Sage Therapeutics, Inc. (SAGE) Earnings Call Transcript & Summary

Good afternoon. Thanks for joining us. I'm Salveen Richter, Biotechnology Analyst at Goldman Sachs, and we're pleased to have Sage Therapeutics with us. And with that, I'm going to turn it over to Jeff Jonas, CEO, in the case he has any opening remarks.

Well, first, thank you, Salveen. Thank you, Goldman. I hope everybody is well at home. And I just want to thank everyone for being here today, and I'll let you begin with questions.

Perfect. So as you think about balancing the ZULRESSO launch here and the 3 new zuranolone indications that you're moving forward with on a pivotal standpoint, and then your -- rest of your R&D pipeline, 324, 718. What's the latest in portfolio management and maximizing capital efficiency here?

Well, one of the things that we've always said is that we want to follow the science at Sage. And -- so our approach to the portfolio has been to develop novel agents that are new chemical entities, NCEs, that we think are fully differentiated from what's in the marketplace. So if you think about what we've tried to do and what we think we've done, we've always started basically with basic science. And that guides, in fact, some of our investments. So if you take a look at zuranolone, which is 217, I know you'll have questions about that later, it's the first and only molecule that's following on the approval of ZULRESSO, that is a GABAergic agent for depression. It's unique. And we've shown both preclinically and clinically that this is an active mechanism. So when we think about our investment, we think about how we derisk this with our probe studies, what the science has told us. And so with zuranolone, obviously, we have 3 shots on goal now for each of distinct approval because we are pretty confident that this is an active molecule. And if you look at what we -- and if you look at the rest of our pipeline, we think we have good data for each of the other assets that we have in clinical development today based on the science that these are molecules that are going to be active in units. For 324, that's a molecule that we've shown with this mechanism, which should be active in essential tremor. For 718, we've shown both in normals, we'll get into, hopefully, more detail, both in the normals and in people with Huntington's, that it has unique effect on cognition, open-label data but nonetheless very pronounced. So as we think about optimizing portfolio, we think that each of these assets have a sound scientific basis with which to justify further investment.

Great. And in December, you reported data from the Phase III MOUNTAIN Study for zuranolone in major depressive disorder. Can you just recap the learnings from this study and how now you've implemented them into these ongoing studies and the overall trial portfolio here?

Well, it's important to remember, MOUNTAIN had 2 components. And the first is what we reported in December. That was the efficacy component. And if you remember, that was one of several studies. The other 2 previous studies with zuranolone were positive and pretty robust. With the MOUNTAIN Study, we found -- we had a few findings there initially on the efficacy side. One was we thought that there was some variability potentially due to food effect and also very good tolerability. And based on our exposure -- sorry, to some reason, my phone is running and I have it on mute. Sorry, this is real life, which I apologize for. I don't know why it's ringing. Sorry. So we saw from efficacy that we just missed the primary endpoint. But we did see, what was very reassuring for us, rapid separation from placebo very early on, which is what we've seen with this mechanism across the board. What we're interested now is seeing its durability. And I think people have overlooked the fact or forgotten or maybe not paid attention that we will have our 6-month blinded data coming out sometime next quarter. Remember, those data were obtained after the completion of the study. And these data are going to answer a very different question. There are 2 questions I want to ask when you think about treating depression versus acute efficacy. Now we know that for this mechanism, we've had 5 acute efficacy studies that have been positive beside MOUNTAIN. But what we would like to know, and this is a very important question, is what happens to people who get better? And that's the question clinicians have been asking. If you get better, what next? Because that to us is what could differentiate SAGE-217 from everything else currently available where you're always talking about chronic therapy. So next quarter, we will have the blinded data made public from the MOUNTAIN Study, and those data will give us a sense of what happens to the people who get better. And we know there are responders. We know because we narrowly missed significance so we know that we'll have a lot of responders, and we'll have blinded 6-month follow-up that will be -- that we'll be able to show next quarter for that for now.

Great. And just thinking about real-life impact right now with COVID 19, how do you think of the impact there with relation to major depression studies that are running? And I think FDA just recently added Zoloft to list of drugs in shortage. And how does that kind of impact your baseline HAM-Ds and related placebo effects in these trials?

Well, on a global level, I think this -- I think we'll be fine with Zoloft. But -- we're using it as a comparator in one of our studies. But it does show the severity and the importance of mental health in our society. It's often overlooked. And these are life-threating disorders. And when you think about what people are going through today, paying attention to mental health as an urgent medical condition is really as important as -- more important than it's ever been. So I think that's the first message. So I think the folks at Sage, we always believe that we're doing something important. And I think this is the type of observation that says, "No, we want to treat to, obviously, take care of COVID, but there are other things that people are going through that don't require treatment. With respect to our own programs, they are moving along quite well. So we've already begun dosing in the 50-milligram waterfall study, which is the placebo-controlled study, and that's moving along very well already. We have a lot many patients in screening, and it's moving as well as it had pre COVID. Now we've been preparing for this for quite some time. We've also begun dosing 50 milligrams in SHORELINE, and that's going along well. If anything, maybe a little ahead of schedule. We both had some new patients as well as re-treatment. And if it keeps on going this way, there is a possibility, we will have some 50-milligram data to be presented this year along with the SHORELINE data that's due this year. The rest of the studies are moving along well. They're either in screening or beginning to enroll. So the team at Sage has done a great job. We've spent a lot of time preparing for what might happen with COVID and knock on wood, our studies remain on track.

And Jeff, you talked about 6-month data that's going to come from the MOUNTAIN Study in the second half. And then as well with SHORELINE, we're going to see the re-treatment study looking at 30 milligrams and maybe now 50 milligrams. Can you help us understand what we should glean from each of these studies?

Sure. If you step back a little bit and think about how psychiatry is practiced today, I've last practiced in the mid-90s. If you think about any of the field of medicine, where one could say this, 'I could go back to practice tomorrow and pretty much be current." The model for psychiatry has remained stagnant for decades. And there's always been an assumption that depression is a chronic disorder that requires basically lifetime chronic therapy. So for clinicians, one of the things we've always sought to do with 217, we often get asked, why not just make it a chronic therapy? And the answer has always been, firstly, because we don't need to. Secondly, because we think the mechanism and the science suggests that there's a brain reset. And third, we would like to offer a fully differentiated option for patients. So what will we learn from the 6-month data and that might reflect on the SHORELINE data? Well, the first thing we have to talk about is you often hear people talk about how we look at our curves a lot. And if you think about this, we -- sometimes we get asked, well, why is it after 15 days, some of the curves move up, some don't. That's because at 15 days, you are looking at the combined nonresponders and responders to a clinician, and for the label. You're really only interested what happens to people who get better because if we don't get better, like in the rest of medicine, you'll try an alternative therapy. So in the 6-month data, what we're hoping to see is what happens after 6 months. And what happens to those patients, who are responders. Now we know even in MOUNTAIN, we'll have a much bigger group of responders in the drug and placebo, and we'll show that data. But what happens after 6 months? And this is blinded follow-up. That will give us a real clue about what SHORELINE might show. And what you -- what we hope to see is that there will be a large group of patients, who remain stable after 6 months regardless of further intervention, whether they're on antidepressants or not, whether they're on monotherapy or not. If we see that in the 6-month data, that will obviously augur well for what we might see in SHORELINE. And so then if you think about what SHORELINE might show us to a clinician, if you get better on zuranolone, what does that mean? Think about the option we could now offer patients. You could have one of any type of drug that you get on and take intermittently or chronically, indefinitely, or let's say 1/3 of the patients or half of the patients get better and don't require any retreatment, you can offer these patients another option. And that is, if you get better, you can go back to work and not require chronic pharmacotherapy until and unless you get ill again. So it is a completely novel offering, and that's always been the target for 217. Sometimes it gets confused with the idea of episodic, but really it's just medical treatment of depression, treat as needed. So we'll see that from the 6-month data. And if we see stability of those patients and continued separation from the placebo, that will be a powerful signal. And we don't know it. Still -- we're still unblinding it. That would be a powerful signal that this drug could be successful as a monotherapy. And of course, we predict SHORELINE would give you good data as well.

And with SHORELINE, given the lack of a placebo arm here, how do we think about that? I guess are you just saying given 6-month durability, if you're seeing a change in impact over time to kind of put that together?

Well, remember, we have a large package of studies looking at depression, and some of the classic placebo-controlled studies. One of the questions has always been, why don't people do real-world studies? Why don't we do studies that reflect what the clinician and the patient experience. And that's what SHORELINE will do. And as you know, we enrolled up to 600 patients, not including the 50-milligram cohort. And this is the largest monotherapy study of its kind, initially that we think it's ever been conducted. So we think this will provide valuable information to clinicians about what happens to patients who get better, who will -- who they're treating with zuranolone. And we also think it will put to bed the idea that you automatically have to get on to another drug immediately. Some patients may have to do that. But we think this is the next step in showing that there should be another way to think about depression.

And Jeff, could you maybe just put this in context of your updated development plan and talk about these 3 pivotal studies and what you're hoping to learn from all of them? And how do you put that whole package together, as you said, to the market?

So yes, if you go back to the basic science, one of the reasons we're enthusiastic about zuranolone is there's only one drug in the world that's ever been approved with a similar mechanism, and that's ZULRESSO. So we're very -- and 217 is not an oral version of it, but has similar activities. We've seen from 2 studies, very robust activity and even in MOUNTAIN, very robust activity until day 15 where we narrowly missed significance. So with that, we're very comfortable based on the signs that we've established that this is an active molecule. It's also important to remember, and I know you know this, Salveen. I mean I worked on Lexapro, Luvox, some other antidepressants. I don't believe there's ever been an antidepressant approved that hasn't had at least one negative study, if not many. It's all about what you've learned and what you hope to achieve. And what do -- how you alter the next study ongoing. And so what we've learned from this drug is that we know it has very -- we have a lot of data, and this gets to how we design the development program. We've seen very robust data with postpartum depression. We've seen very robust data with rapid separation of placebo within the earliest measurements of time points. We've seen good tolerability and good drug-drug interaction in combination or with antidepressants and no evidence of rebound or rapid relapse. So that really guided how we think this drug could enter the marketplace from one of that have worked. And the agency has given us 3 independent pathways with which to accomplish it, with all requiring only one more acute study. And so our thinking was, postpartum depression, clear data. One more study, no follow-up required. And I'll talk about rapid response in a minute. And for the acute depression study, episodic, well, treat as needed over time, only one more acute study. So that's waterfall. These are independent. And then the third is the one that for some reason is brand new, and I know that it sort of doesn't fit into any of the new models, or current models. But it's this rapid response therapy. And we apologize at the sell-side and the buy-side because it's a completely novel concept, but that's the price you pay. The agency and -- there are no drugs approved for enhancing the rapidity of onset for depression. No drug has a claim for rapid onset. You see a lot of comments in the press, but there's no one, I believe, with a label claim for that. Everyone who's treated depressed patients, as I have, knows the major issue is it takes weeks to months, if not months, to get better, while you're experiencing side effects. People sometimes say, we use Cylert, Thyroid, well between other drugs. None of those have been shown to enhance efficacy, except maybe in resistant populations, and none have certainly increased rapidity of onset to fill that treatment gap. And so when we looked at our data and then we went over the FDA guidance, which is really designed to fill that gap of how do you get people better quickly, we realized after discussion with the agency that zuranolone had a profile that may be unique in being able to fill that gap of getting people or jump-starting the therapeutic effect. And what zuranolone offers potentially is -- and what we've seen is rapid onset, and we've seen that in all our studies, also no evidence of rebound or withdrawal effects after the drug is stopped and good safety in combination with SSRIs because we always have that. So we think it makes it unique, and so based on the totality of our data, the agency gave us a pathway for approval for this RRT or jump-start depression, they have a fancier name for it, with only one additional study. And if you think about how that might fit into the armamentarium, it would be very different than what it would be as a so-called first-line because this, in theory, could be every line. Because if you think about this, every patient who gets depressed, would like to get better more quickly. What RRT does? It firstly introduces physicians to a new concept and this new mechanism and it paves the way we think for this drug to become a monotherapy. The last thing it will do is we think we'll leverage the findings we think we're going to get on SHORELINE and on the 6-month data, we hope, which is if a lot of people who get better may not require further therapy for months, if ever, for the cycle. So we think RRT is a great stepping stone for this drug to be a first-line mono-therapeutic agent, but also could be a real benefit for physicians, who don't want to give up using SSRIs prophylactic.

And remind us of the changes that you made apart from just the dose itself, but one other amendments.

Most of our studies are pretty tightly run, which is why we were able to analyze SHORELINE so -- MOUNTAIN so quickly. But the major learnings we had, I think, were, one, the variability -- this is a lipophilic molecule. There was some variability on food effect. So that's an easy instruction. It turns out something like 20 grams of fat, which is like a slice of pizza, a twinkie, which, in fact, and happily I eat too many of, ice cream, you just take the drug with a fatty meal or a normal meal, and that ought to take care of that issue. But the one thing that the food effect is, and I think this is where people have often gotten confused, you're really concerned -- the biggest concern about food effect is when you have dumping, where food actually causes a rise to an unsafe level. That's not the issue we face. We're not seeing a safety issue because of this. We simply have an issue, we'd like to have greater -- less variability in terms of exposure. Increasing the dose will help that obviously. And we have a pretty -- we have a lot of population PK data and dose exposure data that suggests that 50 is the right dose to test. We've given that to the agency. We obviously have a good margin. So we're very comfortable about 50 being the right one. We did also -- we are going to go up to a higher Hamilton scale of 24. We think there's less heterogeneity. And of course, that's why a lot of companies go to treatment-resistant depression because a lot of -- there's always a belief the more severe you are, the more likely you are to have a true depression. We think 24 in all of our studies has been useful as cut-off, so we will be increasing the Hamilton cut-off to 24. We have some other maneuvers we're going to be doing, which we're not going to disclose because it will spoil them. But we think based on our analysis of MOUNTAIN, we have a -- we think we have a good handle on what we want to do moving forward with the rest of these studies.

And how do you assess the patients who aren't taking drug? I mean I know that wasn't a major part of what happened, but how do you prevent that going forward? Is there a way to -- I don't know, measure their blood levels early on? And...

We didn't really have noncompliant. What we saw was not unusual for any psych study. And we did have -- we had diaries and other maneuvers that we used. They were very effective, which is how we knew so quickly about it, but you don't typically monitor real-time because you really -- you have to mimic what goes on in the world. You don't want to have this in the label. It was only a few patients. And really, what that was meant to demonstrate was how close we were for activity. And also, if you think about what that does for the dose exposure curves, when you remove the non -- the people who didn't take drug, and we know that this is an assay sensitive to the nanogram level, you simply shift the exposure curve a little bit to the right, and you get a positive study. That's -- unhappily, that's too bad for us. But it wasn't a big problem. It wasn't any different than any of our other studies. It just turned out with MOUNTAIN, there were enough factors at play that each of those little -- each of these things were like a straw that broke the camel's back, as it were. But we do have a lot of -- we have diaries and other maneuvers that we do to assure compliance.

And then can you talk about your filing strategy here with these 3 pivotal trials? You have multiple shots on goal now? And so how are you thinking about this playing out?

Well, right now, they're moving along very, very well. And I think it's going to depend on sequencing and how they -- frankly, how they enroll and what the timing is. We've done a lot of the work already in preparation for filing CMC and things of that nature. So a lot of that is done. So a lot of it will depend on how these come up in sequence. And this is a classic development, tactical decision, which is if RRT comes in 2 months ahead of postpartum, you might combine it. If it's 6 months, you'd probably do separate filings. And that's really -- that's probably how we think about it. And then determining on what SHORELINE looks like, how much safety we need, that would also help determine what the speed is of -- and 302, we have to go back to that, what we do with the so-called episodic or as needed long-term therapy. So we're not really -- the good news is we're not constrained by any one study. They don't all have to finish. Each one can be -- stand on its own as a unique NDA.

And I just want to confirm that we would be looking at data from all 3 studies likely next year.

Yes. Next year, yes. Those are on track. And we haven't -- just in an abundance of caution and as has always been our practice until we see the enrollment curve. We typically try not to narrow it down. And even though things are going very well and in some sense, maybe ahead of schedule, no one knows what the world is going to be like in another 3 months. So I think it's probably not prudent yet to project anything. But none of us even know we're going back to work yet. So I think it's a little -- not prudent yet to try to narrow those -- that time line down.

We're working right now.

Actually, it's funny, the company at Sage -- people at Sage done great working remotely. And if anything, I think we're working more intensely by Zoom, than -- usually, you can hire in your office, I can always stop my video and then people wonder what I'm doing. So it's gone very well, so.

Great. And then for the RRT trial, what was the clinical barbi that you want to achieve when you add sertraline around, I'm going to say, 217 on top of that, is that a fair antidepressant?

I'd say 217 also, just so you know. We've seen data. Now we have a lot of data in coadministration, which we have in a lot of it. We haven't made public. We believe that in a head to head -- we think the way this is going to be used and the way the agency will ask for it will be for people who want to start with their antidepressant wired up-tapering it per the label, can you get these people better more rapidly. So the design will be coadministration with a placebo-controlled for zuranolone versus people -- versus both arms getting open-label, probably sertraline. And we think if we look at the mechanics and the dynamics of what we've shown in all of our studies, we think that within 2 weeks, our hope and projections are that we should be able to show significance versus sertraline alone at 2 weeks. The -- and that's really all we -- that would be the endpoint and fall out to 42 days. The interesting additional win could be, and we know this, if the data are replicated, like they have in prior studies, does this drug actually enhance effect. And that would be of interest to psychiatrists, we believe. Because if you remember, most antidepressants are better prophylactically than they are acutely. So if you actually have a bigger effect with zuranolone, there's a possibility, hypothetically, we could demonstrate capturing that effect with longer-term prophylaxis. That will be an upside win, rapid action with enhancement. But the regulatory requirement as we've had the discussions will be the endpoint at 2 weeks, showing separation -- significant separation from active therapy.

And then the REDWOOD trial, which we haven't talked about, but that's one that you were looking at for episodic treatment here. So what's playing out with that study? I want to maybe understand that profile.

We're still keeping that on hold. A lot of it is going to depend on design and what we're seeing on SHORELINE and the 6-month data. Because remember, REDWOOD is designed to replicate what maximum use might be if someone were just using this to prevent relapse, and we don't really know what that looks like. That's what SHORELINE was designed to do. And you can imagine where REDWOOD was designed every 2 months, what if we see the bulk of the patients only require retreatment every 6 months or never. So that will help fine-tune what REDWOOD might look like.

And then any updated thoughts here on pricing for 217, given the 3 new indications kind of represent different patient populations?

I think it's probably premature to understand this. I mean I think they're very distinct populations. And I know from talking to a lot of folks, people are still trying to get their arms around what RRT might mean, when you think about any potential patient with depression might qualify for that, how do you -- which is not a bad problem. I think it's fair to say we price for value on this and take that approach at this point.

So moving to ZULRESSO and that launch, could you maybe talk about the impact here that you're seeing from the COVID-19 pandemic and what that means to the launch trajectory at least for now?

Well, with ZULRESSO, in particular, I think the launch trajectory is, as we said, it's going to probably remain flat. We do have sites that are open and treating, but the hospital-based treatments really have been significantly impacted. I think that's what I'd probably just leave it at that. It's -- people are still leery about coming in for lots of therapies. We are treating patients, but clearly not as much as we would have liked.

Okay. And then just moving to the portfolio because that's clearly kind of the next leg of growth, and we're going to see some data sets from these programs. Can you walk us through 324 and 781 -- or 718 and how they differ in mechanism versus the rest of the portfolio and really 217 here?

Well, 217 was designed to look like -- biologically, very much like ZULRESSO because we have the science that's shown that, that's an active mechanism in mood disorders. 324 was designed differently. This was designed to have a longer half-life. It's up to 40 hours in humans to be once-daily therapy, to be used chronically for conditions where we think chronic pharmacotherapy would be required. And the data we've seen suggests it's less sedative. The interest for that is if we've shown -- the decision to go into essential tremor was driven by the fact that for each of these other predecessor molecules, we've shown activity against tremor, and if you -- and very consistently across the patient cohorts. And obviously, we've done that double-blind with ZULRESSO, and we have open-label data with 324, which we were doing and 217. The thinking here is if you look at conventional therapies today, there hasn't been anything really approved for decade for essential tremor. And if people do stay on the standard of care, which is they're often not well tolerated, it's either Inderal or sometimes barbiturates, you're really tiding only about a 30% reduction in tremor. It's really not terribly satisfactory. It's the most common movement disorder, and so -- and there's no really good therapy. We've shown pretty consistent data with this mechanism that we can reduce more than 50% at times with only short dosage, not even from the longer dosage. So we think there's a high probability of success. It's been derisked as much as one can in humans. And so we think that's a unique opportunity for us. That study is, I think, still is in screening and is also moving along very well. And we think that this is -- this will give it a really unique position as a unique pharmacotherapy. And so we'll see. It's a 4-week study. So it's a much longer-term study. And as I say, that should be reading out next year sometime.

And what -- how do we think about the clinical bar there as to what's meaningful?

That's a really good question. I mean you think about this, there haven't been very many successful therapies for this. We believe that 50% that we've seen, anecdotally, the patients were very pleased with it. What we will do is not only look at physical measurements of tremor and probably using a TETRAS, which is the standard scale, but also look at patient-rated outcomes. We'll look at some quality-of-life outcomes to ascertain the value that this reduction in tremor will provide patients. This is one of those situations where the things that -- if you talk to patients with tremor, what really concerned them are often not intuitive, like unable to pick up a glass of water without spilling or women being unable to put their makeup on. Things like that. If you can enhance that, you can really enhance people's quality of life. So we'll be looking at that as well. But we think the standard of care today is 30%. We're optimistic we can certainly surpass that.

Got it. And then you have 718 here where you're looking at Huntington's disease. Could you explain just how the drug's mechanism is particularly suited to Huntington's here?

So 718 is an NMDA-positive allosteric modulator, and we believe it's the most advanced anywhere in the clinic, and if not the only one today. People are following it now. When we started this, we looked at this as a way of enhancing syndromes where you have NMDA deficits, where you have lower levels of the biomarkers 25-hydroxycholesterol. And we thought this would give us a biomarker for activity. But what we found -- remember that we tested this in normals. And what we found there was where these are normal, we've found there pretty consistent elevation and improvement in executive function in a way that was distinct from amphetamine. So it wasn't simply attention. Now there's an analogy to amphetamine that I'll use in a minute. But it had its unique mechanism. People weren't getting enhanced attention, they had better executive function and decision-making and things of that nature. So that was an unusual funding because it's a normal. We went to Huntington's because we know Huntington's have an NMDA deficit. And that was a biomarker approach, basically, in a population we thought had a physiologic vulnerability that 718 could correct. And you saw in the Huntington's data, again, pretty robust improvement in open-label, in executive function, which we think is unique. So now as we looked at it, we saw this drug having an effect in patients with pathology and in normals. And the analysis -- analogy is like when we were -- when I was at Shire, we worked on Vyvanse. And if you give people -- normals Vyvanse, it enhances attention, it also enhances attention to people with ADHD. Regardless of whether you have a dopaminergic deficiency or not in theory. And so that's what we're trying to determine now with 718. Is it this only targeted for people with NMDA deficiencies where the biomarker is active, or might it be also useful in other cognitive states? So we're going to -- and since no one's ever developed a drug with an executive claim -- executive function claim, we think it's incumbent on us to understand what this mechanism looks like across indications because it's unique. And we are going to -- next go into dementia associated with Parkinson's, where we also think that there's low NMDA function. But we'll also then probably go into mild Alzheimer's or some other mild dementia. Because if this is a generalized activity, if we can see a large effect, similar to what we've seen with the Huntington's and in the normals, this may be an important drug that -- with a unique mechanism of action. So that's the data -- those are the data that we'll be developing this year and next year.

And what has it taken so long for NMDAs to move into the clinic? Yours is the most advanced. You've known about this mechanism for a while now.

It's fair -- science is sort of interesting. And firstly, these are tough -- this is a tough area to explore because the safety margins are tight. And if you think about GABAergic agents, your toxicity is usually exaggerated pharmacology, sedation and things of that nature. With these drugs, you do have hyperexcitability, and that's a little -- that's a little more concerning. And so we're a little more cautious about how they need -- and everyone has been cautious with how they've been using. And people have not been able to get around that issue of toxicity and margin. And that's one of the things that's given us a head start in this area. And that's what -- in 904, we think may have a better margin and they have slightly different. That's our earlier molecule. But 718 has performed very well. And we think that's the -- we think our unique chemistry also, in fact, it's modeled against an internal molecule. Remember, the basic nucleus, it looks like a natural molecule in the brain. So that gives us, we think, good -- a head start on structure and activity design. And we actually have a great group of chemists. So I mean the one thing that people -- when we started the company, we used to talk about this a lot. We have tremendous chemical equity in the company. We've made 10 -- thousands of compounds, and we've been able to select in a way that I think many people have not been able to, looking at a compound like 718, based on an exposure-response curve, that we think could be unique in the industry. So we're very excited by it. It's early, but we think it could be very unique.

And so for 718, would it be kind of this cognitive dysfunction data that you're looking at under Huntington's that reads out next year, that really tells you what you're going to want to do with this asset?

Exactly. Because imagine, this is not to diminish this, but when you have a drug like an amphetamine, it's very hard to get a negative study. They're very potent. And one of the things you want to look with -- and I filed , I explore, I've worked on Namenda, different kind of drug. So the hope is 718 effect is that profound. And if it does, then we need to understand what the impact is on the individual physiology of each indication and where patients might benefit most from it. But it's a unique tool right now. And it's something that we have, I think -- it's so different that people have -- people haven't thought about it, but it's a good reflection of the basic science, where people have always understood that enhanced NMDA tone might enhance cognition, but no one's been able to get at it until now. So we think, as I say, it may provide a unique opportunity. And we'll see in the upcoming studies, what kind of benefits we get for cognition in this assorted group of disorders.

And Jeff, as you mentioned, you have been working, I guess, the team has been working on a slew of different chemical-based compounds, and so when you look within your pipeline, is there anything else you want to highlight that's inclusive?

We have a very robust early discovery group. And I guess what I'll say is we probably haven't disclosed a lot of what we're doing yet, mostly because I think fairly, currently, doesn't get value. But I think if you look at what the science of the company has done, we've already established 3 -- 4 clinical pathways that are unique. With new chemical matter in 3 of them. And I think we can continue to do that based on our early discovery group and our translational group. They've been very good. And so right now, our focus is on execution and really getting back to where we were as a company, frankly, with this very large pipeline, tremendous chemical equity, almost $1 billion in cash. And I know no CEO has ever said this, very undervalued for what we have and the catalyst we have upcoming over the next 1.5 years.

Maybe a final question here. So when you look across the competitive landscape or new modalities that are kind of entering the space and these indications that you're in, anything that you think seems disruptive in terms of what you're working on or could change or have impact on how you're planning your trial designs today?

I mean that's a really good question. I think the -- let me say it this way. I think every area we were playing in or studying are areas of such significant unmet medical need that when I put my doctor hat on, like the more the merrier, if we can get more -- it's like how many COVID vaccines do we want, as many as we can get. With that being said, I think that right now in the areas that we are pursuing, we have a great leadership role. I think our chemical equity is unique. And I think that -- we know we have imitators now which is, okay. But I think we're well ahead of the pack. And if you think of what -- if you just go back and look at what we offer just from a standard, a commercial viewpoint, 217, I don't think there's anything like it, if we're successful. 324, open field running. 718, really nothing even -- I don't think on the horizon that we know about. People are talking about it, but we're gratified that people have gotten excited about CNS. I know you've been with us long enough to remember when everyone thought we were nuts. But -- so I think there are competitors. There are people imitating us. I think people are looking at depression with different molecules. I think the one thing that distinguishes Sage is that these are all homegrown, internally Sage developed, new chemical matter with composition of matter, of patents, and I think that really puts us in a tremendous leadership position in the CNS space.

Well, with that, thank you so much, Jeff, really appreciate you joining us today.

Thank you. And thanks, everyone, who's listening. Stay healthy, everybody.

Bye. Thank you.

Thanks. Thank you.