study 310.

The research and development noncash charge related to stock based compensation totaled $1 $8 million and most recently completed fourth quarter.

Total general and administrative expense for the fourth quarter ended December 31, 2023 was approximately $12 $1 million as compared to $11.8 million for the comparable period of 2022, an increase of approximately $243000. The increase was primarily driven.

And by an increase in compensation expense due to higher employee related costs the.

Maged S. Shenouda: The general and administrative non-cash charge related to stock-based compensation totaled $8.1 million in the most recently completed fourth quarter. For the fourth quarter ended December 31, 2023, the net loss was $25.2 million, or 84 cents per basic and diluted share compared with a net loss of $37.9 million, or $1.28 per basic and diluted share in the comparable period of 2020. Turning to the results for the full year ended December 31, 2023, total research and development expense was approximately $54.8 million.

General and administrative noncash charge related to stock based compensation totaled $8 $1 million in the most recently completed fourth quarter.

For the fourth quarter ended December 31, 2023, net loss was $25 2 million or <unk> 84 cents per basic and diluted share compared with a net loss of $37 $9 million or $1.28 per basic and diluted share in the comparable period of 2022.

Turning to the results for the full year ended December 31, 2023, total research and development expense was approximately $54 8 million as compared to $113 3 million for the year ended December 31, 2022, representing a decrease of $58 5 million.

Maged S. Shenouda: Compared to $113.3 million for the year ended December 31, 2022, representing a decrease of $58.5 million. Again, the decrease was primarily driven by a reduction in study costs associated with the completion of two phase three trials and the long-term open label safety trial study three. For the year ended December 31, 2023, total general and administrative expense was approximately $48.9 million, which was compared to $47.9 million for the year ended December 31, 2022. Again, the increase was primarily driven by an increase in compensation expense due to higher employee-related costs.

Again, the decrease was primarily driven by reduction in study costs associated with the completion of two phase three trials and a long term open label.

T trial study three.

For the year ended December 31, 2023, total general and administrative expense was approximately $48 9 million as compared to $47 $9 million for the year ended December 31 2022, okay.

Kevin increase was primarily driven by an increase in compensation expense due to higher employee related costs.

Maged S. Shenouda: For the year ended December 31, 2023, the net loss was approximately $98.8 million, or $3.28 per basic and diluted share, compared with a net loss of $157 million, or $5.30 per basic and diluted share, for the year ended December 31, 2022. As of December 31, 2023, we have cash, cash equivalents, and short-term investments of approximately $96.3 million, compared to approximately $148.3 million as of Cash Uses and Operations for the full year 2023 were $51.7 million.

For the year ended December 31, 2023, net loss was approximately $98 $8 million or $3.28 per basic and diluted share compared with a net loss of $157 million or $5 30 per basic and diluted share for the year ended December 31 2020.

Two.

As of December 31, 2023, we had cash cash equivalents and short term investments of approximately $96 3 million.

Compared to approximately $148 3 million as of December.

31 2022.

Cash used in operations for the full year 2023 was $51 $7 million.

Operator: Based on our current clinical development plan, our current cash position provides us with ample runway into 2025. Of note, this time period includes data readouts from both phase three trials, Reliance 2, Study 302, and Relight, Study 304, as well as the initiation of our planned phase one trial of our modified release 507 formula. Operator, I will now ask the operator to please open the call for questions.

Based on our current clinical development plans, our current cash position provides us with ample runway into 2025.

This time period include data Readouts from both phase III trials reliance to study 302, and re light study three or four as well as the initiation of our planned phase one trial of our modified release cycles haven't formulations.

I'll now ask the operator to please open the call for questions operator.

Operator: Thank you. Ladies and gentlemen, we will now begin the question and answer session. Should you have a question, please press star five by the one on your telephone keypad. You will hear a three-tone prompt acknowledging your request. Questions will be taken in order. Should you wish to cancel your request, please press star followed by 2. If you are using a speakerphone, please lift the handset before pressing any button.

Thank you ladies and gentlemen, we will now begin the question and answer session should you have a question. Please press star followed by the one on your telephone keypad.

Hey, Tom.

From technology and request questions will be taken in the order received should you wish to cancel your request. Please press star followed by the deal.

Are you seeing your speaker phone please lift the handset before pressing any Keith.

One moment. Please for your first question.

Your first question comes from the line of Marc Goodman from New Partners. Please go ahead.

Unknown Speaker: One moment, please, for your first question. Your first question comes from the line of Marc Goodman from New Partners. Please go ahead. Hi, good afternoon. This is Basma on behalf of Marc.

Hi, Good afternoon. This is <unk> on for Mike.

For Alliance two could you. Please your line is again, how many patients were enrolled before the protocol amendments.

Sergio Traversa: For Alliance 2, could you please remind us again how many patients were enrolled before the protocol amendments? And do you expect that, due to the inclusion of these patients prior to the amendments, there will be any source of, I would say, noise or disruption to the trial, or were you able to go back and check the inclusion criteria? But thank you. That's Sergio here.

Do you expect that due to the inclusion of these patients prior to the amendments that there'll be any sorts of noise or hum.

To the trial or what are you able to go back and check that inclusion criteria.

Thank you.

But thanks to you that that's a great question.

<unk> previously to the amendment that we enroll about AED.

Sergio Traversa: That's a great question. Let me be previous to the amendment. We enroll about 8090 patients. And so, As of now, I mean, we will include them in the final analysis, and the like. We have noticed, if I can expand for a bit, we have noticed that there was a big difference in patients enrolled when the COVID restriction was in place and after the COVID restriction was lifted. So of these 80-90 patients, about half were enrolled after the COVID restriction was lifted. So, I mean, the data is blinded, so we don't really know how the data will look, but we don't have any reason to believe that this patient would carry any particular baggage, also because the sites that were the issue with data were generated in the previous trials. They have never been praised in RADIAS-2.

E 90 patients and Saudi.

As of now.

We.

They will be included in the in the final analysis.

And.

The like.

We have noticed if I can spend for it for a bit we've noticed that there was a big difference.

In patient enrolled.

When the Covid restrictions bear in any place.

And and.

After the Covid restrictions were lifted so all of these 80 90 patients about half way enrolled after the Covid restrictions were lifted. So I mean these are behind us. So we don't really know how the data will look like but we don't have any reason to believe that the right.

The these patients would carry any particular baggage also because the.

The the sites that are where the issue with data was generated in the previous trials.

They've never been phrased it really has to sell at the bottom line is that yes. These patients will be included in the in the final analysis, but we don't have any particular reason to believe that that would carry any any particular burden on the final review and we do have it on the call Doctor and do Cutler that is.

Sergio Traversa: So the bottom line is that, yes, this patient will be included in the final analysis, but we don't have any particular reason to believe that it would carry any particular burden in the final review. And we do have Dr. Andrew Cutler, who is our special advisor for clinical development, on the call. And maybe, Andrew, if you are online, you may want to expand a little bit on the question that is, right, will these patients enrolled prior to the protocol amendment carry any weight on the final result? Well, thank you very much. I'm here.

Sure.

So you know advisor for clinical development and maybe Andrew If you are online you may want to expand.

A little bit on the question that is will these patients are enrolled a previous to the protocol amendment carry any weight on the final results.

Well, thank you very much I'm here.

Unknown Speaker: Excuse me. I think it's a very reasonable question, but I'm pretty confident. I would say I'm very confident that we should be successful. The previous study really was very close to being positive. It just missed.

Excuse me I think it's a very reasonable question, but im pretty confident.

I'd say im very confident that we should be successful. The previous study really was very close to being positive adjusted mist and so you don't have to be perfect. Here, we just have to be better.

Unknown Speaker: And so you don't have to be perfect here. We just have to be better. I think the changes that have been made, particularly with respect to analyzing the quality of the site and the protocol amendment will affect the quality of the second cohort here, which is going to be the majority of the patients. I think we'll go through. So I'm very confident that, despite having some patients enrolled previously, you know, I still think we're going to be successful overall. Thank you. That's very helpful. I hope that answers your question. Yes, thank you. Thank you. And your next question comes from the line of Uy Ear from New Zealand. Please go ahead, for taking our questions. So I have a couple.

And I think the changes that have been made particularly with respect to analyzing the quality of the sites and the protocol Amendment will make the quality of.

The second cohort here, which is going to be the majority of the patients I think will carry through.

I am very confident that despite having some patients enrolled previously.

I still think we're going to be successful overall.

Thank you. Thank you I hope that answer your question.

Yes. Thank you.

Okay.

Thank you and your next question comes from the line of Billy <unk> from Mizuho. Please go ahead.

Taking our questions. So I have a couple so just following up on the previous question.

Sergio Traversa: So just following up on the previous question, you know, at these sites that enrolled patients previously, could you maybe elaborate on or remind us just like, were most of these patients referred by physicians and, you know, were there large volumes of patients or were just a few patients at these sites? Yeah, so that's sort of the first question, and I'll ask a second question. Yeah, sure. Thank you. We went to the two sides, with together they enrolled about 20% of the study 301, the adjunctive treatment study, and that they've never been present in 302. And then, you know, there were a couple of issues there. We don't really know why the data for these two sites were the opposite or completely different from the other 41 sites in the trial. But, you know, just to accept that, you know, that was reality. But they've never been in the study 302.

At the sites that enrolled patients previously.

Could you maybe elaborate on or remind us just like where are most of these patients referred by physicians and.

Or will there large volumes of patients or just a few patients at these sites.

Yeah. So that's sort of the first questions I'll ask a second question after that thanks.

Yeah sure. Thank you Lee.

So the there are two sites.

With together they enroll about 20% of the study 301, the adjunctive treatment study.

And that they have never been crowded in tier two and they've got a couple of issues that we don't really know why the data over these two sites, where the opposite a completely different from the other 41 sites in the trial, but we just have to accept that.

There was reality, but they've never been in the in the study to go to it now.

Sergio Traversa: And now, we will be limiting the number of patients enrolled at each site. So we won't have any site that will, like, make a major impact on the final number. So we feel confident that with these measures, what happened in study 301 will not happen. Yeah, another quick thing, another modification we made was requiring medical records to ensure that these were legitimate patients who actually were taking an antidepressant, and that was not done in the 301 study. So that's another improvement we've made. All right, thanks. And maybe, um, more presently, could you provide some color on maybe the proportion of patients who've so far been enrolled in Reliance 2 and, um, and you know, and maybe Relight as well. And, and, and after that, maybe just briefly, Maged, like, just tell us, help us think about how to, to model the cadence of spending? Is it sort of relatively flattish?

We will we are limiting the number of patient enrolled.

For each site. So we won't have any site that will.

Make a major impact on the final numbers. So we feel confident that with these measures.

The.

We want.

What's happening in the study 301 will not happen again.

Okay, if I could add one other quick staying another another modification, we made was requiring medical records.

To ensure that these were legitimate patients who actually were taking an anti depressant and that was not done in the 301 study. So that's another improvement we've made.

Alright, Thanks and maybe.

More presently.

Could you provide some color on maybe the proportion of patients who have been.

So far in role in reliance too and.

And you know and maybe re light as well.

Handset and fall and after that and maybe just briefly maggot.

Just tell us help us think to think about how to tomatoes, the cadence up spending is it sort of relatively flattish or what it's sort of go down towards the end of the year. Thanks.

Sergio Traversa: Or would it sort of go down towards the, Yeah, I'll take the first one. We may not want to go into real details about the number of patients, but like we passed half of the trial at the end of last year. And well, it's progressing steadily with some variability, maybe week to week. But you know, it's on track. And, you know, we are confident that we will have top-line data in the second half of this year. And when we get closer, we'll be a little bit more precise.

Yeah, I'll take the first one.

We'd be we.

We may not want to go like in real details about number of patients, but like we passed.

Half of the trial at the end of last year and enrollment is progressing steadily with somebody ability may be week to week, but I used to say, it's the it's on track and we are confident that the.

Topline data in the second half of Bcf.

When we get closer we'll be a little bit more precise.

Sergio Traversa: And but, you know, we stay with these slightly broad guidance about the second half of this year, the reason being that we are screening quite a bit of patients. I mean, I don't, but the number of screen patients is very large. What we have noticed with the improvement in the protocol, clearly, the screening failure went up significantly. We were around 50% on the previous trial. I think I mentioned that before. We are now approaching 80%.

And but we stay with these a little bit broad guidance about sac in the half a bcf and reason being that we are screening a quiet could beat of patients I mean, I don't Brian, but the the big the number of screen patient is very large what we have noticed with the.

With the improvement on the protocol clearly the screening failure. It went up significantly and we were around 50% on the previous trial I think I mentioned that before we are now approaching 80%. So the selectivity in enrolling patients is it's much higher.

Sergio Traversa: So I mean, the selectivity in enrolling patients is much higher. We did look, and I can expand on the reasons why these patients are not enrolled in the screen, and they are legitimate reasons. And so these are the patients that generated the issues in the previous trials. And definitely, we don't want this kind of patient again in the new trials. So you know, the screening process is going very, very well, and the screen failure rate for legitimate reasons is much higher.

We did look if I can expand on the reason why these patients are not enrolled and it would be a screen and they all legitimate reasons and so these are the patients that generated the issue in the previous trials and definitely we don't want these kinds of patients.

Again in the new trials. So you know the the screening process. It's a it's it's going very very well and the screening failure for legitimate reasons. It's much higher so we do believe that the quality is very very good in this trial I know, Andrew if you want to add something.

Sergio Traversa: So we do believe that the quality is very, very good in this trial. I know, Andrew, if you want to add something. No, no, I think you've said it.

No no I think you've said it well it's in line with what I said earlier, we're really trying to make sure we have the right patients.

Unknown Speaker: Well, it's in line with what I said earlier. We're really trying to make sure we have the right patient, legitimately with the illness, and not patients with mild depression or who are not legitimate patients. So we're really trying to be careful about selecting the right patient. Maged, I think Maged, the second one was for you.

With legitimate lead with the illness and not patients with mild depression or who are not legitimate patients. So we're really trying to be careful about selecting the right patients.

Yeah.

Magazine the magazine to stick on the mine is both for sure.

Maged S. Shenouda: Sure. Yep, yep. So, hi, Loy.

Yeah, So hi, thanks for the question.

Maged S. Shenouda: Thanks for the question. G&A expense should, you know, follow the pattern we had in 2023 on a quarterly basis. You know, a lot depends on enrollment patterns, but our current expectation is that R&D should pick up a little bit in the third quarter and then, excuse me, in the first quarter. In the first quarter, and then again, you know, increase in the second quarter and then, you know, stay at that level through the third and fourth quarters, as you can sort of see enrollment pick up in 302, and then pick up in 304 as well.

G&A expense should.

Following the pattern, we've had in 2023 on a quarterly basis.

You know a lot depends on enrollment patterns for our current expectation is that R&D should tick up a little bit.

In the third quarter.

And then excuse me in the first quarter in the first quarter and then again.

You know increase in the second quarter and then.

Stay at that level through the third and fourth quarter as you can sort of see enrollment pick up.

Hum 302, and then pick up in three or four as well so I hope that helps.

Maged S. Shenouda: So, I hope that helps. Very helpful. Thank you. Sure, my pleasure. Thank you. And your next question comes from the line of Andrew Tsai from Jeffries. Please go ahead. Hey, good afternoon.

Very helpful. Thank you.

Sure My pleasure.

Thank you and your next question comes from the line of Andrew Tsai from Jefferies. Please go ahead.

Hey, good afternoon. Thanks for taking my question. So first one I noticed in your prepared remarks, he said, how you're monitoring sites in real time, making changes accordingly, so what exactly are you monitoring for and what kinds of changes are you making.

Unknown Speaker: Thanks for taking my question. The first one I noticed in your prepared remarks, you said how you're monitoring sites in real time, making changes accordingly. So what exactly are you monitoring for? And what kinds of changes are you making on a day to day basis?

On a day to day basis.

Unknown Speaker: And then secondly, are there any learnings or thoughts that you might have on SAGE's recent rejection of their MDD study, sorry, not study, but the approval, and if there's any read-through or any lessons learned that you think you could apply to REL 1017, thanks. But thank you, thank you, Andrea. And thanks for the call.

Then secondly.

Are there any learnings or thoughts that you might have on sages recent rejection further MTT study.

Sorry, not study but.

The approval.

And if theres any read through or any lessons learned that you think you could apply to.

101, seven thanks.

Sergio Traversa: I will ask you to repeat the second question, because I didn't understand it 100%. But the first question: I think Andrea can go a lot more in detail, since he has been running his business for 30 years and has done many, many CNS clinical trials. But there is no magic, right? You monitor, in general, every, like, three, four patients, four, five patients enrolled by the site, what their blinded data looks like. Of course, they're blinded, so you don't know if they are good.

Thanks, Sue and thanks, you Andrew and thanks for the call I will ask you thereafter to repeat the second question because I didn't get it.

But.

The first question is I think Andrew I can go a lot more in detail as soon as he is Ron Ron Aside for 30 years and is on many many CNS clinical trials, but there is no magic right you monitor in Genoa, you monitor it.

Every like three four patients four five patients enrolled by decide how the blinded data. They looked like of course is blinded. So you don't know it.

Good but you definitely can have a good understanding if there is something wrong right. When you have data that are there.

Sergio Traversa: But you definitely can have a good understanding if there is something wrong, right? When you have data that the variability week over week of the first four weeks is one week up, one week down, and you go up and down, you know, usually that's not the behavior that placebo and the drug do when there is a trend. So that's one signal. And then, you know, the overall quality of the site, right? How, you know, the quality is the document, documenting data; they put the data in the database. So there is no one single factor. Is there a combination that can give you some sense of if the site is providing the service that we would like to? Andrea, I mean, you have done this for a long time. Do you want to add anything?

Variability week over week of the first four week is one week, one week up one down and you go up and down you know usually that's not the behavior of the placebo and the drug do right when did it as a trend.

So there's one signal and then the overall quality of the sites right how the qualities.

Document document and data they could the data in the database. So there is no. One single factor is there a combination that can give you some sense. If the site is providing light to service debt.

We would like and I mean, you have done this for a long time do you want to add anything yes, yes.

Unknown Speaker: Yes, there are various quality indicators you look for. And I think we're watching the reminders in the store much more closely here. You look for things like, "Are the rating scales consistent? Are they kind of all moving in the same direction?"

Yes, there are various quality indicators you look for.

And I think we're watching we're minding the store much more closely here you look for things like our the rating scales consist entirely kind of all moving in the same direction.

Unknown Speaker: You look for adherence to the protocol and what we call protocol violations, which indicate sloppiness. You know, this time we're being careful not to let, as Sergio said, any sites just kind of get off to the races and recruit too many patients or too fast. So there are a variety of quality indicators you look for and consistency things you look for, as Sergio said, and we're watching that. And then if there's a site that has issues, we're actually stopping their enrollment.

You look for adherence to the protocol and what we call protocol violations, which indicate sloppiness.

You know this time, we're being careful to not let as Sergio said any sites just kind of get off to the races and recruit two too many patients or too fast. So there are a variety of quality indicators, you look for and consistency things you look for.

As Sergio said, we're watching those and then if there is a site that has issues, where we're actually stopping their enrollment.

Unknown Speaker: We're trying to figure out what's going on and deciding if we want to continue with them or not. Hope that answers your question, Andrew. And if you don't mind, I'll repeat the second one, because I didn't understand it.

Trying to figure out what's going on in deciding if we want to continue with them or not.

Hope that answer your question, Andrew and that if you don't mind to repeat the second one because I didn't get it.

Unknown Speaker: Oh, perfect. Um, you know, Sage recently had their NDA rejected for MDD. And I'm just curious if the reason behind that rejection has any bearing or reads through to your product as methadone, basically. Sergio, maybe I could help. Maybe I could help with this one, because I was very involved. I was very involved with that. It's really apples and oranges. Their paradigm was very different.

Perfect.

Yes.

Suddenly had their N D. A projected four M D D.

And I'm just curious if.

The reason behind that rejection has any bearing or read through to your.

Ask method basically.

Yes, maybe I could help maybe I could help yes.

Go ahead I was very involved I was very involved with that it's really apples and oranges.

They're they're in paradigm was very different it was the two week treatment paradigm with a very different mechanism.

Unknown Speaker: It was a two-week treatment paradigm with a very different mechanism, and really, the problem was they didn't have a good story for how two weeks of treatment would hold a charge. And in their phase two study, there was a suggestion that the efficacy continued beyond the two weeks. However, it was not well replicated in phase three.

And really the problem was they didn't have a good story for how two weeks of treatment would hold a charge.

And in their phase two study there was a suggestion that the efficacy continued on beyond the two weeks. However, it was not well replicated in phase III. So the FDA had concerns about that it's a very different paradigm very different medicine, I don't see it as a.

Unknown Speaker: So the FDA had concerns about that. It's a very different paradigm, very different medicine. I don't see it as an. Unknown Speaker An issue or anything that would influence what we're doing.

Competition is an issue or anything that would influence what we're doing.

Unknown Speaker: Make sense? Okay. Thank you very much. Thank you Andrews, both Andrews.

Makes sense.

Okay. Thank you very much.

Thank you and us both handy.

Yeah.

Operator: Thank you once again, that is a star and one to ask a question. And your next question comes from the line of Andrea Tan from Goldman Sachs. Please go ahead. Good afternoon.

Thank you once again that is star and welcome Jesse question and Youre.

Next question comes from the line of Andrea <unk> from Goldman Sachs. Please go ahead.

Good afternoon, Thanks for taking our questions. Since you are Andrew just curious if you're able to share with reliance <unk> and <unk> studies are powered to detect them and remind us what you're assuming here for placebo response.

Unknown Speaker: Thanks for taking our questions. Sergio or Andrea, just curious if you're able to share what Reliance Q and the Relight studies are powered to detect and remind us what you're assuming here for the placebo response. That's great.

That's great. Thank you Andrew for the question, but we haven't filed with the FDA. The final Statistical plan you usually do it at the very end there was no advantage to do with it.

Sergio Traversa: Thank you, Andrea, for the question. But we haven't filed the final statistical plan with the FDA yet. You usually do it at the very end. There is no advantage to do it before.

Sergio Traversa: But, you know, it's a fair assumption that, according to the expert, in adjunctive treatment, that is like two, two and a half points. So the trial is designed to detect that kind of a change from placebo. And that would be the minimum, right? We hope we can do better than that based on phase two data. But that's a fair assumption.

Before but is it fair assumption that usually what you want to detect is a clinically meaningful.

Effect that according to the expert in adjunctive treatment is like two two and a half points. So the trial as is as designed.

Designed to detect that kind of a change from placebo and that is right that would be the minimum right. We hope we can do better than that based on the phase two data, but that's a fair assumption that would be the <unk>.

Sergio Traversa: That would be the statistical plan. And with 300 patients involved, it is feasible, and it's realistic. And then maybe just one quick question on row P11 here, just to confirm which indication you're looking to study this in. Yes, we actually did not discuss the indication.

Statistical plan.

And with 300 patients involved.

It's a it's but it is a it is feasible.

Realistic.

Mhm.

And then maybe just one quick question on rail.

Just I wanted to confirm which indication youre looking to study that.

Okay.

Yeah, yes.

We actually did not discuss the indication reason being that we don't really know exactly what kind of indication we will look at that and like with the we have to do phase one and for like pharmacokinetic all the parameters of new formulations and look at new concept low dose chronic treatment.

Sergio Traversa: The reason being that we don't really know exactly what kind of indication we will look at. We have to do phase one and for pharmacokinetic, all the parameters, the new formulations, the new concept, low-dose chronic treatment. What we can see is the effect that this had on the rodent model that, according to the expert, is somewhat relevant for what should happen in humans. And what we have seen is that there is a material decrease in body weight with no diet, but continuing the high-fat, high-glucose diet.

What we can see is the effect that had on the road and model that according to the expert.

Somewhat relevant for what should happen in human and what we have seen is that they've used the material decrease in AR in body weight with no diets with continuing the high fat high glucose diet. So despite like high fat in agricola that.

Sergio Traversa: So despite a high-fat and high-glucose diet, the rodents lost weight, not as much as GRP1, but enough to make it a valuable drug to treat obesity. But at the same time, we have seen a material decrease in glucose levels, probably a little higher than metformin. And we have seen a very material effect on fatty liver. And all this, like continuing a diet with high-fat and high-glucose. So it kind of works on all the parameters of metabolic syndrome. So weight, glucose, and fatty liver.

And they lost weight and not as much as the DLP, one but enough to make it like a valuable.

<unk> to treat obesity, but at the same time, we have seen a material decrease in our in the glucose level like similar probably a little higher than than much more win and we have seen a very material effect on fatty liver and all these like continuing a dialogue with the high fat.

Hi, glucose so it kind of works on all the span of parameter metabolic syndrome, so wait glucose and and fatty liver. So I mean to the past Samsung that indication would be a metabolic one.

Sergio Traversa: So I mean, there's a fair assumption that the indication will be a metabolic one. We haven't decided yet, and it will be decided after phase two through a concept specifically identifying what the indication will be. That it could be maybe not obesity by itself, but it could also be in combination with GLP1, and to overcome some of the limitations of GLP1, like muscle loss. But we need to see the data. And there is a wide range of possibilities all on the metabolic area that are suitable.

We haven't decided that yet.

And it will be decided that the phase two proof of concept specifically what the indication.

Will it be that Delek would could be may be not obesity by itself, but no. It could be also a combination with the G. L. P. One and to overcome some of the limitation of the DLP, one like muscle loss, but don't be in it and we have it.

We need to see the data and there is a wide range of possibility all on the metabolic area.

And that does suitable and we'll try to do something that is.

Sergio Traversa: And we'll try to do something that is a reasonable, good way to get the drug approved in a relatively short amount of time. I don't have the straight answer, but that's where we are now, waiting for efficacy data to make the final decision on where to go. Maybe just one follow-up there. Have you seen evidence to date preclinically that you are avoiding loss of muscle? when you've tracked the weight loss in these rodents.

It reasonably well.

Good way to get the drug approved in a relatively short amount of time.

I don't have this great question.

The straight answer, but that's where we are now waiting for efficacy.

Efficacy data to make the final decision of where to go.

Got it maybe just one follow up there have you seen evidence pre.

Pre clinically that.

You are avoiding loss of muscle.

When you extract that the weight loss and these robbins.

Sergio Traversa: Well, in the preclinical, no, we haven't looked at, we haven't seen it, because we haven't looked at it. And the, but it's a fair assumption that, right, since there is no change in diet, the, the, the, the, the, the, the, the, the, the, the, the, the, the, the, the, the, the, the, the, the So, psilocybin is a 5H2A agonist, and it acts at the metabolic level. Basically, it increases the metabolism of fat. So, mechanistically, it is not really expected to have loss of muscle mass, unlike GLP-1.

Well in the preclinical.

No we havent looked at we Havent seen it because we haven't looked at that and the but is it fair assumption that.

It seems there is no change in diet right the D D.

The demand on the road and don't lose weight, because they stop eating all day reduce the food intake like with G. L. P. One so at the EM psilocybin five Ht agonist.

Now agonists and eight are at Axa metabolic level, so pretty much it increase the metabolism of fat. So mechanistically is not really expected to have.

The loss of muscles. Unlike the G. L P. One.

Unknown Speaker: Thank you, everyone. Thank you, Andrea. Thank you. And your last question comes from the line of Velma Sidiati from Guggenheim. Please go ahead. And good afternoon. Thank you for taking our question. This is Delma from Yatin.

Okay. Thanks, everyone.

Thank you Andrea.

Thank you and your last question comes from the line of Matt <unk> from Guggenheim. Please go ahead.

Good afternoon. Thank you for taking our question this is Scott.

Unknown Speaker: So following up to the previous questions, can you clarify if you already performed the real-time stat checking in the previous reliance studies? Or is it something that you have implemented new only now? And then I wanted to ask you about the statistical plan, if that is run by a third party or internally within the company. Thank you. Thank you for the question. If I understand correctly, the first question is whether we did implement monitoring of the sites in the study in previous studies, and the straight answer is no. And, you know, it was COVID; it was a little bit more complicated to do it than now, and we didn't do it.

I'm wondering up to the previous questions can you clarify CRA beautiful, Ontario, Thanks, Scott checking in the previous three land studies.

Or is it something that you have implemented Neil only now and then I wanted to ask you about the statistical plan that if that is done by a third party or in <unk>, We got.

Within the company. Thank you.

Sure.

Thank you for the question.

If I understood correctly. The first question is that we did implement.

Monitoring of the sites in the study in the previous studies and straight answers now and it was cold. It was now a little bit more complicated than to do it now and the no.

We didn't do it so but that's only one of the of the changes operational debt.

Sergio Traversa: So, but that's only one of the operational changes that were made in the new protocol. And so that was one, but, you know, the required medical record is probably the biggest one. And so the old goal, as we discussed a few times or many times, is to really enroll patients that are affected by biological depression, and they have a history. This is an adjunctive trial. So the patient has to come in already on some antidepressants and have access to medical and pharmacy records. It's a good proxy to be sure that the patient is a real patient. These are things that we didn't do in the previous trial for a variety of reasons. And so, can you repeat the second one? And yeah, I was asking if the statistical plan is designed by a third party or us internally within your company. Yeah, no, it is.

They're made in the new profitable and so that was one but the required for medical record is probably the biggest one and and so they all go as we discussed.

Few times that many times is to really enroll patients that are affected by biologics all depression and they have a history of these as an adjunctive trial. So the patient has to come in.

Really on some antidepressant and you know to have access to medical and Pharmacy Records.

A good proxy to be sure that the patient is there is a real patients. These are the things that we didn't do in the previous trials for a variety of reasons.

Sorry can you repeat the second one.

And yes, I was asking is the statistical plan is defined by a third party cannot be regaining our company.

Yeah, no. It is a well it is.

Sergio Traversa: Well, it is, design is a collaboration. And, and so by these, it is we have the help of it like a large independent statistical company that advises us on the statistics. Thank you. Thank you. There are no further questions at this time. Mr. Traversa, please go ahead. Well, thank you. And, in summary, we remain confident that we do have an approvable drug in Vial1017 and are excited by the potential of our novel psilocybin and derivative programs.

Design is a collaboration.

And so but these are but it is we have the help of it like a large statistical comment company independent.

Advise us on the status of the statistics.

Got it thank you.

Thank you.

Thank you there are no further question at this time Mr. <unk>. Please go ahead.

Well, thank you and in summary, we remain confident that we do have an approvable dragging rather than 17 and are excited by the potential of our novel Psilocybin and derivative program. So we look forward to reporting on progress with our pipeline pipeline into the in the months ahead.

Sergio Traversa: So we look forward to reporting on progress with our pipeline pipeline in the months ahead. And to close, I'm grateful to the Relmada team for their continued hard work and dedication to executing on our mission. And I would also like to extend my sincere thanks to the patients and clinical partners involved in the REL1017 trials for their participation in the advancement of this promising investigational medicine through development. Thank you very much to everyone. Thank you. That concludes our conference today. Thank you for participating. (inaudible)

And to close I am grateful to the <unk> team for their continued hard work and dedication to executing on our mission and I would also like to extend my sincere. Thanks to the patients and clinical partners involved in there are 10 17 trials for their participation in the advancement of this promising investigational Madden.

Two development. Thank you very much to everyone.

Thank you that concludes our call.

From today. Thank you for participating you may all disconnect.

Okay.

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