Greetings. Welcome to the Relmada Therapeutics results of registrational Phase III RELIANCE I trial for REL-1017 as an adjunctive treatment for major depressive disorder. At this time, all participants are on a listen-only mode. A question and answer session will follow the phone 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 conference over to your host, Timothy McCarthy of LifeSci Advisors. You may begin.
Thank you, Jamali. Thank you all for joining us this afternoon. With me on today's call are Relmada's Chief Executive Officer, Sergio Traversa, Maged Shenouda, Relmada's Chief Financial Officer, Dr. Paolo Manfredi, Relmada's Chief Scientific Officer, and RELIANCE program Principal Investigator, Dr. Maurizio Fava, the Chairman of Harvard's Psychiatry Department. Please note that certain information discussed on the call today is covered under the safe harbor provisions of the Private Securities Litigation Reform Act. We caution listeners that during this call, Relmada's management team will be making forward-looking statements. Actual results could differ materially from those stated or implied by those forward-looking statements due to risks and uncertainties associated with the company's business.
These forward-looking statements are qualified by the cautionary statements contained in Relmada's press release issued today and the company's SEC filings, including in the annual report on Form 10-K for the year ended December 31st, 2021, and subsequent filings. This conference call also contains time-sensitive information that is accurate only as of the date of this live broadcast, Wednesday, December 7th, 2022. Relmada undertakes no obligation to revise or update any forward-looking statements to reflect events or circumstances after the date of this conference call. I would like to turn the call over to Sergio. Sergio?
Thank you, Tim, as always, and good afternoon to everyone, and thanks for joining. Earlier this afternoon, we announced the top-line results from RELIANCE I, our first of two Phase III sister two-arm placebo-controlled pivotal studies evaluating REL-1017 at 25 milligram as a potential adjunctive treatment for MDD. RELIANCE I evaluated the use of REL-1017 in addition to a standard antidepressant for patients who have had inadequate response to at least one and up to three standard antidepressant therapies in the current depression episode. In this trial, REL-1017 was administered for 28 days. I'll give a brief summary, then, I believe, Dr. Maurizio Fava has been kind enough to accept, the offer, to present the data in detail. We'll also have a chance to ask any question that we will try to answer.
RELIANCE I did not achieve the primary endpoint of a statistically significant improvement in depression symptoms compared to placebo as measured by the Montgomery-Åsberg Depression Rating Scale, or MADRS, on day 28. As was observed in the monotherapy study of REL-1017, RELIANCE III, RELIANCE I exhibits similar implausible results in certain study sites that also affected the monotherapy study, where placebo dramatically outperformed REL-1017. In this study, the REL-1017 treatment arm, 113 patients, showed MADRS reduction of 15.1 points at day 28 versus 12.9 points for the placebo arm on 114 patients, which is a clinically meaningful difference of 2.2 points on the MADRS, as well as a statistically significant difference in the response rate, with a response rate of 27.2% on placebo versus 39.8% in the REL-1017 arm.
As was observed in the monotherapy study of REL-1017, RELIANCE III, unplausible results were observed in two of the same high-enrolling RELIANCE I study sites, where placebo dramatically outperformed REL-1017. While the patient population in RELIANCE I was different than RELIANCE III in that subjects enrolled should already have been diagnosed with depression and did not respond adequately to at least one up to three courses of antidepressant therapy. A limited number of the same high-enrolling sites had an unplausible rapid and sustained placebo response that outperformed REL-1017. To better understand the unplausible results seen in RELIANCE I, post-hoc exploratory analysis was conducted excluding the two high-enrolling sites. Data demonstrated that excluding the two high-enrolling sites from the study that showed unplausible placebo response, the REL-1017 treatment arm showed a 4.1-point difference versus placebo with a p-value of 0.02.
A second post-hoc confirmatory analysis using the well-established band-pass method that includes only site with plausible placebo response showed a robust difference between REL-1017 and placebo. While the overall top-line RELIANCE I results are disappointing, we believe these post-hoc analyses show a clear efficacy signal for REL-1017. We note that this efficacy signal was also observed with the post-hoc band-pass method analysis in RELIANCE III, our recently completed monotherapy MDD trial of REL-1017. We understand, though, that these post-hoc exploratory analyses are not sufficient alone to be used in an FDA submission. I would like to highlight that as it did in RELIANCE III, REL-1017 again demonstrated very favorable tolerability and safety as in RELIANCE I, confirming the results of Phase I and Phase II study with no opioid-like effects, no withdrawal effect, and no psychotomimetic effects.
Looking ahead, as previously discussed on our recent third quarter earnings calls, we applied several protocol and operational changes and made certain improvement to how they're currently evolving, in RELIANCE II, the second ongoing Phase III two-arm placebo-controlled pivotal study evaluating REL-1017 as a potential adjunctive treatment for MDD is being conducted. We accept online result from this study next year. As a reminder, once we have finalized and determined how to best execute on this announcement, we'll provide a firmer timeline for top-line results from RELIANCE II and potential additional studies. We anticipate data from the long-term open-label of safety study the first half of 2023, and they will be part of the planned NDA filing package.
In closing, we remain highly confident in the potential of REL-1017 to be a safe and effective new therapy for the treatment of MDD, and that the issue faced in RELIANCE one and three are related with execution of the studies, and in particular, site and patient selection. It is important to note that we have the financial flexibility to continue advancing REL-1017 in the clinic due to strong balance sheet with cash equivalent, and short-term investment of approximately $184 million at the end of the third quarter of 2022. I will now pass the call to Dr. Maurizio Fava, that will discuss more details about RELIANCE one results. Maurizio, line is yours.
Thank you. Thank you, Sergio. I'm gonna kind of recap a little bit the design. I think to mention this was a parallel comparison design of 28 days in which we were comparing 25 mg of REL-1017 against placebo in patients who had certain characteristics post antidepressant treatment. The primary endpoint was a change in MADRS, and the secondary endpoints were change in CGI-S and change in MADRS score at day seven and remission response rates at day 28. There was a follow-up assessment at the end of the 28 days.
The key inclusion criteria for the study, as opposed to the Study 303 that was a monotherapy, patients had to be stable for at least six weeks on an antidepressant treatment, with a duration of the episode of 8 months - 36 months. 8 weeks to 36 months. With a HAM-D score of at least 19, or 24, and 24 on the MADRS. The demographics of the sample, this was, this involved 227 patients randomized, 114 to placebo, 113 to REL-1017. The mean age was quite typical of an adjunctive trial. Approximately 43 years.
The BMI was on the lower side given the restricted range of BMI that we had required. Of course, more women than men were randomized. The percentage of patients with either Hispanic or African American, about 82 patients were either Hispanic or African American out of the 227 subjects. As Sergio has mentioned, the difference in terms of change was not statistically significant at day 28. In fact, as you can see in the first 14 days, the two curves are pretty overlapping.
You can start to see a separation that at day 28 was for the active, 15.1 points and 12.9 points on placebo. Again, a 2.2 point difference on the MADRS, which is considered clinically meaningful, although not statistically significant because of the standard deviation in the trial. Due to the variability of, you know, a few sites. The good news is that among the secondary outcome measures, there was a statistically significantly greater response rate on active of almost 40% versus 27%.
Almost a 13% difference in response rates, which was statistically significant and a 9% difference in remission rates which was not. When we removed the two high enrolling centers, I wanna point out that these were exactly the same centers that with no plausible results in the 303. If you remember, we ran the trials in parallel, both 303 and 301. Therefore, sites could participate in both. These two sites had no plausible placebo responses in 303, they had the same issue in the 301.
When we removed those two sites, the statistical significance was obtained at the level of 0.02, with a difference of over four points versus placebo. Removing only about 40 patients out of the 227 from these two sites. Being, you know, myself a big, you know, supporter of the band-pass method, I'll show you the results. From a safety perspective, there were no serious treatment related adverse events in RELIANCE I.
As you can see that, when you look at the percentages, 11% versus 8% for headaches, upper respiratory 7% versus 5%, nausea 7% versus 4%, diarrhea actually higher on placebo, constipation higher on placebo, and dizziness, 6% versus 1.8%. Very well-tolerated treatment across the active. Again, no AEs related to QTc prolongation, no evidence of increased suicidality or dissociative events or abuse potential. From a safety perspective, we confirm what we saw in Phase II and what we saw in 303 and now in 301.
Uh, uh, the, uh, the, you know, the well-characterized, uh, you know, band-pass showed an even greater, uh, um, uh, difference in terms of, uh, drug placebo difference when we looked at all the sites that had a plausible, um, uh, placebo response. But even just removing two and the same two that also were implicated in, um, affecting the results of three oh three, there was statistical significance. So, um, uh, uh, you know, overall, uh, we, you know, the, the study did not meet the, the p- you know, primary outcome, uh, uh, measure pre-specified. Uh, but, uh, uh, you know, the, uh, uh, the signal was there in terms of response rate. And removing the two sites which, uh, you know, we, we determined in three oh three to be, uh, these abnormal patterns of improvement on placebo, uh, we achieved statistical, uh, significance.
I'd like to thank all of you for your attention. I'm happy to take any questions as the principal investigator for 301.
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. A confirmation tone will indicate your line is in the question queue. You may press star two 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. One moment please while we poll for questions. Our first question comes from the line of Marc Goodman with SVB. I'm sorry. Our first question comes from the line of Uy Ear with Mizuho. Please proceed with your question.
Hi, guys. Can you hear me?
Yes.
Sure.
Thanks for taking my questions. I guess my a few questions. My first question is, can you elaborate on the factors that contributed to the high placebo response at these two sites? You know, as previously, I think in RELIANCE III, part of the issue was patients who were not truly depressed but have one-off situation of depression. Just wondering what the factors here are. Secondly, are these two sites the highest enrolling sites or are there other sites that have higher patient numbers? I guess my last question is, what are the protocol and operational changes are you planning for RELIANCE II? Do you need to consult with the FDA or have you already consulted with the FDA? Thank you.
Thank you. I think Maurizio has a question.
Sure.
He can answer.
These two sites were among the top enrolling sites. As you can see, they enrolled 40 subjects out of the 227. They were, what we consider high enrollers.
The question is, you know, if you notice, our placebo change of about 12 points, I would say within the, you know, the normal range of what we see in retrospective studies. You know, if you remove those two sites, you know, let me go back and show you. If you remove the two sites, the placebo change at day 28 becomes, you know, again 12.8, so still in around 12, which is kind of in a normal range. The difference is that, you know, in those two sites you have this paradoxical, you know, 10-point difference in the reverse direction for active.
When you remove that, you suddenly have a greater, a 4.1 difference. While in Study 303 there was a general tendency across all sites to have higher placebo response, in this, in this study, the placebo I would say was in, you know, all things considered, in a normal range. We did have these two sites, with this very paradoxical, pattern of the placebo outperforming by 10 points or more, the drug. That's exactly what they did in the other study.
In terms of how do we interpret that, you know, there may be issues of ratings, you know, because it's very odd that at the same site, drug, you know, underperforms where, you know, all the other sites show a benefit of the drug over placebo. These are the only two sites that show a marked worsening of the drug or, you know. I would say in terms of the explanation, something very unusual has happened in these two sites. They're not part of 302, which is a good thing. We're setting up a series of refinements in terms of subject selection.
Also we're gonna tighten up the quality of assessments to make sure that the ratings are conducted properly. We're putting in place 'cause in the case of these two sites, there may be an issue of, you know, implausible ratings rather than subject selection.
Okay. Thank you.
You're welcome.
Our next question comes from the line of Marc Goodman with SVB Securities. Please proceed with your question.
Yes, thanks for taking my question. This is really on the call for Marc. I have a question regarding the trial design. Given the study was 90% power for two points of difference in MADRS score, and the delta end up being 2.2 points. Can you provide more color on the lack of statistic here? I know you mentioned the standard deviation issues, but any additional color would be helpful.
If I understand correctly, you're saying a difference of 2.2 with a larger sample size could be statistically significant. As you remember, we were planning, you know, we, based on the feedbacks of the DMC, we terminated enrollment about two-thirds of the way in the trial, with 227 sub-subjects randomized. If I understand correctly, you're asking, had we gone further in the study, could that 2.2, you know, have become statistically significant? Is that your question?
Yep.
You're correct. You're correct. It could have. It could have. You know, you know, we conducted the, you know, the analysis with a smaller, you know, the interim analysis with a smaller sample size. At that point, the curves were too close to encourage us to continue. Had we done the interim analysis with a little bit more subjects, probably the recommendation would have said keep going.
You know, you know, you know, it's one of those things where, you know, you never know, you know, post-hoc, you know, it's kind of easier to say, "Well, had we gone further, with the trial, we might have achieved statistical significance." We clearly achieved it even with a smaller sample size with response rates. That was very, that was very good. Again, you know, unfortunately those two centers really hurt us.
Right. If I may, Maurizio, because of these two sites with this, you know, the placebo outperforming by nine, 10 points the drug, the variability just increased dramatically. That's kind of, you know, was not, I don't believe it was anticipated in the statistical plan.
Got it. Can you also talk about onset of action and the treatment effect over time during the four-week treatment period? I know you mentioned there's like no separation during the first two weeks. Can you maybe compare the data for both arms versus the prior Phase II study?
Yeah.
Yeah. Yeah. Go ahead. Go ahead.
The separation here was at day 14. You know, we didn't see it as early as in the Phase II. That could be, you know, because you have to realize that by day seven we had an average of 11 points on placebo. Even though the placebo response overall was in the normal range, the rapidity of the response was quite significant. That, that might have prevented us our ability to detect a signal earlier. Does that address your question?
Got it. Yeah. That's very helpful.
Yeah. In the Phase II, the placebo response at day seven was, I believe, eight points, including the study was an in-clinic that usually has a higher placebo response. In Study 301 and in Study 303, this placebo response has been like very high very quickly. Right. It is not very difficult to explain since these patients were supposed to have taken an antidepressant for two months and not to respond to an antidepressant. All of a sudden they take a placebo, and they get all better, you know, very quickly in a few days. Difficult to explain, but I don't have the we don't have the real explanation.
In clinical trials, expectations modulate the response rate. In general, one of the reasons why we see higher placebo response rates in Phase III than in Phase II is because the sites and the patients have greater expectations of the treatment. You know, as methadone at this point is a well-known among investigators, entity. There's a lot of interest, a lot of excitement. That, you know, we do see that expectations can modify. In fact, you know, the, you know, as methadone because of the Phase II study results, it starts to have a rapid effect. All these things tend to contribute to more rapid placebo response and more robust placebo response.
Got it.
As I said, you know, at the end of the day, at day 28, you know, a change of about, you know, 12 points, is, you know, It's kind of in the range, if you wish.
Yes. Thanks for the additional color. Very helpful.
Our next question comes from the line of Andrew Tsai with Jefferies. Please proceed with your question.
Hi. Thanks, guys, for taking the questions. I guess my first one is, you know, bigger picture. Will you likely need to start another Phase III on top of RELIANCE II? At the end of the day, we do need two successful studies, right?
Well, I think, you know, I think it depends on the interpretation of the FDA, whether the Phase II trial can be considered as positive trial. You know, again, I'm not, you know, it would require discussions with the FDA, whether or not the Phase II would be considered, you know, sufficient and supported if we only had one, that is, you know, RELIANCE II positive. Can we use both? I think this is leave it to the regulatory experts. Certainly we clearly had a robust positive effect in the Phase II trial.
If we have a robust effect in Phase III, RELIANCE II, and with the band-pass, both 301 and 303 showing a robust effect with the band-pass, one could consider that supportive. I think we have to look at the big picture here.
Yeah. Thanks. You know, when we compare the two. Oh, go ahead, sorry.
Yes. anyway, if I may, corporate-wise, it would be very prudent and, you know, we are nicely capitalized, very prudent to start at least one more study. Maybe not with the very exactly the same design, but in terms of spreading the risk. It would be, you, beneficial to have more than only one ongoing.
Very clear.
We haven't decided. We just got the data yesterday, it.
Mm-hmm.
We really crunched the time to put them out today.
Got it. I guess as a follow-up to that question, you know, when I compare this study at day 28 to the last study at day 28, I guess the MADRS reduction for 1017 around 15 points, it does look consistent across the two studies. Placebo does look a little bit better, and maybe it drove a better delta this time. You know, as you think about a new study, I know it's still early, could it make sense to push up a higher dose, or would the next subsequent study be focused mostly on controlling the placebo response? Thanks.
Well, I mean, Andrew, I can give you my lay two second and I'm not the super expert of that, but I think the issue is the placebo response, especially the early placebo response to control placebo, especially early. Site selection would be in the raters. The rating would be the focus. You know, Maurizio, Dr. Fava and Paolo, they are on the call, so let me talk more about the different dose.
Yeah. I think that, you know, with Study 303 showing with the band-pass a robust effect, with Study 301 showing the robust effect, with the band-pass or with the removing the two sides, with highly implausible results and even, you know, response rates are statistically higher with 25 mg and 25 mg working very well in Phase II, I don't think it's an issue of pushing the dose. I think it's an issue of controlling the placebo. If there's gonna be a study, as Sergio mentions, in RELIANCE IV, the focus has to be on managing the placebo response, really designing the study in a way that weeds out the placebo responders.
Thank you. very last quick question is for RELIANCE III, how far along are you enrolled out of the target, say, 350 patients?
About 25%.
Thanks. Thanks again.
Our next question comes from the line of Andrea Tan with Goldman Sachs. Please proceed with your question.
Hey, everyone. Thanks for taking my question. Maurizio, maybe a question or a clarification on some comments you made here just regarding placebo response. I guess when I look at the overall population at 12.9 versus the 12.6 for the post-hoc analysis, I think you've mentioned that that's generally in the normal range for a placebo response. I guess could you help us understand if it's so much an issue that it's a high placebo response at those sites versus REL-1017 maybe underperforming there? Curious what factors, in your opinion, might lead to those patients have, you know, maybe being less responsive to the drug. Is there anything that you can detect from patient baseline characteristics that might kind of inform that these patients would be less responsive? Thanks so much.
Thank you. These are great questions. Yeah, the placebo response, when you take historical failures, you know, can range, you know, between 10 and 13 or 14. It's you know, it's 12.6 or 12.9 is kind of in the normal range. However, the variability caused by those two sites, because they had the, was a significant problem. You know, practically speaking, when you're trying to eliminate or address this problem, I think that you have to look at several factors. One is, you know, subject selection. Clearly in Study 301, the subjects were kind of had a more reasonable placebo response.
They, you know, so they were more likely to have true conditional major depressive disorder. Because we had discussed in Study 303 that with the pandemic we have a lot of people who meet criteria for depression but don't necessarily have a disease. They have more stress-induced depression than, you know, self-limited or short-lived. You know, here the placebo was not necessarily the big issue. The issue in my mind for those two sites is that they perseverated in showing a greater than 10-point difference in favor of placebo. That is very, very odd because you can say, "Well, that can happen in one trial," you know.
Happening in the same site, two sites, and happening in the same direction. Whereas all the other sites show the opposite trend, that is drug improving more than placebo. You know, as a clinical investigator, I have some concerns about the ratings. You know, the ratings conducted at that site, at those two sites. That would be my guess that something happened in the ratings that would explain why in two parallel studies, the same problem, the same implausible pattern was reported. I don't know if it addresses your question.
Sure. Yeah, I guess. I mean, I guess maybe it's. I'm sorry for digging in on this, but I guess it's. I understand that placebo is greater, you know, nine, 10 points greater than the treatment arm. If placebo is in the range of what's normal, doesn't that imply the issue might be more on the, on the treatment arm where there's. That's like, what's the most surprising part versus the placebo? Does it only just matter that the direction is implausible?
Well, both are important. That is, you know, what I'm trying to say is that nested within any antidepressant effect, there is a placebo effect. That's why, you know, in some ways you're, you know, you typically don't subtract the placebo from the drug. It's an additive effect, two points, three points, four points. You know, there is a placebo effect nested within each active. The fact that you have 10 points in the opposite direction is very hard to justify because it's as if these patients had no placebo response whatsoever. You know, all those assigned to drug had no placebo response, but all those assigned to placebo had a placebo effect. That, that kind of doesn't quite make sense.
Now you could say, well, what if the drug had a nocebo effect, had some sort of a negative effect? Well, then it would not be limited to two sites. You would see it in other sites. That's where, you know, in my mind, that's the odd aspect of these two sites is that they somehow mysteriously attributed no placebo whatsoever to the drug in both studies and in some ways had this paradoxical placebo being 10 points better than drug. I don't know if it addresses your question.
No. Thank you.
Yeah. Andrea, if I.
Thank you.
Andrea, if I may.
Go ahead, Sergio.
Just to give you like.
Mm-hmm.
One example. One site had a placebo response over 20% improvement from baseline in both studies. 20% meaning All the patients, that's an average, all the patients on placebo on that site were cured after one week or after two weeks. That's the magnitude of the.
20 MADRS points. There was a 20 MADRS points.
Right.
They had a drop of 20 points on MADRS. Somehow the same sites with the same. You could say, "Hey, these are sites that are very nice to patients. They provide tremendous support." Then you should see the some of that placebo benefit assigned to drive, right? You know. But we didn't see it. Normally I would say for high placebo response sites, you see drug and placebo looking the same. Having no signal detection because the drug is no better than placebo, but you don't see a drug being 10 points lower.
Got it.
Okay.
Okay. Thank you so much for the color.
You're welcome.
Our next question comes from the line of Jay Olson with Oppenheimer. Please proceed with your question.
Oh, hey, this is Matt on for Jay. really appreciate all the color, and thanks for taking our questions. We were wondering if you've received any additional feedback on the RELIANCE III results since you top-lined, and especially if you've received any feedback or commentary on the band-pass method on that study? As a corollary, what you would expect physicians to comment or provide feedback about this study and the post-hoc analyses? Another question we had was just based on the modifications that for RELIANCE II data, such as excluding those problematic sites, what placebo response range would you expect in those results? definitely really appreciate it. Thank you.
Sure. Clearly we're, you know, we're gonna try to lower further the placebo response in RELIANCE II and in the eventual study that Sergio's mentioned. With a number of methodological approaches that can that are known to further reduce the placebo response. Now the band-pass is a way of basically saying, "Let's look at only the sites that had a plausible response." At least a 3% improvement and no more than a 33% improvement on placebo. When you do that on Study 303, you clearly see a very nice signal. When you do it in Study 301, you clearly see a nice signal, both in the five-point range.
The critical thing is to try to get the average placebo response rate as much as we can and on most of the sites, within a range that, you know, 3%- 33% improvement and no more than that. We clearly did better on 301 than 303, which we would have expected because it's an augmentation study. I said, if we just did not have those two sites, we would be now talking about a positive trial.
Okay. Understood. That's helpful. Thank you.
You're welcome.
Our next question comes from the line of Joon Lee with Truist. Please proceed with your question.
Good evening, guys. This is the last time for Joon. Thanks for taking my questions. Can you comment if there have been any changes in the percentage of patients rolling over into the open label extension study? Would we expect the readout from the open label study to come before RELIANCE II top line? Thanks.
So.
Yeah, maybe I can take that.
Yeah, Paolo, maybe you should take that.
Sorry, the question was about rollover patients in two Study 310 and so.
Yes. I previously you mentioned I believe you previously mentioned it was about 75% rolling over. I wonder if there's been any changes in the percentage of those patients rolling over.
No, there are still, very high numbers rolling over and staying in two and Study 310, being retained there.
Okay. On the timeline readout, will that come in before the RELIANCE II top line?
Yes. The Study 310 should be ready in the first half of 2023. It's an open label study. It's going very well in terms of safety.
Yeah. The enrollment is done with the long-term safety. We're not enrolling any more patients.
Got it. Okay. Thank you.
There was 600 and some change, Paolo. Do you remember what the roughly number is? It was around 600 that the enrollment.
Yeah, around 600. Yes.
Our next question comes from the line of Uy Ear with Mizuho. Please proceed with your question.
Hi, guys. Thanks for taking up my follow-up question. I just wanna get a better sense of the raters. If, you know, if the issue seems to be one of a rater-rating problem with these two sites, can you elaborate on, you know, whether these raters are site specifics and or do they go from place to place, or is it centralized or is it? I just wanna get a sense of why these two sites have, it seems like the raters are reversing things, I guess, in a sense. Thanks.
Okay. No, we did not use, you know, centralized raters. The raters were site raters. It's, you know, traditionally that has not been a significant issue in clinical trials. That is, most trials use site raters. In this case, you know, the good news is that we have the recording. We can now go back, the post-hoc, but we can do some quality assurance post-hoc on those sites.
Do you think that the rating issue could also be part of the issues, in the Study 303 for these two sites?
Yes. Yes. I think that, 'cause they had the same pattern. It's possible that they had issues. Again, we, you know, we're trying, we're puzzled by the results in those two sites. You know, the most logical explanation, puzzle explanation is they had issues with ratings.
Okay. All right. Thank you.
You're welcome.
We have reached the end of the question and answer session. I'll now turn the call back over to Sergio Traversa for closing remarks.
Thank you. Thanks everyone for the interest and for participating in the call. Thank you Maurizio and Paolo for helping out on answering the question on the clinical and scientific side. The drug development, there are setbacks and, you know, this one, these data look a little better than the other one as it was expected. We didn't get where we want to be yet, but, you know, moving forward it looks promising. The signal is very clear of the efficacy and well tolerability and safety of REL-1017.
You know, the question is just to improve and we're working on that very hard, improving the execution and the operation of the trial, and improving by simplifying protocols and improving site selection, patient selection and rating, as Maurizio has pointed out. Hopefully the next call on the results of a clinical trial will be different than this one. I remain very confident that we do have a drug and we'll continue to work in getting, you know, the drug to the market and make it available to patients. Thanks again to everyone, and looking forward to the next call.
This concludes today's conference, and you may disconnect your lines at this time. Thank you for your participation.