Good afternoon, everyone. I'm Sumant Kulkarni, a 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, NUPLAZID for Parkinson's disease psychosis, and DAYBUE for Rett syndrome. They target significant unmet needs.
We are also ahead of a significant phase II 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 Thomas Garner, and Al Kildani heads up IR and knows everything about the company. 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.
Anyone listening in to 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.
I think we're ready to launch into these questions.
Great introduction. Thank you.
Great. So that's easy. No forward-looking statements. All right. We'll do that. So a commercial question for you. You've had some really nice traction with your approved products, such as NUPLAZID and DAYBUE. 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 annualizing at fairly sizable sales rates. What's the secret sauce in the commercial side of Acadia?
Thanks for the question. Good afternoon, everyone. Starting with NUPLAZID, 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. In fact, over the last few years, we've actually seen accelerated growth for it. 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 NUPLAZID 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, we've also been focused very much on ensuring that HCPs who see patients living with PDP are aware that when you see these patients, you should be treating them, and NUPLAZID is the first and only approved therapy for patients living with PDP. So I think a dual approach there. One is around education. The second is really around focusing the messaging, the segmentation, and our sales force effort on the right customer at the right time.
As it relates to DAYBUE, which is our treatment for Rett syndrome, again, first and only approved treatment there. I think we've learnt a great deal about this marketplace since we've launched. This was a completely new treatment, completely new category in essence. Since we've launched, we've learnt to turn around not only the asset itself and its profile, but again, how we go about commercializing that.
Again, rare disease is somewhat unique. You have to really get down to N-of-1 as it relates to understanding the patient, but also thinking about the HCP who is part of that story. Again, there has been a significant amount of education required, both for the clinical community, but also for the patient community and the caregiver community.
There has been a very strong advocacy play. Again, that is part of the playbook for rare disease. I think what is common across the two is a real steadfast focus on execution. We have to make sure that we execute appropriately, and that has been a focus certainly since I have been with the company for the last two years.
Got it. On the topic of NUPLAZID, I have said this several times. I think 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 NUPLAZID.
Now we are seeing more shoots of excitement in this space as AbbVie, which is covered by my colleague Garry Nachman here. They have tavapadon 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?
Mm-hmm. Well, I think if you think about Parkinson's disease, we estimate that there is 1 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. To your point, I think it is exciting that there are new players coming into the marketplace.
As we think about the efforts that we have undertaken to really drive awareness, as I have 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 are not particularly au fait with because they are just concentrating on the actual movement side of things.
If you think about that 1 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. I think it points to a few different facts. Education is clearly critical. Driving awareness in the right way, and through the right channels will really 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.
On NUPLAZID, 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?
Mm-hmm. We are thinking about this in a multifaceted way. The education part I've spoken about. We have both branded and unbranded campaigns. We actually have a branded campaign for NUPLAZID that just talks to the benefits that an HCP can think about, but also a patient.
One of the key opportunities that we've seen for NUPLAZID 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. 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 NUPLAZID is there as a treatment option.
For us, this has meant expanding from about 5,000- 6,000 HCPs in the U.S. to roughly 10,000- 10,500. 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.
Right. I'll switch to DAYBUE 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 Rett syndrome.
Correct.
There are some other approaches in the wings. 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?
Yep. Just for the folks in the room, DAYBUE, we launched back in 2023. As Sumant 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 Sumant's point, one of the key foundational things that we've been trying to drive is long-term persistency.
Capturing patients quickly, capturing patients early, ensuring that they see the benefit that DAYBUE has to offer. Then one of the goals is obviously to keep them on drug for as long as possible. 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've been on drug for long term.
70% of our existing DAYBUE patients have been on treatment for greater than 12 months or longer. We recently launched our new formulation of DAYBUE, which is called DAYBUE STIX, 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 DAYBUE, 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 DAYBUE back to the brand. There's roughly 1,000 patients living with Rett who have tried DAYBUE but since stopped.
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 STIX, we now have multiple growth opportunities for the brand beyond where we would've been without the new formulation.
Right. Do you think STIX is eventually going to become the leader of the franchise?
Given what we have seen during the second quarter, I would say yes. If you look at our overall dynamic in Q2, 60% of our business was coming from the oral solution, which is the formulation we launched with. 40% was coming from DAYBUE STIX, which is the new formulation.
But if you take June in isolation, that actually flips. 60% of our prescriptions that we saw in June alone were for the new formulation. 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 Rett is complex. Children living with Rett are very fragile, and many parents don't want to rock the boat, so they will keep them on the oral solution.
Got it. On DAYBUE, 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. If you look at kind of our penetration within the marketplace today, we still think that there is significant headroom to grow in patients who we have not yet been able to reach or educate about the benefits that DAYBUE offers. We did actually expand our sales team last year for DAYBUE, and I think that that is one of the reasons that we have seen such strong uptake with STIX, is that they have executed that launch particularly well.
I think moving forwards, it is going to be that combination of continuing to drive naive patient starts. 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.
Now we have got the opportunity to reengage with these patients who have discontinued, which is a probably significant group. This is patients who have already tried DAYBUE. They have already tried for a reason. We now can reengage with them.
Yeah. So clearly, the unmet need in Rett 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 DAYBUE to play within a marketplace that might have these gene therapies approved?
First thing I would say is we are pleased to see additional treatment options coming to the market for these children. Rett is a devastating, long-standing disease, and I think having multiple modalities here is only a good thing. Having said that, we believe that DAYBUE is, as recognized by Centers of Excellence, and we saw this through the recent Delphi consensus paper. I think DAYBUE is recognized as standard of care. It's recognized as a foundational therapy for Rett.
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 DAYBUE is going to have a role to play both pre, post any patient who may have received gene therapy.
Obviously, there's still questions just regarding gene therapy more broadly. Obviously, non-reversible treatment. DAYBUE, you can reverse. I think we'll probably see this field move on as we see second, third generation gene therapies come to the market as well.
Let's move on to your ex U.S. efforts on DAYBUE. Probably my most important question. The European Medicines Agency, the brand name there is D-A-Y-B-U minus the E. How do you say that?
DAYBU.
Okay. Got it. All right. Let's move on to DAYBU then. The European market. You're right now a U.S.-focused company for the most part.
Correct.
How do you expect to penetrate the European market with that product?
Okay. As you mentioned, Sumant, 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 building out our European infrastructure, and they've been in place for the last year.
Highly experienced, highly tenured team, rare disease experience. We feel very confident we've got the right people in Europe to drive this forward. We plan to launch in Germany first. We're going to follow the normal launch cadence, and they'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 U.S.
In EU, we estimate between 8,000 -1 2,000 people living with Rett syndrome compared to the 6,000 in the U.S. 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 U.S. But I think taken together, we're excited about the opportunity to really expand beyond our U.S. core franchise.
Got it. 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 o n 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 commercial framework?
Yeah. 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 led us to take a different approach as to how we were articulating the benefit that you can see with DAYBUE. We've 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. We really did listen carefully to the feedback. I think we then adapted our approach, and then we engaged with both the advocacy and specialist treating community to really support our narrative.
Got it. We talk about Europe as one entity, but clearly it's a collection of several countries.
Yep.
What's your country by country strategy, and how do you expect that to play out?
You're indeed correct. There are 27 member states that fall under that CHMP opinion. We are working on where we see the biggest opportunity. Obviously, we do want to deliver on our promise of 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 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.?
We've not declared 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.
Got it. Let's move on now to a pipeline product. You're the commercial guy. We have a phase II/it's going to become a seamless phase III trial on a product called remlifanserin which is, you have a lot of experience with pimavanserin. What excites you most about this dataset that's coming up in the September to October timeframe in Alzheimer's disease psychosis?
First thing I would say, and you asked me as the commercial person, this is a huge commercial opportunity. Alzheimer's disease in the U.S., currently estimated 7 million, 7.5 million people living with Alzheimer's disease. With an aging population, that number is estimated to be 8 million, 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 do the math, and we're talking about 2.8 million - 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, we've built this program based upon many of the learnings from pimavanserin, which is NUPLAZID, which has already had earlier readouts in a similar space. 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. If successful, we think it could work 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 COBENFY and a program for Alzheimer's disease psychosis. What's your take on, as a commercial person, how could you best differentiate remlifanserin from a muscarinic agonist approach to COBENFY?
Yeah. First thing I would say is, we have to see how the data plays out here. We are looking forward to seeing our data. Obviously, we're keeping a close eye on what happens with the COBENFY ADEPT programs as they progress as well.
I think fundamentally, we believe that our profile, as you think about a population who is elderly, they need something that is going to fit with ongoing complex etiologies. You need something that's clean, 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 this market in the future.
Right. Bristol's obviously slightly ahead in terms of timelines. The phase III reporting out at some point this year or next, I guess. As a commercial person, what is your general preference on whether you would like to be first as pioneers in the ADP market, or would you like to see how the market evolves and then capitalize on the opportunity?
Well, there is no approved therapy today for Alzheimer's disease psychosis, so it goes without saying that the market shaping that is going to be required here is not going to be insignificant. 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 am less concerned about us really being on the leading edge. I think given the size of this marketplace, being a fast follow is not necessarily a bad thing.
Right. Okay, so Al, a few questions for you.
Sure.
There is a relatively vast pipeline at Acadia, which we do not really talk about as much. Day to day, how does the organization think about prioritizing all that, just as from where you sit?
Sure. There is a great deal of prioritization in terms of the focus on the pipeline. We have obviously got remlifanserin in two ongoing trials, Lewy body dementia phase II being the second. Behind that, we have got ACP-211, which is being studied in major depressive disorder. We expect a readout on the phase II on that in the latter part of next year.
Then we have got other programs behind that, and that is one of the things we are really excited about, to have both a strong commercial platform as well as a pipeline that is very robust, and we have the ability to fund the development of that pipeline. So something we are very excited about, and we are really excited about all the programs in the pipeline, and we are also looking to continue to add to them over time as well.
If I may, we shared at our R&D Day last year what we saw as the peak revenue potential. If you just take the ACP-204 program, remlifanserin, you take ADP plus LBDP. By our internal estimates, that is a $4 billion opportunity right there, but as we are seeing from other players who are operating in other spaces similar to ADP, so Alzheimer's disease agitation as an example, we are already seeing what looks like very encouraging early uptake for some of these other brands. I think that that is informative as well, just as we think about potential.
I actually have to go back to DAYBUE. You have a trial running in Japan.
Correct.
What are your plans as an organization in Japan?
We are evaluating the best approach for Acadia to ensure that we can bring DAYBUE quickly to patients living with Rett in Japan. I think we are looking at more of a partnership approach here, just given the size of Acadia. This would be our first foot step into the Japanese marketplace, and then we will evolve further from there.
We have a minute or so left. From a commercial perspective, you have NUPLAZID, you have DAYBUE. You could have remlifanserin at some point. And other products in your pipeline. What is your bandwidth to take on a new product that might be brought in from the outside?
Yeah.
Already approved, for example.
Yeah. We have close to $1 billion of cash on our balance sheet, which gives us a significant amount of optionality as we think about BD. 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 are bolstering our mid-term pipeline, which, as Al has 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 Acadia sized and Acadia appropriate. We are thinking beyond neuro and neuro rare. We think that there is an opportunity there to expand the aperture even wider still. But we are not in a position where we have to transact any BD, and I think we will be choiceful and really thoughtful about the assets that we bring in based upon those two groups that I mentioned.
Got it. Great. On that note, we are out of time, and thank you for being here, and thanks, everyone, for tuning in.
Thank you.