Minerva Neurosciences, Inc

Welcome to Minerva Neurosciences' year-end 2020 conference call. At this time, all participants are in a listen-only mode. There will be a question-and-answer session following today's prepared remarks. This call is being webcast live on the Investors section of Minerva's website at ir.minervaneurosciences.com. As a reminder, today's call is being recorded. I would now like to turn the call over to William Boney, Vice President of Investor Relations and Corporate Communications at Minerva. Please proceed.

Good morning. A press release for the company's fourth quarter and year-end 2020 financial results and business highlights became available at 7.30 Eastern Time today and can be found on the investor section of our website. Our annual report on Form 10-K was also filed electronically with the Securities and Exchange Commission this morning. and can be found on the SEC's website at www.sec.gov. Joining me on the call today from Minerva are Dr. Remy Lutheringer, Executive Chairman and Chief Executive Officer, and Mr. Jeff Race, Executive Vice President, Chief Financial Officer, and Chief Business Officer. Following our prepared remarks, we will open the call for Q&A. Before we begin, I would like to remind you that today's discussion will include statements about the company's future expectations, plans, and prospects that constitute forward-looking statements for purposes of the safe harbor provisions under the Private Securities Litigation Reform Act of 1995. We caution that these forward-looking statements are subject to risks and uncertainties that may cause actual results to differ materially from those indicated. These forward-looking statements are based on our current expectations and may differ materially from actual results due to a variety of factors that are more fully detailed under the caption risk factors in our filings with the Securities and Exchange Commission, including our annual report on Form 10-K for the year ended December 31, 2020, filed with the SEC earlier today. Any forward-looking statements made on this call speak only as of today's date, Monday, March 8th, 2021, and the company disclaims any obligation to update any of these forward-looking statements to reflect events or circumstances that occur after today's call, except as required by law. I would now like to turn the call over to Remy Luthringer.

Thank you, Bill, and good morning, everyone. Thanks for joining us today. I'm very pleased to present an update on progress and our earnings report for the full year 2020. In May last year, we announced top-line results from the double-blind portion of the phase 3 trial with Roliparidone in negative symptoms of schizophrenia. Although the study did not meet statistical significance, we remain highly encouraged by the promising signals that emerged. We look forward to sharing data from the Phase III nine-month open label extension, which will be available in the first half of this year. Following our Type C meeting with the FDA in November 2020, during which the FDA cautioned us that an NDA submission based on the Then current data from the Phase IIb and Phase III studies would be highly unlikely to be filed. We continue our dialogue with the agency. We are providing information to the FDA on several topics highlighted in the meeting minutes. Furthermore, we will also initiate a pivotal bioequivalence study in approximately 48 healthy volunteers, comparing the formulation employed in the Phase IIb and Phase III trials, as well as at least one new formulation designed in conjunction with our commercial supply partner, Catalan Inc., to facilitate large-scale manufacturing. We are working to address the FDA's requests and comments, and we are motivated by the agency's encouragement to continue the development of Roliparidone for the treatment of negative symptoms of schizophrenia. Among emerging therapies in development for negative symptoms, Roliparidone is the most clinically advanced, we remain committed to bringing Roliparadone as quickly as possible to patients in need of such a treatment. We are looking forward to 2020-wide with a significantly improved cash position following the recent sale of our rights to the self-directed royalty to Royalty Pharma, from which we received $60 million up front and will receive a further $95 million subject to the achievement of certain milestones. First, I would like to provide a more detailed update on our lead program, Roliparidone, a drug which has the potential to treat negative symptoms. Our primary objective in 2021 is to continue the development path forward to meet the regulatory requirements to submit an MDA for Roliparidone. First, the nine months open label extension of the phase three trial has been completed on schedule a few weeks ago. And I am happy to report that no patient was discontinued due to COVID-19 illness. The total of 333 patients, around 65% of those enrolled entered the nine-month open-label extension, in which those patients already being treated with Roliparidone remained on treatment on the same dose received in the 12-week double-blind phase, 32 mg and 64 mg. Those patients who received placebo in the 12-week double-blind phase were randomized to either 32 mg or 64 mg. We are very pleased that a total of 202 patients, around 61%, completed the open-label extension of the study. Data are expected to be available in the first half of 2021. These data are important because, as we observed in the Phase 2b six-month extension, they may demonstrate if improvement of negative symptoms is sustained or increased over the one-year duration, if improvement of negative symptoms leads to improved functioning, whether rolyperidone maintains or improves positive symptoms and or agitation, and whether the safety and tolerability profile of rolyperidone is maintained over the one-year administration period. I look forward to sharing a detailed presentation of the findings when data become available. In parallel, we continue to move forward with activities necessary to support the submission of a new drug application for roliparidone. First, we intend to initiate the bioequivalence study I described earlier. Importantly, we believe that by showing bioequivalence across formulations, we will address the specific comment made by the FDA about the Phase IIb formulation. Second, we are in the process of submitting the requested scientific literature in support of the psychometric properties of the primary and key secondary endpoints used in our clinical development, as requested by the FDA. Following the completion of the pivotal bioequivalence study, we plan to request a pre-MDA meeting with the FDA to discuss certain matters, including data from the phase three open label extension, data from the bioequivalence study, and potential NDA submission of Roliparidone for the treatment of negative symptoms of schizophrenia. I will now move on to recent developments in the cell direction program. You will remember that in mid-2020, Minerva exercised its right to opt out of a joint development agreement with Janssen, for the future development of Cell2Excent. As a result, we are entitled to collect mid single digit royalties on potential future worldwide sales in certain indications with no further financial obligations to contribute development costs to Janssen. On January 19 of this year, we announced that Royalty Pharma had acquired Minerva's royalty interest in Cell2Excent and that we received an upfront payment of $60 million, with the potential to receive up to further $95 million in additional payments contingent on achieving certain clinical, regulatory, and commercialization milestones. Cetorexone is currently in phase three clinical development by Janssen Pharmaceutical, a subsidiary of Johnson & Johnson, for the adjunctive treatment of major depressive disorder with insomnia symptoms. We are delighted to have partnered with Royalty Pharma, the leader in acquiring pharmaceutical royalties across the life science industry. It has enabled us to secure significant non-dilutive funding, both immediate and potentially over the long term, that will support our top priority, the continued development of Roliparidone, our lead asset. In summary, we remain committed to developing Roliparidone as a potentially transformative treatment in the treatment of the negative symptoms of schizophrenia. I look forward to sharing data from the Phase III Open Label Extension with you soon and the Pivotal Bioequivalent Study in the coming months, as well as continuing to update our investors on the ongoing dialogue with the FDA. I will now turn it over to Jeff to discuss our financial performances.

Thank you, Remy. Earlier this morning, we issued a press release summarizing our operating results for the fourth quarter and year ended December 31st, 2020. A more detailed discussion of our results may be found in our annual report on Form 10-K filed with the SEC earlier today. Cash, cash equivalents and restricted cash as of December 31st, 2020 were approximately $25.5 million. compared to $46 million as of December 31st, 2019. In January 2021, the company received a $60 million cash payment from Royalty Pharma in connection with their acquisition of the company's royalty interest in Seltzer Exxon. We presently expect that the company's existing cash and cash equivalents, which include its financial resources at year-end 2020, combined with the $60 million payment received in January from Royalty Pharma, will be sufficient to meet its anticipated capital requirements for at least the next 12 months from today, based on our current operating plan. The assumptions upon which this estimate is based are routinely evaluated and may be subject to change. Research and development expenses were $3.6 million and $28.5 million for the fourth quarters of 2020 and 2019, respectively. R&D expenses were $22 million and $58.1 million for the years ended December 31st, 2020 and 2019, respectively. The decrease in R&D expense for the fourth quarter ended December 31st, 2020 was primarily due to a $19 million charge taken in December 2019 for the impairment of the in-process research and development related to Mn117, following the results of the Phase IIb trial in MDD, which failed to meet its primary and key secondary endpoints. The decrease in R&D expense for the year ended December 31st, 2020, was due also to the approximately $11 million from the completion of the Phase IIb clinical trial of Mn117 in December 2019 and the completion of the double-blind portion of the phase three clinical trial of Roliparidone in May 2020. Non-cash stock compensation expense included in R&D expenses was $3 million and $2.6 million for the years ended December 31st, 2020 and 2019 respectively. G&A expenses were $3.7 million and $3.8 million for the fourth quarters of 2020 and 2019, respectively. G&A expenses were $17.3 million and $17.7 million for the years ended December 31st, 2020 and 2019, respectively. The decreases in G&A expenses for the fourth quarter and year ended December 31st, 2020 were primarily due to lower pre-commercial expenses in 2020, offset by higher insurance costs. Non-cash stock compensation expense included in G&A expenses was $6.7 million and $6.5 million for the years ended December 31st, 2020 and 2019, respectively. Net loss was $7.3 million for the fourth quarter of 2020, or loss per share of 17 cents, basic and diluted, compared to net loss of $29.9 million for the fourth quarter of 2019, or loss per share of 77 cents, basic and diluted. Net income was $1.9 million for the year ended December 31, 2020, or income per share of 5 cents, basic and diluted, compared to a net loss of $72.2 million, or loss per share of $1.85, basic and diluted, for the year ended December 31st, 2019. Collaborative revenue was $41.2 million and zero for the years ended December 31st, 2020 and 2019, respectively. The increase in collaborative revenue was the result of the company's exercising its right to opt out of the co-development agreement with Janssen during 2020. As a result of the opt-out, the company has no further performance obligations and recognized revenue of $41.2 million, which had previously been included on its balance sheet under deferred revenue. Now I'd like to turn the call over to the operator for any questions. Operator.

Thank you. To ask a question, you need to press star then 1 on your telephone. To withdraw your question, please press the pound key. Our first question comes from the line of Tom Schrader with VTIG. Your line is now open.

Hi, this is Julian on for Tom. Thank you for taking my questions. I'm wondering if there are any data points from the upcoming open label extension analysis that could maybe specifically address some of the pushback you got from the FDA in your recent Type C meeting. And then on the bioequivalent study, is it fair to assume this is the gating step to filing an NDA, or would the CMC package here likely be the last detail?

Hi, Remy speaking. So, obviously, great questions. I really think that indeed you're right. I mean, the extension data will be really very important because, as you know, negative symptoms is a chronic part of the disease, and you need to really demonstrate that, I mean, this effect is sustained over time. So as I mentioned in my presentation, I mean, we are really looking forward to check again because we have already, obviously, this data from the phase 2b. remember we had six months extension on top of the three months of the 12 weeks double-blind phase so we could see in this study a continuous improvement of negative symptoms and also an improvement in terms of functioning so so first of all I mean we will be able to confirm that the negative symptoms continue to improve second does this transform into a functional improvement and As you know, what is really important is that these patients are able to function again, that they can go back to have a job, that they have a decent family life, so functioning is extremely important. So we will be able to check this because we are measuring PANS and PSP all along the extension, over the nine months extension, so we will have data over one year. We will also be able to check what is going on in terms of positive symptoms and what we can call relapses to see if I mean we we have limited number of relapses as we had in the phase to be so this will be obviously very important and last but not least as you know I mean we really put this extension in place to confirm the efficacy data but also to check the box about 12-month exposure of other drugs, so we will also be able to check in terms of safety and long-term safety. So, in my opinion, extremely important data, and if you remember, yes, indeed, it's no longer placebo-controlled, but it is still blinded for the doses, so we will really also have the possibility to check between 64 mg and 32 mg. And for your second question about the bioequivalent study, Yes, indeed. I think this is really the important study. If we can, as in this preliminary study we did some time ago, demonstrate again bioequivalence between the different formulations, I think this is really the driver of moving towards the pre-NDA meeting.

Great. Thank you.

Thank you. Our next question comes from the line of Jason Butler with JMP Securities. Your line is now open.

Hi. Thanks for taking the questions. A couple on the open label extension. Can you just give us a sense of how many patients from the placebo arm of the double-blind trial rolled over into the open label extension? And then secondly, how are you thinking about releasing the data? Will you release the data in conjunction with a medical meeting or – Could we get it as soon as you finish the analyses that you've outlined in the press release? Thanks.

Good question, Jason. So clearly, I mean, in terms of placebo patients who went to the extension phase, I think it was quite equivalent between the three treatment arms. So we had the more or less the same number of placebo patients who switched to either 32 or 64 milligrams because this is what happens when they're going into the extension. And I think this data, as I think I, hopefully I was able to convince everybody, I think this data is extremely important because this will be an additional piece of information about the efficacy of our molecule. I think that we will have a specific announcement and a specific event about this release of this data because they are so important. So as soon as we have the data available, we'll think about the best format to communicate the data.

Great. And then just one more, Rami, on the MITT analysis. Any updated thoughts on, you know, or interactions with FDA or your advisors on the the agency's willingness to accept the analysis excluding that single outlier site?

So, you know, as always, it's a matter of review, yes, because the FDA will go into the data more deeply. I mean, they will really check all the data we have to really confirm that, I mean, these 17 patients from this site, really, I mean, the assessment of efficacy as well as assessment of some vital signs that was not done according to how it should have been done. So when you're looking to, you know, to what has been done in the past, particularly by the Psychiatric Division, I mean, a lot of files or a lot of NDAs have moved forward with modified IDT population. I mean, so clearly, I mean, we are confident that, I mean, These 17 patients should not be in the analysis, and their precedents were in the FDA. Again, after having reviewed very carefully the data, we're happy with the modified ITT population to be considered. And this is what came out basically from the type C meeting. They really confirmed that based on a matter of review, they are willing to consider ITT and MITT data. Okay, great. Thanks for taking the questions. Thank you, Jason.

Thank you. Our next question comes from the line of Barron Ammon with Jefferies. Your line is now open.

Yeah, hey, good morning, guys. This is Jeet on for Barron. Just a couple of questions from me. Again, on that modified IDT point, Remy, are there any specific examples of agents being approved in the neuropsych space that actually went ahead with a modified ITT analysis that perhaps included or excluded a group of patients. And just in terms of the open label extension data, are we going to see endpoint data such as PSP or CGIS to kind of make the point on improvements in patient performance and status? Thanks.

Yeah, so definitely there are precedents. I mean, and as I just mentioned before, I mean, in the space of psychiatry and specifically with the psychotic division, I mean, without going into the details, but I mean, you have approvals like Spravato, you have approvals like Brexprepazol, where I mean, definitely the modified IDT population has been accepted by the FDA. So again, I think we are not doing something special here. I mean, what is important is that the FDA gets comfortable with this site. This site did not provide plausible data. So this is what I can say about this. Can you repeat the second question? Sorry, what is the second point you're saying?

Yeah. The second question was just on the open label extension data we'll be getting. Are we getting PSP and perhaps CGIS data, just to talk about patient performance?

Sure, sure, sure. As I mentioned before, we continue during the open label to measure all the efficacy parameters, including PANS, PSP, CGI, and so on. So definitely, yes, indeed, we will have this. And I think we will be able to really to re-demonstrate, as we demonstrated already, that the PSP improvement is very linked to the improvement of negative symptoms. If you remember, PSP total score was already significant in the double-blind phase. But indeed, we will have all this data. We will have, again, the analysis of from where the functional improvement is coming. Is it related to negative symptoms? And more specifically, you know, We will also have abolition there. So all this will happen and will be presented, definitely, yes. Great. Thank you so much. You're welcome.

Thank you. Our next question comes from the line of Joel Beattie with Citi. Your line is now open.

Hi. Thanks for taking the question. The first one is on bioequivalence. Could you compare the differences in the three different formulations for us from phase two, phase three, and then also what you plan to be in the commercial supply? And then, you know, along with that comparison, could you tell us about what you plan to show in the bioequivalence study to help comfort FDA?

Yeah. So, again, I mean, as you know, I mean, what we are trying to demonstrate is here that the the exposure of the drugs, so the AUC of the drugs, or the different formulation are the same because, as I mentioned in the past, I mean, the efficacy, when you're doing the PKPD analysis, the efficacy of Roliparadone is coming mostly from the parent compound and it is related to exposure, so to AUC and not at all to CMAX. So this is extremely clear from our PKPD analysis which have been done by some key external people who are really specialists in the space. So what we tried to achieve between the phase 2b and the phase 3, if you remember, Joel, was to keep this AUC, which our preliminary PK study showed, but we wanted to reduce the Cmax of parent compound and one of the metabolites, BFB520, because we wanted to even further improve the safety margin in terms of effects on QTC prolongation. So this is a difference between a Phase IIb and Phase III formulation, and we were able to do it. Remember, we presented this in one of our webcasts. where we could show that, I mean, we kept the AUC and we reduced Cmax of, again, parent and B520, this metabolite. Now, between phase three and the final formulation, nothing major has changed. It is just some percentage of some ingredients and this should not change at all the bioequivalent. So it is really to confirm once more that, I mean, and we already have the information, that, I mean, this is completely comparable between phase three and the final formulation, which is currently produced by Catalan.

Hello? Got it. Thanks. And then one other question on the MITT. For the 17 patients, is there any way to get kind of like real actual data from those patients, or is that something that does not exist?

Here you have to explain to me what you mean by real actual data.

Yeah, I guess, you know, it sounds like the data was so implausible that it doesn't reflect actual readings. Yes. So have you been able to confirm, for example, that those patients were dosed and actual readings and assessments were taken?

Sure, sure, sure. That's okay. I understand. So definitely I think there is no doubt about it that the patients exist. Why it is also clear is that, I mean, a lot of the data for efficacy and for, again, some vital signs, have just been carried forward from the baseline. So there is no modification of this data over time, which is completely implausible. So clearly, I mean, and I gave some examples in the past. So clearly, I mean, patients exist, but the assessments have not been done in the right way. Thank you. You're welcome, John.

Thank you. Our next question comes from the line of Myles Minter with William Blair. Your line is now open.

Thanks for taking the questions and apologies for the background noise. This is a clarification question. I believe for the MITT analysis to be sort of accepted by the FDA, that that would be a process of review. But out of the type C meeting, they're actually stating that the NDA in its current format would be unlikely to be filed. So that would mean that it wouldn't get a review. So my question is, is that the correct interpretation? And then was the... unwillingness to recommend a filing or acceptance of that filing, was that just due to the fact you didn't have this open label safety data set on hand and now you're ticking the boxes and you have everything in place? Or am I completely misinterpreting that? Thanks.

So, I mean, as you know, Minerva is an extremely... transparent organization and we gave exactly the terms of what we received in the minutes. So this is to answer one of your points. It is clear that the open label data were not available at the time and we are really hoping that this open label data will be an additional piece of information confirming that, I mean, rhodoperidone is an efficacious drug. So, afterwards, I mean, will we go to the level of preview? I think, I mean, if you go according to these guidelines, so this is guidance from end of 2019, if we are able to convince the FDA about our face-to-be data, this is obviously related to the bioequivalent study, which will make the phase to be one of the two studies you have in your efficacy data package. If this shows bioequivalence, I mean, if we can demonstrate bioequivalence, I don't see really a reason why we could not move to the review process. And this is what our advisors are telling us. And, you know, what the FDA also said is that, I mean, if this goes to review, I mean, this will go to an outcome. So it's... It's, I think, a dynamic process. As I mentioned in my presentation, we really are having the dialogue open with the FDA. We gave them the information about the psychometric aspects of the different scales. We gave them how we managed the calculation of the total score of PSP. So it's a continuous dialogue, and I'm extremely confident But I mean, if we are doing a great job in explaining even better our data and the way we have analyzed them and what is in the data, I think we will have a positive year from the FDA and we will be able to move forward with the NDA.

Yeah, I understand. That's very helpful. And my second question is just on the bioequivalent study. I understand the last time you were talking about that to us, it was around about 36 patients and now it's gone up to 48. Is that just an additional cohort for the commercialization formulation or is there added patients for some other reason in that trial? Thanks very much.

Yeah, so when we spoke together, I mean, you know, I was speaking about the guideline. No, we have done a real power calculation, powering calculation, sorry. And it ends up with 48 subjects. So we are going to the safe side, basically. I mean, having more subjects or healthy subjects because we are not dealing with patients here. It's healthy subjects. So the powering is indicating that 48 is a number to go. Obviously, as you know, because this is a crossover trial, whereas a subject is his own control. And basically, here, you might also have some dropouts. I mean, you never know because a healthy volunteer finds a job and he does not want to do period three. So clearly, we are also anticipating or including in our modeling and in our power calculations that maybe one or two subject might drop out. So it's really to be on the safe side, basically. Sorry to interrupt you. Something very important is that we also have submitted our protocol to the FDA, and we are definitely waiting if they have any feedback. So it's done again in a very open and constructive mindset with the FDA.

lots of interactions with the FDA and looking for the open label data. So thanks very much.

Thank you.

Thank you. Our last question comes from the line of Douglas Salve with HC Wainwright. Your line is now open.

Hi, good morning, and thanks for taking the questions. Just, Remy, in terms of the open label extension, we're going to get data for the 64 and 32 milligram doses. you've sort of honed in on the, you know, the 64 milligrams. You've seen a more sort of consistent effect across the studies now. But is there anything that you could see from the 32 milligram that would perhaps make you sort of revisit that in terms of the, you know, your sort of thoughts for the molecule going forward? Thank you.

Yeah. So, I mean, technically, I mean, yeah, I have not given up on 32 mg because I remember the Phase IIb and it was very clear that 32 mg was really different from placebo. When you're looking to the effect size of the delta we have in the Phase III, 32 mg is again showing a nice improvement. Obviously, I mean, placebo had also a larger improvement. That was why I think we could not show a p-value at the end of the day. When you're looking to integrate it, when I speak integrated, I mean, the combined phase 2b and phase 3 double-blind data, I mean, the two doses are highly significant with very decent effect sizes. So indeed, if the extension data are again pointing towards the fact that 32 mg continues to improve negative symptoms over a period of one year, I think 32 mg is an important dose. I'm not saying that this will be part of the final finding of the MDA, but I mean, 32 has still clearly shown that we have a pharmacological effect with this dose. let us have the data, let us analyze the data, and we will see what we're doing with 32 mg, but all is pointing towards the fact that 32 is clearly showing a pharmacological effect of an improvement of the patients.

Okay, great. Thank you. And just as a follow-up, in terms of your analysis that made you confident that the effect was really AUC, not Cmax, which makes sense, I'm just curious, you referenced some PD markers. I'm just curious what PD markers you focused in on. Thank you.

For the PKPD analysis, I mean, it was definitely based on the PANS negative scores. I mean, so here we are really referring to PANS negatively. So we did plasma exposures versus negative symptoms coming out from the PANS. And clearly, when you're looking at what is explaining as improvement of the PANS negative score, it is AUC and not at all CMAX. So this is from where I'm making this comment. It's a very, very careful analysis between PANs and parameters and the different pharmacokinetic parameters.

Okay, great. Thank you.

You're welcome.

Thank you. There are no further questions. I will now turn the call back to Rumi Luthringer for closing remarks.

Yes, thank you so much. Thank you really everybody for all these great questions. I wanted also to take this opportunity to thank patients and families and caregivers who have participated to this phase three study. As you have heard, some of these patients went to the end of the 12 weeks, more than 200 patients. So thank you again for this opportunity. hopefully to develop an extremely innovative drug which would be one of the first treatments for negative symptoms. So I'm looking forward to update you on the next upcoming milestones, open label data and biofilms data. So thank you again and looking forward to speak with you soon. Bye.

Ladies and gentlemen, this concludes today's presentation. Thank you once again for your participation. You may now disconnect. Everyone, have a great day.