Good afternoon, everyone. I'm Simanth Kulkarnia, Senior Biotechnology Analyst at Canaccord Genuity, and it's my pleasure to have Acadia Pharmaceuticals here with us today. Acadia has a couple of products out on the market already, New Placid for Parkinson's disease psychosis and Debut for Rett syndrome. They target significant unmet needs, and we are also ahead of a significant phase 2 data set for a product called Remlifanserin for Alzheimer's disease psychosis. So a really interesting time for the company, and we'd like to thank you guys for being here. For Acadia, we have Chief Commercial Officer Tom Garner, and Al Kildani heads up IR and knows everything about the company. So we'll keep this really interactive. Please feel free to raise your hands. We'll get a mic across to you if you have any questions in the audience. And anyone listening into the webcast, if you have any questions for me, please feel free to email them, and I'll get them across as well. As I said, we'll keep it interactive. So if you have a few remarks to make, please go ahead and do so, and then we'll go straight into Q&A.

Great introduction.

So that's easy. No forward-looking statement. All right. We'll do that. So commercial question for you. You've had some really nice traction with your approved products at New Plaza and Debut.

What can you say the organization's commercial strengths have been, given that you started off as a relatively small company, and now you have these two products that are analyzing at fairly sizable sales rates. so what's the secret sauce in the commercial side of Acadia so thanks for the question good afternoon everyone so starting with New Placid which is our treatment for Parkinson's disease psychosis I think as you mentioned we've seen very nice traction for that brand over the last 10 years and in fact over the last few years we've actually seen accelerated growth for it I mean just in the last quarter alone we saw 20% year-over-year growth in terms of new-to-brand prescriptions. I think what is underpinning that for New Placid is two things. One, we've really been kind of leaning in heavily to educate people living with Parkinson's disease that actually hallucinations and delusions is part of the disease course. So we're trying to drive awareness that way. At the same time that we've also been focused very much on ensuring that HCPs who see patients living with PDP are aware that, you know, when you see these patients, you should be treating them. And Newplazid is the first and only approved therapy for patients living with PDP. So I think kind of a dual approach there. One is around education. The second is really around focusing the messaging, the segmentation, and our Salesforce effort on the right customer at the right time. As it relates to DEBU, which is our treatment for Rett syndrome again first and only approved treatment there you know I think we've learned a great deal about this marketplace since we've launched this was a completely new treatment completely new category in essence and since we've launched we've learned to turn around not only the asset itself and its profile but but again how we go about commercializing that so again rare disease is somewhat unique you know you have to really kind of get down to n equals one as it relates to understanding the patient but also thinking about the HCP who's who's part of that story so again there's been a significant amount of education required both for the clinical community but also for the patient community and the caregiver community there's been a very strong advocacy play again that's kind of part of the playbook for rare disease and I think what's common across the two is is a real steadfast focus on execution you know we have to make sure that we execute appropriately and that's been a focus certainly since I've been with the company for the last two years.

Got it so on the topic in New Placid I've said this several times I think you know the Parkinson's disease space has been devoid of new products for a long long time you guys have done a really good job on the psychosis side of things with the 700 million product in New Placid now we're seeing more kind of shoots of excitement in the space as like like AbbVie, which is covered by my colleague Gary Nachman here, they have to pop it down, waiting in the wings. How do you expect that sort of enthusiasm on the underlying Parkinson's indication products that seem to be coming translate to maybe potentially more demand for your product?

Well, I think if you think about Parkinson's disease, we estimate that there's a million people in the United States living with Parkinson's disease today, and we think that that number over time is actually going to grow. So to your point, I think it's exciting that there's new players coming into the marketplace. As we think about the efforts that we've undertaken to really drive awareness, as I've mentioned, we understood, certainly over the last few years, that one of the issues that people with Parkinson's face is they understand the movement disorder side of things. But some of the other conditions that they face, psychosis being one, they're not particularly okay with because they're just concentrating on the actual movement side of So if you think about that million patients in the U.S., 50% of patients living with Parkinson's disease may experience hallucinations and delusions during their disease course. I don't think many are aware of that. And one of the goals that we've had is to really drive awareness, as you think about just the broader education of Parkinson's disease, to the point where if you look over the last two or three years since we've had our More to Parkinson's campaign, where Ryan Reynolds has actually partnered with us, We've seen a threefold increase of awareness of Parkinson's disease psychosis amongst people living with Parkinson's disease. So I think a few points to a few different facts. You know, education is clearly critical. Driving awareness in the right way and through the right channels will really kind of drive uptake in the right direction. And I think there is more work to be done for sure. But I think having more players in the market, you look at most pharmaceutical products, generally helps awareness and diagnosis of the disease moving forwards.

So on New Placid, you have your plans in place now. You have a DTC campaign. You mentioned that. What more can be done to drive that product to achieve its full potential?

So we are thinking about this in kind of a multifaceted way. So the education part I've spoken about, we have both branded and unbranded campaigns. So we actually have a branded campaign for New Placid that just talks to the benefits that a HCP can think about, but also a patient. One of the key opportunities that we've seen for New Placid in terms of additional growth is really tapping into customers who see patients living with Parkinson's disease psychosis, but they aren't necessarily treating today. So to kind of bridge to that, we actually expanded our sales team earlier on this year. It was roughly a 40% expansion. And we believe that this gives us an opportunity to tap into many more writers who may see these patients but may not be aware that Newplazid is there as a treatment option. So for us, this has meant expanding from about 5,000, 6,000 ACPs in the U.S. to roughly 10,000, 10,500. half thousand our team is now calling upon those and our goal is to make sure we're having the right message with the right customer at the right time to really drive that uptake forwards against that backbone of education so I'll switch to debut now a bunch of questions on that you've known the product profile for some time it's been out in the market for some time it's doing nicely it's really the only game in town right now for red syndrome there or some other approaches in the wings.

So given all that, the product's growing nicely now, long-term persistency is one of the keys there. How do you expect to achieve that given the product? And now you have the new STIX formulation as well.

So just for the folks in the room, so Debut, we launched back in 2023. As Samant mentioned, first and only approved treatment for Rett syndrome, which affects essentially young children, mostly young girls here in the U.S. It's about 6,000 patients living with Rett syndrome by our estimations. To Samantha's point, you know, one of the key kind of foundational things that we've been trying to drive is long-term persistency. So capturing patients quickly, capturing patients early, ensuring that they see the benefit that Debut has to offer. And then one of the goals is obviously to keep them on drug for as long as possible. So So our current persistency rates point to the fact that 12-month persistency is north of 50%, 55%. 18 months, we keep about 50% of patients. In addition, we have a growing group of patients now who have been on drug for long term. So 70% of our existing DEBU patients have been on treatment for greater than 12 months or longer. We recently launched our new formulation of DEBU, which is called DEBU Sticks. and this is a powder that you can reconstitute in any non-dairy-based liquid, that has been a really nice opportunity for us because I think it's helping us engage both patients who are naive to Debut because we've taken out some of the excipients that exist with the prior formulation, but at the same time, it's also providing an opportunity to bring patients who have maybe discontinued Debut back to the brand. And there's roughly 1,000 patients living with Rett who have tried Debut but since stopped. And actually, during the quarter, we saw a very nice uptick in terms of returning patients. And we believe that, again, taken together with the advent of Styx, we now have multiple growth opportunities for the brand beyond where we would have been without the new formulation. Do you think Styx is eventually going to become the leader of the franchise? given what we have seen during the second quarter i would say yes so if you look at our overall dynamic in q2 60 of our business was coming from the oral solution which is the the formulation we launched with 40 was coming from debut sticks which is the new formulation but if you take june in isolation that that actually flips 60 of our prescriptions that we saw in june alone were for the new formulation. So for sure, it's moving in that direction, although I would caveat that I do expect that there will be a group of patients who want to continue on the oral solution for the long term, just given the fact that RET is complex, children living with RET are very fragile, and many parents don't want to rock the boat, so they will keep them on the oral solution.

So on debut, you have STIX. You still have the old formulation on.

It looks like STIX is going to become the eventual leader what can you do to drive more sales there in terms of educational efforts those kinds of things well we have more work to do that is for sure i mean if you look at kind of our penetration within the marketplace today we still think that there's significant headroom to grow uh in patients who have just we've not yet been able to reach or educate about the benefits that debut offers so we did actually expand our sales team last year for debut and i think that that's one of the reasons that we've seen such strong update with STIX is that they have executed that launch particularly well. I think moving forwards, it's going to be that combination of continuing to drive naive patient starts. You know, if you look at kind of our penetration rate by age, as patients get older, they become less engaged with healthcare, especially as they age into their teenage years. That is an opportunity for us. And then now we've got the opportunity to re-engage with these patients who have discontinued, which is a probably significant group. And this is patients who have already tried DEBU, so they've already tried for a reason. We now can re-engage with them.

So clearly the unmet need in RET syndrome remains very high. There's a couple of gene therapy approaches out there that could make it to the market at some point. How do you expect DEBU to play within a marketplace that might have these gene therapies approved?

First thing I would say is, I mean, we are pleased to see additional treatment options coming to the market for these children. RET is a devastating, long-standing disease, and I think having multiple modalities here is only a good thing. Having said that, we believe that DEBU is as recognized by Sense of Excellence, and we saw this through the recent Delphi consensus paper. I think DEBU is recognized as standard of care. It's recognized as a foundational therapy for RET. And we believe that irrespective of whether a patient may or may not receive gene therapy, and we think that to begin with, that may be isolated to a relatively modest number of patients, given the wraparound care that's needed, potential questions around cost, et cetera. We believe that DEVU is going to have a role to play, both pre-post any patient who may have received gene therapy. And obviously, there's still questions just regarding gene therapy more broadly. Obviously, non-reversible treatment, DEBU, you can reverse. And I think we'll probably see this field move on as we see second- and third-generation gene therapies come to the market as well.

So let's move on to your ex-U.S. efforts on DEBU. It's probably the most important question. The European Medicines Agency, the brand name there is D-A-Y-B-U, minus the, how do you say that?

D-A-B-U.

Okay, got it. All right. So let's move on to debut then. The European market. You're right now a US-focused company for the most part. How do you expect to penetrate the European market with that product?

Okay. So as you mentioned, Samantha, we had positive CHMP opinion a few weeks ago, in fact, and we are now getting ready for EC decision, which actually gives us then the green light to launch in Europe. We have a small but mighty team based in Zug who are kind of building out our European infrastructure, and they've been in place for the last year. Highly experienced, highly tenured team, rare disease experience, so we feel very confident we've got the right people in Europe to drive this forward. We plan to launch in Germany first. You know, we're going to follow the kind of normal launch cadence, and we're also anticipating submitting pricing and reimbursement dossiers as soon as we see our EC decision come through. Just as a reminder, the opportunity in Europe is actually greater in size than what we see in the US. So in the EU, we estimate between 8,000 to 12,000 people living with Rett syndrome compared to the 6,000 in the US. So significant opportunity. Obviously, there are going to be some puts and takes as to how we think about the business opportunity. Pricing, access dynamics may be different to what we see in the US. But I think taken together, we're excited about the opportunity to really expand beyond, you know, our U.S. core franchise. Got it.

So I'm going to rewind a bit on what happened with this product in Europe in terms of the approval process. You had a negative trend vote, which you then turned into a positive opinion on approval, eventual approval. What really drove that and what does that mean for the product from your ability to utilize what drove that change in mind into a kind of commercial framework?

So, yeah, so when we went through the process, we were disappointed with the initial CHMP opinion, which was negative. The team then regrouped. We took the feedback that we received from CHMP, and that kind of led us to take a different approach as to how we were articulating the benefit that you can see with Debut. We really tried to ensure that they understood the RSBQ endpoint in a greater depth than they had before. We also listened to some of the feedback that they had just regarding the studied patient population, and that's why our anticipated European label may be slightly different to what we have in the U.S., but I think we still feel very confident that we have an opportunity here that's significant and are looking to taking this forward. So, you know, we really did listen carefully to the feedback. I think we then adapted our approach, and then, you know, we engaged with both the advocacy and specialist-treating community to really support our narrative.

So we talk about Europe as one kind of entity, but clearly it's a collection of several countries. So what's your country-by-country strategy, and how do you expect that to play out?

So you're indeed correct. There are 27 member states that fall under that CHMP opinion. So we are working on where we see the biggest opportunity. Obviously, we do want to deliver on our promise for making this product broadly available to people living with Rett syndrome. As I mentioned, we are going to follow the fairly standard cadence, which is launching in Germany first, because that's our earliest opportunity to work through kind of pricing and reimbursement dynamics. At the same time, we are then going to be submitting our reimbursement dossiers in other priority markets. And we're going to be listening carefully to the feedback as we work with payers and clinicians and building upon the experience that we already have through our name patient programs in Europe.

How do you expect relative pricing to be in Europe compared to the U.S.?

So we've not declared kind of officially the pricing corridor that we expect in Europe. Some of this is going to be largely down to the negotiations that we have at the country level, and we'll be sharing more information in due course.

So let's move on now to a pipeline product. And you're the commercial guy. We have a phase 2 slash, you know, it's going to become a seamless phase 3 trial on a product called Remlifanserin, which is, you know, you have a lot of experience with Pimovanserin. You can see that the names are very similar there. What excites you most about this data set that's coming up in the September to October time frame in Alzheimer's disease psychosis?

So first thing I would say, and you asked me as the commercial person, I mean, this is a huge commercial opportunity. So Alzheimer's disease in the U.S. currently estimated 7, 7.5 million people living with Alzheimer's disease. With an aging population, that number is estimated to be 8, 8.5 million by the time we get to the end of the decade. So huge opportunity. We estimate that 30% of those patients may end up with psychosis. So, you know, you do the do the maths and we're talking about 2.8 to 3 million patients potentially in play. So vast opportunity. We think that this is a market where there's space for multiple players. Having said that, you know, we've built this program based upon many of the learnings from Pimavanserin, which is New Placid, which has already had, you know, earlier readouts in a similar space. so we're excited by the opportunity I think we're excited by the science and we're also excited by the profile that we believe we can bring to this marketplace as if successful we think it could work very very very nicely right you mentioned differentiation you mentioned the market is potentially large enough to support several players we could have competition here we have Bristol Myers with Cobenthi and the program for Alzheimer's disease psychosis.

What's your take on, as a commercial person, how can you best differentiate remlefanserin from a muscarinic agonist approach? Yeah.

First thing I would say is, I mean, we have to see how the data plays out here. You know, we are looking forward to seeing our data. Obviously, we're keeping a close eye on what happens with the Cabanthia debt programs as they progress as well. I think fundamentally you know we we believe that our profile as you think about a population who is elderly they need something that is going to kind of fit with you know ongoing complex etiologies you need something that's kind of clean easy easy to take has a minimal side effect burden we believe that we can bring that to the marketplace and that in itself could be a differentiator as we think about, you know, this market in the future.

Right. So Bristol's obviously slightly ahead in terms of timelines, the phase three reporting out at some point this year and next, I guess. As a commercial person, what's your general preference on whether you'd like to be first as, you know, pioneers in the ADP market, or would you like to see how the market evolves and then capitalize on the opportunity?

Yeah. Well, I mean, there is no approved therapy today for Alzheimer's disease psychosis so it goes without saying that kind of the the market shaping that is going to be required here is not going to be insignificant so as you think about where we play in that overall picture again coming with what we believe is going to be a highly differentiated asset I'm I'm I'm less concerned about us really being on the leading edge you know I think given the size of this marketplace you know being a fast follow is not necessarily a bad thing right okay um so al a few questions for you you you have you know there's a relatively vast pipeline at acadia which we don't really you know talk about as much so day to day how does the

organization think about prioritizing all that you know just as from where you sit sure i mean there is a great deal of prioritization in terms of the focus on the pipeline we've obviously got remlefantorin in two ongoing trials Lewy body dementia phase two being the second and then behind that we've got ACP 211 which is being studied in major depressive disorder we expect a readout on the phase two on and that in phase two and next in this in the latter part of next year and then we've got other programs behind that and that's one of the things we're really excited about to have both a strong commercial platform as well as a pipeline that you know is very robust, and we have the ability to fund the development of that pipeline. So something we're very excited about, and we're really excited about all the programs in the pipeline, and we're also looking to continue to add to them over time as well.

And if I may, I mean, we shared at our R&D day last year kind of what we saw as the peak revenue potential. I mean, if you just take the 204 program, Rebler-Fanserin, you take ADP plus LBDP, by are kind of internal estimates that's a four billion dollar opportunity right there but as we're seeing from other players who are operating in you know other spaces similar to ADP so also Alzheimer's disease agitation as an example we're already seeing kind of what looks like very encouraging early uptake for some of these other brands and I think that that is informative as well just as we think about potential I actually have to go back to debut you You have a trial running in Japan.

What are your plans as an organization in Japan?

So we are evaluating the best approach for Acadia to ensure that we can bring Debut quickly to patients living with RET in Japan. I think we are looking at more of a partnership approach here, just given kind of the size of Acadia. This would be our first kind of footstep into the Japanese marketplace, and then we'll evolve further from there.

We have a minute or so left. From a commercial perspective, you have New Placid, you have Debut, you could have Rambli Fancin at some point, and other products in your pipeline, what's your bandwidth to take on a new product that might be brought in from the outside, already approved, for example?

Yeah, so we have close to a billion dollars of cash in our balance sheet, which gives us a significant amount of optionality as we think about BD. so our approach at the moment is thinking about assets that we could bring in that have near-term commercialization opportunities on one end and on the other end is making sure that we're bolstering our midterm pipeline which is how Lo's shared is particularly strong with early stage assets that work for us in terms of generating long-term value we look at things through a few different lenses we want them to be a kind of acadia sized and acadia appropriate we are thinking beyond neuro and neuro rare we think that there's an opportunity there to expand the aperture even wider still but we are we're not we're not in a position where we have to transact an ebd you know i think we will be choiceful and really thoughtful about the assets that we bring in based upon those kind of two groups that i mentioned great on that note we're out of time and thank you for being Thank you, and thanks everyone for tuning in. Thank you, thank you.