Q1 2021 Relmada Therapeutics Inc Earnings Call
Good afternoon, ladies and gentlemen, and thank you for standing by and welcome to the Royal motto Therapeutics incorporated first quarter 2021 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 should you require operator assistance.
Operator: Good afternoon, ladies and gentlemen, and thank you for standing by. Welcome to the Relamata Therapeutics Inc. first quarter 2021 Financial Results Conference call.
Operator: At this time, all participants are in a listen-only mode. A question-and-answer session will follow the formal presentation. Should you require operator assistance during the conference, please press star zero to signal an operator. Please note, this conference is being recorded. I will now turn the conference over to your host, Tim McCarthy, with Lifesai Advice.
During the conference. Please press Star Zero to St. Gallen Operator. Please note. This conference is being recorded.
Now I'll turn the conference over to your host Tim Mccarthy with lifestyle advisors.
Timothy McCarthy: Thank you, operator, and thank you all for joining us this afternoon. With me on today's call are our chief executive officer, Dr. Sergio Traversa, and Chief Accounting and Compliance Officer Chuck Enst. This afternoon, Romada issued a news release, providing a business update and announcing financial results for the first quarter ended March 31st, 2021. Please note that certain information discussed on the call today is covered under the Safe Harbor provision of the Private Security Litigation Reform Act.
Thank you operator, and thank you all for joining US. This afternoon with me on today's call are Chief Executive Officer, Dr. Sergio Teresa and Chief accounting and compliance Officer Chuck <unk>.
This afternoon, Roma and issued a news release, providing a business update and announcing financial results from the first quarter ended March 31 2021.
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 from modest management team will be making forward looking statements.
Timothy McCarthy: We cautioned listeners that during this call, Ramada's management team would be making forward-looking statements, and 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 primary statements contained in RELMATA's press release issued today and the company's SEC filings, including in the annual report on Form 10K and subsequent filings. This conference call also contains time-sensitive information that is accurate only as of the date of this live broadcast, May 12, 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'd like to turn the call over to Sergio. Sergio?
Actual results could differ materially from those stated or implied by these forward looking statements due to risks and uncertainties associated with the company's business.
Forward looking statements are qualified by the price statements contained and real modest 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 May 12 2021.
<unk> undertakes no obligation to revise or update any forward looking statements to reflect events or circumstances. After the date of this conference call now I'd like to turn the call over to Sergio Sergio.
And.
And good afternoon to everyone.
Sergio Traversa: and good afternoon to everyone. Please welcome you to Ramada's first quarter, 2021. From today, I will provide an update on the comprehensive development program for the land page of this. Treatment of the Price, the 10, 17, and the upcoming mouth. I will turn for a case or achieve, and the class officer, and we will spend it today for our magazine for the view of by the chief of recent data that we presented at three recent scientific conferences.
And I was giving you two roadmap thats first quarter 2021 conference call.
Debate.
They on the comprehensive development program, and Portland and age from B.
Treatment of the price.
And 17 and.
And the upcoming milestones.
I will.
Oh, okay.
Alright.
Yeah.
And we're spending today and for all the magnets and afford a view.
Hi.
The recent data and we presented.
Presented the three recent scientific Congress.
Sergio Traversa: With that, I'll begin with an update on reliance, that is, the ongoing strategy program, consists of a third one, the Cibocon of Pivocal Studies, reminds one and reliance, and which includes participants per study of 25%. A focus group OLS that stays for a long-term open-label safety study that is enrolling both. Rollover participants from the TIVA studies as well as novel participants. This study is designed to evaluate REL-1017 as an adjunctive treatment for major depressive disorder, MPD, and..., includes small and 25 milligram or about 1017. I just got somebody told me that I'm breaking up, so I'll try to switch.
With that I'll begin with an update on rely on said that is the goal.
For all of them.
Yes.
And from system.
Mr. Bonn placebo control people don't stop.
And your lines.
Thanks.
Before.
Sandy.
Besides that.
Yeah.
Reliance OLS that stays for the long term open label safety study that is involved in bullet rollover from D. C bonds from the studies as well and noble Powerpc.
These studies are designed to evaluate brel <unk> <unk> as an adjunctive treatment for major depressive disorder and <unk>.
And.
Include smart people and.
And 25 milligrams or 10, 17, and I just got somebody told me that I'm breaking up so I'll try to switch.
Yeah.
No it should be better.
Sergio Traversa: Now it should be better, and I was saying placebo and 25 milligrams of REL-1017, and both are on top of standard antidepressant treatment for participants. We have already unsuccessfully tried a minimum of one up to three antidepressant therapy. The primary endpoint is change in Madras score at day 28. Key secondary endpoints include change in Madras score at day 7 and change in C-GIS, the stage for severity, at the score at day 28.
And let's say and placebo and 25 milligram a route 10 17 and both are on top of standard antidepressant treatment for part D. C bonds were already and successfully tried the minimal one up to three antidepressant therapy.
The primary endpoint is change in my address score at day 20 key secondary endpoints include change and macro score at day, seven and change and the C V. I S. The state's force severity.
And the score at day 28.
The first phase II trial reliance one continues to enroll as expected and additional sites.
Sergio Traversa: The first phase three trial, Reliance 1, continues to enroll as expected, and additional sites are coming online nicely. In addition, we recently began enrolling participants into the second phase 3 trial, Reliance 2, which is a mirror study of Reliance 3. Top-line data from these two trials are expected in the first half of. The Reliance Long-Term Open Label Safety Study is also underway, and the role in participants will be as planned. Reliance OLS will include both participants from the Pivalva Studies as well as the Novo. The data for this long-term open-label safety study will be part of the NDA filing.
Coming on line nicely. In addition, and we recently became enrolling participants into the second phase III trial reliance too, which is the mirror study of our line is one.
Line data from these two trial expected in the first half of next day.
And do you rely on long term open label Safety study is also underway and the rolling participant as planned and reliance OLS would include both participants from the pivotal studies as well as de Novo Park view six months data from these long term open label safety study will be the part of the NDA file.
Sergio Traversa: We remain on track to initiate the study, evaluating the use of our REL-1017 as a monotherapy for MDD at the current time, at a very high level. The most significant difference between this trial and the ongoing clinical studies is the patient population. The patient population planned for the MDD monotherapy study will consist of people who are diagnosed with depression, and they are not currently taking standard antidepressant therapy.
And package and we remain on track to initiate the study evaluating evaluating the use of our Ralph and 17 as a monotherapy for IMTT during the current quarter.
Very.
And maybe high level. The most significant difference between this trial and the ongoing clinical studies is the patient population the <unk>.
Patient population and planned Torre M. D. D. Monotherapy study will consist of people who are diagnosed with depression and theyre not currently taking standard antidepressant therapy.
And we anticipate the completion of this study by year end 2021.
Sergio Traversa: We anticipated completion of this study by year-end 2021. Moving on, I would now like to provide an update on the human abuse potential or HAP studies. And as we discussed previously, we discontinued study 120 that was assessing REL-1017 versus oral ketamine as an active control because a pre-planned-blinded analysis of the initial study completers showed that a significant material group of participants did not respond. to the active control catamine. And so, most likely, this lack of response was due to the poor bioavailability of oral ketamine. And this would have resulted in non-conclusive findings, so we decided to stop it.
Moving on I would now like to provide and update on the human abuse potential or the Hap studies and.
And as we discussed previously we discontinued the study 120, there was assessing route 10 17 versus oral ketamine as an active control and it's part of a preplanned blinded analysis of the initial study computers and showed that <unk> a significant.
Material group of participants did not respond to the active control Academy and and so most likely the cycle response was due to the pork and bioavailability of oral ketamine and.
And this would have resulted in non conclusion findings, so we decided to stop it and.
And we are now working toward initiating and new ketamine controlled study we call. Each student studied 126, which will use as an active comparator intravenous IV cats, I mean that has a established history cause and effect the positive control.
Sergio Traversa: And we are now working toward initiating a new catamine control study. We call it study 126, which will use as an active comparator intravenous IV ketamine that has a history as an effective positive control.
We plan we plan to complete this study by year end of D. C zone, and the 2021 and the second Hap study. The abuse study study one and 24 is comparing Ralph and 17, two obstacles and he is progressing as planned and we continue to expect to complete this study and all day.
Sergio Traversa: We plan to complete this study by year's end, so end of 2021. The second HAP study, the abuse study, is to study 124 and is comparing REL-1017 to OxyCodon. It's progressing as planned, and we continue to expect to complete the study by the end of the current quarter. These HAP studies are a standard component of the NDA submission for many CNS drugs and will inform the assessment of REL-1017 for the schedule.
Current quarter.
These have steadied out a standard component of the NDA submission for many CNS drugs.
And we will inform the assessment of residents and 10 17 and for the scheduling.
And the <unk> studies also represent an important opportunity to add to the existing very strong body of literature that are clearly differentiates royalty and 17 from the parent drug for ischemic methadone and any potential perceived that association with opioid effect or distortion symptoms.
Sergio Traversa: The Upstudies also represent an important opportunity to add to the existing, very strong body of literature that clearly differentiates REL-1017 from the parent drug, racemic methadone, and any potential perceived association with an opiate effect or distortatives. I'm also happy to share the RELMADA team just completed presentation of a total of nine posters at three different scientific congresses. I will provide a brief overview of the data for RELT-1017 that we are presenting. However, before I do that, I will turn the call over to Chuck for his review of the financials. Thank you, sir. Good afternoon.
I'm also happy to share that with my grandmother, just completed presentation of a total of nine pasta.
Over three different scientific Congresses, and will provide a brief overview of the data for Realtors and 10, seven and tend to be presented however, before I do that I will turn the call other Chuck for his review of the financial Chuck.
Chuck.
Thank you O'neil.
And good afternoon, everyone.
Chuck Enst: Today we issued a press release announcing our business and financial results for the first quarter ended March 31st, 2021, which I will now review. For the first quarter ended March 31st, 2021, total research and development expense was approximately $14 million, as compared to $4.5 million for the comparable period of 2020. The increase was primarily related to an increase in costs associated with the execution of a broader clinical program, Ferrari L 1070. Total General and Administrative expense for the quarter ended March 31st, 2021, was approximately $8.4 million, as compared to $5.5 million for the comparable period of 2020.
Today, we issued a press release announcing our business and financial results for the first quarter ended March 31 2021.
Which I will now review.
For the first quarter ended March 31, 2021, total research and development expense was approximately $14 million.
And as compared to $4 $5 million for the comparable period of 2020.
The increase was primarily related to an increase and costs associated with the execution of a broader clinical program where.
And we're already El pen 17.
Total general and administrative expenses for the quarter ended March 31, 2021 was approximately $8 $4 million.
And as compared to $5 $5 million for the comparable period of 2020.
The increase was primarily due to an increase and stock based compensation.
Chuck Enst: The increase was primarily due to an increase in stock-based compensation. For the first quarter ended March 31st, 2021, we recorded a net loss of approximately $22.2 million, or $1.34 per basic and diluted share, compared to a net loss of $10.7 million, or 72 cents per basic and diluted share, in the comparable period of 2020. On March 31st, 2021, the company had cash equivalents and short-term investments of approximately $102.7 million, compared to $117.1 million on December 31st, 2020.
The first quarter ended March 31, 2021, we recorded a net loss of approximately $22 $2 million.
Or a dollar and 34 cents per basic and diluted share.
Impaired to a net loss of $10 $7 million or 72 cents per basic and diluted share.
And the comparable period of 2020.
On March 31, 2021, the company had cash cash equivalents and short term investments of approximately $102 $7 million.
<unk> $217 $1 million on December 31st 2020.
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 two.
Timothy McCarthy: 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 2022. I will now hand the call back to Sergio for further remarks on the most recent progress.
I will now hand, the call back to Sergio for further remarks on the most recent progress.
Joe.
Sergio Traversa: As I mentioned, I'm happy to outline the recent data that we presented in nine posters across three different medical meetings. First, at the American Society for Pharmacology and Experimental Therapeutics, and we shared preclinical data that confirmed the lack of any neurotoxic features that are potentially linked to only the lesion.
Thank you Chuck I appreciate it.
And as I mentioned and I'm happy to outline and the recently that and we presented nine posters across three different medical meeting first.
First at the American Society for Pharmacology, and experimental Therapeutics, and Michelle preclinical data that confirms and lack of any neurotoxic feature.
That that potentially linked to only lesion and this was totally not a surprise, but it is important because these are these the fact it is impacted a safety and development of other and Dr. Blockers like MK data, one and besides and find these continue to support the consistent safety profile across.
Sergio Traversa: This was totally not a surprise, but it's important because this effect has impacted safety and development of other MDR blockers like MK-H-O-1, and these findings continue to support a consistent safety profile across pre-clinical and clinical studies. Next, at the Society of Biological Psychiatry, we shared a total of six posters that outline new work to understand the underlying mechanism of REL 1017. What we found was very interesting and included additional support for a role in neural plasticity, and inside regarding its binding to MDR subunits, in particular the 2D subunit, which appears to explain both the lack of dissociative side effect, as well as the rapid and sustained antidepressant effect.
Preclinical and clinical studies.
Next are the society of biological Psychiatry, we share a total of six posters that outlined new work and to.
And to understand the underlying mechanism route 10 17, what we found was very interesting and included additional support for our role in euros neuroplasticity.
And the insight regarding its binding to and N and M. D. R subunits and particular, the two diesel unit, which appears to explain both the lack of the social side effect as well as the rabbit and sustained antidepressant effects and lastly, we share the D E. P. A day American say cash.
Sergio Traversa: And lastly, we share with IDAPA, the American Psychiatric Association, the data from the Phase 2 study that showed that REL 1017 demonstrated the statutes, statistically significantly rapid and sustained efficacy with large effect size, in addition to favorable safety and tolerability profile and absence of any sign of withdrawal after any treatment.
And the Psychiatry Association and the data from the Phase two study that showed that raws tens of intent from 10, 17 and demonstrated a statistically significant and rapid and sustained efficacy with larger fixed sites. In addition to favorable safety and tolerability.
Profile and absence of any sign of withdrawal after and and treatment and summary, tens and tens and 17 develop and program remains extremely active and we anticipate multiple key data readouts over the next 12 months.
Sergio Traversa: In summary, the Red 1017 development program remains extremely active, and we anticipate multiple key data results over the next 12 months. Importantly, as Chuck noted, we have a strong balance sheet driving this robust R&E effort, and we have cash to support us through these expected data processes. As always, I'm grateful to the Ramada team for their continued hard work and dedication to executing on our mission. And I would also like to extend my sincere thanks to the participants and clinical partners involved in the RELT-1017 clinical trials for the effort in advancing this important therapy through the clinic as many expeditions as possible.
Importantly, as Chuck noted, we have a strong balance sheet driving these robust R&D effort and we have cash to support us through these expected that data point.
And as always and I'm grateful to the room other team for their continued hard work and dedication to executing on our mission and.
And I would also like to extend my sincere thanks to the participants and clinical partners involved and the relative 10 17 clinical trials for their effort in advances these important therapy.
Through the clinic as expeditiously as possible I do believe it and now we can open up for questions and operating.
Sergio Traversa: I do believe that now we can open up for questions and answer them. You can go ahead and open the line for questions. Thank you.
You can go ahead and open the line for questions. Thank you.
Thank you.
At this time, we will be conducting a question and answer session. If you would like to ask a question. Please press star one on your telephone keypad and confirmation tone will indicate your line is and the question queue, if and anytime you wish to remove your question from the queue. Please press star two.
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. If at any time you wish to remove your question from the queue, please press star 2. For participants using speaker equipment, it may be necessary to pick up your handset before pressing the star keys. One moment, please, while we poll for a question. Our first question is from Andrew Psy with Jeffrey.
And for participants using speaker equipment may be necessary to pick up your handset before pressing the star keys, one moment, please while we poll for questions.
Our first question is from Andrew Tsai with Jefferies.
Thanks, Good afternoon, and congrats on all the progress or Joe and team.
Andrea R. Tan: Thanks. Good afternoon and congratulations on all the progress, our GON team.
My first question is on the Oxycodone study the data reading out soon I'm very clear that you know all three doses and need to be stat, Sig and versus placebo.
Sergio Traversa: My first question is about the OxyColon study, and the data will be coming out soon. Very clear that, you know, all three doses need to be Statsi versus placebo. I'm sorry, not placebo, but Oxy, sorry, S methadone, and then it is similar to placebo. But can you describe just how similar S. Methadone should be to placebo on the vast liking score? Because from time to time, I think of a scenario where what happens if S. Methadone is showing 60 to 65, for example, just outside of the typical placebo range? How would we interpret that reason?
I'm, sorry, not placebo the oxy.
Sorry, I forgot that down and then similar to placebo, but can you describe.
Just how similar that's methadone should be to placebo on the Vas liking score because from time to time I think of a scenario, where what happens if S. Methadone is showing 60 and a 65 for example, just outside of the typical placebo range. How would we interpret that result, I guess.
Sergio Traversa: Thank you, Andrew. Good afternoon.
Thanks.
Yeah.
And thank you Andrew good afternoon, and thanks for the question well look the and <unk>.
Sergio Traversa: And thanks for the question. Well, look, it's a key question. So oxycodone 40 milligrams is what we use as a comparator. It's not a very high dose, but it's high enough. That is clearly likeable by patients or people, participants that like to take narcotics as a recreational drug abuse. It's a CNAS drug. You may expect, we may expect, that it's not a placebo, right? You take benzodiazepine, or you take a sleeping pill. It's not possible.
It's a good it's a key question so.
Okay, Gordon and 40 milligrams that is what we use as a comparator is not very high dose, but is high enough that is clearly likable.
By patients and people participants that they'd like to take a and I'll call it because the recreational drug abuse.
And as a CNS drug.
Do you we might have you might expect that we may expect that yeah. It's not placebo right you take and benzodiazepine, you'll take a sleeping pill is not placebo, you'll feel or something else.
Sergio Traversa: You feel something. And if this feeling will be pleasant or not is very difficult to say, although all the data that we have seen so far, nobody really likes it. We have Peter or 100 patients, and there is really no likability at all. If you really take it in phase one, if you take a high dose like 150 milligrams, and some patients have pained in nausea, so it's not a very pleasant feeling. So to answer directly your question, the most important thing to differentiate all three doses of methadone from 40 milligrams of oxycodone.
And if this feeling will be pleasant or not is very difficult to say, although all the data that we have seen so far and nobody really likes it we have Peter 100 patients and and there is really no like ability at all if you really take and phase one and could take a high those like 150 milligrams.
And you know some patient pay and nausea, so that is not a very pleasant.
Really pleasant feeling so to answer directly your question. We you know the and the most important to differentiate all three of those is a S. Mastodon from 40 and made it goes on all the Oxycodone.
Sergio Traversa: We don't expect to be very different from placebo, but it's not required that, you know, we are similar to placebo. So I would focus everybody's attention on oxycodone. Placebo is there just because we have something to compare, but it's not, we are not comparing methadone to placebo. Right? I'll answer your question there. Oh, yeah, that's very clear. Yeah, thank you. Yeah, very good.
And we don't expect to be very different from from placebo and there's also there's not required that.
We are similar to placebo, so I would focus and everybody's attention to the Oxycodone placebo. There just because we have something to compare but it is not we are not comparing and as matt that onto to placebo.
I Hope I answered your question from David Oh.
Yeah. That's yeah. Thank you yeah very good and so my follow up question is let's just say you know data is clearly positive completely clean what it be then be fair for investor and is assumed that the second abuse liability study versus ketamine is pretty much derisked because you would have seen data on for example.
Sergio Traversa: And so my follow-up question is, let's just say, the data is clearly positive, completely clean. Would it then be fair for investors to assume that the second abuse liability study versus ketamine is pretty much de-risk because you would have seen data on, for example, dissociation, and hallucination from the oxycodone study? The straight answer is yes. I would say that, you know, I'm an old pharmacist, and I always say that drugs tend not to change the way they work during overtime.
Dissociation hallucination from the Oxycodone study.
And a D. A straight answer yes, the I would say that yeah, and I'm, an old pharmacist and I always say that drug drugs tend not to change.
The way they work and.
And then over time, so we don't see anything that would show any of these social upheaval any hallucination or anything there would be like ketamine or M and M N D E and toxic.
Sergio Traversa: So we don't see anything that would show any dissociative effects or any hallucinations or anything that would be like ketamine or like an MNDA toxic effect. There is no guarantee, I mean, it's not 100% guaranteed, but it's unlikely that in a different study it will show up as very different from what we see so far. So yes, the answer is yes. We do believe that there is the risk component when we see the oxygen data. Perfect.
Effect.
And there is no guarantee I mean, it's Nick.
100% guaranteed but it's unlikely that in a different study.
It will show up as and is a very different from what we see so far so yes. The answer is yes.
We do believe that the visit and the risk and component when we would see day Oxycodone data.
Andrea R. Tan: Perfect. Thank you, Sergio.
Perfect. Thank you Sergio.
Thank you Andrea.
Our next question is from Joon Lee with twist.
June Lee: Our next question is from June Lee with Churist.
Hi, Thanks for taking our questions.
June Lee: All right, thanks for taking our questions. I believe the DEA is on the record saying that Dextramusferone is, is a lax addiction liability. What's the basis for that, for the year making that claim? And is that based on any specific study?
And I believe the DEA is on record, saying that extra methodology is it.
And it lacks addiction liability and what's the basis for that and for the.
We're making that claim and is that based on these specific study.
And if so what doses are used and that's related to that are you aware of E. Making similar claims about S ketamine and that's compared to ketamine.
Sergio Traversa: and if so, what doses were used? And related to that, are you aware of the A
Sergio Traversa: making similar claims about S-Ketamine that are compared to ketamine. Thank you.
Thank you.
Hey, Joe and good afternoon. Thanks for the question, Yes, we actually we asked the same question to the day, where they are the data that are the base the statement that S methanol and music exam from abuse risk and respiratory depression and they did.
Sergio Traversa: Hey June, good afternoon. Thanks for the question. Yes, we actually asked the same question to the DA, where the data that they based the statement that S-Metodon is exempt from abuse risk and respiratory depression came from, and they did not do any proprietary study that is not published. They base their statement and their opinion on what is available, and there is quite a bit of literature available, including the phase one that Ramada did with the single dose and multiple doses of Smethodon. So they look at whatever is available, and they draw conclusions. That's pretty much how they did it.
Not do any profit studies study.
That is not published they based their statement and their opinion on what is available and there is quite a bit of lead times were available, including the phase one and that our ramada did and with the single dose and multiple dose almost method and so they look at whatever is available and you can draw that conclusion.
So that's pretty much how they did it a D and the comments on S. Ketamine and while it's had somebody look has kept them and it is and it's been on the market for quite a bit of timing few European countries as an anesthetic to replace ketamine and Theres a lowered those other all of our semi cap.
Sergio Traversa: The comments on eschatamine, well, scatamine, look, scatamine has been on the market for quite a bit of time in a few European countries as an anesthetic to replace ketamine and is a lower dose of racemic ketamine. Technically, pharmacologically, there is no difference between S-Katamine and Rathemic-Katamine. So it's pretty much the same thing, just different names.
I mean.
Technically pharmacologically there is no difference between that Scott and and racemic cats and and so it's pretty much. The same thing just different does so I would be sort of price if a D. A wood schedule as ketamine and a different way than racemic kept them and and.
Sergio Traversa: So I would be surprised if the DA would schedule S-Katamine in a different way than Rasemi-Katamine. And Johnson and Johnson, which is Pramato, they performed the abuse study comparing nasal eschatamins probato versus intravenous ketamine, and pretty much, they were the same thing; there was no real difference. Eschatamine is pretty much, will remain the same schedule as Rosemic Catamine. With that said, maybe I can add one thing, that catamine and Escatamon are both scheduled three, that is very different from Schedule 2, and there is probably more difference between Schedule 2 and 3 than any other scheduling between 3, 4, and 5.
And the Johnson and Johnson and we just brought that they perform D. A.
Abuse study, comparing and nasal and sky.
It provides the worst was intravenous ketamine and pretty much snow day at the same thing so.
And then there was no no real no real difference out ex cats, I mean, there's pretty much with will remain the same schedule that is that and.
And sort of see me cut I mean, we did say and maybe I can add one thing that ketamine and discuss them and they are both scheduled and three that is very different from scheduled two and there is probably more different between scheduled two and three than any other scheduling and between three four and five.
And the reason being that the major worry of D. S. P. A is not really just the abuse potential is the safety and while narcotic opioid oxycodone.
Sergio Traversa: And the reason being that, you know, the major warrior of the FDA is not really just the abuse potential but the safety. And while narcotics, opioids, oxycodone, percresset, whatever is like a mu-opio opiate agon, as that dangerous side effect, that is respiratory depression that we have not seen with acetatone. Catamine and eschatamine don't cause any respiratory depression. That's why they're used in kids, and they're used as an anesthetic because they are very safe.
Perfect day, whatever is like a more opioid agonist.
Is that dangerous side effects that these respiratory depression that we have not seen with the S. Methadone ketamine and that's got them and they don't do any respiratory depression, and that's why they use and kids and their uses and anesthetic because the other big states. So that's the reason that they are in schedule III and not because they are.
Sergio Traversa: So that's the reason that they are in Schedule 3, not because they are less abusable than narcotics or you get a lower high with ketamine or as ketamine, but because, really, they are not very dangerous in terms of overdosing. So I hope that helps. Yeah, just one more thing. There was a pre-planned intern for the HAP study using ketamine, which led to sort of a steady premature termination because of the lack of the effect there. It's similar in turn look was done.
Yes, and usable and.
And then they'll Claudio day, there you get less high with cat, it's Katherine and but because they really they are not they're not very dangerous in the income overdosing. So hope that helps.
Yeah, and just one more thing you there was a pre.
Preplanned interim for the Hap study, using ketamine, and which led to sort of city.
City.
And mature termination because of the lack of effect there. It's similar and term look was done for the study using oxycodone and and.
Sergio Traversa: For the study using oxycodone, and was there anything out of the ordinary that
Was there anything out of the ordinary that that you.
You saw on a blinded basis and that study or that.
Sergio Traversa: that you saw on a blinded basis in that study?
And the oxycontin and behave as it should based on historic data in terms of AR and the city and the liability.
Sergio Traversa: or the oxycontin behaves as it should based on historic data.
Sergio Traversa: in terms of eliciting likability. Yes, that's a great question. The oxycodone study is going much faster than the ketamine study because there are a lot more subjects that like to abuse opioids than they like to abuse ketamine-like products. So we will have the blinded, whatever you call it, like quality control, but it's going to be very close to the end of the study. So fortunately, unfortunately, it will not help much. I believe it would be like, probably, the end of May or early June, and you know the last patient is supposed to be out before the end of June.
Ah Yes, no. That's a that's a that's a great question did the oxycodone.
<unk> is growing much faster and then the cat I mean, because there is a lot more subject that like to abuse opioids, then they like to abuse cats, I mean like product. So we will have the.
Blinded.
What I would call it like quality control, but is going to be very close to the end of the study and a.
Fortunately or unfortunately, it will not help much I believe it would be like probably and the May early June and you know the last patient is supposed to be out before the end of June so Wendy.
And we won't be able to do much in term of Oh, taking action like we did a weed cat I mean with that said cats, I mean, especially oral cap them and as a you know a history of not being like bioavailability is really valuable and not being very likable and.
Sergio Traversa: So we won't be able to do much in terms of taking action like we did with Kat. I mean, with that said, Catamine, especially oral ketamine, has a history of not being as bioavailability is very variable and not being very likable in terms of like abuse potential, while oxycodone, 40 milligram is not a very high dose, but definitely it is much more likable than oral ketamine So we do believe that it's going to be unlikely that we will see what we saw with the ketamine study.
Turmoil like abuse potential, while Oxycodone and 40 milligram and it's not a very high dose, but definitely it is much more like a bold and oil cuts I mean 100 milligram.
So we do believe that and it's gonna be unlikely that we will see what we saw with that.
With.
And study, we have seen and the qualification period, where you would select the the participants they have too and they are tested and they have to recognize and like the control wildcat them in the percentage of patients that were excluded from the modification was over 50% the indie Oxycodone study.
Sergio Traversa: We have seen in the qualification period where you select the participants, they are tested, and they have to recognize and like the control while ketamine, the percent of patients that were excluded from the qualification was, you know, over 50 percent. In the oxycodone study in qualification, you know, the percent of people that are participants that they liked the control, which was 40 milligrams of oxygic acid, was very high, was close to 100%. That we feel more comfortable about this study. Clearly, oxycodone is a much easier control than the
And qualification you know the percent of people that are participants that are they like the control. There was 40 milligram Oxycodone was very high and it was close to 100%. So that we feel more comfortable about these studies clearly oxycodone and it's a much more a easier comp.
Control than other than ketamine.
Looking forward to the data and thanks for taking our questions.
June Lee: Looking forward to the data, and thanks for taking our questions.
Likewise, and thank you John.
Operator: Likewise. Thank you, John. Our next question is from Yatinsin about Guggenheim Park.
Our next question is from Yadkin and Asia with Guggenheim Partners.
Hey, guys. Thank you for taking my question just a couple other on the H M. P side, all human abuse liability study some cash.
Yatinsin: Hey guys, thank you for taking my question. Just a couple on the HAP side, or the human abuse liability study. So I think, Sergio, you were just talking about scheduling. Can you maybe help us understand how each of these studies helps you from a scheduling perspective? If you show a static difference versus oxy and ketamine, do we know you're not going to get the same level of scheduling? And then the other part of the question is, what type of scheduling? Of scheduling, would you be okay with, do you expect some form of scheduling with 1017? So that's the first question. I do have another follow-up.
I think sorry, you were just talking about the scheduling and can you maybe help us understand and how each of these studies help you from scheduling perspective, if you show a stat Sig Diff'rent watersheds oxy and ketamine do we know you're not going to get the same level of scheduling and then the other part of the question is.
What type of scheduling would you be okay with do you expect some form of scheduling with a 10 and 17. So that's the first question and I do have one other follow up.
And thanks, so yeah.
Sergio Traversa: Thanks, Yadine. So let me ask you the question a little bit more in an expanded way to be very clear. So the scheduling is determined by a process that involves the CSS, that is the controlled substance stuff, that is a piece or part of the FDA. The CSS advises the FTA, then the FDA kind of gives a recommendation to the DA, and the DA makes the final conclusion. All this happened after approval.
Yeah. So let me let me ask the question a little bit more expanded our expanded way. So to you know to be to be Barry to be very clear. So the scheduling is determined by a process that involved the CSS that these the controlled substance stuff that is a piece or part of the F D a to CSS.
Advises the F D a.
And then the FDA kind of give recommendations to the D. A and the D. A makes the final conclusion and all this happened after approval the day, a as 90 days after a proven through determined and scheduling and scheduling and is based on a.
Sergio Traversa: The DEA has 90 days after approval to determine the scheduling. The scheduling is based on a... and it's called an A-factor analysis that includes the pharmacology, the mechanism of action, the receptor affinity, the danger, how dangerous the drug is, and includes the likability, how much potential abusers like the drug. Clearly, the likeability is a key factor, as well as safety, right?
And it is called a factor analysis that includes.
And the pharmacology of the mechanism of action and the receptor affinity the danger and know how dangerous the dry and includes the likeability how much you know potential abuser like the drug and clearly the likeability. It is a key factor as well as safety right.
If you show safety like CASM and then the F. D. A is clearly they look at things and it would be in a different way.
Sergio Traversa: If you show safety like ketamine, then the FDA is clearly going to look at things in a different way. So to answer directly your question, the data that we will see, and hopefully, we hope, we will see, they are statistically different from oxycodone, all three doses of S-metodon. We cannot say, like, this is an FDA and D-A decision. We cannot, like, tell you are 100% certain, but it's going to be extremely unlikely that it will be the same schedule as schedule two.
So to answer directly your question.
If we the data that we will see and hopefully that we hope we will see a.
They are statistically different from ER Oxycodone and all three doses of as Mastodon, we cannot say for like pieces and SDA and D. A decision and we cannot lucky.
And the percent certainty, but it's going to be extremely unlikely that.
It would be the same scandal of Oh, and scheduled to and D could be you know higher scheduled and it will depend on what the.
Sergio Traversa: I mean, the could be higher schedule, then it will depend on what the ketamine study will show, but definitely being scheduled when you see a total, you know, statistically different score from oxycodone 40 milligrams, that would be a big surprise that would happen. That's also with the body of data that are already available that show a very high safety profile and there is no respiratory depression, you know, the most frequent of most like the, The dose limit for toxicity is nausea.
CASM in study will show, but definitely being scheduled to when you see a total you know statistically different.
And score from Oxycodone, and 40 milligrams that that would be extremely surprises that that that would happen and that's also with the the old body of data that the average available that show like a very high safety profile and there is no respiratory depression and most are.
Frequently for the most liked and they did it.
The dose limiting toxicities, and nausea, and and so that's a it doesn't make us pretty comfortable that if we show. These results is now going to be scheduled to.
Sergio Traversa: And so that makes us pretty comfortable that if we show these results, it's not going to be scheduled too. And to the second part of your question, what kind of, you know, what schedule we will be happy with?
And and do the second part of your question, what kind of you know whats casualty, we wouldn't be happy with well taxed from a door fun is or behind the counter and so there's not even a prescription and now we definitely do not expect as Mastodon force because it's a new chemical entity when it's pretty unlikely it's impossible, it's not going to be and.
Sergio Traversa: Well, tax on atorphine is behind the counter, so there's not even a prescription. Now, we definitely do not expect it to be as effective as methadone, first because it's a new chemical entity, and it's very unlikely. It's impossible.
Sergio Traversa: It's not going to be an over-the-counter drug of anything like that. But, you know, the bands of yazepine and sleeping pills and, you know, they are Schedule 4, 5. It trusts me directly, and this is not the guidance for what the scheduling of Methadone will be, but I would say Schedule 4 or 5 is pretty much the same as a non-scheduled drug. Schedule 3 is very benign, and there are many drugs that are Schedule 3, and they are prescribed very widely. Got it. Let me answer your question directly. I would be happy with scheduled key and above, but I don't think commercially it would make any sense. Schedule 2 would be an issue.
Over the counter at all Oh, and anything like that but then all the bands of the European and sleeping pills and you know they are scheduled for five.
And if you ask me directly and this is not the guidance and what the scheduling all that's met him and will be but I would say is scheduled for one five is pretty much the same as as the Nonscheduled schedule. III is very right is very benign and there is many drugs that are scheduled tree and no doubt and their prescribed.
Maybe widely.
Got it so I would let let let me answer your question directly I would be happy with scheduled T and the ball I don't think commercially it would make any difference scheduled to would be it would be an issue.
Yatinsin: We cannot hide that. Yeah, very, very helpful. Then the other question I have is about the monotherapy study. Can you maybe help us understand a little bit more in detail, any particular feedback you got from the FDA, the type of patient you're gonna enroll, any standard medication that is allowed,
But we cannot Hy tech.
That's very helpful and the other question and I have is on the monotherapy study can you maybe.
Help us understand and little bit more and details of any particular feedback you got from the FDA the type of patient you're going and I know any standard.
Hum medication that is allowed it seems like you are guiding for completion of this study. This year do you mean, the data will become available just yet and I'm just maybe you know.
Sergio Traversa: It seems like you are guiding them for completion.
Sergio Traversa: You know, data will become available this year or maybe just maybe provide Yes, two parts, right. The feedback from the FDA, I'm not sure I'm allowed to say anything, but let me try to phrase it in a nice way. The monotherapy protocol is very similar to Reliance 1 and 2, to the add-on therapy. The only difference is the patient population. They are not taking any treatment.
And provide some color there thanks.
Yeah, Yeah, yes, the two.
Two parks right and the feedback from the FDA and I'm not sure I'm allowed to say anything but [laughter].
Let me try to phrase it and are in a in a in a nice way. The monotherapy protocol is very similar to the reliance.
Reliance one and two to the add on therapy. The only difference is the patient population they have not.
And taking any treatment and why the other one and they are taking a treatment. So we are in process or with the two phase III as add on therapy and so let's put it. This way we don't expect that there is anything.
Sergio Traversa: Why the other one? They are taking a treatment. So we are in the process with the two, phase three, as add-on therapy. And so let's put it in this way.
Sergio Traversa: We don't expect that there is anything that is particularly worrisome about the monotherapy. It's the same thing. So the FDA was okay with the add-on therapy. We do believe that they are okay with the monotherapy as well.
That is a particularly worries on about the monotherapy and the same thing so that the FDA was okay with the add on therapy.
And we do believe that they are okay with that.
The monotherapy as well.
Yeah.
And I Hope I asked you and yeah.
Sergio Traversa: I hope I can answer you in some way. The data, well, yes, the patient population for monotherapy is much larger than about, I would say, at least two to three times larger. The patient population will add-on therapy. So recruitment is, we've been guided to like six, seven months for recruitment. And we are planning to start before the end of this quarter, that is, the next two, three, four weeks. So we should be on time to get it done by year-end.
Some way thank you yep okay.
And the data well see the patient population.
Relation for monotherapy, it's much larger than that about I would say.
At least two to three times, the patient population or add ons that'd be so recruitment is that and we've been guided to like six to seven months.
And then and we are planning to start before the end of the.
This quarter that is over the next 234 weeks.
So we shouldn't be on time to get it done by year by year end, and we always a little cautious in terms of top line because it's.
Sergio Traversa: We are always a little cautious in terms of the top line because it's always, it takes some time to, you know, clean the data and the statistical analysis, and year-end, it comes around Christmas. So I'm sure you don't want to have, you know, to write a note on Real Mada on December 24th. There would not be so, so. Yes, but it should be done around Christmas.
It's always it takes some time to clean the data and the statistical analysis and ear and it comes around Christmas and so I'm sure you don't want to have the right and no income room, either on the December 24th.
And it would not be so and so.
Yes, but it's it should be done around that and I went there and.
Got it very helpful. Yeah, There's always JP Morgan I don't know, if there's going to be viewed swallowing and personal and he's always jump and working and in general and size is usually a nice stage.
Sergio Traversa: Got it, very helpful. Yeah, there is always JP Morgan. I don't know if it's going to be virtual or in person. There's always JP Morgan, in general, is usually a nice stage if we have some good data to share. But, you know, we haven't even started, so I don't want to give you any particular guidance. It's too far away to give you anything. It's going to be around here for a while. Our next question is from Salveen Richter with Goldman Sachs. Hi, thanks so much for taking our questions. This is Sony.
And have some good data to share.
But yeah, we haven't even started so I don't want to give you any particular guidance. It's a it is too far away to be just from some specifics and soon to be around there.
Thank you.
Our next question is from Salvia and Richter with Goldman Sachs.
Hi, Thanks, so much for taking our questions. This is sonya on for Celgene.
Operator: Our next question is from Salvin Richter with Goldman Sachs. Hi, thanks so much for taking our questions. This is Sonia on behalf of Salvin.
And so I E. You presented some data and I'm honored all 10, and 17 worthy effect with a function of percent last years since the onset of M. D D.
Sonia: So at APA, you presented some data on REL-1017, where the effect was a function of percent life years since the onset of MDD. I was just wondering if those findings will influence the design of your monotherapy trial at all. Thank you, Sonia.
And just wondering if those findings will influence the design or if you're a monotherapy trial at all.
Thank you Sonya yeah, that's it and that's a it's a very good question and the straight answer is no. They know the overall idea is to make as much as possible. The overall like standard population. So we don't want to pre select and we should have to stratify.
Sergio Traversa: Yeah, that's a very good question. The straight answer is, "No." The overall idea is to mimic as much as possible the overall, like, standard population, so we don't want to pre-select, and we should have to stratify the patients based on how long they have been affected by depression. And, you know, it was extra work, but, you know, the FDA likes to see real world studies. So, you know, we prefer to do it in a, like, standard way without stratifying.
We discuss it but we should have had to stratify the patients based on how long they have been affected by depression, and you and I was the next day work, but are you know and the FDA likes to see like real word and so.
That is so you know we prefer to dusk, Louisiana.
Standard way without stratified and so we went and enrolled patients at depression for 20 years and patient day with depression, and Florida like.
Sergio Traversa: So we will enroll patients that have depression for 20 years and patients that have depression for like two months. So that's a straight answer is no. There was no impact from these data.
And two months so that's a straight answer is no.
And there isn't there was no impact from from these data the way we read Oh, you know these data that have been important one.
Sergio Traversa: The way we read, you know, these data that have been important for one, specific reason. The NMNDA antagonists, like Hesmetodon, have this picture; they are neural plastic, so they increase the functionality and the number of synapses in the brain, the communication between brain cells. That is very different from your SSRI. You may remember, I was involved in the development of Proza for quite a few years, for five or six years.
Ossific reason.
No the NMDA antagonist like Mastodon, and they had this pizza and.
And you were all plastic so they you know they increase the functionality and the number of Synopsys and are in the brain. The communication between brain cell that is very different from Oh, SSRI and you may remember I did that it was involved and the development of pros that for quite a bit from years for private and 60.
And this is a rise of cinryze and the old traditional antidepressants they tend to be more they are symptomatic right and they treat the symptoms of depression and.
Sergio Traversa: And they sensorize the old traditional antidepressants, they tend to be more symptomatic, right? They treat the symptoms of depression. And if you satisfy the patient from the long-term depressed patient and the short-term depressed patient, you don't see any difference with traditional antidepressants because, you know, they don't really have a neuroplastic effect. Unlike what we have seen with methadone, where the neuroplastic effect is more evident, especially when this patient is treated for a week.
And and if you would.
You're satisfied the patient from.
Long term the presentation and and.
Short term depressed patient you don't see any difference with traditional antidepressant because they don't have really a neuroplastic effect.
And like what we have seen is methadone that Oh, and then euro plastic effect is more evident, especially these patient about three years and for a week right. So if you have been depressed for 25 years and and.
Sergio Traversa: So if you have been depressed for 25 years and, you know, you get treated for a week, it's unlikely you will see the kind of drastic effect that you actually have seen in patients that were depressed for a shorter time.
You've got three day for a week.
And it's unlikely that you would see like a drastic effect that you actually you have seen and patient they've had depressed for a shorter time, so most likely and patient had been depressed for a long time, he's going to take a little bit more longer treatment and.
Sergio Traversa: So most likely, patients that have been depressed for a long time, it's going to take a little bit longer treatment, and so that's probably what we may see in phase three. But the understanding and the learning from this data is that it's confirmed, there's confirmation that an immediate antagonist or S methadone has a different mechanism, and they do something different to patients with depression. So I would say in quotes and very carefully that we are looking more at a disease-modifying effect instead of just a symptom. I hope that helps. Thank you. Once again, if you have a question, please press star 1.
And so that's we probably and we may see something and the phase III.
But yeah the from the the understanding and the learning from these data as that is confirmed as a confirmation that a and then maybe antagonism I'll ask Matt to them. They have a different mechanism and they do something different to patients with depression. So it's a I would say.
And quotes and very carefully that we are looking more of a disease modifying effect instead of being a symptomatic.
And I hope that helps.
Thank you.
Yeah.
Once again, if you have a question. Please press star one our next question is from Jay Olson with Oppenheimer.
Jay Olson: Our next question is from Jay Olson with Oppenheimer. Oh, hey, Sergio, thank you for taking the questions, and congratulations on all the progress. Since Sage has an important catalyst coming up with data from their MDD study, can you just talk about what some of the differentiating features are for an NMDA agonist versus an NMDA antagonist versus agam and what you think would motivate MDD patients to prefer S methadone versus their analone. Thank you. Okay. Thank you, Jay. You always ask me tough questions.
Oh, Hey, Serge you. Thank you for taking the questions and congrats and all the progress.
Since Sage has an important catalysts coming up with.
Data from their M. D. D study can you just talk about what some of the differentiating features are four and M. D. A agonist versus sorry, and NMDA antagonist versus a Gaba Pam and what you think would motivate M. D D patients two to prefer.
And as methadone versus around one and thank you.
Thank you Jay you already asked me to ask questions.
The day well you know the day, there is quite a bit of differences between the allosteric modulator. Andy you know the the Gaba modulator like Sage and practices, then and M. N D. A channel blocker like ex methadone and so the mechanism is totally different although ultimately.
Sergio Traversa: Well, you know, there are quite a bit of differences between the allostatic modulator and the GABA modulator like Sage and Praxis, and NMNDA channel blockers like Smetodon. So the mechanism is totally different, although, ultimately, at the end, we do believe that also the GABA modulator may have some influence on the NMNDA process and activity, but it comes from a different angle and quite a bit the opposite angle So probably mechanistically, they're very different.
And we do believe that also the Gaba modulator and they may have some influence on the N and M D. A.
And the process and activity, but could come from a different from a different angle and quite a bit the opposite angle, so probably mechanistically, they're very different.
Sergio Traversa: Um, in terms of activity, probably, I mean, you know, I know what is available publicly from Sage and from Praxis, but they tend to have a, you know, they are rather fast acting, but they tend to, like, have a shorter-term efficacy profile. So they are more suitable, and this is, you know, that's what Sage is claiming, and, you know, they're definitely a lot more than I do. But, you know, they're more suitable for an episodic, short story.
In term of activity, probably and I know I.
And you know what there's available publicly from from Sage and from from practices, but they tend to have and you know they are rather fast acting, but they tend to like have a shorter term efficacy profile. So they are more suitable and these and yeah. That's what stages is claiming and.
And they're definitely not a little more and I do but.
No and they they are more suitable for episodic short term and treatment of depression and when you do.
Sergio Traversa: long-term treatment of depression, and we do believe there is a market for that too. So it's, you know, it's a very large market. So there is enough space for drugs with different profiles. So, yeah, they are quite a bit different. The bottom line is that, you know, there's very little correlation between the two, different mechanisms of action, different clinical profiles. We hope they all work.
Believe there is a market for that too. So it's yeah. It's a very large market. So there is enough space for drugs with different profiles. So yeah. So there are quite a bit different that the bowl and line is that you know there is a very.
Little correlation between between the two different mechanism of action different clinical profile.
And we hope they all work.
Sergio Traversa: Likewise, and thank you for that. I guess since you had a number of posters that you presented at recent medical meetings, can you just talk about any feedback that you got from physicians and KOLs at those conferences? Yeah, so the, right, unfortunately, virtual is not the same thing to sit there and hear the whole talking and the, right, the direct comments when they see the poster, so it's a little bit of guessing here, but the feedback was definitely positive, and it looks like, Look, the fact that S-Metod is different from an opioid is very clear to me. You see all the data. You have seen them as well.
Likewise, and thank you for that I guess since you had a number of posters that you presented at recent medical meetings can you just talk about any feedback that you got from physicians and kols at those conferences.
Yeah, So D D and unfortunately, we had a small it's not the same thing to sit there and do here like day, then the whole talking and the right direct comments when they see the poster. So I'd say that there was a little bit of guessing here, but you know the feedback was definitely positive and then you know the.
It looks like and you know based on data and its method on the east starting to.
Differentiator not only from racemic method and I Love. The fact that that's marathon and it's different from and opioids, It's very clear to me and I know you'd see all the day, you have seen them as well and but all of a sudden turmoil like and the other NMDA antagonist right. Because the question that I've been and we have been asked and we asked our salaries and why.
Sergio Traversa: And also in terms of, like, the other NM-NDA antagonist, right? Because the question that I've been asked, and we have been asked, and we have asked ourselves, is why S-Madon, even at very high doses, forget the narcotic effect; that is not there. But even the hallucination and dissociation, the ketamine-like effect is not there, even at doses that, you know, patients or healthy volunteers cannot tolerate. And that one is, was one of the angles that came up from this study, right?
Smather don't even at very high doses forget Narcoleptic effect net debt, it's not there, but even the hallucination and dissociation. The ketamine like effect is not there even though those as that yeah.
And the patient sort of healthy volunteer they cannot tolerate and that's when it was one of the angle that AR was came out from from this study and there is a mechanism and why.
Sergio Traversa: There is a mechanism, I don't want to go into too much detail on an earning call, but the specific activity for the subunit 2D of the NMNDA receptor, unlike ketamine, which seems more, it works on the 2D, but it also has as affinity for the A and B, they are more closely related to the physiological activity of the NMNDI system and glutamate.
And it goes too much and detail and earning call, but the the you know the specific activity for the sub unit two D of the NMDA receptor and like Cats, I mean that seems more it works and the two D. But he also is as affinity for the a M. B. They are more related with the physiological ex.
T V. Do you have the NMDA system, and they can automate and that could explain and I should explain the fact that that's method and does not have this the social theme and elucidation and effect even at high doses. So yeah. The it seems that the differentiation process is.
Sergio Traversa: And that could explain or should explain, you know, the fact that S Methadon does not have this dissociative and hallucination effect, even at high doses. So, you know, it seems that the differentiation process is moving ahead rather successfully. We are learning too, right? It's not, you know; we saw the clinic also. We are looking for the reason that the clinical profile looks like that. And, you know, we make good progress in really understanding how it's method and works. And it's fascinating.
Is moving ahead and rather successfully we have learning too right.
It's not and you know.
We saw the cleaning and also we are looking of the reason that the cleaning up of price and it looks like that and then and you know we made good progress you'd really understanding how it's Matt doesn't and works and it's fascinating.
Excellent and Super helpful. Thank you for taking the questions.
Jay Olson: Excellent. That's super helpful. Thank you for taking the question. Not quite, eh?
And likewise Z.
Our next question is from Marc Goodman with SBB Leerink.
Operator: Our next question is from Mark Goodman with SVB Lairn. Hi, this is Julianne from Mark. Thanks for taking my question. Can you provide more color on the enrollment of the reliance trials? They're still targeting 55 sites for each study. And how should we think about the COVID impact on the clinical conduct of these trials as the pandemic condition continues to improve? Thank you.
Hi, This is Julian call from Mark since we're taking my question. So kept probably more color on the enrolment of the reliance trials and we're still targeting 55 sites, where each study and how should we think about the COVID-19 impact on the clinical conduct of these trials.
At the and damage condition continues to improve and.
Mark Goodman: Thank you, Julian, and my regards to Mark. The, well, let me start with the COVID impact, in terms of enrollment, we have not seen, especially now with the vaccine, and you have not seen really any impact of, you know, the flow of enrollment, and if any, you can clearly read that everywhere. I mean, there's been an increase in patients affected by depression following the COVID situation. You know, people have COVID and have consequences with depression related to the aftermath of the virus, but also, you know, the old economic situation and everything that we know. We know enough about it.
Thank you.
Yeah.
Thank you Julian and my regards to Mark a D D.
Well, let me start with the COVID-19 impact in terms of enrollment, we have not seen especially and out where the vaccine and we have not seen really any impact of L.
That would slow the enrollment and.
And if any.
And then clearly you can read that everywhere I mean, they've been and increase in patient and affected by depression. Following the COVID-19. The Nicole with the situation you know and people that had COVID-19 didn't have no consequences with the pressure related to the aftermath of the virus, but also you know the old eco.
And what makes situation and the old you know everything that we know enough about it.
And so the no there's been no impact from from the COVID-19 situation on the enrollment it's a bit early to like.
Mark Goodman: So, no, there has been no impact from the COVID situation on the wrong. It's a bit early to, like, give exact guidance on how we are going. We started like three months ago, December, and January to enroll the first one, and then recently, a few weeks ago, we started to enroll the second one. So, you know, it's moving.
Give exact guidance on how we are going and you know and we start to like three months ago and December and January to enroll the first one and then recently a few weeks ago. We started from enrolled the second one. So you know it is moving to the sites are now and then most of the sides of it already in place for the well definitely for the very last one.
Sergio Traversa: The sites are, you know, most of the sites are already in place for, Well, definitely for Reliance 1. Reliance 2 is coming very fast, so we learned from the first one, so it's been a lot more efficient in activating sites and starting to enroll patients. So far, so good, and we don't really expect any major impact, barring catastrophic events that are not predictable, but COVID definitely is not. It's not an issue. That's very helpful.
And two is coming very fast so we learn from our from the first one so there've been a lot more efficient and activating sites and and.
And starting to enroll patient so so far so good and we don't really expect and major impact and barring catastrophic event that.
That and not predictable by the COVID-19 definitely is not it's not and it's not an issue.
Okay, that's very helpful.
Sergio Traversa: I also have a quick question for you to ask me. I think there was an increase in stock-based compensation in one-Q. So should we expect similar levels of spending for the remainder of the year, or is this more of a one-time payment? I do believe that this is a question that Chuck can answer. Yeah, yes, I am. Yeah, we've had a few fluctuations in stock-based compensation based on either... folks leaving the company and their stock options being
And I hope I have a quick question for SG&A I think there was an increase in stock based compensation and <unk>. So should we expect similar levels of spending and put a reminder of the year or is this moral and a one time payment.
Yeah, I do believe and that this is a question that Chuck can answer you.
Okay.
Yes, I am.
Yeah, well, we've had a few fluctuations based compensation based on.
Either.
Folks, leaving the company and their stock options being.
Brought back and in house, but the stock based compensation expenses that you saw in Q1.
Chuck Enst: brought back in-house, but the stock-based
Chuck Enst: compensation expense that you saw in Q1 of this year is a reasonable trend that you can expect.
This year is is a reasonable trend that you can expect.
Throughout the next few quarters.
Chuck Enst: This is a reasonable trend that you can expect.
Got it yeah, that's very helpful. Thanks for taking my question.
Julianne: Got it. Yeah, that's very helpful. Thanks for taking that question. We have a follow-up question from June Lee with Truitt.
Yeah.
We have a follow up question from Joon Lee with truest.
Thanks Julie.
Operator: Sorry, I was on you, sorry, and thanks for taking our follow-up question. Per FDA guidance, the HAP study should be conducted on experienced recreational users with recent history.
Yeah.
Sorry, I was and I was on mute sorry, and thanks for taking a follow up question.
S T a guidance to Hap studies should be conducted and experienced recreational users with recent history.
And the same general pharmaceutical class or pharmacological class.
June Lee: in the same general pharmaceutical class or pharmacological class. So for the Hapstity trial using Oxycontin as an active comparator, those subjects are experienced with Oxycontin or Oxycodone, not necessarily methadone. Is that fair or something?
So for the half study using oxy continents, and active comparator those subjects are experienced and oxycontin and oxycodone on that that class not necessarily a methodology is that a fair assumption.
Sergio Traversa: Yes, it is a very assumption. Look, methadone is used widely as a replacement for maintenance, but it's not a highly abusable opioid for a variety of reasons. Two, in particular. One is that it has a long half-life, so you don't have the pick that you have with oxycodone or immediate release. That's what drug abuse or recreational use they want to hide, right?
Or yes. It is a fair assumption the Macedon is used widely as a replacement for maintenance, but is not that high and yet usable opioids.
And for a variety of reason two in particular, one is that theres a longer half life. So you don't have the peak that you have with ER oxycodone or immediate release, that's what the drug abuse Oh, the recreational day. They wanted to hide right. If you have a you know slow onset is not something they like and particular the second one is that.
Sergio Traversa: If you have a slow onset, it's not something they like in particular. The second one is that racemic methadone; part of racemic methadone is dextromatone. And dextrometadone is an MNDA, and it really does not have any, we do believe that it does not have any narcotic effect. So it's, you know, it's not something that even recreational drug abusers like a lot.
Does he make methadone and possible method on these extra method and index from anthem and he's an M. D E and it really does not have any and we do believe that does not have any any narcotic effect. So it's and it is not something that even recreational drug abusers they like a lot.
Very helpful. Thank you.
June Lee: Very helpful. Thank you. Ladies and gentlemen, we have reached the end of the question and answer session, and I would like to turn the call back to Dr. Traversa for closing remarks. Thank you, Operator. So thank you all for joining the call today, and we are very pleased to share the recent progress with you as the REL-1017 clinical development program continues to advance. You are excited about the important catalyst ahead of us, and we'll keep you updated on clinical trials and activities throughout the remainder of 2021. Thank you again for joining us on the call. And enjoy the rest of the day. Thank you. This concludes today's conference. Thank you for your participation. You may disconnect your lines at this time.
And that's something.
Ladies and gentlemen, we have reached the end of the question and answer session and I would like to turn the call back to Doctor traversing for closing remarks.
Thank you operator.
So thank you all for joining on the calls a day and day, we're very pleased to share. The recent progress with you and as the rather than 17 clinical development program continues to advance and get excited about important catalysts ahead of us and we will keep you updated on clinical readouts and activities throughout the remainder of 2021.
Thank you again, all for joining us on the call and enjoy the rest of the day. Thank you.
This concludes today's conference. Thank you for your participation you may disconnect your lines at this time.