Q1 2022 Relmada Therapeutics Inc Earnings Call

Ladies and gentlemen, thank you for standing by and welcome to the World Manav Therapeutics, Inc. First quarter 2022 earnings call. During the presentation, all participants will be in a listen only mode. Afterwards, we will conduct a question and answer session.

Operator: Ladies and gentlemen, thank you for standing by, and welcome to the Relmada Therapeutics, Inc. first quarter 2022 earnings call. During the presentation, all participants will be in a listening mode.

Operator: Afterward, we will conduct a question and answer session. At that time, if you have a question, please press the 1 followed by the 4 on your telephone. If at any time during the conference, you need to reach an operator, please press star 0.

At that time, if you have a question. Please press the one small part of four on your telephone if at any time during the conference you need to reach an operator. Please press star Zero as a reminder, this conference is being recorded Thursday may five 2022, I would now like to turn it over to Tim Mccarthy lifestyle Advisors. Please go ahead.

Operator: As a reminder, this conference is being recorded Thursday, May 5th, 2022. I would now like to turn the conference over to Tim McCarthy of Lifestyle Advisors. Please go ahead.

Thank you Ingrid and thank you all for joining US. This afternoon with me on today's call are Chief Executive Officer Sergio Traverse.

Timothy McCarthy: Thank you, Ingrid, 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 news release providing a business update and announcing financial results for the three months ended March 31st, 2022, and filed its quarterly report on Form 10-Q with the SBA. Please note that certain information discussed on the call today is covered under the Safe Harbors provision of the Private Securities Litigation Reform Act.

Chief Financial Officer magazine later.

This afternoon <unk> issued a news release, providing a business update announcing financial results for the three months ended March 31st 2022.

<unk> 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's provision of the private Securities Litigation Reform Act, we caution listeners that during this call real modest management team will be making forward looking statements.

Timothy McCarthy: We caution listeners that during this call, Relmada's management team will be making forward-looking statements. However, 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 20, 30, 2021 and subsequent.

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.

Forward looking statements are qualified by the cautionary statements contained in real modest press release issued today and the company's SEC filings, including in the annual report on Form 10-K for the year ended December 'twenty, 30th 2021 and subsequent filings.

This conference call also contains time sensitive information that is accurate only.

Timothy McCarthy: This conference call also contains time-sensitive information that is accurate only as of the date of this live broadcast, May 5th, 2022. 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.

As of the date of this live broadcast May five 2020 to monitor 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'd like to turn the call over to Sergio started yet.

Yeah.

Thank you Tim it's always good afternoon to everyone and I'm pleased to welcome you to the rollout of <unk>.

Sergio Traversa: Thank you, Tim, as always. Good afternoon to everyone, and I'm pleased to welcome you to the Relmada First Quarter 2022 conference. During today's call, I will review our recently achieved milestones and the anticipated timelines associated with the multiple expected clinical trial readouts for REL1017. That is our lead product candidate that we're currently developing as an adjunctive and monotherapy treatment for patients with major depressive disorder or MTD. Following my comments, Maged Shenouda, our Chief Financial Officer, will review our financial results and balance sheet, and we will take, Thank you. Thank you. As many of you know, we expect 2022 to be a catalyst switch year for revolution.

Sergio Traversa: We intend to generate REL1017 clinical data readouts beginning mid-year for the ongoing reliance phase retreat. Specifically, we anticipate completing the enrollment of Reliance 3, the ongoing monotherapy registration of Phase 3 trials. Followed by top line data readout by mid-year 2022, and followed by top line results from Reliance One and Reliance Two respectively. These anticipated timelines remain unchanged from the buyer's guide. As a reminder, Reliance 1 and Reliance 2 are two ongoing Phase 3 sister two-arm placebo-controlled pivotal studies evaluating REL1017-25mg as a potential adjunctive treatment for MDD.

First quarter 2022 conference call.

During today's call I will review, our recently achieved milestones at the anticipated timeline associated with the multiple expected clinical trial readouts or rather than 17 that he is our lead product candidate that we're currently developing as an adjunctive and monotherapy treatment for patients with major.

Sergio Traversa: Reliance III is the ongoing Phase III, two-arm, placebo-controlled, registrational study evaluating REL1017, 25 mg, as a potential monotherapy treatment for MDD. All participants in the Reliance trial take a loading dose on day one of 75 mg, that is three tablets of REL1017. We have made significant progress in advancing our development program.

Sergio Traversa: To this end, in February 2022, we reported top-line data from our second CAP, or Human Abuse Potential Study, which compared RELC-1017 versus intravenous CAT. Our first HAP study comparing RELTEN17 versus oxycodone was successfully completed in July 2021. Most importantly, the findings from these two HAP studies were consistent and confirmed the 2019 DEA Statement on S-Methadone that states, The D.E.E.E.E.E.E.E.E.E.E.E.E.E.E.E. The D.E.E.E.E.E.E.E.E.E, significant respiratory depression action and addiction viability. We believe.

Sergio Traversa: The Toxicodon comparative data significantly de-risk the Schedule II potential for Relm1077, and then the ketamine comparison data significantly reduce the risk that drug candidates can treat potentially. As we have said previously, we believe that the data generated today from our growing development program indicates that REL1017 could be initially proposed as a Schedule V drug, with potentially becoming a non-Schedule drug following one or two years of marketing experience. Moving on to the current status of the phase three program, we continue to anticipate.

Disorder or <unk>.

Following my comments magnets you knew that was chief financial Officer, who will review.

Our financial results and balance sheet, and we will take.

Then your questions.

As many of you know, we expect 'twenty to 'twenty two to be a catalyst switch the Portland market.

We intend to generate.

17 clinical data Readouts, beginning midyear for the ongoing reliance phase III trial.

Sergio Traversa: The completion of enrollment in Reliance 3, the ongoing monotherapy, registration of phase 3 trial, followed by the top line data read out by... Reliance 3 aims to randomize up to 364 patients who have been diagnosed with depression and are not currently taking standard antidepressants. The study includes two arms, placebo, and 25 mg of reltan-17. Patients may have tried no more than one standard antidepressant in their current major depressive episode to be eligible for the study and have to be off treatment for at least 30 days.

Specifically, we anticipated completing the enrollment of reliance to meet the ongoing monetary it'd be a registrational phase III trial.

Sergio Traversa: Conducting Reliance 3 as a Phase 3 study could meaningfully reduce the time for a potential approval of RELS 1017 as an MDP monother. Now, I will now provide an update on the ongoing Reliance 1 and Reliance 2 studies, each of which is designed to include up to 364 participants per study across 55 sites per study. Reliance 1 and Reliance 2 are designed to evaluate REL1017 as an adjunctive treatment for MDD, and both include two arms, placebo and 25 milligrams of REL1017. Both arms are studying the use of RAL-1017 in addition to a standard antidepressant for participants who have had an inadequate response to at least one and up to three standard antidepressant therapies.

Sergio Traversa: The primary endpoint is the change in MADRA score of the drug versus placebo at day 28. Key secondary endpoints include the change in MADRA score on day 7 and change in the Clinical Global Impression Severity Scale, the CGIS, score at day 28. Day 28 was chosen as a primary endpoint in agreement with the FDA and with an understanding that depression is a chronic disease and that day 28 will support REL1017 as a chronic treatment. Both Reliance One and Reliance Two are progressing as planned.

Followed by top line data readout by mid.

2022, and followed by topline results from reliance one.

Sergio Traversa: And we continue to expect the availability of top-line data in the second half of. The Reliance Development Program also includes Reliance OLS, the long-term open-label safety study that is enrolling both rollover participants from all three pivotal studies, as well as de novo participants. Reliance OLS is ongoing and continues to involve participants as planned. Data from this long-term, open-label safety study will be part of the planned NDA file. As the Relm 1017 development program advances, we continue to expand our senior team. To this end, I am very pleased to report today that we have appointed Gino Santini as Corporate Development Strategic Advisor.

And reliance tourists.

These anticipated timelines remain unchanged from prior guidance.

As a reminder, reliance one and Berlin as to our two ongoing phase III system, two arm placebo controlled pivotal studies evaluating <unk> 10, 17 25 milligram.

As a potential adjunctive treatment for MTBE.

Well that is the ongoing phase III through arm placebo controlled Registrational study evaluating <unk> thousand 17 25 milligram.

As a potential monotherapy treatment for obesity.

All participants in the reliance trials take a loading dose on day, one of 75 milligram that is three tablets of relative uncertainty.

We made significant progress in advancing our development program to design in February 2022, we reported topline data from our second.

Pat or human abuse potential study, which compared <unk> 17 versus intravenous carefully.

Our first Hap study comparing <unk> 17 versus oxy called them was successfully completed in July 2021.

Most importantly, the findings from these two <unk> studies were consistent and confirmed the 2019 D. A statement on this message.

<unk>.

<unk> hired someone lapsed cigna.

Significant respiratory depression action and addiction liability.

We believe.

That oxycodone comparative that significantly de risk the scheduled two potential for relative uncertainty.

And then the ketamine comparison data significantly de risks the drug candidate scheduled fleet for them. So.

As we have said previously we believe that the data generated to date from our growing development program indicate that represents 17 could be initially proposed is a scheduled five drug with potentially two eventually a non scheduled drug following Wanda <unk> of marketing this period.

Moving on to the current status of the Phase III program, we continue to anticipate.

The completion of enrollment and rely on the street the ongoing monotherapy Registrational phase III trial, followed by the top line data readout by the media.

Rhode Island, three aims to randomize up to 364 patients who have been diagnosed with depression and not cognizant, taking a standard antidepressants.

The study includes two arms placebo and 25 milligram <unk> 17.

Patient may have tried no more than one standard antidepressant, India current major depressive episodes to be eligible for the study.

And have to be off treatment for at least 30 previously dates.

Conducting reliance treat as a phase III study could meaningfully reduce the time for a potential approval of our resident 17 has a NIM MTP monotherapy.

Let me now provide an update on the ongoing rollout of this one.

Two studies each of which is designed to include up to 364 participants first study.

55 sites first.

Reliance one and relentless two are designed to evaluate <unk> as an adjunctive treatment for AMD and both include two arms placebo and 25 milligram of <unk> 17.

Both arms are studying the use of <unk>. In addition to our standard antidepressant for participants who have had inadequate response to at least one and up to three standard antidepressant therapy.

The primary endpoint is the change in model score of the drug versus placebo at day 28.

Key secondary endpoints include the change in macro score on day, seven and change in the clinical global impression of severity scale. The C. G. I F score at day 28.

Please read the eight was chosen as the primary endpoint in agreement with the FDA with an understanding that the pricing is a chronic disease and the date 28, which support resident 17 as a chronic treatment.

Both reliance one and realized two are progressing as planned and we continue to expect the availability of topline data in the second half of this year.

The reliance development program also include reliance or L. S. The long term open label safety study that is enrolling book rollout.

The rollover participants from all three pivotal studies as well as the de Novo bucket.

But as long as oil is ongoing and continues to evolve.

<unk> is flint data from these long term open label safety study will be part of a planned NDA filing package.

<unk> 17 development program advances, we continue to expand our signal to defend I'm very pleased to report today that we appointed Gnl's MTV U S corporate development strategic adviser.

Sergio Traversa: He's a veteran global biopharmaceutical industry executive with strong P&L experience that demonstrated value creation skills. Gino has a successful track record in both operational and strategic roles, working in three different continents and in various areas of the pharmaceutical value chain. He is a former member of the executive team at Reli Levy, most recently as president of U.S. Rupert Operations and SVP of Corporate Strategies and Business Development. He has a broad global network in the pharmaceutical biotech, VC, private equity, and the investment banking community. He retired from Lilly in December 2010, after a career of 28 years.

Background global biopharmaceutical industry executive with strong P&L experience that demonstrated value creation skills.

He has a successful track record in both operational and strategic role working three different continents and in various areas of the pharmaceutical value chain. He is a former member of the executive team rely maybe most recently as president of U S operation and SVP of corporate strategy and business development.

As a broad broad global network and the pharmaceutical biotech, we see private equity and investment banking companies.

Tired from Lilly in December 2010, after three of 28 years. Gino currently serves on board, so multiple public and private biopharmaceutical company.

Sergio Traversa: She now currently serves on the boards of multiple public and private biopharmaceuticals. I also would like to highlight that WELL-1017 data were presented last month in two poster presentations and one oral presentation at the Academy and Related Compound International Hybrid Conference 2022. In addition, REL 1017 preclinical only lesion data were recently published in the peer-reviewed journal Frontiers in Pharmacology. This compelling data confirmed that REL1017 does not produce ulnar lesions, unlike what has been seen in other NMDAR blockers.

I also would like to highlight that <unk> 17 data.

We have presented last month, and two poster presentations and one oral presentation at the Academy and related compound International hybrid conference 2022.

In addition, resident 17 preclinical only lesion data were recently published in the peer reviewed journal frontiers in pharmacology. This.

These compelling data confirmed that <unk> does not produce only lesions. Unlike what has been seen in other NDA car logos in railcar 17 three.

Sergio Traversa: In REL1017, treated rats, early ulnar lesions, which usually appear one day after treatment with NK801, which is another NMDAR channel blocker that was used as a positive control in the study, were not observed. These results further contribute to the safety profile of health insurance.

Treat the rats thirdly, only lesion usually appears one day after treatment with MK eight to one another and R&D our channel blocker that was used as a positive control in the study we have not observed.

These results further contribute to the safety profile of <unk> 17.

Finally.

Sergio Traversa: I would like to highlight that May is Mental Health Awareness Month, which serves as a reminder for us why we are so or why we are so passionate about Advancing Our Common Mission at Redmond. To mark the occasion and increase visibility around mental health, we are participating in a number of initiatives this month, including sponsoring the 33rd annual Lifesaver Gala 2022 that is hosted by the American Foundation for Suicide Prevention.

I would like to highlight that may ease him.

The mental health awareness month, which serves as a reminder for US. That's why we are so for why we are so passionate about the advanced formulation upfront model.

To Mark the occasion and increased visibility around mental health, we are participating in a number of initiatives, including sponsoring the 33rd unwell Lifesaver Gal a 2022 hosted by the American Foundation for suicide prevention.

Sergio Traversa: Several members of our team will be participating in local walks sponsored by the National Alliance on Mental Illness. With that, I will now turn the call over to Maged for a review of the financials. Maged, the stage is all yours.

Members of our team will be participating local wallets walks.

Concert by the National Alliance on mental illness.

With that I will now turn the call over to magnet for a review of the financials and I guess the state is all yours.

Maged Shenouda: Thank you, Sergio. Today, we issued a press release announcing our business and financial results for the three months ended March 31, 2012, which I will now discuss for the first quarter ended March 31. Total Research and Development. Approximately $25 million, compared to $14 million for the comparable.

Thank you Sergio.

Today, we issued a press release announcing our business and financial results for the three months ended March 31, 2022, which I will now review for.

For the first quarter ended March 31, 2022, total research and development expense was approximately $25 million as compared to $14 million for the comparable period of 2021.

Maged Shenouda: The increase was primarily related, of course, associated with the ex- Broader Clinical Program, Barrell, Tennessee. Non-cash R&D expense for the first quarter 2022 amended. Total general and administrative expense for the first quarter ended March 31st, approximately compared to $8.4 million for the comparable, an increase of approximately $4.9 million; the increase was primarily due to the increase in stock-based compensation.

The increase was primarily related to an increase in costs associated with the execution of a broader clinical program Burrell 10 17 non.

Noncash R&D expense for the first quarter 2022 amounted to $1 $3 million.

Total general and administrative expense for the first quarter ended March 31, 2022 was approximately $13 $3 million as.

As compared to $8 $4 million for the comparable period of 2021.

An increase of approximately $4 $9 million increase was primarily due to the increase in stock based compensation. This noncash charge totaled $10 $7 million in the most recently completed first quarter.

Maged Shenouda: This non-cash charge totaled $10.7 million. For the first quarter ended March 31, 2020, we recorded a net loss of $39.7 million, or $1.49 million. Compared to a net loss of $22.2 million, or $1.34 per basic and diluted share in the comparable period.

For the first quarter ended March 31, 2022, we recorded a net loss of $39 $7 million or $1 40 per basic and diluted share compared to a net loss of $22 $2 million or $1.34 per basic and diluted share in the comparable period of 2021.

Maged Shenouda: As of March 31, 2020, we had cash, cash equivalents, and short-term investments of $120.6 million, compared to cash equivalents and short-term investments of approximately $1.5 billion. $211.9 million.

As of March 31, 2022, we had cash cash equivalents and short term investments of $226 million.

Compared to cash cash equivalents and short term investments of approximately $211 $9 million at December 31, 2021.

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

Operator: I will now ask the operator to please open the call for questions. Sergio, thank you. If you would like to ask a question, please press the 1 followed by the 4 on your telephone. You will hear a three-tone prompt to acknowledge your request. If your question has been answered and you would like to withdraw your registration, please press the 1 followed by the 3.

So I actually think Q, if he would like to answer a question. Please press the one held by the four on your telephone you'll hear a three pronged doesn't answer. Your question. If your question has been answered and you would like to withdraw your registration. Please press. The one followed by Nestle one piece for the first question.

Operator: One moment, please for the first question. Our first question comes from the line of Andrew Tsai with Jeffries. Please proceed with your question. Thanks for taking my questions. The first question is actually on the kinetics of the phase three monotherapy data coming out, but it also applies to adjunct studies.

Yeah.

Our first question comes from the line of Andrew Tsai with Jefferies. Please proceed with your question.

Andrew Tsai: So I guess my question is, you know, how do you foresee the curves to look like, you know, for the F-method in particular, as well as placebo, from day seven to day 28? You know, should we be expecting no kind of rebound in terms of efficacy, or is some rebound actually okay in your view? Well, thanks, Sergio.

Thanks for taking my questions.

The first question is.

Actually on the kinetics of the phase III monotherapy data coming out Oh, well. It also applies to the adjunct studies. So I guess my question is how do you foresee the curves to look like.

Methadone in particular as well as placebo.

From day seven day 28.

Should we be expecting no kind of rebound in terms of the efficacy or some rebound actually okay and in your view. Thanks.

Well thanks Andrea.

Sergio Traversa: Well, of course, we don't have data, especially monotherapy, we don't have any data, not short term, not long term. But we have very strong adjunctive treatment data, and we have experience.

Jim.

I take this one well of course, we don't have data, especially monotherapy and we don't have any data not short term or long term, but we have very strong adjunctive treatment data and we have experience. So we have a data from other compound that also work on via an NDA.

Andrew Tsai: So we have data from other compounds that also work on the NMDA channel. So just based on what we have seen for phase two and, you know, based on the experience of other similar compounds, we don't expect any loss of efficacy over time. It's really based on the mechanism. And if we do believe, and we do believe in this neuroplastic effect, then you know, longer term, the efficacy of the drug should just improve. So we don't expect any loss of efficacy after day seven; we expect it to be stable and, hopefully, better than day seven. Right, okay, very good.

Channel. So just based on what we've seen for phase two and based on what is the experience from other similar.

Similar compounds, we don't expect any loss of efficacy overtime.

Based on the mechanism and if we do believe and we do believe that Europe plastic effect than longer term.

The efficacy of the drug.

So just improve.

So we don't expect any loss of efficacy after data, we expect to be stable.

Hopefully better than data.

Andrew Tsai: And secondly, it's more of a high-level question, maybe more open-ended, is just, you know, I guess, you know, conceptually, you know, what do you guys think you've done for these phase three studies to maximize their product success? You know, what are you doing differently than the other companies with depression programs? Anything in the inclusion criteria or COVID protocols, you know, maybe something about the placebo response or even the drug effect? Any color would be great.

Right, Okay, very good and secondly, it's more of a high level question, maybe up more open ended as just you know I guess conceptually you know what what do you guys think you've done for.

Are these phase III studies and maximize their part of their success what are you doing differently than the other companies with depression programs.

In the inclusion criteria are COVID-19 protocols.

Maybe something about the placebo response, or even a drug effect any color would be great.

Well thanks Andrea.

Sergio Traversa: Well, thanks, Andrew. This one, it will take some time to go more in detail about what we have done. But, you know, top down, we have done everything it is possible to think about it to make the effect of the drug confirm what we have seen in phase two. Now, without making too many strong statements without the data, but based on phase two, we do believe the drug is safe, is well tolerated, but also that the drug works, you know, has very strong efficacy.

It will take some time to it.

Go more in detail of what we have done top.

Top down we have done everything it is possible to think about it to make the.

The effects of the drug to confirm what we have seen in phase II, so without making too many.

Strong statement without the data, but based on phase two we do believe the drug is safe as well tolerated, but also that the drug works as a very strong efficacy and so we don't see any reason why that drug.

Sergio Traversa: And so we don't see any reason why the drug should not confirm the same effect in the phase three program. What is the potential, right, the potential risk of what everybody is afraid of in every trial, but especially in depression trials, the placebo effect. So what we have been focusing on is everything it is possible to do to control the placebo effect. That means Dr. Antonio Sotomayor, M.D., Ph. D., Ph.

Should not confirm the same effect in the phase III program.

What is that.

The potential.

The the potential risk of what everybody's afraid in every trial, but especially in depression trials the placebo effect.

What we have been focusing upon is everything is possible to do.

To like control the placebo effect that means it's tight selection trying to get sites, we are experiencing in our <unk>.

Sergio Traversa: D., U.S. Centers for Disease Control and Prevention, And so from the side, the raters, the looking at the profile of the patients that the safer interview that should support like a patient selection that would exclude patients that are not affected by by depression and to like, Support to be sure that the patients, the compliance, the patient's state, the drug, that's a little video that is uploaded every day showing that the patient is taking the deal, so it's taking the, is taking the tablets, reading a statement, free every Madras interview that the patient has to read that states that these that have 50% chances to be on placebo, a pattern that produces the placebo effect. And so right, there is no magic, there is no magic bullet of magic strategy that can guarantee you the results.

<unk> clinical studies.

Rater selection the raters actually train by a company that is called DNI.

Make any publicity for anybody, but that's not the issue.

It is.

Company that administer the safer interview to the patient at the same time they trained doing this.

And so from so besides the raiders.

Looking at the profile of the patients that they're safer interview.

That should support like it patient selection that would exclude patients they're not affected by by depression.

To like.

Support.

To be sure that the patients the compliance of the patient pay.

That's it.

It'll be deal it is uploaded everyday showing the patients who've taken the detail that's all.

It's taking that he's taking the tablets.

Reading a statement.

Every motherless interview that the patient has to read the states that they used to have 50% chances to be on placebo a patent that produces the placebo effect and so there is no magic there is no magic bullet.

Strategies that can guarantee that the results, but we do believe that all we have done.

Sergio Traversa: But we do believe that all we have done so far to support the quality of patient compliance and should should support good control of the placebo effect. I don't answer, but I hope I can answer you. I want to answer you. Right, I think it's important. Yeah,

So far to support quality of the patients compliant and that should.

Should support right.

Hey, good control of the placebo effect.

I hope I.

I answer, but I hope I answered I wanted to answer.

Okay.

Andrew Tsai: And then the very last question is, you know, in addition to kind of monitoring for discontinuation rates and the rollover rates, which you've disclosed before on a blinded basis. Let's be clear. Are you looking at anything else on a blinded basis? I don't know. Total mattress changes.

Right I think it's important.

And then very last question is.

In addition to kind of monitoring for.

Discontinuation rates and the rollover rates, which you've disclosed before on a blinded basis and let's be clear are you looking at anything else on a blended basis I don't know total Madras changes and then are you able also to confirm the DMC Committee is still seeing no signs of opiate or obviously it effects.

Thanks.

Sergio Traversa: And then, are you able also to confirm the DMC committee is still seeing no signs of opiate or dissociative effects? Thanks. Yes, yes, I answered first.

Yes, yes.

I answer first.

Sergio Traversa: The second question is easier, yes, the DMT is not meeting of the DMC and their statement to continue this plan. We have not heard anything different about any severe side effects or any change in the problem. And yes, the answer is yes.

The second question it is easier to get the DMT is not from the loss.

Meeting of the DMC and they are taking to continue with this plan we have not heard anything.

Different about they need.

The CV side effects.

Any change in the program and yes. The answer is yes, if there were any anything that would.

Sergio Traversa: If there were anything that would suggest changing something in the study, that would also mean if there were withdrawal symptoms of anything that is unusual that would pose any risk for the patient, then we would have known. So we assume that from the review, there was no sign of any withdrawal. And the, the, remind me of the first question that they lost a little bit.

Suggest to change something in the in the study that would also mean intermediate withdrawal symptoms of anything that is unusual that would pose any risk for the patient than we would have no. So we assume that.

From the review there was no signs of abating as well correct.

And the remind me the first question that they lost a little bit.

Andrew Tsai: If you're, if you're seeing anything else, right, if you're seeing anything else on the blinded side. I'm not trying to avoid it. No, no.

If youre seeing anything right, if you're seeing anything else on a blinded basis basically im not trying to avoid it.

No no I love the blinded data that extremely useful.

Sergio Traversa: Look, the blinded data, they are extremely useful for safety; then, if there is no sign of any serious side effects, we assume that the placebo does not give serious side effects. Yes, it's nothing. So it's a fair assumption that the drug is safe and well-tolerated. On efficacy, it would be highly risky to look at blinded data and make any statement. Until you know what the placebo does, it's impossible to draw any conclusion. Probably, we would see if there is zero effect, right? If everything were a zero, right?

For safety then if there is no sign of any any severe side effects you assumed debt. We assumed the placebo does not appear to be decided in fact, we have seen nothing so it's a fair assumption that the drug is.

Safe and well tolerated on the efficacy.

But it would be highly risky to look at blinded data and to make any statements.

Yeah.

Until you know what the placebo does it's impossible.

To draw any conclusion.

Bubbly.

We would see if there is zero effect right and so everything would be zero, but you assume that.

Nothing has worked itself the truck would not work.

That's all you can tell at this point.

We don't believe right you can see a zero effect, but that's not that's not an indication of them and so we have to be a little patient here.

Andrew Tsai: You assume that. Nothing is working, so the drug would not work. That's all you can tell. We don't believe we will see a zero effect, but that's not an indication of any final result. So we have to be a little patient. Okay. Very good. Fingers crossed, and thank you for taking my class. A pleasure, Andrea, as always.

Understood very good fingers crossed and thank you for taking my question.

A pleasure as always.

Our next question comes from your line of Tan with Goldman Sachs. Please proceed with your question.

Operator: Our next question comes from the line of Andrea Tan with Goldman Sachs. Please proceed with your question. Hey, everyone. Thanks for taking my question. Sergio, maybe just two for you.

Hey, everyone. Thanks for taking my question.

Sir do you maybe just two for you just curious if you could speak a little bit more on your estimates of the size of the monotherapy opportunity and then do you envision positive data from reliance could prompt inclusion on AR Unbilled 10, 17th label or do you think you would need to run an additional study and submit a supplementary filing thereafter.

Andrea Tan: Just curious if you could speak a little bit more on your estimates of the size of the monotherapy opportunity, and then do you envision positive data from Reliance 3 could prompt inclusion on RAL 1017's label, or do you think you would need to run an additional study and submit a supplementary filing thereafter? Thanks, Andrea, and good afternoon to you as well.

Hello, Thanks, Andrea and good afternoon to you as well thanks for the question well the and moving forward in the next the next calls.

Sergio Traversa: Thanks for the question. Well, moving forward, on the next call, we will probably be more precise on the size of the market. And with Gino on board, one of the roles of his help would be to give us guidance and help us in determining what the size of the different opportunities is.

We will be probably a little more more precise on the size of the market and well Gino onboard.

One of the of the day.

So they have devoted any help would be to really gave us guidance and help us in determining what the size of the all the different.

Sergio Traversa: Now, monotherapy, it's very much related to the..., with the clinical data. That's where there will be the big difference, right? Because competition for adjunctive treatment, there is no antidepressant approved, and there are only three drugs, and they're all antipsychotics.

Opportunities as a monotherapy.

It's very much related with the.

With the clinical data.

That would be the big difference because competition in adjunctive treatment. There is no antidepressant approval.

The only three drugs and they all anti psychotics, so that make the.

Sergio Traversa: So that makes the task not easier, but definitely a little bit more favorable, because, you know, if REL1017 makes it to the market as an adjunctive treatment, that would be the only antidepressant available. And so there is going to be more price power and less competition; monotherapy, the competition, is generic 26-27 drugs with one exception that I believe is pretalix. It's the only branded antidepressant left. And so price will be critical, and price competition.

Not easier, but definitely a little bit more favorable because the front.

Rather than 17 makes it to the market as an adjunctive treatment.

Would be the only antidepressant available.

So there is going to be more price power and less competition direct monotherapy the competition.

Is generic 'twenty six 'twenty seven drug with one exception that I believe you could tell us as the only branded anti.

Antidepressant less and so price will be critical off price competition.

Price competition can only be overturned but one factor is clinical data.

Sergio Traversa: Price competition can only be overturned by one factor; it's clinical data. If the data in phase three monotherapy were even close to phase two, it would be even closer to phase two. Then we do believe, I do believe we have a good chance because you go against drugs that have an effect size of about 0.3, and they work in about 30 to 40 percent of the patients. They take a month at least to show any efficacy, and they are not exempt from side effects. And if the data is good, what we hope and we expect to be that you have a drug that you take one tablet in the morning and it works

The data in phase II monotherapy would be even.

Everywhere close to the phase III.

Then we do believe I do believe we have a good chance because you go against drugs that have a.

In effect side about 0.3.

And they work in about 30% to 40% of the patients taken months at least to show any efficacy and they are not exempt from side effects.

If the data what we hope and we expect to be that you have a drug that you take one tablet in the morning and it works after a few days.

Sergio Traversa: It is effective chronically, and it's effective in whatever we've seen in phase two in non-responder to traditional antidepressant response rates were very close to 60 percent, so six out of 10 patients responded. And that's going to be very difficult for payers to recommend as a front-line antidepressant. So the clinical data will really drive the size of the market, and price will be a very important factor.

It is effective.

Sonically.

And is effective in what they might be seen in phase two in non responder to traditional antidepressants.

<unk> rate was pretty close to 60% so six out of 10 patients responded.

And that's going to be very difficult.

<unk> two <unk>.

Recommended as a front line.

Is it traditional antidepressants so the clinical data will really drive the size the size of the market.

And price will be very important.

An important factor.

Andrea Tan: We'll be more like towards the next few months; we will work more closely with the payers, and we will have a better understanding of what they want to see, to make a decision to put Relm 1017 as a front-line therapy, even as a reimbursement. I hope I answered your question. Perfect, Sergio.

We'll be more like towards the end of last few months, we will more closely with the payers and we will have a better understanding of what they want to see.

To make it.

Right.

To put rather than 17 as a frontline therapy, even if the reimbursement.

I hope I answered your question.

Perfect and then on the second part just if you I guess may be based off of an initial conversations with the FDA. If you have an idea of whether you would need to run an additional study there or if this could be somehow a group internal and existing wave off any account getting used case.

Sergio Traversa: And then on the second part, just if you, based on your initial conversations with the FDA, have an idea whether you would need to run an additional study there or if this could be somehow grouped into an existing label for the adjunctive use case. Yeah, to be direct, we did not address this aspect with the FDA; the FDA was in line with running a phase three instead of a phase two. So that could be read as a positive indicator.

Yes.

To be direct we did not address with the FDA. This aspect. The SBA was in line with running a phase III instead of a phase at least too so that could be read as a.

Positive indicators and but again the data will drive the data will be compelling.

Sergio Traversa: And again, the data will drive, the data will be compelling, we don't see any reason why we should have to run a second monotherapy trial. And if the two adjunctive trials are positive like we got to the FDA with every three trials with compelling data positive, plus the long-term safety, and it doesn't show any issue.

We don't see any reason why we should.

I have to run a second monotherapy trial.

If the two adjunctive trial that would be positive. If you go to the FDA with three trial with compelling data positive plus the long term safety.

Doesn't show an issue we've kind of seen that there is.

Sergio Traversa: We've kind of seen that there is the potential for the risk of abuse, but it doesn't seem to be there at all. So that would make a very powerful package for the FDA. Now, yes, if everything goes the way we hope and we think that the three trials will be successful, we won't see any safety or risk problems, then we assume that we won't have to run a second phase three monotherapy trial. We don't think we'll add any more information to what is already available. Great. Thanks, Sergio.

The potential of all the risk of abuse.

It doesn't seem to be there, though so that that would make a very powerful package for the FDA.

So yes, if everything goes the way, we hope and we think the three trial will be successful or we won't see any safety and.

Risk then we assume that we won't have to run a second phase II monotherapy trial. We don't think we've had any more information on what is already available.

Great. Thanks for your time.

Thank you Brad.

Ladies and gentlemen, as a reminder to register for a question. Please press the one followed by the four on your telephone keypad.

Operator: Thanks for that. Ladies and gentlemen, as a reminder to register for questions, please press the 1 followed by the 4 on your telephone keypad. And our next question comes from the line of Yaten Suneja with Guggenheim Partners. Please proceed with your question. Hey guys, thank you for taking my question. I have a couple very quick ones.

And our next question comes from the line of <unk>.

<unk> <unk> with Guggenheim Partners. Please proceed with your question.

Hey, guys. Thank you for taking my question I have a couple of very quick ones.

Yaten Suneja: The first one is, can you just talk about how you might be modeling the placebo rate given that this is now outpatient versus the inpatient that you conducted and what your expectations are over the four-week time frame because, in your study so far, we've just seen two-week data. So that's first. Sure, let me answer the first one and then give you the line, and you can ask the rest. The Placebo Effect is a critical topic that we have really thought about from every different angle. Let me give you the numbers that we thought about putting into the statistical model. In clinic, in-patient treatment; they tend to have a higher placebo effect.

First one is can you just talk about how you might be modeling the placebo rate, but given that this is now outpatient versus inpatient that you conducted and what your expectations are over the four week time frame because in your study so far we've just seen two week data. So that's the first question.

Sure. Let me answer the first one and then give me the line that you can ask the second one.

The placebo effect right. This has been a has been is a critical topic that we have really talk about in from every different angle. Let me give you the numbers.

We when we talk about.

Putting into the statistical model so.

In.

Clinique inpatient treatment they tend to have a higher placebo effect. So the reason advantage in running an outpatient trial. The way we are doing with the with the reliance program at the end.

Sergio Traversa: So there is an advantage in running an outpatient trial the way we are doing with the Reliance program. On the other hand, our phase two was seven days of treatment. So placebo was taken for seven days. And placebo tends to have a gradual increase over time for a variety of reasons. So would you believe that these two factors balance?

Other side, our phase II was seven days.

Treatment. So placebo was taken for seven days placebo tend to have a gradual increase overtime for a variety of reasons. So we do believe that these two factors the balance themselves right. If you look at the placebo effect in phase two was but if I remember correctly eight points.

Sergio Traversa: If you look at the placebo effect in phase two, was, I believe, if I remember correctly, eight points after seven days. That's a pretty high placebo response. We have seen numbers in other trials that go from four, five, six. So they tend to be lower in an outpatient setting.

Seven days, that's a pretty high placebo response, we have seen remember in other trials that go from 456, so they tend to be lower.

In the outpatient setting so the inpatient played a role in the placebo effect or is that was it was higher than in outpatient.

Sergio Traversa: So the inpatient played a role, and the placebo effect was higher than in the outpatient, on the assumption that now we have a trial for four weeks. I will tell you a number; in the statistical plan, we assume that the placebo will be 12%. So if the placebo delta from baseline to day 28 was 12 points, then with the assumption that REL1017 would behave and perform the way it did in phase 2, then the trial would be highly successful.

And the assumption that now we have a trial at four weeks.

I think I remember in the statistical plan, we assumed that the placebo will be 12 point.

If the placebo Delta from baseline to day 28 would be 12 points then.

And with the assumption that the 10 17, it will behave and perform the way. It is done in phase II and the trial would be highly successful.

Sergio Traversa: Anything below a 12 point delta from baseline for placebo to day 28, would be like, I don't know what kind of term I should use, but it would be a very, very, very successful trial. If the placebo performs from baseline above 12 points, it depends. If it is 13, 14, it's still manageable.

Anything below 12 point Delta from baseline placebo to day 28.

Would be like.

And also what kind of term I shouldn't use but it would be available debated successful.

Wow.

If the placebo perform from baseline above 12 points. It depends it is 13 14 is still manageable and we do believe.

Sergio Traversa: We do believe the trial will still be successful. If it is above 15, I don't... see much. I haven't seen many of these.

The trial will be successful if it is about 15.

I don't.

Sergio Traversa: I haven't seen these numbers. In fact, he was about 15, and we have a So you can assume that 12 points delta from baseline to day 28 for placebo is the key number to look at. If it is below that, the trial would be high. If it got slightly above that, we'd still be successful. Thank you very much.

See much.

I haven't seen many of these.

These numbers.

He was about 15, and then we have a problem.

So you can assume that 12 point delta from baseline to day 28 for placebo.

He is the key number to look at it is below that that's why it would be highly successful.

If it got it very likely above would still be successful.

Sergio Traversa: Then can you confirm if patients in all three phase three studies are receiving a loading dose? And what is that dose? Is it the 75 milligram dose, and then they go into the 25 milligram dose?

Got it got very good. Thank you very much and then can you confirm if patients in all three phase III studies are receiving a loading dose and what is that build as it would be 75 milligram dose and then they go into 25 dose and then also can you maybe just talk a little bit about <unk>.

Sergio Traversa: And then also, can you maybe just talk a little bit about specifically the pharmacology that requires a loading dose, if you are happy to do that? Yes, the answer is yes, all three studies are taking the loading dose. I do believe that also for new patients, also the long-term safety study starts with the loading dose, that it is 75 milligrams, three tablets.

Typically about the pharmacology that requires and loading dose if you are using.

Sure.

Yes. The answer is yes, all three studies I was taking the loading those I do believe that also the four new patients also the long term safety study is it starts with the with the loading dose that it is 75 milligram as three tablet.

Sergio Traversa: And I'm happy to share that even taking three tablets the first day, we have seen nothing from a serious, severe, or side effect that is confirmed by the discontinuation rate, which is well below the average for a depression trial, so it's well below 10%. And so, you know, you have over 90% of the patients that complete day 28. And we have seen a pretty low Dr. Andrew Cutler, Unknown Executive, Lin Tsai, Guofang Li, Sergio Traversa, Timothy McCarthy, Andrew Cutler, Relmada, The Pharmacology Base. REL1017 has a long half-life. It's between 25 and 30 hours. That is a natural once-a-day treatment.

And I'm happy to share that even taking three tablets. The first day, we have seen nothing kind of model T was severe or side effects that is confirmed by the <unk>.

The discontinuation of the dropout rate is well below the industry average flora.

Depression trials, so is well below 10% and so you'll have over 90% of the patients that complete day 28, and we have seen a pretty low.

Dropout rates, even in the long term study we have now patient that have.

<unk> been taking the drug for well over six months and the dropout rate is very low.

And in the long term safety study so.

But going back to the loading those.

It's been very well accepted.

The pharmacology is very simple.

<unk> has a long half life is between 25 and 30.

30 hours that is a natural once a day therapy. It is highly bind me too.

Sergio Traversa: It is highly binding to alpha-beta, I believe, to the plasma protein. So that implies the bioavailability is very high. It's well over 90 percent. So we have no problem with absorption. The profile is very clean, very easy to handle, very small molecule. And the The...

Two the plasma proteins so.

That implies the bioavailability is very high as well over 90%. So we have no problem in the absorption of the profile is may is very clean very easy to answer the very small molecule.

Dean.

The.

Sergio Traversa: If you take the regular dose, the steady state is day four, five, taking the loading dose to shorten the steady state at day two, three. So that's the only reason there is the loading dose to shorten, you know, the steady state of the plasma. Got it. Very helpful. Then just a final question. This one just came from a client, and the question is, do you have an opportunity to upsize any of these studies similar to what SAGE did if the blinded data are coming either below your expectation or different than what you might be expecting?

If you take the Red one of those the steady state is a day four five thinking.

Taking the loaded those are short term the steady state of day, two or three so that's the only reason.

And those two short term.

The steady state.

Plasma level.

Got it very helpful. And then just final question on this one just came from a client and the question is do you have an opportunity to upsize to any of the studies similar to what changed it if the blinded data coming either below your expectation or different than what you might be assuming.

Thank you.

Sergio Traversa: That's a good question, and I don't have a direct answer. I would say no, the... Now, I mean, up to 364 patients. I believe it's, well, it's a big number. Let me answer you in this way.

That's a good question and I don't see it right.

So do we.

I would say no.

<unk>.

No I mean pre engineered fix up to 364 patients I believe it's well it's a big number let me ask you this way.

Sergio Traversa: That is probably the most important, the best way to answer. If the drug does not work well with 364 patients, then we definitely have done something wrong. So we just don't see that going beyond that number would add any value. Very well. Thank you so much.

That is probably the most the best way to answer that if the drug does not work well with 364 patients then definitely we have done something wrong. So we just don't see that going beyond that number would add any value.

Sorry about it. Thank you so much I appreciate it.

Thanks, Yeah, I think part of the question.

Sergio Traversa: I really appreciate it. Thank you. And our next question comes from the line of Mark Goodman with SVB Lyrinc. Please proceed with your question. Yes, hi. Sergio. I've gotten this question a couple of times, so I figured I might as well just let you answer it to everybody.

And the next question comes from the line of Mark Delaney with SBB Leerink. Please proceed with your question.

Yes, hi.

Mark Goodman: I guess there are two of them. One is... If the monotherapy study is positive, and then one of the adjunctive studies is positive, but the other is negative, what do you do next? What do you need to do?

Certainly I've gotten this question a couple of times, so I figured I might as well just letting you answer it.

It's everybody I guess, there's two of them one is.

Yes. The monotherapy study is positive and then one of the Adjunctive study is positive but the other is negative.

What do you do next what do you need to do what's your understanding with the FDA.

Mark Goodman: What's your understanding of the FDA? Second question is, if the monotherapy is positive or negative, help us understand what kind of read through that is for the adjunctive studies. What does it mean?

Second question is if the monotherapy is positive or negative help us understand what kind of read through that is for the adjunctive studies what does it mean.

Either way thank you.

Mark Goodman: Either way, thank you. Thank you, Mark, for the questions. The first question is, if two trials are positive and one doesn't work, well, if the one mono and the one adjunctive are positive, we will file.

Thank you Mark one of the questions.

So the.

The first question is if two trials that.

Positive of one doesn't work well he's been one mono and the and one adjunctive are positive. We will trial. There are examples and one is J&J with proviso that.

Sergio Traversa: There are examples, and one is JJ with Spravato that had like five trials, three ability, three failed, two positive, and the patient population was, or the trial design was not the same as what they still got. So, you know, ultimately, the difference between monotherapy and adjunctive therapy in the depression setting is not, it is different, but it's not critical enough that the FDA would not look into it. It's a lot, and a lot will depend on how the data will look.

Probably trials three I mean, three failed to positive.

And Andy.

The patient population was the trial design was not the same as they've still got approved so ultimately.

The difference between monotherapy and adjunctive therapy in the depression setting is not it is different but it's not critical enough that you have to be able to look at it a lot and a lot.

A lot of it depends on how the data looks.

Looks like.

The third trial fails, we the people had zero point in Taiwan.

Sergio Traversa: If the third trial fails with a p-value of 0.51, we do believe the FDA will take these aspects into consideration. So if the data are good and the failure is not a total failure, and it is a zero, that we just don't see how that can happen, then I think we have a good chance here with two studies. Well, Sergio, have you spoken to the FDA? Have you spoken to the FDA at all about whether Amano was positive, and you have one of the adjuncts is positive?

We do believe the FDA will take these aspects the consideration. So the data are good and the failure is not a total failure.

Zero that we just don't see how that's going to happen then I think we have a good chance to do it.

The two studies.

Or would you have been broken out.

Have you spoken to the FDA at all about.

The motto was positive and you have one of your jumped as positive like has that been a discussion point and they were open to.

Sergio Traversa: Like, has that been a discussion point, and they were open to filing with that? No, well, you know, look, the SBA, for whatever I've seen in the last few years, my interaction or what I've seen with the SBA, they won't look, they won't tell you anything until you give them the full data. And, sorry, they will never tell you how to, you know, kind of indicate things like that.

Filing with that.

No the well.

The SBA for but they haven't seen in the last few years my interactions.

But it seems like with the SBA they won't they won't tell you anything until you give them the full data.

And so that will never tell you all of you.

Kind of indicating things like that they usually italia.

Mark Goodman: They usually tell you, you know, go ahead, and then we'll discuss it at the time of the NDA. So no, we have not, we have not discussed it with the FDA, but that's normal. We won't, we won't expect any real guidance from that. They want to see the data. They are very data-driven. And that's all it was.

Go ahead, and then we'll discuss at the time of the NDA.

So no we have not we have not discussed with the FDA, but that's normal we wont we wont expect any real guidance on that they want to see the data they are very data driven.

Okay.

And I thought it was.

Sergio Traversa: The second question was, if the first study is positive or negative, what kind of read through does that help us? Like help us understand what we would know better walking into the last two studies. Yes, so the answer is yes, we have data on as an adjunctive tariff.

The second question Lord.

The second question was if the first study is positive or negative what kind of read through that help us like help us understand what we would know better walking into the last two studies.

Yes, so the we.

We have data on as an adjunctive therapy.

Sergio Traversa: So that's when we feel comfortable, confident that it will show good results, right? Based on phase two and on everything we have done to make phase three to be a high-quality 2022 standard for depression. Now, if monotherapy is successful, then it clearly would be a good indicator that at least the trial was conducted appropriately, it's the same team. So they do exactly the same thing for all the problems.

That's why we feel comfortable confident that will show we show good results based on based on train two and based on everything we have done to make the phase III.

High quality 2022 standard.

Depression now with monotherapy is successful then clearly would be a good indicator that the.

At least that the trial is being conducted the process. Its the same team. So they do exactly the same thing for all the programs. So the way I would read through the successful phase III.

Sergio Traversa: So I would read through the successful phase three monotherapy trial that the adjunctive could be a similar success. Now the question is, what happens if the monotherapy fails? What can we do about that?

Monotherapy trial.

That's the adjunctive.

Could be similar.

Successful.

Now the question is what happens if the monotherapy trial.

What can we read through that.

Sergio Traversa: Well, definitely, it's not going to be a very positive signal, but also, in the adjunctive setting, there is another drug. So the only potential difference is that we don't know. We will know it soon, but for now, we don't know.

Well definitely it wasn't it's not going to be a very positive signal, but also.

The there is in the adjunctive setting there is another drug so the only potential different.

We don't know.

Sergio Traversa: If there is any synergy between an SSRI that by itself doesn't work well, but you add an MNDA channel blocker, then there is this synergy, and you see the good results we have seen, then if the monotherapy failed, and Wundan Minmar for the success of the adjunct. So I can give you the summary, even if I'm a little biased, but if the monotherapy is successful, then clearly a good signal, and a good time for the potential success of the adjunctive.

We'll know it soon but for now we don't know if there is any synergy between.

As to survive that by itself doesn't work well, but you add them NDA channel Blocker then there is the synergy and precede the good result, we have seen.

Then.

The monotherapy failed.

We will not mean much for the success that you had done.

Sergio Traversa: If monotherapy fails, I would not draw the conclusion that agentive treatment will fail as well. The role of the non-satisfactory effect of the base therapy alone, the SSRI or SNRI alone, could be very different in combination with an NMDR channel.

So I can't give you the summary, even if I am a little biased but.

Monotherapy successful then clearly is a good signal good time for a potential success of these chunky if monotherapy fails I would not draw the conclusion that the.

Adjunctive treatment and fail as well there is the role of the.

Non satisfactory effect of the based therapy alone DSS allow USA alone could be very different.

In a combination with in India, China, and in India, or China blocker.

So I hope I gave you the answer that the best way it could yeah.

Sergio Traversa: I hope I gave you the answer the best way I could. Thank you. Magid, can you just give us a sense of what spending is going to be this year, whatever you can disclose? Sure, we haven't given... Thank you for dining with us, and we hope you've enjoyed this. Maggie, can you hold theirs for me?

Thank you Maggie can you just give us a sense of what spending is going to be this year whatever you can disclose.

Sure we haven't given.

Defined guidance, but you can target about 30% to $35 million quarter Mark.

Thanks.

Sure.

You're always going to be easy questions.

[laughter]. Our next question comes the line of Julie Li with Truth Securities. Please proceed with your question.

Operator: Okay. Our next question comes from June Li with Swiss Securities. Please proceed with your question. Good afternoon. This is awesome news for June.

Good afternoon. This is.

Awesome Arthur Joon, thanks for taking our questions.

June Li: Thanks for taking our questions. So, I guess my first question is, you saw strong durability in phase 2. Do you have any plans to assess the durability of antidepressant effects in the ongoing phase 3? And I have a follow-up question after that as well. Thanks for the question. By durability, do you mean beyond day 28? I assume.

I guess my first question is you saw strong durability in phase two.

You have any plans to assess for durability of antidepressant effects in the ongoing phase III.

And I have a follow up question after that as well.

Thanks for the question for durability, you mean beyond day 28.

Sergio Traversa: Well, we will, after day 28, the trial becomes open label. So we will have some Madras score numbers measured, but it is open label. So for the FDA, that would mean nothing. And in general, it would not be like very strong, very strong data. So, yes, we will have some data, but not that we'll be like a major indicator of anything. It's open label.

Assume it.

Well, we will after day 28, the trials become becomes a open label. So we will have some more growth.

Score numbers.

Measure, but yeah.

It is open label so for the FDA that would mean nothing and in general.

It would not be like a very strong and very.

Some data.

<unk>.

So yes, we will have some data about.

That would be like.

Yeah.

And major indeed.

Indicators of.

If anything it's open label.

Okay. Thanks.

Sergio Traversa: Okay, thanks. Um, and then I guess sort of on this at the bottom, sorry, one more thing about that the FDA has not required any efficacy data after day 28. So they're very happy.

And then I guess sort of on the business.

Sorry, one more thing on that the FDA has not required any efficacy data after the 20th so they're very happy but they can see the day 28 as the long term effects of chronic effects.

Sergio Traversa: They consider day 28 a long-term effect, chronic. Okay, thank you. We'll keep that in mind.

Okay. Thank you.

June Li: So we're going to ask about BD. Do you have any, you know, expect any discussions with a potential BD partner once you have first positive phase 3 data, hopefully mid-year? Or is your plan sort of to just hold off on that until you have results from all the studies? Uh, yeah.

We'll keep that in mind.

So.

Can I ask about BD do you have any are you expecting any discussions with the potential BD partner. Once you have first positive phase three data hopefully mid year.

Do you plan to just hold off on that until you have results from all the studies.

Yeah.

I'm well.

Sergio Traversa: Well, as you may imagine, we already have and are in constant contact with potential partners and all the potential licensees or partners won't start to do work on the molecule or the program after phase three. They know very well what we are doing, and you know they have done their own diligence. We don't think that anything will happen before at least the first phase three data read, and um.., and the but they want to be ready after the data is really good so it can be competitive, then they want to really have the work done.

As you May imagine we already have we are in constant contact with potential partner and.

All the potential.

License or partners.

They won't start to do work.

Work on the molecule in the program.

After phase III.

They know very well, what we are doing and.

They have done their own due diligence.

We don't think that nothing will happen before the at least the way.

The first phase III data.

And.

And the but they want to be ready after the data is really good it can be competitive than they already have the.

Sergio Traversa: But we have Gino on board now who will help us out with making this kind of decision. What I can tell you is that when a potential partner does real due diligence, it's a big distraction. It's not due diligence that takes a couple of days.

Perfect answer.

While we are we have Jean on board now that seems to be.

He will.

Help us out on making these kinds of decisions, but I can tell you is that when a potential partner does really real due diligence is a big distraction.

That takes a couple of days you are talking about two months process.

Sergio Traversa: We're talking about a two-month process, and we have already done it. So right now, even if we want to, we won't have the bandwidth and the capacity to go through a serious due diligence process with any potential partner. I think we will postpone everything at least after the first phase series. Okay, thank you, Sergio. Thank you. Ladies and gentlemen, as a reminder, to register for questions, press the 1 followed by the 4 on your telephone keypad.

And we have done it so right now even if we want to we want that they like.

The bandwidth of the capacity.

To go through a few of us due diligence.

The process with any potential partnership.

But I think we will postpone everything at least after the first phase III readout.

Okay. Thank you Sergio.

Thank you.

Ladies and gentlemen, as a reminder to register for a question and pass the one top of mind for any telephone keypad.

Operator: And our next question comes in on the line from Vamil Devan with Missoula Securities. Please proceed with your question. Hi, great.

Next question comes from the line of <unk> with Mizuho Securities. Please proceed with your question.

Alright, great. Thanks for taking my question. So I think on the same.

Vamil Devan: Thanks for taking my question. So, I think it's on the same theme as most of the other questions, just trying to get ready for this data here coming up. So, there are a couple of questions I have.

Most of the other question just trying to get ready for this data here coming up so a couple of questions I have one I don't know if you have disclosed or you can just close or the number of patients that you've screened for the various phase II trials for any sense or the <unk>.

Screen failure rate that you're seeing I know you've put a lot of.

Steps in place here to get the right patients I'm, just trying to get a sense of if that's been successful or not and then I'm also curious as you mentioned, you're you don't have the phase two data in monotherapy.

To kind of drive your powering assumption. So can you talk about sort of what's your powering assumptions are for the monotherapy trial, specifically and how it compares.

To what you've done for the trials.

Sure.

No.

Vamil Devan: One, I don't know if you have disclosed or can disclose sort of the number of patients that you've screened for the various phase three trials or any sense of sort of the screen failure rate that you're seeing. I know you put a lot of steps in place here to get the right patients. I'm just trying to get a sense of if that's been successful or not.

Yes, I believe we have disposals.

Is that even though the numbers what the.

The screening failure rate. It is in line with the industry. It is between 50 and 60% depending on the period and depending on the on the trial that is in line.

The we have an extra as you mentioned, but we try to be.

Yeah. It is more effective in selecting patients they are affected by a depression.

Possible and we use the second line of diagnosis, we use the safer interview.

And the safer into view, depending on again time and different trial.

Sergio Traversa: And then, I'm also curious, as you mentioned, you don't have phase two data in monotherapy to kind of drive your powering assumptions. So, can you talk about sort of what your powering assumptions are for the monotherapy trial specifically and how they compare to what you've done for the adjunctive trial? Sure, but after noon, we'll meet.

Sergio Traversa: Yes, I believe we have disclosed what the screening failure rate is. It is in line with the industry, between 50 and 60 percent, depending on the period and depending on the trial. It is in line. We have an extra, as you mentioned, we try to be as effective in selecting patients that are affected by depression as possible, and we use the second line of diagnosis; we use the SAFER interview. And the SAFER interview, depending on, again, time and different trials, the further failure rate, meaning patients that get to SAFER but they are not randomized, it's another 10 to 20 percent.

Sergio Traversa: So you can assume that out of 100 patients that get, that get, that get the SAFER interview, can select it and go through the screening process, about 35 to 40, they make it to randomization. That is in line, but probably a little bit below, the industry average. We don't have a lot of data published, but we got that from our CEO. And so we are pretty strict in terms of selecting and selecting patients. But the fatal rate is 50 to 60% in the first round and another 10 to 20% in the second.

Sergio Traversa: The second question is about the powering of monotherapy. Well, we did not really have anything to look at directly in monotherapy, so we took the easy way of just assuming. The same assumption we did for the adjunctive therapy, so the statistical plan they are exactly the same, and we do believe in a fair outcome.

So the statistical claim they are exactly the same.

And we do believe the assumption.

Okay. Thank you Sir.

Sergio Traversa: Okay, and I think just to confirm that the powering is based on sort of getting a two-point separation and combination, is that correct? Yes, that's correct. So if the delta between drug and placebo on day 28 is two points on the MATLAB scale, the study will be satisfactory. We hope to go much further than that, but... Yeah, I was going to follow up on that, like what... Worst case scenario.

Confirm I think you said the powering based on getting a two point separation in combination is.

Is that correct.

Yes, that's correct. So the delta between drug and placebo day 28 is two points on the macro scale. This study will be subdued.

Yeah.

Okay, maybe just one other than that.

This is going to follow up on that like what the worst case.

Do you have a threshold for.

Vamil Devan: Do you have a threshold you'd say for what you think would be a really sort of clinically meaningful result that you're looking for, maybe beyond the two point separation? in either model that we are engineering? We have to say what the industry and the FDA and the CAO tell us, the two points: it is clinically meaningful, and it is going to change the way depression is treated. If we show two points delta, probably not.

For what you think would be clinically meaningful results that you are looking for maybe beyond the two point separation.

In either model.

Thank you.

We have to stay at what the you know the industry and the SBA and the chaos.

Two points it is clinically meaningful.

It is going to change the way depression is treated please Joe two point Delta probably not that would be another antidepressant, we'd probably be approved and thought would be us.

Sergio Traversa: It would be another antidepressant, and it would probably be approved. It would probably be used, but it's not going to be like what we are hoping to do, to change, you know, the game changer in the treatment of depression. There are two points we'll make. Three points in the ball, that would be, that would be different, it would make a big difference. So, the standard two points; it is considered clinically meaningful. We do believe that for What we hope to do, and we expect three points in the ball, would be much better, much more clinical.

Yes.

But it's not going to be.

What we are hoping to do the change.

The game changer in the treatment of depression, that's two points won't make it.

Yeah three points in the ball there would be that would be it would make a big difference.

So the standard two points it is considered clinically.

Meaningful.

Do believe that for.

But we hope to do and we expect three points in the bulk would be much better.

Much more clinically meaningful.

Okay, Alright, great. Thanks for taking my questions.

Vamil Devan: Okay. All right, great. Thanks for taking the question. Thank you, Amir.

Thank you Amin.

And our next question is from the line of Jay Olson with Oppenheimer. Please proceed with your question.

Jay Olson: And our next question is from the line of Jay Olson with Oppenheimer. Please proceed with the question. Oh, hey, this is Matt, on behalf of Jay.

Oh, Hey, this is Matt on for Jay Thanks, So much for taking our questions.

Matt: Thanks so much for taking our questions. So, the first thing we were wondering about, I guess, is just any physician feedback that you might have received already on the HAP studies from the recent Ketamine and Related Compounds Conference. I'm just curious if some of that feedback includes how they view the safety and tolerability and abuse potential profile of REL1017 versus generics or other NMDA antagonists in development. And then, secondly, we were just curious, similarly, if you've received any feedback on the publication on ONI lesions in preclinical data.

First thing we were wondering about I guess is just on any physician feedback that you might have received already on the <unk> studies from the recent ketamine and related compounds conference.

Just curious if some of that feedback includes how they view.

Safety, and Tolerability and abuse potential profile of 10.

17 versus generic.

Or other NMDA antagonist in development and then secondly, you were.

Just curious similarly, if you've received any feedback on the publication on the only lesions and preclinical data.

Matt: And, as a corollary, if you're doing any scans in the Phase 3s on human patients to detect any brain imaging abnormalities, that would be interesting as well. Appreciate that. Thank you.

And as a corollary, if youre doing any scans in the phase threes.

The phase III is on human patients to detect any brain imaging abnormalities that would that would be interesting as well I appreciate that thank you.

Sure Hey, Matt. Thanks for the question. So the first question is the feedback from physicians on the human abuse potential study, yes, we got a baby.

Sergio Traversa: So the first question is the feedback from physicians on the Human Abuse Potential Study. Yes, we got very, very confident feedback from KOLs and from whoever understands the data. And one thing that I can share is that nobody was really surprised by the data.

Im confident.

Feedback from Kols and from wherever I understand this.

Data.

<unk>.

But one thing is that I can share is that nobody was really surprised by these data.

Sergio Traversa: The DEA has already made up their mind, and they state it on their website. So the data we generated just confirms what was already known by, you know, the abuse community, if I can call the abuse community that. And so nobody got really surprised by the data.

The DEA as already made made up their mind and they make it on their website. So the data we have generated just confirmed.

What was already known by the abuse and if I can call the abused communities and so theres nobody got really surprised by these data, but definitely the feedback has been very positive has been confirmed.

Sergio Traversa: But definitely, the feedback has been very positive. It's been confirmed that, you know, the risk of, you know, the potential for abuse is not there. So that's that's one on the on the only lesion that one was. There was more interest than I thought, but there are concerns about the only lesion in the long-term use of NMNDA antagonists. This probably is the background that was created by MPA801 that was potentially effective, but the toxicity was very high. However, the feedback was very positive, saying that there was no risk of only lesions.

That the risk of the potential for abuse is not there.

So.

That's one on the on the all new lesion Boltzmann wise.

We got more there was more interested than I thought.

And by the <unk>.

They are concerned about the the only lesion in the long term use of our <unk> and <unk>.

NDA in Thailand.

But he is the background there was created by unpaid April one.

There was potentially.

Effective but that toxicity was very high so we have been.

The feedback was very positive.

Maybe it's no risk of one lesion.

So consider that.

Sergio Traversa: Consider that REL1017 has a very long history in humans through the racemic, that it means nothing in terms of efficacy and mechanism, but in terms of safety, it can give some indication. It's been in humans for 50 years. At very high doses, much higher than we're using, there's been no report of any brain damage or anything, or any long-term effects, in that case. In phase 3, to my knowledge, we are not doing anything in terms of MRI or any detection of brain damage.

17 is a very long history, and you went through different semic.

If it means nothing in terms of efficacy and the mechanism, but in terms of safety can give some some indication has been human for 50 years.

Very high dose is much higher that we're losing theres been no report.

Of any.

Brain damage or anything or any long term effect.

Yeah.

In that case.

So the in the phase III.

To my knowledge no we are not doing anything in term of our MRI of any.

Detection level.

Sergio Traversa: We don't expect any; there was no sign of any signal that there is a potential for brain damage. We actually hope, based on everything we have seen so far, and based on the neuroplastic effect, we do believe that there is a potential for an improvement in brain function, and in the, you know, dendrite functionality, and the dendrite connection, which when there is a chronic strain, chronic stress, can generate some form of dendrite atrophy.

Brain damage.

We don't expect any any there was no sign of any signal that there is a potential for his brain brain damage, we actually hope.

Based on everything we have seen so far and peso and euro plastic effect, we do believe that there is a potential for improvement.

<unk> function.

And.

Then drive functionality and that connection when there is a chronic straight Tony's class.

Ken generating some form of Eventbrite atrophy, so the brain Phantom too if you look at the brain of patients that are affected by depression for.

Sergio Traversa: So the brain can tend to, if you look at the brain of patients that are affected by depression for all their life or for many, many years, there is some morphological change in the brain structure.

All their life for many many years and that.

There is some more follow more philosophy changed in the brain stuff there so rather than 17 should show in.

Matt: So, REL1017 should show, if the patients start to take it early enough, fatigue for the long term could potentially, and I use the conditional here because we don't have the data, but based on the mechanism, can, could potentially improve brain functionality, not only to prevent damage. Okay, got it. That makes perfect sense.

And if it's the patient start to take it the early enough at things from a long term could potentially.

And they use a conditional here because we don't have the data, but based on the mechanism can put two could potentially.

Prove the brain functionality.

Not only not to damage it.

Okay got it that makes perfect sense really appreciate that and one other thing we were just wondering about since it has not.

Sergio Traversa: And the one other thing we were just wondering about, since this has not been asked yet, is just the current status of the Arbormemphis psilocybin compound. I'm just curious where that currently stands and any thoughts on the next steps of development and potential indications. Thanks so much.

The current status of the <unk> compound just curious where that currently stands and any thoughts on next steps of development and potential indications. Thanks. So much.

Yes sure.

Sergio Traversa: Yeah, sure. We keep a low profile on the silo siding for a few reasons, but the main one is we are really busy with the development 17 program. But, you know, the silo siding is moving nicely forward.

We keep a low profile on the <unk>.

For a few reason, but the main one is we are really busy with the C 17 program, but the prototyping is moving nicely forward or the <unk> the manufacturing.

Finishing up the manufacturing process.

Sergio Traversa: I believe we are the manufacturing, finishing up the manufacturing process. I don't know if we disclosed it or not, but I'm going to disclose it anyway. We will make psilocybin with a proprietary synthesis. So we won't buy it, we make it ourselves, and that is economical, and you can have as much as you want and it's much cheaper than buying it from a third party.

I don't know, if we disclose that I'm not going to disclose it anyway Deane.

We will do.

Make silo side being with appropriate Sally.

Synthesis.

So we won't buy it and we make it ourselves and that is.

It's a it's economically and you can have as much as he wants and it's much cheaper than that than buying from third parties.

Sergio Traversa: And so when that is finished, and we will update the community on the next step, we are also doing a certain number of preclinical studies. And the goal of the preclinical studies is to show, and the FDA wants to see it, to show and confirm that psilocybin, which is a 5H2A agonist, has a neuroplastic effect as well. And so it's currently being tested in animals like rodents, zebrafish, and some form of flies with a certain model that detects the neuroplastic effects of compounds.

And so when would that will be finished.

And we will update the community on the next step.

We are doing also a certain number of.

Preclinical studies and thank all of the preclinical studies to show.

And the FDA wants to see it be to show and confirm that.

Psilocybin debt is at five <unk>.

Neuro classic effect as well.

And so it is being currently tested in.

Animals, many broadband zebra fish.

And maybe some some form of fly with certain model that.

<unk>.

In neuro plastic effects of compounds.

Sergio Traversa: So Preclinical Ongoing and Manufacturing. The Big Difference will be, you know, and we will discuss with the FDA, what kind of information, if any, they want to see on the preclinical and safety of psilocybin. We're using a dose that is substantially lower than what everybody else in the psilocybin space is using, and we're using a low-dose chronic. And so that should, or could play a role in our conversation with the FDA.

So preclinical ongoing and.

10 manufacturing.

The big difference.

Will it be.

We will discuss with the FDA.

What kind of information if any information they want to see on the preclinical and safety.

Tyler I mean, we are using a dose that is.

Substantially the lawyer lower.

Everybody else in the silo saving space.

<unk> is using and we're using low dose chronic and so that should could play a role in our conversation with the FDA.

Sergio Traversa: And if the information is already available for psilocybin in terms of safety, and it is sufficient, then, and I use the conditional again, then we may be able to go straight into a phase, that would save a couple of years of time and would be a catalyst that we will have data probably 12 months after we start phase two. But it's too early to make a big statement.

And if the information already available or cellulose fiber in terms of safety.

They are sufficient then and they use the conditional again, then we may be able to move straight into a phase two.

That would save it.

A couple of years off time and would be right.

Catalyst that we're going to have data probably 12 months. After we started the phase III.

It's too early to make a big statement, we still have to see the results of a preclinical and and finish the amount of factoring and then discuss with the FDA, probably we will give an update.

Sergio Traversa: We still have to see the results of the preclinical studies and finish the manufacturing, and then discuss with the FDA. Probably, we'll give an update toward year end after the phase three results. Okay, got it. That makes sense.

So our year end.

After the things that you.

The readouts.

Okay got it that makes sense. Thank you very much I. Appreciate you taking my questions. Congrats on the progress thanks for asking.

Sergio Traversa: Thank you very much. I appreciate you taking the time to answer the question. Congratulations on all the progress.

Sergio Traversa: Thanks for asking. And their last question is a follow-up from the line of Yatin Seneja with Guggenheim Partners. He's received a question.

Okay.

And our last question is a follow up from the line of Yadkin.

<unk> with Guggenheim Partners. Please proceed with your question.

Hey, guys. Thank you for allowing the follow up just quickly.

Yatin Seneja: Hey guys, thank you for allowing the follow-up. Just quickly, can you provide a little update on the enrollment, especially for the monotherapy study? Just like where you are, how close to reaching full enrollment, and could you narrow the timeline on the data or the current guidance? Narrow the time on the data. We play with the media, so I would not go more in detail than that. The reason is that there are variables like data cleanup, and so it's impossible to really give a very specific week or even month.

Can you provide an update on the enrollment, especially on the monotherapy study.

Just like where you are how close to reaching full enrollment in could you narrow the timeline on the data.

Our current guidance stands.

Yeah. Thanks, Yeah, I think it will narrow the time on the data I would say with the media. So I would not I would not go.

More details than that reason that the.

Valuables like the data clean up and so it's a it's impossible to really give a specific like weeks or even months. So we keep a like a month plus my understand that as a buffer.

Sergio Traversa: So we keep it like a month plus minus as a buffer. The internal enrollment is actually going very well. We took some measures earlier this year, and we brought on board who?

In general the wrong, it is actually going very well.

It took some major earlier D C.

And we brought on board.

Okay.

Sergio Traversa: an infrastructure that mimics the CRO. So we have our own medical liaison, which we call MSLs. We have our own CRA, the Clinical Research Associate, and they all go to the sites and they follow the study very closely. And we also have one or two people that do the data cleanup internally. So we want to be ready and try to speed up the enrollment and data read as fast as possible. At the same time, I'm sure you agree, we look at quality first, right? Enrolling patients in depression is very easy. You can find as many patients as you want. But to find quality in terms of enrollment, it's a little bit more difficult.

And infrastructure that mimic the CFO , so we have our own.

Medical liaison to call them ourselves, we have our own.

CRA that clinical research.

Our research our associates and they all go to sites and they follow the study.

Very closely.

And we do have also.

One or two people that do the data clean up internally, so we want to be ready and to try to speed up.

The enrollment and the data read that as fast as possible at the same time yet.

I'm sure you agree we look at quality firms right now enrolling patient in depression is b you can find as many patients as you want but to find quality and tell them what the enrollment.

A little bit more.

Difficult.

Sergio Traversa: And we totally focus on quality. We want to get it right the first time, not the second time.

Totally focus on quality, we want to get it right.

And the first nine months.

But the enrollment season.

Sergio Traversa: But enrollment is going very well. There are no further questions, I just Okay, well, thanks, and in closing. Closing statement: I am very 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 the effort in advancing this important product candidate through the clinic as expeditiously as possible.

It's going to be is going very well.

Thank you.

Yeah.

There are no further questions at this time.

Okay, well, thanks and in closing.

Closing statement I am very grateful to the <unk> team for their continued hard work and dedication to executing on our mission.

Also like to extend my sincere thanks to the participants.

And cleaning of partners involved in the ramp in 17 clinical trials for the effort.

Advancing this important product candidates through the clinic as expeditiously as possible.

Sergio Traversa: With that said, I wish everybody and everyone a wonderful end of the day, and we'll speak soon for the next quarterly call. Thank you very much. That does conclude the conference call for today. We thank you for your participation and ask that you please disconnect your line. [music]

With that said I wish everybody and everyone a wonderful.

It depends of the day and we'll speak soon or at the next quarterly call. Thank you very much.

That does conclude the conference call for today, we thank you for your participation and ask that you. Please disconnect your line.

Okay.

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