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

Thanks for joining us again at the Bank of America Healthcare Conference. I'm Tazeen Ahmad. I'm one of the senior med biotech analyst here at the bank. It's my pleasure to have our next presenting company, Sage Therapeutics. Up on stage with me are several members from the management team. Those include Chris Benecchi, who's, of course, Chief Business Officer; Kimi Iguchi, who is Chief Financial Officer; and Mike Quirk, who's Chief Science Officer. Hi, everybody. Thanks for making the trip out west.

Thanks for having us.

So let's start off with an overview of the company and maybe Kimi, you can do the honors and talk about the platform and some of the recent events that have occurred, and then we can go into more specifics.

Sure. Thanks, Tazeen, and thanks for having us here to the conference. We really appreciate it. Looking forward to the discussion. So for those of you who aren't familiar with Sage, Sage is a company that's been focused in the area of brain health. And we've made a tremendous amount of progress by really focusing on the NMDA and GABA platforms. And from that have been able to create a very differentiated pipeline that hopefully we'll talk a lot about today. We also have a very exciting Zurzuvae, which is our first oral product for PPD. So this is for women with postpartum depression. So we have the launch that's off to a great start, very strong start that I know Chris will elaborate on a bit as well. And so beyond Zurzuvae, we have a very vast pipeline and a lot happening this year in 2024. And so we have our NMDA program dalzanemdor, which has multiple data readouts throughout the year. And also SAGE-324 program in essential tremor that we'll read out as well. So a lot going on in the pipeline and a lot to talk about in 2024. And we do that, and I'm happy to say, with a very strong financial foundation. We have a strong balance sheet that will allow us to go through all of these milestones that we're talking about. And so we're looking forward and making a lot of progress and looking forward to continuing to update everybody on the progress we're making on -- seeing our vision of creating a better brain health.

Okay. Thanks for that overview. So maybe on the topic of Zurzuvae, also known as zuranolone. You guys are off to a strong start, as you mentioned, to the launch, you came in above expectations for the quarter. Maybe, Chris, can you talk in general about the dynamics of what you've been seeing -- you and your partner have been seeing as the launch is kind of coming out of the gates?

Yes. As Kimi noticed, we are off to a strong start, both in terms of the revenue as noted as well as demand. We reported on the first quarter earnings call that we had more than 1,200 prescriptions, more than 700 shipments, and that represents prescriptions actually going to the specialty pharmacy with product ultimately getting into the hands of women that are living with PPD, which is a great thing. And there are many more women out there who we know that we need to reach. Our ambition with this product is to be a first-line therapy with the potential of becoming standard of care. So there is more in front of us as we go forward. I think with that being said, as you think about the bear thesis that we faced as we got ready to launch this product. What we heard was that OB/GYNs would not write this product. We heard that payers wouldn't pay for the medication, then in effect, would step us through a generic SSRI. And lastly, there was some question about would the products in market real-world experience reflect what we saw in the ROBIN and SKYLARK study in line with the label for the product in terms of efficacy and safety. So when you ask about what the recipe for success is, it largely is, again, first, have we been able to motivate OB/GYNs to prescribe the medication? And I think what we talked about during the first quarter earnings call is that OB/GYNs reflect the largest percentage of prescribers here. They're really leaning in and treating women with postpartum depression. In terms of the second component, that is the market access ecosystem and what's actually happening. We're very pleased to see the progress that we've made there. First with commercial coverage, 2 of 3 PBMs are online. We continue to work on the third reflective of the 2 to 3 p.m. Subsequently, there are national plans as well as regional plans that have come online with coverage for Zurzuvae. And its coverage in a first-line position without onerous prior authorizations and step edits, which means moms don't have to step through, women with PPD don't have to step through a generic SSRI in order to get this medication. 65% of commercially insured patients are covered or under contract in that way. Medicaid, we have nearly half of the Medicaid states already online. So the coverage that we've seen so far has really been in terms of our expectations of what we would see a bit ahead of the game, which is great. And again, it's helping women. And lastly, but certainly not least, the product is performing in market with respect to the efficacy and the safety profile in the hands of a very competent and experienced neuropsych account management team that are active and engaged with clinicians on a regular basis. And that effort is really supported by nonpersonal promotion. So again, when you talk about the formula for success, depth and breadth of prescribing with OBGNs leading the way, access and reimbursement with Zurzuvae in a first-line position with the potential to ultimately become standard of care and subsequently making sure the medication continues to get pulled through the efficacy and safety profile that we have. And we believe that's the recipe that we'll carry us forward.

Okay. So you've said a lot and maybe let's dig in a little bit into some of those things. So as you said, initially, it seems that the presumption was that OB/GYNs would not be leaders in prescribing, but they have turned out to be at least in the early stages. Why do you think that is?

Well, OB/GYNs are on the front line of care. They're the clinician that sees a women with PPD or that has the potential to experience the signs of the PPD up and through birth and then shortly thereafter. I think that, that plays an important role in all of this. There are approximately 1 in 8 Libresse, 500,000 or so women that express the signs and symptoms of PPD, fewer than half are diagnosed and fewer than half of those are traded, which just isn't acceptable, right? We have to do a better job reaching women that are suffering with PPD. As I said, OB/GYNs are really on the front lines of care. And as we've learned, Zurzuvae has the potential to be the real catalyst for change, not only with respect to treatment but also in terms of screening and diagnosis. And we've seen OB/GYNs already embrace that. And when you take a step back and you think about historically what may have happened in an OB/GYN practice in the absence of an approved therapy, an orally approved therapy for the treatment of PPD. It has been suspect detect and refer. Now we're seeing screen diagnose and treat. And with the ACOG guidelines in place that really support from an OB/GYN perspective, that they should be screening and diagnosing and they also have practice guidelines around zuranolone or Zurzuvae right now. Again, they're going to be on the forefront of care for so many women, which is really exciting.

Okay. Does your sales force or yours -- and Biogen sales force detail OB/GYNs differently than the detail psychiatrists.

So I think they understand that there are difference in practice patterns within a psychiatry practice and an OB/GYN practice. They deliver the same messaging in terms of efficacy and safety, but they understand that there is a distinctness in terms of the way that physicians practice in those individual settings and they're dynamic in the way that they approach us as well as in primary care. We are seeing a handful of prescriptions coming through primary care as well. We have gone out and expressly identified neuropsych account managers who have background and experience, not only in launching medications like Zurzuvae, but who have established relationships in OB/GYN practices and in psychiatry practices where they are recognized already as highly credible experienced voices that clinicians look upon and trust. And we've really been able to leverage that to establish not only relationships. But to be successful in the way that we've launched the Zurzuvae.

Okay. And so on a go-forward basis, do you think you need to make any tweaks to how you're marketing just based on like the early adopters, do you want to devote more time to OB/GYNs or is it kind of you've already made the plan and you're just going to see how it goes.

Well, the plans are always dynamic. I think you always continue to refine and adjust based on what you learn in the specific moment. I think that in terms of the sales force effort, we'll continue to refine the way in which we identify targets and we call on targets. We're also going to continue to invest moving forward in nonpersonal promotion. What we've learned is that nonpersonal promotion in effect digital marketing efforts, things like banner ads and search engine optimization, elements like that can be particularly affected in reaching physicians that we call on as well as physicians that we don't call on. And that's going to be really important as we go forward as well as peer-to-peer education. We want to make sure that not only are we effective with the sales force that we have, but the surround sound is really strong in our efforts to promote the product. And in addition to that, what I would say is there's an opportunity here for us to really educate women that are living with PPD to have informed discussions with their clinicians. That's an important piece of this as we go forward.

And how important is DTC in educating women about the signs and symptoms? Maybe I'm mistaken, but it does seem like something that women are in general aware of, but do you think that it would be helpful to have more direct advertising?

So direct-to-consumer advertising plays a role for sure in terms of the completeness of the surround sound that you can provide to not only educate women that are living with PPD and their families. But again, you have to remember that physicians or consumers as well. They see it as well. I think in terms of the effort of DTC, it fits in and amongst at the right time nonpersonal promotion. The first step, obviously, is to go out and make sure that your clinician audience is very well educated and prepared for anything that you do from a consumer perspective and then at the right time to take that investment and be smart with how you deploy it. And what I'm talking about when I say smart is making sure that you use things like connected TV, they are very efficient and effective in their ability to reach consumers as they're consuming that content and enabling them to have really informed discussions going forward. So it plays a role at the right time.

And what percent of women start to display symptoms of PPD before birth?

Yes. Yes. Well, I mean I think there's a couple of different ways that you can look at it, right? So we do know that a history of major depression is a major risk factor for it. So clearly, there will be patients that have already had history of either anxiety or depression, they may already be under the care of a psychiatrist, and that's part of sort of the patient journey from that perspective. And so there, there's already that awareness that's raised from that. And I think it's what it's like 50% if you have a history from that perspective. And then there will be women that will be showing de novo during the third trimester as well in that perspective.

So in terms of the data that we're seeing interestingly right now, one of the things that's of note is that nearly half of the women that are in the Zurzuvae pool have not had an antidepressant in the previous 12 months, the preceding 12 months leading up to that diagnosis and treatment, which tells us that the patients that we're already seeing, a number of them are monotherapy patients. There are also others that are out there that are adjunctive therapy patients that receives Zurzuvae with maybe another medication. One of the things that we think about is that not only is it important to have monotherapy use, but in the right circumstances when a clinician wants to use both medications, the medication is available for that adjunctive use.

Okay. The reason I ask is I'm just curious as to whether the strong start that you've seen can be enhanced by trying to maybe in a sense, 5 women who could become at risk when delivering the baby of showing prominent science for example, postpartum depression?

So the thing that I talked about just a couple of minutes ago was Zurzuvae being the catalyst for a positive change in the -- not just the treatment of women with PPD. But screening and diagnosis is really paramount there. Oftentimes, it takes a medication -- an FDA-approved medication for the change in medical practice to happen. And I think that's some of what we're seeing here is that now that there is an oral FDA-approved medication screening and diagnosis is going to increase. What that means is that clinicians will not necessarily wait until the baby is born to begin to identify mothers that are at risk that, that will happen. I think, as you know, far in advance based on prior history or perhaps the way that they're already expressing the signs and symptoms of PPD leading up to the last trimester and then subsequently afterward.

Okay. And I think you said this in your intro, but you've got good coverage with private payers and then also seemingly so with government. So is the status of what type of insurance a woman has indicative of any -- like the level of pushback she might get in getting the drug?

So what we've said is that we've been highly encouraged by the coverage that we've gotten so far, both commercial and Medicaid coverage. It really has been remarkable. That's in part due to the fact that we've been talking to many of these payers now for several years, talking about the unmet need at a plan level and the implications that it can have on a mother and her family when PPD goes untreated. We've also been able to relay the data leading up and through launch. And this is a medication that really demonstrates that with just a 14-day course, it can have a profound impact on a woman that's living with PPD. I think that's really an important piece of all of this. I think in terms of how coverage has come online, we've always said that we want to make sure that we're not only accessible, but we're also affordable. That means that when we think about coverage, it is both commercial coverage and Medicaid coverage as well. I think the approach that we've taken has enabled us to really have the kind of success that we've had so far with 65% of the commercial. That's already under contract without an onerous [ PN step ] so the mom can use this, women with PPD can receive this medication in a first-line position and why we see nearly half of the Medicaid states already moved to making decisions -- formulary decisions that enable a woman with Medicaid to access the product. With respect to the affordability piece of it, what's really important to note is that for a patient that is commercially insured, what we're seeing is that for those that opt into the co-pay assistance programs, Zurzuvae For You, they're paying a $0 co-pay. And for a woman that has Medicaid coverage, she's paying $0 or a low single-digit dollar co-pay, so that the medication is now both affordable and accessible for so many of those women regardless of coverage type.

And then how important is it that the new mom receive access to the drug as soon as possible?

So when you are a woman that expresses the signs and symptoms of PPD you're in a crisis, you need medication, you need the support of your clinician and you need medication. We want to make sure that the medication gets to that woman as rapidly as possible within days, if possible. So everything that we're doing right now around the engineering of the system, the SP, getting the medication to the mom is with the goal of having it in the hands of that woman with PPD within days, and that's what we're really focused on.

Okay. Is there room for improvement on that based on what you're seeing so far?

So there are some moms that are able to -- women with PPD that were able to get the medication within days. The other that's taking a bit longer is coverage has taken a little bit of time to unfold. What we want to make sure of is that from a physician education perspective that they understand that when a payer may need more information, the urgency of doing that because of the impact that it has on the medication Zurzuvae getting to the one with PPD as rapidly as possible. Also making sure that patients know when a 1-800 number calls to validate your mailing information, you have to pick up the phone. So much of this is about education and making sure that the engineering of the system is working and working well. So that's squarely where we're spending a lot of time is making sure that whether you're a physician or a patient, you understand what to expect and the medication you can get there as rapidly as possible.

Okay. And then maybe one more question on this. We'll move to pipeline a little bit more is in terms of how you're thinking about what proportion of sales every quarter is going to be comprised of some level of inventory, how should we be thinking about that? Maybe it's a question for Kimi.

Yes. Great question, and we've gotten that question quite a bit. And I think what we talked about in the first quarter, it was that our revenue in the first quarter was made up of a combination of shipping to wholesalers to deliver units to patients, but also a level of stocking by those wholesalers. And that's really based on them seeing the increasing level of demand. So they're seeing the prescriptions and so they're trying to prepare for that. I will say that these wholesalers that -- this is their business, our specialty pharmacy distribution network is -- goes to a wholesaler and then a handful of specialty pharmacies. So it's somewhat of a contained system. I think that as we learn more and see the demand grow and inventory levels, we'll be able to provide a little bit more color going forward.

Okay. So as this launch progresses and volume increases, we should be able to get more color from the company on, let's say, what percent might be inventory.

Yes -- over time, yes.

Okay. Got it. Okay. So now let's move on to pipeline, 718 in particular. You've got a couple of readouts this year remaining wanted to talk about confidence level for each of those. Maybe let's start off with Huntington. And maybe if you could talk about the rationale of why you think the Huntington would be amenable to this particular treatment and what would be good data.

Yes. So thank you. So just to set context, SAGE-718 or dalzanemdor is our wholly owned NMDA receptor positive allosteric modulator and it's being developed for the treatment of cognitive impairment across a range of neurodegenerative conditions. And so when we think about the confidence in the rationale, it's important maybe to start from the 50 years of research that really has implicated the NMDA receptor as being one of the most critical proteins involved in neural circuits across a range of cognitive domains. Historically, people use to focus on learning in memory over the last 10 years, it's been a lot more focused, the role that NMDA receptors play in high order cognitive functions such as working memory, multitasking, et cetera. So we know that the receptor itself is critical in these brain networks. And we also have quite a bit of evidence to suggest across different disorders of cognition, there are pathophysiologies that cause disruption of the NMDA receptor. Now those pathophysiologies can be very distinct, whether it's amyloid and tau interacting with the protein in the context of Alzheimer's or in the context of Huntington's disease, where we have specifically identified that there is an endogenous modulator NMDA receptor function, 24s-hydroxycholesterol which has actually decreased in the brains of Huntington's patients, specifically early in the disease course when they're showing primarily cognitive deficits. We often think of Huntington's disease as a motor disorder. But in fact, cognitive impairment is clearly seen by patients, the families or caregivers as one of the unmet medical needs in this space. And so when we set up 718 program, we really focused in on the breadth of opportunity, but also how do we look at different indications. So asking about Huntington's disease. Because we had this rationale or retired to the endogenous modulator because Huntington's is an orphan disease where there are no approved treatments for cognitive change, and because of the substantial unmet medical need, we really have defined that as a lead indication for the program. And so thinking about the program that we wanted to design, there are several elements to that. So we have 3 studies, 2 of which will read out this year. The first study that we'll read out middle of this year is the surveyor study. And then later through Q3, Q4, we expect to see data from the DIMENSION study. And focusing on the DIMENSION study first, dimension is that true well-powered, placebo-controlled study, where we're looking at approximately 178 patients randomized to either placebo or drug, they're dosed for up to 3 months. And we're using as an endpoint, the HD-CAB, was it's a composite cognitive endpoint, it has several tests of cognition embedded within the composite. And it was designed by the leaders in the field, the Huntington's field to tap into those domains of cognition most impactful in that patient population. And that's really what is designed to be that robust placebo-controlled data set. The surveyor study, which read out middle of this year, which would be Q2, Q3, is designed to provide context or interpretability around that study. So it consists of 3 groups. A healthy volunteer group that is not receiving drug or placebo, but it is demographically matched to the patient population. And then a group of patients that are randomized to either drug or dalzanemdor. Now those patient groups are small. It's only about 20 patients. So it really is not powered to detect a placebo drug different. What we are looking for in the surveyor study is 2 things. One, do we see that the HD-CAB is sensitive between the patients and the healthy volunteers? And how big is the difference between those different groups. And that really allows us to understand the dynamic range and what improvement could look like. The other aspect is within the survey, we have a number of other endpoints, some that related to function, some not related to patient reported outcomes. And we're looking at trends in the data correlations between the endpoints that allow us to provide an understanding of the interpretability of the HD-CAB. So once we have the DIMENSION study later this year, we can go to various stakeholders, whether they are regulators, whether they are the physician community, whether they are ultimately payers and say, look, here's the change that we see in DIMENSION. And here's what this means for patients. We think combining these 2 together really gives us the most robust data package for subsequent conversations.

Would the SURVEYOR study be predictive of what to expect for DIMENSION?

Yes. So like I said, it really isn't designed to show that drug placebo-controlled difference. We are tending to look for more trends in the data. And that's how we will be approaching that readout.

Okay. And if everything goes well, what would be the next steps after that?

Well, again, we think that this is an orphan population, and we do understand that there is clearly, no approved therapies for cognition. There's a clear unmet medical need there. Data matters. And so if we had a robust data across both of those studies and really had the right data package, we would want to meet with the regulators and define the most efficient path to getting this drug to patients in a meaningful way. And that would be how we would look at the data going forward.

So do you think that this the 2 trials together could potentially be sufficient to...

I think we would at least would look at the data and want to make sure that we have the appropriate conversations at that time.

There is not much precedent, but do you think you'd have to do some sort of confirmatory study if this was allowed?

I think this is to be exactly the types of questions that we have with data in hand.

Okay. How many patients do you think would be eligible for your treatment would be the entire range of Huntington?

So we are looking in terms of how we have designed the study. We are looking for patients that are earlier in the disease trajectory, right? So these are patients that are in the late pre-manifest, early manifest kind of stage. They are defined by -- for the study as patients that have some degree of functional impairment, they have to have clear cognitive impairment, but they're not on the very severe end of the motor sort... And I think that would be the appropriate population to look for initially and how we think about providing this therapy to patients, how it would evolve over time, both in terms of clearly, there's genetic testing for Huntington's that you could imagine, but that would be how we would initially look at the patient group.

Is there any learnings from all the other companies that have tried and failed to develop drugs in Huntington that you think could help you?

Yes. So I think it's important to put in the context with most groups that have looked at Huntington's, you have the symptomatic motor ones, tetrabenazine type where you clearly see acting in the core. It's not really an active direct comparison. And then on the other extreme, you really have those drugs -- those companies that are looking for disease-modifying therapies. And again, we don't see that as a direct correlate here, right? With disease-modifying therapies, you tend to be running longer trials and looking at, can you see a change in the slope of deterioration. With dalzanemdor, what we're looking for is actually an improvement above their baseline. So we're not requiring there to be a decrease and then trying to detect a change from that. So it really isn't a one-to-one comparison to how we look at those other therapies that have been out there in clinical trials recently.

And then -- what has FDA told you so far about the trial design? And do you get a sense that they would be amenable that these endpoints are all positive to potentially allow an accelerated path?

Yes. I think what I can say is that through various engagements at the agency is not just with us but with the HD community, they clearly recognize that there is an unmet medical need in the space. They recognize that cognitive impairment has a direct impact on patients' quality of life. And I think they're looking for innovation and would be receptive to different approaches to bring forward that level of innovation that's needed by the community.

Okay. And then maybe let's talk about Alzheimer's and what you expect there?

Yes. So the other trial that we're expecting to read out from dalzanemdor this year is the LIGHTWAVE trial. This is also expected to be in late 2024. So again, that's Q3, Q4. The LIGHTWAVE trial, this is your classic Phase II signal finding study. So it is on the smaller side, but appropriate for a Phase II signal-finding study where we're using the waves for coding as the primary endpoint. The waves for coding is a test of executive function. It's similar to the single-digit modality test. It's very similar to where we saw some of the strongest signals from our open-label study in Alzheimer's, and it really is the placebo test of that earlier data. That having been said, we have additional endpoints in that study such that are maybe more typical of an Alzheimer's trial such as the R bands. And the goal of the study is really have that information coming out of that, that would allow us to make the appropriate assessment decision to go into the broader Phase III program. So with Alzheimer's, we think that this is going to be more of a classical get the Phase II data, look at the endpoints and have it in a Phase II meeting, design the Phase III trial and then make that appropriate investment going forward.

So Alzheimer's, fortunately for patients has become really crowded and there are a couple of options already available and potentially more not too far down the path. As you think about what kind of differentiation to be looking for, this is a small study, as you said. But ultimately, how would you think about designing a study that would really make it clear that -- because payers are being careful about how they're reimbursing? So important things to look for would be safety and cognitive improvement. How would you think about that?

Clearly, safety and clearly efficacy in the cognitive improvement. But I think the way we would look at it is, first, we're excited that there has been so much movement in the field. I think it's a boon for patients. But when you look at the context of where a lot of the drugs are moving forward, you tend to have, again, these disease-modifying therapies. And what we're learning is to one extent, there's no magic bullet, one therapy that treats everything. So you're probably going to be in a position where you're going to be looking at different combinations of therapy. The other issue is where you have these new disease-modifying that may slow the trajectory of the disease, that is the opportune time to complement that with a medicine such as dalzanemdor, that could potentially bring people above their baseline, right? So one of the challenges with the disease modifying. It's very hard for the patient to know whether or not they are progressing slower than they would have otherwise, right? They really don't see a sense of change. Our expectation for dalzanemdor if it works in the way we imagine is you will actually be able to detect that your cognition is improving from where you are. So you have that much more immediate feedback. And then you think about what the payer dynamics could be with a drug that has more of an immediate signal to detect. I think that allows for some options whether you talk about value-based agreements or other innovative ways to work within the payer dynamics.

Do you think that mechanistically your drug is more likely to work in one of these indications relative to the other? You did have a study readout for Parkinson's, which did not indicate that you would move forward. But if you think about the differences among Parkinson's, Huntington's, Alzheimer's, if you were to try to put a likelihood of success on the 3 of them before even knowing that the PD was not moving forward? What would you have said...

Yes. Going back when we designed the program, it really was looking at these as independent tests of the hypothesis. There is rationale for why NMDA receptors could be compromised across all 3 of those patient populations. That being said, the underlying pathology is different. The symptomatology is different. In the Parkinson's case, you have much more prominent motor potential compounds. You tend to have waxing and waning in on-off periods that may make it harder to detect change. So when we look at it, we really did look at them as different patient profiles, different pathophysiology such that no one trial had a direct read-through to the others, and that's why we're really excited through to see all the readouts as they come through this year.

Okay. Got it. With that, we are out of time. So I wanted to say thank you all for coming out West and seeing us in Las Vegas this morning. Thanks everybody who joined us in the room. I hope everybody enjoys the rest of the session, and thanks again.

Thank you. Thank you very much for having us. And it's going to be an exciting year for Sage with the launches of Zurzuvae, and with all these data readouts that might just want.

And we'll all be looking for the press releases every day.

Thank you.

Thank you.