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spk05: Greetings and welcome to the Romada Therapeutics fourth quarter and full year 2021 earnings call. At this time, all participants are in a listen-only mode. A brief question and answer session will follow the formal presentation. If anyone should require operator assistance during the conference, please press star zero on your telephone keypad. As a reminder, this conference is being recorded. It is now my pleasure to introduce your host, Tim McCarthy of LifeSci Advisors. Thank you, Tim. You may begin.
spk03: Thank you, Paul, and thank you all for joining us this afternoon. With me on today's call are Chief Executive Officer Sergio Traversa and Chief Financial Officer Megan Shenouda. This afternoon, Realmata issued a news release providing a business update announcing financial results for the three and 12 months ended December 31st, 2021. 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 these forward-looking statements due to risks and uncertainties associated with the company's business. These forward-looking statements are qualified by the cautionary statements contained in Relmada's press release issued today and the company's SEC filings, including in the annual report on Form 10-K for the year ended December 30, 2020, and subsequent filings. This conference call also contains time-sensitive information that is accurate only as of the date of this live broadcast, March 23rd, 2022. Realmata 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?
spk09: Thank you, team, as always, and good afternoon to everyone. I'm pleased to welcome to the RealMada fourth quarter and full year 2021 conference call. During today's call, I will review our recently achieved milestones and provide an update on anticipated clinical trial readouts timeline for REL 1017, our lead product candidate that we are currently studying as an adjunctive treatment and monotherapy for patients with major depression disorder or MTT. Following my comments, Maggie Chinuda, our chief financial officer, will review the financial results and recently strengthened the power sheet, and we will then take your questions. Looking ahead, we expect 2022 to be a catalyst-rich year for RealMada. We kicked off 2022 by reporting top-line results from the second Human Abuse Potential, or HAP, study, which I will recap shortly. we intend to generate REL 1017 clinical data readout beginning mid-year for the ongoing Reliance Phase 3 trial. We anticipate completing the enrollment of Reliance 3, the ongoing monotherapy registration of Phase 3 trial, followed by top-line data readout by mid-year 2022. In the third and fourth quarter of this year, we expect top-line results from Reliance 1 and Reliance 2, respectively. These are two ongoing phase 3 sister, two-arm placebo-controlled pivotal studies evaluating REL-1017 as a potential adjunctive treatment for MDD. The goal of this comprehensive development program is to address the significant need for a new therapeutic option to the 17 million individuals in the U.S. who suffer from MDD. The current antidepressant therapies have significant limitations, in terms of efficacy. They can take up to four to six weeks to show any effect. Up to 65% of patients do not respond to their frontline antidepressant treatment, and up to 40% of patients take combination therapy. Furthermore, there are only three FDA-approved adjunctive treatments for MDD, all of which are antipsychotic. which offer limited efficacy and can cause long-term side effects. It is evident that new treatment options are needed, and we believe REL1017 has the potential to be a safe and effective option for these patients and their caregivers as a monotherapy and adjunctive treatment. We made significant progress in advancing our development program. To this end, In February, we reported positive top-line data from our second HAP study, which compared REL1017 versus intravenous ketone. As a reminder, our first HAP study comparing REL1017 versus Oxycodone was completed in July 2021 and presented in a poster presentation late last year at the 60th Annual Meeting of the American College of Neuropsychopharmacology. Both studies were designed in accordance with the FDA 2017 abuse potential guidance and the 2022 clinical and regulatory standards by incorporating extensive input from FDA staff on the measures and the comparators on trial design. While we went into extensive detail during our February investor call on the ketamine study results, I would like to recap just the main findings. The primary endpoint, as is typical in these studies, was a drug-like score comparison of three doses of REL-1017 to ketamine. Ketamine dose at 0.5 milligrams per kilogram in Perinos administers over 40 minutes. The three doses of REL-1017 were the same as in the oxycodone study that we presented last year. and they were the 25 milligrams, the therapeutic dose, the 75 milligrams, which is three times the therapeutic dose, and 150 milligrams, which is six times the therapeutic dose, and this is the maximum tolerated dose. 51 subjects completed all arms of the study. The FDA guidance on abuse potential trials details that the statistical analysis should be based on data from participants who complete the study, the all-completed population. Data based on the all-completed population for both of the HAB studies showed a statistically significant difference from ketamine and oxycodone at all tested doses of REL1017, and they were statistically equivalent to placebo at all tested doses of REL1017. In summary, the finding of these two HAB studies are consistent with the 2019 DA statement on S-methadone that states that the D-isomer lacks significant respiratory depressant action and addiction liability. The results of the oxycodone and ketamine HAP study also confirm and support the previous data published regarding the potential for abuse of REL1017. We believe that the oxycodone comparative data significantly derisks the Schedule 2 potential for REL1017, and that the ketamine comparison data significantly derisks the drug Schedule 3 potential. Collectively, the data generated today from our REL1017 program indicates that REL1017 could be proposed as a Schedule 5 drug, and eventually non-scheduled following one or two years of marketing. In order to support the regulatory, potential regulatory submission seeking approval for REN1017 as a monotherapy, as well as adjunctive treatment, the FDA confirmed that based on what is known at this time, RealMada will not be required to conduct a two-year carcinogenicity carcinogenesis initiative study of REN1017 with an understanding that sufficient preclinical safety data have been generated today. The FDA also confirmed that Realmada does not need to conduct a TQT cardiac study in humans to support cardiac safety in a potential regulatory submission for REL 1070. The data provided to date, as well as the data to be generated from the ongoing Phase III program, would be adequate to evaluate and confirm the cardiac safety of REL 1070. Moving on to the Phase III program, we anticipate the completion of enrollment of Reliance III, the ongoing monotherapy registration of Phase III trial, followed by a top-line data readout by media. Reliance III aims to randomize up to 364 patients, and is targeted for individuals who are diagnosed with depression and unrecorded taking standard antidepressant therapy. Importantly, This is prior to the anticipated conclusion of Reliance I and Reliance II, the adjunctive MDD studies, which I will discuss momentarily. As a reminder, conducting Reliance III as a Phase III study could meaningfully reduce the time for a potential approval of REL 1017 as an MDD monotherapy. Let me now provide an update on the ongoing Reliance I and Reliance II studies, each of which is designed to include up to 364 participants per study across 55 sites per study. As a reminder, Reliance I and Reliance II are designed to evaluate REL1017 as an adjunctive treatment for MDD, and both include two arms, placebo and 25 milligrams of REL1017. Both arms are studying the use of Relatin-17 in addition to a standard antidepressant for participants who have had inadequate response to at least one and up to three standard antidepressant therapies. The primary endpoint is the change in Madras score at day 28. Key secondary endpoints include the change in Madras score at day seven and change in clinical global impression severity scale, the CGIS score at day 28. Day 28 was chosen as the primary endpoint in agreement with the FDA with an understanding that depression is a chronic disease and that day 28 would support REL 1017 as a chronic treatment. Both Reliance 1 and Reliance 2 are progressing with top-line data expected in the second half of this year. The Reliance Development Programs also includes the Reliance OLS, the Long-Term Open Label Safety Study, that is enrolling both rollover participants for all three pivotal studies, as well as the NOVA participants. Reliance OLS is ongoing and enrolling participants as planned. Data from this Long-Term Open Label Safety Study will be part of the planned NDA filing package. I would also like to add that the recent pre-planned interim safety analysis conducted on a periodic base by an independent data monitoring committee, the IDMC, confirmed the lack of safety signals and concluded with the recommendation for the studies to proceed as planned. This analysis reviewed data from all of the ongoing reliance trials, including the open-label safety studies. I would like to highlight that the Phase II data were published in the peer-reviewed American Journal of Psychiatry. It's the most widely read psychiatry journal in the world, late in 2021. The manuscript for the details, finding that from the Phase II study assessing REL1017 as a junkie treatment for NDD. The primary endpoint demonstrated B, RAPID. significant and sustained efficacy versus placebo REL 1017. As our robust REL 1017 development program continues to advance expeditiously, we continue to be supported by a strong balance sheet, which was further enhanced by the successful oversubscribed follow-on offering that closed in the fourth quarter of last year and generated gross proceeds of $172.5 million. With that, I will turn now the call to Maggot for review of the financial, including further details on the completed public offer. Maggot, the stage is yours.
spk01: Sure. Thank you, Sergio, and good afternoon, everyone. Today, we issued a press release announcing our business and financial results for the three months and 12 months ended December 31, 2021, which I will now review. For the fourth quarter ended December 31, 2021, total research and development expense was approximately $25.3 million as compared to $14.9 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 for REL 1017. Research and development expense for the most recently completed fourth quarter included a non-cash charge of $1.5 million related to stock-based compensation expense. We also ended the fourth quarter of 2021 with a prepaid R&D expense balance of $8.6 million related to advance payments to our CRO. Total general and administrative expense for the fourth quarter ended December 31, 2021 was approximately $8.9 million as compared to $6 million for the comparable period of 2020. The increase was primarily due to increase in personnel costs, stock-based compensation, and consulting services. The non-cash charge related to stock-based compensation expense included in general and administrative expense totaled approximately $6.6 million in the most recently completed fourth quarter. The fourth quarter ended December 31, 2021. We recorded a net loss of approximately $34.4 million or $1.80 per basic and diluted share. compared to a net loss of $20.8 million or $1.30 per basic and diluted share for the comparable period of 2020. For the year ended December 31, 2021, total research and development expense was approximately $90.6 million as compared to $36 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 for REL 1017. Research and development expense for the year included a non-cash charge of $15.9 million related to stock-based compensation expense, which included the novel psilocybin one-time acquisition payment of $10.2 million to ArborMentis in the third quarter of 2021. There was also a one-time cash payment of $2.5 million related to this acquisition. Total general and administrative expense for the year ended December 31, 2021 was approximately $35.1 million as compared to $24.9 million for the comparable period in 2020. The increase was primarily due to an increase in personnel costs, stock-based compensation, and consulting services. The non-cash charge related to stock-based compensation expense included in general and administrative expense totaled approximately $24.7 million for 2021. For the year ended December 31, 2021, we recorded a net loss of approximately $125.8 million or $7.16 per cent per basic and diluted chair compared to a net loss of $59.5 million or $3.81 per basic and diluted chair in the comparable period of 2020. On December 31, 2021, the company had cash and cash equivalents and short-term investments of $211.9 million, which compares with $117.1 million on December 31, 2020. This includes $161.2 million in net proceeds from the public offering closed in December 2021, through which we sold 10.1 million shares of our common stock at $17 per share. I will now ask the operator to please open the call for questions. Operator?
spk05: Thank you. We will now 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 that your line is in the question queue. You may press star 2 if you'd 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.
spk10: Thank you.
spk05: Our first question comes from Andrew Tsai with Jefferies. Please proceed with your question.
spk00: Okay. Thanks, everyone, and good afternoon. Just curious on the DMC Safety Committee disclosure, which is routine, I'm curious if there were any kind of AEs of special interest that they were looking for. I mean, can you confirm if they were looking for withdrawals, dependents, addiction, euphoria, and so forth, were they looked at in this blinded Review? Thanks.
spk09: Thank you, Andrew. I was sure you wouldn't pick it up. Look, the committee is totally independent, so they only communicate to us if there is anything that would be only worried in terms of safety that includes anything, and I do believe includes with travel symptoms or anything that would be out of the normal course or out of the ordinary. We haven't heard anything. We got just a very simple and brief communication that the trial can continue as planned. That was it. So there was nothing that would be of any worry. To be honest, Andrew, you have seen a lot of data over the last few years, and there's been no signal that safety would be of any real big worry. We're always worried about everything, but safety is probably not what we are worried the most. Hope I answered your question.
spk00: Of course, that's a great caller. And then I'll try to ask this one is just I'm wondering if you can give us a flavor of what we can expect to see in the top line release in mid-2022 for Reliance 3. Presumably we'll see day 7, day 28 efficacy, AE rates. Will we see curves? Will we see response rates, remission rates? and so forth. Have you thought about what you plan to disclose? Thanks.
spk09: Well, yes. Look, we will disclose everything that we will receive from the statistical group that run the statistical analysis with a caveat that clearly we want to leave details for the presentation publications. But in terms of top line, we usually receive the primary and secondary points. I don't know if we would receive the curves or not. We tend to be very quick. We don't want to hold the data for too long inside the company. So whenever we have something that is material, we tend to do it very, very quickly in a day or two. So it's a way to tell you that It depends on what we receive from the statistical group. Definitely primary and secondary endpoints.
spk00: Great. All right.
spk10: Thank you. Thank you, Andrew.
spk05: Thank you. Our next question comes from Andrea Tan with Goldman Sachs. Please proceed with your question.
spk04: Hey, everyone. Thanks for taking my question. Maybe sticking on with the monotherapy study, Sergio, just curious if you could help frame expectations ahead of this study and What you've seen is specifically from your prior studies that gives you confidence in ROL1017 demonstrating a benefit here as a monotherapy. And then I have a follow-up, thanks.
spk09: Yeah, well, good afternoon, Andrea, and thanks for your question. So the, what we kind of, you know, can be applied to the monotherapy is clearly, you know, the lack of any, you know, potential for abuse that we have seen, and the safety. That's pretty common to all the studies. What we don't have is any data on efficacy as a monotherapy. We do have very strong efficacy data for the adjunctive therapy, but not as a monotherapy. That's what really would be the most interesting data point. There is not much else that we can apply or infer from phase two into the monotherapy data. We can kind of, I don't know, speculate that patients that failed one or two or three previous antidepressants, they are not completely different from patients that have not failed any previous antidepressants. So we don't see a major difference between the two patient populations, but yeah. we would be very anxious to see these efficacy results as a monotherapy as well.
spk04: Got it. And then is there anything that can be inferred or will there be any read-through from the monotherapy results to the adjunctive pivotal studies here?
spk09: Well, that's a very difficult question to answer, but... If the study is successful as a monotherapy, then we could infer, just because we already have data as an adjunctive treatment positive, so we can infer that probably there is some indication of efficacy across all the patient population, across all the adjunctive and monotherapy population. If it doesn't go the way that we hope and we believe, then it gets more speculative, right? Let's say it fails as monotherapy, but we have positive phase two as an adjunctive cell. I would say, I'm bent to say that if this study in monotherapy is not positive, I would not read through much into the adjunctive. And I want to go a little bit more in detail. What we don't know, if there is any role of the inadequate response therapy to the underlying antidepressant therapy is an adjunct. We don't know if there is any synergistic effect between a non-effective SSRI or SNRI and an NMDA channel blocker. That's what we learned from the monotherapy and the adjunctive therapy trials. There's a lot of speculation, so we want to see the data, and then we can be more accurate and realistic.
spk04: Got it. And then maybe just one last question. Just given that you are looking to include data from Reliance OLS in your filing package, could you just remind us on the timeframe there for the amount of follow-up and when you think you might have a completion for that portion?
spk09: Well, we have a rolling NDA, so we will start to file, you know, the modules like the preclinical and the TMC well in advance than when we have the, you know, the clinical data. The goal is to, it takes about six months realistically. It's a big, right, potentially for two indications, and there's a new chemical entity, so it's a big NDA. And so we calculate six months as a fair time to do it correctly. And you know what happens when you don't do it correctly. That's not the situation that we want to find ourselves. So, you know, if everything goes according to the plan, we should be able to complete the MBA by mid-2023. Perfect. Thanks, Sergio. Thank you, Andrea.
spk05: Thank you. Our next question comes from June Lee with Truist Securities. Please proceed with your question.
spk08: Hi, thanks for taking our questions and congrats on all the progress. So now that you have completed two successful human abuse potential studies, has your outlook changed on possibly looking towards XUS opportunities in regions where they have maybe stricter substance abuse laws? I believe China may have been one of them. and do you have any plans to enter the EU at some point? And I have a follow-up.
spk09: Thank you, John. It's a bit too early, and we are extremely busy and committed to the US phase three program. In terms of areas where there is more sensitivity, to substance abuse or as Japan is the one that is the most sensitive. Europe, we had a few interactions with the EMA, with the European FDA, and there was no specific mention or specific interest in the abuse potential of the drug. There were preliminary conversations, so I don't know if it was the right time for the regulators to go deeper in these aspects. So we will do something, we will look into that, but a little bit later on. We really would like to face the program correctly and to do it right. That's the real focus.
spk08: Okay, sure. Great. And then, in addition to the Phase IIa data that you published in American Journal of Psychiatry, you also published data showing rapid rise in BDNF in human subjects, those with S methadone. So, can you elaborate on the significance of that, and what do you plan to do with that information? Are you following that up with any other studies? Thank you.
spk09: Yeah, that's a great question. Well, what we have done already, we have used this data. This new data. and to strengthen the IP. So we put the BDNF data and the neuroplastic effect into a patent filed in 2018 that is under review. And the clear indication is that mechanistically an MNDA channel broker, they are very different from anything that is like SSRI, SNRI, the traditional mechanism of action. And it would indicate clearly that uh, scientific and mechanistically, there is a neuroplastic effect with an increase in functionality and increase in, in the proliferation of dendrites, uh, connection between nerve and nerve cells. And, uh, that happened very quickly. And these, you know, uh, BDNF brain derived neurophobic factor is a growth factor. So, uh, there should be some correlation between the BDNF increase and the neuroplastic effect. Just to be clear, John, the FDA does not consider BDNF as a surrogate for clinical efficacy in depression. So we won't use it with the FDA and say, oh, increase the BDNF and there is efficacy. That's not going to fly. But clearly for IV, it's very interesting. It's been confirmed by the extended and sustained effect of the drug after the therapy is stopped. So at least for one week, after interruption of the treatment, you still see a very nice and prolonged and sustained antidepressant effect. So the clinical result, they match very, very clearly the scientific and mechanistic expectation. So we will continue eventually for other indication to try to understand better and to leverage this potential for neuroplastic effect of the drug. It's very important data, very important data.
spk08: Yes, and then if I could follow up with one quick question. When you do complete enrollment in the monotherapy study, would you disclose completion of enrollment?
spk09: Yeah, you probably will. We usually, companies usually do, and we don't want to be different from anybody else in these aspects. All right.
spk06: Looking forward to the data.
spk09: Yeah, a few weeks. You know, the status station, usually they take a very wide range of timing when they lock the database and when they provide the top line. They usually tell us like two to four weeks. For satisfaction, it's a narrow range. For us, a little bit less narrow. So you assume that when we complete enrollment, probably around the month, we will have the top line data.
spk08: Sounds good. Thank you.
spk10: Thank you, Jonathan.
spk05: Thank you. Our next question comes from Yatin Samidja with Guggenheim. Please proceed with your question.
spk07: Hey, guys. Thank you for taking my question. A couple questions for me. Can you talk about what you might be seeing on the distribution rate, what assumptions you might have, and how many are more?
spk10: Sorry, Yatin. You broke up.
spk07: Can you just talk about the discontinuation rate, what you might have assumed in the study and how it might be trending? How is the conversion from randomized to the open label?
spk09: Yes, we can. I don't know how specific it should be before Margaret shut me down, but the dropout rate is significantly, not statistically, but it's very... Much lower than what we assume. We look at historical, and we discuss with the CRO that has a lot of experience in running depression studies. And we assume mid-double digits, around 15% in the statistical plan, to be sure that we reach a number of patients that can be evaluated that is high enough for the power of the study. And what we have seen so far across the board is much lower than that. I would say it's low to mid-single digits. So according to the CRO, that's not been seen before in the present study. Now, I'd like to be always direct and open. What we can read through that is safety, compliance, tolerability. It doesn't look to be an issue. I would not make the big step on reading anything into efficacy because half of the patients are taking placebo. Got it. In terms of rollover, that's also a number that it's a very good number. So about three out of four patients, they accept and they're happy to continue from the 28 days to rollover into the long-term safety. That's much higher than the average for this kind of stuff. Got it. Again, safety, vulnerability, and acceptance and compliance, they do very good.
spk07: Got it, got it. Very helpful. Then one more question. So I think one of the pushback or the things that we generally discuss with investor is the performance of the placebo arm in phase two. So can you just talk about how much cushion we might have in the phase three studies, how you might be controlling it, any reason to believe that the monotherapy placebo rate might be different than the adjunctive one? Just give us some comfort and color around it.
spk09: No, I can share what we discuss on a daily basis. We are fully aware that placebo effect is strictly related with the quality of the patient population, meaning the patient should be a depressed patient to enter the study. For the Phase II, Do remember the delta from baseline to day seven of the placebo was around eight to nine points. That's a little bit lower than what has been seen historically, slightly lower. But there is one point. The study was seven days on placebo. Placebo effects tend to increase over time. So seven days to have a placebo delta from baseline of eight, nine points at day seven is not unusual. It's actually, even on the high side, we have seen placebo effect of four, five, six points in other studies at day seven. So there is really nothing unusual there. It is something unusual. It's slightly higher. That was also expected because in clinic studies, they tend to have a higher placebo effect than outpatient studies. So the second part of your question, what we are doing to try to minimize as much as possible the placebo effect. There is no magic, no secret that we use that nobody else has used, but we try to put together all the experience. And Dr. Fava is the principal investigator. He's published a lot about the potential for placebo effect. And so he's kind of an expert. on, I would say, on trying to control as much as possible unusual placebo response. With that said, there is tidbits here and there, like there is a statement that the patient is reading before he's administered the MADRAS scale every time. They state that he has 50% chances to take placebo. The nurses are trained not to make comments about the patient looking good or better that could, you know, alterate the response of the patient. So all these, together, they can make some difference. We do believe that what really makes the difference at the end of the day is the quality and, you know, to be sure that the patient's role is the patient is affected by, you know, NVD, by major depression. And to do that, we do, we use as a strategy, development strategy, what we have used in Phase two, that is the safer questionnaire. So the patient is re-diagnosed using a different diagnostic tool that is the safer questionnaire before it gets randomized. So it can meet all the inclusion criteria based on the size and the Madras scale before it gets randomized. But before it gets randomized, it goes through another phone call. So it's not a very, it's not a long process or And it goes to another, you know, diagnosed but using the safer questionnaire. According to everybody that, you know, we have consulted, that is the best way possible to control placebo because it reduces the percent of patients that should not belong or should not be involved in this kind of study because they're not patients affected by depression. That was a long answer, but I wanted to be specific.
spk07: Got it. Thank you so much. Thank you, Yadin.
spk05: As a reminder, 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. Our next question comes from Jay Olson with Oppenheimer. Please proceed with your question.
spk06: Oh, hey, thanks for taking the question. Can you remind us how the human abuse study results compare to Spravato? And would the human abuse data appear in the FDA approved labels so they could be used for promotional purposes?
spk09: Thank you, Jay. Good afternoon. Well, the first question, how the comparison with ketamine of REL1017 compared with Spravato, they are totally different. As ketamine, it is low-dose ketamine. The isomer of racemic ketamine, but works exactly the same as racemic ketamine, according to all the literature. So the J&J ran the study because probably it was asked by the FDA, but clearly the expectation was Not that S-cathamin is less potentially abusable than racemic. Cathamin is exactly what happened. You have seen the data of REL1017. I don't know how many zeros after the period in terms of p-value compared to catamin. So the data are completely different. And if the abuse data, the non-abuse data, or the lack of meaningful abuse potential data for REL1017 will be on the label, can be used promotional? Well, the straight answer is that the FDA will decide. We won't emphasize much about the lack of abuse potential of resident 17 as a promotional tool. It's efficacy, rapid acting, sustained efficacy, they are a lot more powerful. With these data, I don't think anybody would think that there is any risk of abuse. So at the time of potential approval, it probably, you know, people assume won't be the focus of the attention of the clinician. So personally, if you ask me directly, maybe some centers that mimic what the DEA has already published in 2019, that the isomer lack abuse potential and a risk of respiratory depression. That's that could speculate, that could be in the label by mimicking the DA statement.
spk06: Okay, great. Thank you. And maybe as a follow-up, can you talk about any findings from your market research as you test the REL 1017 profile with prescribers as you plan for your commercial launch, and especially if you have any feedback from payers in the U.S., and then if you are considering a partner, XUS. Thank you.
spk09: Yeah, so we did, it's never too early to discuss with the payer, so we keep everybody that is in the chain as updated as possible. From my experience, the payer really consider seriously to get into a conversation when they have phase three data. you know, before data from their perspective, show me the data and then we can discuss. Like really top-down and is, you know, the monotherapy, it's a bit more challenging in terms of, you know, reimbursement and depending on the price because, you know, the frontline therapy that is currently proposed supported by the payers is generic SSRI. They work a little bit, and they're relatively safe, and they're extremely pain-intensive. So that's a little bit of a hurdle to overcome as a monotherapy. Adjunctive, there is no antidepressant approved, so that would be a great... It's going to be very difficult to have an adjunctive treatment where there's no competition in terms of antidepressants, and it works fast, and... We don't believe it will be priced at the esketamine range, so it would be potentially affordable by a mass market patient population. So that one we don't believe is going to be a major challenge to get reimbursement, and I don't know how to call it, but it's a frontline adjunctive treatment. With that said, going back for a second to monotherapy, if the data in phase three will be any close to the phase two data that we have seen in monotherapy, meaning the monotherapy will mimic somewhat the adjunctive phase two data, it's going to be difficult for the payers not to reimburse a drug that works much faster. There is pharmacoeconomic data too. If you can get out improve your depression status quicker you are more productive that's more European but I do believe the u.s. also focus on these aspects too right and so the pharmacoeconomic if you can improve and go to work a lot faster than if you take an SSRI that's probably is a lot more value than then you know to save some reimbursement or some pay as money using, you know, starting with an SSRI. So if you have a rapid acting and sustained efficacy drug, it's going to be difficult not to reimburse this, even as a monotherapy. You know, the key will be clinical data.
spk06: Okay, great. And any plans to find an ex-U.S. commercial partner?
spk09: Well, yeah, as always in this kind of like situation, pre-phase three data, there's always some conversation in there, but we don't believe that nothing will happen. We are too close to phase three data. Nobody will sign an agreement or paying the adequate price a few months before phase three data. So straight answer is not before phase three data. We don't expect anything to happen outside the U.S. before phase three data. We also would like to retain the global rights.
spk10: There is a volume having the global rights. Okay, got it. Thank you, Dave.
spk05: Thank you. There are no further questions at this time. I'd like to turn the call back over to Sergio Traversa for any final remarks.
spk09: Thank you. Thank you, operator. Well, thank you very much, everyone, on the call for the interest, the time and the interest in our program. And I would like to thank also the Ramada team for the effort and the energy they're putting in this program and the clinician and the patient that really helping to complete this ambitious but realistic program to offer patients a good or better solution to treat depression. With that said, I wish everyone a wonderful rest of the day. Thank you.
spk05: This concludes today's conference. You may disconnect your lines at this time. Thank you for your participation.
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