Minerva Neurosciences Inc (NERV) 2021 Q3 法說會逐字稿

Welcome to the Minerva Neurosciences Third Quarter 2021 Call. (Operator Instructions) 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 Geoff Race, President of Minerva. Please proceed.

Good morning. A press release with the company's third quarter 2021 financial results and business highlights became available at 7:30 a.m. 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. Fred Ahlholm, Chief Financial Officer. Following our prepared remarks, we will open the call for Q&A.

Before we begin, I'd 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.

Those 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 September 30 2021 filed with the SEC earlier today. Any forward-looking statements made on this call speak only as of today's date, Monday, November 8, 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, Jeff, and good morning, everyone. Thanks for joining us today. I would like to focus this morning's update on our lead program, roluperidone. On September 30, 2021, we announced the results from a pivotal bioequivalent study where the results met key pharmacokinetic objectives and demonstrated bioequivalence across the various formulations. Recall the objective of this study was to compare the formulations employed in the Phase IIb and Phase III trials as well as a planned commercial formulation designed in conjunction with our commercial supplier to facilitate large-scale manufacturing.

This type of study, the area under the curve 2 large detectable concentration: AUC labs, the area under the curve extrapolated to Infinity, AUC Infinity; and the maximum plasma concentration Cmax are the most commonly used plasma pharmacokinetic parameters to evaluate bioequivalents between various formulations.

Roluperidone, our earlier work has shown that efficacy in patients with negative symptoms of schizophrenia is mostly driven by plasma exposure of the drug, i.e., AUCs, whereas safety margins improved by reducing Cmax of the drug. Furthermore, as roluperidone is intended for chronic use and the assessed formulations are controlled release, AUC Infinity is the most relevant of the AUC measurement when single-dose data are collected and used for determining bioequivalence.

In this study, the 2 most important objectives were to establish: firstly, the comparability on the fasted conditions of the 64-milligram tablet of the Phase III formulation of roluperidone compared to the 64-milligram dose based on the administration of 232-milligram tablets of roluperidone used in the Phase IIb study. And secondly, the comparability and the fasted conditions of a 64-milligram tablet of the planned commercial formulation of roluperidone compared to the 64-milligram dose based on the administration of 232-milligram tablets of roluperidone used in the Phase II study. The data showed that both objectives were met. The AUC Infinity were bioequivalent and the Cmax of the reformulated Phase III and planned commercial formulations had been reduced substantially compared to the Phase IIb formulation.

In this study, we also demonstrated bioequivalence in terms of AUCs and Cmax between the 64-milligram formulation of the planned commercial tablets and the fasted conditions compared to the formulation used in the Phase III. And bioequivalence, both in terms of AUC Infinity and Cmax of the 64-milligram dose of the planned commercial formulation in the fed and fasted conditions. In summary, I believe the bioequivalence study results represent important progress along Minerva's critical part towards submission of an NDA for roluperidone.

Moving on to our recent correspondence with the FDA. Last week, we announced that the FDA had denied the company's request for a pre-NDA meeting for roluperidone and proposed that the Type C guidance meeting will be more appropriate. Therefore, the company plans to request a Type C meeting.

And so to conclude my update this morning. The successful completion of the bioequivalent study represents an important component of the NDA package. Subject to the timing of and feedback from the FDA, we continue to work towards the submission of a new drug application in the first half of 2022. Finally, I would like to take this opportunity to welcome Dr. Ramana Kuchibhatla as our new Head of R&D at Minerva.

I will now turn it over to Fred for the financial update.

Thank you, Remy. Earlier this morning, we issued a press release summarizing our operating results for the third quarter ended September 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.

Cash, cash equivalents, restricted cash and marketable securities as of September 30, 2021, were approximately $65.7 million compared to $25.5 million, as of December 31, 2020. Our cash position was strengthened significantly in January 2021, with a receipt of a $60 million upfront cash payment from Royalty Pharma in connection with Royalty Pharma's acquisition of the company's royalty interest in seltorexant.

Under this agreement, Minerva has the potential to receive up to a further $95 million in additional payments, contingent upon the achievement of certain clinical, regulatory and commercialization milestones by Janssen. As a result of the sale of Minerva's interest in the seltorexant royalty stream to Royalty Pharma, Minerva will recognize noncash interest expense related to the amortization of this future revenue stream as compared to the cash payments ultimately received from the Janssen.

Accordingly, for the 3 and 9 months ended September 30, 2021, Minerva recognized $1.7 million and $4.6 million, respectively, in noncash interest expense related to this agreement. The $60 million payment received from Royalty Pharma has been included on our balance sheet under liability related to the sale of future royalties. As we recognize interest expense, the liability related to the sale of future royalties will increase. Until such time that we begin to receive the royalty, the related royalty payments, which will thereafter, reduce the liability on our balance sheet, while the upfront payment and future milestone payments will continue to be included on our balance sheet as a liability, as I described earlier.

In accordance with the terms of our agreement with Royalty Pharma, in the event that Janssen was to discontinue the seltorexant program for any reason, Minerva has no obligation to repay any amounts received from Royalty Pharma. We expect that the company's existing cash and cash equivalents will be sufficient to meet its anticipated capital requirements for at least the next 12 months based on our current operating plan. The assumptions upon which this estimate is based are routinely evaluated and may be subject to change.

For the 3 months ended September 30, 2021 and 2020, research and development expense was $4.5 million and $4.6 million, respectively, a decrease of approximately $0.1 million. For the 3 months ended September 30, 2021 and 2020, noncash stock compensation expense included within R&D was $0.5 million and $0.8 million, respectively.

For the 9 months ended September 30, 2021 and 2020, R&D expense was $13.3 million and $18.5 million, respectively, a decrease of approximately $5.2 million. For the 9 months ended September 30, 2021 and 2020, noncash stock compensation expense included within R&D, was $1.8 million and $2.2 million, respectively. The decrease in R&D expense for both the 3- and 9-month periods ended September 30, 2021, versus the same periods in 2020 was primarily due to lower cost for the Phase III clinical trial of roluperidone for which the 3-month core study portion of the trial was completed in May 2020.

For the 3 months ended September 30, 2021 and 2020, general and administrative expense was $3 million and $3.5 million, respectively, a decrease of approximately $0.5 million. For the 3 months ended September 30, 2021 and 2020, noncash compensation expense included within G&A was $0.6 million and $1.2 million, respectively. For the 9 months ended September 30, 2021 and 2020, G&A expense was $10.7 million and $13.5 million, respectively, a decrease of approximately $2.8 million.

For the 9 months ended September 30, 2021 and September 30, 2020, noncash stock compensation expense included within G&A, was $2.2 million and $5.6 million, respectively. The decrease in G&A expense for both the 3- and 9-month periods ended September 30, 2021, was primarily due to noncash stock compensation charges resulting from certain stock option awards approved in June 2020 as well as from additional stock compensation expense incurred under a severance agreement during 2020.

Net loss was $9.2 million for the third quarter of 2021 or net loss per share of $0.22 basic and diluted as compared to a net loss of $8.1 million or a net loss per share of $0.19 basic and diluted for the third quarter of 2020. Net loss was $28.6 million for the 9 months ended September 30, 2021, or a net loss per share of $0.67 basic and diluted, as compared to net income of $9.3 million or net income per share of $0.23 basic and diluted for the 9 months ended September 30, 2020.

The decreases in net income for both the 3- and 9-month periods ended September 30, 2021, were primarily due to the company's opting out of its joint development agreement with Janssen Pharmaceutica for seltorexant during the second quarter of 2020. As a result of opting out of the agreement, the company immediately recognized $41.2 million in collaborative revenue, which had previously been included on the balance sheet under deferred revenue.

Now I would like to turn the call over to the operator for any questions. Operator?

(Operator Instructions)

Our first question comes from Andrew Tsai with Jefferies.

Okay. First one is just on the time lines of the Type C meeting. Congratulations, by the way, on completing the bioequivalence study. My understanding is the FDA generally takes at most 75 days to schedule a Type C last year. It 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 2 to 3 months? Or can you give a more granular time line you think? That's my first question.

Yes, Andrew, Remy speaking. Thank you for your question. So as you know, I mean, as the time lines for Type C meeting is very low, yes. I mean, so definitely it is a process of 75 days. But it is also true that last year when we had our Type C meeting, we think the things came back much quicker from the agency. So I think today, we have to stick to this -- after, say, 75 days basically. And obviously, we have immediately reacted and so your estimate is probably adequate so it is a 75-day process indeed.

Got it. And another question is just more about the FDA, why they think a Type C meeting would be more appropriate than a pre-NDA? I mean 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?

So obviously, I'm not deprived of the FDA, yes, but I think to ask about specific about monotherapy is a completely fair question. And as you know, we have done our development in monotherapy for very obvious reasons, as the first one being the fact that if you want to claim for a specific effect on negative symptoms, this is, at minimum, in my opinion -- and it has been recently published by a group of experts or KOLs. This is probably the only way I mean to do a study, monotherapy versus placebo, in order to really pick up a specific effect on negative symptoms.

So I think it is a really important debate here or question. Keep also in mind that, I mean, common practice, and it's mostly focused on positive symptoms. Indeed, what I mean common practice is to try to keep someone who has a diagnostic of schizophrenia treated with antipsychotics. So when you are putting this 2 pieces together, I mean 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 few months ago -- now time is running, we have disclosed the results of the open-label extension, where I mean, definitely, you can see an improvement of negative symptoms.

But this is in parallel, you have technically some improvement in terms of positive symptoms or minimum stability of positive symptoms staying at a very low level, after monotherapy with roluperidone. And if you remember, we had an extremely low relapse rate, yes, I mean also basically patients who are presenting with positive symptoms of psychotic symptoms over this period of 1 year where we followed the patients. So when you're putting all this together, again, I think the fact to have a very, very good discussion about monotherapy, based on our data, I'm really hopeful that I mean, we have the right output and the right input and the right output in the end of the day for this meeting in order to move forward again.

Our next question comes from Tom Shrader with BTIG.

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 did they see in your request for a pre-IND meeting? And then kind of a follow-up is, do you expect to have to go to this meeting with a -- with the next trial sort of flushed out? Or would that be a subsequent discussion?

Good questions. So clearly, the FDA has not seen a lot of -- to be very clear nothing about the extension data part when we see the press release we have put out about these results. And as you know, when you're doing a meeting request, you are not going into the details. You are mostly going through some of the questions you might have to put in your briefing book until you might -- you want to discuss during the pre-NDA meeting. So long story short, I mean, the short answer is that they have no, I have to say, insight into this data. So -- and I think if I read into your question, I think it is an important piece of information, yes, clearly, to be able to demonstrate what we have demonstrated.

Now concerning an additional trial, I know very well that, I mean, people think that we should do a trial and we should have started the trial. People think that I mean we have been at. I think when you're looking to the guidance of 2019, November 2019, I think we are ticking as a boxes because we are dealing with a magnetic need with 2 well-controlled studies. So I think we have a lot here 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 I mean if you're thinking one second about the nature of the study, you need to know which kind of study, and this will not be the topic of the discussion. We will be focused on monotherapy. But afterwards, obviously, we can always discuss about what would be a study. But again, I am very clear I think we have what we need in order to have the right discussion and this clarification and monotherapy makes a lot of sense to me. And hopefully, the agency will see the data package we have, like a package, which can be submitted for an NDA.

Our next question comes from Jason Butler with JMP Securities.

I appreciate the updates. Remy, just another one on the Type C meeting. Did -- has FDA at all indicated whether it now accepts the bioequivalence data, bridging the Phase II formulation or the Phase IIb formulation, the Phase III 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?

Jason, so for the first question about bioequivalence, the answer is no, the FDA has not sent us data. The only thing I 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 are just going through the different points of topics you would like to discuss. So I mean, obviously, you are not going into the details of the results. So clearly, I mean, they have not a complete granularity of this data.

This side, as you know I mean, this was a pivotal bioequivalent study, which is basically something which is going according to some guidance. And clearly, I mean, either you are bioequivalent or you are not. I mean, 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 a valid 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 I mean we are still trying to stick to our guidance, again, based on the outcome and based on the -- when we get the feedback from the FDA and the outcome, but we are still sticking to the submission of our NDA during 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 -- that if we stay -- how to say, with the time lines we have given.

Okay. Great. And then just one more, just to clarify. So obviously, there's the monotherapy topic. But in addition to that, are the topics that you plan to propose discussing with FDA at the Type C meeting are essentially overlapping with what you would have talked about at the pre-NDA meeting?

So part of the monotherapy, which was a part of it is because, obviously, we have developed a drug monotherapy for the reasons that was explained before. Yes, I mean, some of the topics are overlapping. The only difference, if you want to find a difference is that, I mean, we -- in the pre-NDA meeting, we're also going through the different modules of your NDA, like CMC, like preclinical and so on, I mean -- and not only focusing on the clinical aspects. So this is a difference if you want to see a difference.

This said, as you know, for example, for the CMC, you can have some specific meetings to check or to tick the boxes as we have done, by the way, also in the past, I mean. So I think we have really ways to really tick all the boxes before we are going to do our submission. But -- so I think this is the difference. I mean less focusing on ticking the box for nonclinical aspects and focusing more on the clinical aspects.

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

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 -- or I guess we've -- with investors, there's obviously been a conversation whether the best sort of use of the roluperidone is sort of an adjunctive versus monotherapy. When you think about going to the agency in your discussion, has it been primarily focused or exclusively focused as a monotherapy? And do you think beyond the open-label extension data, sort of what do you think are your best sort of points of evidence just to utilize to support that setting?

So this is obviously an important question as well, yes. And I mean, 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 diagnostic of schizophrenia, first of all, do not taking -- do not take, sorry, as a treatment, if they have the possibility. I'm speaking here about the commercially available treatment who do not take the treatment if they, how to say, have the possibility to stop that 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 is that I mean the current existing treatments are definitely not improving negative symptoms. They are I mean, metanalysis, I mean a lot of metanalysis 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, I mean, a lot of work has been done over the last few years to see if we can reduce the dosage of the adjunctive topics and does it have an impact on the number of elapses. Or this is a very active research going on in terms of better understand as a phenotype of the patients at different stages of the disease, and I think it is very clear or becoming more and more clear.

So 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 (inaudible) we have when we started in addition to demonstrate the specific effect. And I think our data are showing that, I mean, this is possible because, keep in mind, that we take -- we took in the 2 studies -- we took patients that were treated or stabilized on positive symptoms or psychotic symptoms vis-à-vis psychotics. They needed to have a minimum score of negative symptoms and that we switched them to our treatment in monotherapy. And when you see that these patients are staying stable on positive symptoms at very low level and that the relapse rate is extremely low for 1 year period of treatment.

We have an additional piece of information. We are confirming that some patients can be without antipsychotics continuously on board. So all this, I think has to be reexplained, have to be rediscussed in order to show the full power of the data. We have generated the patient population who might benefit from monotherapy. Obviously, I'm not saying that antipsychotic are not important or these treatments are not important because obviously, I'm not planning or I'm not saying that, I mean, roluperidone will treat an acute episode of positive symptoms with agitation, with severe hallucinations, dilutions. So I think we are just trying to fill a gap where I mean there is no existing treatment here.

And I mean, I guess just 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? Or do you think the label would be -- or do you think it would be appropriate for the label to be sort of more agnostic whether it would be used as an adjunct for monotherapy?

I obviously don't have the final answer on this. There is no -- there's a meeting in test. That is what I think basically is that you can give up a drug in add-on. We never have promoted this more than that. We have just done the safety aspects of the DDI studies, which are needed in order to give our treatment in add-on to antipsychotics. But again, I think to give you 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 -- really a significant number of patients who can benefit from monotherapy with our drug result having antipsychotics onboard all along, I think this is what you have to do and what we have demonstrated, and hopefully, the FDA will get this.

So this is where we are. So this is what I'm thinking. It can be given add-on but probably the best outcome in most of the cases is not to put antipsychotics continuously involved.

I'm showing no further questions. At this time, I'd like to turn the call back to management for any closing remarks.

Yes. Thank you, everybody, for today's call and for all the questions and for listening to our earnings call. And I'm really looking forward to update you very soon about progress we will make over the next coming few weeks and months. Thank you again, and have a nice day. Bye-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.