Sage Therapeutics, Inc.
Q1 2015 Earnings Call Transcript

Published: 14 May 2015

[Operator:]

Good morning and welcome to SAGE Therapeutics 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, sagerx.com. This call is property of SAGE Therapeutics and recordings, reproduction or transmission of this call without the expressed written consent of SAGE Therapeutics is strictly prohibited. Please note that this call is being recorded. I would like to introduce Paul Cox from SAGE.

[Paul Cox:]

Good morning. Today, we announced clinical progress with our lead program, SAGE-547 and reported our first quarter 2015 financial results. Those press releases can be found on the Investors & Media section of our website at sagerx.com. During today’s call, we may make forward-looking statements, including statements that are our future expectations, clinical development and regulatory timelines, the potential success of our product candidates, financial projections, 2015 milestones and upcoming events and presentations. Actual results may differ materially as discussed in the risk factors section of our Annual Report on Form 10-K filed with the Securities and Exchange Commission on March 6, 2015 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, where we disclaim any obligation to do so. On the call is Dr. Jeff Jonas, Chief Executive Officer; Dr. Steve Kanes, Chief Medical Officer; and Kimi Iguchi, Chief Financial Officer. Following prepared remarks, we will open the call for questions. I would now like to turn the call over to Jeff.

[Jeff Jonas:]

Thanks, Paul and thanks everybody and good morning. We are all excited to host our first conference call, especially on the heels of announcing what we believe a really profound data regarding SAGE-547, our most advanced internally developed product candidate. Before I get into that though, I would like to tell some of you about SAGE who of those you are not familiar with the company. SAGE is a leading neuroscience company and we are committed to developing novel medicines that treat life threatening and central nervous system disorders. Our focus in CNS stems on the fact that there has been a positive innovation in this area, despite the fact that central nervous system disorders represent 35% of the worldwide disease burden. Our approach is to do CNS drug development differently. We are focusing on identifiable patient populations, where there are clear clinical trial endpoints that could be assessed rapidly and unambiguously. We believe this will give us the ability to move efficiently and rapidly to bring new medicines to patients. SAGE’s programs are based on the proprietary chemistry platform developed by SAGE scientists. We are focused on correcting imbalances of two critical brain stimulating systems called GABAA and NMDA. These are responsible for a large number of CNS disorders, both psychiatric and neurological. To-date, we have a large chemical library and extensive chemical equity spanning more than 1,700 compounds. Many of these compounds have strong pharmaceutical properties. This pipeline is led by SAGE-547. This is an allosteric modulator of GABAA, a positive allosteric modulator. It operates GABAA in a way that’s different than most conventional therapeutics, which typically work at the synapse and function more like a light switch. Allosteric modulation is a gentler way of modulating GABAA, working more like a dimmer switch. SAGE-547 is in late stage development for the treatment of a rare and critical seizure disorder called super-refractory status epilepticus. Patients who suffer from status epilepticus are in life threatening state of persistent seizures that last 5 minute or more. Status epilepticus can be caused from a variety of underlying disorders. These patients are typically treated as outpatients first with benzodiazepines and if not, if there is no response, they will then be treated with second line anti-epileptic agents. If these seizures persist, this becomes a medical emergency and the patients will be admitted to the ICU and placed into a medically induced coma. At that moment, these patients would be termed refractory status epilepticus. After 24 hours, there will be an attempt to remove the patient from a coma, a weaning attempt, but this is an attempt to wake the patients from an anesthesia and to see if the seizures have resolved. The majority of these patients failed to resolve and go back into a medically induced coma and at this moment, this would be termed super-refractory status epilepticus, SRSE. SRSE is a critical disorder that must be treated for which there are no approved therapies. You first must treat the underlying disorder, but also for the patient to have meaningful existence, you must treat their seizure. I personally observe these patients and I can tell you that this is devastating for both the patients and their families. In the U.S. alone, approximately 25,000 patients will be diagnosed with SRSE. This is the dire disorder. It’s serious, sudden and disabling and deadly. Two-thirds of these patients will either die or become seriously disabled. SAGE-547 and the data we will announce today, is currently in registration development for the treatment of people with SRSE. We initiated clinical development of this drug in March of 2014 and moved it rapidly into Phase 3 exemplifying our approach to clinical development. We have initiated Phase 3 development and we anticipate enrollment by the middle of this year. So, let me turn now to the data. Earlier today, we announced that we have successfully completed a Phase 1/2 trial of SAGE-547 in patients with SRSE. This trial was an open label trial, but in patients who had [indiscernible] treatment failures to first, second and third line agents. This trial was intended to evaluate the safety, efficacy and tolerability as well as the pharmacokinetics of two IV administered dose regimen cohorts of SAGE-547. Patients who are administered SAGE-547 intravenously for 5 days, while weaning from third line IV general anesthetics administered to a state of what’s known as burst depression that is a state where brain waves are virtually quiet. After treatment, patients are monitored for a total of 30 days to assure safety. 25 total patients were enrolled at 18 trial sites in the United States. Of these, 22 were evaluable for efficacy, 16 at the standard dose regimen, and 6 patients at the higher dose regimen. Patients were judged to be non-evaluable if their treatment was disrupted or no weaning attempts from general anesthesia were attempted. Of the 22 total evaluable patients, 77% were successfully weaned off their anesthetic agents, while SAGE-547 was being administered during the maintenance phase of therapy. In addition, 70% of the total evaluable patients were successfully weaned off SAGE-547 without recurrence of SRSE in a 24-hour period following treatment. We have now obtained biomarker data that helps validate this clinical activity that we have been observing in our studies. Continuous EEG was evaluated as an exploratory endpoint in 14 patients. SAGE-547 showed clear pharmacodynamic activity as measured by continuous EEG in patients who had previously failed third line therapy, while burst depressed under general anesthesia. This effect was seen regardless of the underlying third line anesthetic agents employed indicating we believe clear evidence of additive pharmacologic activity. Additional secondary endpoints were obtained to help evaluate the meeting of an SRSE response. These included measures of consciousness in functional stages over a 30-day follow-up period. By the last follow-up day as a group, the patients that were successfully weaned off third line IV general anesthesia in SAGE-547 showed a clinically meaningful improvement compared to the non-responder group. Safety and tolerability of SAGE-547 were also assessed in the Phase 1/2 trial. SAGE-547 demonstrated a favorable tolerability and benefit risk profile that supports development in this acutely ill patient population that represents an area of severe unmet medical need. Overall, 64% of the patients experience at least one serious adverse event, though none were drug related as determined by the Safety Review Committee. Individual serious adverse events reporting at least two patients were respiratory failure, pulmonary embolism, sepsis, convulsion or metal failure, independent of treatment response 6 patients that’s occurred within the study period, all driven by the underlying medical conditions. Recall, that severe illness is one of the principle causes of SRSE. A total of 207 adverse events were reported in 23 patients. The most common adverse events were fever, hypotension, diarrhea, peripheral edema, anemia and BUN increase. All of which were reported in four or more patients. One case each of fever and BUN elevation, were deemed related by the investigators. Responses were unrelated to underlying condition, age, gender, status epilepticus severity at baseline as determined by the status epilepticus severity score, duration of status epilepticus prior to enrollment or concomitant therapy. To summarize, we are extremely encouraged by these results, which we believe are truly unprecedented for patients affected by SRSE and are groundbreaking potentially for patients and for SAGE as a company. We believe this approach is not only important in validating the activity of SAGE-547, but helps to validate our overall approach to modulating GABAA and helps de-risk the likelihood of success for our follow-on molecules, SAGE-689 and SAGE-217. Let me turn now to our Phase 3 program, the STATUS trial. This is the trial that’s designed to assess the efficacy and safety of SAGE-547. It requires up to 126 evaluable patients with SRSE age two years older. We anticipate utilizing up to 150 sites in the U.S. and the EU. It will be a one to one randomized trial of SAGE-547 versus placebo plus the standard of care for a total of six days. And enrollment is on track to begin by mid-year. The planned primary end point will be successful resolution of status epilepticus after weaning the patient off all third line anti- epileptic agents and 547 or placebo without resumption of status epilepticus within 24 hours after completion of the blinded SAGE-547 or placebo administration. Patients who do not respond to initial blinded therapy of SAGE-547 or placebo may be eligible to be treated with an open label higher does regimen of SAGE-547. In addition, we recently began enrollment in our Phase 3 expanded access protocol Study 302, which makes SAGE-547 available the patients in the U.S. age two years older who are affected with SRSE. This allows for expedited therapy for patients who are located in hospitals that are not participating in the STATUS trial and who cannot be transferred to trial sites for medical or other reasons. Our hope is to convert Study 302 sites who participate with emergency cases into future Phase 3 STATUS sites, potentially accelerating further our STATUS trial enrolment. Full date from our STATUS trial combined with the safety data from Study 302 and other parts of our SAGE-547 program are expected to support potential future NDA submission. In summary, SRSE is a devastating disorder. There are no available therapies and will also on the horizon. We believe that SAGE-547 offers the potential to be the first approved medicine for these patients. In understanding our platform and how GABAA modulation may impact patient benefit. We are also using SAGE-547 in exploratory trials to establish the versatility of a GABAA platform and to increase the value of our extensive chemical equity as we explore new indications beyond epilepsy. We are using SAGE-547 because we believe we have established CNS pharmaco-activity. So, we can use this agent as a signal finding methodology to help guide the design of second generation molecules in broader CNS indications. Two trials are ongoing. The first is essential tremor. This is debilitating neurological disorder where involuntary and rhythmic shaking occurs for no known cause. The other is the postpartum depression trial also ongoing. We believe postpartum depression represents unique opportunity in psychiatry, because this is a distinct and readily identified form of major depression estimated to affect up to 20% in women following child. The top line data from both of these studies are on track to be announced by mid-year. And we plan to use the data from our dosing regimens and the pharmacodynamics we see to guide design of second generation GABAA receptor modulators for both of these disorders. SAGE has further opportunities in the pipeline. In terms of second generation molecules we have SAGE-689 and SAGE-217 both are allosteric modulators. They both utilize similar magnetic pathway to SAGE-547, but are more potent at the relevant receptors. Both the designs have pharmaceutical properties that optimize the potential utility in their chosen clinical settings. In effect, they are bespoke molecules which we have been able to select from our large platinum chemical equity. SAGE-689 is being developed as an adjunctive therapy IV for the treatment status epilepticus. SAGE-217 is being developed as an orally available therapy for orphan epilepsy. This is the highly potent molecule that has the potential to be utilized only once a day as a therapy. Both of these programs are progressing through our NDA filling activities and we are on track to initiate Phase 1 programs in each by the end of this year. Finally, I would like to quickly touch on our NMDA program. We have been working hard you identity areas of unmet need where NMDA directed molecules maybe of clinically utility. At this time we are developing translation of models for select orphan disorders where we hope to establish proof of concept in order to establish indications where we can test these molecules. Our goal is to develop first in class therapies for certain orphan indications. This approach will replicate that of what we done in SAGE-547. We have reduced the risk of development by first targeting homogenous populations where an NMDA mechanism of action should provide benefit and where we can clearly establish with their drugs. We will then establish proof of principle to guide further investment and potentially larger indications. I would like to thank you all for your attention. And now I would like to pass this call over to Kimi to talk about our financial results. Kimi?

[Kimi Iguchi:]

Thank you, Jeff. I am happy to report that SAGE is in a very strong financial position today. Earlier this morning we issued a press release detailing our financial results. Before I summarize the highlights for you, let me remind you that in July 2014, we went public with a successful initial public offering raising net proceeds of $94 million excluding operating costs. Debt financing funded the SAGE-547, Phase 1/2 clinical trial and the start of the IND enabling work for our follow-on programs SAGE-689 and SAGE-217. Since then we have executed on all of these programs and as such report the following financial results for the first quarter of 2015. Research and development expenses were $12.9 million. General and administrative expenses were $4 million. We reported a net loss of $17.6 million and we ended the quarter with 25.8 million shares outstanding. Cash and marketable securities at the end of the quarter totaled $113.2 million. In April 2015, we successfully completed a follow-on offering of 2.6 million shares, which resulted in net proceeds of approximately $129 million excluding operating costs. We are very pleased to close the follow-on offering which significantly enhanced our cash position. As we look forward to the rest of 2015, we do expect to see increases in operating expenses as we initiate a global Phase 3 development program for SAGE-547 in SRSE. We advance our follow-on product candidates into the clinic. We continue to expand our development and discovery capabilities and we develop and grow our infrastructure and organization. Based on our current operating plan and with the additional capital from our recent financing, we expect our current cash balance will fund our operations through mid-2017. With that said let me hand it back over to Jeff before the Q&A session. Jeff?

[Jeff Jonas:]

Thanks, Kimi. 2015 is really positioned to be a game changing year for SAGE. The subsequent financing has really helped to prepare us for the following key milestones in 2015. Beginning our enrollment in the Phase 3 STATUS trial, announcing top line data for our exploratory trial in essential tremor and postpartum depression on track for mid-year, completing the IND enabling activities for our follow-on product candidates, SAGE-689 and SAGE-217, advancing both of these programs into Phase 1 by the end of the year and announcing our next product candidate and lead indication by the end of the year. We think we have had a great year at SAGE and I want to thank all of the team at SAGE and the patients and physicians who helped and worked with us and what they have helped us accomplish so far. So now, I would like to open the call for questions-and-answers. Operator?

[Operator:]

Thank you. [Operator Instructions] Our first question is from Cory Kasimov with JPMorgan. You may begin.

[Unidentified Analyst:]

Hi, good morning. This is Morgan [ph] on for Cory. Thanks for taking our questions. I just had a quick one regarding the recurrences seen on the Phase 1/2 trial, how do you think the FDA is going to view these, are they just a function of the underlying conditions and what are you doing to address them going forward?

[Jeff Jonas:]

Thanks again for the – thanks for the question. We expect – obviously these are very severely ill patients. So the recurrence are not surprising, although albeit there were only a small number. The primary end point this was discussed. And the primary end point remains the resolution of status epilepticus within 24 hours of cessation of SAGE-547 precisely because of the recognition that these patients have many, many severe disorders. And that there was an understanding that further outcome is likely to be confounded by the underlying disorders. That said the Phase 3 program as I think you may recall does incorporate a retreatment arm. So we will have some further information about the utility of retreatment in patients, who are non-responders.

[Unidentified Analyst:]

Okay, great. Thanks.

[Operator:]

Thank you. Our next question is from Paul Matteis with Leerink. You may begin.

[Paul Matteis:]

Hey, guys congrats on the full data and thanks for taking my questions. I have a few. My first is I am wondering you have consistently cut this data based on an efficacy evaluable population of patients which makes sense given that there are some many confining variables and other conditions, but that shows a 77% rate in 22 patients. I am wondering how will these data be cut for the primary efficacy analysis in Phase 3, would you be using a nine of 22 to calculate the responder rate or a nine of 25, all of the patients that are actually randomized?

[Jeff Jonas:]

Our discussions of – we intend to use the evaluable patient population that has been discussed in terms of the analysis. As you see, I am a little under the weather. The patients who actually don’t make a rating or who can’t or don’t receive drug that are randomized or not relevant to the population, so that - so we are planning to the evaluable in the pivotal program.

[Paul Matteis:]

Okay. That’s helpful. And then all this - so can you just confirm that the Phase 1/2 study now is - has been stopped and are all the sites that participate in this trial going to rollover and participate in the Phase 3?

[Jeff Jonas:]

Yes. I am going to turn this over to Steve Kanes, the Chief Medical Officer for that.

[Paul Matteis:]

Perfect.

[Steve Kanes:]

Yeah, all the sites - so have done enrolling in the trial, the sites are all aware and we do intend to roll all of those sites over into the Phase 3 program.

[Paul Matteis:]

Okay, that’s great. And then one more on the tremor and PPD programs, obviously these are pretty small studies and the PPD study is open label. So I guess what – in your opinion what would constitute success in these studies that would be sufficient to move second-gen products forward into additional proof-of-concept. And if you do move these forward, how quickly do you think you could get going new trials with second-gen molecules? Thanks.

[Jeff Jonas:]

Both of these - both the studies are different in design. So the tremor program was a double-blind placebo-controlled trial in an acute setting. So that should give us reasonable good juristic data bad activity as we dose escalate. So that was designed to be somewhat definitive largely based on that patient population. The PPD trial was designed more as a signal finding study. So let me just – and so that approach is – the theory behind that is pretty straightforward. We were looking for women who were severely ill in inpatients with very high AMDs who are treatment resistant, then you may hear the similar theme for what we had done with super-refractory status epilepticus that is women who had failed of these one documented trial of an SSRI. It’s a signal finding study. So the way we interpret this is that, if we think we have the dose and we think we do a dose then a negative study has very high negative predictive power and you can stop the program. If we have a – on the other hand if we were to find some responses that were robust and unequivocal, we believe that could constitute a positive signal that would justify further investment. It’s a pretty classical way of approaching an open label program where you acknowledge that the strength of the positive signal is weaker than the strength of a negative signal, but the positive signal can be enhanced by the nature of the patient population. So for example in PPD, treatment-resistant inpatient very severe would give some more confirmation for investments. If we were to have a positive signal in either of these studies, as you know we have a large chemical library, a lot of chemical equity and we’re pretty comfortable, we could move the products pretty forward reasonably rapidly into the clinic with a positive signal.

[Paul Matteis:]

Okay. Fair enough. And hey just one more quickly on the patients who had recurrences STATUS, those patients they had recurrence anywhere from like a week to a few weeks after therapy. Would they still be deemed responders in the Phase 3 study, would there be clinical successes?

[Jeff Jonas:]

Yes they would. They would be deemed responders in the clinical program. As I mentioned the - this is an interventional trial, so the recognition of that has been built into the trial where the primary endpoint is the ability to resolve STATUS. We’re actually pretty pleased with the low level of relapse frankly in the severely ill patients and if you go back and look at the 30-day data, what you see is that it is still markedly different from the patients who did not respond at all. So overall it’s a very consistent picture of a high level of activity.

[Paul Matteis:]

That’s great. Congrats on the results. Thanks.

[Jeff Jonas:]

Thank you.

[Operator:]

Thank you. Our next question is from John Newman with Canaccord. You may begin.

[John Newman:]

Hi, thanks a lot for taking my question. I just had a couple of them actually, if you give us a sense as to the distribution of U.S. versus EU site for Phase 3? And during your prepared remarks you mentioned that patients may be eligible for a higher dose of 547 in the Phase 3 if they are not responsive to other placebo or 547. What exactly determine whether or not they are in fact eligible to go to that higher dose? Thanks.

[Jeff Jonas:]

Thanks so much. I’m going to let - turn this over to Steve Kanes to answer.

[Steve Kanes:]

So yeah with respect to the first question, we’re looking at about a quarter to a third of the overall sites being in Europe for the Phase 3 program. With regard to retreatment, we view failure on the primary efficacy endpoint, which Jeff has already mentioned as resolution of STATUS for 24 hours after weaning off SAGE-547 and general anesthesia. If the patients have failed on that endpoint, they would then be eligible for retreatment. So only the failures, documented failures would be eligible for an open label retreatment.

[John Newman:]

Okay. And I know that these patients are very, very sick and that you previously discussed the patients that unfortunately died during the study. I just wanted if you could give us a little bit more detail in terms of the six. If I can remember correctly there were few that had drug overdoses before entering the study that you had patients with brain cancer. Just wondering if you could describe a bit more about just the conditions with those patients and of course understanding that they are very, very ill?

[Steve Kanes:]

Two of the patients were responders and those patients both as I said had underlying conditions, one of them had an infectious cause, one of them had a brain tumor, metastatic brain tumor. So even though they were able to be – responders and woke up during their treatment, they ultimately had their, decided personally to withdraw their care and passed away during the 30-day follow-up. They were - among those, the non-responder group now three patients who, after they did not respond during the initial treatment, the family decided to not pursue keeping the patients on life support for the full 30 days. There was one patient that was not evaluable and who died, we don’t know whether they would have been a responder or non-responder.

[John Newman:]

Great. Thank you.

[Operator:]

Thank you. Our next question is from Salveen Richter of SunTrust. You may begin.

[Salveen Richter:]

Hi, thanks for taking my question. Just wanted to get a sense of higher conversations with the FDA are going regarding this trial. Just give a sense of breakthrough status of whether this is a path you are taking and then secondly timelines around the Phase 3 program? Thanks.

[Jeff Jonas:]

Thanks, Salveen. We – the focus of the company has been to move into Phase 3 rapidly. And as you know early in the stage of development the role of breakthrough is really to help accelerate the program. So from that standpoint we believe our timelines are as - accelerate as one could have hoped for considering our first Phase 1 formalized patient was in March. That being said the breakthrough designation is one that we are looking at. We are aware that of the guidance which requires controlled data or validated historical data. So that’s something we have to discuss with the agency in terms of looking through a breakthrough. There has been somewhat of a hurdle for breakthrough designation in CNS companies as you probably are aware, there are about 70 breakthrough designations that have been granted and only four have been in CNS and all of those high-controlled double-blind studies. So right now it was not a machine critical feature for us especially given the acceleration into Phase 3. We will look at this now that we’re pretty comfortable based on some interactions that this is a breakthrough qualified illness and the nature of doing that is something we are still exploring, but we’re pretty comfortable right now with the timelines and having moved to Phase 3. Did I miss the other half of your question?

[Salveen Richter:]

Is timelines are on the Phase 3 study?

[Jeff Jonas:]

Sorry, Salveen. We are not – we have always guided between one and two years to complete assuming 100 to 200 patients. Obviously, given the effect size we have seen in the Phase 2 program, we think we have been able to accommodate a well-powered study with only 126 patients. So, we are obviously optimistic we can roll on the shorter side of that, but until we actually launch and get our enrollment figures nailed down, we are not going to – we think it’s not prudent yet to revise our estimate. I mean suffice it to say that we are going to do everything we can to accelerate the enrollment. And I think Steve’s team has done a great job. We’ve had more than 100 sites already contact us to participate in the trial and so we’re very comfortable that we’ll be able to move this along quickly.

[Salveen Richter:]

Perfect. Thank you.

[Operator:]

Thank you. Our next question is from Tim Lugo with William Blair. You may begin.

[Tim Lugo:]

Thanks for taking the question. You mentioned identifying continuous EEG as a biomarker in SRSE patients. Can you repeat again how many patients you have continuous EEG data on, and if you discuss using this as a biomarker in your most recent FDA meetings and maybe what their thoughts were around the validity of that as a biomarker?

[Jeff Jonas:]

I am going to answer the first part of this and I will turn some of this over to Steve. We are really using this as an exploratory measure to validate the clinical pharmaco activity of the drug. And that’s why we were so excited to utilize it. However, it is not – this was a post-hoc analysis somewhat complicated using a computer power spectrum analysis. So, it’s really one that we are using to help validate the clinical findings and not to use it as an endpoint. The endpoint remains the clinical endpoint as discussed with the agency. We view the biomarker data that was one that is confirmatory of the activity of the drug in these patients. And what’s been encouraging is that correlates well with response. And we see activity in patients who are otherwise not maximally burst depressed, but as burst depressed as they could be on maximal therapy. Let me just turn over to Steve to add some more color.

[Steve Kanes:]

Right. One of the questions we wanted to answer was or one of the effects we wanted to demonstrate was that adding SAGE-547 on top of all of the existing treatments, both general, anesthetic and antiepileptic had a measurable effect. And to that extent, we are able to see that very clearly with the continuous EEG. But from our perspective, the clinical endpoint is not going to be based on the biomarker outcome, it will be based on the clinical response as we have been describing.

[Tim Lugo:]

Okay. And how many patients again do you have continuous EEG on, is it 17, I think…

[Steve Kanes:]

It’s 14 patients, yes.

[Tim Lugo:]

Okay. And maybe another question for you, Steve, with the data today are we going to – will there be anything incremental at Friday’s meeting in Miami?

[Steve Kanes:]

There will be some additional details deep into the individual etiologies, breakdowns on the standard dose versus high dose. So, some of them were deeper details on those responses.

[Tim Lugo:]

Okay, great. And maybe one last question for 217, you mentioned development potentially in orphan epilepsies such as Dravet and Rett, but you don’t state it will be Dravet and Rett, is there still something – what are the decision points coming up for choosing those next indications? Are you willing to see something from the competition? Are there some other orphan disorders that you potentially might move into besides Dravet and Rett that you are not mentioning?

[Jeff Jonas:]

So, 217 right now as you know is an orally available compound based on the animal data we see is likely to be a very prone once daily oral therapy. We think it has the potential that brought utility, but our focus as you mentioned is in the orphan epilepsies. We are looking at a number of orphan epilepsies besides Dravet and Rett. So, those are two, where they are established preclinical models that we are exploring now, but we will leave the option open to look at other syndromes, where there is high frequency of epileptic seizures as a key component of the clinical syndrome, where this mechanism of action may have utility. We don’t see the need to confine it to one or two orphan epilepsies. I guess, I would add that, because these are new chemical entities, the narrowing of their applications to one particular orphan indication is not necessary for us. So, we have a broad opportunity to look across the spectrum of epilepsies for that compound. So, that’s going to be our approach. We are not ready to describe how we will do that, but you can take it from us that we believe that based on the pharmaco-activity we are seeing in with 547, they were comfortable that 217 makes it to the clinic and it is on target to be in humans by the end of this year that this drug has the potential to be pharmaco-active across the broad spectrum of epileptic disorders.

[Tim Lugo:]

Okay, thank you for that. And maybe one last one for the PPD trial, I assume these patients have been admitted into a hospital, they must be pretty severe. I guess, how translatable do you think the data will be to maybe more general PPD patients?

[Jeff Jonas:]

Our concern – our interest with PPD was to look at a very severe population with the belief and I came from Forbes, as you know in my prior life, I have done a lot of these trials that the more severe patients tend to be more homogenous especially with respect to the nature of the diagnosis, but it’s characterologic etcetera, etcetera. So, we are looking at very severe patients with very high MDs or inpatients. They are not that common in just we end up. So, these are patients who have [indiscernible] healthcare, unable to do infant care things like that. So, as I mentioned earlier, this is a sort of speculative study. And so we will be just looking for some sort of signal that either validates or tells us we can stop this program. And as mentioned this is on track to report out by the middle of the year. We are comfortable however that this is a unique population. There are unique neuroendocrine features about this population that then theory distinguished them from other forms of depressive disorder, remembering a depression is so much heterogeneous. So, that’s how we are thinking about it. Our approach will be as with status is to see if we have a strong signal, if you had a strong signal or no signal, we are not going to drag this through if the signal is not very strong.

[Tim Lugo:]

Thanks for answering all the questions.

[Jeff Jonas:]

You bet.

[Operator:]

Thank you. This concludes the Q&A session. I would now like to turn the call back over to Jeff Jonas for closing remarks.

[Jeff Jonas:]

I want to just thank everyone again for your attention today. I want to thank the team at SAGE, our patients and the physicians who participated in our trials, the university that helped us and I just want to again thank all of you. I think 2015 is going to be a really exciting year for SAGE. We have a lot of milestones coming up that we hope will add value to the company and add value to patient care. So, with that, I would like to close the call and again thanks everybody and have a great day.

[Operator:]

Ladies and gentlemen, this concludes today’s conference. Thank you for your participation and have a wonderful day.