Q2 2021 Relmada Therapeutics Inc Earnings Call

Thank you for standing by and this is the conference operator welcome to the a lot of therapeutics second quarter, 2021 and coal.

Operator: Thank you for standing by. This is the conference operator. Welcome to the Relmada Therapeutics Second Quarter 2021 Earnings Call.

As a reminder, all participate in Houston and relied on the conference is being recorded.

After the presentation that will be and opportunity to ask question. Just on the question. She you may put star and 1 on your telephone keypad.

Operator: As a reminder, all participants are in listen-only mode, and the conference is being recorded. After the presentation, there will be an opportunity to ask questions. To join the question queue, you may press star, then one on your telephone keypad. Should you need assistance during the conference call, you may signal an operator by pressing star and zero. I would now like to turn the conference over to Mr. Tim McCarthy from Lifestyle Advisors. Please go ahead.

And you need assistance during the conference call you may signal and operating up by pressing star and D. R.

And would now like they tend to come from side to change if the P and the coffee from lifestyle by day thing.

Go ahead.

Thank you Rachel and thank you all for joining US. This afternoon with me on today's call are Chief Executive Officer, Sergio sure versa, and Chief accounting and compliance officer Chuck <unk>.

Timothy McCarthy: Thank you, Rachel, and thank you all for joining us this afternoon.

Good afternoon, <unk> issued a news release and providing the business update and announcing financial results for the 3 and 6 months ended June 30th 2020, 1 and filed its quarterly report on form 10-Q with the SEC.

Timothy McCarthy: With me on today's call are Chief Executive Officer Sergio Traversa and Chief Accounting and Compliance Officer Chuck N. This afternoon, Relmada issued a news release providing a business update and announcing financial results for the three and six months ended June 30, 2021, and filed its quarterly report on Form 10-Q with the SEC. Please note that certain information discussed on the call today is covered under the safe harbor provision of the Private Securities Litigation Reform Act.

Please note that certain information discussed on the call today is covered under the safe Harbor provision of the.

Private Securities Litigation Reform Act, we caution listeners that during this call grandmother management team on making forward looking statements.

Results could differ materially from those stated or implied by these forward looking statements due to risks and uncertainties associated with the company's debt.

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 30, 2020, and subsequent filings.

These forward looking statements are qualified by the cautionary statements contained and from modest press release issued today and the company's SEC filings, including and the annual report on form 10-K for the year ended December 30, <unk> 2020, and subsequent filings.

This conference call also contains time sensitive information that is accurate only as of the day of this live broadcast August 10.2021.

Timothy McCarthy: This conference call also contains time-sensitive information that is accurate only as of the date of this live broadcast, August 10, 2021. Ramada undertakes no obligation to revise or update any forward-looking statements to reflect events or circumstances after the date of this conference call. Now, I would like to turn the call over to Sergio.

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

And I would like to turn the call over and started yet Sergio.

Thank you, Dan and good afternoon, and as always and to everyone. I'm pleased to welcome do remind us second quarter 2021conference call on today's call I will provide an update on the comprehensive development program for our lead product candidate.

Sergio Traversa: Thank you, Tim. Good afternoon.

Sergio Traversa: And as always, and to everyone, I'm pleased to welcome you to Relmada's second quarter 2021 conference call. On today's call, I will provide an update on the comprehensive development program for our lead product candidate for the adjunctive treatment of depression, REL 1017, highlight the substantial market opportunity for this compelling product candidate, and review upcoming Milestones. Following this, I will turn the call over to Jack Enns, Chief Accounting and Compliance Officer, for a review of the fine.

For the adjunctive treatment of Depression Route 10, 17 highlight this and stomach substantial market opportunity per day is compelling and it.

And review upcoming milestones.

And this I will turn the call over to Chuck and its chief accounting and compliance officer for a review of the financials.

I will then provide a brief overview on our recent acquisition all day.

And well open and commercial rights to it and all the psilocybin and their rebate program and Florida Neuro degenerative indications.

Sergio Traversa: I will then provide a brief overview of our recent acquisition of the development and commercial rights to a novel psilocybin and derivate program for neurodegenerative indications. With that, I'll begin by reiterating the significant news shared last week in our top-line result from the Abuse of Human Potential, or HAP, study, evaluating REL1017 versus oxycodone 40mg as the active control As many of you already know, REL1017 is also known as S-Methadone, which is the dextro or right-side isomer of racemic... While there is considerable existing published data supporting a lack of clinically relevant opioid, including a very clear statement from the Drug Enforcement Agency, the DEA.

With that I'll begin by reiterating the significant news she had last week, he and I was taught.

Line result from the abuse.

And potentially or Hap study evaluating rather than 17 versus Oxycodone 40 milligram is that the active control.

As many of you already know the rest and 17 and he's also known as Hess, mastodon, and extra or rightsize eyes, and Oh racemic bad debt.

While there is considerable and considerable existing published data supporting and lack of clinical relevant opioid and include.

Including a very clear statement from the drug enforcement agency. The DEA. We conducted these work for F. D. A guidance and as it is commonly done for CNS active drug and to some.

The comprehensive data package for our new drug application or N. B a relative 10.17 is an adjunctive treatment for M. D D.

Importantly, our study was designed in a matter that followed the F. D. A 2017 guidance on the assessment on the abuse potential of drugs.

Sergio Traversa: We conducted this work for FDA guidance and as it is commonly done for CNS active drugs. To support the comprehensive data package for our new drug application or NDA for relp1017, an adjunctive treatment for MDT. Importantly, our study was designed in a manner that followed the FDA 2017 guidance on the assessment of the abuse potential of drugs. Top-line results for the primary endpoint showed that all three doses of REL1017 evaluated in recreational opiate users demonstrated a highly statistically significant difference versus those rated for oxycodone 40mg.

Topline results for the primary endpoint and showed that all 3 doses of route 10, 17 evaluated and recreation on opioid users demonstrated a highly statistically significant difference.

And as those rating for obstacles on 40 milligrams and notably the highly statistically significant difference what's going on.

Between the active control and 150 milligrams of route 10, 17, which is the maximum tolerated dose and these 6 time the proposed therapeutic dose.

The results for the secondary endpoints, which include and scores for global overall liking and the desire and taking the drug again.

Consistent with those of the primary endpoint they demonstrated no evidence of any meaningful abuse potential more specifically the results demonstrated that route 10, 17 was similarly highly statistically significant and differences burst oxycodone at all doses and debt.

Sergio Traversa: Notably, the highly statistically significant difference was confirmed between the active control and 150 mg of REL1017, which is the maximum tolerated dose and is six times the proposed therapeutic dose. The results for the secondary endpoints, which included scores for global overall liking and the desire to take the drug again, were consistent with those of the primary endpoints. They demonstrated no evidence of any meaningful abuse potential.

Placebo results were consistent with the approved drugs that are unscheduled and scheduled for all scheduled by.

The secondary endpoint and see that further stretching and strength at <unk>.

You bet on results of this study is important and that they all seem from the Fda's review of the fewer future NDA for Ralph Desert Tencent.

We believe that these collective results have addressed any receivable concern regarding human abuse liability as a potential risk for FDA approval by establishing clear separation from the active control and is scheduled to new opioid agonist. In addition, the results on route density.

Sergio Traversa: More specifically, the results demonstrated that RAL1017 was similarly highly statistically significant in differences versus oxycodone at all doses, and the placebo results were consistent with approved drugs that are unscheduled, Schedule IV, or Schedule V. The secondary endpoint data further strengthens the overall results of the study and are important in that they also inform the FDA's review of the future NDA for rare diseases. We believe that these collective results have addressed any residual concern regarding human abuse liability as a potential risk for FDA approval by establishing clear separation from the active control that is scheduled to muddle up your act.

And P and in comparison to placebo were comparable or better kudos are achieved by mainly drugs that they've been FDA approved as either unscheduled and scheduled 5 are scheduled for.

And would like to note that we are again joined today by Dr. Charles Chuck Goldblum, Betsy is the form of scientific director of the National Institute of drug abuse addiction and abuse of sector Dr.

Dr. <unk> will be available to answer any questions regard do they have studied during the Q&A session.

With that I will now provide and update on reliance and the ongoing phase III program for route and 17, which consists of 2.6 debt to arm.

Placebo control people to rely on 1 and really as to each of which will include 364 participants first study across 55 sets. It all thank you includes rely on oil as the long term open label safety study, which is enrolling both rollover participants.

Sergio Traversa: In addition, the results for RAL1017 in comparison to placebo were comparable or better to those achieved by many drugs that have been FDA approved as either unscheduled, Schedule 5 or Schedule 6. I would like to note that we are again joined today by Dr. Charles Chuck Gorodetsky, who is the former Scientific Director of the National Institute of Drug Abuse Addiction Research Center. Dr. Gorodansky will be available to answer any questions in regard to the HAP study during the Q&A session.

From the pivotal study as well as de Novo petition.

As a reminder, these studies are designed to evaluate the route 10, 17 isn't an adjunctive treatment for major depressive disorder or M. D. D. And includes 2 arms placebo and 25 milligrams or 10.17, both of which are on top of standard antidepressant.

And for participants.

And have already and successfully tried and minimal 1 and up to 3 existing antidepressant therapies.

Sergio Traversa: With that, I will now provide an update on Reliance, the ongoing Phase III program for REL 1017, which consists of two sister, two-arm, placebo-controlled pivotal studies, Reliance I and Reliance II, each of which will include 364 participants per study across 55 studies. It also includes Reliance OLS, the long-term open-label safety study, which is enrolling both rollover participants from the Pivotal As a reminder, these studies are designed to evaluate REL1017 as an adjunctive treatment for major depressive disorder, or MDD, and include two arms, placebo and 25 mg of REL1017, both of which are on top of standard antidepressant treatment for partiality.

The primary endpoint is change in the moderate score at day 28.

Key secondary endpoints include the change and Mad Rush to score at day, 7 and changing C. G. I ex the clinical global impression on severity score at day 28.

Ooh reliance 1 and it really has 2 are progressing with topline data expected the first half of next year.

Reliance on L. As the long term safety study is also ongoing and enrolling participant at this point.

Data from these long term open label safety study would be part of the NDA filing package.

In addition, we have started dosing and rely on the street to evaluate the use of route and 17 as a monotherapy before and it.

As a reminder, the most significantly different between this trial and the ongoing clinical studies the population the plant.

And did the monotherapy study will consist of being Redeveloped individuals who are diagnosed with depression.

And I'm not currently taking standard antidepressant therapies, we anticipate completing the study prior to the conclusion of rally and Swan and rely on too.

Moving on planning for our second human abuse potential study. This 1 necessity and route 10, 17 versus intravenous ketamine, which has been and established debt and establish history isn't effective positive control and he's on corn.

Sergio Traversa: who have already unsuccessfully tried a minimum of one and up to three existing antidepressants. The primary endpoint is change in the Madras score at day 28. Key secondary endpoints include change in the Madras score at day 7 and change in CGI-S, the Clinical Global Impression Severity score, at day 28. Both Reliance One and Reliance Two are progressing, with top-line data expected in the first half of

We will be the more precise on the timing of the topline results of the study and the next couple of months based on the speed of recruitment and broadly expect those results.

And the DCF for the first quarter of 2000 and twin chip.

I wanted to take a moment to reaffirm the need for a new therapeutic option with the potential clinical profile that route 10, 17 prison, the fresh and it's coming.

Sergio Traversa: Reliance OLS, the long-term safety study, is also ongoing and enrolling participants as planned. Data from this long-term open-label safety study will be part of the NDA filing. In addition, we have started dosing in Reliance 3 to evaluate the use of REL1017 as a monotherapy for MDD. As a reminder, the most significant difference between this trial and the ongoing clinical study is the population; the planned MDD monotherapy study will consist of individuals who are diagnosed with depression, and I'm not currently taking standard antidepressants. We anticipate completing this study prior to the conclusion of Reliance 1 at Reliance. Moving on, we are planning for our second human abuse potential study.

But for many who suffer current option on not effective enough over 17 million individuals and the U S suffer from MTT and there are currently limited therapeutic option to help these patients traditional antidepressants can take up to 4.6 weeks to show efficacy and significant side effects.

And we're approximately 65% of empty the patients do not respond well to the first antidepressant treatment and approximately 30%.

Well then be the patients do not respond to any of the current order and get a presence.

Adjunctive treatment option and a crucial because they enable that change and therapy without requiring significant time, and ssris and other drugs and required when switched agents to the drought and.

And are there potential side effects.

Despite these challenges the only.

Currently 3 F D. A approved adjunctive treatment for major depressive disorder, and all 3 of them are whole anti psychotics.

Sergio Traversa: This one is assessed in RELM 1017 versus intravenous ketamine, which has been an established test and has an established history as an effective positive control, and is on. We will be more precise on the timing of the top-line results of this study in the next couple of months based on the speed of recruitment, and broadly expect those results by the end of this year or the first quarter of 2020. I wanted to take a moment to reaffirm the need for a new therapeutic option with the potential clinical profile that REL 1017 presents. Depression is coming. But for many who suffer, current options are not effective.

Based on its novel mechanism of action and they collect the positive data generated to date, including phase 3 results that showed a statistically significant.

And to stay and antidepressant effect with a favorable safety and Tolerability profile, we believe resident and 17 has the potential to be the first.

Laura antidepressant FDA approved for adjunctive treatment.

And now passing the call over to Chuck for ease of your financials and I will then touch on our recent acquisition of the development and commercial rights to another and psilocybin and database program for neuro degenerative indication.

It's all yours.

Thank you Sergio and good afternoon, everyone.

Today, we issued a press release announcing our business and financial results for the 3 and 6 months ended June 30th 'twenty 'twenty 1.

Which I will now review.

[laughter].

For the second quarter ended June 32021, total research and development expense was approximately $17.3 million.

As compared to $5.3 million for.

Sergio Traversa: Over 17 million individuals in the U.S. suffer from MTT, and there are currently limited therapeutic options to help this. Traditional antidepressants can take up to four or six weeks to show efficacy and have significant side effects. Moreover, approximately 65% of MDD patients do not respond well to the first antidepressant treatment, and approximately 30%..., of MDD patients do not respond to any of the current oral antidepressants. Adjunctive treatment options are crucial because they enable a change in therapy without requiring the significant time that SSRIs and other drugs require when switching agents due to withdrawal and other potential side effects.

And for the comparable period of 2020, the increase was primarily related to and increasing costs associated with the execution.

A broader clinical.

Program.

Well 10.17.

Total general and administrative expense for the second quarter ended June 30th 2021 was approximately $91 million as compared to $7.4 million for the comparable period of 2020.

This increase was primarily due to increases in personnel cost stock based compensation and consulting services.

Yeah.

For the second quarter ended June 30th 2021 we recorded a net loss of approximately $26.6 million or $1.56 per basic and diluted share compared to a net loss of $11.1 million or 73 cents per basic and diluted share in the comparable period of 2020.

Hmm.

Turning to the results for the 6 months ended June 30th 2021total.

Sergio Traversa: Despite these challenges, there are only three FDA-approved adjunctive treatments for major depressive disorder, and all three of them are antipsychotics. Based on its novel mechanism of action and the collective positive data generated to date, including phase two results that showed statistically significant, rapid, and sustained antidepressant effects with a favorable safety and tolerability profile. We believe REL1017 has the potential to be the first oral antidepressant FDA approved for adjunctive treatment of them.

Research and development expense was approximately $31.4 million as compared to $9.8 million for the comparable period of 2020.

Again, the increase was primarily related to an increase and costs associated with the execution of a bottle clinical program for well 10.17.

For the 6 months ended June 32021, general and administrative expense was approximately $17.5 million as compared to $12.9 million for the comparable period of 2020.

The increase was primarily due to increases in personnel cost stock based compensation and consulting services.

For the 6 months ended June 32021, we recorded a net loss of approximately $48.8 million or $2.90 per basic and diluted share from.

Sergio Traversa: I'm now passing the call over to Chuck for his review of the financials, and I will then touch on our recent acquisition of the development and commercial rights to a novel psilocybin and database program for neurodegenerative indications. Chuck?

Paired to a net loss of $21.8 billion or $1.45 per basic and diluted share and the comparable period of 2020.

On June 30th 'twenty, 'twenty, 1 and the company had cash cash equivalents and short term investments of $109.1 million compared to $117.1 million on December 31st 2020.

Chuck N: Thank you, Sergio. And good afternoon, everyone.

Chuck N: Today we issued a press release announcing our business and financial results for the three and six months ended June 30, 2021, which I will now review. For the second quarter ended June 30, 2021, total research and development expense was approximately $17.3 million, as compared to 5.3 million dollars for the Comparable Period of 2020. The increase was primarily related to an increase in costs associated with the execution of a broader clinical program.

We continue to expect that this strong cash position will support us through at least the multiple data readouts, we anticipate through the first half of 2020.2.

I will now hand, the call back to Sergio for his further remarks on the most recent progress Sergio.

Thank you Chuck.

And last month, we announced the acquisition of development and commercial rights to another silo side of it and the VIP program from Harbor mandates for all ex Asia territories, including the U S and Europe.

At this time and we'd have to bear with US we cannot share too much about the program for competitive reasons, but importantly, what we can share and said we'd program and will focus on neuro degenerative disorders and is distinct from and complementary to the real time 17 program.

Chuck N: [inaudible] Total general and administrative expense for the second quarter ended June 30, 2021, was approximately $9.1 million, as compared to $7.4 million for the comparable period of 2020. This increase was primarily due to increases in personnel costs, stock-based compensation, and consulting services. For the second quarter ended June 30, 2021, we recorded a net loss of approximately $26.6 million, or $1.56 per basic and diluted share, compared to a net loss of $11.1 million, or $0.73 per basic and diluted share, in the comparable period of 2020. Turning to the results for the six months ended June 30, 2021.

With this focus on and Psychiatry is agreement expand our development pipeline and in particular and Leverages, our core expertise and mechanism mechanism of neuroplasticity quite at the same time expand that we're working to indication outside of the price on and cytokines.

In summary.

Well it doesn't say 10, and 17 development program and remains on track and was recently further de risked by the results would be half Oxycodone study. They were consistent with our studies to date and confirmed the extensive body of literature, indicating the lack of abuse potential morale and 17.

Looking ahead, we anticipate multiple key data readouts over the next 12 months, and then and had it and potential long term growth driver with the acquisition and development of commercial rights to it and all of the silo Seidman and derivative program.

Chuck N: Total research and development expense was approximately $31.4 million, as compared to $9.8 million for the comparable period of 2020. However, the increase was primarily related to an increase in costs associated with the execution of a better clinical program for REL 1070. For the six months ended June 30, 2021, general and administrative expense was approximately $17.5 million, as compared to $12.9 million for the comparable period of 2020. The increase was primarily due to increases in personnel costs, stock-based compensation, and consulting services.

And importantly, as Chuck noted, how our robust R&D initiative are supported by a strong balance sheet.

In closing I remain grateful to the red mud and team for their continued hard work and dedication to executing nowhere and mission.

I would like to extend and also my sincere thanks to the participants and clinical partners involved as well.

And 17 clinical trials for their effort in advancing this important therapy and it sort of clinic and.

It's the dishes as possible will also like to thank Doctor go radetzky for being able to participate to the skulls and yeah total core Skus modeled day, well recognize authority in the old field, alright abuse, and the quality and so on and it would be it is a greater portion.

And if there is any question regarding our study debt to be addressed to doctors go on debt.

To get them educated.

And they're very critical and that's it.

We can now open the call for questions and operator can you. Please open up.

Chuck N: For the six months ended June 30, 2021, we recorded a net loss of approximately $48.8 million, or $2.90 per basic and deleted share, compared to a net loss of $21.8 billion or $1.45 per basic undulated share in the comparable period of 2020. On June 30, 2021, the company had cash, cash equivalents, and short-term investments of $109.1 million, compared to $117.1 million on December 31, 2020. We continue to expect that this strong cash position will support us through at least the multiple beta readouts we anticipate through the first half of 2022. I will now hand the call back to Sergio for his further remarks on the recent progress. Sergio?

Thank you well now begin the question and answer session Kimco and the question you May Press Star then 1 on your telephone and K pad.

He retired and I can only think the only class C. We didn't think it would take if I take out the handset my fault I think okay.

To withdraw your question. Please press star 2.

Your first question comes from Marc Goodman from Leerink.

Leerink. Please go ahead.

Okay.

Sergio can you remind us where the 55 sites are of reliance 1 just you know kind of break down and U S versus O U S and just give us a sense of whether everything's kind of moving forward. You know as you had planned I mean, obviously COVID-19 is.

Having some impact again on a bunch of clinical studies out there. So just curious how it's doing there.

And with your study.

And second.

Just curious are.

Are you working with the same people.

And S T E and the division and that you were working with at the beginning who signed off on your Phase III program and the reason I ask is we've had a couple of.

Setbacks recently and other companies and just you know sometimes it's because there's changes that FDA and so I'm, just just kind of checking the box, making sure there's no changes there.

Thank you Mark well the first part of your question, it's easy and the 55 sites and all in the U S. So we are you guys company, we have nothing no operational nothing outside of the U S. Except some collaboration with the way and I and universities like a Switzerland.

And I believe and Italy, too and so at the end.

But for development and then all the sites and the U S. A.

Sergio Traversa: Thank you, Chuck. Last month, we announced the acquisition of development and commercial rights to another phytocybin and derivative program from Arbor Mantis for all ex-Asia territories, including the U.S. and Europe. At this time, you will have to bear with us; we cannot share too much about the program for competitive reasons. But yeah, importantly, what we can share is that the program will focus on neurodegenerative disorders and is distinct from and complementary to the REL 1017 program, with its focus on psychiatry.

And how the study is going well and we started a few months ago and it is it is debt yep mm.

A large program we are actually running 4 different clinical trials and now that we have finished with the human abuse potential study. So it is a 2 phase III and there is a long term safety and then there is the monotherapy that just the start that the eighties and recruiting Oh, it will be more precise on the timing but.

Are you asking about the impact of Covid AR, we did not feel like the the D and any major complains of any major feedback from the sites about the about the impact of Covid. Nowadays the last few months has been pretty quiet now there is a little bit of research so yeah.

And we'd be more specific and that next 2 or 3 months, but you know straight answers debt.

We don't expect any major delay or any major impact from it from the Covid a lot of work is now a dawn on them.

Sergio Traversa: Unknown Speaker Disagreement expand our development pipelines and, in particular, leverages our core expertise in the mechanism of neural prosthesis while at the same time expanding our work into indications outside of depression and psychiatry. In summary, the RELTEN1017 development program remains on track and was recently furthered by the results of the HAP oxycodone study that were consistent with our studies to date and confirmed the extensive body of literature indicating the lack of abuse potential of RELTEN1017, and the team has anticipated multiple key data readouts over the next 12 months and has added a potential long-term growth driver with the acquisition and development of commercial rights to another si

Mostly like the interviews for the Mad Rush the day. They all you know most of them their dog remotely and both the operator on the readers and the patient and that's really like that they go on path to go to the hospital.

And I believe they go and how to study the only once a week for 4 weeks 4 visits and Dallas and yourself.

Taking your question on the F D I b.

<unk>.

You don't really know what happens on I believe you mentioned 2.1 must be a kid you and get on 1 it must be axiom and we don't really know what the specific oh, what a and b.

The way I can best answer the question is debt. The we do believe that these are specific topics related to the programs not the general like approach from the Psychiatry division and debt from our perspective, we.

We did not have any particular.

History with D. S P. A no delays no.

No no no question raised beyond the normal course of business. So we did not have any any of these issue or topic. So hawk clearly.

Sergio Traversa: Importantly, as Chuck noted, our robust R&D initiatives are supported by strong balance. In closing, I remain grateful to the Relmada team for their continued hard work and dedication to executing our mission. I would also like to extend my sincere thanks to the participants and clinical partners involved in the RELM-1017 clinical trials for their effort in advancing this important therapy through clinical trials as expeditiously as possible. I would also like to thank Dr. Gorodetsky for being able to participate in these calls, and Dr. Gorodetsky is one of the well-recognized authorities in the whole field of abuse and narcotics and so on.

We did about filing and NDA, yet so we cannot exclude everything and Lloyd blends and filed the NDA, So far and yeah, I would say, it's been pretty benign and.

And helping ourselves to develop these problem day, 1 thing that they clearly recognize there is an issue that there is a need.

And then Michele and and Charlotte.

They've been extremely cooperative.

And I hope I answered it ex.

All your questions satisfactory way thanks.

Thank you. Your next question comes from Andrea <unk> from Goldman Sachs. Please go ahead.

Hi, everyone. Thanks for taking the questions and I'll start you on maybe 1 for you and can you provide more color on the nature of your discussions with the FDA regarding reliance and he just wondering if this could be considered a registrational dataset and are you thinking that you would like to include the data within the initial filing package.

Sergio Traversa: And it is a great opportunity if there is any question regarding our study, to be addressed to Dr. Gorodetsky and to get an educated and very credible answer. We can now open the call for questions, and operator, can you please open it up?

And that's.

Thank you and debt.

For the question.

I have to be a little soft on this 1 because you know the abuse day at that they're very fresh and clearly a day well be yeah.

Do you have to be a we look at these data and we will provide them as soon as we have something that is reported on to the to the F. D. A to topline is not enough and yes. There is you know the the monotherapy, we don't have any data yet from the monotherapy. So it would be a little bit too aggressive too.

Operator: Thank you; we will now begin the question and answer session. To join the question queue, you may press start, then one on your telephone keypad. You will hear a tone acknowledging your request. If you are using a speakerphone, please pick up the handset before pressing any keys. To withdraw your question, please press start and two. Your first question comes from Mark Goodman from SVP Lyrinc. Please go ahead.

And you know 2 to go there I could do the F D a and to claim a policy and stocking tasty and and doing a registrational studies and trials, but we have now you know we have the they have studied we have your animal studies on the package the preclinical package and the special population is becoming a.

Marc Harold Goodman: Sergio, can you remind us where the 55 sites of Reliance One are, just, you know, kind of break down US versus US and just give us a sense of whether everything's kind of moving forward, you know, as you had planned? I mean, obviously, COVID is having some impact again on a bunch of clinical studies out there. So, just curious how it's going there with your study. And second, just curious, are you working with the same people at FDA in the division that you were working with at the beginning who signed off on your phase three program? And the reason I ask is we've had a couple of [inaudible] Just kind of checking the box, making sure there are no changes there. Thanks.

Pretty strong so yeah. It's a it's I cannot answer your question directly yet because I don't have the answer about the Oh, yes. There is a chance that the you know we we may.

And do something different from the monotherapy and to make it the radio stations and registration trial and the only difference would be to expand the number of patients, but it's a bit too early to be straight and I said, we will update everybody as soon as we get some certainty but.

But what we can and what we cannot do.

Yeah.

Okay. Thanks, so much.

Thank you. Your next question comes from Andrew Tsai from Jefferies. Please go ahead.

Okay, great. Thanks, and good afternoon, and maybe a question for Chuck Ah Ah you know our understanding is you know the eventual and scheduling and that's methadone or any drug out there and well boil down to the eighth after analysis. So I was wondering if you can talk about some of the I guess 7 other fab.

And there's what what are they and then as it relates to them talk about the strength of the data and evidence you've seen for S and methadone and as it relates to those factors and at the end of the day are these factors equally weighted or and does the abuse liability study carry more weight and then I have a follow up please.

Sergio Traversa: Thank you, Mark. Well, the first part of your question is easy. The 55 sites are all in the U.S., so we are a U.S. company. We have nothing, no operation, nothing outside of the U.S., except some collaboration with very high-end universities like in Switzerland and, I believe, Italy, too. And so, but, you know, for development and all the sites in the U.S. How is the study going? Well, we started a few months ago. It is, it is that, yep, a large program.

Yeah.

Yeah.

Chuck is all yours.

Chuck total desk.

Yep.

I don't have the 8 factors in front of me.

I think that they would put a good deal wait.

This points on this abuse liability study.

Probably the single most predictive kind of study that you could run to predict.

Predict before the drug gets on the market and what the abuses and local study and the preliminary data that we've seen so far the analysis looks very very positive.

Sergio summarized book.

Sergio Traversa: We are actually running four different clinical trials now that we have finished with the human abuse potential study. So there is a two phase three, then there is a long-term safety, and then there is the monotherapy that just started as recruiting. We will be more precise on the timing. But you're asking about the impact of COVID; we did not feel like there were any major complaints or any major feedback from the sites about the impact of COVID. Now, the last few months have been pretty quiet.

And I think that there's no specific 1 of the factors and F. D. A keys on to look at the whole picture to look at all of the data that we have but I think they'll put a good deal of weight.

And on a study like this 1 and it was going on.

Well done on its most recent methodology.

Statistical analysis follows all of the recommendations and the data looks very positive and it looks like this looks like a drug that has very low if any abuse liability and.

And it's certainly consistent with either no skilled cooling, which would be difficult because of international treaty obligations or very low level scheduling like and floral fonts.

Sergio Traversa: Now, there is a little bit of research to do. So, you know, we'll be more specific in the next two, three months. But, you know, the straight answer is that no, we don't expect any major delay or any major impact from COVID. A lot of work is now done remotely, like the interviews or Madras. They are all, you know, most of them are done remotely, and both the operator, the raters, and the patient actually like that they don't have to go to the hospital.

Makes sense, thanks and.

And my second question is I mean to your knowledge are there precedents, where I guess the highest dose of a drug has shown and I don't know 65 on Vas and ended up getting a favorable D. A scheduling and I know this is wrong to think about it but I just wanted to know if it's calm and I guess for a positive and abuse liability side, you said kind of <unk>.

L a and quote unquote shallow dose response positive, meaning that the drug ultimately got a favorable scheduling.

Oh handling and other yeah, and you know I think there are there are examples even within the opioids and there's certainly some examples with me and the anti epileptics.

Sergio Traversa: And I believe they go, in our study, only once a week for four weeks, so it's four visits to the hospital. I am taking your question on the FDA. We don't really know what happens. I believe you mentioned two. One must be a case, and the other one must be action.

And even on anti migraine drug where drug wear.

The drug is significantly different from a positive control as it was here with oxy Codell and they show a very slight.

Liking and even though it seems to be somewhat non specific so far.

And.

It might show some difference from placebo.

Sergio Traversa: We don't really know what the specifics are. The way I can best answer the question is that we do believe that these are specific topics related to the programs, not the general approach from the psychiatry division. From our perspective, we did not have any particular issue with the FDA, no delays, no questions raised beyond the normal course of business. We did not have any of these issues or topics so far. Clearly, we have not filed an NDA yet, so we cannot exclude everything. But so far, the FDA has been pretty benign in helping us to develop this program. One thing is that they clearly recognize that there is a need for an NDA. They've been extremely like corporate.

And still be he was already either on schedule again or smell its already low I mean like the drug and so that's.

Sabrina February.

So your hurdle wall, which didn't do indeed show significant differences.

And from placebo, even at the doses that were only 2 or 3 times.

Or above the recommended therapeutic dose and still wound up mcdonalds scheduled for.

So I think that there are certainly precedence.

Being a very low abuse potential and not necessarily absolutely zero.

And so and still be consistent with very low scheduling.

Thanks for all the color.

Okay. Yeah. Thanks question at turnkey and late from Trust Securities. Please go ahead.

Sergio Traversa: I hope I answered all your questions in a satisfactory way. Thanks. Thank you. Your next question comes from Andrea Tan from Goldman Sachs. Please go ahead.

Hi, Thanks for taking the question.

Where are you in terms of enrolment for the ongoing live items programs are are you on track to report topline data and first half of next year and we expect data from the buy and the week before of Alliance 1 and 2 so you know what does that mean and or we're getting beat up really early and extra or first quarter or 2.

Andrea R. Tan: Hi everyone. Thanks for taking the call.

Sergio Traversa: I have to be a little soft on this one because, you know, the abuse data are very fresh, and clearly, the FDA will look at this data and we will provide it to them as soon as, you know, we have something that is reportable to the FDA. The top line is not enough. And yes, there is, you know, the monotherapy. We don't have any data yet on monotherapy, so it would be a little bit aggressive to go directly to the FDA and to claim about the stock in phase 3 and do a registration trial.

But I would love to hear some color on that and then can you remind us what the design of rely on 3 is the doses and the study arms used and that study and that's a phase 2 correct.

Thank you John Yeah, I'll I'll answer and in the similar way the same way as the asset and Andrea F N B.

It's a bit too early to say how the recruitment is going back clearly recruit mi was maybe the the data point that would make them more.

Or because it is more of a clear and so has the number of sites and I have the number in front of me because I answered and to come prepared what they call. So we have a 52 sites are on on 301 is the first 1 and started now and then.

Sergio Traversa: But we now, you know, we have the HAP study, we have the animal study, so the package, the preclinical package, and the special population is becoming pretty strong, so I cannot answer your question directly yet because I don't have the answer, but yes, there is a chance that we may do something different from the monotherapy and make it a registration trial for what we can and what we cannot.

Late in December.

27 sites already act he got on branding and to you too and 10 sites and 3 to treat so he was he's probably smaller so it's a it's normal to have a smaller site number and ER and we also start to really recently, so I mean, the vast majority of decides they are up and running considered debt.

Good Paul.

Lin Tsai: Thank you. Your next question comes from Andrew Tsai from Jeffries. Please go ahead. Okay, great. Thanks. And good afternoon. Maybe I have a question.

Both of these sites they have shared.

Not many but some on and you're wanting to go to so and the size.

Finish the Oh reached the top of the number of patients that they can enroll and 3.1 day will dramatically switch to enrolling patient and 3 O..2 are the long term safety study, it's open and threw everybody and including new patients and 3 and 3 that is the mono therapy and the reason that we say.

Lin Tsai: Okay, great. Thanks, and good afternoon.

Chuck Gorodetsky: Maybe a question for Chuck. You know, our understanding is that the eventual scheduling of S-methadone or any drug out there will boil down to an eight-factor analysis. So, I was wondering if you could talk about some of the other seven factors. What are they? And then, as it relates to them, talk about the strength of the data and evidence you've seen for S-methadone as it relates to those factors. And at the end of the day, are these factors equally weighted, or does the abuse liability study carry more weight? And then I have a follow-up question, please. Thanks.

Hey that it will be.

And as before is that that would not make major comment on the number of patients because we are still and that thinking.

And the process and mode and ER and all should we be F. D. A to see how to maximize the the outcome and maximize the boswell debt trial. So we may expand the number of patients and make it a registration study as I mentioned due to Andrea and but there.

Chuck Gorodetsky: I don't have the eight factors in front of me, but I think that they would put a good deal of weight on this abuse liability study at this point. It's probably the single most predictive kind of study that you could run to predict before the drug gets on the market what the abuse is liable to be. And the preliminary data that we've seen so far in the analysis looks very, very positive, as Sergio summarized it. So I think that there's no specific factor that FDA keys on.

Reason that we believe we'd be finished early is that the recruitment all.

Naive patients or a piece of that and not currently on our anti depression, it's much faster.

Then that and as an adjunctive treatment is different.

Total call. It's exactly the same the only difference is that the the patient population, but clearly there are more patients that are.

Not on treatment and especially that are more willing to start with and then you want the depressant dentists and to add something to a current that depression. So it is related with day not on the number of patients, but he is related to the the speed of recruitment.

Chuck Gorodetsky: They'll look at the whole picture. They'll look at all of the data that we have. But I think they'll put a good deal of weight on a study like this one. It was done, it was very well done. It used the most recent methodology. The statistical analysis follows all of the recommendations. And the data looks very positive. This looks like a drug that has very low, if any, abuse liability.

Oh, Yes, my answer is satisfactory.

Yeah, Yeah, and just maybe an update on day, 1 and I don't.

On this.

Got it and then 4 as a monotherapy.

And it's possible that you might want to consider a higher dose or is higher dose still not really useful and year over year 20.

And 25 milligrams.

And.

Yeah, Thanks, John and I use the same dose is the same profitably that weighted.

Unknown Speaker: [inaudible]

And with the difference and patient population, 2 antibody and milligrams and we don't get all the data from the very early animal studies to the phase 2 and 25 milligrams is the optimal dose and it's probably not very different from the 50 milligrams and turn them on efficacy and side effect and the reason that the 25.

Unknown Speaker: All scheduling like in 405.

Unknown Speaker: Where I guess the highest dose of a drug has shown, I don't know, 65 on VAS and ended up getting a favorable DEA scheduling? I know this is wrong to think about, but I just want to know if it's common, I guess, for a positive abuse liability study to kind of show a quote unquote shallow dose response, a positive meaning that the drug ultimately got a favorable DEA scheduling.

He is not because of total IBD safety or is just the real reason is to reduce the tab.

The placebo effect less harm less placebo effect, so using only the 25 and you only have 2 arms. It is minimal placebo effect and thermal number arms that'd be going ahead, and adding the 50 and we don't believe.

Unknown Speaker: Well, handling that again, you know, I think there are examples, even within the opioids. And there's certainly some examples, I mean, the anti-epileptics and even an anti-migraine drug where the drug is significantly different from the positive control, as it was here with oxycodone. It may show a very slight liking, and even that seems to be somewhat nonspecific so far, and might show some difference from placebo. And still be either on schedule again or schedule very low, I mean, like the drug Faberge.

Good of inquiries, the placebo effect, but and would not there and improve.

Improve or increase.

The efficacy of the drug.

That's the real reason and choosing and twenty-five and and these across the board all the trials and they use 25.

Got it and thanks, so much from Carla.

And Holistically.

Yeah.

Thank you. Your next question is from Jay Olson from Oppenheimer. Please go ahead.

Oh, Hey, congrats on the progress and thanks for taking the question have you seen any published reports of increasing diagnosis rates for M. D. D. During the pandemic and have you seen any differences between the baseline characteristics of pace.

Unknown Speaker: Dr. David L. Fischer, MD, M.D., M.D., M.D., M.D., M.D., M.D. So I think that there are certainly precedents for there being a very low abuse potential, but not necessarily absolutely zero, and it still being consistent with very low scheduling.

Patients enrolled and your studies versus previous M. D. D clinical trials and then I had a separate question if I could.

Yeah, well, thanks, Jay and thanks for the question and.

On the if we Havent been reported there are things that somebody that we just you know and.

Unknown Speaker: be consistent with very low scheduling.

Smoke on on the call probably something on day.

Operator: Thank you. Your next question is from June Lee from Trust Securities. Please go ahead.

Very big increase in number of patients diagnosed for depression.

June Lee: Hi, thanks for taking our question. Where are you in terms of enrollment?

And that and so it needs a yes there.

And that reports out that showed that there is an increase up to like 400% that's hard to believe but I.

Unknown Speaker: and others. Thank you for joining us. Thank you.

Sergio Traversa: Are you on track to report top-line data in the first half of next year? And you expect data from Reliance 3 before Reliance 1 and 2. So, you know, what does that mean? Are we getting data really early next year, or first quarter, or second quarter? Love to hear some color on that. And then can you remind us what the design of Reliance 3 is?

I read that number somewhere.

In terms of the nature of the depression related with the and EMEA and we don't I don't really see the patient profiled and enrolled and.

And and so that's when I would pass on it.

And we have criteria for inclusion and exclusion and.

And debt I don't believe that related with that and EMEA or not and somebody I don't I don't know if there has been a change in how the profile with the depressed patient no change with that with the pandemic I assume probably some you know some relation between the pandemic and then some.

Unknown Speaker: the design of Reliance 3, the doses and the study arms used in that study, and that's phase 2.

Sergio Traversa: Thank you, John. Yeah, I'll answer in a similar way, the same way as Andrea Tan.

Yeah manifestation of depression, and must be economic crises and jobs and so they all have an impact.

Sergio Traversa: It's a bit too early to say how the recruitment is going, but clearly, recruitment was maybe the data point that would make more sense because it is a clearer answer, the number of sites. And I have the number in front of me because I answered and came prepared for the call. So we have 52 sites on 301, the first one started very late in December; 27 sites already active, up and running in 302, and 10 sites in 303.

And then I do believe that are actually read it at and believe it debt COVID-19 itself.

Virus has an impact on the brain and day, there could be some post COVID-19.

The non like non job related effect, but the volume should be hated effect on that on the on.

On the <unk>.

How did the press patients shows these symptoms, but none of them.

And I would love to be able to give you a more specific question, but I was on that I don't really see D. The patient profiles and feature dark.

Sergio Traversa: So 303 is probably smaller, so it's normal to have a smaller site number, and we also started very recently. So I mean, the vast majority of the sites that are up and running consider that a good part of these sites is shared.

The old.

Okay, great. Thank you and then could you talk about the differences between the Gaba and NMDA.

Mechanisms and since both appear to provide.

Rapid onset of efficacy and M D D and what would cause a physician to prefer 1 mechanism versus the other and M. D D.

Sergio Traversa: Not many, but some on 301 and 303. So when the sites finish or reach the top of the number of patients that they can enroll in 301, they will automatically switch to enrolling patients in 303. The long-term safety study is open to everybody, including new patients. And the 303, that is the monotherapy, the reason that we say that it will be finished before is that I would not make a major comment on the number of patients because we are still in that thinking process and mode and also with the FDA to see how to maximize the outcome and maximize the value of that trial.

Yeah, Yeah, Yeah, that's it and it's also very good crashed and well yeah. The Dan.

And then kind of.

And going toward the same direction D, but from opposite the opposite the site right really 1.1 is and activates and the other was an inhibitor.

So it's a it is how do you see.

They are different and some on mechanism probably and this is just looking at the data available probably the biggest difference and what we believe.

Physicians would prefer to be and M. D. A mechanism is that you know them and D E tends to.

That being stable or improve the efficacy overtime, but the government does the opposite.

And then in Saudi and if it's true and the F. D. A strongly believe that the.

The <unk>.

Depression is a chronic illness.

And do you want to have a drug that you can take for a long time and from a safety, but also debt.

Sergio Traversa: So we may expand the number of patients and make it a registration study, as I mentioned to Andrea. But the reason that we believe it will be finished early is that the recruitment of naive patients or patients that are not currently on antidepressants is much faster. They are not on treatment and are especially more willing to start with a new antidepressant, then to, you know, add something to the current.

Keep the epic is to increase the efficacy overtime.

Great and I'm, sorry, you're asking a question.

Yeah, that's perfect. Thank you.

Thank you. Your next question it's on.

And that's all from Guggenheim Securities.

Go ahead.

Hey, guys. This is Eddie on for you out and thanks for taking the questions. So can you give us a little.

And more sense of how the alliance trial is powered specifically on the placebo arm sort of how you're modeling and what a placebo effect could be here and whatever.

Sergio Traversa: So it's related to the, not the number of patients, but it's related to the speed of recruitment. Oh, yeah, my answer is satisfactory. Yeah, yeah, we'll update on that as well. And then, as monotherapy, do you think it's possible that you might want to consider higher doses?

And then.

Right.

Okay.

Yeah.

All right.

Okay.

And why.

Yeah.

Hold on.

Yeah.

Hum.

Okay.

Hi, Eddie.

Okay.

Yeah.

Unknown Speaker: Uy Ear, Unknown Executive, Lin Tsai, Yatin Suneja, Guofang Li, Sergio Traversa, Timothy Yeah, thanks, John.

Okay.

Okay.

And Andy I don't know if it's just me, but I only caught he had the first like 22nd of your question and you hear me better known and Paula.

And it's much better much better.

Unknown Speaker: [inaudible] Yeah, thanks, John. No, he's the same dose. It's the same protocol, with the difference in patient population. 25 milligrams. If we look at all the data from the very early animal studies to phase two, and 25 milligrams is the optimal dose, it's probably not very different from 50 milligrams in terms of efficacy and side effects. The reason that the 25 is not because of tolerability or safety, or it's just the real reason to reduce the placebo.

Yeah, Okay, Yeah, what can this health crisis and the borrower yeah, Yeah sure I'd be happy to do that so as you know.

And you definitely and remember the phase II data and get the and the effect size. It was something around 0.70.0.9.

And I assume that throws that philosophy and that they work with us and effect size about 0.3 and it got approved.

So yeah on the effect size in a all right then and 17 was yeah kind of 3 times what flow.

And because I think that clearly.

Clearly the phase 2 so we don't want to although we believe we are at an extremely effective drug and we didn't want to take too much freight. So we make it very concerned with the assumption in the phase III programs across the board a rule of thumb coming from the expertise T. You lose about 25.

Unknown Speaker: Less arms, less placebo effect. So using only the 25, you only have two arms; that is the minimal placebo effect in terms of the number of arms that we can have. And adding the 50, we don't believe could have increased the placebo effect but would not have improved or increased the efficacy of the drug. So that's the real reason for choosing 25, and it is across the board. All trials use 25.

Percent of effect size. When you go from phase 2 to phase 3 for a variety of reason that clearly are these.

And loss of effect size can be modulated and it can be adjusted EBITDA using for example, like having.

Operator: Thank you. Your next question is from Jay Olsen from Oppenheimer. Please go ahead.

Only 2 arms instead of 3 and phase 3 versus phase 2 so that clearly.

Jay Olsen: Oh, hey, congrats on the progress and thanks for taking the questions. Have you seen any published reports of increasing diagnosis rates for MDD during the pandemic? And have you seen any differences between the baseline characteristics of patients enrolled in your studies versus previous ones?

And it makes it should make it and.

And my take on different but even assuming the.

And the some loss all the effect size, we want you to be concerned with you. So we India assumptions statistic I would assume that we'd have about half.

And the effect size that we hadn't and phase 2.

Sergio Traversa: Yeah, well, thanks, Jay. Thanks for the question. The if we have been reported, I think somebody that we just spoke to on the call published something on the very big increase in the number of patients diagnosed with depression. And so it's, yes, there are reports out that show that there is an increase up to like 400%. It's hard to believe, but I read that number somewhere. In terms of the nature of the depression related to the, you know, the pandemic, we don't, I don't really see the patient profile; they are enrolled. And, and so that's when I would pass.

Okay.

Gotcha.

Moving to digital and 2.5 because you're looking for.

That should be moving.

And doesn't start with you.

Okay, and then on the monotherapy study like I said on these naive patients or is there a certain washout period before their last sort of treatment of anti depressants.

Yeah.

And I believe mostly that and naive I do believe they're allowed to and I don't remember the exact how much time they have to have to pass before they can get into the trial, but there is a considerable amount of time, a wash out before they can get into the trial as you know it has now is now well known.

On the maritime and when I was working on through walks it and it was not known but it says from ice to have a pretty significantly probable effect.

So the last thing you want to do is to have a patient's debt. It's not only depressed he gets into with the withdrawal effect from headset and so right. So I believe you and I don't remember I can't give you the exact number offline, but it's not a week or 2 it's like 3 months or something like that.

Sergio Traversa: We have criteria for inclusion and exclusion, and I don't believe they're related to the pandemic or not. So I don't know if there has been a change in how the profile of the depressed patient changed with the, with the pandemic. I assume probably some, you know, some relation between the pandemic and some, you know, manifestation of depression, the mask. You know, economic crises and jobs, and so they all have an impact, and then I do believe that, I actually read it, more than believe it, that COVID itself, the virus has an impact on the brain.

Oh 2 months.

And then they have to be clean and not taking any antidepressant before it to get it.

Thank you.

And it does conclude the question and answer session I would like to turn the conference that day that you said you know what your desktop and he put.

And we're not.

Well. Thank you operator, thank you all and.

For joining us on the call today, and we have maybe.

I've been pleased and we are pleased to share on recent progress with you and there rather than 17 cleaning and clinical development program and continues to advance.

Sergio Traversa: And there could be some post COVID, not like a non job-related effect but a virus-related effect on the on the How did the depressed patient show his symptoms? But I would love to be able to give you a more specific question, but I don't I don't really see the patient profile of the patient involved. Okay, great. Thank you.

We are excited about important catalyst that lie ahead of us and we'll keep you updated on clinical readout and activity through the remainder of 2021. Thank.

Thank you again for joining us on the call and enjoy the rest of day day. Thank you.

Thank you and this does conclude the conference for today. Thank you from participating you may now disconnect.

Sergio Traversa: And then, could you talk about the differences between GABA and NMDA mechanisms since both appear to provide rapid onset of efficacy in MDD and what would cause a physician to prefer one mechanism versus the other in MDD? Yeah, that's also a very good question. Well, yeah, they end up kind of going toward the same direction, but from opposite sides, right?

Yeah.

Okay.

Yeah.

Yeah.

Yeah.

[music].

Okay.

[music].

Yeah.

Yeah.

Yeah.

[music].

Yeah.

Unknown Speaker: I believe one is an activator and the other one is an inhibitor. So it is pretty different in terms of mechanism. Probably, This is just looking at the data available. Probably the biggest difference between what we believe and what we think. Physicians will prefer the NMNDA mechanism is that the NMNDA tends to be stable or improve efficacy over time while the GABA does the opposite. And so, if it's true and the FDA strongly believes that the... Depression is a chronic illness; then you want to have a drug that you can take for a long time in terms of safety, but also that keeps the efficacy or increases the efficacy.

Yeah.

[music].

Okay.

Yeah.

Uh huh.

Uh huh.

Uh huh.

Okay.

Yeah.

Uh huh.

Uh huh.

Uh huh.

Okay.

Okay.

Yeah.

Okay.

Okay.

Yeah.

And.

Yeah.

Yeah.

[music].

Unknown Speaker: [inaudible]

Yatin Suneja: Thank you. Your next question is from Yatin Suneja from Guggenheim Security. Please go ahead. Hey, guys, this is Eddie. I'm...

Yatin Suneja: Hey guys, this is Eddie Onfrey Yatin. Thanks for taking the questions. So can you give us a little more sense of how the Reliance trial is powered? Specifically, on the placebo arm, sort of how are you modeling what a placebo effect could be here and what are the [inaudible] I'm going to call you in a few minutes, so if you want to come back, and let's get going

Okay.

[music].

Unknown Speaker: Eddie, I don't know if it's just me, but I only could hear the first like 20 seconds of your question. Can you hear me better now? Yes.

Unknown Speaker: Yeah, I can ask the question about power. Yeah, yeah, sure. I'll be happy to do that.

Sergio Traversa: So, as you definitely remember the phase 2 data, the effect size was something around 0.7, 0.9. I assume that the fluoxetine that I work with has an effect size of about 0.3, and it got approved. So, you know, the effect size of REL1017 was, you know, kind of three times what fluoxetine has. Clearly, it's a Phase II, so we don't want to, although we believe we have an extremely effective drug, we don't want to take too much risk, so we make a conservative assumption in the Phase III program across the board.

Yeah.

Yeah.

[music].

Yeah.

[music].

Sergio Traversa: The rule of thumb, coming from the expert, is you lose about 25% of effect size when you go from Phase II to Phase III for a variety of reasons, but clearly, this loss of effect size can be modulated, and it can be adjusted using, for example, like having... [inaudible] the effects side that we had.

Sergio Traversa: 0.7 to 0.35 to 0.4. That should be the idea. That's what I was trying to say. That's what I was trying to say.

Unknown Speaker: And then on the monotherapy study, like I said, are these nave?

Sergio Traversa: I believe they are mostly naive. I do believe they are allowed to. I don't remember how much time they have to pass before they can get into the trial, but there is a considerable amount of time for washout before they can get into the trial. As you know, it is now well known that my time when I was working on fluoxetine was not known, but SSRIs. They So the last thing you want to do is to have a patient that is not only depressed, but he gets into withdrawal effects from SSRIs.

Yeah.

Yeah.

[music].

[music].

Hum.

Hmm.

Yeah.

Hum.

And.

Hum.

And.

[music].

Sergio Traversa: So I believe in that. I don't remember. I can give you the exact number offline, but it's not a week or two; I believe it's three months. Andrea Tan, Yatin Suneja, Guofang Li, Sergio Traversa, Timothy McCarthy, Relmada, Yatin

Operator: Thank you. This does conclude the question and answer session. I would like to turn the conference back over to Sergio Traversa for any closing remarks.

Sergio Traversa: Well, thank you, operator. Thank you all for joining us on the call today. We are pleased we have been able, and we are pleased to share our recent progress with you and, you know, the BREL-1017 clinical development program. It continues to advance.

Operator: We are excited about the important catalysts that lie ahead of us and will keep you updated on clinical results and activity through the remainder of 2020. Thank you again for joining us on the call. Enjoy the rest of your day. Thank you. Thank you. This does conclude the conference for today. Thank you for participating. You may now disconnect.

Unknown Speaker: Music Music Music Music Music Music Music Music Music Music Andrea Tan, Uy Ear, Unknown Executive, Lin Tsai, Yatin Suneja, Guofang Li, Sergio Traversa, Timothy McCarthy, Relmada, Yatin Suneja, Guofang Li, Sergio Traversa, Timothy McCarthy, Relmada, [inaudible] [inaudible] It's Excellent to Have You Back! It's Excellent to Have You Back! It's Excellent to Have You Back!

Yeah.

[music].

Unknown Speaker: Andrea Tan, Uy Ear, Unknown Executive, Lin Tsai, Yatin Suneja, Guofang Li, Sergio Traversa, Timothy McCarthy, Relmada, Andrea Tan, Uy Ear, Unknown Executive, Lin Tsai, Yatin Suneja, Yatin Suneja, Guofang Li, Sergio Traversa, Yatin Suneja, Guofang Li, Yatin Suneja, Guofang Li, Goodman, Uy Ear, Unknown Executive, Lin Tsai, Yatin Suneja, Guofang Li, Sergio Traversa, Yatin Suneja, Guofang Li, Sergio Traversa, Yatin Suneja, Guofang Li, Sergio Traversa, [inaudible]

Yeah.

[music].