Q4 2020 Relmada Therapeutics Inc Earnings Call
[music].
Greetings and welcome to the realm of of Therapeutics incorporated.
Operator: Welcome to the Relmada Therapeutics Inc. 4th Quarter and Full Year 2020 Financial Results Conference Call. At this time, all participants are in a listen-only mode. A question and answer session will follow the formal presentation. If anyone should require operator assistance during the conference, please press star zero on your telephone keypad. Please note this conference is being recorded. I will now turn the call over to your host, Tim McCarthy.
Weighted fourth quarter and full year 2020 financial results conference call. At this time all participants are in a listen only mode. A question and answer session will follow the formal presentation. If anyone should require operator assistance. During the conference. Please press star zero on your telephone keypad. Please note.
This conference is being recorded I will now I'll turn the call over to your host Tim Mccarthy. Please go ahead.
Timothy McCarthy: Thank you, operator. And thank you all for joining us this afternoon.
Thank you operator, and thank you all for joining US. This afternoon with me on today's call are Chief Executive Officer, Dr. Sergio Theresa.
Timothy McCarthy: With me on today's call are our Chief Executive Officer, Dr. Sergio Traversa, Chief Financial Officer, Maged Shenouda, and Chief Accounting and Compliance Officer, Chuck Enns. This afternoon, Relmada issued a news release providing a business update and announcing financial results for the fourth quarter and full year ended December 31st, 2020. Please note that certain information discussed on the call today is covered under the Safe Harbor provision of the Private Securities Litigation Reform Act.
Financial Officer magazine, Duda, and Chief accounting and compliance officer.
Our trucking on.
This afternoon from out of issued a news release, providing a business update and announcing financial results for the fourth quarter and full year ended December 31, 2020.
Please note that certain information discussed on the call today is covered under the safe Harbor provision of the private Securities Litigation Reform Act.
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 and subsequent filings. This conference call also contains time-sensitive information that is accurate only as of the date of this live broadcast, March 23rd, 2021. Relmada undertakes no obligation to revise or update any forward-looking statements to reflect events or circumstances after the date of this conference call. Now, I'd like to turn the call over to Sergio. Sergio?
We caution listeners that during this call from out of the management team will be making the forward looking statements.
Actual results could differ materially from those stated or implied by these forward looking statements due to the risks and uncertainties associated with the company's business.
These forward looking statements are qualified by the cautionary statements contained and real.
<unk> press release issued today, and the company's SEC filings, including and the annual report on form 10-K and subsequent filings.
This conference call also contains time sensitive information that is accurate only as of the date of this live broadcast March 23 2021.
The amount of undertakes no obligation to revise or.
Or update any forward looking statements to reflect events or circumstances. The answers. After the date of this conference call.
Now I'd like to call and I'll turn the call over to Sergio Sergio.
Yeah.
Sergio Traversa: Thank you, team, and good afternoon to everyone.
Thank you team and good afternoon to everyone.
Sergio Traversa: I'm very pleased to welcome you to Relmada's first ever earnings conference call. We do believe that the company has reached a maturity time that is a good time, the right time, to have a call. And since we expect a significant number of near-term catalysts moving forward, we intend to host update calls on a quarterly basis. The plan for today, because this is our first earnings call, and some of the people connected may not be very familiar with the company, I will begin with a brief overview of Relmada, our promising lead product candidate for the adjunctive treatment of depression, REL1017, and the large market opportunity that we are targeting.
And I'm very pleased to welcome you to read them out of the first ever.
Earnings Conference call and we do believe that the company has reached and maturity.
And the time debt is a good time of the right time to have a cold and the since we expect the sort of significant.
The significant number of near term gasoline and moving forward, we intend to host the update calls on the quarterly basis.
The plan for today, because this is our first earnings call and some of the people connected and made it may not be very familiar with the company I will begin with the brief overview of the mob.
The promising lead product candidate flow the adjunctive treatment of the question well 10 17.
And the large market opportunity that we are targeting.
Sergio Traversa: I will then turn the call over to Maged for his review of our financials, and after that, I will provide an update on our most recent accomplishments and a review of upcoming milestones, and do my best to leave as much time as possible for your questions.
And then turn the call over to Magnus we used to view of our financials, the and depth of debt I will provide an update on our most recent accomplishment and a review of upcoming milestones and the do my best to leave as much time as false and both flora for your questions.
Sergio Traversa: As a brief background on how we arrived at this critical point in our corporate evolution, Relmada is a late-stage central nervous system, CNS company, focused on the development of REL1017, which has the potential to address the significant medical needs of major depressive disorder, MDD. There are about 17 or more million people in the US who are affected by MDD, and they have limited safe and effective therapeutic options. A standard antidepressant can take up to four to six weeks to show efficacy, and up to 65% of patients do not respond or do not respond well to their first antidepressant treatment, and there are about 30% of patients that don't respond to four different antidepressants. REL1017 has been developed as a new chemical entity that is orally administered as a once daily pill. We have patent protection up to 2033, with additional patent files that could extend the exclusivity to 2038 and beyond.
Is the is a brief background on how we arrived at this critical point you know of.
But the evolution there.
Well now that he's the late stage central nervous system CNS company focus on the development of residence of intake which is.
And the potential to address the significant.
The significant unmet medical needs of major depressive disorder and D D day.
And about 17 or more.
The median people and the U S. The affected by MTV and they had a limited safe and effective therapeutic options.
Our standard antidepressant can take up to four to six weeks to show efficacy and the.
Up to 65% of the patients do not respond the do not respond well to the first time through the price on treatment and.
And there are about 30% of the patients that don't respond up too.
The four different FMC depressed and treatment.
Resident and 17 is being developed as the new chemical entity and it's orally administered as a once daily pill.
We have patent protection up to 2033 with the additional patents filed that could extend exclusivity to 2000 and put through 'twenty.
Sergio Traversa: We have over 50 issued and filed patents for REL1017 and fast-track designation for the adjunctive treatment of MDT. So, based on the novel mechanism of action and phase two data that showed statistically significant rapid and sustained antidepressant effects with a favorable safety and tolerability profile, we do believe that REL1017 has the potential to be the first FDA-approved antidepressant for the adjunctive treatment of MDT. In the phase two study, REL1017 achieved statistically significant significance compared to placebo on all evaluated efficacy measures.
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Well the 50, it shouldn't filed patents for wealth and 17 and fast track designation for the adjunctive treatment of MDC.
And based on the novel mechanism of action and the phase II data that showed statistically significant rapid.
Rapid and sustained anti depressant effect with the favorable safety and Tolerability profile and we do believe that well 10 17 has the potential to be the first FDA approved anti depression for the adjunctive treatment of the MDT.
In the phase two study of <unk> 10 17 of.
Achieved statistically significant.
The significance compared to placebo and all evaluate the debt because of admission.
Sergio Traversa: Specifically, there were solid effects we observed on the Madras scale, that is a well-established measure of the severity of depression, with p-values below 0.03, and a large effect size, 0.7 to 1, from day 4 to day 14. The extended efficacy up to 14 days was well beyond the seven days of dosing in the study. And it may suggest potential neuroplasticity and synaptogenic efficacy. Very importantly, there were no notable adverse events observed in the trial, with no evidence of treatment-induced dissociative psychotomimetic effects or opioid withdrawal symptoms.
Specifically.
The solid effects, we observed on the matter of scale that these are well established measure of the severity of depression with P values below on the.
Okay, and the large effect size zero point and seven up two one from the four two day 14, the extended the efficacy up to 14 days was well beyond the seven days of dosing and the stuff and.
It may suggest the potential of Neuroplastic and see and up the journey effect.
Very importantly.
And there were no notable adverse events observed and the trial with no evidence of treatment and use the social at the site that the medical opioid withdrawal.
Symptoms.
Sergio Traversa: In December last year, we initiated Reliance One, which is the first trial in our phase three program of REL 1017 for the adjunctive treatment of depression. I will review the ongoing phase 3 program and discuss the upcoming milestone shortly. But before I do that, I will turn the call over to Maged for his review of the finances. Haggerty's all yours. Thank you, Sergio. And good afternoon, everyone.
In December of last year, the initiate the reliance one debt. These the first two.
And that of our phase III program.
And 17 for the adjunctive treatment of Depression, I will review of the ongoing phase III program and discuss the upcoming milestones shortly but before I do that I will turn the call to over to Maggie who is the view of the financial.
And that is all yours.
Thank you Sergio and good afternoon, everyone today we.
Maged S. Shenouda: Today, we issued a press release announcing our business and financial results for the fourth quarter and full year ended December 31, 2020, which I will now review. For the fourth quarter and year ended December 31, 2020, total research and development expense was approximately $14.9 million and $36 million, respectively, as compared to $1.6 million and $7.9 million for the same period in 2019. The increase was primarily related to an increase in costs associated with the execution of a broader clinical program for REL 1070. Total general and administrative expense for the fourth quarter and year ended December 31, 2020 was approximately 6 million dollars and 24 million, and 24.9 million dollars, respectively, as compared to 2.9.
The press release announcing our business and financial results.
For the fourth quarter and full year ended December 31, 2020, and we'll try and I will now review.
For the fourth quarter and year ended December 31, 2020, total research and development expense was approximately $14 9 million and $36 million.
You should of particularly as compared to $1 6 million and $7 9 million for the same periods and 2019 the.
The increase was primarily related to an increase and costs associated with the execution for a broader clinical program for rock Tenn and 17.
Total general and administrative expense for the fourth quarter.
Respect year ended December 31, 2020 was approximately $6 million and 24 million $24 $9 million respectively.
As compared to $2 nine and two.
Maged S. Shenouda: 2.9 million and 7.2
And $2 9 million and $7 2 million for the same periods of 2019 the.
Maged S. Shenouda: For the fourth quarter and year ended December 31,
Increase was primarily due to an increase.
Maged S. Shenouda: We recorded a net loss of approximately $20.8 million, or $1.28 per billion.
Allergies and stock based compensation.
For the fourth quarter and year ended December 31, 2020, we recorded a net loss of approximately $28 million, the $1 28 per basic and diluted share and $59 5 million or $3 and 36.
Maged S. Shenouda: for $1.28 per basic and diluted share and $59.5 million, or $3.81 per share, basic and diluted, respectively, compared to a net loss of $4.5 million, or $0.40 per basic and diluted share, and $15 million, or $1.62 per basic and diluted share, for the same periods. At December 31, 2020, the company had cash, cash equivalents, and short-term investments of $117.1 million, compared to $1 We expect a strong cash position to support us through at least multiple data readouts we anticipate through the first half of 2022. I will now hand the call back to Sergio for additional remarks. Thank you, Maged.
Accuse.
And $3 81 per share basic and diluted respectively compared to a net loss of $4 $5 million or <unk> 40 per basic and diluted share and $15 million of $1.62 per basic and diluted share and the same periods of 2019 at.
At December.
The 31 and 2020, the company had cash cash equivalents and short term of investments of $117 $1 million compared to $116 $4 million at December 31, and 2019, we expect the strong cash position to support us through at least multiple data readouts.
We anticipate through the first half of 2022.
I'll now hand, the call back to Sergio for additional remarks Sergio.
Thank you Mike.
Sergio Traversa: As we had a recent announcement a bit last week, I would like to start with an update on the Human Abuse Potential, or HAP, studies. We recently announced that the Early Discontinuous Study 120, which was assessing REL17 lycin versus oral ketamine as an active component. As a pre-planned and blinded analysis of the initial study completers, by representing approximately 20% of the planted 40 patients, showed that a large percentage of these patients did not separate oral ketamine from placebo, which we believe was due to the poor bioavailability of oral, Very important, no dissociative or psychotomimetic events were observed in any of the treated subjects in all art, to avoid futility, we discontinue this study and we will submit a new study design protocol to the FDA within the next month and proposing an intravenous ketamine as an active comparator that has a very established, very good and established history as an effective positive comparator.
And as we had the recent announcement that'd be the last week and would like to start the with an update on the human abuse potential or.
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And we recently announced that the early reads from the senior study of 120, which was the assessing rose 17 liking versus oral care at the mean as an active control is.
Is it.
The Preplanned and blinded analysis of the initial study complete theirs.
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And the percent of the planned at 40 patients showed that the large percentage of these patients did not separate all of the cats I mean from placebo, which we believe was due to the poor bioavailability of oral care of them.
The important no the social people of psychotomimetic events were observed in any of the treat the.
The prostate subject in all of ours.
Two of them to avoid the futility and we discontinued the study and we will submit the new study design and protocol to the FDA within the next months and proposing and intravenous cash I mean as an active comparator that there is the V establish and very good and the.
Established history, as the and effective positive control.
Sergio Traversa: We anticipate the top-line data from the IV ketamine control study by the end of the year. Again, we would like to emphasize that neither in the discontinued study, nor in the previous clinical studies in our program, or historically in existing literature, S-methadone has been associated with any psychotomimetic, albutinogenic effect, and we are encouraged by the confirmatory aspects of these results. The HAP study 124 that is comparing RAL1017 to oxycodone continues as planned, and we will expect top-line data from this study by the end of the second quarter.
And we anticipate the top line data from the IV Ketamine and controlled study by the end of the D. C and again, we would like to underscore the neither in the discontinued study, noting the previous clinical studies, and our program or historically and existing.
And the nature to them.
S method the has been associated with any psychotomimetic, I would say Nokia and its effect.
And we are encouraged by the confirmatory aspects of these results.
The Hap study, one and 24 that is comparing rather than 17. The oxycodone continues as planned and we will.
Expect topline data from the study by the end of the second quarter.
Sergio Traversa: This HAP study will be important in supporting the NDA submission for REL 1070, specifically for the FDA evaluation and the DEA determination of sclerosis. But it will also represent an important opportunity to add to the existing strong body of literature that clearly differentiates REL1017 from methadone and any perceived association with dissociative symptoms or opioid effects. I will now share the key aspect of Reliance.
These hap study would be important and supporting the NDA submission for <unk> sensitive.
And specifically for the FDA evaluation and the DEA determination of scheduled but the real also represents an important opportunity to add to the existing.
And somebody of the Swiss or debt clearly the fantasy real 10, 17 from messaging and Amy perceived Association.
These symptoms for opioid effect.
I will now share the key aspects of will rely on the city's our phase III program from a rail consider and seed.
Sergio Traversa: It is our phase 3 program for wealth and civility. The pivotal studies, Reliance 1 and 2, consist of two sister two-arm placebo-controlled trials that include 364 patients per study across 55 sites. These studies will evaluate 25 milligrams of REL1017 and placebo on top of the patient's existing antidepressant. These are patients who have failed to respond to minimum one up to three previous courses of antidepressant therapy in the current depression epidemic. The primary endpoint of this trial is changing the MAZDA score at day 28. Key secondary endpoints include change in Maslow's score at day 7 and CGI's score at day 28.
Both of those studies rely on this one and to consist of two system two arm placebo controlled trial that include 364 patients. The first study across 55 site.
These studies will evaluate 25 milligram of relevance of Athene and placebo on top of the patient thinks.
The antidepressant treatments.
These are patients who have failed to respond to a minimum one up to three previous courses of antidepressant therapy in.
And the current the.
Fresh and three episodes.
The primary endpoint of this trial and these changing mazo score at day 28, Keith.
Key secondary endpoints.
The change in matter of score at day, seven and CGI S score at day 28 20.
Sergio Traversa: We believe that our phase three program is optimized to reduce the placebo effect risk based on the design of the two-arm study, the strong focus on site selection and their training, and the multiple levels of screening to ensure accurate patient diagnosis. Our first phase 3 trial, Reliance 1, is enrolling as expected, and sites have come online nicely. We continue to anticipate top-line data from Reliance 1 in the first half of 2022.
We believe that our phase the program is optimized and we use the placebo effect risk based on the design is the two arm study the strong focus on site selection and the training and.
And through multiple levels of screening to ensure accurate patient diagnosis.
Our first phase III trial of reliance one isn't moving as expected the sites.
Come on line nicely.
We continue to anticipate the topline data from live on reliance one and the first half of 2020 true.
Sergio Traversa: The second phase 3 trial, Reliance 2, is a mirror study of Reliance 1, and is expected to begin in minutes; data from this trial's top line are also expected in the first half of. Reliance OLS, the Open Label Safety Study, began recently, and it is enrolling patients. These trials include patients from Reliance 1, Reliance 2, but also De Novo. We are also on track to initiate our study evaluating the use of REL1017 as a monotherapy for MDD in the second half of this year.
The second.
The history of trial reliance too is the mirror study of reliance one and is expected to begin immediately.
Data from this trial top line out of a suspected and the first half of next year.
The alliance all as the open label safety study.
And it began recently and the.
It is enrolling patients.
The tried and true patient from the alliance one rely on the true, but also de novo patients.
We are also on track to initiate our study evaluating the use of <unk> 17, as the monotherapy four mbd in the second quarter.
Sergio Traversa: We are currently evaluating options for this study design, and we will provide greater details once this is finalized. As you have just heard, this is an extremely busy clinical development period at Relmada with several key data readouts over the next 3 to 15 months. Importantly, as Maged highlighted, we have a strong balance sheet with enough cash to support us through all of these expected data.
Currently evaluating options for the study design.
And we will provide greater details one of these is finalized.
Is it as you have just heard of it is an extremely busy clinical development periods. The other with several key data readouts over the next three to 15 months and importantly, as Mike highlighted we have a strong balance sheets with enough cash to support.
Work us through all of the respective data point.
Sergio Traversa: I would like to take a moment to express my gratitude to the Relmada team for their hard work and dedication to executing on our mission. I would also like to extend my sincere thanks to the patients and clinical partners involved in the REL1017 clinical trials for their efforts in advancing this important therapy through the clinic as expeditiously as possible. With that, we will now open the call for. Thank you. Thank you. Yes. Can you please open up? Absolutely not.
I would like to take a moment to of strike and the express my gratitude to the Roma the team for their hard work and dedication to executing on our mission.
Also like to extend my sincere thanks to the patients, including the partners involved and the route 10 70 and clinical.
So the effect efforts.
Advancing this important I'm trying to piece through the clinic as expeditiously as possible.
With that we will now open the call for <unk>.
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So based on.
Yes can you please open up slightly.
Currently at this time, we will be conducting a question and.
Operator: At this time, we will be conducting a question and answer session. If you would like to ask a question, please press star 1 on your telephone keypad. A confirmation tone will indicate your line is in the question queue. You may press star 2 if you would like to remove your question from the queue. For participants using speaker equipment, it may be necessary to pick up your handset before pressing the star keys. Our first question comes from Andrew Tsai with Jeffries. Please go ahead.
The trial of recession, if you would like to ask a question of please press star one on your telephone keypad and confirmation tone will indicate your line is and the question queue. You May press star two if he would like to remove your question from the queue for participants using speaker equipment. It may be necessary to pick up your handset before pressing the star.
And our keys.
Our first question comes from Andrew Tsai with Jefferies. Please go ahead.
Operator: Andrew, your line is live.
Andrew Your line of life.
Lin Tsai: Oh, hey, good afternoon. Thanks for taking my questions and congrats on all the progress, guys. So maybe for those in the audience, help us understand, remind us at a high level, you know, you have these two abuse liability studies coming out fairly soon. So remind us, what would you like to see on the VAST likability scores for both of these studies? What would positive data be like as we think about the three 1017 doses versus the two comparator doses versus placebo? Just maybe talk us through that, and I have a follow-up. Thanks.
Oh, Hey, good afternoon, and thanks for taking my questions and congrats on all of the progress guys.
So maybe four of those in the audience help us understand remind us at a high level. You know you have these two abuse liability studies.
Reading out various fairly soon so remind us what would you like to see on the vast likeability scores for both of these studies what positive data would be like.
As.
And we think about the 310 and 17 doses versus the two competitors versus placebo.
Maybe talk us through that and I have a follow up thanks.
Sure. Thank you Andrew and Maggie you want me to take this.
Sergio Traversa: Sure. Thank you, Andrea and Maged. Do you want me to take this? and others. So, very, very top down.
And.
And the.
So maybe talk though these have not very compelling.
If the study is.
Studies and.
Sergio Traversa: These are not very complicated studies. And if you look at every study, the data point that we expect and that people should look at as soon as the data are available is that each of the three different doses of RAL-1017 of S-methadone, so 25, 75, and 150 milligrams, will have to be statistically different from the control. In this case, it's 40 milligrams of oxycodone and ketamine IV in 120 studies. These are really the two things that matter.
And if you look at the like every study the data point that we expect and the debt.
And people should look at the as soon as the data of available is the.
The E.
Each of all of the three day.
Implicate doses of the.
The royalty on 17 of S method on so 25, 75 and 150 milligrams.
And we'll have to be statistically statistically different from the control in this case is 40 milligrams of <unk>.
The friends on and the the Cat I mean, sorry, the kids I mean.
And the IV in the the 120 studies he was really the the two things that the that models are one thing that I would like to clarify is the question that we've been asked that sometime or frequently.
Sergio Traversa: One thing that I would like to clarify as a question that we have been asked more frequently recently, S-methadone to be descheduled or non-scheduled; it does not need to be the same as placebo. It is an antidepressant. It is a CNS-active drug, so it's possible and easily possible that it will differ from placebo if you take many CNS-active drugs that are not placebos. But the key point is that it has to be statistically significantly different from control. I hope I answered your question.
The estimated.
The Q b desk schedule or on a non settle it does not need to be.
The same as placebo at decent antidepressant. It is the CNS active drug so it's it's the possible.
And easily possible debt it will differ from.
Placebo, if you take the.
And mainly of CNS active drug theyre, not placebo and the but the key point is that there has to be statistically significantly from control.
I hope I answered your question.
Not very clear of surgery. Thank you and my second question is I don't know if you thought this through.
Sergio Traversa: Through, but for the oxycodone study that's reading in Q2, I guess, what would be some AEs of interest that would indicate euphoria, for example? And can we expect those AEs to be disclosed in the upcoming top-line data beyond just likability scores? So basically, I'm just wondering, how are you thinking about sharing the top-line results when it happens? Thanks.
And but the Oxycodone study of trading on Q2, I guess, what would be some ease of interest that would.
Indicate euphoria of for example, and can we expect.
Those aes to be disclosed and the upcoming topline data and.
Beyond just lack of ability scores so basically I'm just one.
But how are you thinking about sharing the topline results when it happens.
Oh Wow.
Sergio Traversa: Well, it's a good question, and we'll decide when we see the data. But, you know, top line, usually you receive really just very limited information; that's the one that matters. And then, you know, a few weeks later, you receive the more detailed data. I assume there is anything notable, you know, the data will be provided to us, and we will, of course, disclose it. You know, ultimately, what really matters is the VAS score and the statistical significance.
It's a good question and no.
We have decided when we see the data, but the top line.
Usually you received really just very limited information of that the one that matters and then the few weeks later you received.
The the more detailed data I assume the res anything notable.
You know the data would be provided to us and we will of course, we will disclose it all.
Ultimately the what really matters is the.
Yeah.
The vos.
Score and the the statistical significance.
Sergio Traversa: We have, you know, we have treated many patients with S-methadone now, and we know how the profile looks pretty well. So we have, you know, phase one, phase two, so we're not expecting any surprises.
And wondering we have yes, we have pre the notes.
Many patients it is math of them now and we.
And we know how of the profile looks like pretty well.
Yes.
One phase two so we're not expecting any type of price from understanding that it's on its profile.
Lin Tsai: Thank you guys. I appreciate it.
Yep. Thank you guys appreciate it.
Thank you Andrew.
Next question comes from Marc Goodman with Leerink. Please go ahead.
Marc Harold Goodman: Yes, just to confirm a few things. One is when the oxy data comes out, that will be a press release. You're not waiting for the ketamine data since now they're both not coming out, you know, near the same timeline, right? Is that true? Yes, market. Good afternoon, by the way.
Yes, just to confirm a few things one is one of the oxy data comes out that will be a press release, you're not waiting for the academy and data since now theyre, both not coming.
He can mirror the same timeline right is that true.
Yes, the market the good afternoon, but yes, it's absolutely true reason being that the the.
Maged S. Shenouda: Yes, it's absolutely true. The reason being that the oxycodone data is by far more significant, they're both material, but the oxycodone is far more important, then. Right, I'm just making sure that we will get that press release whenever it is in the second quarter.
The Oxycodone data is by far more.
The bill of material, but the Oxycodone on these are more important than that right.
The big assure that we will get that press release whenever it is and the second quarter and then secondly on oxi and perhaps study so.
Marc Harold Goodman: And then secondly, on Oxy, the hep study. So your view is that none of the doses can be relatively light oxy, right? I mean, the 150 can't be like oxy even though it's multiple times the 25 that you're going to be using.
Your view is that none of the doses.
Can be realm.
Relatively light boxes, and the the $1 50 can't be like Oxy, even though.
Though it's multiple times, the 25, but youre going to be using.
Marc Harold Goodman: in the real world, right?
And the real and the real World right.
Sergio Traversa: Correct. Look, we have, this is not really a tossing a coin kind of trial. We have 13 patients treated with 150 in phase one, and none of them showed any opioid-like effect or oxycodone-like effect. We have 21 patients in phase two that were the 50 milligram arm that was loading those; they took 100. None of them showed any opioid-like, oxycodone-like effect. And so we do have enough evidence that the one, even the 150, does not have any effect even close to what the effect of oxycodone can be. Of course, you know, we have to show it in the control study. But, you know, we have quite a bit of evidence already, already out there. And then lastly, could you please give me just an update?
Okay.
Correct and look we have and this is not really a debt the thoughts and your call and kind of trial and we.
Have 13 patients treated with 150 in phase one.
And one of.
Them showed any hope you like.
Effect of Oxycodone of like effect, we have 21 patients in the phase two and that was the 50 milligram arm debt as the loading those they took 100 none of them showed any opiate like ER oxycodone on like effect.
And so the.
And the we do have enough evidence that the.
The one even the 150 and does not have any.
Even close to what the effect of Oxycodone and it can be of course.
We have to show it and the control study.
But we have quite of bit of evidence already already out of there.
And then lastly could you just.
Sergio Traversa: A, B, C, D, E, F, G, H, I, J, K, L, M, N, O, P, L, M, N, O, P, Q, R, R, S, T, U, V
Just any update on enrollment and how many sites are up and running sort of reliance one.
Thank you.
Yeah, you'll call me on that and they did he is evolving very quickly. So we don't have the exact.
Sergio Traversa: Yeah, you caught me on that. It's evolving very quickly, so I don't have the exact number. Maged, do you know, we are getting close to all the sites enrolled because we will start Reliance 2 very soon. So we wanted to wait to have Reliance 1 well up and running before starting the second one. I don't have the exact number, but it's close to having all of them up and running.
A number of Mega deal do you know and they were getting close to all the sites and all of it because we will we will start.
Very soon the reliance too so we wanted to wait to ever last one well up and running before to start the second one.
And I don't I don't have the exact number but it's close to having all of them up and running.
Thank you.
Operator: Next question, Julie, with True with Securities: please go ahead.
Next question, Thank you Marc and.
Julie with true.
Please go ahead.
Julie: Hi, thanks for taking our questions and thanks for the update. So for the upcoming human abuse potential study, has there been a similar pre-planned analysis for the HAB study using oxycodone as an active comparator as what was done for the ketamine study? And if so, was the oxycodone arm behaving as they should be based on the historic data? And also, what's the explanation for the oral ketamine not separating from the placebo in your ketamine HAB study? And I have a follow-up question. Thank you.
Hi, Thanks for taking our questions and thanks for the update so for the upcoming human abuse potential study has there been a similar preplanned analysis for the the half set of using Oxycodone as an active comparator as what was done for the ketamine study and if so.
With the sickle and optical it on arm behaving in a thing should be based on the historic data and you know of.
And what's the explanation for the oral academy and not separating from the placebo and you're and you're telling me Hap study and I have a follow on thank you.
Okay. So the first one is if the quality.
Sergio Traversa: Okay, so the first one is, if quality control, yes, the answer is yes. We usually, everybody, I think, usually does blinded quality control data, just to be sure that there is nothing like unexpected, nothing weird about data, and it's mostly done for safety. So and then we have seen that with oral ketamine, it was kind of, you know, also looking at futility, which is not very complicated to understand. You know, up to five arms, there was no likability at all.
So yes. The answer is yes, we've usually everybody the thing usually does a blinded the quality control data just to be sure of that the there is nothing.
And like unexpected on nothing weird about data and and it's mostly done and for safety.
And we have seen debt the oral Catherine.
It was kind of our thoughts.
And also looking at utility that is like not very complicated to to understand it.
Of the five arms there was no like it'd be at all and one of the five arms.
Sergio Traversa: And one of the five arms, even though it was blinded, but it has to be ketamine because every patient takes every arm. So yeah, and it was pretty straightforward that there was an issue with the ketamine, but the aiding is a control, a valuable control. So we will do the we haven't, we have not done it yet. And they, the oxycodone study started a couple of months after the ketamine study. The only reason being that the site that is doing it needs a little bit more time to get up and running, repeating with other things. So we had to wait a couple of more months.
And it was blinded, but there has to be kept I mean, because the every.
The takes every arm so the and.
And he was pretty straightforward that the.
And it wasn't an issue with the cash I mean, but behaving as the hit the control the valuable and control. So we will do the we haven't we haven't done it yet and the the Oxycodone study started a couple of months after.
After the indicate the mean study and the only reason being that the size of that is doing it and they need to live and more time to get up and running and it might be thinking of the other thing so get the weight.
Couple of more months. So you know at some point of view and do the the analysis, but if there is nothing notable.
Sergio Traversa: So, you know, at some point, we do the analysis, but if there is nothing notable, we will not, we will not even know it happened. They only will notify us if it's something that we show that there is any unexpected effect or side effects or anything like it happened with ketamine that said, look, this thing doesn't look like it's going in the right direction. I think you were alerted because the ketamine arm didn't separate from placebo by whoever was conducting the study.
We would not.
And we will not even know it.
That is it happened the only will notify us of something that will show that.
And any unexpected the fact of side effects or anything like it happened with Kathleen debt. Some of these things it doesn't look like it's going the right direction.
And so you weren't you work on are alerted because.
And I mean arm didn't separate from placebo by whoever it was conducting the study.
Sergio Traversa: But for the Octocodon, you know, HAP study using Octocodon, you don't know, and you won't know if there's no real issue with the study. Right, right? We will only be notified if there is something that we in the material that we need to know. And the only side effect or safety issue or something that makes the study will not generate any valuable, useful results like ketamine. Right.
For the Oxycodone.
Hops that are using of Oxycodone.
You don't know and then you won't notice on the there's no real issue with the the study.
Right right. The day, we would only be notified of the BW something debt.
And that tells you that we need to know and.
And the only side, the fact or something safety or something that make our debt. The study will not generate any valuable useful results like get the right right and then following up on Mark's question and that's the hundreds of the arm or any one of the debt.
Marc Harold Goodman: Mark's question is whether the hundredth of the arm or any one of the dosing arms actually does not separate from the active comparator.
The dosing arms.
Excellent and does not separate from the active comparator.
And here.
Marc Harold Goodman: Statistically, then do you automatically get a schedule two? Or, you know, what's this sort of decision tree after?
Statistically and do you automatically get of scheduled two or what's the sort of the decision tree after that.
Marc Harold Goodman: and Yatin Suneja. Thank you.
Sergio Traversa: I mean, the ideal situation would be as you described, none of the doses being likable. But if one of the doses happens to be likable, what's the process? Yeah, this is a great question, John.
And the ideal situations and it won't be as you described and none of the doses are likable.
One.
And that might also this happened to be likable.
And what's the process.
The one.
This is of Great question John.
There are the.
We and our hygiene that they'd like ability of the results of the study is important but it's not the only factor that will determine the.
Sergio Traversa: Yeah, the there are the. We are not hiding that the likability of the results of this study is important, but it's not the only factor that will determine the scheduling or non-scheduling of S-Methadone. There are eight factors that the FDA considers when it determines the recommendation for the DEA. One is likability, and it's very important.
One of the debt.
And as casually and working on.
Non scheduling of as Matt said on the there is a and the eight factors that the FDA considers when the determined the recommendation for the D. E. One is like ability and it's very important and.
If you don't like something is from.
And the more difficult you get.
And is it or you get the dependence on it but the other factor like look the FDA at the end.
Sergio Traversa: The real focus is on safety. And the reason that oxycodone or opioids are a lot more under scrutiny and the focus of the FDA is not because they're more abusable than ketamine or alcohol or PCP. It's because they're dangerous, right?
Is the the real focus is on safety and the reason that the oxycodone or the Orca is there's a lot more on the scrutiny and the the focus of.
Yeah.
And it's not because they are more abuse of ball than cat I mean on the alcohol or all of the P. C D and E because they're dangerous right the overdose and opioid hey, you can have respiratory the freshman and unfortunately, you can have some serious consequences if you overdose Kathleen.
Sergio Traversa: If you overdose an opioid, you can have respiratory depression, and unfortunately, you can have some serious consequences. If you overdose ketamine, it happened, but you fell asleep, or it's used as an anesthetic specifically because it does not cause respiratory depression. So, and the dangers are the, you know, the potential risk is a very important factor in determining the schedule, right? That's why ketamine is Schedule 3, not because it's less abusable than oxycodone, it's because it's less dangerous than oxycodone. There are eight of these factors, so likability is one, and then you have, you know, dangers, the history, the pharmacology, and, and, and so on. So, clearly, likability is important.
The S can tap and but the fell asleep or as soon as it is an anesthetic specifically because it does not keep rescue the authority of the question so and.
And the the dangers are the the potential risk is the very important factor in determining the schedule and that's why I kept them and its schedule III.
And because there's less abusable and Oxycodone is because it's the dangerous and oxycodone instead of the eight of the sectors of Likeability is one and then you'll have you know the dangers of the history of the pharmacology and and and so on total.
And clearly Likeability is the is important.
Sergio Traversa: To answer directly your question, if by chance, one of the doses of X methadone will not separate statistically from 40 milligrams of oxycodone, then it will depend on the FDA's overall analysis and how they will consider the other factor. Consider that X methadone in the past has been used, not used, and has been tested at 900 milligrams, and nothing happened. People did not like it, and nobody experienced any serious side effects. 900 milligrams is 36 times. I believe it's nine times four, or 36 times the therapeutic dose. And so we definitely feel comfortable that safety is not the major potential risk for us. [inaudible]
The answer directly your question.
If by chance one.
One of the doses of X methods on the will not separate statistically from the 40 milligrams of Oxycodone and Danny will depend on the SBA overall and now.
Of these days and how they will consider the other factor consider debt.
What we commented on in the past has been used.
And that's been tested at 900 milligrams and nothing that people did not like it and.
And not nothing experienced any serious side effects and 900 milligrams is the 36 times I believe.
And at <unk> and.
Thanks.
Is it 36 times, the therapeutic dose and so.
Definitely we feel comfortable that the yeah.
Safety is not the major potential.
Potential risks for out of Florida, It's Matt.
Operator: Next question is Yatin Suneja with Guggenheim Securities. Please go ahead.
Yeah.
So it's not on automatic.
Little too.
One of the dose the past.
Eddie: Hey guys, this is Eddie on 3Out, and thanks for taking the question. So, you talked about for Reliance One the sort of checks that you do, the screening, the multiple levels of screening that you're taking, so can you just talk a little bit more about these steps and how you're ensuring that you're not enrolling professional patients, and then what would be a placebo range for the Madras improvement that would give you confidence that you had a proper screening process? and then I will have a follow up on the human.
Okay.
That's helpful.
Next question, Tim and Asia with Guggenheim Securities. Please go ahead.
Hey, guys. This is eddie on for that and thanks for taking the question. So just you talked about from reliance one.
Schedule it sort of the Chi.
Checks that you on.
And the screening multiple levels of screen that you take and so can you just talk a little bit more about.
The steps and higher ensuring that you're not the only professional patients and then what would be of placebo range for the Madras improvement that would give you confidence that you'd had a proper screening.
The screening process.
On the novel.
And on site.
Sergio Traversa: Great. So, let me let me let me take the lead on this one. So how do we avoid or reduce the risk of having non-depressed patients in phase three in reliance? The besides, you know, the two arms that are easier to the placebo effect are less effective than multiple arms, specifically for patient selection. And, you know, one point that we'd like to make, to make, we have been advised by, you know, our advisor that the major risk in running a phase three trial for depression is actually patient selection because it's also connected with the placebo effect.
Great.
And then let me let me, let me take the and the let me take the issue and so the how do we avoid the juice.
The risk of having non depressed patients in the phase III and rely on.
And the BC.
And are the two arms that these easier too.
And.
So on the plus the placebo effect is lower than multiple arms.
Typically for the patient selection.
And you know at one point I would like to make to make we of being advised by you know price of that.
That's the major risk and in running a phase II.
We try and force depression is actually the patient selection because it's also connected with the the placebo effect. So we have multiple screen and that the so on the site.
Sergio Traversa: So we have multiple screening that the screening side selects the patient, and they propose that the patient meets the criteria to be involved in the study. Then we have the CRO that they themselves will review the data, and they will evaluate if there is any risk of having you know this patient is may not be depressed, may have some other issue, or maybe a personality disorder. The data was also seen by, I believe, I was CMO for safety control. And clearly, there is an opinion here.
On the screen the patient.
And and they propose that the patient and meet the criteria to be enrolled in the study.
Then we have the.
On the CRO debt and themselves they will review the data and they will ease of use.
They will evaluate it.
And if the reason the risk of.
And this patient is is the may not be the price may have some other issue on that.
And it would be a person obviously disorder.
The data also.
And also seen by our belief of the CMO and the.
The.
For the safety control and clearly the reason of opinions here.
Sergio Traversa: There is probably the most important step beyond these three steps is the review done by a group. Mage, can I say the name? Yes, it's not nothing. CT and I, it's a group that was not, I believe, from MGH or Harvard. And what they do, they re-diagnose the patient. So only the site and CT and I have contact directly with the patient. So it's a phone interview, and they administer a different scale. So it's not Hamilton; it's not Madras.
There is probably the most important of the steps that would be beyond the three steps is the review.
Dawn by our group.
Can I say the name yet so thats not true.
The C P&I as it is.
Group that was of BD was not from MGH of hardware.
And what they do they read diagnose the patient so only the sites and C D and I to have of contact directly with the state.
It's just the phone interview.
And they are administered of different scale. So it's not having it done and it's not a matter of dominion's sort of skeptical of safer debt.
Sergio Traversa: They administer a scale called SAFER that is considered more the patient as an entity, right? For example, they look at the history of the patient that's been depressed in the past, or there has been an event that has generated the current episode of depression. So it gives a little bit more of a complete picture.
Net is considered more of the patients as it is and is it is an entity right. For example, the they look at the history of the patient has.
And depressed and the past.
And are there has been and event that has generated the call and debuts on the pressures and I think the it gave us a little bit more complete picture and they have the last day on the patient if it is suitable for the trial and so we have four different ways of which the one and the last one.
Sergio Traversa: And they have the last say on whether the patient is suitable for the trial or not. So we have four different ways in which the one, the last one, the CT and I, it's right. We do believe it's effective. We use it in phase two, and you have seen the results. It was pretty well done, pretty effective. Yeah, that's great. Thank you for that color.
And I, it's right and we do believe is effective we use it in the phase II.
<unk> seen the results and it.
Was force pretty.
Very well done.
The fact that that's the way I hope I answer and say yes.
Yeah, No that's great. Thank you for that color and then for the for the Academy and abuse liability studies can you just.
Sergio Traversa: And then for the ketamine abuse liability studies, can you just give a little more logistics on how they run a trial with multiple different routes of administration? And will the placebo also have to be IV, or sort of how does that work in terms of making sure the patients are giving an accurate comparator if they're getting oral versus IV drugs? Yes, the answer is yes, there's going to be an IV placebo and an IV oral.
Give like the little more of logistics on how they run the trial with multiple different routes of administration and will the placebo also have to be IV or sort of how does that work in terms of making sure. The patients that can be and accurate comparator, if theyre getting the oral versus IV drugs.
Yes the.
Yes. The answer is yes, there's going to be a.
And you see the IV placebo and the IV oral.
Okay. Thank you.
Next question Jay Olson with Oppenheimer. Please go ahead.
Operator: Next question is Shea Olson with Oppenheimer. Please go ahead.
Oh, Hey, guys. Congrats on the progress and thank you for taking my questions.
Shea Olson: Oh, hey guys, congrats on the progress and thank you for taking my question.
I was curious about the.
The start up activities that remain to be completed before initiating the reliance to the.
Shea Olson: I was curious about the
unknown: Inaudible.
Shea Olson: before initiating the reliance on them.
Maged S. Shenouda: second pivotal trial, and also the phase two monotherapy trial, and whether or not you expect to initiate the phase two monotherapy trial before or after Reliance 2 starts. Yeah, Maged is really helpful in looking at the operation as a whole. Maged, do you want to take this? Sure, sure, thanks. Thank you, Jay, for the question.
The second pivotal trial and also the phase two mono therapy trial, and whether or not you expect to initiate the.
Phase II monotherapy trials before after reliance to starts.
Yes, Maggie the Mega of is really helpful and and.
And the operation is entirely kind of do you want to take this.
Sure.
Thanks, John and thank you, Jason and the question.
Maged S. Shenouda: So with regard to Alliance 2, I can safely say that we're
So with regard.
Since two I can safely.
Safely say that we're close to initiating that study I think and on most of the operational pieces are in place right now we're not quite there yet.
Maged S. Shenouda: are close to initiating that study. I think most
Maged S. Shenouda: Most of the operational pieces are in place right now. We're not quite there yet, but look for that to officially start and kick off shortly. So with regard to, can you repeat the second question, Jay?
But look for us for that to officially start kick off the shortly.
And so.
With regard to the can you repeat the second question and saying Oh.
Shea Olson: I was wondering, for your Phase II monotherapy trial, what remains to be done before you can initiate that study, and should we expect that before or after Reliance II starts?
And I was wondering for your phase two monotherapy trial.
And what remains to be done before you kind of initiate that study and should should we expect that before after remains to initiate it.
Maged S. Shenouda: So I'll answer the second question first. So expect that after.
So on.
The answer the second question first.
And so expect that after the lines two starts.
Maged S. Shenouda: Reliance 2 starts. We still have a fair amount of work. We've completed the protocol. We've submitted it to the FDA. We're about to submit it to the FDA. And, you know, we have also selected
We still have a fair amount of work and we've completed the <unk>.
So the call we submitted the two the F D a whereabouts and submit it to the FDA and we have also selected the CRA.
Maged S. Shenouda: to the CRO. So I think, you know, a lot
So I can't give them a lot of a lot of the pieces are coming together, but our expectation remains that we will start that study by the end of the first half of them. So.
Maged S. Shenouda: A lot of the pieces are coming together, but our expectation remains that we'll start that study by the end of the first semester.
Shea Olson: Okay, great. Thank you. And are there any details about the study design for the monotherapy?
Oh, Okay, great. Thank you and are there any details about the study design for the monotherapy study that you can share.
Maged S. Shenouda: Designed for the monotherapy study that you could share with us.
Maged S. Shenouda: Um, I think we're going
I think we're not quite prepared to do that and yet so give us some time and we'll be able to.
Maged S. Shenouda: I think we're not quite prepared to do that yet. So give us some time, and we'll be able to, you know, give you a more full characterization of the study. You can expect it to be very similar to the Reliance One and Reliance Two studies, and you know, in that it'll be two arms.
Give you a more full characterization of the study and you can expect it to be very similar to the reliance one of our lines two studies and you know.
And that it'll be two arms.
Maged S. Shenouda: So SIBO versus 25 milligrams of REL1017.
Placebo versus 25 milligrams of rock Tenn, and 17.
Maged S. Shenouda: de Novo patients. But beyond that, we're not, you know, we're ready to disclose the number of sites and such, you know, and any limitations on patients.
De novo patients, but beyond that we're not ready to disclose number of sites and so.
Such you now and any limitations on patient selection.
Shea Olson: Okay, got it. We'll look forward to the yeah, the biggest difference is going to be the patient. So adjunctive treatment versus monotherapy. That's going to be Okay, got it.
Okay got it looks like J&J the yeah the the.
The biggest difference is going to be the the.
The patients so adjunctive treatment versus monotherapy, that's kind of the dividend.
Okay got it.
Shea Olson: Thank you. Pleasure, Jay.
Thank you again for taking the questions.
Operator: Once again, if you would like to ask a question, please press star 1 on your telephone keypad. Our next question comes from Salveen Richter with Goldman Sachs. Please go ahead.
Thank you pleasure Jay.
And once again, if he would like to ask a question. Please press star one.
Your telephone keypad. Our next question comes from Sylvia and Richter with Goldman Sachs. Please go ahead.
Andrea: Hi, everyone. Thanks for taking the question. This is Andrea on FirstSolving. Sergio, maybe a question for you just based on what you saw from the oral ketamine study. I understand the positive control didn't separate here, but does this give you any increased confidence in the profile of REL1017 and what you might expect to see versus the oxy? Well, good afternoon, Andrea.
Hi, everyone and thanks for taking the question and this is Andrew on the first Valvoline and you and maybe a question for you just based off of what you saw from the the oral ketamine study understand the positive.
Controls and at separate here, but does this give you any increased confidence and the profile of route 10, and 17 and and what you might expect to see vs. The oxy.
Yeah.
Well done and good afternoon, and Andrea and thanks for the question well.
Sergio Traversa: Well, good afternoon, Andrea. And thanks for the question. Well, yes, with the limited, that is the limitation that was a blinded analysis. So we don't know who took what, but they all took all arms.
Yes, with the limited the.
That is the limitation.
And that was a blinded analysis. So we don't know who's the Duke was the old took all of the arm. So we have seen.
Sergio Traversa: So we have seen no evidence of dissociation, hallucination, delirium, and out of body experience in any of the patients that have been reviewed that were 20% of the planned total. So clearly, S-Methadone did not show anything because, even when blinded, there was no sign of this in any of these patients. So yes, it gave us a good level of confidence that the profile confirms what we have seen historically in the literature that we have seen in phase one and in phase two.
No.
And so.
The association of hallucination, the lithium and out of body experience in any of the patient is being reviewed the was 20% of the planet.
And then the total so and then it's a clearly.
Ed Smith of and did not show anything because even blinded and everyone's no sign on piece of any of the answer yes.
And it gave us a good.
A good level of confidence that Oh.
The the profile of confirms what we've seen.
And in the historically and the lethal true, but we have seen in the phase one and the phase two and really the.
Sergio Traversa: And clearly, we have to prove it, but we see it a little bit, like it's unlikely that a drug will behave differently in two similar studies just with a different control arm. So nobody liked it, or nobody has experienced anything that would be likable in the ketamine study. Yeah, probably it's possible, but we see it as unlikely that we'll totally change our behavior. So yes, the answer is yes, and it gave us, you know, supported the confidence that we have that Smethadone is not a likable drug.
Yeah, we have to prove it but we see the little bit like unlikely that a.
Drug will behave differently and.
And to see Middle of study adjusted.
With the different the control arm total.
And if nobody liked it the nobody has experienced the anything that could be likable and the cut them and study.
Total as possible, but we see the as unlikely that we've changed.
And the behavior.
So yes. The answer is yes gave us.
<unk> supported the conversations that we have that the Smith at all of its not the case.
The likable.
Sergio Traversa: I would like to turn the floor over to Sergio for closing comments.
Comparable.
Yeah, I would like to turn the floor over to.
To Sergio for closing comments.
Sergio Traversa: Okay, well, thank you, operator. And thank you all for joining our call today. It was our first one, so it will be remembered, but we look forward to the year ahead. And we'll provide further updates throughout 2021. So thank you all again and hope you will enjoy the rest of the day.
Okay, well, thank you operator and thank.
Thank you all of you for joining our call today.
It was our first one of them. So it's a it will be run Panther, but we look forward the to the year ahead, and we'll provide further data and the throughout the two.
And when do you want.
So thank you all again and hope you will enjoy the rest of the way.
Operator: This concludes today's teleconference. You may disconnect your lines at this time, and thank you for your participation.
This concludes today's teleconference. You may disconnect your lines at this time and thank you for your participation.
Thank you.
Okay.