Good day, ladies and gentlemen, and welcome to the Relmada Therapeutics, Inc.'s second quarter 2022 earnings conference call. Today's conference is being recorded. At this time, I would like to turn the conference over to Brian Ritchie of LifeSci Advisors. Please go ahead, sir.
Thank you, operator, and thank you all for joining us this afternoon. With me on today's call, our Chief Executive Officer, Sergio Traversa, John Hixon, Head of Commercial, and Chief Financial Officer, Maged Shenouda. This afternoon, Relmada issued a news release providing a business update announcing financial results for the three and six months ended June 30, 2022, and filed its quarterly report on Form 10-Q with the SEC. Please note that certain information discussed on the call today is covered under the safe harbor 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 31, 2021, and subsequent filings. This conference call also contains time-sensitive information that is accurate only as of the date of this live broadcast, August 11, 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. Now, I'd like to turn the call over to Sergio. Please go ahead, Sergio.
Thank you, Brian, as always, and good afternoon to everyone. I'm pleased to welcome you to the Relmada second quarter 2022 conference call. During today's call, I will review our recently achieved milestones and provide an update on the anticipated timelines associated with the multiple expected clinical trial readouts from REL-1017, our lead product candidate that we are currently studying as a paradigm-shifting novel treatment for patients with major depressive disorder or MDD. Following my comments, Maged Shenouda, our Chief Financial Officer, will review our financial results and balance sheet, and we will then take your questions. We are approaching multiple key catalysts from our ongoing late-stage Reliance clinical development program. Specifically, we anticipate completing the enrollment of Reliance III, the ongoing monotherapy registrational phase III trial shortly.
More specifically, we expect to enroll the last patient in this trial before the end of August, probably earlier than that. Visits will be followed soon thereafter by a top-line readout of the study in the second half of this year. We also continue to expect top-line results from Reliance I and Reliance II in the second half of 2022. As a reminder, Reliance I and Reliance II are two ongoing phase III sister two-arm placebo-controlled pivotal studies evaluating REL-1017 25 mg as a potential adjunctive treatment for MDD. Reliance III is the ongoing phase III two-arm placebo-controlled registrational study evaluating REL-1017 25 mg as a potential monotherapy single-agent treatment for MDD. All participants in all of the Reliance trials take a loading dose of 75 mg on day one, three tablets of REL-1017.
We are also delighted to share that the FDA very recently granted Fast Track designation to REL-1017 as a monotherapy single agent for the treatment of major depressive disorder. Our commercial preparations have also continued with an expansion of our senior management team. Most recently, we are thrilled to welcome John Hixon to Relmada's head of commercial. John has over 36 years of sales and marketing experience within the biopharmaceutical industry, including a 31-year career with Eli Lilly and Company. John is on the call, so before I go further, John, would you like to say a few words? Is it your first conference call with Relmada? You just joined and, I'd be happy if you can say a few words. John.
Well, hi, everyone. Thank you, Sergio. It's a real pleasure to be with all of you, and I just want to say that I'm thrilled and humbled and excited to be a part of this Relmada team. As Sergio said, I've got a pretty broad background in commercialization. All 31 years with Eli Lilly were in commercialization related roles. I was fortunate to spend eight years outside of the U.S. in Spain, South Korea, and Australia. While in Australia, my team and I launched Zyprexa, the atypical antipsychotic. Then when I returned to the United States, I became the last global marketing director for Prozac as it was late in its product life cycle. Once that role ended, I shifted over to be the brand launch leader for Cymbalta, Lilly's next antidepressant and pain drug.
After launching this drug and being with it for several years post-launch, I shifted over to new product planning, where I worked with discovery and development scientists and provided assessments of commercial viability of Lilly's portfolio and also was actively engaged in various business development opportunities. Again, I just thrilled to have this opportunity. I know the depression space well. Depression is something that, like perhaps many of you, has impacted members of my family and close friends. Having this opportunity to bring forward a new approach to treat depression if the drug is approved is just very exciting for me and one that I'm very passionate about. I think the drug is truly an exciting new treatment option. Again, thank you very much. Let me turn this back over to Sergio so we can continue on with you all. Thank you.
Thank you, John, and we are really very happy to have you on board with us. Moving on to the current status of the phase III program. As I said earlier, we continue to anticipate the completion of enrollment in Reliance III, the ongoing monotherapy single-agent registration of phase III trial, with the last patient enrolled before the end of August, followed by the top-line data readout shortly after the completion of the four-week treatment. Let me provide an update on the ongoing Reliance I and Reliance II studies. As a reminder, Reliance I and Reliance II are designed to evaluate REL-1017 as an adjunctive treatment for MDD, and both include two arms, placebo and 25 mg of REL-1017.
Both studies are studying the use of REL-1017 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 MADRS, the scale that is used to evaluate the severity of depression, and MADRS score at day 28. Key secondary endpoints include the change in MADRS score at day seven and change in Clinical Global Impression Severity scale, the CGI-S score at day 28. Day 28 was chosen as a primary endpoint in agreement with the FDA, with a common understanding that depression is a chronic disease and that success of descent points on day 28 will support REL-1017 as a chronic treatment for depression.
Both Reliance I and Reliance II are progressing as planned, and we continue to expect the availability of top-line data in the second half of this year. The Reliance development program also includes Reliance OLS, the long-term open label safety study, is enrolling both rollover participants from all three pivotal studies as well as de novo participants. Reliance OLS is ongoing and continue to enroll participants as planned. Data from this long-term open label safety study, we now expect in the first half of 2023 will be part of the planned rolling NDA filing package. Finally, while Maged will review our financials in detail shortly, I would like to emphasize how strong our financial position we are currently in.
You can recall that we completed an oversubscribed follow-on offering for gross proceeds of $172 million in late December 2021, when the capital markets for biotech companies were far less challenging than they are today. This financing has provided us with the maximum financial and operational flexibility as we ended the second quarter with cash equivalents and short-term investments of approximately $222 million. With that, I will now turn the call over to Maged for review of the financials. Maged, the stage is yours.
Sure. Thank you, Sergio. Today, we issued a press release announcing our business and financial results for the three and six months ended June 30, 2022, which I will now review. For the second quarter ended June 30, 2022, total research and development expense was approximately $30.9 million as compared to $17.3 million for the comparable period of 2021. The increase was primarily related to an increase in costs associated with the execution of a broader clinical program for REL-1017. Non-cash R&D expense for the second quarter of 2022 amounted to $1.2 million.
Total general and administrative expense for the second quarter ended June 30, 2022, was approximately $14.6 million, as compared to $9.1 million for the comparable period of 2021, an increase of approximately $5.5 million. The increase was primarily driven by an increase in stock-based compensation. This non-cash G&A charge totaled $11.1 million in the most recently completed second quarter. For the second quarter ended June 30, 2022, the net loss was $39.9 million, or $1.33 per basic and diluted share, compared to a net loss of $26.6 million, or $1.56 per basic and diluted share in the comparable period of 2021. Turning to the results for the six months ended June 30, 2022.
Total research and development expense was approximately $55.9 million as compared to $31.4 million for the comparable period of 2021. Again, the increase was primarily related to an increase in costs associated with the execution of a broader clinical program for REL-1017. Non-cash R&D expense for the first half of 2022 amounted to $2.5 million. For the six months ended June 30th, 2022, total general and administrative expense was approximately $27.9 million as compared to $17.5 million for the comparable period of 2021. The increase was primarily driven by an increase in stock-based compensation.
This non-cash G&A charge totaled $21.7 million in the most recently completed six-month period. For the six months ended June 30, 2022, the net loss was approximately $79.7 million or $2.73 per basic and diluted share, compared to a net loss of $48.8 million or $2.90 per basic and diluted share in the comparable period of 2021. As of June 30, 2022, as Sergio said, we had cash and cash equivalents and short-term investments of approximately $212 million, compared to cash equivalents and short-term investments of approximately $211.9 million at December 31, 2021. I will now ask the operator to please open the call for questions. Operator?
Thank you. Ladies and gentlemen, if you would like to ask a question, please signal by pressing star one on your telephone keypad. If you're using a speakerphone, please make sure your mute function is turned off to allow your signal to reach our equipment. Again, press star one to ask a question. We pause just for a moment to assemble the queue. We take our first question from Andrew Tsai with Jefferies. Your line is open. Please go ahead.
Thank you and good afternoon. Thanks for taking my questions. Thanks for the update. First one is that it sounds like Reliance III, the monotherapy, reads out in maybe two months, give or take. I think you said Reliance I, the first of two adjunct studies, was tracking a few weeks behind Reliance III. Is that still the case? You know, if so, would you consider bucketing both data sets together, or would you choose to press release the two data sets at different times?
Good afternoon, Andrew, and thanks for the question. Let me address the second part. No, we are not planning to release Reliance III and Reliance I together for a couple of reasons. One, they probably are not close enough that we could pack all the data together. The second one, that is the most important, is that we want to be sure that everybody will have enough time to digest. It's going to be quite a bit of data, top line, primary, secondary endpoint as much as we can disclose. The two trials, they have their own independent life although they are similar. But you know, single agent monotherapy needs a different conversation compared to what is called the adjunctive treatment therapeutic choice.
We will publish the top-line data separately for these, you know, couple of reasons. In terms of timing, I mean, moving forward, I mean, now we do have a pretty clear idea what the timing is. We expect the last patient to be enrolled in Reliance III, we said before end of August, probably is going to be not too far away from today. You calculate last patient in four weeks, 20 days treatment, so you go somewhere in September, and then two to four weeks after that, we will have the, you know, the top-line results.
Very thanks.
You can do the math, right? It's gonna be, you know, end of September, maybe very early October, this range. We are getting there.
Yeah.
Reliance I.
Yeah.
That one is a little bit, say, more difficult to time so precisely, but you can assume that, you know, I would say six to eight weeks after, maybe a little earlier than that, we should be done with that. Same process.
Great. Thanks. Two more-
We will announce it. Yeah, we will announce the last patient out for both trials.
Perfect.
Last-
Thanks. Yep, and that's very clear. Second question is, can you remind us the last time the DSMB looked at the blinded safety data? I think the last time was March. Did they happen to look again? If so, any updates on that front, I guess? Just to be clear, i f the DSMB did see like, I don't know, withdrawal, euphoria, dissociation, any of these across the phase IIIs and the open label portion, they would have alerted you, just to be clear?
Yes. The straight answer is yes. We would know they would have alerted us if there would have been any issue related with withdrawal symptoms or you know, anything, any safety signal would be signaled. They meet regularly on a time base, so sometimes we don't even know if they met them. The last time I remember was June. You know, they meet regularly, and we haven't heard anything except continue as planned as a recommendation. It's always, I mean, this business in biotechnology, you're developing drugs, it's you can never make really assumptions that you know, with zero risk. We are at the very end of the massive program. We have all phase I, phase II data.
We did this very large abuse potential with like 100 patients treated with you know many different doses. We have not seen one single issue related with safety. I would say that we feel very very confident about the safety is not going to be like a real issue or a roadblock. Safety abuse all these you know we have so many information. They all very consistent suggest that there is no safety or abuse issues.
Fantastic. All right, thanks for taking my questions. Best of luck. Fingers crossed.
Thank you, Andrew. I'm sure we'll speak soon with data.
Of course.
Thank you. We take our next question from Yatin Suneja with Guggenheim. Your line is open.
Hey, guys. Thank you for taking my question. I have just one question, and this is on the tolerance side. I think what we have seen from you is seven-day data. Can you just put in context, Sergio, with this type of a mechanism, NMDA targeting mechanism, should we expect any sort of tolerance development? Just trying to get a sense that how much more benefit we should expect out to 28 days relative to seven days that you have produced. Anything that you can point out to, whether it's ketamine or other NMDA channel blocker that have produced. Thanks.
Yeah. Thank you, Yatin. Thanks for the question. Yes. Like, there are data historically. Let me start from, like, scientifically and, like, from the science, there is no indication that NMDA channel blockers generate any tolerance or anything like that. Clinically, there are a few examples. Ketamine, I would not, you know, I would not use it as a, like, very good comparison as ketamine, they are given intermittently for, you know, practical reasons. One is nasal and, you know, it, you can't go to the clinic to take a drug every day and not to drive for 24 hours. It's, they have limitations that make the intermittent treatment regimen the only one that is really feasible.
That's in terms of, like, the developing tolerance may not be the best comparison. Dextromethorphan, that one of our peer competitors is trying to get approved, it didn't show any sign of any tolerance. The efficacy continued to be there and improving up to six weeks, if I remember correctly. Yatin, you know that much better than I do. You know the program well. Dextromethorphan didn't show any, doesn't show any tolerance. Memantine for whatever, right, they're very difficult to evaluate the efficacy for an Alzheimer's drug, but at least they didn't show really any particular loss of the effect. Maybe one of the ones that we are looking into is dextromethorphan combined with quinidine.
I believe now it's part of Otsuka, and it's a chronic treatment for pseudobulbar affect. Also, you know, it's chronic treatment doesn't show any loss of efficacy over time. All in all, we don't expect that drug REL-1017 will show anything different. Clearly, if we take the phase II data as a proxy, and we do, we should see a very sharp and fast effect at day four, five, seven, that range. And, you know, it cannot continue to increase efficacy beyond, like, much beyond that. Otherwise, the model will go below zero, and that's not possible. But we do expect, like, a continued improvement up to day 28. Definitely not a loss of efficacy.
Yeah. Got it. One more, if I may. I think in the past you have talked about, on a blinded basis, what the dropout rate is for the study. Could you give us an update now that you are very close to the completion, what it is or how it is trending? Are there any differences that you're seeing between adjunctive versus monotherapy? And then also if you can comment on the percentage that might be rolling over to the OLE. Thank you so much.
Yeah. Thank you. Yatin, you always ask me tough questions. Look, it's always dangerous to draw any conclusion from blinded data and you know that better than anybody else, right? We look at the blinded data mostly, almost exclusively for safety reasons, and we have seen nothing, as I mentioned a few minutes ago. In terms of efficacy, until you know what the placebo effect is, any number does not really tell you the truth. What we can tell you that on a blinded basis, with all the caution talking about blinded, they look somewhat similar or very similar to the phase II, right? phase II goes to day 14. phase III goes to day 28. They're not directly compared.
Whatever we have seen, it looks very, very similar to phase II. That's all we can share. Look, we look at it, blinded data we get them two to three months later, and so it's not very updated information. Yeah, these are not very updated information, so they still can change. You know, the message is that they look very, you know, very similar to phase II. Of course, we know what the phase II placebo did because it's been published and we have the unblinded data. We don't know what placebo is doing in the phase III. That's the big question mark. In terms of like overall color, they are very overlapping the phase II data, both monotherapy and adjunctive, and they look very similar. I hope I, you know, I give you an answer.
Yeah. Thank you.
That's the best answer I can give you.
Thank you, Sergio.
Thank you.
We take our next question from Andrea Tan with Goldman Sachs. Your line is open.
Good afternoon. Thanks for taking my questions. My first one here is just, can you speak a little bit more on what Fast Track designation gives you here as it relates to the monotherapy indication? Just remind us maybe the nature or extent of your conversations with the agency regarding the use of Reliance III to support an expanded label.
Yeah. Good afternoon, Andrea, and thanks again for the question. It's actually a very interesting question. This one came. I don't want to say that came as a surprise because we filed the application because we hope and we expect to get the Fast Track designation. What's very interesting is that there are 28 drugs approved in the United States for depression. The fact that REL-1017 has been awarded Fast Track designation for indication, but you have a lot of choices that probably they are not ideal. It tells us that the FDA, at least at the very minimum, believes that there is a need for something new as a single agent treatment of depression.
That we are very pleased to see that. You know, maybe that they think or whatever that REL-1017 can bring something new and good for patients. What does that mean? There have been only nine, I believe, if I counted correctly, Fast Track designations awarded this year. It's not something the FDA gives away very easily. But it has some advantages, you have more access to the FDA, right? They tend to give you an answer quicker, and you have some more, like, informal exchange of information and communication with the FDA. It makes, you know, the process, I don't wanna call it easier, but definitely faster. You know, there is more communication with the FDA. That is always good. Hope I answered your question.
Got it. Maybe a follow on there. Just has the agency, I guess, maybe in these conversations you've been having with them, you know, maybe suggested that Reliance III can be used as, I mean, maybe can it be used as a pivotal study to support expansion into the monotherapy setting?
Well, yes, we do. I mean, I think it is a very fair assumption that Reliance III will be a pivotal trial that will support the approval of REL-1017 as a monotherapy single agent treatment of depression. Clearly it's, yeah, we will present to the FDA a full package and talk with Reliance I and Reliance II, they will have a lot of information well enough to make a decision on what would be the best use for REL-1017. You know, single agent is important. It's very right. The fact that we received this designation for Fast Track, you know, that we see it as a very positive signal to get that indication.
Perfect. Then maybe if I can ask one question to John. Just, I would be curious to hear your thoughts on the evolving depression landscape, just in the context of the new drugs that are potentially going to be approved over the course of this year. Curious how you think REL-1017 compares to these drugs and your expectations for where it might be able to be used in the treatment paradigm.
Yeah. Thanks, Andrea. That's a good question because there continue to be a lot of dynamics in the depression market space. You know, the way I see things and a lot of my viewpoint is based upon interactions with psychiatrists and KOLs in regards to this. Everybody's looking for new approaches to treat depression because everyone in the field understands that only so much remission is really truly achievable for so many patients. Patients tend to, it's not really the best term, but they do tend to grind through a lot of different treatments to try to get to the one that offers the benefit.
You know, I think with the other agents that are in a similar phase as ours is in, you know, it's good to bring new options to the marketplace because that just creates new and better, hopefully better opportunities for clinicians and patients to get to well, truly realizing that that still is a difficult goal. When I look into the future with you know, further developments out there, such as the psychedelics, that brings another interesting dynamic that I think will be challenging from a payer reimbursement standpoint, without a doubt. When I look back at where REL-1017 is, I just.
Given particularly the phase II data that I've had a chance to dig in on, that data suggests that this drug has the opportunity to truly provide fast antidepressant relief to patients, and they've been looking for that since probably the second year of the SSRIs being on the market when everyone realized that it really did take a month or more to get any type of a benefit. I think that REL-1017 is going to be able to fulfill that, again, based upon what I've seen in the phase II data. With a strong effect size, it could be game-changing out there versus other antidepressants. If that's a strong signal. On top of it appears to be safe.
The fact that it can be administered orally just is kind of that grail that people have been looking for to be able to really get patients to well. I think the prospects for our drug are very positive based upon that. As long as the phase III data comes close to what we've seen in phase II, I think we've got a wonderful opportunity to really get patients into a much better situation. I hope I didn't ramble too long there, and I answered your question sufficiently, Andrea.
Yeah. Great. Thank you so much, John.
Thank you.
Thank you. We take our next question from Joon Lee with Truist Securities. Your line is open.
Hey, thanks for taking our questions. Are you also using a loading dose in phase III as you did in phase II? Are there other antidepressants that also use loading doses? Were the loading doses also used in your human abuse potential studies?
Hey, Joon. Good afternoon, and thanks to you as well for the question. Yes, we do use the loading dose. We used it in phase II and all three phase III trials. Patients take three tablets, 75 mg the first day of treatment. Yeah, the reason we're doing that is it is to shorten the steady state. It is a long half-life. If you don't use the loading dose, it takes four to five days. With the loading dose, it's shortened to two to three days. That is very important because one of the features of REL-1017 is the rapid acting. The sooner you get to efficacy and blood levels, plasma levels, the better.
Is there?
Your question. Go ahead.
Oh, no, no. Thanks for the clarification.
Go ahead.
There, the FDA wasn't worried at all that, having that, three times a dose on the first day might possibly have such an effect that might lead to an unblinding of the randomization?
No, no. No, we have seen nothing in phase II, and we have seen nothing in phase III as well. It's a very benign drug, and the loading dose in phase II for the highest dose was actually 100 mg or four tablets or, well, solution in phase II. It was a corresponding of four tablets. There was no sign of anything that could, like, signal any, like, that you're taking the drug is not the placebo. To answer the other part of your question, there are other antidepressants that use loading dose. I don't have anything on the top of my mind. I do know that there is few of them, of which one John knows very, very well.
They require titration, because if you take the full dose the first day, you get some, you know, some side effects. You need to start with a lower dose so that you need to titrate to the effective dose. I don't have anything on my mind of adding onto your question that use loading dose. You know, tolerability, we see it as a big advantage. If you can give, like, three times the therapeutic dose to hasten the, you know, the steady state and to hasten the, you know, the onset of the effect, I don't think other drugs don't do it. They don't do it just because they don't have enough safety and tolerability. They can do that. Otherwise, yeah, there's no reason not to do it.
Great. Thank you so much.
Thank you for the question.
Yep.
Thank you, Joon.
Very clear. Thank you.
Once again, ladies and gentlemen, please press star one to ask a question. Star one to ask a question. We take our next question from Jay Olson with Oppenheimer. Your line is open.
Oh, hey, thanks for taking the question. Maybe for John, I'm just curious about the due diligence he did, and congrats to him on joining Relmada. If you could please comment on the feedback that you got from KOLs that you spoke to, and what are some of the lessons learned from your work at Eli Lilly and elsewhere that you hope to leverage at Relmada? What are the greatest challenges you expect to face in the launch of REL-1017, and how do you plan to overcome those obstacles? I have one follow-up, if I could.
Jay, thank you very much for the questions. The due diligence that I did was extensive. Really the way I did it was since I've been in the space a long time, I'd been watching Relmada's data from afar anyway. When this opportunity arose for me, besides being very excited, I spoke to a lot of my psychiatry friends and I just said, "Hey, what are your thoughts about this drug based upon what you know at this point in time?" I have to say that every single one of them said that this drug looks extremely exciting to them. I'm quoting them and their viewpoint given what they've seen so far.
Then when I, you know, probe a little bit further, you know, as to why that was, they say, "Well, it does appear to work rapidly. It does appear to be safe." While it, you know, carries the esmethadone name, you know, they said that strong data and safety data will certainly win out over any type of reluctance or concern that some clinicians may have because the field is still looking for something that really is going to be efficacious and safe and easy from a patient administration standpoint. So that was very consistent in terms of the due diligence, which made the decision easy for me.
I've been doing other projects in the depression space, so it just cemented the decision that I was thrilled, and an easy yes for me to join the team. In terms of lessons that I learned from Lilly, gosh, there are a lot. I would draw first on my experience with Prozac, where the company obviously brought forward a revolutionary, iconic antidepressant. As more and more competitors came in, I have to say, I think the organization, particularly my marketing organization, we started to move away from some of the basics of staying with our own positioning with Prozac and started to kind of follow what the competitors were doing.
What we learned late in the life cycle was to go back to our knitting and remain with the positioning concept that got Prozac to where it was. We employed that very same principle with Cymbalta as we prepared to launch it, realizing we were gonna be antidepressant number 11, 12, or 13 into the U.S. marketplace. We needed to have a unique own-able and differentiating positioning concept around depression hurting. Hurting both emotionally and physically. That's something I really want to employ with Relmada, is to come up with a positioning concept that will differentiate it from all of the other potential new entrants coming in around the same time period.
The challenges to face, going back to the esmethadone, you know, that's something that we know will be something we're gonna have to work through and scheduling. When I look at other analogs such as Epidiolex, the epilepsy drug that's a derivative of marijuana, it's a cannabinoid, it came out as a Schedule V, and then after about a year or two on the market, it became descheduled. I think that may be a very good analog for us to dig into and understand and to follow. I hope I answered your questions, Jay. Thank you.
Yeah. That was super helpful. Thank you so much, and congrats again for joining Relmada. If I could maybe squeeze in one follow-up question for the team. Since most registrational MDD studies have more than 28 days of randomized treatment, can you just comment, maybe Sergio, on what sort of guidance you would give to physicians for treatment durations beyond 28 days of REL-1017 and specifically how do you analyze data beyond 28 days? How long should a patient be on therapy?
Yeah. No. We have to see the phase III data first and, but right, we discussed it internally. There is really no specific in general for antidepressant and John can help me out on that. There, you know, beyond the study period, you don't have a lot of guidance you can give. Also because every patient is a patient is different from the other one. In terms of safety, that's the guidance that we can clearly give. We have the long-term safety study ongoing. We have quite a bit of patients already completed six months, and we have quite a bit of patients completed 12 months. Really there is no sign for any long-term safety or tolerability issues.
In terms of safety and tolerability, we will be able to tell the doctor we have that data at least until 12 months. We feel very comfortable that nothing surprising will show up. In terms of efficacy, when you have that kind of safety and tolerability, it depends on the patient. There are patients that take the treatment chronically. There are patients that when they are out from the depression episode, they want, you know, to stop and eventually retake it if they get depressed again. It's very difficult to answer this question in a very simple way. It will be up to the doctor what, you know, they will do.
Okay.
The day 28.
Great. Thank you very much.
From the conversation with the FDA, day 28, it means chronic treatment. That will not stop at day 28. When it's, you know, you had the label for chronic treatment, technically you can use it as long as you would like to, as long as the patient require the treatment.
Okay. Thank you. That's helpful.
Thank you.
We take our next question from Uy Ear with Mizuho. Your line is open.
Hey, guys. Thanks for taking my question. Just wondering if you guys have already sort of or plan to schedule a pre-NDA meeting with the FDA. Just curious to know if there's anything that needs to be aligned in terms of the NDA package, either on the preclinical level or the CMC level. Thanks.
Thank you, Uy. Thanks for the question. Yes, we will schedule a pre-NDA meeting. We would like to have at least one phase III data top-line results before we approach the FDA. I believe they will take us a lot more seriously if we have good phase III data. We will schedule a pre-NDA meeting. Yeah, we will provide the full package that will go from, you know, preclinical CMC to the clinical. Clearly, the phase III, the clinical part will be the one that will be the topic of discussion. From communication with the FDA that go back to months ago, we do believe that the preclinical package is done, so there is no more request for any non-human studies or in vitro studies. In CMC.
Well, Maged is on the call. Maged is actually the lead on the manufacturing. We are well advanced. We have well enough product not only to complete the phase III, but also to go beyond that. I believe, Maged, correct me if I'm wrong, but we are making the commercial batches. So CMC will probably be filed with the FDA. We have it all in NDA, so we'll be filed before we file the clinical package. Maged, do you have anything to add?
No, that's a great summary, Sergio. Thank you. Thank you for the question.
Can I sneak in another question, if I may, Maged?
Sure.
Just wondering, the amount of cash that you end the quarter with. Could you remind us what that would take you through?
Sure. We ended the quarter with $212 million. Based on our internal estimates, that'll take us out to mid-2024.
Okay, thanks.
Sure. Thank you for the question.
Thank you. It appears there are no further questions at this time. I'd like to turn the call back to Sergio for any additional closing remarks.
Sure. Well, thanks everyone for the time and interest in our program. In closing, I am and remain very grateful to the Relmada team for their continued hard work and dedication to executing our mission. I would like also to extend my sincere thanks to the participants and clinical partners involved in the REL-1017 clinical trials for their effort in advancing this important product candidate through the clinic as expeditiously as possible. It is a very large program. The question I had, if you asked me the same question like 1.5 years ago, what was worrying me the most was that, you know, can we actually do a program of this size and this complexity? Well, now I can give you the answer. We actually did it.
We are almost there, and that's thanks to the, you know, the team and the patients and the clinicians that help out on this. Thanks a lot. With that, I believe the call can be concluded. I wish everybody a wonderful rest of the day and a wonderful evening. Thank you very much.
Ladies and gentlemen, that will conclude today's conference. We thank you for your participation. You may now disconnect.