SAGE Therapeutics Inc (SAGE) 2016 Q1 法說會逐字稿

Good afternoon and welcome to SAGE Therapeutics first-quarter 2016 earnings conference call.

(Operator Instructions)

This call is being webcast live on the investor and media section of SAGE's website at SAGERx.com. This call is property of SAGE Therapeutics and recordings, reproductions and transmissions of this call without express written consent of SAGE Therapeutics is strictly prohibited. Please note this call is being recorded.

I would like to introduce Paul Cox from SAGE.

Good afternoon. Today we reported our first-quarter 2016 financial results along with recent corporate highlights and upcoming milestones. The press release and the presentation slides used on this call can be found on the investor and media section of our website at SAGERx.com.

On slide 2 of the presentation is the agenda for today's call. We will begin the call with prepared remarks by Dr. Jeff Jonas, our Chief Executive Officer, and Kimi Iguchi, our Chief Financial Officer. Following the prepared remarks we will open the call for a Q&A session and we will be joined by Dr. Steve Kanes, our Chief Medical Officer.

On slide 3 is our Safe Harbor statement. During today's call we may make forward-looking statements including statements about our expectations with respect to clinical development and regulatory events and timelines, the potential success of our clinical trials and product candidates, financial projections and the expected timing of 2016 milestones and upcoming events and presentations. Actual results may differ materially.

The risks and other factors that could cause actual results to differ are discussed in today's press release and in the risk factors section of our annual report on Form 10-K filed with the Securities and Exchange Commission on February 29, 2016 and other reports filed with the SEC. Any forward-looking statements represent our views as of today only. We may update these statements in the future but we disclaim any obligation to do so.

I would now like to turn the call over to Jeff.

Thank you and welcome to our call. During the first four months of 2016 we continued to make progress toward our goal of becoming a wholly integrated biopharmaceutical Company and a leader of innovation in CNS drugs development space.

SAGE remains committed to developing and advancing a portfolio of differentiated and innovative CNS product candidates. And as I hope you will see today 2016 is a potentially transformational year for SAGE as we expect critical milestones across our pipeline. For our lead program, SAGE-547, for super-refractory status epilepticus or SRSE we continue to anticipate top-line results from our ongoing Phase 3 STATUS trial in the second half of this year.

The design of this trial is shown on slide 4. The STATUS trial is expected to enroll up to 140 patients to achieve 126 evaluable patients at up to 150 sites in the US, Canada and Europe. This is the first prospective, randomized, double-blind, placebo-controlled study in SRSE ever conducted, and it's being conducted with agreement on design under a special protocol assessment or SPA with the FDA. And as a reminder SAGE-547 was granted orphan drug designation in the US for status epilepticus including SRSE and is being developed currently under fast-track designation.

As shown on slide 5, we also expect to significantly broaden our pipeline this year, contingent on the results of two near-term data readouts this quarter. These readouts include our ongoing Phase 2 placebo-controlled proof-of-concept study of SAGE-547 in severe postpartum depression or PPD and the results of our Phase 1 development program from SAGE-217, our oral GABAA modulator, which is our first new chemical entity or NCE in clinical development. These readouts are important steps towards establishing SAGE's position as a leading CNS innovator by broadening our portfolio across multiple product candidates in several CNS indications.

Of course, we are also continuing to prepare for a potential future commercial launch if the STATUS trial is successful and we gain regulatory approval of SAGE-547. During the second quarter we further demonstrated our evolving CNS leadership by featuring several data presentations across multiple indications at the AAN or the American Academy of Neurology annual meeting. Further, we have more planned presentations on PPD, the most near term at the Society of Biological Psychiatry Annual Scientific Meeting, or SOBP, this month.

Slide 6 shows a summary of our presentation at AAN. At AAN we presented detailed data regarding the lack of effect of underlying disorders and underlying treatment approaches on the outcome of the open-label Phase 1/2 study of SAGE-547. And this was presented in a peer-reviewed setting for the first time.

As seen on slide 7 we demonstrated that the key efficacy endpoint response rate, 17 of 22 in evaluable patients, in the Phase 1/2 study was not related to age, gender, ethnicity for morbid medical conditions, underlying medical conditions or previous antiepileptic or third line agent treatment. We further identified additional treatment characteristics that were subsequently incorporated into Phase 3 STATUS trial protocol including data suggesting that for patients on three third line agents, one additional day (technical difficulty) which is, in fact, reflected in the Phase 3 design.

Further, a post hoc analysis of the Phase 1/2 data shows that 18 of the 22 evaluable patients or 82% were successfully weaned off both anesthetic agents and 547 within six days without the need to reinstate anesthetic agents in the following 24-hour period, which is the key efficacy endpoint of the Phase 3 clinical trial. We further identified an exploratory pharmacodynamic biomarker as seen on slide 8 that significantly correlated with the plasma concentration of SAGE-547 during Phase 1/2 studies despite high baseline variability and the presence of background medications.

Importantly, on slide 9 we show that SAGE-547 also demonstrated a favorable tolerability safety profile with no drug-related serious adverse events or SAEs. There were six deaths in the trials which were deemed to be related to the patients' underlying medical disorders and not SAGE-547.

Additionally, we were extremely pleased to detail more of our work around the high burden of illness associated with SRSE, this serious and disabling disorder, as well as a significant health payer resource allocation by these patients. As seen on slide 10 we worked closely with academic collaborators at the Massachusetts General Hospital and we were able to establish the health economic burden of illness in SRSE in the US through a hospital claims data analysis looking at 20% of all US inpatient discharges from 2012.

In our presentation at AAN we highlighted significant morbidity, lengthy hospitalization and significant utilization of ICU resources and overall hospital resources associated with SRSE. And these data are summarized in slide 11.

This incidence of economic burden data is an example of the work we are currently undertaking right now at SAGE in anticipation of a potential commercial launch for SAGE-547. This, of course, assumes that the STATUS trial is successful and we obtain regulatory approval.

In summary, these results show the need for a new treatment option for SRSE. They highlight the significant burden of illness associated with SRSE and importantly they underscore the data-driven rationale that informs our Phase 3 STATUS trial design.

Turning to the other indications within our GABA pipeline, we were also excited to highlight the proof-of-concept data using SAGE-547 in essential tremor at the AAN meeting. And along that same line we look forward to presenting our initial proof-of-concept data for SAGE-547 in four PPD patients at the SOBP meeting next week.

Both of these two data sets underscore our clinical development strategy of using a probe study to further study the potential of our GABA pipeline to impact new indications where we believe GABA dysfunction plays an important role. To accomplish this we employ a unique development approach using SAGE-547, our intravenous agent where we have shown brain activity through an EEG biomarker, to find signals of clinical activity in other specific CNS disorders which we believe are related to GABA dysfunction. This approach led to our promising early clinical proof-of-concept results for SAGE-547 both in essential tremor and postpartum depression.

As seen on slide 12, at AAN we presented detailed data for the first time from this placebo-controlled proof-of-concept study of tremor, showing significant reduction of tremor in 25 patients. This study also helped establish our assessment and statistical methodology for the anticipated Phase 2 essential tremor trial using SAGE-217 pending results from the Phase 1 proof-of-concept study for that candidate.

In the essential tremor proof-of-concept study SAGE-547 was well tolerated as seen on slide 13. Of the 25 patients enrolled, three patients reported at least one adverse event on blinded SAGE-547 compared to five patients reporting at least one adverse event while on placebo. Of the 17 patients in the open-label higher dose SAGE-547 portion, eight patients reported at least one adverse event.

The only adverse event reported more than once across all SAGE-547 treatment periods were fatigue and dizziness predominantly at the higher dose of SAGE-547. There was one discontinuation in the higher dose of SAGE-547 due to hypotension with recovery rapidly following drug discontinuation. There were no reports of SAEs or serious adverse events.

Turning to postpartum depression, next week we are scheduled to present detailed data for the first time at SOBP from our initial open-label proof-of-concept study for SAGE-547 in postpartum depression including a secondary endpoint and a timeline of response. As many of you already know, to replicate and validate that initial activity signal in PPD we are currently conducting an additional placebo-controlled proof-of-concept study with SAGE-547 currently planned to enroll up to 32 patients diagnosed with severe PPD. We continue to expect the study to read out in this second quarter.

We believe the early signs of activity in all of these indications supports further development activities focused on modulation of the GABA receptor system. These data give us confidence in potential indications for multiple planned Phase 2 trials of SAGE-217 including essential tremor, orphan epilepsies and possibly severe postpartum depression which you can see outlined on slide 14.

SAGE-217 is our next-generation positive allosteric modulator that has been optimized for selectivity of synaptic and ex-synaptic GABAA receptors and for a profile that allows once-daily oral doses. The Phase 1 study should read out later this quarter. And if we see the desired PK/PD and safety profile that we are looking for we intend to move forward with this molecule and initiate multiple Phase 2 programs that I mentioned, all indications where we believe oral chronic therapy is the preferred course. Our decision to commence a Phase 2 clinical trial of SAGE-217 in severe PPD will, of course, depend on the outcome of the ongoing proof-of-concept study with SAGE-547.

Turning back to our pipeline on slide 15, we continue to invest in the future of earlier stage work in our pipeline both for GABA and MDA. For GABA we expect SAGE-689 to enter Phase 1 clinical development in the second half of this year if we are able to satisfy the FDA's request for additional non-clinical study data.

Just as a reminder, SAGE-689 is a next-generation positive allosteric modulator of GABAA receptors that has been optimized to have a wide therapeutic window, rapid clearance and a potent anti-seizure effect. We believe SAGE-689 has the potential for indications for a high degree of anti-seizure activity and sedations are desirable before the introduction of general anesthesia such as in status epilepticus in the emergency room but also in other potential indications.

Moving to our NMDA platform, we are very pleased to be highlighting pre-clinical work of our first NMDA program, SAGE-718, during the upcoming SOBP meeting this month. As many of you already know, NMDA receptors are a critical excitatory system implicated in a broad range of CNS disorders and an area of research that we are seeking to help pioneer. SAGE-718 or 718 is currently in IND-enabling studies and is a first-in-class oxysterol-based, positive allosteric modulator of NMDA with an optimized PK profile intended to support oral dosing.

In terms of indications we are focusing on two where NMDA hypofunction or dysfunction has been established: Smith-Lemli-Opitz Syndrome or SLO syndrome and anti-NMDA receptor encephalitis, both biomarker linked orphan populations with no approved treatment. These initial indications will allow us to explore activity of SAGE-718 and this mechanism and then potentially expand into broader CNS populations that exhibit similar biomarker activity.

At SOBP we plan to present data on SAGE-718 showing that the molecule is a potent and selective NMDA receptor PAM. And in pre-clinical add-on models of psychosis and cerebrosterol deficit disorders that SAGE-718 demonstrated activity suggesting potential utility in indications characterized by NMDA hypofunction such as SLO syndrome as well as potentially even schizophrenia. Assuming successful completion of non-clinical work we expect to begin clinical development of SAGE-718 in 2017.

As we hope you can see on slide 16, this is an exciting time here at SAGE and an important year for the potentially transformational milestones that we believe will help define the clinical Of our development program in the future ranging from data from our Phase 2 clinical study that will define whether there is that near-term path to regulatory approval and commercial launch in SRSE to other data that if positive may lead to a significant expansion into later stage trials for a number of other CNS indications to the exciting work that continues to come out of our discovery group yielding numerous potential compounds. As Kimi will touch on shortly we have done this in a capital efficient manner with a financing strategy that has put us in a strong position heading into our data readouts this year.

Finally, just to recap again what we expect during the remainder of 2016: top-line results for Phase 1 clinical program of SAGE-217 during the second quarter of 2016; top-line results from our Phase 2 placebo-controlled proof-of-concept study of SAGE-547 in severe PPD during the second quarter of 2016; top-line data from the Phase 3 STATUS trial of SAGE-547 SRSE in the second half of 2016; potential Phase 2 clinical trial initiations for SAGE-217 in at least two indications including essential tremor, orphan epilepsies and possibly severe PPD during the second half of 2016; the initiation of Phase 1 development for SAGE-689 during the second half of 2016, assuming we satisfy the FDA's request for a additional non-clinical study data; and initiation of clinical development of our first NMDA candidate, SAGE-718, in 2017.

I want to thank you for your attention. With that I'm going to turn it over to Kimi.

Thank you, Jeff, and good afternoon. On slide 17 we have a summary of our financial results for the first quarter.

Cash and cash equivalents at the end of the quarter totaled $299.7 million. This includes funds from our recent public offering in January which raised approximately $140.4 million in net proceeds.

Research and development expenses for the first quarter were $23.6 million including $1.6 million of non-cash stock-based compensation expense. That's compared to $12.9 million for the same period of 2015 which also included $0.5 million of non-cash stock-based compensation expense.

General and administrative expenses for the first quarter were $7.1 million including $2.1 million of non-cash stock-based compensation expense compared to $4.0 million for the same period in 2015 including $0.8 billion of non-cash stock-based compensation expense. We reported a net loss in the first quarter of $30.5 million compared to $16.9 million for the same period of 2015.

To go back on Jeff's points, we've strategically funded the Company over the last 24 months with an eye towards putting ourselves in a strong position to execute on the following. First, completing our Phase 3 STATUS trial in super-refractory status epilepticus; investing in the necessary infrastructure for a potential commercial launch in SRSE if we achieve positive Phase 3 results and are able to obtain regulatory approval; and continuing to invest in broadening our product portfolio and clinical pipeline for investments in our ongoing proof-of-concept study of SAGE-547 in severe PPD along with advancing development of SAGE-217, SAGE-689 and our NMDA modulator platform led by SAGE-718.

In the coming quarters we expect to see continued increases in operating expenses as we complete our Phase 3 STATUS trial for SAGE-547 in SRSE, continue to advance our discovery and clinical development efforts, engage in activities directed at a potential NDA filing and commercial launch and further grow our infrastructure and organization. Based on our current operating plans we expect cash and cash equivalents will be sufficient to fund our operations into the beginning of 2018.

Before we open the call over to Q&A I'd like to remind you that we plan to attend a number of conferences in the second quarter which are listed on slide 18. These include the Society of Biological Psychiatry, the 71st Annual Scientific Meeting, which is being held in Atlanta from May 12 to the 14; the 2nd Congress of the European Academy of Neurology in Copenhagen from May 28 to the 31st; the American Society of Clinical Psychopharmacology, the 2016 Annual Meeting is being held in Scottsdale from May 30 to June 3; the Goldman Sachs Global Healthcare Conference in Palos Verdes from June 7 to June 9; and the Eilat Conference on New Antiepileptic Drugs held in Madrid from June 26 to June 29.

So now I'd like to open the call for Q&A. So I will turn it over to the operator.

(Operator Instructions) Ritu Baral, Cowen.

Hi everyone. Thanks for taking the question. I want to focus on the next update data points you guys have which would be the PPD data. Obviously you are reiterating 2Q.

Can you give us an enrollment update at this point given that you've restated that guidance? And then as we look towards the data that you're going to be top-lining, can you give us an idea of what do you think -- how should we look at that data? What is clinically important difference on (inaudible) or within these severe PPD patients, should we be looking at that (inaudible) adjusted, should we be looking at a different number if we were to look at it versus baseline?

Thanks for your question and hi everybody. So a couple of points. One is we're not -- the study is planned to report out on basically this quarter. We're not going to provide any more interim enrollment guidance.

That's been our policy for all our studies, save for letting people know when we're going to -- when we're planning to report out the top-line data. So apologies for that but our plan is still as I said to report out at the end of this quarter.

With respect to the study itself, we were planning to enroll up to 32 patients, although the study for what we're hoping to achieve is frankly a bit overpowered. So what we did, remember this was intended to be a rather strict study to show a large signal of difference between drug and placebo and the primary endpoint at the HAM-D and basically we are for this study, and you can see this on clintrials.gov probably, planning this was only 80% power to show a 10 point difference in the HAM-D. Our belief was based on the pre-clinical data that we had with respect to the role of extrasynaptic modulation in this disorder plus the data we had seen in our albeit open-label study earlier this year that we wanted to see a rather binary response.

So that's how the study is powered. The primary endpoint is the difference from placebo.

One caveat I would just add is that as with most studies of this nature it's conceivable that there will be a subpopulation of drug patients who respond dramatically which is what our pre hoc hypothesis specifies. And so there may be some secondary analyses but the primary is the difference on the HAM-D.

So is that 10 point sort of the minimal import (technical difficulty) difference that you will be looking for and what your assumption to change (technical difficulty)

We're really -- let me go back. Many SSRIs have been approved with far smaller differences or deltas on the HAM-D. One of the interests at SAGE is really to only bring forward drugs that have a dramatic alteration in terms of patient benefit.

So we pre-specified a rather large potential HAM-D change that we thought would be unequivocally an improvement to the patient. As I mentioned, the secondary variable that we will look at, and this is something we can't really account for, but we will look at is whether there's a difference in the number of patients who have what otherwise we call the complete remission. And that would be a HAM-D below 7.

So that's how we're thinking about it. Obviously we will take a look at the data when we see it, but we believe that based on the pre-clinical data and based on the published data, the data we've seen and some of the other data we've looked at that we are conceptualizing postpartum depression more as an acute deficiency state and as a result we believe acute supplementation ought to give us a binary response. Otherwise we think that the pre-specified hypothesis would be disproven.

Sure. So just following up on that placebo, what is your anticipated change in HAM-D for placebo?

I'm going to turn it over to Steve Kanes who is our Chief Medical Officer.

We're not anticipating a large placebo response in these patients. We know that when you start treating patients there is always some placebo response in depression. So we are not anticipating a large placebo response, and as Jeff said the most important part is the separation from placebo in the study that we've designed.

Is that like less than 5 points, less than 10 points?

No, it wasn't powered for that way. So I don't think we could specify beyond that.

All right, great. Thanks for taking the questions.

You bet. Actually, one point I would make, actually, let me -- I don't want to make another point about this.

If you remember the data we have shown there was very little drop on the HAM-D from screen to baseline which would suggest that you would not expect in this particular population, which you know has been ill for at least four weeks, that you would not expect to see a large placebo drop, which you often see in outpatient depression trials. So we did have some data early on that suggested you wouldn't see that kind of regression to the mean. So let me just give you that as a separate little item.

Paul Matteis, Leerink.

Great guys, thanks very much and congrats on the progress. Jeff, a question on your point about conceptualizing PPD as an acute deficiency state.

On clinicaltrials.gov you allow patients to enter if they had depressive symptoms during the third trimester and based on my understanding that would be a time when allopregnanolone levels are high. So I'm wondering if you think that PPD depending on the timing of onset, before or after childbirth, if there is differences between those two different types of patients and if you'd expect both to respond to SAGE-547?

I think you probably know from the early clinical literature there was always a myth that pregnancy was protective. I don't think we believe that any longer.

What we find in PPD I think these may be people with some affective diathesis that may be exacerbated by the rapid decrement of endogenous allo right after birth. So I don't necessarily see those as dichotomized syndrome. I don't know if you want to add anything to that, Steve.

One of the things when we talk to experts in the field is that there is a thought that either allopregnanolone or other hormonal support at the very tail end of pregnancy in women who are predisposed to developing postpartum depression actually starts to tail off prior to delivery and that they may very well represent an independent risk factor. This is one of the reasons why there was a change in guidance to allow for screening in third trimester for people at high risk. So we're trying to align the inclusion criteria with the people we think would most benefit from treatment.

Okay, that's helpful. And then one other question. So this is an inpatient study, and I guess in the earlier study there were some patients who were already institutionalized while other patients were recruited and were at home and then were put inpatient in the trial.

It seems like that's a pretty key variable here. Is that something that you're stratifying and controlling for between groups? Do you think that's an important thing here to take account for?

There are a couple of points. One is typically these women are not hospitalized and that's probably independent of their severity at this point because they typically are in a caretaking mode. So we don't think that's a stratification requirement.

The other point is to make is that these are all women in terms of symptomatology we believe a reasonably homogeneous and that is we are looking for women who are very severely depressed who have been sick for at least four weeks, mostly will have a history of unresponsiveness to other medications. So we believe that the demographic inclusion criteria are likely to give us a reasonably homogeneous population.

Okay, great. And at the presentation next week, what kinds of granular analyses will you be doing from the four patients?

For that presentation, you know we have another one coming up later which we haven't made public yet, but for the one at SOBP we'll be showing more of the treatment course and in terms of the velocity of therapeutic response and also a summary of the secondary endpoint. One of the areas that we've been queried about we thought it would be useful to show was the totality of the response and that is was this a one-off response or were other measures of benefit consistent with the HAM-D? So we will be showing all those data at SOBP.

Okay, great. Thanks a lot, Jeff.

Salveen Richter, Goldman Sachs.

This is Tom on for Salveen actually. Thanks for taking our questions.

So just one question on the health economics study you did on data that you presented at AAN. So given these results, does this change in any way how you're thinking about pricing for 547 assuming it's approved? Does it narrow the range you're thinking about or broaden it or how should we think about that?

I think when we think about the economic burden as you know we think right now it can guide pricing, I think we've always made it a point to say that in terms of our thinking about pricing we wanted to make the value proposition clear and not require rather abstracted pharmacoeconomic type of analyses. Right now we're not prepared to narrow the range or give a range. I think that's really going to depend on the effect size that we see in the Phase 3 trial.

As I've said before we are doing payer work now both here and in Europe but we're not really prepared to peg a price until the Phase 3 data come in. At that point we will obviously be communicating with much more detail both our pricing strategy and our go-to-market strategy.

Okay, great, thanks for taking the question.

Cory Kasimov, JPMorgan.

Hey, guys, thanks for taking the questions. I guess, first of all, I want to go back to something I know we've discussed in the past but not surprisingly we've gotten a fair number of questions over the last couple of months just on your overall level of confidence in the powering assumptions you have for the Phase 3 STATUS trial. And can you just review perhaps the risk or lack thereof of these assumptions and the amount of buffer that you've built into the design of STATUS? And then I have one follow-up.

And so remember we haven't really given the specific powering but it is powered at a 90% range. And as you know, we've used, and this was -- we used the Rossetti paper which we still think is the best paper that demonstrates the response to a single attempted wean in patients with clearly diagnosed SRSE. And as you know, this was an area that we discussed critically with the FDA in determining the size and power of the study which led to our SPA.

One of the typical confusions that uneducated people may make or uninformed is to conflate SRSE with RSV and SE which is sort of like saying a basal cell carcinoma is like melanoma. So we're pretty comfortable with the powering assumption. It is 90% powered.

The endpoints, as you know, are reasonably unequivocal and unambiguous which is the ability to be free of status epilepticus at the end of this acute intervention for 24 hours. Beyond that we do feel we have a fair bit of cushion because as you know we believe that based on the Rossetti paper and actually discussions with many of our thought leaders the general consensus is that when patients are accurately diagnosed with SRSE the best response rate to a single attempt at wean, not an aggregate wean, is probably about at least no more than 35%.

Okay, that's helpful. And then regarding the 217 program, that upcoming data, is there anything in those pending results that we could see beyond just safety that could give investors further confidence in that molecule? Or is it really just a safety look that you are taking at this study?

No, actually I'd say that given one of the interesting pieces about this mechanism is that in normal that you will be able to see the pharmacologic activity that should read through into the pathological conditions that we're seeking to treat. So we will be able to see by example effects on EEG and pharmaco EEG which we've already demonstrated with 547 has a very nice dose relationship.

So we've developed a biomarker, this is some of the data we presented at AAN which is reasonably unique to this class of compounds. So we will be looking at things like sedation, we will be looking at things like pharmaco EEG so in fact by the end of Phase 1 when we put out this data not only will we have a good sense of safety but we will have a good surrogate for activity and potentially the margin of activity that before you hit sedation for this drug.

So I think that when we look at the 217 data we will know about -- I've said this publicly, we are pretty comfortable, it's moving along well. We think this is going to be a very potent once-daily oral molecule that will be unique and we're very comfortable that there will be good read-through from the Phase 1 data into the likelihood that this drug will be able to enter and do well and perform well in Phase 2.

Okay, thanks a lot, Jeff. Appreciate it.

John Newman, Canaccord.

Hey guys, thanks for taking the question. So Jeff, I just wondered if you could talk a little bit about some of the things that you hope to learn from the Phase 3, 547 study after you look at the primary endpoint. What are some of the other factors that you think will be important for us to pay attention to?

Thanks for the question. I think the first thing that we'll learn is the value of this acute interventional therapy in terms of their benefit to these patients. It's really important to point out that despite the underlying disorder this is sometimes misunderstood.

Despite the underlying disorder unless you treat the status epilepticus normal life is impossible. So the value for this is unequivocal and as you know this is why this particular interventional endpoint was accepted as the only endpoint for this study under the SPA. So that, of course, is first and foremost the most important outcome that we can achieve, which is the ability to attenuate and stop status epilepticus regardless of the underlying disorder after 24 hours.

After that, of course, we will be looking at standard safety and efficacy. We will also, of course, be looking at some of the more subtle interactions with other underlying agents. We will look at hemodynamic tracings.

We will be able to look at the extent of burst suppression. We will -- because this study, although it's very complicated, is being conducted in the ICU we will have a wealth of data in terms of the value of the acute intervention here that we hopefully will corroborate the activity of the drug. Beyond that we will obviously be following out to 21 days.

Of course, the FDA and thought leaders all recognize that outcome is unrelated to the resolution of status. It is driven by the underlying disorder which we can't, of course, hope to cure. But we will be getting those kinds of data, as well.

Finally, we do have several pharmacoeconomic measures built in, we haven't made those public, that we hope will support what we hope will be a very good value proposition for this agent moving forward in terms of the ability to get patients out of status epilepticus, move down their level of care and otherwise help provide more rapid resolution of their hospitalization.

Great, thank you.

Tim Lugo, William Blair.

Question. So we're already in May and you said second half of 2016 for STATUS but can you give us any more granularity? Is it possible that we do get these results in Q3 or is Q4 more likely, just any sort of additional guidance?

Hey, Tim, I know it's really important for everyone to try to understand when these data are coming out and I know people are trying to build models around it. We really are trying to be very disciplined both in terms of not giving interim looks at the enrollment updates.

So we're really going to say that we are still planning to release top-line data by the end of this year. I guess I will just leave it at that.

Fair enough. For SAGE-217 then, what are your views on testing that compound with CBD-based products for potential drug-drug interactions? Obviously CBD has been an interesting topic recently.

That's a really interesting question. It's something that might be conceivable as we move forward, especially in the status epilepticus space. We don't see any pharmacologic reason right now that there should be a DDI issue, a drug-drug interaction issue.

It may be something that's requested by the agency since I think it's a really good point, it's one we will consider. Probably more broadly we do recognize that the epilepsy space has room for several innovative products. So as we move forward in the clinical program for 217, that's something we will pay attention to, we're not committing to it yet.

But as you also know that 217 mechanism we'll be publishing some of this later this year shows profound interactions with several drugs in terms of increasing their activity. So for example, if you look at drugs, for example, like propofol which we all know is basically inactive at therapeutic doses at the extrasynaptic receptor in combination with our drug we actually enhance propofol, which is normally 1/1,000 as active at the extrasynaptic activity receptor, we enhance its activity in animal data. So these are kind of things that we will be looking at as we move 217 forward.

Thanks for clarifying that.

You bet.

I am not showing any further questions at this time. I would like to turn the call back over to Jeff for final comments.

Well, firstly, I want to thank everybody for your attention today. I know it's been a busy week for earnings.

And, again, I think we are looking forward to 2016 being a very transformational year with all the data readouts we have coming out, potential new in initiations of Phase 2 trials for 217. We're very optimistic and have a lot of confidence in the STATUS trial. We think it was designed for success.

We're very excited about the plans to broaden our pipeline but not only with 217 but potentially with 689 entering the clinic towards in the second half of this year. And we're continuing to grow the organization and prepare for our launch. So with that I want to thank all of you for your attention and I hope you all have a great rest of the evening.

Ladies and gentlemen, this does conclude today's presentation. You may now disconnect and have a wonderful day.