Good afternoon, everyone. I'm Sumanth Kulkarni, a Senior Biotechnology Analyst here, and we are really pleased to have Acadia Pharmaceuticals. Thanks for making the trip all the way for Acadia.
Thanks for having us. Thank you.
For Acadia Pharmaceuticals, we have Chief Financial Officer Mark Schneyer and Chief Commercial Officer Tom Garner. We also have Al Kildani, who knows everything about the company out back there in the audience. At this time, I'd also like to acknowledge my teammate, Elliot, who's in the audience. He does all the work, so thanks a lot for that.
Thank you.
You guys can give a quick intro on yourselves, and then we'll head straight into Q&A.
Yeah, sure. At Acadia , we're a neurological and rare disease company. We're a commercial stage company with a development pipeline behind it. We have two commercial assets. Our guidance for this year for both assets combined is over $1 billion in net sales. The first asset is NUPLAZID. It treats a disease called Parkinson’s disease psychosis. The second asset is DAYBUE, which treats a disease called Rett syndrome. Both are branded assets, or they're first and only approved drugs in their indications. We just had an R&D day back in June where we shared some information of our kind of near and slightly earlier stage pipeline. The two most latest stage assets are ACP-101, with the potential to treat Prader-Willi syndrome. We have a readout from our ongoing phase III trial in early fourth quarter of this year.
The second kind of latest asset, ACP-204, we're running trials on two indications, the first being Alzheimer’s disease psychosis and the second being Lewy body dementia psychosis. That one, the Lewy body dementia psychosis trial, is going to start this quarter. The readout for the phase II portion of the ADP trial for 204 will be in the middle of next year. Altogether, we disclosed kind of three pipeline assets or five pipeline assets at our R&D day where we listed the kind of peak sales commercial potential in the range of $12 billion, on a risk-adjusted basis, more like $2.5 billion. We also shared for the two commercial stage assets that our peak sales potential is in the $1.5 billion- $2 billion range.
We're still pretty active or remain active in the business development ecosystem in our spaces as we look to continue to build a growing and sustainable company and bringing in additional assets through business development. With that, Sumanth, happy to hand it back to you for Q&A.
I think Mark's given a very nice overview of the company. My name's Tom Garner, Chief Commercial Officer here at Acadia . I've been with the company now for about nine months. Prior to this, I spent the majority of my career in big pharma. Moving to Acadia has been great, and I think as a company, we're really motivated by positively impacting the meaningful moments that families look for in diseases where unaffected families don't experience these. Looking forward to today's discussion.
Great. On that note, I'll start with DAYBUE or trofinetide, which is approved for Rett syndrome. You've been seeing some really nice growth. You mentioned long-term persistency is a key strength. Can you talk about some of the factors that have been so important in keeping patients on DAYBUE?
Yeah, I'll take that. As a reminder, we spoke during our Q2 call that the persistency that we're seeing for DAYBUE continues to look very solid. Through 12 months, the number remains above 50%. For the first time, we actually disclosed that at 18 months, our persistency rate is above 45%. We're really seeing a nice kind of plateauing now in terms of the ongoing persistency. I think there's a few reasons that underpin that. First and foremost is you don't get to these levels of persistency without patients really seeing benefit from the treatment. Clearly, with 18 months' persistency north of 45%, 50%, we feel good that the patients who are staying on DAYBUE are staying on DAYBUE because they continue to see clinical benefit.
On top of that, as we think about some of the actions that we have undertaken within the team, we really remain very, very closely engaged with the Rett families as they start DAYBUE and as they go through their treatment journey. We can engage them in their treatment journey. We're looking to educate HCPs just on the ongoing benefit that we will see, that they will see with DAYBUE, really trying to elucidate the clinical benefits that they can expect to see in a disease that, such as Rett, is really heterogeneous. There are a few different angles that we're playing this forward. As we think about our field force execution, really being able to ensure that we're sharing best practices from centers of excellence into the community, which is a real focus right at the moment, has been key.
I wouldn't be a stock analyst if I didn't nitpick. You said 50% persistency rate at 12 months, 45% at 18 months. What's driving that difference? Do you expect that to trend back up at, let's say, a 24-month time point as people come back maybe?
Yeah, I mean, some of this I would say is just maturity of the data, obviously. We have more patients who have gone through 12 months than we do have going through 18. That number, the 45 number, is actually, if we look at it pretty closely, probably closer to 50 than it is 45, I would say. Again, that's just kind of something that we continue to keep a very close eye on. I think what's most telling though is that the shape of the curve really has kind of plateaued now. It looks fairly stable. We'll continue to monitor closely as more patients go through the 18-month mark and then we begin to look at two years. Obviously, we'll share that information with you.
I think from an analytical perspective, if you had a static patient base, it's more like a Kaplan-Meier curve, right? Yes, you'll have at any point in time, you know, a patient can stop therapy for a whole variety of reasons, right? As they're getting out to that kind of longer term, it's really plateauing. You're not going to have it spike. What could happen is newer cohorts that are starting now, if they have much greater persistency than the earlier cohort, it kind of can lift the whole curve. Yes, over time, some of that can lift, but what you really see is a curve where a patient starts, 100% of them start, a certain period of time, they no longer take it. We've gotten to a place where we have stability in the patient base. For all the experience Tom has on commercializing medicines, to say at 12 months for a chronic therapy that greater than 50% of your patients are staying on, that's a very strong persistency number.
Right. And just to close this one out, just on Mark's point, you know, as a reminder, 70% of our active patient group now have been on treatment for greater than 12 months. Again, you know, it's just this expanding and growing group of patients that we have on treatment.
Right. I think you said 987 patients received DAYBUE in the second quarter. Could you give us a sense of what percentage of those patients were treated at centers of excellence versus not?
Okay. If you look at kind of our usage within COE since launch, taken in totality, around 40% have come from a COE. 60% have come outside of a COE. Again, just as a reminder as to kind of source of business, 65% of Rett patients are treated outside of the primary care of a center of excellence. That to us is a very big population. Within that population, we're fairly underpenetrated. We only have about a 20% penetration rate within there. This has been one of the reasons that we've really expanded our field team now to really tap into that big group of patients who are looking for treatment options. We know that clinicians who see Rett patients are aware of DAYBUE. They want to start DAYBUE, and we are making sure that we can meet that patient where they are.
We're educating the HCP on how to get started. We're making sure, again, as I mentioned, we're sharing experience from COEs into the community setting to ensure that they have the confidence to not only start the treatment but keep their patients on treatment for a long time.
On the field force expansion, at what point do you see the potential for an inflection, or do you think it's going to be more of a steady build?
If you go back to Q4, we had about 920 active patients on treatment. That number went up to nearly 950 in Q1, and now, as you said, we're close to 990 at the end of Q2. Our anticipation is that we will continue to see steady progress through Q3 into Q4. We're really planning that you'll see a more meaningful inflection as we kind of exit the year because it just takes a little bit of time for our new field team to bed in. As a reminder, we expanded our footprint by about 30%. Some of these representatives, although they're highly experienced, are new to their territories.
They have to meet their customers, and it's worth noting that outside of the center of excellence, just given the fact that they don't see such a high volume of Rett patients, it just takes a little while longer to get that patient started.
A bit of a bigger picture question now that you're on the field force, and this is a rare disease. You've expanded the sales force now. Do you think that this is a one-product sales force, or they could add more products to the bag?
I think we would evaluate that question carefully, but clearly there would likely be some capacity to potentially take on additional products as needed.
Going back to DAYBUE, when do you expect to start seeing patients who've been on DAYBUE and discontinued come back to the product, especially given nothing else is approved for Rett syndrome right now?
We are seeing on a quarterly basis, we do see patients who have discontinued come back. I think if you look over the last few quarters, that number's actually increased kind of step-wise. I mean, it's still kind of in the low double-digit number. However, having said that, that's going to be one of our goals moving forward as well because as much as we want to get new patient starts, patients who have maybe tried the product and are kind of on the fence about restarting, we want to ensure that we continue engaged with them. If they wish to start, we can get them started quickly. That's been a goal of the team moving forward.
Got it. On your ex-U.S. efforts, you have some named patient programs that are ongoing with this product. What are your early thoughts on that? How are you thinking about Acadia as it attempts to morph into an ex-U.S. organization as well?
For DAYBUE, just as a reminder, we have an approval in the U.S. and we have an approval in Canada. We're in the process of seeking an approval in the European Union as well, which we anticipate Q1 of next year. At the same time, we have also received a number of unsolicited patient requests, direct patient requests from HCPs outside of those markets for access to DAYBUE. That number has increased since we've launched the product. We're looking at ways that we can meet that demand where the regulatory or legal framework allows. We have now set up named patient programs ex-U.S. We have a partner called FarmaMondo, who is serving the rest of the world. We have a partner called Clinigen, who is helping us in Europe. We're working with a company called Rafa to support patients in Israel. All of those programs are moving forward.
What we're seeing already is there's been really high engagement and interest in gaining access to the product, which we're not surprised by given we're the only approved treatment for Rett. As we think about kind of our global expansion, we've been clear. Beyond the U.S., Canada, Europe remain a focus. As we begin to think about outside of those markets, Japan is clearly in play. We're conducting a phase III study there for DAYBUE. Other markets outside of that we will continue to evaluate in due course should the need be there.
I'll switch now to NUPLAZID for Parkinson's disease psychosis. What's the key factor that's helping you to grow NUPLAZID, which saw a really solid second quarter performance?
I'd say two things. First is field team execution. The team has been really engaged and actively focused on where we need to grow the business, how we grow the business in partnership with the second piece, which is our DTC efforts. We've had two big campaigns go live through the second half of last year. The first was More to Parkinson’s, which is an unbranded awareness campaign for patients to go and seek out care from their healthcare provider as it relates to psychosis related to Parkinson’s disease. That’s where we have partnered with Ryan Reynolds. We know that that campaign has worked very well for us. As we announced during the Q2 call, we're actually going to expand that agreement into the first part of next year. Secondarily, we've also been working on our NUPLAZID.com website.
We're amplifying our DTC efforts from a branded point of view, and we're seeing some really nice metrics there. Through Q2, we saw a 17-fold increase year over year in terms of site traffic to our NUPLAZID.com website. That just gives us an opportunity to really begin to engage with that patient group more accurately and directly to ensure that they're having not only the appropriate dialogue with their healthcare provider about hallucinations, delusions associated with Parkinson’s disease, but they can also think about what's an appropriate treatment to them. Us being able to differentiate NUPLAZID is a key component of that strategy.
I'll delve a bit into the political environment here. We've heard some rumblings on DTC in biopharmaceuticals, how that might potentially change in the U.S. because we're one of the few countries that allows DTC. Do you think that's going to happen? If yes, how are you going to mitigate around that given it looks like NUPLAZID is very sensitive to that kind of promotion?
I wouldn't want to say whether there's going to be a yes or a no as to what may or may not happen as it relates to healthcare advertising. What I would say is that yes, we know that NUPLAZID is highly promotionally sensitive, but it's not only promotionally sensitive to DTC, it's also promotionally sensitive to what we are actually doing in the field. DTC is just one element of how we think about our marketing mix overall for NUPLAZID. It's not like we're a big pharma company who is spending millions and millions of dollars on DTC. This is just one component of how we're engaging with the PD community.
If there's any legislation that limits certain activities, at least the first thing people are talking about is terrestrial television, which we don't use, right? It seems that the first thing that would be the target or seems to potentially be the target is not the vehicle we're using to communicate with our community. Obviously, we're compliant with all laws and regulations. If things change that may limit our activities, we will be compliant with that, but we'll still look for the best ways to communicate and educate with our key audiences.
Another government-based question, the Inflation Reduction Act.
Yes.
How do you expect Inflation Reduction Act-based changes on the price of NUPLAZID to play out? Will that require a rethink on the size of your field force or prior to the product being subject to price negotiation?
Yeah, great question. I think for us, as a reminder, everybody who's listening to this and in this room, NUPLAZID is about a 70% - 75% Medicare patient population. That makes it sensitive to legislation such as the Inflation Reduction Act. We are a small manufacturer under the legislation, which provides us with a number of benefits, including what you're alluding to potentially is like the future of negotiation. Yes, we anticipate that without a change in law, the first year that we would potentially be subject to negotiation would be 2029. In 2029 and 2030, the negotiation would be limited because we're a small company. After that, we would be treated like any other company under the legislation. Yes, in the future world, the pricing dynamic for NUPLAZID is likely to be lower than it is today, but it still would be a branded pharmaceutical drug.
When we look at investments, the way we look at it is what's the lifetime value of a new patient ad, because we're marketing and commercializing and educating to get those new patients, not really just to have refills from the existing patients. That's more from a financial perspective, I would say, kind of annuity value. When we get out there and we say, all right, even if the price is lower than it is today and the amount of money that we'll spend on field force and other promotional efforts, it still exceeds our rate of returns at negotiated prices within some reasonable range of what we think it will be to support the brand in volume growth out through February 2038, which is when our IP last due.
Of course, we evaluate everything over time, and we'll want to make sure that we're exceeding our return thresholds as we dial up or down. The legislation as it exists today, there's not a bull's eye on like at this date, we would need to operate differently than we are today.
I'm glad you brought up the intellectual property 2038. Given that you had a couple of really nice wins at lower court and even won appeal, it looks increasingly likely that you'll have that runway all the way to 2038, but then you have IRA coming in potentially 2029. Do you see any differences in the way that generic challengers are positioning themselves to take advantage of what could otherwise be a larger product or a smaller product, depending on what happens with the IRA in terms of their, I guess, propensity to change?
At the moment, the only two we're engaging with are the closer that we've been in litigation with, but exactly how they or others might operationalize in their business against ours, it's too early to see any of that.
Okay. I'll move to some pipeline questions, but I won't ask you any deep data type questions. I'm going to ask you something on ACP-101, which is intranasal carbetocin for hypophagia and Prader-Willi syndrome. That data set is coming early Q1 2025. As Chief Commercial Officer, what would you, let's say I'm a doctor you're detailing to, what's the key thing you would like to see in that data set to make me prescribe that to a Prader-Willi patient?
First thing I would say is obviously we are looking forward to the readout. It's right around the corner. I can tell you that commercial preparations are ongoing. The team is very actively engaged. I think what we are thinking about as it relates to ACP-101 versus, you know, the recently approved medication from Soleno is clearly we have a very different study design here. We have a prospective phase III randomized placebo-controlled study. It's running over 12 weeks. I think should that study look positive and similar to what we saw in the original phase III, we feel good that we're going to be able to parlay a clear story to physicians and to patients, quite honestly, as to if you utilize this medicine, this is what you can expect to see as you get started versus a randomized withdrawal study.
Clearly we have to see what the data looks like. I think in addition to that, there are going to be some differences that we can already see on paper as we think about our profile, as it relates to side effect profile, as it relates to potential monitoring, because we know that intranasal carbetocin looks like it's fairly benign from a side effect profile as well, which given the complex needs of the Prader-Willi population, we believe could be a benefit.
I'll switch to ACP-204 now for Alzheimer's disease psychosis. There's a phase II program running. How closely are you watching Bristol's trials on Carbamfine for ADP, and would you prefer to have competition set the tone in the ADP market, or would you like to be the first in that?
Again, another program that we're really excited by, and having worked at Bristol for nearly 21 years, clearly it's always interesting to see what your prior employer is doing. I think ADP is going to be very different to, as we think about NUPLAZID in Parkinson’s disease psychosis. It's a far bigger marketplace. Seven million patients with Alzheimer's living in the U.S., 30% of which will experience psychosis during their lifetime. It's a very, very large and substantial population. We believe, again, taking all of the learnings that we've taken from NUPLAZID into the ACP-204 program, that we can have a differentiated profile here. We've built upon that experience that we've already had with that product as we've developed it further. I think we've already shown within this marketplace that we can compete pretty effectively.
Taken together, we believe that irrespective of whether we're first to market or second to market, especially in a market that's as large as that, there will be opportunities for us to be very, very successful.
You have a relatively large pipeline that's focused on a lot of different things. As a commercial person, do you have any favorites and why?
I'll parlay what Liz says. It's very difficult to pick your favorite child. I think you're right. We've got a really interesting and robust pipeline. We've got a few different medicines there that are going to be aligned with the profile that we look for, which is either first in class or best in class. That's the goal that we're aiming to fulfill. We're aiming to meet the needs of patients that do not have great options. We've seen that both with NUPLAZID and we've seen it with rett. Moving forward, hopefully the Prader-Willi as well. We're really delivering on our mission of helping patients have those meaningful moments that matter.
I'm not going to give you a direct answer because I'm excited by all of them, but I think the near-term prospects that we have with both ACP-101 and ACP-204 as a commercial person, that's exciting because they're not too far away.
This is a CFO question. You have lots of programs going. How do you think about dollar prioritization and resources spent on one product versus another?
I think we're in a fortunate position where we don't have to make that choice. We're making, I think, going back to what Liz, our Head of R&D, always says, when we're thinking about business development, a molecule has to earn its way into our pipeline. When it's in the pipeline, it has to earn its way to continue to be in the pipeline. For us, we really look at, as we run a trial and the trial reads out, what does the data tell us? What does it read out relative to our expectations going on? What may have changed in the competitive environment currently or in the future? Does it justify continuing investment? That's how we look at all of our assets. It's not necessarily a ratio of sales.
We're not constrained by the, if we have financial capacity to add to the portfolio rather than saying, all right, if we have this number now, next year it's got to be that or less. We don't have those financial constraints, thankfully. It's really, what's the investment profile look like? If it's a good one, we're going to continue to invest. If it's not a good one, we're going to put it on the side and go look at something else.
Right. A bit of an offshoot of that question. You have lots of internal programs. How are you thinking about the potential to bring more programs in from external sources? Do you have the bandwidth to do that?
Yeah, we definitely have the operational bandwidth to do it and the financial capacity to do it.
Is there a preference for size of indication, stage of asset, or anything like that when you think about these things?
I would say our preference is to, I think what we want to bring in are kind of more NUPLAZIDs and DAYBUEs. So molecules that have opportunities to be first in class or best in class to bring real medical benefit to patients. I think if you think about Acadia and our size, it's more likely that we're going to bring them into our pipeline than to the commercial portfolio, likely. Don't want to exclude anything. Our preference would be, because it's more interesting to us and more interesting to the audience here, for those to be clinical assets. The actionability on attractive assets at that size and meeting all our parameters, it's just, it's harder to execute on that. We've done some. It's easier to execute on things that are earlier.
We look at the preference would be, you know, mid to late clinical stage, but we don't exclude it to just those. If we can find attractive assets that we can bring in at a lower price earlier, we'll do that. If you look, go back to R&D day, we unveiled some new assets to Wall Street that we had brought back into the portfolio over the last couple of years as those were earlier in their life cycle.
Got it. Thanks a lot. I think that's about our time. Thank you for making the trip here. Thank you to everyone in the audience and for tuning into the webcast as well.
All right. Thank you.
Thank you.