Sage Therapeutics, Inc.
Q4 2015 Earnings Call Transcript

Published: 8 May 2016

[Operator:]

Good afternoon, and welcome to SAGE Therapeutics First Quarter 2016 Earnings Conference Call. At this time, all participants are in a listen-only mode. This call is being webcast live on the Investors & 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 expressed written consent of SAGE Therapeutics is strictly prohibited. Please note this call is being recorded. I would like to introduce Paul Cox from SAGE.

[Paul Cox:]

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 Investors & 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 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 milestones and timelines, the potential success of our clinical trials and product candidates, financial projections and the expected timing of 2016 milestone 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, though we disclaim any obligation to do so. I would now like to turn the call over to Jeff.

[Jeff Jonas:]

Thank you, and welcome to our call. During the first four months of 206, we continued to make progress toward our goal of becoming a fully integrated biopharmaceutical company and a leader of innovation in the CNS drugs development space. Sage remains committed to developing and advancing a portfolio, a differentiated and innovative CNS product candidate. And as I hope you’ll see today, 2016 is a potentially transformational year for Sage, as we expect critical milestones across our pipeline. For our lead program, SAGE-547, the 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 was shown on Slide 4. The STATUS Trial is expected to enroll up to 140 patients to achieve 126 evaluable patients and 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 a theme conducted with agreement on design under a special protocol assessment or SPA with the FDA. 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, on the results of two near term data read out this quarter. These read-outs 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 GABAA modulator, which is 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’re 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 presentation 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 proven approaches on the outcome of the open-label Phase 1/2 study of SAGE-547, and this was presented in the peer review 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, co-morbid medical condition, underlying medical condition, or previous antiepileptic or third line agent treatment. We further identified additional treatment characteristics that were subsequently incorporated Phase 3 STATUS Trial protocol including data suggesting that for patients on three third line agents, one additional day of [indiscernible] was needed, which is in fact reflected in the Phase 3 design. Further, post-talk analysis of the Phase 1/2 data show that eighteen of the 22 evaluable patient or 82% were successfully weaned off both anesthetic agent and 547 within six days without the need to reinstate anesthetic agent in the following 24 power period, which is the key efficacy end point of the Phase 3 clinical trial. We further identified an exploratory pharmacodynamic biomarker as seen on Slide 8 that significantly co-related with the plasma concentration of SAGE-547 during Phase 1/2 study despite high baseline variability and the presence of background medications. Importantly on Slide 9, we show that SAGE-547 also demonstrated tolerability safety profile, with no drug related serious adverse event or SAE. There were six tests in the trial, which were deemed to be related to the patient underlying medical disorders and not SAGE-547. Additionally, we were extremely pleased to detail more of our work around high burden of illness associated with SRSE, a serious and disabling disorder, as well as a significant healthcare resource allocation by these patients. As seen on Slide 10, we work closely with academic collaborations at the Massachusetts general hospital. And we were able to establish the health economic burden illness in SRSE in the US through the hospital claims data analysis looking at 20% of all US in-patient discharges from 2012. In our presentation at AAN, we highlighted significant morbidity, lengthy hospitalizations and significant utilization of ICU resources and overall hospital resources associated with SRSE. And these data are summarized in Slide 11. This incidents in 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 for SRSE. 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 for SRSE, a highlight to significant burden of illness associated with SRSE, and importantly they underscore the data driven rationale that inform 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 the 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, impact new indications where we believe GABA plays an important role. To accomplish this we employ a unique development approach. Using SAGE-547 our intravenous agent, we have shown brain activity through an EEG biomarker to find signals of clinical activity and other specific DNS, 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 help establish our assessment and statistical methodology for the anticipated Phase 2 essential tremor trial using SAGE-217, ending 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 one across all SAGE-547 treatment periods [indiscernible] 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 and postpartum depression, including secondary end point and the timeline of response. As many of you already know to replicate and validate that initial activity signal of PPD, we are currently conducting and 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’s read out in this second quarter. We believe the early signs of activity all of these indications supports further development activities focused on modulating of the GABA receptor systems. These data give us confidence and potential indications for multiple planned Phase 2 trials with 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 with selectivity as synaptic and extrasynaptic GABAA receptors. And for a profile that allows once daily oral dose. The Phase 1 study should read out later this quarter, and if see the desire to PK/PD and safety profile that we are looking for, we intend to move forward with this molecule and initiate multiple Phase 2 program that I mentioned. All indications were we believe oral chronic therapy using the preferred course. Our decision to commence with Phase 2 clinical trail 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 early study working our pipeline both for GABA and NMDA. 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 FDAs request for additional non-clinical study data. Just as a remind SAGE-689 a next generation positive allosteric modulator of GABAA receptors. This has been optimized to have a wide therapeutic window, rapid clearance and anti-seizure effect. We believe SAGE-689 has the potential for indications with a high degree of anti-seizure activity and sedation are desirable before the introduction of general anesthesia such as status epilepticus in the emergency room, but also in other potential indications. Moving to our NMDA platform, we are very pleased with the 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 located in a broad range of CNS disorders and in area of research that we are seeking to help pioneer. SAGE-718 or 718 is currently in IMD enabling studies and is a first in class [indiscernible] modulator of NMDA, with an optimized PK profile intended to support oral dosing. In terms of indication we are focusing on two, where NMDA hypofunction or disfunction has been established. Smith-Lemli-Opitz Syndrome or SLO syndrome and Anti-NMDA Receptor Encephalitis both biomarker [indiscernible] population with no approved treatment. These initial indications will allow us to explore activity of SAGE-718 and its mechanism. And then potentially expand to broader CNS population that exhibit similar biomarker activity. AT SOBP, we plan to plan to present data on SAGE-718 showing that the molecule is potent and selective NMDA receptors. And in preclinical animal models of psychosis and cerebrosterol deficit disorders that SAGE-718 demonstrated activities suggesting potential utility indications characterized by NMDA hypofunction such as SLO syndrome, as well as potentially even [indiscernible]. Assuming successful completion of non-clinical work, we expect to begin the clinical development SAGE-718 in 2017. As we hope that you can see on Slide 16, this is an exciting time here at SAGE, and an important year for potentially transformational milestones that we believe will help to find the clinical path of our development plan in the future. Ranging from data from our Phase 3 clinical study that will define whether there is near-term path with regulatory approval and commercial launch in SRSE to other data that are positive, mainly to a significant expansion in later stage trial for a number of other CNS indications. Through the exciting work that continues to come out of a discovery group yielding numerous potential compounds. As Kimi will touch on it shortly, we have done this in a capital efficient manner with the financing strategy that has put us in a strong position heading into our data readout this year. Finally, just to recap again what we expect during the remainder of 2016; topline results for Phase 1 clinical program of SAGE-217 during the second quarter of 2016, topline results from our Phase 2 placebo-controlled, proof-of-concept study of SAGE-547 in severe PPD during the second quarter of 2016. Topline data from the Phase 3 STATUS Trial of SAGE-547 in SRSE in the second half of 2016, potential Phase 2 clinical trail initiations with SAGE-217 in at least two indications including the essential tremor and 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 FDAs request for 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, and with that I’m going to turn it over to Kimi.

[Kimi Iguchi:]

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 in the same period of 2015 including $0.8 million 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 executive on the following; first, completing our Phase 3 STATUS trial super-refractory status epilepticus, investing in the necessary infrastructure for potential commercial launch in SRSE if we achieve positive Phase 2 results in our April regulatory approval. And continuing to invest in broadening our product portfolio and clinical pipeline through our investment and 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 continued increases in operating expenses as we complete our Phase 3 STATUS Trial to SAGE-547 in SRSE, continue to advance our discovery and clinical development efforts, engaging activities directed at potential NDA filing and commercial launch, and further grow our infrastructure and organization. Based on our current operating plan, we expect cash and cash equivalents will be sufficient to fund our current operations into the beginning of 2018. Before we open up 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, 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 31; the American Society of Clinical Psychopharmacology, 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. We will now like to open the call for Q&A. So I will turn it over to the operator?

[Operator:]

Thank you. [Operator Instruction] Our first question comes from Ritu Baral with Cowen.

[Ritu Baral:]

Hi everyone, thank you for taking the question. I want to be – I want to focus on the next update data point that you guys have, which is the PPD data, you’re reiterating 2Q, can you give us an enrollment update at this point, given that you restated that guidance? And then as we look towards the data that you’re going to be toplining, can you give us an idea of what do you think, how should we look at that data, [indiscernible] or within these severe PPD patient, should we be looking at that, should we be looking it at different number as we were to look at it versus the baseline?

[Jeff Jonas:]

Alright, thanks for your question and hi everybody. So, couple of points, one is, we’re not – the study is planned to be report out on basically this quarter, we’re not going to provide anymore interim enrollment guidance that’s been our policy for all our studies say for letting people know when we’re going to plan, when we’re planning to report out the topline data. So, apologies for that, but our plan is – as I said, 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 a, this was intended to be a rather straighten study to show a large signal of difference between drug and placebo and the primary endpoint is the HAM-D and basically we are for this study, you can see this on ClinicTrials.gov probably. This was only 80% powered to show a 10 point difference in the HAM-D. Our belief was based on the preclinical data that was – that we had with respect to the role of extrasynaptic modulation in this disorder, plus the data we achieved 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, 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 patient who respond dramatically, which is what our pre-hawk hypothesis specifies and so there may be some secondary analysis, but the primary is the difference of the HAM-D.

[Ritu Baral:]

So is that 10 point sort of the minimal input difference that you will be looking for and what’s your assumption to change?

[Jeff Jonas:]

We’re really – let me go back, many SSRIs have been approved with far smaller differences on the HAM-D, one of the interest that Sage is really to only bring forward drugs that have a dramatic alternation in terms of patient. So we pre-specified rather large potential [indiscernible] that we thought would be unequivocally an improvement to the patient. As I mentioned the secondary variable that we’ll look at and this is something we can’t really account for, but we will look at is whether there is a difference in the number of patients who have, otherwise we call it complete remission and that will be handy below 7. So that’s how we’re thinking about it. Obviously, we’ll take a look at the data when we see it, but we believe that based on the preclinical data and based on the published 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.

[Ritu Baral:]

Sure, so just following upon that, what’s your anticipated to change in HAM-D for placebo.

[Jeff Jonas:]

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

[Steve Kanes:]

Yeah. We're not anticipating a large placebo response in these patients. We know that when we start treating patients, there is always some placebo response in depressions, but we're not anticipating a large placebo response, and it's just that -- the most important part is the separation from placebo in the study that we've designed.

[Ritu Baral:]

Is that like the five point, 10 point.

[Jeff Jonas:]

Well it wasn't powered to that way, so I don't think we’d stretch by beyond that.

[Ritu Baral:]

Great. Thank you for you for the questions.

[Jeff Jonas:]

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, it was very little drop on the HAM from screen to base wide, which suggest that you would not expect in this particular population which you know had 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 trial. So, we did have some data early on that suggests that you would see that kind of progression to the mean. So let me just give you that a separable item.

[Operator:]

Our next question comes from Paul Matteis with Leerink.

[Paul Matteis:]

Great guys. Thanks very much and congrats on the progress. Jeff, a question on your point about conceptualizing PPD as an acute deficiency state, you know 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 -- after child birth if there is differences between those two different types of patients, and if you'd expect both the respond to SAGE-547?

[Jeff Jonas:]

I think you know you'd probably know from your extent of literature there was always a miss that pregnancy was protective. I don't think we believe that any longer. What did we find in PPD, I think these maybe people with some effect of diathesis that maybe exacerbated by the rapid decrement of allo -- endogenous allo right after birth. So I don't necessarily see those as dichotomize syndrome. I don't know if you want to add anything to that Steve?

[Steve Kanes:]

One of the things that when we talk to experts in the field is that, there is a thought that either allopregnanolone or other hormonal support at the very challenge of pregnancy in women who are pretty disclosed to developing post-partum depression actually start to tail off prior to deliver 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 with high risk. So, we're trying to align the inclusion criteria with the people we think with most benefit from treatment.

[Paul Matteis:]

That's helpful. And then, one other question, so this 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 trail. It seems like that's a pretty key variable here. Is that something that you are stratifying and controlling for between groups? Do you think that that's an important thing here to take account for?

[Jeff Jonas:]

There are couple of points, one is typically, see the women are not hospitalized and they're probably independent of their severity at this point, because they typically are in a care-taking 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 symptomology, we believe we will be homogeneous and that is, we're looking for women who are very severely depressed who've been sick for at least four weeks, mostly will have a history of unresponsiveness to other medication. So, we believe that the demographic inclusion criteria is likely to give us a reasonably homogenous population.

[Paul Matteis:]

Great, and at the presentation next week, what kinds of granular analysis will you be doing from the four patients?

[Jeff Jonas:]

For that presentation, we have another one coming up later which we haven't made public yet. But for the one at SOBC, we'll be selling more of the treatment force and in terms of the velocity of therapeutic response and also a summary of the secondary endpoint. One of the area that we've been fluid about, and 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 benefited consistent with the HAM-D, so we will be showing all those data at SOBC.

[Operator:]

Our next question comes from Salveen Richter with Goldman Sachs.

[Unidentified Analyst:]

This is Tom on for Salveen actually. Thanks for taking the question. So just one question on the health economics that you did on -- data that you presented at ASCO. Given these results, would this change in anyway, how you are thinking about pricing for SAGE-547, if it is approved? Does it narrow the range you are thinking about or broaden it or how should we be thinking about that?

[Jeff Jonas:]

I think and we think about the economic burden as you know. We think right now, we can't guide pricing. I think we've always made it a point to say that in terms of our thinking of our pricing, we want to make the value proposition clear and not require rather abstracted pharmacoeconomics types of analogy. 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 payor work now both here and in Europe, but we're not really prepared just sort of peg a price until the Phase 3 data come in. At that point we'll obviously be -- we'll be communicating with much more detail both our pricing strategy and our go-to-market strategy.

[Operator:]

Our next question comes from Cory Kasimov with JP Morgan.

[Cory Kasimov.:]

I guess, first of all I want to go back to something that you'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 and the powering assumptions you have for the Phase 3 STATUS Trial. 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?

[Jeff Jonas:]

So remember, we haven't really given the specific powering, but it is powered at a 90% range. And as you know, we've got -- we've used -- and this was -- we use the Rossetti paper which we still think is the best paper that demonstrates the repose to a single attempted wean in patients with clearly diagnosed SRSE, and as you know this is a -- 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 inflate SRSE with RSD and SE, which is sort of like saying a basal cell carcinoma is like melanoma. So we are pretty comfortable with the powering assumption. It is 90% powered, the endpoint as you know are reasonably unequivocal and unambiguous which is ability to give you 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 attempted wean, not an aggregate wean is portably about -- at least not more than 35%.

[Cory Kasimov:]

Okay. All right that's helpful. Then regarding SAGE-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?

[Jeff Jonas:]

No I actually -- I say that given one of the interesting pieces about this mechanism is that, in normal that you will be able to see the pharmacologic of activity that should read through into the pathologic conditions that we're speaking to treat. So, we'll be able to see by example effects of EEG and pharmaco EEG which we've already demonstrated with SAGE-547 has a very nice dose relationship. So, we've developed a biomarker that some of data we presented at AAN which is reasonable unique to this classic compound. So, we'll be looking at things like sedation, we'll be looking at things like pharmaco-EEG. So in fact by the end of Phase 1, we put out this data, not only we'll have a good sense of safety, but we'll 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 2017 data, we'll know about. I've said this publicly, we're pretty comfortable. It's moving alone 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 Phase 2.

[Operator:]

Our next question comes from John Newman with Canaccord.

[John Newman:]

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 SAGE-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?

[Jeff Jonas:]

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, it's sometimes misunderstood. Despite the underling disorder, unless you treat the status epilepticus normal light isn’t possible. 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, 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 and other underlying agent, we'll look at hemodynamic tracings, we'll be able to look at the extent of Image result for burst suppression, because this study, although its' very complicated, it's being conducted in the ICU. We will have a wealth of data in terms of the acute, the value of the acute intervention here that we hopefully will corroborate the activity of the drug. Beyond that, we'll obviously be following out to 21 days, of course the and FDA and thought leaders all recognized that outcomes is unrelated to -- with the STATUS, it is driven by the underlying disorder which we can't of course hope to cure. But we'll be getting those kinds of data as well. Finally we do have several pharmacoecomic measures built in. We haven't made those public and we hope we'll 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.

[Operator:]

Next question comes from Tim Lugo with William Blair.

[Tim Lugo:]

We're already in, and you said second half of 2016 first STATUS. But could you give us any more granularity? Is it possible that we do get these results in Q3, or is Q4 more likely to any sort of additional guidance?

[Jeff Jonas:]

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 -- I'm trying to be very disciplined both in terms of not giving interim looks at the enrollment update, so we're really going to say that we are still planning to release top-line data by the end of this year. So, I'll just leave it at that.

[Tim Lugo:]

For SAGE-217 then, what are your views on testing that compound with a CBD based products or potential drug-drug interactions, obviously CBD has been an interesting topic recently.

[Jeff Jonas:]

That's a really interesting question. We -- its' 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 has to be a DDI issue, a drug-drug interaction issue. It maybe something that's requested by the agency since we've -- I think it's a really good point, it's one we'll consider. What's probably more broadly, we do recognize that the epilepsy space has room for several innovative products. So as we move forward in the clinical progress for SAGE-217, that's something we will pay attention too. We're not committing to it yet. But as you also know that SAGE-217 mechanism will 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 you all know is basically inactive at therapeutic doses that the -- at the extra-synaptic receptor in combination with our drug, we actually enhance propofol which is normally 1 in 1000 as active at the extra-synaptic activity of receptor. We enhance its activity in animal data. So these are the kinds of things we may be looking at as we move SAGE-217 forward.

[Operator:]

And I'm not showing any further questions at this time. I'd like to turn the call back to Jeff for follow-up comments.

[Jeff Jonas:]

Well, first I want to thank everybody for your attention today. I know it's been a busy week for earnings. And again, I think we're looking forward to 2016 being a very transformational year with all the data readouts we have coming out, potentially new initiations of Phase 2 trials for SAGE-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 not only in SAGE-217, but potential the SAGE-689 entering the clinic 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 will have a great rest of the evening.

[Operator:]

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