Good afternoon, everyone. This is David Anselin from the Piper Sandler Biopharma team, and welcome to the 37th Annual Piper Sandler Healthcare Conference. So we have Supernus with us and lots to talk about. We have CEO Jack Khattar. Jack, delighted to have you here. And, well, I'll just go right into ONAPGO because I think everyone wants to hear about where things stand. We're all keenly interested in the supply constraints. So just walk us through, just as a refresher, the constraints the manufacturer started to experience related to the drug hardship product, and just give us an update if you can on how things are progressing regarding resolution.
Yeah. Thanks for having me, and good evening, good afternoon. Before I get started, just the forward-looking statements I'll be making through the session, so please check the SEC filings for the risk factors associated with the business. As far as ONAPGO is concerned, I mean, clearly we're working pretty diligently right now on different approaches trying to resolve the situation, first with the current supplier, what we can get from a capacity perspective so we can get and ramp up as much production as possible. And then in parallel, we're working on alternative options for us, including another supplier that already manufactures the same product for supply in Europe. So we're looking at that avenue clearly.
So we're looking at every angle, talking to the FDA about the shortage situation, see if there is any help they can offer also from that perspective, especially if you're looking at qualifying somebody else. Clearly, you need their help from that perspective. So right now, I still don't have specifics as far as bookends or worst case, best case, so to speak, as far as because I really want to have full confidence before we communicate something. I mean, the great thing so far is since we made the announcement, I mean, the reaction from the field has been phenomenal from the physicians, very supportive. They really respect the way we're handling the situation with full transparency, prioritizing their patients, all that. They really appreciate all that. And they're basically, "When you're ready, we're here to support you. This is a very different product than anything on the market.
We need it. There was a lot of need for something like this. So just let us know. So we certainly, if we go back to them, we want to make sure we have full certainty that this is it. The situation has been resolved as to when they can initiate new patients and get started on it.
Okay. So I have a few follow-up questions. So wanted to just make sure there's no confusion here. Just to be clear, the current manufacturer just was, I guess, and I'm paraphrasing here, but overwhelmed by the demand and essentially couldn't meet demand, but it wasn't an issue with, say, problems making the cartridge or API sourcing or anything that's related to actually sourcing of the product or making the cartridges, just simply not being able to meet demand. Is that right?
Yeah. I mean, this is not an issue of API or any specific component, or it's not an issue where FDA walked into a facility and shut it down and they can't produce. No. This is more really of a capacity issue. And it's more like a perfect storm, unfortunately, where this is a production line that is shared. It's not fully dedicated to us, and they have clearly other clients who have their own demands, their own requirements. We don't have full transparency about these requirements and the shift on these requirements. So that's what's making it a little bit more difficult for us. And in a way, it's not our direct supplier. It's also the supplier of our partner. So it gets it a little bit complex, not to get into all the weeds, but that's really the situation that got us into.
If you were to bring on another manufacturer, how long do you think that onboarding process would take?
I mean, typically, this is generally speaking. Typically, I mean, these things will take time. It's not something you can flip overnight. Clearly, it will take several months. It could take up to a year, normally, depending on how ready the supplier is. Are they FDA approved? Is it exactly the same product? Is it the same equipment? All that. Now, in this scenario, it's exactly the same product that is being produced as we speak for Europe, for the European market, but it's being produced according to European specs, not U.S. specs. So I mean, there are details that we'll have to work out, paperwork that has to be done, the package that has to be put together to be filed. FDA will have to review it and see how quickly they can do that, how quickly they can inspect the facility, all that.
So I mean, that will take time. But that's why I don't have the full clarity yet on all these details to communicate any specific timeline as to when something like this could come online.
So it sounds like if I'm hearing you correctly, it sounds like the better scenario would be for your existing manufacturing partner to dedicate more capacity to ONAPGO. But it's not yet clear if that can happen. But it also sounds like whatever happens with your existing partner, it would probably behoove you to bring on a backup supplier.
I mean.
Over time, that makes sense.
Long-term, we need another supplier. Given the potential of this product and the demand that we've seen, we need a long-term supplier, and the supplier will have very good capacity to be able to help us, so from that perspective, we're working on not just a short-term Band-Aid type of solution. We're working on a long-term solution so we don't face this issue again later on.
Okay. What's the extent to which patients that have a submitted patient enrollment form, and I don't know if you know this or have color on this, but what's the extent to which a submitted PEF, that patient has moved on to AbbVie, VYALEV? I mean, what are you hearing in the field?
Yeah. I mean, this is really hard to tell because you don't have any specific tracking to see whether a specific patient whose form is in hand, and all of a sudden, they're now taking something else. There is no way to track that specifically. So we don't know. Interestingly, after we announced the situation, interestingly, physicians continue to submit more forms. They haven't stopped, so to speak, of course, realizing fully that we may not be able to initiate them right away. But that's interesting as far as their reaction to the news has been really good.
Yeah. So that actually leads to my next question, which is, and you kind of answered it, but are you seeing patient demand build as you work to resolve the constraints? And so it sounds like the answer is yes, but maybe peeling back the onion a little bit, what's the extent to which some movement disorder specialists have sort of said, "Okay, I can't have new starts, so we're going to put the brakes on submitting PEFs"? So maybe talk to what you're hearing on that front.
I mean, it's going to be a mixed situation where some physicians might just continue to fill in the forms and submit them. I mean, we still have the sales force out there trying to help them assess all that, keeping the awareness around the product and so forth. So there is still that kind of activity. But as long as everybody realizes, we don't have the certainty on when we're going to initiate the patient. So as a physician, if you think this is something you will just like to try versus something that the patient is in a desperate situation that they need something, then of course, you'll put them on something else. You're not going to put them at risk by just waiting for a medication, not knowing what time they'll be able to get on it.
So taking a step back, I wanted to talk about underlying demand for ONAPGO before the constraints develop. And where I'm going with this is I'm interested in where you were pulling in patients. Did demand include those with more moderate Parkinson's? Were some of these patients previously on APOKYN? I think you've talked to these different buckets, but just help us understand where the patients were coming from.
Yeah. I mean, a lot of the initial ones are the low-hanging fruit, so to speak. These are patients who don't have too many choices left at this point. They're well progressed into the disease, and their next step is really deep brain stimulation or invasive surgery. So those are the patients which we expect will probably get them first. You also see patients who have struggled for a while. It may not have a specific time frame attached to it. It doesn't have to be 10 years or nine years or eight years, but they may have struggled for a while, even if they're only four years into the diagnosis with a lot of the oral medications. And therefore, the physician wants to put them on something else. They want to try the subcutaneous continuous treatment with something like apomorphine.
Yeah. Okay. So you have talked to US peak sales, $200 million-$300 million, but demand was quite strong, initial demand, and also VYALEV launched well. So let's assume the supply issues get resolved sooner rather than later. I'm not putting a time frame on it, but can you talk to the extent to which you would revisit those peak sales assumptions? Because what we were seeing was quite striking.
Yeah. I mean, I don't disagree that the launch has been great. Put the supply issue on the side. Clearly, the demand has been overwhelming. That's why we have the situation we're in, in a way. And whether the $200 million-$300 million was conservative or is conservative, we will have to revisit that, of course, after we resolve the supply situation. Long term, I don't see that. I don't see the potential of the product changing long term because, again, medically, clinically, this is a product that will be needed, is needed, as physicians have confirmed to us even recently. This is not something just because of a supply interruption, all of a sudden, it's going to go away completely because it just offers them something different. It's not another Levodopa type of treatment. So it really gives them something unique.
That's why, from a long-term perspective, I mean, it's not going to go anywhere. We'll fix this. We'll put it behind us, and we'll move forward.
So wanted to ask about the portion of advanced PD patients who you think could be appropriate for an infusion pump and also the portion of moderate PD patients who could be appropriate. And the reason I ask is because we've talked to key opinion leaders, and the feedback is that there's a real audience, not just in advanced patients, but also patients with more moderate disease. So how are you thinking about that?
Yeah. I mean, we expected that at some point, maybe not initially at the launch, that at some point, the treatment will start to migrate and shift towards more moderate patients. I mean, we know that from experience in Europe because the product has been on the European market for so long. So that is something we know about from real experience. But we didn't know to what extent it will happen and at what speed it will happen in the US market. Now, unfortunately, at this point, we don't have as many data points to tell us whether it's happening and at what speed this is happening as far as migrating towards more moderate. I mean, the other issue you have is the definition of advanced Parkinson's. To one physician, it means something. To another physician, it means something else.
Again, a physician who has a patient who's only four years into the diagnosis, but they're really struggling with all these oral treatments, and they still have a lot of episodes, they're going to consider them for the pump, although this patient only was diagnosed four years ago, not 10 years, and so forth. So the definition of advanced, moderate is kind of not that concrete. Yeah.
And where does that leave APOKYN? We've seen some pretty significant pressure on APOKYN. So is that because of VYALEV? Is that because of ONAPGO? Both? Generic? What's happening there?
Well, I mean, APOKYN, clearly, in the category, you've had ONAPGO. You have VYALEV. You have Crexont. You have a lot of competitive activity in the category. Also, from a sales force perspective, we have ONAPGO and GOCOVRI. We don't promote APOKYN, so to speak, on its own. But APOKYN, as a product, is a very different product. Actually, it can be used with any of these medications because it's for the rescue medication, acute treatment, or for the morning stiffness and rigidness that a lot of patients have. So if you want something quick and it does work within minutes, it's a really incredible product and gets you moving, and then you can do other things.
Yeah. And just another ONAPGO question before we move on to the other parts of the product portfolio. Just help us understand how to think about exclusivity runway here. I know you have the orphan, the seven years of orphan, but beyond that, how are you thinking about technical barriers? It is a drug-device combo. So just help us contextualize the potential runway here.
Yeah. I mean, we have the orphan drug designation. The actual exclusivity is still under review by the FDA, so they haven't ruled on it. But regardless, I mean, these are products that are fairly complex, as evident by the fact that it took us quite a bit to get them. Not just us. Everybody else in this space who went through a similar pathway, so to speak, regulatory, it's fairly challenging to get these drug-device combinations. Doesn't mean it's not doable, of course. As we always say, with time and money, you can do anything. So it doesn't mean somebody will not be able to develop something like it or similar to it.
Yeah. But to be clear, though, you can't decouple the drug from the device. You have to develop the.
Together.
Okay. And the reason I asked was because with APOKYN, the drug cartridge was approved as a generic. Of course, you have to get the patent through you. So that happened with APOKYN. So why is this case for ONAPGO going to be different than what happened with APOKYN?
Well, I mean, the NDA for ONAPGO is everything together. All these components together make up the product. You have to have all these components to have ONAPGO as a reference drug.
Got it. And that was not the case with APOKYN. Okay. All right. So let's move on to ZURZUVAE. So obviously, another addition to the product portfolio. So can you talk to underlying volume trends since you took over half of the asset? And also wanted to get your thoughts on penetration of the product in the postpartum depression incidence population.
Yeah. I mean, starting with that, you have about 500,000 women every year experiencing symptoms of postpartum depression. Diagnosis levels in the 45%-48%, it varies, but around that level as far as diagnosis. And then 60%-70% are treated, right? So it really boils down to, in the end, to 100,000+ , whatever the exact number ends up being. And the last time Sage, for example, communicated as to how many patients we've had on the product so far since launch, it's around the 14,000 patients. So clearly, we haven't scratched the surface yet. There's a lot to be done, especially with a product which is we're building the category. I mean, we're really building the market. Now, it's a very unique product. There's nothing like it.
It works really rapidly, day three, and 14-day course of therapy, and you're done versus the alternative that people are using today, which is unfortunate for a lot of patients to be taking SSRIs and have to wait weeks for the situation to resolve.
Sure. Just remind us, if you can, how big the sales organization is for ZURZUVAE, the extent to which you could see additional sales force expansion, and then also just how you and Biogen are thinking about DTC?
Yeah. I mean, as far as the size of the sales force, it hasn't been disclosed, but this is a specialty area. I mean, OB-GYNs, I think there is maybe 20 or 22,000 OB-GYNs. So I mean, this is not an area where you have sales force. So it's within typical specialty sales force kind of from a size perspective. As far as expansion, I mean, we just expanded very recently. I mean, recently, Q4 last year into Q1 this year. So we're just starting to get the benefit of that expansion. We, meaning us and Biogen combined. So any further expansion, clearly, we'll have to discuss it with our partner, Biogen, and jointly make that decision, whether that's something that warrants expanding. I mean, typically, at Supernus, as you probably know us by now, we make things stepwise approach.
We evaluate them before we just jump in and make sure we get that return on that investment, and I would assume we'll use the same approach here with our partner.
Looking at ZURZUVAE more specifically and the sales or my understanding is I believe it's over 70% of the volumes are coming from OB-GYNs, if I'm not mistaken. So with that in mind, would it be fair to say that if this is primarily an OB-GYN product, and I don't see why it wouldn't be, then there's a point maybe you're already at that point where the sales org is pretty much right-sized? I mean, is that a good way to think about it? Or is there a larger, maybe primary care practitioner or psychiatry audience? But it sounds like it's mostly OB-GYNs. Is that correct?
It is. I mean, at this point, the main touchpoint is OB-GYN. I mean, now, pediatricians, for example, they actually screen for PPD. I didn't know that until recently, interestingly. So when a mom comes in with a newborn for a checkup, they do screen for postpartum depression. And if they detect something or pick up something, they'll refer the mom to potentially an OB-GYN or maybe a psychiatrist, depending on the situation. But yes, I mean, typically, OB-GYN is your first touchpoint. And that's why Biogen and Sage did a great job in trying to build the market initially and doing a lot of the education for OB-GYNs because think about it this way. OB-GYNs are not trained to screen, diagnose for depression and treat depression. And that is something you need to get them comfortable with.
Once they get comfortable and actually they write, they tend to be strong repeat writers. We've seen that from the data.
Okay. Remind us what gross margins are like on ZURZUVAE, and can you contrast that with the gross margins on ONAPGO?
ONAPGO is more like APOKYN because that's under the same arrangement we have with STADA and Britannia. So it's more in the 60% gross margin. But ZURZUVAE is more like our other products.
Okay. And going back to sales force and sizing, this is more of a Qelbree-related question. Thoughts on further sales force expansion there?
On Qelbree, I mean, we continue with all the time. We evaluate that. Every three months, six months, we evaluate where are we and whether we can always expand. I mean, as the brand continues to grow, I mean, in ADHD, you could be at the 300, 350 reps. It could justify something like this. I don't know yet at this point whether it is a point for us to expand or not. That remains to be seen. But at this point, we don't have any specific plan to say, "Yes, we're going to expand or not.
Yeah. Another question on the cost side. Just remind us of the magnitude of Sage-related synergies we'll see in 2026, or at least where they're annualized?
Yeah. I mean, on an annualized basis, we're very well on track for up to $200 million that we talked about. So owning the business from August 2025 through August 2026, we would have realized somewhere around close to that number.
Okay. So Sage did have early-stage assets, and they had discovery and research capabilities. And I know you only took over Sage only recently, but it's been a few months. So where is your collective thinking on these early-stage assets, and should we expect advancement of any of these going forward?
Yeah. We've done preliminary. We started the process. We've done the first couple of phases of evaluation. I mean, there is some really good science there. They've been doing this for quite a number of years. There's a lot of molecules and different platforms, some of which they've talked about publicly, some of which they haven't talked about. So it's pretty exciting stuff. Early stage, of course, very early stage. So at the right time, once we make an assessment in addition to the stuff that we had at Supernus, because we had our own discovery. So now it's more looking at the portfolio in totality, which program makes more sense than the other in advancing further. But once we make these decisions and it's a program we're committed to, clearly, at that time, we can disclose what that program would be.
Yeah. That sort of leads to another question here, which is that you have, as you alluded to, your own earlier-stage assets, and you've highlighted a handful that are going to move through early-stage development. So are you thinking about those internal Supernus assets any differently now that you've onboarded Sage, or is it just too early to?
No. I mean, we put them together. I mean, they're all Supernus molecules right now at this point, right? So we evaluate them equally as to which one is the better one to move forward from that perspective. Yeah.
Okay. And then another ZURZUVAE question here. And I've asked this before. I'm sure you get this question a lot. But looking at Biogen, it doesn't fit with their core neurology and immunology focus. So I guess with that in mind, how open are you to a discussion, at least, about buying out the 50% of the assets you don't already own?
I mean, look, we're always open to anything. I mean, we try to be open-minded about any potential here. They are committed to the brand. We are committed to the brand. I mean, that's the nice thing about it. We both like the asset, and we're willing to invest behind it. But that discussion can always happen at any time. Yeah.
Sure, and then more broadly about M&A and another question you get all the time. Do you continue to lean into prioritizing commercial-stage assets? Are you open to taking on development risk? Or just latest thoughts on M&A priorities?
Commercial assets will continue to be a priority for us. And then underneath that will be later-stage things that are more advanced than our own pipeline. Clearly, it doesn't make much sense for us to bring in another phase I or pre-phase II program. But something post-phase II, early-phase III, that is something we would be interested in.
All right. Well, I'll leave it there. We're out of time. Thanks, Jack. Thanks, everyone in the audience for joining us.
Thank you.
All right.