Minerva Neurosciences, Inc. Q2 FY2021 earnings call

• Completed open-label portion of Phase 3 trial with roluperidone in schizophrenia and working towards NDA submission in first half of 2022.
• Enrolled in pivotal bioequivalence study with roluperidone in healthy volunteers.
• Making progress in assembling components for NDA submission, including clinical pharmacology, non-clinical, and CMC activities.
• Discussed ongoing dialogue with FDA regarding topics from Type C meeting.
• Explained bioequivalence study design to address FDA's concerns about formulation differences between Phase 2b and Phase 3.
• Plans to present OLE data at medical meetings and provide updates on development, including bioequivalence study and pharmacology.
• Brainstorming on next steps for roluperidone, including understanding clinical data and planning for expanded indications.

No detailed financial performance of product segments with revenue contribution % discussed in the transcript

• Continue work towards submitting NDA in first half of 2022.
• Anticipate completing activities for NDA submission over coming months.
• Look forward to continuing dialogue with FDA for pre-NDA meeting.

Q: First question is on just the open-label extension. I've had the impression, you've interacted with the FDA from time-to-time over the course of 2021, and you've addressed with some of the things that come up -- 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?

A: Yes. So definitely, no, we have not discussed the open-label extension data with the FDA. The interaction we have on a regular base 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, presented. And we definitely will obviously put this part of 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.

Q: 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 3 different formulations. I guess how many different doses, what exactly do we want to see in the top line data basically?

A: 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, I mean, if you remember during the Type C meeting of 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 the mind of everybody, 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 putting them gastro-resistant in order to minimize the food effect because we had a food effect, a positive food effect in the Phase 2b formulation. And that's the reason why you had to give the tablets, a distance from food. So we definitely were successful to minimize the food effect, and by putting this tablet gastro-resistant. So this is what we did. But I mean, again, the main objective is to show bioequivalence in terms of exposure of the compound. Now we have included a third, how to say, tablet, which is the commercial tablet, because with our provider -- because we are already working 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. So nothing has changed in terms of active ingredients. It is only to, how to say, industrializes our tablet. So again, 3 formulations, 48 subjects. Why 48 healthy subjects? Because it's considered as a pivotal study, so you need to power it accordingly. So the reason why you need this number of subjects to be powered 90%, and basically the subjects are in their own controls. And so the 3 conditions can be compared. We also have added, obviously, arms with food and without food in order to reconfirm the fact that, I mean, we are controlling for a positive food effect, which we had in Phase 2b, which we do not have with Phase 3 tablet formulation. So a quite large study that’s powered to be considered as a pivotal study. And the final answer about bioequivalence between the tablets and also the answer about the food effect.

Q: 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.

A: Yes. So Mike, obviously, a very, very important question, and so I'm happy to answer it -- to be able to clarify. So basically, it was at the same level because as I explained already, when we picked up during the blind review, before opening the blind of the study, we picked up the site with these 17 patients. So 1-7 patients. And when we submitted the final Statistical Analysis Plan, we proposed to the FDA or we put in the document, obviously, that I mean, we will analyze the data, the ITT data and the mITT data. And we put them at the same level. But obviously, we can only speak here about a nominal P-value for the moment because it is not primary endpoint. This was ITT. But as you have seen from the minutes of the Type C meeting -- and it's always a matter of review. As you know, the FDA is always telling you it is a matter of review because they have to go deeply into the data. They accepted the fact that, I mean, mITT will be confident, and we should submit our file with ITT and with mITT. So this is how the events or the interactions with the FDA went. So again, I mean, it's a matter of review, but I think the mITT is clearly identified. It's clearly recognized by the agency. And from there, we will see as what is next. But I mean, I'm very confident because as we discussed, as you go through already before, quite a lot of precedents where I mean, if you have really a very good rationale, a very good reason why you should exclude some subjects, you can go with the mITT. And so in the space, even of CNS, so we are definitely in the topic here where mITT is something to be considered.

Q: 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 -- and then secondly, do you have any plans for an expanded access program either here or in the U.S. or Europe?

A: Great question, Jason. So obviously, yes, we will present at medical meetings. And I think there are some presentation at ECNP, the European College of Neuropsychopharmacology. And we will also be present at the American College of Neuropsychopharmacology end of the year. So definitely, yes, we will disseminate this data. And as we speak, I mean, 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 I mean we went much larger in order to have this data becoming aware to a very large part of the scientific and medical community. For your, how I say, broader approach, I mean, 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. So I mean this is put into the context. And definitely, we will also give updates, obviously, about the bioequivalence study. We will give updates about the pharmacology. Because I think the pharmacology of our drug is containing very hot topics like the Sigma target in addition to the other targets. So all this, we will do it. But between today and to have the NDA submitted, I think we will really stay focused on R&D and preparing the best trial and get this done. Afterwards, a new life starts, but here, we will focus on the different topics you mentioned.

Q: 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 starts?

A: Obviously, I mean, we -- this is in parallel. We are -- really continue to brainstorm. First of all, we continue to get the maximum out of our data. So I'll give you an example. We are currently working on how much the improvement in negative symptoms is linked to the functional improvements in -- from -- with PSP total score. We are also focusing on the subscores of PSP. We -- if you remember, we have a signal in terms of cognition. We also worked on this. And with -- internally and with our KOLs, we are definitely working on what would be next. Hopefully, cost approval in terms of studies, based on the terms of studies, which we could carry out inside the ecosystem of schizophrenia and definitely also transdiagnostic. So I guess the right answer to your question is that we’re anticipating also in having a good understanding of the clinical side, understanding of what is the right CRO to use if you are running a study. So this is one activity because as you know, I mean, this is important to have the right setup here. But I mean, we are also putting together our plan in order to -- in terms of clinical trials and expanding the indications. And I'm quite sure that I mean this is a point we will discuss when we have, in second half of this year, the pre-NDA meeting with the FDA. So we're making sure that we have all the different options open in order to run trials in the best conditions with the best sites, with the best organization. And I think slowly but surely, we have a very effective and efficient plan in place in terms of clinical trials, which we can also discuss, if needed, with the FDA. So we are ready. But for the moment, first, let us have a very good meeting, a very good final discussion with the FDA before we are starting any clinical trial. But I mean, we are working on it.