Minerva Neurosciences, Inc. Q3 FY2021 earnings call

• Roluperidone pivotal bioequivalence study results: Met key pharmacokinetic objectives, showing comparability of formulations and reduced Cmax.
• FDA communication: FDA denied pre-NDA meeting request for roluperidone and proposed Type C meeting; company plans to request Type C.
• Cash position: Cash, cash equivalents, restricted cash and marketable securities as of September 30, 2021 were approximately $65.7 million. Received $60 million upfront from Royalty Pharma in 2021 with potential for further $95M.
• Expenses: R&D and G&A expenses decreased; R&D expense decreased due to lower costs for roluperidone Phase III trial; G&A expense decreased due to non-cash stock comp changes.
• Welcome: New head of R&D, Dr. Ramana Kuchibhatla, welcomed.

There is no detailed breakdown of product segment financials by absolute terms and revenue contribution. However, key focus was on roluperidone: On September 30, 2021, a pivotal bioequivalence study for roluperidone met key pharmacokinetic objectives, demonstrating comparability under fasted conditions of various formulations, with AUCinf being relevant for chronic use and the study showing bioequivalence for key parameters and reduced Cmax of reformulated phases compared to Phase IIb.

• Plan to submit New Drug Application (NDA) for roluperidone in the first half of 2022.
• Type C meeting timeline: Typically a 75-day process, but past experience suggests quicker outcomes from FDA.

• Forward-looking statements subject to risks and uncertainties detailed in SEC filings.
• Uncertainty around FDA's response to Type C meeting and subsequent trial planning.

Q: First one is just on the timelines of the Type C meeting. My understanding is the FDA generally takes at most 75 days to schedule a Type C. Last year, sounds like you received minutes within 20 days of your Type C meeting and you came back to the Street a day afterwards, I believe. So, basically, can we expect that Type C meeting outcome to happen, say, within two to three months? Can you give a more granular timeline you think?

A: As you know, the timelines for Type C meeting is based on a process of 75 days. But it is also true we had that – last year, when we had our Type C meeting, things came back much quicker from the agency. So, I think, today, we have to stick to this, as I say, some deferred guidance basically. And obviously, we have immediately reacted, and so your estimate is probably adequate. So, it is a 75-day process indeed.

Q: Another question is just more about the FDA, why they think a Type C meeting would be more appropriate than a pre-NDA? Should we be inferring maybe the FDA is still very unsure of whether the topics that you guys discussed in the last Type C meeting may not have been fully addressed? I guess the root of the question is, what prompted the FDA to do this instead?

A: Obviously, I'm not at the pleasure of the FDA. Yes. But I think to ask about – specific about monotherapy is a completely fair question. As you know, we have done our development in monotherapy for very obvious reasons. The first one being the fact that, if you want to claim for specific effects or negative symptoms, this is, at minimum, in my opinion, and it has been recently published by a group book of experts or KOLs, this is probably the only way to do a study, monotherapy versus placebo, in order to really pick up the specific effect on negative symptoms. So, I think it is a really important debate here, a question. Keep also in mind that common practice, and it's mostly focused on positive symptoms, indeed, but the common practice is to try to keep someone who has a diagnostic of schizophrenia treated with antipsychotics. So, when you're putting these two pieces together, you might have a discussion around why monotherapy? And I think we have a really good set of data together. Because remember, we recently – or a few months ago now – time is running – we have disclosed the results of the open label extension where, definitely, you can see an improvement of negative symptoms, but this is in parallel, you have definitely some improvement in terms of positive symptoms or, at minimum, stability of positive symptoms, staying at a very low level after monotherapy with roluperidone. Also remember, we had an extremely low relapse rate. So, basically, patients who are presenting with positive symptoms of psychotic symptoms over this period of one year where we followed the patients or so. So, when you're putting all this together, again, I think a very, very good discussion about monotherapy based on our data.

Q: Let me add my congratulations for the bridging study. That's a nice result. Very related to the previous question, is this the first time the FDA will have heard you present the open label extension? And how much of the data that they see in your request for a pre-IND meeting? And then, a kind of a follow-up is, do you expect to have to go to this meeting with the next trial sort of flushed out? Or would that be a subsequent discussion?

A: Clearly, the FDA has not seen a lot. To be very clear, nothing about the extension data part of, obviously, the press release we have put out about these results. As you know, when you're doing a meeting request, you're not going into the details, you're mostly going through some of the questions you might have to put in your briefing book and you want to discuss during the pre-NDA meeting. So long story short, the short answer is that they have no specific insight into this data. If I read into your question, I think it was an important piece of information, clearly, to be able to demonstrate what we have demonstrated. Now, concerning an additional trial, I know very well that people think that we should do a trial or we should have started the trial. People think that we have enough. I think when you're looking to the guidance of 2019, November 2019, I said we are ticking the boxes because we are dealing with an unmet medical need with two well-controlled studies. So, I said we have a lot yet to share and to discuss with the agency. And we'll see what comes out from this meeting. And based on the outcome, we will decide. But if you're thinking one second study, you need to know which kind of study and this will not be the topic of the discussion. We really focus on monotherapy. But afterwards, obviously, we can always discuss about what we'll be studying. But again, I am very clear. I said we have what you need in order to have the right discussion and this clarification on monotherapy makes a lot of sense to me. And hopefully, the agency will choose a data package we have, like a package which can be submitted for an NDA.

Q: Remy, just another one on the Type C meeting. Has FDA at all indicated whether it now accepts the bioequivalence data as bridging the Phase II formulation or the Phase IIb formulation to the Phase III and commercial formulations? Or is that still not a discussion you've had? And then, in the scenario where you have the Type C meeting and do decide to continue to submit an NDA, would you still think you need a pre-IND meeting on top of the or in addition to the Type C meeting?

A: For the first question about bioequivalence, the answer is, no, the FDA has not seen this data. The only things they have seen is, again, what we have released or what we have publicly released. And obviously, when you're doing the meeting request, as I explained just before, you're just going through the different points of topics you would like to discuss. So, obviously, you're not going into the details of the results. So, clearly, they have not the complete granularity of this data. This said, as you know, this was a pivotal bioequivalence study, which is basically something which is going according to some guidance. And clearly, either you're bioequivalent or you're not. Something that, in our case, we are bioequivalent for the key parameters, as I explained in my talk just before. So, I don't think that there will be any surprise there. Now, concerning your second question, I think this more focused discussion about monotherapy, and obviously, totality of evidence is the right discussion and this was definitely a discussion we wanted to have during the pre-NDA meeting as well. So, I think depending on the outcome of this meeting, we will see. But we are still trying to stick to our guidance, again, based on the outcome and based on when we get the feedback from the FDA and the outcome. But we are still sticking to the submission of our NDA in the first half of next year. So this is what I think I can say about this, but I'm very hopeful that this will be helping us to basically stay with the timelines we have given.

Q: I'm just curious. Remy, when you think about sort of your discussion with the agency, the focus – or how important do you think it is because there's been – with investors, there's obviously been a conversation whether the best sort of use of roluperidone is sort of adjunct versus monotherapy. When you think about going to the agency and your discussion, has it been primarily focused or exclusively focused as a monotherapy? Beyond the open label extension data, what do you think are your best sort of points of evidence just to utilize to support that setting?

A: This is, obviously, an important question. Obviously, I could give a very, very long answer. But I think the best answer to your question is to – first of all, I think the scientific community is really recognizing that a lot of patients with a diagnostic of schizophrenia, first of all, do not the take the treatment, if they have the possibility. I'm speaking here about the commercially available treatments. Do not take that treatment, if there was a possibility to stop the treatment. So this is one point. So, there is a need of an alternative treatment. The second aspect is that it's quite clear as well that the current existing treatments are definitely not improving negative symptoms. A lot of meta-analyses are pointing to the fact that you have a worsening of negative symptoms due to the treatment on top of the negative symptoms of the diseases. And it is also true that a lot of work has been done over the last few years to see if you can reduce the dosage of the anti-psychotics and does it have an impact on the number of relapses. This is a very active research going on in terms of better understanding the phenotype of the patient at different stages of the disease. And I think it is very clear or becoming more and more clear that the significant part of patients with schizophrenia and having really – being bothered with negative symptoms and not functioning, do not need continuous treatment with antipsychotics. So, this is one of the hypothesis we had when we started in addition to demonstrate the specific effect. And I think our data are showing this is possible because, keep in mind, that we took in the two studies, we took patients that were treated, were stabilized on positive symptoms or psychotic symptoms with antipsychotics. They needed to have a minimum score of negative symptoms. And we switched them to our treatment in monotherapy. And when you see that these patients are staying stable on the positive symptoms at very low level and that the relapse rate is extremely low over one-year period of treatment, we have an additional piece of information here confirming that some patients can be without antipsychotics continuously onboard. And so, all this, I think, has to be reexplained, has to be rediscussed in order to show the full power of the data we have generated and the patient population who might benefit from monotherapy. Obviously, I'm not saying that antipsychotics are not important or the adjacent treatments are not important. Because, obviously, I'm not planning – or I'm not saying that roluperidone will treat an acute episode of positive symptoms, with agitation with hallucinations, delusions. So, I think we are just trying to fill a gap where there is no existing treatment here.

Q: Remy, one follow-up to that is do you think that you have sort of enough data to support or would you seek a specific labeling sort of recommendation for roluperidone to be monotherapy? Do you think it would be appropriate for the label to be sort of agnostic, whether it be used as an adjunct or monotherapy?

A: I obviously know the final answer on this. The reason I don't is the meeting. What I think basically is that, you can give up a drug in adjunct. We never have promoted this more than that. We have just done the safety aspects of BDI studies which are needed in order to give our treatment in adjunct to antipsychotics. But, again, I think this is the best chance to patients to really improve in terms of negative symptoms. And at the end of the day, in terms of functioning and again because there is a significant – eally a significant number of patients who can benefit from monotherapy with our drug without having antipsychotics onboard all along, I think this is what you have to do and what we have demonstrated. And fortunately, the FDA will get this. So, this is where we are. This is what I'm thinking. Can be given adjunct, but probably the best outcome in most of the cases is not to put antipsychotics continuously onboard.