Earnings Call Transcript - NERV Q2 2021

Operator, Operator

Welcome to the Minerva Neurosciences Second Quarter 2021 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 Boni, Vice President of Investor Relations and Communications at Minerva. Please proceed.

William Boni, Vice President of Investor Relations and Communications

Good morning. A press release with the company's second quarter 2021 financial results and business updates became available at 7:30 AM Eastern Time today, and can be found on the Investors section of our website. Our quarterly report on Form 10-Q 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 Luthringer, Executive Chairman and Chief Executive Officer; and Mr. Geoff 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 SEC, including our quarterly report on Form 10-Q for the quarter ended June 30, 2021, filed with the SEC earlier today. Any forward-looking statements made on this call speak only as of today's date, Monday, August 2, 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.

Remy Luthringer, Executive Chairman and Chief Executive Officer

Thank you, Bill. And good morning, everyone. Thanks for joining us today. Following the completion of the open-label portion of the Phase 3 trial with roluperidone in schizophrenia, and the Type C meeting with the FDA, Minerva continues to work towards the submission of a New Drug Application in the first half of 2022. Toward this end, we have completed enrollment in a pivotal bioequivalence study with roluperidone in healthy volunteers. We also continue to make progress in assembling the components required to submit an NDA for roluperidone, including clinical pharmacology, non-clinical and CMC activities. We anticipate completing these activities over the coming months, and we look forward to continuing our dialogue with the FDA in anticipation of submitting a request for a pre-NDA meeting.

Geoff Race, Executive Vice President, Chief Financial Officer and Chief Business Officer

Thank you, Remy. Earlier this morning, we issued a press release summarizing our operating results for the second quarter ended June 30, 2021. A more detailed discussion of our results may be found in our quarterly report on Form 10-Q filed with the SEC earlier today.

Operator, Operator

Our first question comes from Andrew Tsai with Jefferies.

Andrew Tsai, Analyst

First question is on just the open-label extension. I mean I've had the impression that you've interacted with the FDA from time to time over the course of 2021, and you've addressed some of the things that came up during the Type C meeting. So if that's true, I guess, how have those discussions progressed? Have you discussed the open-label extension data with the FDA yet? Or should we expect that to happen later on in the Q4 pre-NDA meeting?

Remy Luthringer, Executive Chairman and Chief Executive Officer

Yes. Remy speaking. Yes. So definitely, no, we have not discussed the open-label extension data with the FDA. The interactions we have on a regular basis since the beginning of the year are about the topics which have been raised during the Type C meeting. So for the moment, the open-label extension data, as you have seen, have been published and presented. And we will obviously include this part in our package or our briefing book to be submitted to the FDA for the pre-NDA meeting. And I guess it's an important piece of information, if you keep in mind the results we obtained.

Andrew Tsai, Analyst

Great. And as a follow-up for the bioequivalence study, can you just give us a little bit more clarity around the design of the study? I know 48 patients enrolled. It sounds like you're evaluating three different formulations. I guess how many different doses, what exactly do we want to see in the top line data basically?

Remy Luthringer, Executive Chairman and Chief Executive Officer

It’s a great question. So basically, first of all, I mean, the protocol has been shared with the FDA. And as I said during the last earnings call, we did not start the study before having the feedback from the FDA, and we got the feedback from the FDA. Obviously, I mean we could start the study. So basically, if you remember during the Type C meeting, the FDA was questioning about differences in terms of formulation between the Phase 2b and Phase 3. So the main objective here is to demonstrate that the Phase 2b formulation has the same exposure or equivalent exposure to the Phase 3 formulation, which has been used. Just to refresh everyone’s memory, what we did mostly between the formulation of the Phase 2b and the Phase 3 formulation, there is no major change. The only thing we did was to really improve the tablets by making them gastro-resistant in order to minimize the food effect because we had a positive food effect in the Phase 2b formulation. And that's the reason why you had to give the tablets at a distance from food. So we were successful in minimizing the food effect by making this tablet gastro-resistant. This is what we did. But again, the main objective is to show bioequivalence in terms of exposure of the compound. Now we have included a third tablet, which is the commercial tablet since we are already working on a lot of scale-up and to be ready also at this level, after, obviously, having a positive outcome with the FDA. Here, I mean some ingredients had to be changed. Nothing has changed in terms of active ingredients; it is only to, how to say, industrialize our tablet. So again, three formulations, 48 subjects. Why 48 healthy subjects? Because it's considered a pivotal study, so you need to power it accordingly. The reason why you need this number of subjects is to achieve a power of 90%, and basically, the subjects are in their own controls. And so the three conditions can be compared. We've also added, obviously, arms with food and without food in order to reconfirm the fact that we are controlling for a positive food effect, which we had in the Phase 2b, which we do not have with the Phase 3 tablet formulation. So a quite large study that’s powered to be considered a pivotal study. And the final answer about bioequivalence between the tablets and also the answer about the food effect.

Operator, Operator

Our next question comes from Myles Minter with William Blair.

Myles Minter, Analyst

I just wanted to go back to the mITT analysis of the Phase 3 trial. I know that was prespecified in the Statistical Analysis Plan. I'm wondering whether you could tell me at what point of the statistical hierarchy that analysis on the primary endpoint in the mITT population actually sat? I'm aware you disclosed nominal P-values here, and I understand it has to be nominal. But I'm trying to understand the potential degree of multiplicity to apply to that. So I just want to know where it sat in that original SAP? If you could provide any color on that, that would be great.

Remy Luthringer, Executive Chairman and Chief Executive Officer

Yes, Mike, that's a crucial question, and I'm glad to clarify. Essentially, the numbers remained the same because, during the blind review phase prior to unblinding the study, we obtained data from the site with these 17 patients. When we submitted the final Statistical Analysis Plan to the FDA, we indicated that we would analyze both the ITT and mITT data at the same level. However, for now, we can only discuss a nominal P-value because that is not the primary endpoint—it pertains to the ITT. As noted in the minutes from the Type C meeting, the FDA acknowledges that the inclusion of mITT is subject to review, as they need to evaluate the data thoroughly. They accepted our proposal to include both ITT and mITT in our filing. This is how our interactions with the FDA progressed. I believe that mITT is clearly defined and recognized by the agency. Moving forward, I am optimistic because, as we've discussed previously, there are many precedents indicating that if there's a solid rationale for excluding certain subjects, mITT can be accepted. In the CNS field, we are in a position where mITT is definitely a viable option.

Myles Minter, Analyst

Okay. Fair enough. And then on the bioequivalence study, obviously, the protocol is being run past the agency and that they are aligned with it. I'm curious as to whether you've had conversations with them about their comfort level with this commercial formulation from Catalent that you will likely not have clinical and safety data outside of the healthy volunteers prior to submitting for NDA. Like are they happy with the fact that the Phase 2b and the Phase 3 formulations, you have clinical data around that, but maybe you won't have that for the commercial formulation? There's no chance to make you like try and run an additional study or something, yes?

Remy Luthringer, Executive Chairman and Chief Executive Officer

Yes, I think clearly not just because we clearly described what are the differences between the commercial and the Phase 3 formulation in our protocol. We have all the solution data or what you need in terms of CMC to feed into your CMC package for the NDA. So I think clearly, there will be no surprises at this level. Because I mean, the modifications are really minor. It's purely technical, and it does not change overall the active part of the tablets. And we have been pretty clear in the protocol. So I do not foresee any problems there.

Operator, Operator

Our next question comes from Jason Butler with JMP Securities.

Jason Butler, Analyst

Just wondering, obviously, now you have the OLE data. What are your plans to continue to build awareness of the data and the drug over the next year or so as you progress through regulatory submissions? Obviously, presentation of data at medical meetings, but beyond that, any plans to bring on board MSLs or even a non-branded awareness campaign? Or do you have any plans for an expanded access program either here or in the U.S. or Europe?

Remy Luthringer, Executive Chairman and Chief Executive Officer

Great question, Jason. So obviously, yes, we will present at medical meetings. I think there are some presentations at ECNP, the European College of Neuropsychopharmacology, and we will also be present at the American College of Neuropsychopharmacology at the end of the year. So definitely, yes, we will disseminate this data. As we speak, over the last few weeks when we got the data, we have also discussed quite extensively with some of our KOLs involved in advising us, but we went much larger in order to have this data becoming known to a very large part of the scientific and medical community. For your broader approach, we might think about a webcast, but we have not decided yet, which will really give again a complete update about our development and our package. Because I think it is important to put this into context. We will also give updates about the bioequivalence study. We will give updates about the pharmacology. Because I think the pharmacology of our drug contains very hot topics like the Sigma target in addition to the other targets. So all of this, we will do it. But between today and having the NDA submitted, I think we will really stay focused on R&D and preparing the best trial and getting this done. Afterwards, a new life starts, but here, we will focus on the different topics you mentioned.

Operator, Operator

Our next question comes from Douglas Tsao with H.C. Wainwright.

Douglas Tsao, Analyst

So just given all the activity that you have going on, but obviously, you have a lot more freedom now with the Royalty Pharma financing. I'm just curious given the breadth of opportunities, how are you thinking about proceeding with other trials for roluperidone in some of the earlier indications or settings that we've talked about? I mean, obviously, you're prioritizing the NDA submission, but I'm just curious how you're thinking about that and when we might see some of that other clinical work start?

Remy Luthringer, Executive Chairman and Chief Executive Officer

We are actively brainstorming and maximizing the value of our data. For instance, we are examining the relationship between improvements in negative symptoms and functional improvements based on the PSP total score, along with focusing on the PSP subscores. We have identified a signal related to cognition, which we are also addressing. We are collaborating internally and with our key opinion leaders to determine our next steps. Ideally, we aim for cost approval for studies that we could conduct within the schizophrenia ecosystem and transdiagnostic areas. The key point is that we expect to gain a strong understanding of the clinical aspects, including selecting the right contract research organization for our studies. This is essential for ensuring an effective setup. We are also developing our plan for clinical trials and expanding indications. I believe this will be a topic of discussion at our pre-NDA meeting with the FDA in the latter half of the year. We are committed to exploring all options to conduct trials under the best conditions, with the most suitable sites and organizations. Our approach to clinical trials is gradually becoming effective and efficient, and we are prepared to discuss our strategy with the FDA if necessary. At this moment, we look forward to a productive meeting and a constructive dialogue with the FDA before initiating any clinical trials, and we are making progress in this area.

Operator, Operator

I have no further questions at this time. I'd like to turn the call back over to Remy Luthringer for closing remarks.

Remy Luthringer, Executive Chairman and Chief Executive Officer

Thank you for all the great questions and participation in this call. This is a crucial time for Minerva, and the outcomes of the bioequivalence study will be significant since it was a key point raised by the FDA during the Type C meeting. I am eager to update you soon on this and our ongoing progress, including our preclinical package, which we haven't discussed today, as we prepare our NDA package. There is a lot happening, and I look forward to sharing more updates with you soon. Thank you for joining us.

Operator, Operator

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